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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 Abstract （562）   HTML （41）    PDF（pc） （3051KB）（2332）       Knowledge map    Save 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) andBcl-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. Table and Figures | Reference | Related Articles | Metrics

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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 Abstract （302）   HTML （28）    PDF（pc） （4234KB）（437）       Knowledge map    Save 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. Table and Figures | Reference | Related Articles | Metrics

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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 Abstract （346）   HTML （38）    PDF（pc） （5561KB）（1778）       Knowledge map    Save 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. Table and Figures | Reference | Related Articles | Metrics

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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 Abstract （494）   HTML （21）    PDF（pc） （3448KB）（2156）       Knowledge map    Save 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. Table and Figures | Reference | Related Articles | Metrics

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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 Abstract （275）   HTML （16）    PDF（pc） （3405KB）（565）       Knowledge map    Save 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. Table and Figures | Reference | Related Articles | Metrics

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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 Abstract （338）   HTML （23）    PDF（pc） （4611KB）（1715）       Knowledge map    Save 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. Table and Figures | Reference | Related Articles | Metrics

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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 Abstract （497）   HTML （23）    PDF（pc） （2159KB）（782）       Knowledge map    Save 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. Table and Figures | Reference | Related Articles | Metrics

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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 Abstract （283）   HTML （18）    PDF（pc） （1929KB）（801）       Knowledge map    Save 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. Table and Figures | Reference | Related Articles | Metrics

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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 Abstract （402）   HTML （21）    PDF（pc） （2435KB）（415）       Knowledge map    Save 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. Table and Figures | Reference | Related Articles | Metrics

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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 Abstract （275）   HTML （19）    PDF（pc） （2051KB）（873）       Knowledge map    Save 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. Table and Figures | Reference | Related Articles | Metrics

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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 Abstract （420）   HTML （29）    PDF（pc） （2318KB）（2920）       Knowledge map    Save 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. Table and Figures | Reference | Related Articles | Metrics

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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 Abstract （417）   HTML （16）    PDF（pc） （1460KB）（1089）       Knowledge map    Save 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. Table and Figures | Reference | Related Articles | Metrics

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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 Abstract （348）   HTML （12）    PDF（pc） （1603KB）（405）       Knowledge map    Save 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. Table and Figures | Reference | Related Articles | Metrics

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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 Abstract （1010）   HTML （48）    PDF（pc） （2669KB）（1529）       Knowledge map    Save 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. Table and Figures | Reference | Related Articles | Metrics

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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 Abstract （388）   HTML （25）    PDF（pc） （1268KB）（1393）       Knowledge map    Save 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. Reference | Related Articles | Metrics

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Research progress of m6A 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 Abstract （786）   HTML （32）    PDF（pc） （1743KB）（1452）       Knowledge map    Save 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. Table and Figures | Reference | Related Articles | Metrics

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Compliance of oral nutritional supplements in postoperative patients with digestive tract cancer:an analysis based on COM-B model SU Liqing, ZHANG Jie, DOU Wenyue, LI Mengxue, ZHANG Yumeng, CHANG Jian Journal of Shanghai Jiao Tong University (Medical Science)    2024, 44 (10): 1213-1220.   DOI: 10.3969/j.issn.1674-8115.2024.10.001 Abstract （251）   HTML （12）    PDF（pc） （1574KB）（788）       Knowledge map    Save Objective ·To explore the influencing factors of oral nutritional supplement compliance in postoperative patients with digestive tract cancer based on COM-B model, and to analyze the mediating role of medication belief and self-efficacy in oral nutritional supplement. Methods ·A total of 300 postoperative gastrointestinal cancer patients were selected by convenience sampling method. The General Information Questionnaire, Morisky Medication Adherence Scale, Digestive Cancer Patients Nutrition Knowledge, Attitude and Practice Questionnaire, Multidimensional Scale of Perceived Social Support, Beliefs about Medicines Questionnaire and General Self-Efficacy Scale were used. A mediating effect model was used to analyze the influencing factors of compliance with oral nutritional supplements. Results ·The score of Morisky Medication Adherence scale was 1.61±1.38, which was at a low level. Oral nutritional supplement compliance was significantly positively correlated with nutrition knowledge, social support, medication belief and self-efficacy (r=0.391, 0.401, 0.438, 0.410, all P<0.01). Medication belief had a partial mediating effect between nutrition knowledge and adherence to oral nutritional supplements (effect size =0.097, accounting for 18.00% of the total effect). Self-efficacy had a partial mediating effect between nutrition knowledge and oral nutritional supplement compliance (effect size =0.044, accounting for 8.16% of the total effect). Self-efficacy had a partial mediating effect between social support and oral nutritional supplement compliance (effect size =0.044, accounting for 16.67% of the total effect). Conclusion ·The compliance of oral nutritional supplements in postoperative patients with gastrointestinal cancer is at a low level. The individualized nursing intervention can increase the nutritional knowledge of patients, improve the social support, reduce the concerns of patients about oral nutrition, and improve the self-efficacy of patients, so as to promote the compliance of patients with oral nutritional supplements. Table and Figures | Reference | Related Articles | Metrics

