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    Journal of Shanghai Jiao Tong University (Medical Science) 2024 Vol.44
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    An integrated prognostic model of nuclear-encoded mitochondrial gene signature and clinical information for hepatocellular carcinoma
    Aishanjiang Kedeerya, FU Yi, LAI Donglin, WU Hailong, GONG Wei
    Journal of Shanghai Jiao Tong University (Medical Science)    2024, 44 (1): 1-12.   DOI: 10.3969/j.issn.1674-8115.2024.01.001
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    Objective ·To establish a prognostic model for the overall survival (OS) of hepatocellular carcinoma (HCC) based on mitochondrial genes and clinical information. Methods ·The gene expression and the clinical data of 369 HCC patients and 50 controls with normal liver were downloaded from The Cancer Genome Atlas (TCGA) database. The nuclear-encoded mitochondrial genes (NEMGs) were obtained from the MitoCarta3.0 database. The "DESeq2" R package and univariate Cox analysis were used to select NEMGs [ubiquinol cytochrome C reductase hinge protein (UQCRH), ATP citrate lyase (ACLY), phosphoenolpyruvate carboxykinase 2 (PCK2), Bcl-2 homologous antagonist/killer1 (BAK1), Bcl-2-associated X protein (BAX) and Bcl-2/adenovirus E1B interacting protein 3-like (BNIP3L)] in HCC that were associated with OS of HCC and participated in dysregulation of oxidative phosphorylation, tricarboxylic acid cycle and cell apoptosis. Multivariate Cox analysis was applied to select independent risk factors for OS of HCC. A comprehensive prognostic model and a prognostic nomogram with 6-NEMG risk characteristics and TNM staging were established. By using the median of prognostic scores as a cut-off, HCC patients were classified into low-risk and high-risk group. Kaplan-Meier survival curve analysis was conducted and log-rank test was performed to evaluate the survival rates between the low-risk and high-risk group. The area under the curve (AUC) values of receiver operating characteristic (ROC) curve were calculated via using the "timeROC" package. The prognostic model for HCC was validated by using the GEO HCC cohort (GSE14520) for 1, 3 and 5 years. Finally, the relative expression level of 6-NEMG was validated in 34 clinical samples of HCC from Xinhua Hospital, Shanghai Jiao Tong University School of Medicine by using real-time quantitative polymerase chain reaction (qPCR) method. Results ·Compared to 6-NEMG risk signature only (AUCs for 1, 3 and 5 years were 0.77, 0.66 and 0.65, respectively) or TNM stage only (AUCs for 1, 3 and 5 years were 0.66, 0.67 and 0.63, respectively), ROC curve analysis showed that this integrated prognostic model displayed better predictive performance for 1-year (AUC, 0.78), 3-year (AUC, 0.73) and 5-year (AUC, 0.69) OS of HCC. The Kaplan-Meier survival curve analysis showed that the OS of HCC patients in the high-risk group was significantly worse than that in the low-risk group (P=0.001). In addition, predictive performance of the prognostic model (AUC for 1, 3 and 5 years is 0.67, 0.66 and 0.74, respectively) and prognostic differences between the high-risk and low-risk group (P=0.001) were further validated in GEO (GSE14520) external cohort, and these results were consistent with the TCGA data. In addition to BNIP3L, dysregulation of five other NEMGs in the clinical HCC cohort was validated. The correlation analysis in GSE14520 and HCC clinical cohort showed a positive correlation between prognosis score and the size and number of tumors. Conclusion ·A new prognostic model that combines 6-NEMG risk characteristics with TNM staging for predicting OS in HCC patients was constructed and validated. This model may help improve the prognosis prediction of HCC patients.

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    Observation on A-PRF promoting regeneration of osteochondral defects in rabbit knee joints
    ZHU Zeyu, LÜ Chengqi, LIU Xuling, CHEN Yulu, ZOU Derong, LU Jiayu
    Journal of Shanghai Jiao Tong University (Medical Science)    2024, 44 (1): 13-22.   DOI: 10.3969/j.issn.1674-8115.2024.01.002
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    Objective ·To explore the role of advanced platelet-rich fibrin (A-PRF) in osteochondral regeneration. Methods ·Bone-marrow mesenchymal stem cells (BMSCs) and knee joint chondrocytes were obtained from New Zealand rabbits. A-PRF was obtained by low-speed centrifugation of the heart blood of rabbits. The histological structure of A-PRF was observed by an optical microscope. The release of growth factors in A-PRF was detected by ELISA, including platelet-derived growth factor, transforming growth factor-β, insulin-like growth factor, vascular endothelial growth factor, epidermal growth factor and fibroblast growth factor. A-PRF's cytotoxicity and capability for promoting the proliferation of rabbit BMSCs were detected by live/dead double staining and MTT methods. The effect of A-PRF on the gene expression of type Ⅱ collagen, aggrecan, alkaline phosphatase (ALP) and osteocalcin (OCN) in rabbit BMSCs was detected by real-time fluorescence quantitative polymerase chain reaction (qRT-PCR). Transwell chambers were used to determine the effect of A-PRF on the migration ability of rabbit BMSCs and the chondrocytes. Rabbit knee osteochondral defect models were established, and 18 rabbits were randomly divided into 3 groups. The A-PRF group (n=6) was implanted with A-PRF in the defect, the A-PRF+BMSCs group (n=6) was implanted with rabbit BMSCs on A-PRF, and the control group (n=6) did not undergo implantation. The rabbits were sacrificed 12 weeks after surgery and the knee joint specimens were stained with hematoxylin-eosin (H-E), toluidine blue and safranin O/fast green. Based on the surface morphology and histology of the knee joints, the International Cartilage Repair Society (ICRS) scoring system was used for macroscopic and histological scoring. Results ·A-PRF had a loose network structure and can slowly release growth factors. No cytotoxicity to rabbit BMSCs was observed after adding A-PRF, and the the capability for promoting the proliferation of rabbit BMSCs was significantly increased at 24, 48 and 72 h after adding A-PRF (all P<0.05). Chondrogenesis-related gene Ⅱ collagen and aggrecan, as well as osteogenesis-related genes ALP and OCN were significantly up-regulated (all P<0.05). After adding A-PRF, the migration abilities of rabbit BMSCs and chondrocytes were significantly enhanced (both P<0.05), and the migration ability of rabbit BMSCs was significantly higher than that of chondrocytes (P=0.025). The joint surface morphology in the rabbit knee joint defect models was observed. It can be seen that the defects in the A-PRF group and the A-PRF+BMSCs group were basically restored, while the the defects in the control group were only covered by soft tissue. In the ICRS macroscopic score, there was no statistical difference between the A-PRF group and the A-PRF+BMSCs group, but the scores of the two groups were all significantly higher than those of the control group (all P<0.05). According to the histological results, both the A-PRF group and the A-PRF+BMSCs group formed osteochondral repair, but the cartilage in the A-PRF group was more mature, while the control group formed fibrous repair. In the ICRS histological score, there was no statistical difference between the A-PRF group and the A-PRF+BMSCs group, but the scores of both the groups were significantly higher than those of the control group (both P<0.05). Conclusion ·Autologous A-PRF has good biocompatibility and the capability for promoting the proliferation of BMSCs. It can promote the repair of cartilage and subchondral bone both in vitro and in vivo.

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    Expression of adhesion G protein-coupled receptor F1 in pancreatic ductal adenocarcinoma and its mechanism of promoting cancer progression
    CHEN Suyuan, Mutailifu Musitaba, LI Dongxue, ZHANG Zhigang
    Journal of Shanghai Jiao Tong University (Medical Science)    2024, 44 (1): 23-34.   DOI: 10.3969/j.issn.1674-8115.2024.01.003
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    Objective ·To analyze the expression changes of adhesion G protein-coupled receptor F1 (ADGRF1) in the occurrence and development of pancreatic ductal adenocarcinoma (PDAC), and explore the impact of ADGRF1 on the proliferation of PDAC cells and the potential molecular mechanisms that promote PDAC progression. Methods ·The expression of ADGRF1 at mRNA level was analyzed based on the Gene Expression Omnibus (GEO) database and The Cancer Genome Atlas (TCGA) database, respectively. The expression of ADGRF1 in normal pancreatic ductal epithelial cells (hTERT-HPNE) and various PDAC tumor cells was detected by using real-time fluorescence quantitative PCR (qPCR) and Western blotting. Immunohistochemical staining (IHC) was used to detect the differential expression of ADGRF1 in cancer tissues and adjacent tissues of PDAC patients. After knocking down ADGRF1 with small interfering RNA (siRNA) transfection, the changes in the proliferation ability of PDAC AsPC-1 and SW1990 cells were detected through CCK8 assay and plate cloning experiment. Stable overexpression of ADGRF1 was constructed in PDAC Patu8988 cell line, and the proliferation changes induced by overexpression of ADGRF1 were evaluated through CCK8 assay. RNA sequencing (RNA-seq), gene set enrichment analysis (GSEA), and immune infiltration analysis were utilized to predict signaling pathways associated with ADGRF1-mediated promotion of PDAC cancer progression. Results ·Analysis of the TCGA database and GEO database revealed higher expression of ADGRF1 mRNA in PDAC tissues compared to normal pancreatic tissues (all P=0.000). qPCR and Western blotting results demonstrated up-regulation of ADGRF1 mRNA and protein levels in various PDAC cells compared to hTERT-HPNE cells (all P<0.05). IHC results confirmed higher ADGRF1 expression in PDAC cancer tissues compared to adjacent tissues. Furthermore, downregulation of ADGRF1 inhibited the proliferation of PDAC AsPC-1 and SW1990 cell lines, while overexpression of ADGRF1 promoted the proliferation of Patu8988 cells (all P<0.05). RNA-seq, GSEA enrichment analysis, and immune infiltration analysis revealed that ADGRF1 expression was related to signaling pathways such as interferon-α (IFN-α), tumor necrosis factor-α (TNF-α), and nuclear factor κB (NF-κB). Conclusion ·ADGRF1 is highly expressed in PDAC cells and tissues, and promotes the proliferation of PDAC cells via immune-related signaling pathways.

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    Effect of ceria nanoparticles on activity of DSS-induced colitis in mice by eliminating active oxygen species
    LU Yuhan, SHI Yahong, LONG Manmei, WANG Zi, WU Yingwei
    Journal of Shanghai Jiao Tong University (Medical Science)    2024, 44 (1): 35-42.   DOI: 10.3969/j.issn.1674-8115.2024.01.004
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    Objective ·To investigate the effect of ceria nanoparticles-polyethylene glycol (CeNP-PEG) on scavenging reactive oxygen species (ROS) and alleviating disease activity in dextran sulphate sodium (DSS)-induced colitis mice. Methods ·CeNP was synthesized with the hydrates of cerium acetate, oleamine, and xylene, which was modified with polyethylene glycol-stearyl phosphatidylethanolamine (mPEG-DPSE) to obtain CeNP-PEG. Then CeNP-PEG was purified. The particle size and zeta potential of CeNP-PEG were measured by using transmission electron microscopy (TEM) and dynamic light scattering (DLS). Mouse macrophages (Raw264.7) were cultured in vitro and induced to a pro-inflammatory phenotype (M1 phenotype). M1 macrophages were treated with 0.5 μg/mL and 1.0 μg/mL CeNP-PEG, respectively, and then Western blotting was used to detect the expression changes of the proteins related with nuclear factor-κB (NF-κB) signaling pathway. DSS-induced colitis mice models were constructed, and CeNP-PEG (1.0 mg/mL) was intravenously administrated for 3 times via tail vein during the modeling period. Meanwhile, the body weight, fecal characteristics, and frequency of rectal bleeding in mice were monitored in the normal control group (Normal group), the model group (DSS group), and the CeNP-PEG treatment group. The disease activity index (DAI) was calculated to evaluate the intestinal inflammation. The level of ROS in mouse intestinal tissues was detected by dihydroethidine (DHE) staining and the mRNA expression levels of inflammatory cytokines interferon-γ (Ifn-γ), interleukin-6 (Il-6), Il-1β and tumor necrosis factor-α (Tnf-α) were detected by real-time quantitative PCR (RT-qPCR). Results ·The hydrated particle size of synthesized CeNP-PEG was (6.96±0.27) nm, and the average zeta potential was (-6.02±1.31) mV. Western blotting results showed that the expression of p-P65 increased in the pro-inflammatory macrophages compared with the control group. The expression of NF-κB inhibitor-α (IκB-α) decreased, and their expressions tended to recover after the intervention of different concentrations of CeNP-PEG. In the DSS-induced colitis models, mice in the CeNP-PEG treatment group lost less weight than those in the DSS group (P=0.000) and had lower DAI scores (P=0.000). The RT-qPCR results of intestinal tissues showed that the mRNA levels of Ifn-γ, Il-1β, Il-6 and Tnf-α in the DSS group were significantly up-regulated compared with those in the Normal group (P=0.000), and all of them significantly decreased in the CeNP-PEG treatment group. The results of DHE staining showed that the fluorescence intensity of intestinal tissues in the DSS group was significantly enhanced than that in the Normal group, and the fluorescence intensity decreased in the CeNP-PEG treatment group. Conclusion ·CeNP-PEG can inhibit the expression of intestinal inflammatory factors and the activation of NF-κB-related inflammatory pathway of pro-inflammatory macrophages, eliminate intestinal ROS, improve the intestinal inflammatory microenvironment, and alleviate the disease activity of DSS-induced colitis in mice.