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Application of online courses combined with teach-back method to laryngectomy patients and family carers HUANG Jialu, LI Shan, ZHANG Caiyun, XU Fei Journal of Shanghai Jiao Tong University (Medical Science)    2024, 44 (10): 1221-1228.   DOI: 10.3969/j.issn.1674-8115.2024.10.002 Abstract （220）   HTML （5）    PDF（pc） （1389KB）（370）       Knowledge map    Save Objective ·To explore the effect of online courses combined with the teach-back method among patients with laryngectomy and their family caregivers. Methods ·Convenience sampling was used to select patients with laryngectomy treated in the Department of Otolaryngology, Shanghai Changhai Hospital from July 2022 to June 2023 and their family caregivers. The participants were divided into a control group and an observation group using the random number table method. The intervention was conducted in two different wards. General information of the two groups of patients and caregivers was collected. After admission, the control group watched offline videos recorded by the department. The videos introduced laryngocarcinoma-related knowledge and standard procedures of airway stoma care, suctioning, nasal feeding, etc., which were divided into 4 sessions with 30 min each. The patients watched one session per week. The observation group watched the same videos (8 lessons) online on their own after admission, while the nursing staff used the teach-back method for health education, consolidating 2 lessons once a week, 45 min/session for 4 weeks. The effectiveness of the intervention was evaluated by using Caregiver Preparedness Scale (CPS), Family Caregiver Task Inventory (FCTI), and Chinese Quality of Life Instruments for Cancer Patients-Head and Neck Cancer (QLICP-HN) at baseline (1st week), before discharge (4th week), and one month after discharge (8th week), as well as the incidence of adverse events during home care. Results ·The study included a total of 120 pairs of patients and caregivers, with 60 pairs in each group. Five pairs in each group were excluded due to various reasons, leaving a total of 55 pairs in each group. There were no statistically significant differences between the two groups in terms of general information of the patients and the caregivers, QLICP-HN scores of the patients, and CPS and FCTI scores of the caregivers at baseline (P>0.05). Before discharge and 1 month after discharge, the CPS scores of the caregivers and the QLICP-HN scores of the patients in the observation group were significantly higher than those in the control group, and the FCTI scores were significantly lower (lower scores indicating better nursing care), with statistically significant differences (P<0.05). Within 1 month after discharge, the incidence of adverse home care events in the observation group was lower than that in the control group (5.5% vs 29.1%), and the difference was statistically significant (P<0.05). Conclusion ·The online courses combined with the teach-back method help improve the readiness to care and caregiving competence of family caregivers of post-laryngectomy patients, improve patients' quality of life, and reduce the incidence of adverse events during home care. Table and Figures | Reference | Related Articles | Metrics

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Effect of prehospital multimodal prehabilitation on preoperative function and postoperative recovery in patients with gastrointestinal malignant tumors TAI Rui, SUN Jufang, LIN Ying, ZHANG Yaqing, HUANG Chen, FANG Fang Journal of Shanghai Jiao Tong University (Medical Science)    2024, 44 (10): 1229-1234.   DOI: 10.3969/j.issn.1674-8115.2024.10.003 Abstract （230）   HTML （5）    PDF（pc） （1303KB）（284）       Knowledge map    Save Objective ·To explore the effect of a prehospital multimodal prehabilitation program on the preoperative functional status and postoperative recovery of patients with gastrointestinal malignant tumors. Methods ·A total of 78 patients with gastrointestinal malignant tumors, hospitalized in Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine from June to December 2023, were enrolled. They were divided into the standard group (SD group, n=40) and the prehospital multimodal prehabilitation group (PMP group, n=38) by using random number table. From the time the operation was agreed upon by both the doctor and patient to the day before the operation, the SD group followed the routine preoperative guidance, while the PMP group received a home-based prehospital multimodal prehabilitation program. The general data of patients were collected, and the six-minute walk distance (6MWD) was compared between the two groups at baseline and on the day before operation.The length of postoperative hospitalization, time to first flatus, time to first ambulation, time to first oral intake, drainage removal time and postoperative complication rate were also compared between the two groups. Results ·There was no difference in general data and duration of preoperative intervention of patients between the two groups. At baseline, there was no significant difference in 6MWD between the two groups. On the day before operation, the 6MWD in the PMP group was higher than that in the SD group (P= 0.016). Changes in 6MWD in the PMP group were significantly higher compared to SD group during the preoperative period, with values of (23.42±13.59) m vs. (-3.75±12.08) m (P<0.001). Time to first flatus, time to first ambulation and time to first oral intake in the PMP group were earlier than those in the SD group (P<0.05). However, there was no significant difference in drainage removal time, postoperative hospitalization and postoperative complication rate between the two groups (P>0.05). Conclusion ·Prehospital multimodal prehabilitation can improve the preoperative function and accelerate the postoperative recovery in patients with gastrointestinal malignancies. Table and Figures | Reference | Related Articles | Metrics

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Effect of early goal-directed activity on gastrointestinal function recovery after pancreatic surgery YAO Hui, ZHANG Yun, DAI Chenjun, GAO Wenqing, YAO Wenjie, DUAN Xiaolei, YANG Fu Journal of Shanghai Jiao Tong University (Medical Science)    2024, 44 (10): 1235-1240.   DOI: 10.3969/j.issn.1674-8115.2024.10.004 Abstract （184）   HTML （6）    PDF（pc） （1300KB）（331）       Knowledge map    Save Objective ·To investigate the safety and feasibility of early goal-directed mobilization in the recovery of gastrointestinal function after pancreaticoduodenectomy. Methods ·The non-contemporaneous controlled studies were conducted. Subjects who underwent pancreaticoduodenectomy were included. From Sep 2022 to May 2023, forty patients were selected as the control group, and forty patients were selected from June 2023 to February 2024 as the experimental group. The general clinical data of the two groups were collected. The control group was treated with the nursing routine after pancreaticoduodenectomy, and there were no specific requirements for the time and goal of early activity. The experimental group had daily activity goals established for early mobilization, which were performed by the patients and their families, while the rest of their care was identical to that of the control group. The main index of effectiveness evaluation was the time of first flatus and first defecation, and the secondary indexes included the time of first getting out of bed, the time of oral drinking, the time of the gastric tube removal, and the postoperative levels of K+, Na+, and Cl- on the 3rd day of the postoperative period. Safety evaluations included chyle leak, postoperative pancreatic fistula, biliary leak and delayed gastric emptying, postoperative hemorrhage, unplanned reoperation, unplanned extubation, falls and death. Results ·There was no statistically significant difference in the general clinical data of the patients in the 2 groups. After the implementation of early goal-directed mobilization, the time of first flatus was advanced from (3.95±1.68) d to (2.88±0.91) d (t=-3.560, P=0.001), and the time of first defecation was advanced from (4.90±1.61) d to (3.80±1.30) d (t=-3.352, P=0.001). The time of first getting out of bed was advanced from (5.18±1.77) d to (2.30±0.88) d (t=-9.205, P<0.001), and the time of oral drinking was advanced from (4.10±1.89) d to (2.73±1.20) d (t=-3.883, P<0.001). Significant differences were also observed in postoperative day 3 Na+ (t=-2.745, P=0.008) and Cl- (t=-2.033, P=0.045) levels. Conclusion ·Early goal-directed activity programs are safe and effective in promoting the recovery of gastrointestinal function after pancreaticoduodenectomy. Table and Figures | Reference | Related Articles | Metrics

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miR-128-3p inhibits the proliferation of keratinocytes in psoriasis via repressing leptin PENG Jing, YIN Jing, XIA Ping, CHEN Liuqing Journal of Shanghai Jiao Tong University (Medical Science)    2024, 44 (10): 1241-1248.   DOI: 10.3969/j.issn.1674-8115.2024.10.005 Abstract （203）   HTML （15）    PDF（pc） （3550KB）（514）       Knowledge map    Save Objective ·To explore the role of miR-128-3p/leptin (LEP) axis in the proliferation and inflammation of keratinocytes in psoriasis. Methods ·BALB/c mice were randomly divided into a control group (n=10) and a model group (n=10). Mice in the model group were given imiquimod on the back. miR-128-3p overexpression and interference plasmids, as well as LEP interference plasmids, were constructed and transfected into HaCaT cells, respectively. miR-128-3p and LEP mRNA were quantified by real-time quantitative polymerase chain reaction, and LEPprotein levels were detected by using Western blotting. Enzyme-linked immunosorbent assay was used to measure the content of tumor necrosis factor α (TNF-α), interleukin-6 (IL-6), and interleukin-1β (IL-1β) in the culture medium. MTT assay was used to evaluate cell activity and EdU assay was to used to test cell proliferation. The binding site between miR-128-3p and LEP was determined by using a dual luciferase reporter gene assay. Results ·Compared with mice in the control group, mice in the model group showed downregulated expression of miR-128-3p and upregulated expression of LEP at both RNA and protein levels (all P<0.05). The dual luciferase reporter gene assay confirmed that LEP was a downstream target of miR-128-3p. Compared with the negative control mimic (NC mimic) group, expression of miR-128-3p was up-regulated in the miR-128-3p mimic group, and expression of LEP was reduced. The levles of TNF-α, IL-6, and IL-1β were significantly lower in the miR-128-3p mimic group than in the NC mimic group. The relative cell viability and EdU-positive cell rate were also reduced after miR-128-3p up-regulation (all P<0.05). Compared with the negative control inhibitor (NC inhibitor) group, expression of miR-128-3p was down-regulated in the miR-128-3p inhibitor group, and expression of LEP was increased. The levles of TNF-α, IL-1β and IL-6 were increased after miR-128-3pdownregulation. miR-128-3p down-regulation led to an increase in relative cell viability and EdU-positive cell rate (all P<0.05). Further experimental results showed that LEP expression was up-regulated in the miR-128-3p inhibitor+LEP inhibitor group compared with that in the LEP inhibitor group, whereas the levels of TNF-α, IL-6, and IL-1β were elevated, and the relative viability of the cells and the rate of EdU-positive cells were increased (all P<0.05). Conclusion ·miR-128-3p downregulates LEP to inhibit the proliferation and inflammatory response of keratinocytes, thereby inhibiting the occurrence and development of psoriasis. Table and Figures | Reference | Related Articles | Metrics