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    Application and accuracy assessment of a novel 3D-printed osteotomy guide in anterior maxillary segmental distraction osteogenesis
    WAN Teng, JIANG Tengfei, ZHU Min, WANG Xudong
    Journal of Shanghai Jiao Tong University (Medical Science)    2024, 44 (1): 43-49.   DOI: 10.3969/j.issn.1674-8115.2024.01.005
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    Objective ·To evaluate the effects of anterior maxillary segmental distraction osteogenesis (AMSDO) in treating sagittal maxillary hypoplasia in cleft lip and palate (CLP) patients and to report a 3D-printed surgical guide to facilitate the osteotomy. Methods ·Twelve patients with CLP who underwent AMSDO were included in this study. Virtual osteotomy was performed in a 3-dimensional model and the osteotomy line were fabricated into a tooth-borne surgical guide by using 3D-printing technique. Lateral cephalograms taken before surgery (T0), at the end of consolidation (T1) and six months after consolidation (T2) were used to evaluate the effects of AMSDO. The accuracy of the osteotomy guide was measured by superimposing the postoperative CT data to virtual planning. Results ·All the patients went through surgery without serious complications. SNA and overjet changed significantly both from T0 to T1 and from T0 to T2. ANB, facial convexity, and palatal length changed without significance from T0 to T1 and from T0 to T2. SNB remained stable. All the variables remained relatively stable from T1 to T2. The anteroposterior linear root-mean-square deviation (RMSD) between planning and actual results was 0.90 mm, while the angular RMSD in the sagittal plane was 5.07°. Conclusion ·AMSDO is an effective treatment for maxillary hypoplasia secondary to CLP. The accuracy of this 3D-printed osteotomy guide is clinically acceptable, and this can simplify the surgery with fewer complications.

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    Relationship among maternal gut, vaginal microbiota and microbiota in meconium and vernix caseosa in newborns
    MA Jinqian, FAN Pianpian, ZHENG Tao, ZHANG Lin, CHEN Yuanzhi, SHEN Jian, OUYANG Fengxiu
    Journal of Shanghai Jiao Tong University (Medical Science)    2024, 44 (1): 50-63.   DOI: 10.3969/j.issn.1674-8115.2024.01.006
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    Objective ·To analyze the diversity and composition of the maternal gut microbiota and vaginal microbiota in late pregnancy, neonatal meconium microbiota and vernix caseosa microbiota, and analyze the similarities, differences and correlations. Methods ·This is a prospective study. Maternal stool samples and vaginal swabs in late-pregnancy, and neonatal meconium samples were collected from 11 mother-infant pairs at Xinhua Hospital, Shanghai Jiao Tong University School of Medicine from August to November 2018; the vernix caseosa from three sites (forehead, axilla, and inguinal crease) and meconium samples were collected from 14 healthy newborns at International Peace Maternity and Child Health Hospital, Shanghai Jiao Tong University School of Medicine in December 2018. All births were vaginal deliveries. The 16S rRNA gene V3?V4 region sequencing was used. The diversity, composition and similarities/differences of the maternal gut microbiota, the vaginal microbiota, and the neonatal meconium microbiota from the 11 mother-infant pairs, as well as the neonatal vernix caseosa microbiota and the meconium microbiota from the 14 newborns were analyzed. Results ·The number of operational taxonomic units (OTUs), ACE index, Chao1 index, and Shannon index of maternal gut microbiota were all higher than those of vaginal microbiota; the ACE indices and the Chao1 indices of the vernix caseosa microbiota at three sites were all higher than those of meconium microbiota (P<0.01). The β diversity varied among the maternal gut microbiota, vaginal microbiota, and neonatal meconium microbiota (P<0.01). The β diversity of neonatal vernix caseosa microbiota from three sites (forehead, axilla, and inguinal crease) was similar, but different from meconium microbiota (P<0.01). At the phylum level, the dominant bacteria were Firmicutes (52.76%) and Bacteroidetes (41.67%) in the maternal gut microbiota, Firmicutes (74.36%) and Actinobacteria (21.25%) in the maternal vaginal microbiota, and Firmicutes (84.22%) and Proteobacteria (8.80%) in the neonatal vernix caseosa microbiota. The dominant bacterium in the neonatal meconium was Proteobacteria in the two batches of samples (81.11% and 88.72%, respectively). At the genus level, the dominant bacteria were Bacteroides (35.42%) and Faecalibacterium (10.12%) in the maternal gut microbiota, Lactobacillus (69.10%) and Bifidobacterium (11.30%) in the vaginal microbiota, and Lactobacillus (79.81%) and Pseudomonas (3.23%) in the vernix caseosa microbiota. The dominant bacterium in the neonatal meconium was Escherichia in the two batches of samples (55.21% and 31.18%, respectively). Conclusion ·The α diversity of maternal gut microbiota is higher than that of vaginal microbiota and neonatal meconium microbiota, and it is higher in neonatal vernix caseosa than that in meconium microbiota. The Firmicutes is the predominant phylum in the maternal late-pregnancy gut microbiota, vaginal microbiota, and neonatal vernix microbiota. Lactobacillus is the predominant genus in both maternal vaginal and neonatal vernix caseosa microbiota. Proteobacteria in phylum and Escherichia in genus are predominant in meconium microbiota. The microbiota composition is similar in vernix caseosa at different body sites, but there are differences between the vernix caseosa microbiota and meconium microbiota.

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    Clinicopathologic characteristics, gene mutation profile and prognostic analysis of thyroid diffuse large B-cell lymphoma
    DU Zhishan, WANG Yue, SHI Ziyang, SHI Qing, YI Hongmei, DONG Lei, WANG Li, CHENG Shu, XU Pengpeng, ZHAO Weili
    Journal of Shanghai Jiao Tong University (Medical Science)    2024, 44 (1): 64-71.   DOI: 10.3969/j.issn.1674-8115.2024.01.007
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    Objective ·To analyze the clinicopathologic characteristics, gene mutation profile, and prognostic factors of thyroid diffuse large B-cell lymphoma (DLBCL). Methods ·From November 2003 to December 2021, a total of 66 patients with thyroid DLBCL [23 cases (34.8%) with primary thyroid DLBCL, and 43 cases (65.2%) with secondary thyroid DLBCL] admitted to Ruijin Hospital, Shanghai Jiao Tong University School of Medicine were retrospectively analyzed for their clinicopathological data, survival and prognostic factors. Gene mutation profiles were evaluated by targeted sequencing (55 lymphoma-related genes) in 40 patients. Results ·Compared to primary thyroid DLBCL, secondary thyroid DLBCL had advanced ratio of Ann Arbor stage Ⅲ?Ⅳ (P=0.000), elevated serum lactate dehydrogenase (LDH) (P=0.043), number of affected extranodal involvement ≥2 (P=0.000), non-germinal center B cell (non-GCB) (P=0.030), BCL-2/MYC double expression (DE) (P=0.026), and international prognostic index (IPI) 3?5 -scores (P=0.000). The proportion of patients who underwent thyroid surgery (P=0.012) was lower than that of patients with primary thyroid DLBCL. The complete remission (CR) rate in primary thyroid DLBCL patients was higher than that in secondary thyroid DLBCL patients (P=0.039). Fifty-five patients (83%) received rituximab combined with cyclophosphamide, doxorubicin, vincristine, and prednisone (R-CHOP)-based first-line regimen. The estimated 5-year progression free survival (PFS) rate of primary thyroid DLBCL patients was 95.0%, higher than the 49.7% of the secondary patients (P=0.010). Univariate analysis showed that Ann Arbor Ⅲ?Ⅳ (HR=4.411, 95%CI 1.373?14.170), elevated LDH (HR=5.500, 95%CI 1.519?19.911), non-GCB (HR=5.291, 95%CI 1.667?16.788), and DE (HR=6.178, 95%CI 1.813?21.058) were adverse prognostic factors of PFS in patients with thyroid DLBCL. Ann Arbor Ⅲ?Ⅳ (HR=7.088, 95%CI 0.827?60.717), elevated LDH (HR=6.982, 95%CI 0.809?60.266), and DE (HR=18.079, 95%CI 1.837?177.923) were adverse prognostic factors of overall survival (OS). Multivariate analysis showed that Ann Arbor Ⅲ?Ⅳ (HR=4.693, 95%CI 1.218?18.081) and elevated LDH (HR=5.058, 95%CI 1.166?21.941) were independent adverse prognostic factors of PFS in patients with thyroid DLBCL. Targeted sequencing data showed mutation frequency >20% in TET2 (n=14, 35%), KMT2D (n=13, 32%), TP53 (n=11, 28%), GNA13 (n=10, 25%), KMT2C (n=9, 22%), and TP53 were adverse prognostic factors of PFS in patients with thyroid DLBCL (P=0.000). Conclusion ·Patients with primary thyroid DLBCL have better PFS and OS than those with secondary thyroid DLBCL. Ann Arbor Ⅲ?Ⅳ, elevated LDH, non-GCB, and DE (MYC and BCL2) are adverse prognostic factors in thyroid DLBCL. TET2,KMT2D, TP53, GNA13, and KMT2C are commonly highly mutated genes in thyroid DLBCL, and the prognosis of patients with TP53 mutations is poor.

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    Correlation between body compositions and cardiopulmonary fitness in patients with coronary heart disease
    LI Yang, MA Jun, DU Yihong, XU Li, CHEN Hanfen, QIU Xunhan, JIANG Meng, PU Jun
    Journal of Shanghai Jiao Tong University (Medical Science)    2024, 44 (1): 72-78.   DOI: 10.3969/j.issn.1674-8115.2024.01.008
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    Objective ·To explore the correlation between body compositions and cardiovascular fitness (CRF) in patients with coronary heart disease (CHD). Methods ·The CHD patients (CHD group) who underwent elective percutaneous coronary intervention treatment at Renji Hospital, Shanghai Jiao Tong University School of Medicine from October 2022 to June 2023 as well as healthy people (control group) were selected. All the participants completed cardiopulmonary exercise testing (CPET) to determine CRF and bioelectrical impedance analysis (BIA) to determine body compositions on the same day. Results ·A total of 191 patients with coronary heart disease and 188 healthy individuals were included. There was no statistically significant difference in baseline characteristics between the two groups. Compared with the control group, the CRF indicators of the CHD group were significantly reduced (all P<0.05). In terms of body composition indicators, the trunk muscle mass (TMM) of the CHD group was significantly lower than that of the control group (P<0.01), and the trunk fat mass (TFM) was significantly higher than that of the control group (P<0.01). Correlation analysis showed that TMM (R=0.538), lower limbs muscle mass (LMM) (R=0.754), and lower limbs fat mass (LFM) (R=0.593) were positively correlated with peak oxygen uptake per kilogram of bodyweight (VO2peak/kg) in the CHD group (all P<0.01), while TFM (R=-0.563) was negatively correlated with VO2peak/kg (P<0.01). There was no statistically significant correlation between other body composition indicators and VO2peak/kg. According to VO2peak/kg, the CHD patients were divided into low CRF group, medium CRF group, and high CRF group. The results showed that there were statistically significant differences in LMM, TMM, LFM, and TFM among the three groups of patients (all P<0.05). Multiple linear regression analysis suggested that age, gender, TMM, TFM, LMM, and LFM were related factors of VO2peak/kg in the patients with CHD. The VO2peak/kg of CHD patients increased with the increase of TMM, LMM, and LFM and the decrease of age and TFM; the female patients had lower VO2peak/kg compared to the males. Conclusion ·The CRF of CHD patients is significantly lower than that of the healthy population, with higher TFM and lower TMM; in the CHD patients, CRF is negatively correlated with TFM and positively correlated with TMM, LMM, and LFM.

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    Short -axis cine cardiac magnetic resonance images -derived radiomics for hypertrophic cardiomyopathy and healthy control classification
    LIU Qiming, LU Qifan, CHAI Yezi, JIANG Meng, PU Jun
    Journal of Shanghai Jiao Tong University (Medical Science)    2024, 44 (1): 79-86.   DOI: 10.3969/j.issn.1674-8115.2024.01.009
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    Objective ·To analyze the differences and classify hypertrophic cardiomyopathy (HCM) patients and healthy controls (HC) using short-axis cine cardiac magnetic resonance (CMR) images-derived radiomics features. Methods ·One hundred HCM subjects were included, and fifty HC were randomly selected at 2∶1 ratio during January 2018 to December 2021 in the Department of Cardiology, Renji Hospital, Shanghai Jiao Tong University School of Medicine. The CMR examinations were performed by experienced radiologists on these subjects. CVI 42 post-processing software was used to obtain left ventricular morphology and function measurements, including left ventricular ejection fraction (LVEF), left ventricular end-diastolic volume (LVEDV) and left ventricular end-diastolic mass (LVEDM). The 3D radiomic features of the end-diastolic myocardial region were extracted from short-axis images CMR cine. The distribution of the radiomic features in the two groups was analysed and machine learning models were constructed to classify the two groups. Results ·One hundred and seven 3D radiomic features were selected and extracted. After exclusion of highly correlated features, least absolute shrinkage and selection operator (LASSO) was used, and a 5-fold cross-validation was performed. There were still 11 characteristics with non-zero coefficients. The K-best method was used to decide the top 8 features for subsequent analysis. Among them, four features were significantly different between the two groups (all P<0.05). Support vector machine (SVM) and random forest (RF) models were constructed to discriminate the two groups. The results showed that the maximum area under the curve (AUC) for the single-feature model (first order grayscale: entropy) was 0.833 (95%CI 0.685?0.968) and the maximum accuracy for the multi-feature model was 83.3% with an AUC of 0.882 (95%CI 0.705?0.980). Conclusion ·There are significant differences in both left ventricular function and left ventricular morphology between HCM and HC. The 3D myocardial radiomic features of the two groups are also significantly different. Although single feature is able to distinguish the two groups, the combination of multi-features show better classification performance.

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    Alteration of cognitive function in overweight and obese adolescents and its relationship with serum FGF21 levels
    HAN Rui, WU Qian, LIU Dan, CHENG Di, ZHANG Ying, NI Jiacheng, KANG Piao, CHEN Anran, YU Shujie, FANG Qichen, LI Huating
    Journal of Shanghai Jiao Tong University (Medical Science)    2024, 44 (1): 87-97.   DOI: 10.3969/j.issn.1674-8115.2024.01.010
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    Objective ·To evaluate the changes in cognitive function in overweight and obese adolescents, and explore the association between cognitive function and fibroblast growth factor 21 (FGF21). Methods ·A total of 175 adolescents from a senior high school in Shanghai were divided into normal weight group (n=50), overweight group (n=50) and obese group (n=75) based on their body mass index (BMI). General information, anthropometric data and laboratory testing indicators of the adolescents were collected and compared. The cognitive function of the three groups of adolescents was assessed by using the accuracy (ACC) and reaction time of Flanker task and n-back task. Enzyme-linked immunosorbent assay (ELISA) was used to detect the serum FGF21 level of the three groups of adolescents. Partial correlation analysis and multiple linear regression model were used to evaluate the correlation between cognitive task performance and anthropometric data and laboratory testing indicators. Results ·Compared with the normal weight group, systolic blood pressure, diastolic blood pressure, and the levels of fasting plasma glucose, glycosylated hemoglobin and triacylglycerol in the obese group were higher (all P<0.05). Under congruent or incongruent stimulus conditions in the Flanker task, there was no significant difference in ACC between any two groups; compared with the normal weight and overweight groups, the reaction time of the adolescents in the obese group was prolonged (all P<0.05). In the n-back task, there were no significant differences in ACC between any two groups, while the obese group had longer reaction time in the 1-back and 2-back tasks compared to the normal weight and overweight groups (all P<0.05). Compared with the normal weight group, serum FGF21 levels of the adolescents in the obese group were higher (P=0.000). Partial correlation analysis showed that the reaction time of the adolescents in Flanker and n-back tasks was correlated with their BMI, body fat mass, waist circumference, waist-to-hip ratio and FGF21 level (all P<0.05). Multiple linear regression analysis further confirmed that BMI was associated with prolonged reaction time in cognitive-related behavioral tasks in the adolescents (all P<0.05), and FGF21 level was associated with ACC in the 2-back task (P=0.000) and reaction time in the incongruent stimulus condition (P=0.048). Conclusion ·Overweight and obese adolescents have cognitive impairments, and BMI and serum FGF21 levels are associated with changes in their cognitive function.

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    Establishment of discriminative models for predicting the infiltration degree of patients with lung adenocarcinoma based on clinical laboratory indicators
    WANG Mengfei, YANG Shouzhi, QIAO Yongxia, HUANG Lin
    Journal of Shanghai Jiao Tong University (Medical Science)    2024, 44 (1): 98-107.   DOI: 10.3969/j.issn.1674-8115.2024.01.011
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    Objective ·To establish a multifactorial discriminative model for predicting the degree of infiltration in patients with non-small cell lung adenocarcinoma based on clinically accessible laboratory indicators, such as tumor markers, coagulation function indicators, routine blood count indicators, and biochemical indicators. Methods ·A retrospective study was conducted on 202 patients with lung adenocarcinoma admitted to Shanghai Chest Hospital in 2022. Multifactorial Logistic regression analysis was applied to screen independent factors that influenced the predictive infiltration degree of lung adenocarcinoma and to establish a regression model. In addition, machine learning was used to construct a discriminative model, and the area under the receiver operating characteristic curve (AUC) was used to evaluate the discriminative ability of the model to discriminate the degree of infiltration in lung adenocarcinoma patients. Results ·A total of 202 patients with lung adenocarcinoma were included in the study, and divided into pre-invasive lesion group (n=59) and invasive lesion group (n=143). Multifactorial Logistic regression analysis revealed that urea, percentage of basophilic granulocytes, and albumin were independent factors for predicting the degree of infiltration of lung adenocarcinoma (all P<0.05). The predictive model expression was P = eX / (1 + eX ), where X = (0.534×urea) + (1.527×percentage of basophilic granulocytes) - (1.916×albumin) + 6.373. Machine learning results showed that the model performed best when urea, fibrinogen, albumin, percentage of basophilic granulocytes, prealbumin and carcino embryonic antigen (CEA) were included. After comparing the performance of 8 machine learning algorithms (based on ridge regression, least absolute shrinkage and selection operator, neural network, random forest, k-nearest neighbors, support vector machine, decision tree, and adaptive boosting algorithms) using the DeLong test, the ridge regression algorithm with the highest AUC was selected. The AUC of the predictive model was calculated to be 0.744 (95% CI 0.656-0.832), with a sensitivity of 70.8% and a specificity of 70.2%. Conclusion ·A comprehensive differentiation model constructed by urea, fibrinogen, albumin, percentage of basophilic granulocytes, prealbumin and CEA can effectively predict the infiltration degree of the enrolled lung adenocarcinoma patients, holding the potential to provide more precise guidance for the clinical grading and adjunctive treatment of lung adenocarcinoma.

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    Effects of Astragali Radix on T lymphocyte subsets expression in peripheral blood of Hashimoto s thyroiditis patients with normal thyroid function
    LI Ziyun, ZHUANG Xinjuan, JI Ye, TIAN Hairong, YIN Jun
    Journal of Shanghai Jiao Tong University (Medical Science)    2024, 44 (1): 108-115.   DOI: 10.3969/j.issn.1674-8115.2024.01.012
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    Objective ·To investigate the effect of Astragali Radix on T lymphocyte subsets and cytokine expression in Hashimoto's thyroiditis patients with normal thyroid function. Methods ·A total of 120 Hashimoto′s thyroiditis patients with normal thyroid function and complete data were selected from January 2020 to December 2020 in Jinshan Branch of Shanghai Sixth People′s Hospital. The patients were randomly divided into intervention group (n=60) and control group (n=60) by the method of random number table. The treatment plan of the control group was iodine appropriate state diet, and the intervention group was combined with oral Astragali Radix solution (150 mL per time, twice/d) on the basis of the treatment of the control group. The two groups were treated for 6 months. The changes in peripheral blood serum T lymphocyte subsets (CD3+, CD4+, CD8+, and CD4+/CD8+), cytokines [interleukin-2 (IL-2), tumor necrosis factor-α (TNF-α), interleukin-6 (IL-6), and interleukin-10 (IL-10)], hypersensitive C-reactive protein (hs-CRP), erythrocyte sedimentation rate (ESR), thyroid function, autoantibody, liver and kidney function, and other biochemical indexes were compared before and after treatment between the two groups. Adverse reactions were observed during the treatment. The factors influencing the change amplitude of thyroid peroxidase antibody (TPOAb) were analyzed by multifactor linear regression. Results ·Finally, 118 patients, with 59 cases in each group, were included in the study. After 6 months of treatment, the intervention group showed significant improvements in the proportions of CD4+ T cells, the ratio of CD4+/CD8+, and the levels of IL-2, TNF-α, IL-10, hs-CRP, ESR, TPOAb, and thyroglobulin antibody (TGAb) compared to the values before treatment and in the control group (P<0.05). There were no statistically significant differences on the above indicators before and after treatment in the control group (P>0.05). No serious adverse reactions were observed in the intervention group. Multiple linear regression analysis results showed that the use of Astragali Radix, increase of CD4+ level, increase of CD4+/CD8+ ratio, and decrease of hs-CRP level were influencing factors for the decrease of TPOAb level (β=-0.393, P=0.029; β=-0.513, P=0.010; β=-0.351, P=0.035; β=0.434, P=0.023). Conclusion ·Astragali Radix can improve the levels of CD4+ T cells, CD4+/CD8+ratio, IL-2, TNF-α, IL-6, and IL-10 in Hashimoto′s thyroiditis patients with normal thyroid function, and it is safe to use.

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    Adjuvant strategies for patients with T1b invasion after endoscopic submucosal dissection for esophageal squamous cell carcinoma
    ZHU Kaiyuan, SU Yuchen, LIU Zhichao, ZHANG Hong, LI Chunguang, ZHANG Jie, LI Zhigang
    Journal of Shanghai Jiao Tong University (Medical Science)    2024, 44 (1): 116-123.   DOI: 10.3969/j.issn.1674-8115.2024.01.013
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    Objective ·To compare the prognostic effects of radical resection of esophageal cancer, concurrent chemoradiotherapy and simple follow-up observation on the prognosis of patients with T1b invasion of superficial esophageal squamous cell carcinoma after endoscopic submucosal dissection (ESD). Methods ·From May 2016 to May 2021, the clinical data of 67 patients with esophageal squamous cell carcinoma who were pathologically confirmed as pT1b after ESD and treated in Shanghai Chest Hospital were retrospectively analyzed. According to the additional treatment after ESD, the patients were divided into additional surgery group (S group), chemoradio-therapy group (CRT group) and observation group (O group). χ2 test was used to compare the clinical baseline data and pathological information of the three groups of patients. The Kaplan-Meier survival curve and log-rank test were used to compare the disease free survival (DFS) and recurrence free survival (RFS) of the three groups of patients, and the Cox proportional hazards regression model was used on DFS and RFS by univariate and multivariate analysis. Results ·Among all 67 patients, there were 23 cases in the S group, 19 cases in the CRT group, and 25 cases in the O group. There was no significant difference in age (P=0.080), gender (P=0.078), tumor length (P=0.485), tumor location (P=0.655), lesion circumferential ratio (P=0.310), histological grading (P=0.084), depth of tumor invasion (P=0.066) and lymphovascular invasion (P=0.279) among the three groups. During (42.6±16.7) months of follow-up, tumor recurrence was observed in 10 cases (14.9%), including 6 patients (60%) with local recurrence, 2 patients (20%) with regional lymph recurrence and 2 patients (20%) with distant metastasis. The median recurrence time of group S, group CRT, and group O was 40.1, 36.6, and 22.1 months, and the 3-year DFSs were 100%, 89.5%, and 74.5% (P-trend=0.040). Multivariate Cox analysis showed that additional esophagectomy was the key to improving independent protective factors of RFS (HR=0.097, 95%CI 0.010?0.956, P=0.046). Conclusion ·For patients with superficial esophageal squamous cell carcinoma confirmed as pT1b after ESD, additional surgery can significantly reduce the possibility of long-term recurrence.

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    Research progress in ceruloplasmin regulation of lipid metabolism homeostasis
    JIANG Quanxin, CHEN Suzhen, LIU Junli
    Journal of Shanghai Jiao Tong University (Medical Science)    2024, 44 (1): 124-130.   DOI: 10.3969/j.issn.1674-8115.2024.01.014
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    Ceruloplasmin (Cp) is a crucial protein secreted by the liver and plays a vital role in regulating the distribution and transport of copper throughout the body, thereby maintaining copper homeostasis. Additionally, Cp functions as a significant enzyme known as ferroxidase, which is involved in iron metabolism within the body. Numerous studies have suggested a close relationship between Cp and metabolic disorders, such as diabetes and cardiovascular diseases. Recent research has also shed light on the involvement of Cp in the regulation of lipid metabolism. The various activities associated with lipid metabolism, including lipid synthesis, adipose hydrolysis, fatty acid oxidation, lipid transport, and absorption, collectively contribute to maintaining lipid homeostasis. Dysregulation of lipid metabolism can lead to metabolic disorders and cardiovascular complications. Cp regulates lipid metabolism through two main mechanisms. Firstly, Cp participates in the regulation of oxidative stress by modulating iron metabolism through its ferroxidase activity and involvement in redox reaction. Secondly, copper along with copper-dependent enzymes directly participates in the processes such as cholesterol metabolism, lipoprotein metabolism, and fatty acid synthesis. As a result, the role of Cp in maintaining the homeostasis of copper and iron allows it to regulate lipid metabolism by influencing copper or iron-dependent enzymes and related pathways. Although the correlation between Cp and lipid metabolism has been identified, an in-depth exploration of the precise mechanisms by which Cp governs lipid metabolism is warranted. This article provides an overview of the role of Cp in lipid metabolism and highlights the progress in related research, with the aim of providing new insights for the development and treatment of disorders related to lipid metabolism.