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Expression of miR-146a in CD4+ T lymphocytes of patients with rheumatoid arthritis and its correlation with inflammatory cytokines LI Bo, HU Qiuxia, WU Ximei, SHE Ruonan, TAN Jinhui, LUO Junjia, YANG Haitao, ZHANG Haoru Journal of Shanghai Jiao Tong University (Medical Science)    2024, 44 (10): 1249-1254.   DOI: 10.3969/j.issn.1674-8115.2024.10.006 Abstract （173）   HTML （8）    PDF（pc） （1423KB）（240）       Knowledge map    Save Objective ·To investigate the expression of miR-146a in peripheral blood CD4+ T lymphocytes of patients with rheumatoid arthritis (RA) and its correlation with inflammatory cytokines such as tumor necrosis factor-α (TNF-α) and interleukin-6 (IL-6). Methods ·A total of 30 active RA patients who received medical treatment and 30 healthy controls who underwent physical examinations at the People's Hospital of Longhua, Shenzhen from August 2019 to July 2021 were selected. Peripheral blood mononuclear cells (PBMCs) and CD4+ T lymphocytes were isolated from venous blood extracted from RA patients and healthy controls, respectively. Quantitative real-time PCR (qPCR) was used to detect the expression of miR-146a in peripheral blood CD4+ T lymphocytes, and enzyme-linked immunosorbent assay (ELISA) was used to detect the levels of TNF-α and IL-6. After transfection of the peripheral blood CD4+ T lymphocytes of RA patients with miR-146a mimic, the expression of miR-146a, TNF-α and IL-6 was detected again. The correlations between miR-146a expression and TNF-α and IL-6 expression in RA patients, both before and after transfection, were analyzed by using Pearson correlation coefficient. Results ·Before transfection with miR-146a mimic, the expression levels of miR-146a, TNF-α and IL-6 in peripheral blood CD4+ T lymphocytes of RA patients were significantly higher than those of healthy controls (all P<0.001). After transfection, the expression of miR-146a in peripheral blood CD4+ T lymphocytes of RA patients was significantly higher, and the expression of TNF-α and IL-6 was significantly lower (all P<0.001). The results of Pearson correlation analysis showed that the expression of miR-146a in peripheral blood CD4+ T lymphocytes of RA patients, both before and after transfection, was positively correlated with the expression of TNF-α and IL-6, respectively (r=0.959, P<0.001; r=0.916, P<0.001; r=0.971, P<0.001; r=0.861, P<0.001). Conclusion ·miR-146a can regulate the levels of TNF-α and IL-6 in peripheral blood CD4+ T lymphocytes of RA patients, indicating that miR-146a may play a role in the pathogenesis of RA. Table and Figures | Reference | Related Articles | Metrics

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Mechanistic study on the promotion of pancreatic cancer progression through upregulation of ZNF143 by dysregulated fatty acid metabolism YU Siwei, XU Ziqi, TAO Mengyu, FAN Guangjian Journal of Shanghai Jiao Tong University (Medical Science)    2024, 44 (10): 1255-1265.   DOI: 10.3969/j.issn.1674-8115.2024.10.007 Abstract （223）   HTML （14）    PDF（pc） （8407KB）（169）       Knowledge map    Save Objective ·To identify key genes that may be regulated by fatty acid alteration in pancreatic cancer through tumor transcriptome screening, and to explore the expression of zinc finger protein 143 (ZNF143) in pancreatic cancer and its effect on the migration and invasion of pancreatic cancer cells. Methods ·The R language was utilized to integrate transcriptome data, including the GSE164760 dataset from the Gene Expression Omnibus (GEO) database, 179 pancreatic cancer tissue samples and 4 adjacent non-cancerous tissue samples from The Cancer Genome Atlas (TCGA) database, as well as 167 normal pancreatic tissue samples from the Genotype-Tissue Expression (GTEx) database. We conducted screening and analysis of potential differential genes that may be induced by dysregulation of fatty acid metabolism in pancreatic cancer. After treating pancreatic cancer cells with palmitic acid (PA) and oleic acid (OA) for 24 hours, the mRNA levels of candidate genes were detected by qRT-PCR. According to the median expression level of the screened gene, pancreatic cancer patients in the TCGA database were divided into two groups with high and low expression of ZNF143. Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway and Gene Ontology (GO) enrichment analyses were performed for the differential genes of the two groups. siRNA was used to knock down the expression of ZNF143 in pancreatic cancer cells, and the effects on cell migration and invasion were examined by wound healing assay and invasion assay. Western blotting was used to explore the impact of ZNF143 on epithelial mesenchymal transition (EMT)-related proteins and the Wnt/β-catenin pathway. Results ·The bioinformatics database was processed to analyze key genes associated with the up-regulation of genes in lipid metabolism disorders in pancreatic cancer and liver cancer. Among them, ZNF143 was a potential gene associated with fatty acid accumulation in pancreatic cancer. In vitro experiments confirmed that the mRNA level of ZNF143 was significantly up-regulated after treating pancreatic cancer cells with palmitic acid or oleic acid. Both KEGG and GO enrichment analyses demonstrated that the differentially expressed genes associated with ZNF143 were predominantly enriched in adhesion pathways. In functional experiments, the migration and invasion abilities of pancreatic cancer cells transfected with ZNF143 siRNA were reduced, and the expression of EMT-related proteins was also decreased, potentially related to the activation of the Wnt/β- catenin pathway. Conclusion ·Fatty acid accumulation up-regulates the mRNA expression of ZNF143 in pancreatic cancer cells, and ZNF143 may enhance the migration and invasion of these cells by facilitating EMT through activation of the Wnt/β-catenin pathway. Table and Figures | Reference | Related Articles | Metrics