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    Progress of olfactory changes in metabolic diseases and the mechanisms
    WU Qian, LI Huating
    Journal of Shanghai Jiao Tong University (Medical Science)    2024, 44 (1): 131-136.   DOI: 10.3969/j.issn.1674-8115.2024.01.015
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    Metabolic disorders, characterized by a complex pathogenesis, are experiencing a rising prevalence globally and a trend toward younger populations, making them a significant public health concern. Olfaction, a crucial sensory function, plays a pivotal role in an individual′s nutrition and quality of life. There is a bidirectional relationship between obesity and olfactory function. Olfaction is influenced by nutritional status; simultaneously, it plays a vital role in the regulation of food intake, energy expenditure, and lipid metabolism. Moreover, individuals with metabolic disorders such as type 2 diabetes and obstructive sleep apnea syndrome exhibit olfactory dysfunction. Mechanisms underlying olfactory changes in metabolic disorders involve alterations in metabolic states such as hyperglycemia and insulin resistance. These changes can lead to dysregulation of peptide hormones, adipocyte factors, and neurotransmitters, which may potentially act as mediators between metabolic disorders and olfactory dysfunction. Vascular and neural alterations resulting from metabolic disorders can directly damage olfactory nerves or induce abnormal neural transmission. Furthermore, dysbiosis in the gut microbiota induced by metabolic disorders is a potential mechanism for olfactory dysfunction. Cognitive dysfunction is a significant complication of metabolic disorders. Olfactory dysfunction can serve as an early clinical manifestation of cognitive impairment and contributes to early identification and assessment of diseases. This article reviews recent researches on the relationship between metabolic diseases and olfactory changes and the potential mechanisms.

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    Research progress of m 6A methylation modification in regulating tumor immunity
    ZHOU Haixia, ZHANG Jing
    Journal of Shanghai Jiao Tong University (Medical Science)    2024, 44 (1): 137-144.   DOI: 10.3969/j.issn.1674-8115.2024.01.016
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    N6-methyladenosine (m6A) is the most prevalent modification that regulates gene expression in eukaryotes. It regulates splicing, degradation, stability, and translation of RNA. Numerous studies have demonstrated the close association between m6A methylation and tumor development, highlighting its crucial role in regulating tumor immune response. The m6A modification actively participates in governing immune cell differentiation and maturation as well as modulating anti-tumor immune responses. Within the tumor microenvironment, m6A modification can also impact the recruitment, activation, and polarization of immune cells, thereby either promoting or inhibiting tumor cell proliferation and metastasis. Consequently, it plays a pivotal role in reshaping the tumor immune microenvironment. In recent years, immunotherapy for tumors has been increasingly applied to clinical practice with notable success achieved through approaches such as immune checkpoint inhibitor therapy and adoptive cell immunotherapy. Targeting m6A modifications to interfere with the immune system, such as targeting dysregulated m6A regulators through small molecule inhibitors and inducing immune cell reprogramming, can improve anti-tumor immune response and strengthen immune cells′ ability to recognize and kill tumor cells. The m6A modification represents a novel avenue for potential clinical application within tumor immunotherapy. This review provides a comprehensive summary of the regulatory impact of m6A methylation modification on immune cells in the context of cancer, while also delving into novel targets for tumor immunotherapy.

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    Exploration of the relationship between nicotinamide metabolism-related genes and osteoarthritis
    DENG Qingsong, ZHANG Changqing, TAO Shicong
    Journal of Shanghai Jiao Tong University (Medical Science)    2024, 44 (2): 145-160.   DOI: 10.3969/j.issn.1674-8115.2024.02.001
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    Objective ·To explore the relationship between osteoarthritis and nicotinamide metabolism-related genes using bioinformatics analysis, and identify key genes with diagnostic value and therapeutic potential. Methods ·By using "Osteoarthritis" as a search term, GSE12021, GSE55235, and GSE55457 were obtained from the GEO database, with GSE55457 being used as the validation set. After removing batch effects from the GSE12021 and GSE55235 datasets, the standardized combined dataset was obtained and used as the training dataset. Differentially expressed genes (DEGs) were identified from the training dataset. All nicotinamide metabolism-related genes (NMRGs) were obtained from the GeneCards and MSigDB databases. The intersection of DEGs and NMRGs was taken to obtain nicotinamide metabolism-related differentially expressed genes (NMRDEGs). Gene set enrichment analysis (GSEA) was performed on the training dataset, while gene ontology (GO) and Kyoto encyclopedia of genes and genomes (KEGG) analysis were performed on NMRDEGs. Key genes were selected by using least absolute shrinkage and selection operator (LASSO) and support vector machine (SVM) analysis in NMRDEGs to build an osteoarthritis diagnosis model which was validated by using the GSE55457 dataset. Single sample gene set enrichment analysis (ssGSEA) was used to analyze the immune cell infiltration type. Interactions networks and drug molecule predictions were obtained for these key genes' mRNA with the DGIdb, ENCORI, and CHIPBase databases. siRNA was used to knock down the key genes in chondrocytes, and then real-time fluorescence quantitative polymerase chain reaction (RT-qPCR) was used to detect the expression of chondrogenesis-related genes. Results ·Seven NMRDEGs, including NAMPT, TIPARP, were discovered. GO and KEGG analysis enriched some signaling pathways, such as nuclear factor-κB signaling pathway and positive regulation of interleukin-1-mediated signaling pathway. GSEA enriched pathways such as Hif1 Tfpathway and syndecan 1 pathway. Key genes NPAS2, TIPARP, and NAMPT were identified through LASSO and SVM analysis, and used to construct an osteoarthritis diagnostic model. The validated results showed that the diagnostic model had high accuracy. Immune infiltration analysis results obtained by ssGSEA showed significant differences (all P<0.05) in 15 types of immune cells, including macrophages. Seven potential small molecules targeting key genes were identified, along with 19 miRNAs with the sum of upstream and downstream >10, 19 transcription factors with upstream and downstream >7, and 27 RNA binding proteins with clusterNum >19. The results of RT-qPCR showed that knocking down key genes reduced the expression of chondrogenesis-related genes. Conclusion ·Through bioinformatics analysis, key genes related to nicotinamide metabolism, NPAS2, TIPARP, and NAMPT, are discovered, and an osteoarthritis diagnostic model is constructed.

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    Effects of gingipain extract on the biological characteristics of oral squamous cell carcinoma cell HN6
    LI Huxiao, LI Xiaotian, ZHAO Xuri, ZHANG Huanyu, ZHOU Wei, SONG Zhongchen
    Journal of Shanghai Jiao Tong University (Medical Science)    2024, 44 (2): 161-168.   DOI: 10.3969/j.issn.1674-8115.2024.02.002
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    Objective ·To observe the effects of gingipain extract on the biological characteristics of oral squamous cell carcinoma cell HN6. Methods ·The HN6 cell line was selected, cultivated, and divided into different groups based on the protein concentration of gingipain extract from Porphyromonas gingivalis: control group, 3.125 μg/mL group, 6.25 μg/mL group, 12.5 μg/mL group, 25 μg/mL group, 50 μg/mL group, and 100 μg/mL group. After 24 and 48 h of cultivation, CCK-8 assay was used to detect the effects of gingipain extract on HN6 cell proliferation activity. Subsequent experiments were divided into control group, 25 μg/mL group and 50 μg/mL group. Flow cytometry was used to examine the effects of gingipain extract on cell cycle. Scratch assay and Transwell assay were performed to evaluate cell migration and invasion ability. Real-time PCR (RT-PCR) and Western blotting were used to measure the expression of E-cadherin and N-cadherin proteins and genes in cells. Results ·Stimulated with gingipain extract for 24 h, the HN6 cells showed significantly increased proliferation activity in the 25 μg/mL (P=0.025), 50 μg/mL (P=0.000), and 100 μg/mL (P=0.049) groups compared to the control group. After 48 h, proliferation activity was significantly higher in the 6.25 μg/mL(P=0.024), 12.5 μg/mL (P=0.006), 25 μg/mL (P=0.000), 50 μg/mL (P=0.000), and 100 μg/mL (P=0.000) groups compared to the control group. Cell cycle analysis revealed that, after 24 h of gingipain stimulation, the proportion of HN6 cells in the G1 phase decreased, while the proportion in the S+G2 phase significantly increased compared to the control group (25 μg/mL group: P=0.024; 50 μg/mL group: P=0.001). Compared to the control group, the scratch assay demonstrated a significant increase in the percentage of scratch closure as the concentration of gingipain extract increased (P=0.001). Compared to the control group, the Transwell invasion assay showed a significant increase in the number of cells passing through the bottom of the chamber as the concentration of gingipain extract increased. RT-PCR and Western blotting results indicated that as the concentration of gingipain extract increased, the expression levels of N-cadherin mRNA and protein in HN6 cells significantly increased, while the expression levels of E-cadherin mRNA and protein significantly decreased compared to the control group. Conclusion ·Gingipain extract could promote proliferation, migration, and invasion of oral squamous cell carcinoma HN6 cells.

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    Study on intercellular communication and key genes of smooth muscle cells in human coronary atherosclerosis based on single cell sequencing technology
    SI Chunying, WANG Jianru, LI Xiaohui, WANG Yongxia, GUAN Huaimin
    Journal of Shanghai Jiao Tong University (Medical Science)    2024, 44 (2): 169-182.   DOI: 10.3969/j.issn.1674-8115.2024.02.003
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    Objective ·To use single-cell RNA sequencing (scRNA-Seq) technology to interpret the cellular communication landscape of coronary atherosclerosis (CA), and to explore the dominant cell subsets and their key genes. Methods ·The GSE131778 data set was downloaded and preprocessed, and quality controlling, dimension reduction clustering and annotation were carried out. Then cell communication analysis was conducted by using CellChat package to identify dominant cell subsets. The FindAllMarker function was used to screen differentially expressed genes (DEGs) between the dominant cell subpopulation and other cell subpopulations, and its protein-protein interaction (PPI) network was constructed. The DEGs ranked in the top five of the Degree algorithm were taken as key genes. Then, the key genes were matched and mined with the cell communication network analyzed by CellChat to obtain the ligand-receptor pairs (L-R) and the signal pathways mediated by the key genes, and the results were visualized. At the same time, the atherosclerosis mouse model was constructed and RT-PCR was used to detect the expression of key genes in carotid atherosclerosis lesions. Results ·A total of 11 cell subsets were identified in CA lesions, including smooth muscle cells, endothelial cells, macrophages, monocytes, etc. Cell communication results showed that CellChat detected 70 significant L-R and 26 related signal pathways in 11 cell subsets. Smooth muscle cell was the dominant cell subgroup with the most significant interaction frequency and intensity with other cell subgroups in the active state of communication. The results of DEGs screening showed that there were 206 DEGs between smooth muscle cell subsets and other cell subsets, among which ITGB2, PTPRC, CCL2, DCN and IGF1 were identified as key genes. The results of cell communication mediated by key genes showed that CCL2 and ACKR1 formed L-R and participated in the communication network between smooth muscle cells and endothelial cells through mediating CCL signaling pathway. ITGB2 formed receptor complexes with ITGAM and ITGAX respectively, and then formed L-R with C3 to mediate the complement signal pathway, participating in the communication network among smooth muscle cells, macrophages and monocytes. The validation results of hub genes in animal experiments were consistent with the results of bioinformatics analysis. Conclusion ·Smooth muscle cells are the dominant cells in the pathological process of CA, and have extensive communication networks with other cells. They can construct cellular communication networks with endothelial cells, macrophages and monocytes through CCL and complement signaling pathways mediated by CCL2-ACKR1, C3-(ITGAM+ITGB2) and C3-(ITGAX+ITGB2).

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    Effect of neferine on diabetic nephropathy by regulating SDF-1/CXCR4 signal pathway
    WANG Ying, PING Lifeng, LIU Tongtong, LIU Shanshan, LIU Lei
    Journal of Shanghai Jiao Tong University (Medical Science)    2024, 44 (2): 183-195.   DOI: 10.3969/j.issn.1674-8115.2024.02.004
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    Objective ·To investigate the effect of neferine (Nef) on renal tissues of diabetic nephropathy (DN) rats and its related mechanism. Methods ·DN model rats were constructed by feeding high-fat diet combined with intraperitoneal injection of streptozotocin, and the successfully constructed rats were randomly divided into DN group, Nef (low, medium and high) dose groups and Nef high-dose+pathway antagonist (AMD3100) group, with 10 rats in each group. At the same time, 10 common rats were selected as the normal group. The levels of fasting blood glucose (FBG), 24 h urinary protein, serum glycosylated hemoglobin (HbA1c), serum creatinine (Scr), blood urea nitrogen (BUN) and renal index of rats in the six groups were measured. Hematoxylin-eosin (H-E) and Masson staining were used to observe the pathological changes of renal tissues. The content of malondialdehyde (MDA) in renal tissues was determined by thiobarbituric acid (TBA) method, and the activities of superoxide dismutase (SOD) and catalase (CAT) in renal tissues were determined by water soluble tetrazolium (WST-1) method and ammonium molybdate method, respectively. The mRNA and protein expressions of stromal cell-derived factor-1 (SDF-1) and CXC chemokine receptor 4 (CXCR4) in renal tissues were detected by quantitative real-time PCR (qPCR) and Western blotting, respectively. Rat renal tubular epithelium cells NRK-52E were induced by high glucose (30 mmol/L glucose) to establish DN cell model. The cells were divided into control group, high glucose (HG) group, HG+Nef (low, medium and high) dose (i.e.HG+Nef-L, M and H) group, and HG+Nef-H +AMD3100 group. SOD and CAT activities were detected by WST-1 method and ammonium molybdate method, respectively. MDA content was detected by TBA method. The mRNA and protein expressions of SDF-1 and CXCR4 were detected by qPCR and Western blotting, respectively. CCK-8 method and flow cytometry were used to detect cell viability and apoptosis rate, respecti-vely. Results ·Compared with the DN group, the levels of FBG, 24 h urinary protein, HbA1c, Scr, BUN, renal index and MDA content in Nef (low, medium and high) dose groups and Nef high-dose+AMD3100 group were decreased, the mRNA and protein expressions of SDF-1 and CXCR4 were increased, and the activities of SOD and CAT were increased (all P<0.05). The degree of pathological damage and fibrosis of renal tissues was reduced; all of the above changes were dose-dependent. AMD3100 could weaken the renal protective effect of high-dose Nef on DN rats. Compared with the HG group, NRK-52E cell viability, SOD and CAT activities, and the mRNA and protein expressions of SDF-1 and CXCR4 were increased in HG+Nef-L, M and H groups, while apoptosis rate and MDA content were decreased (all P<0.05). AMD3100 could reverse the protective effect of Nef-H on NRK-52E cell damage. Conclusion ·Nef may control blood glucose levels on DN rats and improve antioxidant capacity by activating the SDF-1/CXCR4 signal pathway, playing a renal protective role.