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Correlation between serum SUMO1 level and hypertriglyceridemia in type 2 diabetes mellitus patients ZHANG Xinyan, LI Han, RAN Hui, SU Qing, ZHANG Hongmei Journal of Shanghai Jiao Tong University (Medical Science)    2024, 44 (10): 1266-1272.   DOI: 10.3969/j.issn.1674-8115.2024.10.008 Abstract （178）   HTML （5）    PDF（pc） （1361KB）（328）       Knowledge map    Save Objective ·To explore the correlation between serum small ubiquitin-like modifier 1 (SUMO1) levels and hypertriglyceridemia in patients with type 2 diabetes mellitus (T2DM). Methods ·A total of 239 newly diagnosed T2DM patients were recruited from the endocrinology clinic of Xinhua Hospital, Shanghai Jiao Tong University School of Medicine, between September 2020 and March 2021. Among them, 92 patients had hypertriglyceridemia, and 147 patients did not. Basic information and laboratory parameters were collected. The differences in serum SUMO1 levels between the two groups were analyzed. Factors influencing hypertriglyceridemia in patients with T2DM were analyzed, and the impact of serum SUMO1 levels on the risk of hypertriglyceridemia in T2DM patients was investigated. Results ·Patients with T2DM and hypertriglyceridemia had significantly higher serum SUMO1 levels compared to those without hypertriglyceridemia (1 114.99 pg/mL vs 902.43 pg/mL, P<0.001). Binary Logistic regression analysis suggested that serum SUMO1 levels (OR=1.527, 95%CI 1.200?1.943), glycated hemoglobin (OR=1.202, 95%CI 1.038?1.391), and blood uric acid (OR=1.006, 95%CI 1.003?1.010) were independent risk factors for hypertriglyceridemia in patients with T2DM. After adjusting for various confounding factors and stratifying serum SUMO1 levels into quartiles, the risk of hypertriglyceridemia in T2DM patients with the highest quartile (Q4) of serum SUMO1 levels was 2.707 times higher compared to those in the lowest quartile (Q1) (95%CI 1.231?5.951). Multiple linear stepwise regression analysis revealed that female gender, waist-to-hip ratio, triglycerides and serum creatinine were independent risk factors for elevated serum SUMO1 levels. Conclusion ·Serum SUMO1 level in patients with T2DM complicated with HTG is significantly higher than that in patients without HTG, and the serum SUMO1 level is an independent risk factor for T2DM complicated with HTG. Table and Figures | Reference | Related Articles | Metrics

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Age-related changes of alveolar bone in maxillary posterior based on cone-beam CT ZHAO Meng, JIANG Liting, GAO Yiming Journal of Shanghai Jiao Tong University (Medical Science)    2024, 44 (10): 1273-1278.   DOI: 10.3969/j.issn.1674-8115.2024.10.009 Abstract （195）   HTML （4）    PDF（pc） （2519KB）（213）       Knowledge map    Save Objective ·To measure and analyze age-related changes in cortical bone thickness and alveolar bone height and width in the posterior teeth of the maxilla. Methods ·Cone-beam CT (CBCT) data of the implant patients in the Department of Stomatology, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine were collected from January 2019 to December 2022. There were 40 cases in the youth group (18?30 years) and 40 cases in the elderly group (≥60 years), with a male-to-female ratio of 1∶1. The i-Dixel software was used to measure the thickness of buccal and palatal cortical bone, and the width and height of alveolar bone in three regions of the posterior teeth of the maxilla on the side with regular dentition (part Ⅰ: between the first and the second premolar of maxillary; part Ⅱ: between the second premolar and the first molar of maxillary; part Ⅲ: between the first and the second molar of maxillary), and the differences between different groups were compared. Results ·In part Ⅲ, the buccal cortical bone thickness of the elderly men [(1.49±0.29) mm] was significantly greater than that of the young men [(1.11±0.34) mm] (P<0.001). In part Ⅰ and Ⅱ, the thickness of palatal cortical bone in the elderly women [part Ⅰ: (1.27±0.30) mm; part Ⅱ: (1.28±0.27) mm] was significantly smaller than that in the young women [part Ⅰ: (1.70±0.32) mm; part Ⅱ: (1.58±0.61) mm] (P<0.05). The width of alveolar bone showed a trend of being smaller in the elderly group than in the young group in all three regions, but there were significant differences only between the elderly males [part Ⅱ: (8.61±1.15) mm; part Ⅲ: (11.06±2.40) mm] and the young males [part Ⅱ: (10.29±1.69) mm; part Ⅲ: (13.39±1.59) mm] in the part Ⅱ and Ⅲ (P<0.05). The alveolar bone height in part Ⅰ and Ⅱ was significantly greater in elderly men and women than that in the young men and women, respectively (P<0.05). In the elderly group, the thickness of buccal cortical bone in men was significantly greater than that in women in part Ⅰ and Ⅲ (P<0.05). Conclusion ·The thickness of palatal cortical bone in female maxillary posterior teeth significantly decreases with age; the width of alveolar bone in maxillary posterior region shows a narrowing trend with age, especially in elderly men; the height of alveolar bone in the maxillary posterior region of the elderly increases significantly. Table and Figures | Reference | Related Articles | Metrics

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Establishment and verification of auditory brainstem implant vocoder model ZHANG Qinjie, HUANG Sui, TAN Haoyue, ZHOU Xiang, WANG Junyi, LIU Yuzi, WEN Wen, GUO Jia, WU Hao, JIA Huan Journal of Shanghai Jiao Tong University (Medical Science)    2024, 44 (10): 1279-1286.   DOI: 10.3969/j.issn.1674-8115.2024.10.010 Abstract （192）   HTML （3）    PDF（pc） （2849KB）（220）       Knowledge map    Save Objective ·To develope an auditory brainstem implant (ABI) vocoder based on cochlear implant (CI) vocoder characteristics and ABI electrode array topology, and to verify its reliability. Methods ·An "n-of-m" coding strategy CI/ABI vocoder was constructed based on MATLAB. Within each frame, only the envelopes of the n channels with the highest energy were selected. The interaction coefficient (IC) (range: 1?3), channel numbers (range: 5?22), and electrode array topology (CI/ABI) were adjustable parameters, allowing for the synthesis of simulated speech. Psychoacoustic evaluation was employed, recruiting normal hearing subjects to perform closed-set simulated phoneme perception. The phoneme recognition accuracy (20 vowel questions/condition, 11 consonant questions/condition) was compared with the corresponding conditions of CI and ABI from reference literature to determine the IC value of the vocoder and verify its reliability. Results ·The vocoder successfully synthesized all test stimuli. In the closed-set CI-simulated speech recognition, the simulated vowel and consonant recognition accuracy for IC2 and IC3 conditions showed no significant difference compared to the accuracy reported in the CI reference literature (P>0.05). The difference in vowel and consonant accuracy between IC2 and the literature was smaller than that between IC3 and the literature (vowel |d|=1.6% vs. 20%, consonant |d|=8.4% vs. 9.9%), thus determining the optimal interaction coefficient of this model as 2. Subsequently, when modifying the electrode array topology to ABI, it was found that the simulated phoneme recognition accuracy for a 16-channel ABI was significantly lower than that for the 16-channel CI group, consistent with the reported literature. The simulated vowel and consonant accuracy within the 5?8 channel range for ABI showed no significant difference (P>0.05), also aligning with the trend reported in the literature. Conclusion ·A CI/ABI vocoder based on "n-of-m" coding strategy is established and the optimal IC is determined. The established ABI encoder has been evaluated for high reliability through psychoacoustic experiments. It provides suitable technical means for validating ABI-specific coding strategies. Table and Figures | Reference | Related Articles | Metrics

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Research progress in Menin-MLL interaction and its inhibitors in MLL-rearranged leukemia FANG Xinyue, SHI Lan, XIA Siyi, WANG Jiaxuan, WU Yingli, HE Kejun Journal of Shanghai Jiao Tong University (Medical Science)    2024, 44 (10): 1287-1298.   DOI: 10.3969/j.issn.1674-8115.2024.10.011 Abstract （455）   HTML （14）    PDF（pc） （2449KB）（367）       Knowledge map    Save Acute leukemias caused by mixed lineage leukemia (MLL) gene rearrangements (MLL-r) are characterized by high invasiveness and a poor prognosis, with few specific treatment options available. MLL protein is essential in embryonic development and hematopoiesis. It exhibits histone methyltransferase activity and can interact with various proteins through its functional domains, thus regulating downstream target gene expression through epigenetic modifications. MLL-r leads to the formation of MLL fusion proteins (MLL-FPs), in which the C-terminal is replaced by fusion partner proteins; over 100 such partner proteins have been identified to date. In numerous studies of the molecular mechanism, Menin serves as an important cofacter in the leukemogenesis of MLL-FPs and participates in forming the key complex when interacting with the N terminal of MLL protein, resulting in the disregulation of certain targeted genes, which makes the development of Menin-MLL inhibitors theoretically possible. To date, several small molecules have been identified that inhibit Menin-MLL interaction, including thienopyrimidine derivatives, piperidine derivatives, pyrimidine derivatives, and macrocyclic mimic peptides. Based on these prototypes, at least seven drugs are currently undergoing clinical evaluation, with some promising preliminary data regarding safety, tolerability, and efficacy. This review summarizes the structure and function of MLL, the mechanism of the occurrence of MLL-r leukemia, and current Menin-MLL inhibitors tested in MLL-r leukemia. Table and Figures | Reference | Related Articles | Metrics

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Research progress in the role of endo cannabinoid system in liver diseases BIAN Shu, YU Qian, LIU Liangming Journal of Shanghai Jiao Tong University (Medical Science)    2024, 44 (10): 1299-1306.   DOI: 10.3969/j.issn.1674-8115.2024.10.012 Abstract （168）   HTML （5）    PDF（pc） （1858KB）（183）       Knowledge map    Save The endocannabinoid system (ECS) consists of a variety of long-chain unsaturated fatty acid analogs, mainly anandamide (AEA) and 2-arachidoniyl glycerol (2-AG), along with their specific binding G protein-coupled receptors, cannabinoid receptor 1 (CB1R) and cannabinoid receptor 2 (CB2R). It affects the life process and biological activity of almost all cells in the body by influencing cell material and energy metabolism. In the liver, the physiological expression of ECS is at a low level. The expression and secretion of ECS in the liver can be strongly stimulated by liver injury factors. ECS acts as a trigger in multiple liver diseases. It is known to be related to the process of hepatocyte steatosis and promote the formation and development of non-alcoholic fatty liver disease (NAFLD) and alcoholic liver disease (ALD). It is involved in the inflammatory processes of liver diseases and greatly affects the immune-inflammatory response in liver tissue. It is also involved in the formation of liver fibers and promotes the occurrence and development of liver fibrosis and cirrhosis. Finally, the role and mechanisms of ECS in the occurrence and development of liver diseases are elaborated in detail by listing lipid metabolism-related liver diseases (NAFLD and ALD) and other liver diseases. Table and Figures | Reference | Related Articles | Metrics

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Progress in mechanisms and treatment of sunitinib resistance in renal cell carcinoma CHEN Zixuan, LIU Min Journal of Shanghai Jiao Tong University (Medical Science)    2024, 44 (10): 1307-1315.   DOI: 10.3969/j.issn.1674-8115.2024.10.013 Abstract （429）   HTML （22）    PDF（pc） （2199KB）（367）       Knowledge map    Save Renal cell carcinoma (RCC) originates from the epithelial cells of renal tubules and is the most common type of renal cancer, as well as the urological tumor with the highest mortality rate. Over the past half-century, the morbidity and mortality of RCC have been increasing, posing a significant threat to human health. Although surgical treatment offers the possibility of a cure for most RCC patients, tumor recurrence or metastasis leads to the failure of traditional treatment options to achieve the desired results. The advent of targeted drugs, such as receptor tyrosine kinase inhibitors and immune checkpoint inhibitors, has brought new hope for the treatment of RCC. Targeted therapy has become the mainstay of treatment for advanced RCC. Sunitinib is a receptor tyrosine kinase inhibitor that plays a pivotal role in the treatment of RCC. It inhibits the activity of various receptor tyrosine kinases, including epidermal growth factor receptor, platelet-derived growth factor receptor, and vascular endothelial growth factor receptor. This, in turn, inhibits tumor angiogenesis and cellular proliferation, effectively controlling tumor progression. However, a considerable number of RCC patients develop resistance to sunitinib within 15 months of initiating treatment, presenting new challenges for the treatment of RCC. Therefore, this paper summarizes the mechanism of sunitinib resistance in RCC and reviews the treatment of sunitinib resistance in RCC, in order to provide ideas for overcoming the resistance of RCC to sunitinib, and developing a more effective treatment plan for patients with advanced RCC. Table and Figures | Reference | Related Articles | Metrics