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    Study on the relationship between comorbidities of chronic diseases, phase angle, and muscle mass decline related to sarcopenia in the elderly
    WANG Junlin, HAO Mingxiu, TANG Yinhan, WU Yunyun, JIN Yuhua, HU Yaomin
    Journal of Shanghai Jiao Tong University (Medical Science)    2024, 44 (2): 196-203.   DOI: 10.3969/j.issn.1674-8115.2024.02.005
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    Objective ·To explore the correlation between comorbidities of chronic non-communicable diseases (chronic diseases), phase angle (PhA), and muscle mass decline associated with sarcopenia in the elderly, and the predictive value of chronic disease comorbidities and PhA in muscle mass decline in the elderly. Methods ·By retrospectively screening inpatients aged ≥60 years who were admitted to the Department of Geriatrics, Renji Hospital, Shanghai Jiao Tong University School of Medicine from August 1, 2018 to July 31, 2019, basic information and medical history of the patients (gender, age, number of medications used, number of comorbidities, presence of osteoporosis, smoking history, etc.) were collected, as well as laboratory examination indicators (hemoglobin, albumin, serum creatinine, serum uric acid, ferritin, vitamin D, triacylglycerol, total cholesterol, high-density lipoprotein, low-density lipoprotein, etc.). The age-adjusted Charlson comorbidity index (aCCI) was calculated. The InBody S10 bioelectrical impedance body composition detector was used to test the body composition. Body mass index (BMI), skeletal muscle mass index (SMI), and PhA were collected. Some patients underwent measurement of grip strength. Muscle mass decline was diagnosed by using the SMI values recommended by the 2019 Asian Working Group for Sarcopenia (AWGS) (≤7.0 kg/m2 for males and ≤5.7 kg/m2 for females). According to the measured SMI values, patients were divided into a group with normal muscle mass and a group with muscle mass decline. Univariate and multivariate Logistic analyses were employed to investigate the risk factors associated with muscle mass decline related to sarcopenia in the elderly. Additionally, the receiver operator characteristic (ROC) curve and the area under the curve were utilized to predict the significance of these factors in muscle mass decline. Results ·A total of 359 chronic disease patients were enrolled, including 226 males and 133 females. There were 241 cases in the normal muscle mass group and 118 cases in the muscle mass decline group. The incidence of muscle mass decline related to sarcopenia in the elderly was 32.9%. The univariate Logistic regression analysis showed that age (OR=1.036, 95%CI 1.013?1.060), comorbidities (OR=1.117, 95%CI 1.025?1.217), aCCI (OR=1.123, 95%CI 1.031?1.222), and high-density lipoprotein (OR=3.688, 95%CI 2.065?6.622) were positively correlated with the risk of muscle mass decline in the elderly. BMI (OR=0.514, 95%CI 0.443?0.597), PhA (OR=0.195, 95%CI 0.126?0.303), hemoglobin (OR=0.984, 95%CI 0.972?0.996) and triacylglycerol (OR=0.606, 95%CI 0.424?0.866) were negatively correlated with the risk of muscle mass decline in the elderly. Multivariate Logistic regression model indicated that PhA (OR=0.338, 95%CI 0.119?0.959) and BMI (OR=0.634, 95%CI 0.476?0.844) were negatively correlated with the risk of muscle mass decline in elderly. The area under the ROC curve for predicting muscle mass decline related to sarcopenia in elderly by using BMI and PhA was 0.893 (95%CI 0.855?0.931) and 0.786 (95%CI 0.736?0.837), respectively. The sensitivity was 0.724 and 0.676, respectively. The specificity was 0.916 and 0.762, respectively. When BMI combined with PhA predicted muscle mass decline in the elderly, the area under the ROC curve was 0.917 (95%CI 0.883?0.951). The sensitivity was 0.867, and the specificity was 0.860. Conclusion ·aCCI is correlated with muscle mass decline associated with sarcopenia in the elderly. As BMI and PhA decrease, the risk of muscle mass decline in the elderly increases. The combination of BMI and PhA has a high predictive value in muscle mass decline in the elderly.No predictive value of chronic diseases comorbidities in muscle mass decline related to sarcopenia in the elderly is found.

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    Establishment and evaluation of nomogram for differential diagnosis of systemic lupus erythematosus based on laboratory indications
    YANG Jingyu, CHEN Liubao, WANG Kangtai, YANG Xingzhi, YU Haitao
    Journal of Shanghai Jiao Tong University (Medical Science)    2024, 44 (2): 204-211.   DOI: 10.3969/j.issn.1674-8115.2024.02.006
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    Objective ·To establish a nomogram for the differential diagnosis of early systemic lupus erythematosus (SLE) and other autoimmune diseases based on laboratory indications, and to evaluate its efficacy. Methods ·A total of 535 SLE patients admitted to the First Hospital of Lanzhou University from January 2017 to December 2021 were selected as SLE group, and 535 patients with other autoimmune diseases during the same period were selected as control group. Basic information and laboratory test indicators of the SLE group and control group were collected and compared. The SLE group and control group were randomly assigned to the training set and the validation set at a ratio of 7∶3, respectively. LASSO regression method and multivariate Logistic regression were used to select the main risk factors of SLE. The nomogram for differential diagnosis of early SLE (SLE nomogram) was established according to the selected main risk factors. Bootstrap method was used to conduct internal repeated sampling for 1 000 times to calibrate the nomogram. The receiver operator characteristic curve (ROC curve) and decision curve analysis (DCA) were performed to evaluate the differential diagnosis ability and the value in clinical application of SLE nomogram, respectively. The "DynNom" package of R language was used to convert the nomogram into an electronic calculator, and its consistency with SLE nomogram was verified by data from 3 groups of patients. Results ·LASSO regression and multivariate Logistic regression identified six major risk factors for SLE, including antinuclear antibody (ANA), anti-double-stranded DNA (anti-dsDNA) antibody, anti-ribonucleoprotein antibody/anti-Simth antibody (anti-nRNP/Sm), anti-ribosomal P protein (anti-P) antibody, anti-nucleosome antibody (ANuA) and urinary protein (PRO), which were used to construct the SLE nomogram. The calibration curve of the SLE nomogram had standard errors of 0.009 and 0.015 in the training set and validation set, respectively, and its area under the curve (AUC) was 0.889 and 0.869, respectively. The results of DCA showed that when the risk threshold of SLE nomogram was 0.15?0.95, the model achieved more net benefit. The prediction results of the electronic calculator showed that when ANA (titer 1∶100) was positive in SLE patient No.1, the prevalence was 0.166; when both ANA (titer 1∶100) and ANuA (titer 1∶100) were positive in patient No.2, the prevalence was 0.676; when all of PRO, ANA (titer 1∶100), ANuA (titer 1∶100) and anti-P antibody (titer 1∶100) were positive in patient No.3, the prevalence was 0.990, which was consistent with the differential diagnosis results of the SLE nomogram. Conclusion ·The established SLE nomogram based on ANA, anti-dsDNA antibody, anti-nRNP/Sm, anti-P antibody, ANuA and PRO and its conversion into an electronic calculator can effectively distinguish early SLE from other autoimmune diseases, and have important clinical application value.

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    Study of metabolic association between elevated fasting blood glucose and cognitive deterioration
    WU Lirong, CHEN Ruihua, CHAO Xiaowen, GUO Yuhuai, SUN Tao, LI Mengci, CHEN Tianlu
    Journal of Shanghai Jiao Tong University (Medical Science)    2024, 44 (2): 212-222.   DOI: 10.3969/j.issn.1674-8115.2024.02.007
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    Objective ·To analyze and explore the influencing factors that lead to cognitive deterioration in individuals with elevated fasting blood glucose (FBG) and the metabolic clues associated with changes in the risk of cognitive deterioration. Methods ·Data from the Alzheimer's Disease Neuroimaging Initiative (ADNI) database were downloaded, and the samples with FBG and follow-up data were selected from the database. Clinical information, including age, gender, body mass index, education years, apolipoprotein E4 (APOE4) genotype and race, and corresponding metabolic indicator data, including amino acids, fatty acids, proteins and others were obtained. Based on the FBG levels and diagnosis of cognitive impairment stages in Alzheimer's disease, the subjects were categorized into four groups: normal FBG without/with cognitive deterioration, and elevated FBG without/with cognitive deterioration. The univariate analysis method, the Cox proportional hazards model, orthogonal projections to latent structures discriminant analysis (OPLSDA), and Spearman correlation analysis were employed for data analysis. Results ·A total of 1 317 subjects were included, among which 1 153 had normal FBG level (>3.9 mmol/L and <6.1 mmol/L) and 164 had elevated FBG level (≥6.1 mmol/L). In the normal FBG group, 275 subjects showed cognitive deterioration, while in the elevated FBG group, 53 subjects showed cognitive deterioration. Univariate analysis revealed significant differences in gender and race between the normal FBG and elevated FBG group, and significant differences in age, gender, and APOE4 genotype between the groups with and without cognitive deterioration (all P<0.05). Cox regression analysis indicated that primary influencing factors for cognitive deterioration were APOE4 positivity, elevated FBG, and increasing age in order (HR=2.22,HR=1.38,HR=1.02; all P<0.05). In the analysis of baseline metabolic indicators in the groups without and with cognitive deterioration, as well as metabolic indicators before and after cognitive deterioration at different FBG levels, the results of the analysis of variance revealed that in the cognitively deteriorated population, the ratio of phospholipids carried by high-density lipoproteins (HDL) to total lipids was significantly higher; low-density lipoprotein (LDL) particle concentration and the lipids carried by LDL were significantly higher after cognitive deterioration. Correlation analysis showed that valine and leucine were significantly correlated not only with FBG level but also with phosphorylated tau (pTau) level in the plasma in the cognitively deteriorated population. Cholesterol and the ratio of phospholipids to total lipids carried by HDL were significantly correlated with pTau levels in cerebrospinal fluid (CSF). Conclusion ·Compared to the individuals with normal FBG level, those with high FBG level have a significantly higher risk of cognitive deterioration. Additionally, different metabolic indicators show significant differences between the groups without and with cognitive deterioration, as well as metabolic indicators before and after cognitive deterioration at different FBG levels. Overall, LDL and its lipid content, and HDL-carried phospholipids show an increasing trend during cognitive deterioration, and the branched-chain amino acids valine and leucine are significantly correlated with pTau levels in CSF and plasma, suggesting that these metabolic markers may play an important role in cognitive deterioration.

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    Efficacy and safety of hypertonic dextrose prolotherapy for patients with post-herpetic neuralgia
    YIN Qin, CHEN Liping, XU Heng, YUAN Yan, LIANG Dong, SHEN Wen
    Journal of Shanghai Jiao Tong University (Medical Science)    2024, 44 (2): 223-227.   DOI: 10.3969/j.issn.1674-8115.2024.02.008
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    Objective ·To investigate the efficacy and safety of hypertonic dextrose prolotherapy (DPT) in the treatment of postherpetic neuralgia. Methods ·Seventy-eight patients with postherpetic neuralgia who visited the Department of Pain of The Affiliated Hospital of Xuzhou Medical University from June 2019 to December 2022 were selected. The patients were randomly assigned to a control group and a research group in a 1∶1 ratio, with 39 patients in each group. The control group was treated with traditional analgesic solution, while the research group was treated with traditional analgesic solution combined with DPT. Visual analog scale (VAS) was used to evaluate the patients' pain level before and after treatment, flow cytometry was used to measure the patients' T-cell subsets, and enzyme-linked immunosorbent assay (ELISA) was used to measure the levels of C-reactive protein (CRP), interleukin-6 (IL-6), and IL-10 cytokines. The VAS scores were compared between the two groups of patients before and at 1, 2, 4, 8, and 12 weeks after treatment. CD4+/CD8+, CRP, IL-6, IL-10 levels, and the incidence of adverse reactions before and 2 weeks after treatment were compared between the two groups. Results ·There was no statistically significant difference in sex ratio, age, and disease duration between the two groups of patients. The VAS scores of the two groups of patients at 1, 2, 4, 8, and 12 weeks after treatment were significantly lower than those before treatment, and the differences were statistically significant (all P<0.05). The VAS scores of the research group at 1, 2, 4, 8, and 12 weeks after treatment were significantly lower than those of the control group (all P<0.05). There was no statistically significant difference in basal CD4+/CD8+, CRP, IL-6 and IL-10 levels between the two groups of patients. IL-6 and CRP levels in the research group were significantly lower after treatment than those in the control group, and the differences were statistically significant (all P=0.000). CD4+/CD8+ and IL-10 levels were significantly higher in the research group than those in the control group after treatment, and the difference was statistically significant (all P=0.000). No adverse reactions such as local nerve damage, epidural hematoma, infection, pneumothorax or allergy occurred in both groups of patients during the treatment. Conclusion ·DPT can significantly reduce the pain of PHN patients, improve patients' T lymphocyte subpopulations and cytokine expression, and can be safely applied to the clinic.