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Advances of GADD45b in hepatic glucose and lipid metabolism WANG Renjie, HUA Hui, ZHU ChaoYu, WEI Li Journal of Shanghai Jiao Tong University (Medical Science)    2024, 44 (10): 1316-1322.   DOI: 10.3969/j.issn.1674-8115.2024.10.014 Abstract （296）   HTML （12）    PDF（pc） （2232KB）（411）       Knowledge map    Save Growth arrest and DNA damage-inducible 45b (GADD45b) was initially discovered to be involved in processes such as cell cycle arrest, differentiation and apoptosis. It is an important signal regulatory molecule in cells, responsible for signal transduction under various physiological or environmental stimuli. The GADD45b gene belongs to the GADD45 gene family. This gene is commonly expressed in human and fetal tissues, but the expression is tissue-specific, with high expression in the liver and bone marrow. The GADD45b protein is a small, evolutionarily conserved acidic protein distributed in both the cytoplasm and nucleus. Research has shown that GADD45b is closely associated with signaling pathways such as p38/MAPK and TGFβ/Smad3, and it has functions including improving tissue fibrosis and inflammation progression, inhibiting cell autophagy, and enhancing neural function recovery. GADD45b plays a significant role in tumors, innate immunity, neurological diseases, and disorders of hepatic glucose and lipid metabolism. The incidence of non-alcoholic fatty liver disease (NAFLD) is increasing year by year in China and has become a serious public health issue in the country. Disorders in hepatic glucose and lipid metabolism are major causes of NAFLD. Multiple studies have shown that GADD45b gene and protein exhibit abnormal expression in liver diseases with hepatic glucose and lipid metabolism disorders. Previous research has found that GADD45b can increase the stability of the FoxO1 protein in hepatocytes, and enhance the expression of PGC1a, thereby promoting hepatic gluconeogenesis. Additionally, GADD45b can inhibit fatty acid transport in hepatocytes by binding to FABP1 and reduce hepatic steatosis by interacting with HSP72 protein. Therefore, the roles of GADD45b in promoting hepatic gluconeogenesis, inhibiting fatty acid transport, and reducing steatosis may form the basis for research into treatments for hepatic glucose and lipid metabolism disorders and liver diseases. This paper reviews the characteristics and functions of the GADD45b protein, as well as recent advances in the study of hepatic glucose and lipid metabolism and liver diseases, aiming to provide reference for further GADD45b research. Table and Figures | Reference | Related Articles | Metrics

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Research progress in the relationship between FOXM1 and neoplasm metabolism LI Yu, JIANG Yifan, TONG Rongliang, CHEN Diyu, WU Jian Journal of Shanghai Jiao Tong University (Medical Science)    2024, 44 (10): 1323-1329.   DOI: 10.3969/j.issn.1674-8115.2024.10.015 Abstract （329）   HTML （12）    PDF（pc） （1324KB）（266）       Knowledge map    Save FOXM1 (forkhead box M1) is an important member of the FOX transcription factor family and plays a critical role in driving the progression of multiple malignancies through its transcriptional regulatory functions. Moreover, the overexpression of FOXM1 is associated with poor prognosis in many types of cancer, as it regulates a variety of biological processes such as gene expression, cell proliferation, invasion, metastasis, and apoptosis. Presently, aberrant metabolic reprogramming has been considered as the major characteristic of cancer development, determining the survival, growth, and proliferation of tumor cells. Accumulating evidence suggests that FOXM1 serves as a "bridge" between metabolism and tumorigenesis. This review aims to provide a comprehensive summary of the research progress in the relationship between FOXM1 and tumor cell metabolism, offering theoretical insights for the development of novel anti-cancer drugs targeting FOXM1. Reference | Related Articles | Metrics

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A case of exertional rhabdomyolysis with RYR1 gene variation WANG Guangpu, WANG Yakun, WU Di, BAI Shoujun Journal of Shanghai Jiao Tong University (Medical Science)    2024, 44 (10): 1330-1334.   DOI: 10.3969/j.issn.1674-8115.2024.10.016 Abstract （166）   HTML （6）    PDF（pc） （1777KB）（148）       Knowledge map    Save The etiology of rhabdomyolysis in adults is multifaceted, with one cause being physical exertion, termed exertional rhabdomyolysis (ERM). Characterized primarily by the destruction of muscle cells, ERM results in the release of intracellular contents into the bloodstream, leading to a spectrum of symptoms, including myalgia, dark urine, weakness, and marked elevations in serum creatine kinase (CK) and myoglobin levels. Some patients experience recurrent symptoms, persistently high serum CK levels (exceeding 50 times the normal upper limit), or unexplained severe manifestations. Despite this, the underlying pathogenesis remains elusive in numerous cases. Recent studies have implicated mutations in the RYR1 gene as a potential cause of exercise-induced ERM. This report describes a patient presenting with ERM and a heterozygous RYR1 gene missense mutation. Following treatment with fluid resuscitation, metabolic optimization, and antioxidant therapy, the patient exhibited clinical and biochemical improvement. Table and Figures | Reference | Related Articles | Metrics