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    Application of continuous nursing based on EMS management mode in preschool children with wheezing diseases
    JIANG Yunli, LI Aiqiu, XIAO Yanshang, LI Tiantian, HU Yachen, ZHANG Xiaoxiao, WU Beirong
    Journal of Shanghai Jiao Tong University (Medical Science)    2024, 44 (2): 228-236.   DOI: 10.3969/j.issn.1674-8115.2024.02.009
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    Objective ·To explore the effect of continuous nursing based on EMS [environment management (E), medicine direction (M) and self monitoring (S)] management mode on the preschool children with asthmatic diseases. Methods ·A total of 67 children aged 0 to 6 years with asthmatic diseases admitted to the Department of Respiratory Medicine, Shanghai Children's Hospital, Shanghai Jiao Tong University School of Medicine from December 2019 to November 2020 were selected and divided into observation group (33 cases) and control group (34 cases) according to the random number table method, with 3 cases lost, and finally 32 cases in each group. The observation group received continuous nursing care based on EMS management mode, while the control group received routine care and discharge follow-up through the telephone. The children in the two groups were followed up at 1, 3, and 6 months after discharge to evaluate the results of Test for Respiratory and Asthma Control in Kids (TRACK) and wheezing recurrence; Medication Adherence Report Scale for Asthma (MARS-A) and Nursing Job Satisfaction Questionnaire were used to evaluate medication adherence and nursing job satisfaction 6 months after discharge. Results ·There was no significant difference in demographic characteristics and clinical baseline characteristics between the two groups. Repeated measures analysis of variance showed that effects of time, groups and the interaction of groups×time on the total score of TRACK were statistically significant. The total scores of TRACK in the observation group were significantly higher than those in the control group at 1, 3, and 6 months after discharge (P=0.000). The total scores of TRACK in the two groups gradually increased with time (P=0.000). The recurrence rates of wheezing in the observation group were 25.0%, 18.7%, and 9.4% at 1, 3, and 6 months after discharge, which were significantly lower than those in the control group (50.0%, 43.7%, and 31.3%, respectively, P<0.05). Generalized estimating equation analysis showed that there was a statistically significant difference between the two groups (P=0.013), and the intervention effect of the observation group was better than that of the control group (OR=0.292). The MARS-A score of the observation group was 4.519±0.395 at 6 months after discharge, which was significantly higher than that of the control group (3.994±0.739, P=0.001). The nursing job satisfaction of the observation group was significantly higher than that of the control group (P=0.000). There was a moderate positive correlation between the MARS-A score and the nursing job satisfaction (r=0.389, P=0.001). Conclusion ·Continuous nursing based on EMS management mode can significantly improve the medication compliance and wheezing control level of the preschool children with asthmatic diseases, significantly reduce the recurrence rate of wheezing, and improve the nursing satisfaction.

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    Quality assessment of global obstructive sleep apnea guidelines
    GAO Yiqing, PENG Yu, XU Huajun, YI Hongliang, GUAN Jian, YIN Shankai
    Journal of Shanghai Jiao Tong University (Medical Science)    2024, 44 (2): 237-249.   DOI: 10.3969/j.issn.1674-8115.2024.02.010
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    Objective ·To evaluate the quality of clinical practice guidelines of obstructive sleep apnea (OSA) published worldwide. Methods ·The guidelines of OSA were retrieved in PubMed, Embase, China National Knowledge Infrastructure (CNKI), Wanfang Data, SinoMed, MedSci, The Cochrane Library, and the websites such as Medlive, U. S. Preventive Services Task Force (USPSTF), National Institute for Health and Care Excellence (NICE), New Zealand Guidelines Group (NZGG), Scottish Intercollegiate Guidelines Network (SIGN), and Guidelines International Network (GIN) from establishment to December 2022. Two reviewers screened the literature and extracted the main information independently, using the Appraisal of Guidelines for Research and Evaluation Ⅱ (AGREE Ⅱ) and Reporting Items for Practice Guidelines in Healthcare (RIGHT) to evaluate the quality of the included OSA guidelines. Subgroup analysis was performed according to the publication regions of guidelines. The inter-evaluator consistency test was also performed and the results were expressed as the intra-class correlation coefficient (ICC). All the included guidelines were read entirely and the clinical questions they raised were summarized. Results ·A total of 35 OSA guidelines were included. The ICC value of 0.975 showed a good inter-evaluator agreement. The results of AGREE Ⅱ showed that the average score of all guidelines was (63.60±16.45)%, with a minimum of 23.40% and a maximum of 91.67%. In the six domains, the scores of "Rigor of development" [(56.07±25.89)%] and "Applicability" [(53.57±15.52)%] were relative low. The average reporting rate of RIGHT of all the included guidelines was (67.84±20.03)%, with a minimum of 14.29% and a maximum of 94.29%, and the three domains with the lowest reporting rates were "Review and quality assurance" [(31.40±45.51)%], "Funding and conflict of interest declaration and management" [(56.43±33.95)%] and "Other aspects" [(56.19±36.85)%]. Subgroup analysis showed that guidelines in Asian had a lower score in "Rigor of development" and a lower overall score of AGREE Ⅱ than the guidelines in America and Europe (both P<0.05), and the reporting rates in the domains of "Evidence" and "Other information" of RIGHT of the Asian guidelines were also lower than those in the guidelines in America and Europe (P<0.05). These guidelines focused on 42 clinical questions which were classified to 3 aspects, i.e. screening and diagnosis, treatment and long-term management of OSA. Conclusion ·The quality of current global OSA guidelines varies a lot, and they need to be strengthened in terms of rigor of development, applicability, review and quality assurance, funding and conflict of interest declaration and management, especially those in Asia.

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    Association between body mass index and chronic metabolic diseases in Chinese aged population
    JIANG Ying, LI Qingyao, CHEN Zhiqi, WANG Jialu, LI Yun, XU Renying
    Journal of Shanghai Jiao Tong University (Medical Science)    2024, 44 (2): 250-257.   DOI: 10.3969/j.issn.1674-8115.2024.02.011
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    Objective ·To evaluate the relationship between body mass index (BMI) and chronic metabolic diseases. Methods ·The elderly (≥60 years old) who were underwent physical examination in the Physical Examination Center of Renji Hospital, Shanghai Jiao Tong University School of Medicine from 2014 to 2021 were studied. Their results of biochemical indicators were collected. Their height, body weight, and blood pressure were measured by trained nurses. The history of chronic metabolic diseases was collected by self-reported questionnaire. Systolic blood pressure ≥140 mmHg (1 mmHg=0.133 kPa), diastolic blood pressure ≥90 mmHg, or self-reported hypertension history was defined as hypertension. Fasting blood glucose ≥7.0 mmol/L or self-reported history of diabetes was defined as diabetes. Total cholesterol≥6.2 mmol/L, triglyceride≥2.3 mmol/L, or self-reported history of dyslipidemia was defined as dyslipidemia. The relationship between BMI and hypertension, diabetes, and dyslipidemia was evaluated by using receiver operator characteristic (ROC) curve analysis and binary logistic regression. Results ·Data of 59 083 subjects were collected [30 807 men and 28 276 women, average age: (67.9±6.3) years old]. The prevalence of hypertension, diabetes and dyslipidemia was 76.5% (45 219/59 083), 24.1% (14 225/59 083) and 50.0% (29 544/59 083), respectively. Compared to the elderly people aged 60?74 years, those aged 75 years and above had a higher proportion of hypertension and diabetes, and a lower proportion of dyslipidemia and no metabolic abnormalities. With ROC analysis, the BMI cut-off values for hypertension, diabetes, and dyslipidemia were 24.3, 23.9, and 23.9 kg/m2. The BMI cut-off values for hypertension and diabetes in elderly men were similar to those in elderly women (for hypertension: 24.3 kg/m2 in elderly men vs 24.2 kg/m2 in elderly women; for diabetes: 24.0 kg/m2 in elderly men vs 23.7 kg/m2 in elderly women); however, BMI cut-off value for dyslipidemia was obviously higher in elderly men than that in elderly women (24.0 kg/m2 in elderly men vs 22.5 kg/m2 in elderly women). The BMI cut-off value for chronic metabolic diseases was higher in the elderly people aged 60?74 years than that in the elderly people aged 75 years and above (24.2?24.7 kg/m2vs 22.9?23.8 kg/m2). Conclusion ·Elderly people aged 60?74 years should maintain the BMI below 24.0 kg/m2, while those aged 75 years and above should aim for the BMI below 23.0 kg/m2, so as to reduce the risk of chronic metabolic diseases.

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    Research progress of neuromodulation in the treatment of Parkinson 's disease
    HU Canfang, ZHONG Chuanyu, CAO Li
    Journal of Shanghai Jiao Tong University (Medical Science)    2024, 44 (2): 258-263.   DOI: 10.3969/j.issn.1674-8115.2024.02.012
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    Parkinson's disease (PD) is a common degenerative neurological disorder, characterized by static tremor, bradykinesia, myotonia and postural abnormalities. Dopaminergic drugs are the main drugs in the treatment of PD, but long-term use will lead to drug efficacy loss, and even cause some adverse reactions such as dyskinesia and "on-off" phenomenon. Neuromodulation is a kind of biomedical engineering technology that can stimulate or inhibit the activity of brain neurons and regulate the changes of neuroplasticity by means of electric energy, magnetic field, ultrasound and other methods, so as to achieve treatment and improvement of diseases. In the non-drug treatment of PD, neuromodulation, as a new therapeutic means, has shown good efficacy, and has the advantages of small adverse reactions and easy tolerance. Based on this, this article reviews the research progress of several common neuromodulation in PD, including deep brain stimulation, transcranial magnetic stimulation, transcranial direct current stimulation and transcranial focused ultrasound.

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    Research progress in targeted therapies of chronic lymphocytic leukemia
    DING Yanling, LI Jie, YUAN Jun, LI Yan
    Journal of Shanghai Jiao Tong University (Medical Science)    2024, 44 (2): 264-270.   DOI: 10.3969/j.issn.1674-8115.2024.02.013
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    Chronic lymphocytic leukemia (CLL) is one of small B-cell lymphomas and leukemias, characterized as a clonal disease of mature B cells. The disease is remarkably heterogeneous, with the majority of patients having an indolent course, yet they are currently incurable. Abnormal signaling pathways are indispensable in the pathogenesis of CLL. In CLL, the common abnormalities of signaling pathways include B-cell receptor (BCR) signaling, apoptosis, nuclear factor kappa B (NF-κB) signaling and Notch signaling. According to the target in signaling pathways, a series of targeted drugs, such as Bruton's tyrosine kinase (BTK) inhibitors (ibrutinib, zanubrutinib), phosphorylate phosphoinositide 3-kinase (PI3K) inhibitor (duvelisib) and B-cell leukemia/lymphoma 2 (BCL2) inhibitor (venetoclax), which have significantly changed the prognosis of patients in clinic. Other targeted drugs, such as fenebrutinib, nemtabrutinib and umbralisib, as well as chimeric antigen receptor T-cell (CAR-T) therapy developed in the field of immuno-oncology and T cell engineering, are currently under trial, with more personalized treatment modalities being explored, which may become potential drug targets in the future. In this paper, relevant literature of CLL was reviewed, and recent research progress in molecular pathogenesis and targeted therapies of chronic lymphocytic leukemia was reviewed.

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    Progress of research on m 6A demethylases in gastric cancer
    JIANG Shuang, YU Jiwei
    Journal of Shanghai Jiao Tong University (Medical Science)    2024, 44 (2): 271-277.   DOI: 10.3969/j.issn.1674-8115.2024.02.014
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    Gastric cancer (GC) is one of the most common malignancies in the digestive system. Many patients are found in advanced stage and have a poor prognosis. Surgery and chemotherapy remain the main treatments for gastric cancer. N6-methyladenosine (m6A) is a hot topic in tumor research in recent years. As the most common form of RNA modification in eukaryotes, m6A can regulate various stages of the RNA cycle, including RNA splicing, processing, degradation, and translation, thereby regulating RNA expression and function, playing a critical role in various pathways such as cell differentiation, development, and metabolism. The m6A demethylase can remove methyl groups on RNA, ensuring that m6A methylation is a dynamic and reversible process. As a key enzyme in the m6A methylation process, the imbalance of m6A demethylases fat mass and obesity-associated protein (FTO), AlkB homolog 5 (ALKBH5) and ALKBH3 regulate the progression of gastric cancer through various mechanisms, which is closely related to the occurrence and development of gastric cancer. These m6A demethylases regulate the signaling pathway, alter the proliferation and invasion ability of gastric cancer cells, affect its resistance to chemotherapy drugs, participate in regulating the immune response and mitochondrial metabolism of gastric cancer, and affect the growth of gastric cancer cells. They are expected to become a novel therapeutic target. This article comprehensively summarizes the molecular mechanism of m6A demethylase involved in the occurrence and development of gastric cancer, and the relationship between its expression and function, and biological characteristics of m6A demethylase were reviewed, aiming to provide new research ideas for early diagnosis and targeted treatment of gastric cancer.

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    Systemic lupus erythematosus complicated with pure red cell aplasia: a case report and literature review
    CHEN Qiong, FANG Jie, WEI Qianghua
    Journal of Shanghai Jiao Tong University (Medical Science)    2024, 44 (2): 278-286.   DOI: 10.3969/j.issn.1674-8115.2024.02.015
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    This article reports a single case of a patient with systemic lupus erythematosus (SLE) combined with pure red cell aplasia (PRCA), and reviews 51 additional cases of patients reported by domestic and overseas papers from 1974 to 2021. These 52 (51+1) cases were analyzed to summarize the epidemiological features, clinical features, laboratory inspections, treatments and prognosis of the patients. The results indicated that among all the 52 cases, cases of SLE combined with PRCA were mostly seen in Asian childbearing age women. The median ages of patients diagnosed with SLE and diagnosed with PRCA were 31.5 years and 36.0 years, respectively. The time interval between the initial diagnosis of SLE and subsequent diagnosis of PRCA was significantly longer than the interval for the initial diagnosis of PRCA, suggesting a delayed onset of SLE in these patients (P=0.042). Various clinical features of the 52 patients were reported, including mostly fatigue, joint pains, Raynaud phenomena and rashes, and SLE maybe combined with autoimmune hemolytic anemia (AIHA), thymoma, hypothyroidism and myasthenia gravis (MG). In these reported cases, laboratory indicators showed higher proportions of antinuclear antibody (ANA), anti double stranded DNA antibody (anti-dsDNA antibody), positive urinary protein and low complement levels. Among the 52 patients, 51 cases (98.08%) were treated with glucocorticoids, followed by blood transfusion, cyclosporin A, cyclophosphamide and high-dose intravenous immunoglobulin. Of the 50 patients whose prognoses were reported, 44 showed improvement, while 3 treatments were not effective and 3 resulted in death. This article aims to enhance the understanding of SLE combined with PRCA among doctors.

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    A case of chronic myelomonocytic leukemia complicated with immune thrombocytopenia
    LIU Jiayu, HUANG Fang, HAO Siguo
    Journal of Shanghai Jiao Tong University (Medical Science)    2024, 44 (2): 287-290.   DOI: 10.3969/j.issn.1674-8115.2024.02.016
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    Chronic myelomonocytic leukemia (CMML) complicated with immune thrombocytopenia (ITP) is rare. This article reports the clinical data of a patient with CMML complicated with ITP treated with a combination of venetoclax, ripertamab (an anti-CD20 monoclonal antibody), and hetrombopag. The coexistence mechanism of CMML and ITP needs to be further clarified. Venetoclax combined with anti-CD20 monoclonal antibody and thrombopoietin receptor agonist may be an effective strategy for the treatment of this complication.

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    Adaptation and adaptability survey of the RUBI-PT program for autism spectrum disorders
    LÜ Na, ZHANG Lingli, REN Fang, YANG Hanshu, LI Fei, XU Mingyu
    Journal of Shanghai Jiao Tong University (Medical Science)    2024, 44 (3): 291-300.   DOI: 10.3969/j.issn.1674-8115.2024.03.001
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    Objective ·To explore the adaptation and adaptability of RUBI-PT (the Research Units in Behavioral Intervention Autism Network Parent Training) program in China. Methods ·According to the four steps of cultural adaptation, the RUBI-PT program was adapted, including information collection, preliminary adaptation design, preliminary adaptation test and further adjustment. In the information collection phase, six pediatricians and two psychotherapists were invited to conduct six focus group interviews, and according to the expert opinions, the RUBI-PT program was preliminarily adapted from the aspects of language, treatment format and treatment setting. In the preliminary adaptation test phase, 16 parents of autism spectrum disorder (ASD) children were recruited and divided into two batches to participate in the online RUBI-PT. After the treatment, the project feedback questionnaires were collected, and the adaptability was investigated and analyzed. Finally, the scheme was further adjusted according to the test results. Results ·The preliminary adaptation program of RUBI-PT was adjusted from individual training to group training, including eight core skills sessions, which were implemented in the form of online meetings. The preliminary test results showed that parents′ satisfaction with lesson progress, lesson process, completion of homework and comments to homework were 90%, 80%, 100% and 100%, respectively; in terms of the course difficulty, parents reported that the 7th session (functional communication training) and the 8th session (teaching skills) were the most difficult. Based on the above survey results and the opinions of the expert group, further adjustments were completed, and an adaptation program for localized RUBI-PT was ultimately formed. Conclusion ·After adaptation and adaptability investigation, the RUBI-PT, which is suitable for Chinese families with ASD children to conduct behavioral parent training, has been formed.

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    Exploratory study of interferon regulatory factor 3 promoting proliferation and invasion related to colorectal cancer cells
    XU Wenhui, YANG Chang, LI Ruiqing, BIAN Jing, LI Xiayi, ZHENG Leizhen
    Journal of Shanghai Jiao Tong University (Medical Science)    2024, 44 (3): 301-311.   DOI: 10.3969/j.issn.1674-8115.2024.03.002
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    Objective ·To analyze the relationship between the expression level of interferon regulatory factor 3 (IRF3) in colorectal cancer and its clinicopathological features and prognosis, and to observe the effects of IRF3 overexpression on the proliferation and invasion ability of colorectal cancer cells and the related protein molecular pathways. Methods The Cancer Genome Atlas (TCGA) data were downloaded and used to analyze the correlation between expression levels of IRF3 and the prognosis of patients (including renal cell carcinoma, colorectal cancer, hepatocellular carcinoma, and prostate cancer). Immunohistochemistry was used to detect the differences in the expression levels of IRF3 between cancerous tissue and adjacent normal tissues of 10 patients with colorectal/renal cancer. The C-terminal residue sites of the IRF3 protein were modified to construct HEK-293T cells overexpressing the phosphorylated IRF3-5D (396/398/402/404/405-D). At 12 and 24 h of cell culture, treatment with TANK-binding kinase 1 (TBK1) inhibitor was performed, and Western blotting was used to detect the expression levels of IRF3 and p-IRF3 (Ser386) in the cells. RNA sequencing (RNA-seq) was employed to explore the correlation between high expression of IRF3-5D and the expression levels of tumor-related proteins. Colorectal cancer cells CT26 and COLON26 overexpressing wild-type IRF3 (IRF3-WT) and IRF3-5D were construct, and cell proliferation and migration ability were assessed by using cell counting, scratch assay, and clonogenic assay. Results ·Analysis of TCGA data suggested that the expression level of IRF3 protein in cancer tissues was positively correlated with poor prognosis in patients. Immunohistochemical analysis of pathological tissues from patients with cancer showed that the expression level of IRF3 was significantly upregulated in colorectal cancer tissues and renal cancer tissues, with protein expression concentrated in the cell nucleus. After treatment with TBK1 inhibitors for 12 and 24 h in cell culture, the expression of p-IRF3 (Ser386) protein in HEK-293T cells decreased. The results of RNA-seq and Western blotting showed that the expression levels of multiple proteins associated with poor prognosis [such as IRF9, programmed cell death 1-ligand 1 (PD-L1), etc.] were significantly upregulated under conditions of high expression of IRF3-5D. Overexpression of IRF3-5D in colorectal cancer cells could significantly enhance the proliferation and migration capabilities of cancer cells. Conclusion ·The expression level of IRF3 in colorectal cancer is positively correlated with poor patient prognosis. High expression of IRF3-5D protein in colorectal cancer cells can promote malignant biological behavior of cancer cells. Additionally, IRF3-5D is dependent on the TBK1-mediated activation of the IRF3 activation pathway and upregulates the expression levels of multiple tumor-related proteins.

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    Expression and clinical significance of geranylgeranyl diphosphate synthase1 (GGPS1) in lung squamous cell carcinoma
    WANG Xin, WANG Xiaoxia, LI Yanqing, ZHENG Yongxin, WU Jie, REN Meng, JIA Xiangdong, XU Tianxiang
    Journal of Shanghai Jiao Tong University (Medical Science)    2024, 44 (3): 312-324.   DOI: 10.3969/j.issn.1674-8115.2024.03.003
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    Objective ·To investigate the expression and clinical significance of geranylgeranyl diphosphate synthase1 (GGPS1) in lung squamous cell carcinoma (LUSC) by bioinformatics and immunohistochemistry. Methods ·Firstly, the transcriptome data of LUSC tissues and paired normal tissues were downloaded from UCSC Xena platform. The data were standardized and differentially expressed by R language, and verified by UALCAN database. UALCAN and LinkedOmics databases were used to analyze the relationship between GGPS1 expression and clinicopathological features in LUSC patients. The Kaplan-Meier Plotter database was used to explore the effect of GGPS1 expression on prognosis in LUSC patients. The least absolute shrinkage and selection operator (LASSO) regression analyses were applied to screen gene correlation coefficients and risk scores. The diagnostic value of GGPS1 for LUSC was evaluated by nomogram and calibration curve. The protein-protein interaction (PPI) network of GGPS1 was constructed by using STRING and GeneMANIA databases. R language was used to select the differential genes related to GGPS1, and Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analysis were performed. The expression of GGPS1 in LUSC patients was detected by immunohistochemistry, and its correlation with clinicopathological features and prognosis was analyzed. Results ·Through the TIMER2.0 database, it was found that GGPS1 expression was increased in most tumors and was highly expressed in LUSC. The expression of GGPS1 in LUSC was higher than that in adjacent tissues in UCSC Xena and UALCAN databases (both P<0.05). It was found that the expression level of GGPS1 was higher in patients with late stage in UALCAN and LinkedOmics databases, and the overall survival (OS) of LUSC patients with high expression of GGPS1 was shorter (P<0.05) in the Kaplan-Meier Plotter database. Assessment of LUSC patients based on LASSO regression had good risk prediction efficacy. Constructing an individualised prediction model for LUSC patients has the best prediction accuracy. The results of GO and KEGG showed that GGPS1-related genes were mainly related to protein metabolism, regulation of lipid and cholesterol metabolism, nicotine addiction, phosphatidylinositol3-kinase (PI3K)/protein kinase B (AKT)/mammalian target of rapamycin (mTOR), peroxisome proliferator-activated receptors (PPAR) signaling pathway and so on. The metabolic function of GGPS1 may promote tumorigenesis. The results of immunohistochemistry showed that GGPS1 was mainly located in the cytoplasm, and the expression of GGPS1 in LUSC tissues was higher than that in adjacent tissues (P<0.05). The high expression of GGPS1 was related to tumor size, lymph node metastasis and TNM stage of LUSC patients (all P<0.05), and the OS of patients with high expression of GGPS1 was significantly shorter than that of patients with low expression (P=0.000). Multivariate Cox regression analysis suggested that GGPS 1 could be used as an independent prognostic factor for LUSC. Conclusion ·Compared with normal lung tissue, the expression of GGPS1 in LUSC is significantly increased, especially in patients with large tumor volume, positive lymph node metastasis and advanced stage. GGPS1 overexpression is an independent predictor of poor prognosis in LUSC patients. GGPS1 is expected to become a new molecular target for the diagnosis, treatment and prevention of LUSC.

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    Study on the mechanism of trimethylamine oxide damaging cardiac function in mice with hypertrophic cardiomyopathy
    JIN Bu, CHEN Hanzhang, XU Hudong, CHEN Wanyu, YUAN Ying, ZHAO Tingting, HUANG Xiaolei, HE Jialu, YU Hong
    Journal of Shanghai Jiao Tong University (Medical Science)    2024, 44 (3): 325-333.   DOI: 10.3969/j.issn.1674-8115.2024.03.004
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    Objective ·To investigate the effects of trimethylamine oxide (TMAO) on cardiac function in mice with hypertrophic cardiomyopathy (HCM) and its potential molecular mechanism. Methods ·Mice with myosin heavy chain 6 (Myh6) c.1211G>A (p.R404Q+/-) point mutation were used as the animal model. According to dietary supplementation of TMAO and TMAO inhibitor iodomethylcholine (IMC), the wild type (WT) mice and HCM mice were divided into WT group, HCM group (HCM-1 group, HCM-2 group), WT+TMAO group, HCM+TMAO group and HCM+IMC group, respectively. Left ventricular fraction shortening (FS) and left ventricular posterior wall thickness (LVPW) were assessed by echocardiography in all mice. Enzyme-linked immunosorbent assay (ELISA) was used to detect the serum TMAO concentration of mice in the HCM-1 group and WT group. The regularity of myocardial cell arrangement of mice was evaluated by hematoxylin and eosin staining (HE staining). The proportion of myocardial fibrosis was evaluated by Masson staining. The activity of protein kinase A (PKA) in mouse myocardial tissue was detected by PKA kit. The expression of ryanodine receptor 2 (RyR2) and p-RyR2(S2808) in mouse myocardial tissue was detected by Western blotting. Results ·The results of echocardiography showed that at 12 months of age, the FS of mice in the WT+TMAO group and HCM+TMAO group were lower than those in the corresponding WT group and HCM-1 group, respectively (P<0.05). The LVPW of mice in the HCM+TMAO group was higher than that in the HCM-1 group, while the LVPW of mice in the HCM+IMC group was lower than that in the HCM-2 group (P<0.05). ELISA results showed that the serum TMAO concentration of mice in the HCM-1 group was higher than that in the WT mice (P<0.05). The results of HE staining and Masson staining showed that the HCM+TMAO group had a lower degree of regular arrangement of cardiomyocytes and a higher proportion of fibrosis than the HCM-1 group, while the HCM+IMC group had a higher degree of regular arrangement of cardiomyocytes and a lower proportion of fibrosis than the HCM-2 group (P<0.05). The results of PKA assay showed that the PKA activity in the myocardial tissue of mice in the WT+TMAO group and HCM+TMAO group increased after TMAO treatment, while the PKA activity in the myocardial tissue of mice in the HCM+IMC group decreased (P<0.05). Western blotting results showed that the expression of p-RyR2(S2808) in the myocardial tissue of the WT+TMAO group and HCM+TMAO group mice increased, while it was decreased in the HCM+IMC group mice (P<0.05); however, there was no difference in RyR2 expression among the groups. Conclusion ·TMAO can increase the activity of PKA and induce the phosphorylation of RyR2 at S2808, which can cause ventricular remodeling and impair cardiac function in HCM mice.

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    Predictive value of systemic immune inflammation index and somatic symptom scale -China in the occurrence of in -hospital major adverse cardiovascular events after first -episode of acute myocardial infarction undergoing PCI
    ZHENG Mengyi, MAO Jialiang, ZOU Zhiguo, ZHANG Ruilei, ZHANG Hou, LI Shiguang
    Journal of Shanghai Jiao Tong University (Medical Science)    2024, 44 (3): 334-341.   DOI: 10.3969/j.issn.1674-8115.2024.03.005
    Abstract72)   HTML12)    PDF(pc) (1904KB)(65)       Save

    Objective ·To investigate the predictive value of systemic inflammatory index (SII) and somatization symptom score-China (SSS-CN) for major adverse cardiovascular events (MACEs) in patients with first-episode acute myocardial infarction (AMI) undergoing percutaneous coronary intervention (PCI). Methods ·Three hundred and five first-episode AMI patients who received PCI treatment at the Cardiology Department of Anhui Second People's Hospital from September 2021 to September 2023 were included in the study. Enrolled patients were divided into MACEs group (n=203) and non-MACEs group (n=102) based on whether MACEs events occurred during hospitalization. Descriptive statistical analysis was performed on the general data such as gender, age and laboratory test results of the two groups of patients, and binary Logistic regression test was conducted for statistically significant items according to the analysis results. According to the results, receiver operating characteristic (ROC) curves were further drawn to evaluate the value of SII and SSS-CN in predicting the occurrence of MACEs in hospital. On this basis, coronary syntax score (SS) was combined to evaluate the predictive efficacy of the three combinations, and the optimal cut-off value was determined according to the maximum Jordan index. Results ·A total of 203 patients had MACEs events, among whom 179 (88.1%) had heart failure, 16 (7.9%) had severe arrhythmia, 4 (2.0%) had shock, 2 (1.0%) had recurrent myocardial infarction, and 2 (1.0%) died. Compared with the non-MACEs group, the SII and SSS-CN scores in the MACEs group were significantly increased (1 925.86 vs 934.23, 38.57 vs 23.30; both P<0.05). The binary Logistic results suggested that both SII and SSS-CN were independent risk factors for the occurrence of MACEs. The ROC curve results showed that the prediction efficiency was the best when SII ≥ 952, with a sensitivity of 64.0% and a specificity of 62.7% (AUC 0.675, 95% CI 0.612?0.737). The prediction efficiency was the best when SSS-CN ≥ 28.5, with a sensitivity of 80.7% and a specificity of 77.5% (AUC 0.840, 95% CI 0.794?0.886). The predictive performance was further improved after combining the syntax score (AUC 0.898, 95% CI 0.862?0.933). Conclusion ·The admission SII and SSS-CN scores of first-episode AMI patients are independent risk factors for the occurrence of MACEs during hospitalization after PCI. Early monitoring of SII changes in first-episode AMI patients after PCI or SSS-CN scores for patients with obvious Somatization symptoms can help identify high-risk patients for the occurrence of MACEs in the hospital.

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    Efficacy of smart wearable device BPMpathway in home rehabilitation of patients after total knee arthroplasty
    HONG Yang, WANG Jie, ZHANG Xiafen, ZHAO Dan, CHENG Min
    Journal of Shanghai Jiao Tong University (Medical Science)    2024, 44 (3): 342-349.   DOI: 10.3969/j.issn.1674-8115.2024.03.006
    Abstract119)   HTML9)    PDF(pc) (1443KB)(48)       Save

    Objective ·To evaluate the effectiveness of the tele-rehabilitation program based on the smart wearable device BPMpathway in patients after total knee arthroplasty (TKA). Methods ·Convenience sampling method was used to select patients with knee osteoarthritis after TKA admitted to both the Department of Orthopedics in the Fourth Affiliated Hospital of Soochow University (Suzhou Dushu Lake Hospital) and The First Affiliated Hospital of Soochow University, from April 2021 to December 2022, as the study population. According to the sequence of the patients′ admissions, patients with an odd hospitalization number were allocated to the control group while those with an even number to the intervention group. The control group received the routine home-based rehabilitation training program, while the intervention group was additionally subjected to the tele-rehabilitation program based on the BPMpathway. At baseline, and 1 month, 3 months and 6 months after TKA, the two groups of patients were evaluated by the compliance scale of functional exercise for orthopedic patients, the Hospital for Special Surgery Scale (HSS), and 36-item Short Form Health Survey (SF-36), while the knee joint motion of the patients was measured. Results ·One hundred and ten patients with knee osteoarthritis after TKA were finally enrolled, including 56 patients in the control group and 54 patients in the intervention group. There were no statistically significant differences in the general information between the two groups. The differences in knee range of motion, HSS score, and SF-36 score between the two groups at baseline were not statistically significant. Repeated measurement variance analysis showed that the between-group effect, time effect and interaction effect of knee range of motion, functional exercise compliance score, HSS score and SF-36 total score were statistically significant in both groups (all P<0.05). Meanwhile, knee range of motion, HSS score, functional exercise compliance score, and SF-36 score in the intervention group were significantly better than those in the control group at 1, 3, and 6 months after TKA (all P<0.05). Conclusion ·The tele-rehabilitation training program, conducted by healthcare providers using the smart wearable device BPMpathway, can enhance patients′ compliance with functional exercise during home rehabilitation after TKA. This leads to increased knee mobility, contributes to the recovery of knee function and improves quality of life of the patients. All of these factors have a positive effect on the patient prognosis.

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    Changes of serum high mobility group box 1 and soluble triggering receptor expressed on myeloid cells-1 in patients with multiple injuries and their prognostic significance
    WANG Guijie, DU Chuanchong, LU Ye, ZHAO Jian, SHEN Xie, JIN Donglin, GENG Jiacai
    Journal of Shanghai Jiao Tong University (Medical Science)    2024, 44 (3): 350-357.   DOI: 10.3969/j.issn.1674-8115.2024.03.007
    Abstract70)   HTML9)    PDF(pc) (1840KB)(35)       Save

    Objective ·To detect the serum levels of high mobility group box 1 (HMGB1) and soluble triggering receptor expressed on myeloid cells-1 (sTREM-1) in patients with multiple injuries at different time points, and to analyze their correlation with disease severity, complications and prognosis. Methods ·Ninety-two patients with multiple injuries admitted to the Department of Emergency Medicine of the Suzhou Ninth People′s Hospital from December 2020 to December 2022 were selected. According to the injury severity scores of the patients at admission, the patients were divided into light injury group (n=24), grave injury group (n=58) and severe injury group (n=10). According to whether there was multiple organ dysfunction syndrome (MODS) after admission, the patients were divided into MODS group (n=20) and non-MODS group (n=72). According to the outcome within 28 d after trauma, the patients were divided into death group (n=13) and survival group (n=79). Inflammatory factor indicators in venous blood of patients after admission were detected. Enzyme linked immunosorbent assay (ELISA) was used to detect the serum HMGB1 and sTREM-1 levels at 24 h, 72 h and 7 d after trauma, and the differences of serum HMGB1 and sTREM-1 levels among different groups were analyzed. Multiple Logistic regression was used to analyze the influencing factors of adverse outcomes in patients with multiple injuries. The receiver operating characteristic (ROC) curve was used to evaluate the predictive value of HMGB1 and sTREM-1 for adverse outcomes. Results ·The levels of HMGB1 and sTREM-1 in the grave injury and severe injury groups were significantly higher than those in the light injury group (P<0.05). The levels of HMGB1 at 72 h and 7 d, and sTREM-1 at 24 h and 72 h in the severe injury group were significantly higher than those in the grave injury group (P<0.05). There was a positive correlation between HMGB1 and sTREM-1 levels at various time points (r=0.645, r=0.942, r=0.722; all P<0.05). The levels of HMGB1 at 72 h and 7 d, and sTREM-1 at 24 h and 72 h in the MODS group were significantly higher than those in the non-MODS group (all P<0.05). The levels of HMGB1 at 72 h and 7 d, and sTREM-1 at 24 h and 72 h in the death group were significantly higher than those in the survival group (all P<0.05). Logistic regression analysis showed that HMGB1 at 7 d, admission time and hypersensitive C-reactive protein (hs-CRP) were independent factors of adverse outcomes in patients with multiple injuries (all P<0.05). The ROC curve showed that the area under the curve of HMGB1 for predicting poor prognosis at 7 days after trauma was 0.890, the sensitivity was 83.5%, and the specificity was 92.3%. Conclusion ·The levels of HMGB1 and sTREM-1 are correlated with MODS and survival outcomes in patients with multiple injuries at different time points after trauma, and HMGB1 at 7 d after trauma is an independent factor affecting adverse outcomes in patients with multiple injuries.

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    Relationship of screen time and dietary behaviors with depressive symptoms in junior high school students in five provinces in China
    YANG Ruijun, LÜ Shuhong, LIU Zhiye, ZHANG Xin, LIU Zhihao
    Journal of Shanghai Jiao Tong University (Medical Science)    2024, 44 (3): 358-364.   DOI: 10.3969/j.issn.1674-8115.2024.03.008
    Abstract91)   HTML7)    PDF(pc) (1355KB)(63)       Save

    Objective ·To explore the relationship of screen time and dietary behaviors with depressive symptoms in junior high school students in 5 provinces in China. Methods ·A total of 1 067 junior high school students were selected from Zhejiang and Guangdong in the eastern region, Jiangxi in the central region, Sichuan and Guizhou in the western region of China by using stratified random cluster sampling method for a questionnaire survey, which included general demographic characteristics, health behaviors, diatery behaviors, and depressive symptoms. Univariate analysis was used to analyze the report rates of depressive symptoms, daily screen time and dietary behaviors of the students with variant demographic characteristics, and Logistic regression analysis was used to analyze the relationship of daily screen time and dietary behaviors with depressive symptoms and the interaction effects as well. Results ·The report rate of depressive symptoms was 12.9% in the junior high school students in 5 provinces. The students who were in the western region, were not only children, had a weekly allowance of over 100 yuan, had smoked or consumed alcohol, had daily screen time≥2 h, or had unhealthy dietary behaviors, had higher reporting rates of depressive symptoms (P<0.05). A total of 15.2% students had daily screen time≥2 h, who had a higher reporting rate of depressive symptoms than the others after the confounding factors being adjusted (OR=1.89, 95%CI 1.22?2.95). A total of 29.5% of students had unhealthy dietary behaviors, who had a higher reporting rate of depressive symptoms than the others after the confounding factors being adjusted (OR=2.16, 95%CI 1.47?3.19). A total of 6.4% of students had both daily screen time≥2 h and unhealthy dietary behaviors, who had a higher reporting rate of depressive symptoms than the students having daily screen time<2 h and healthy dietary behaviors after the confounding factors being adjusted (OR=4.26, 95%CI 2.24?7.56). After adjusting for the confounding factors, the analysis of the interaction between daily screen time and dietary behaviors showed an additive interaction with the relative excess risk due to interaction (RERI) of 1.21 (95%CI 1.02?1.51), the attributable proportion due to interaction (AP) of 0.19 (95%CI 0.13?0.31), and the synergy index (S) of 1.35 (95%CI 1.12?1.69). Conclusion ·The junior high school students with both long screen time and unhealthy dietary behaviors are more likely to suffer from depressive symptoms in China; long screen time and unhealthy dietary behaviors have an additive interactive effect on depressive symptoms.

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