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Promotive effect of cancer-testis antigen CT57 on proliferation, invasion, migration and epithelial-mesenchymal transition of liver cancer cells LUO Lange, ZHENG Chao, LEI Ming Journal of Shanghai Jiao Tong University (Medical Science)    2024, 44 (11): 1335-1346.   DOI: 10.3969/j.issn.1674-8115.2024.11.001 Abstract （266）   HTML （17）    PDF（pc） （8853KB）（464）       Knowledge map    Save Objective ·To investigate the effect of cancer-testis antigen family member CT57 on proliferation, migration and invasion of the human liver cancer cells and tumorigenesis in nude mice, and the possible mechanism. Methods ·Bioinformatics methods were used to analyze the differential expression of CT57 in several cancer tissues and normal tissues, and its effect on the prognosis of liver cancer patients. Lentiviral vectors were used to establish liver cancer cell lines with stable knockdown and overexpression of CT57, which were confirmed by Western blotting. CCK-8 cell proliferation assay, soft agar colony formation assay and cell cycle experiment were used to detect the effect of CT57 on the proliferation and colony formation ability of liver cancer cells. Wound healing and Transwell assays were used to detect the effect of CT57 on the migration and invasion of liver cancer cells, and the expression of epithelial-mesenchymal transition (EMT) markers was detected by quantitative real-time PCR (qRT-PCR). To explore the effect of CT57 on liver cancer cells in vivo, CT57 knockdown liver cancer cells (experimental group) and control liver cancer cells (control group) were used to conduct subcutaneous tumor formation experiments in nude mice. Results ·Bioinformatics analysis of multiple tumors and corresponding normal tissues in The Cancer Genome Atlas Program (TCGA) database showed that CT57 was highly expressed in most tumor tissues, including liver cancer, and the expression level of CT57 was significantly correlated with the prognosis of liver cancer patients. Cell proliferation assay, soft agar colony formation assay, and cell cycle experiment showed that knockdown of CT57 inhibited the proliferation and colony formation of liver cancer cells and led to cell cycle arrest. In wound healing and Transwell assays, knockdown of CT57 inhibited the invasion and migration of liver cancer cells, while overexpression of CT57 promoted it. The results of qRT-PCR indicated that overexpression of CT57 resulted in downregulation of epithelial cell markers ECAD (E-cadherin) and OCLN (occludin), and upregulation of mesenchymal cell markers VIM (vimentin), TWIST1 (twist family bHLH transcription factor 1), and MMP2 (matrix metallopeptidase 2). In the in vivo experiments, knockdown of CT57 significantly reduced the tumor formation rate of liver cancer cells, tumor volume, and tumor weight in nude mice. Conclusion ·Knockdown of CT57 leads to cell cycle arrest, thereby inhibiting the proliferation of liver cancer cell and subcutaneous tumorigenesis in nude mice; CT57 promotes the invasion, migration and EMT of liver cancer cells. Table and Figures | Reference | Related Articles | Metrics

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Function and mechanism of cancer-testis antigen CT63 in chronic myeloid leukemia KONG Ruxin, ZHOU Yaqun, WEI Tingyi, LEI Ming Journal of Shanghai Jiao Tong University (Medical Science)    2024, 44 (11): 1347-1358.   DOI: 10.3969/j.issn.1674-8115.2024.11.002 Abstract （276）   HTML （9）    PDF（pc） （22763KB）（211）       Knowledge map    Save Objective ·To explore the effects of the cancer-testis antigen (CTA) family member CT63 on proliferation, differentiation, and tumorigenicity of chronic myeloid leukemia (CML) cells, and uncover the underlying molecular mechanisms. Methods ·The link between CT63 expression and the prognosis of myeloid leukemia patients was analyzed using bioinformatics methods (TCGA database). A K562 cell line with CT63 knockdown was established. The knockdown efficiency of CT63 was confirmed by qRT-PCR and Western blotting. Live-cell imaging and CCK-8 methods were adopted to evaluate the inhibitory effect of CT63 knockdown in CML cells. A subcutaneous tumorigenesis assay in nude mice was conducted to examine the effects of CT63 on tumorigenesis, tumor growth, and differentiation of K562 cells invivo. Phorbol 12-myristate 13-acetate (PMA)-induced monocyte/macrophage differentiation experiment was carried out to investigate the role of CT63 in the differentiation of K562 cells in vitro. Mitochondrial function was assessed to determine the impact of CT63 on CML cells both in vivo and in vitro. Results ·The Kaplan-Meier survival curve indicated that low expression levels of CT63 were correlated with longer survival in patients with myeloid leukemia. Down-regulation of CT63 in K562 cells inhibited proliferation and promoted differentiation. Live-cell imaging and CCK-8 assays displayed that knockdown of CT63 inhibited cell proliferation and extended cell doubling time in K562 cells. In the subcutaneous xenotransplantation model, down-regulation of CT63 inhibited tumor growth in nude mice. K562 cells expressing lower levels of CT63 were more prone to differentiate into monocyte/macrophage both in vivo and in vitro under PMA exposure condition. Knockdown of CT63 suppressed the activity of mitochondrial respiratory chain complex Ⅳ. This led to decreased expression of mitochondrial markers, including cytochrome C oxidase Ⅳ (COX Ⅳ), pyruvate dehydrogenase, succinate dehydrogenase A (SDHA), and voltage-dependent anion channel (VDAC), thus affecting the mitochondrial metabolic activity of K562 cells. Conclusion ·CT63 is related to the prognosis of myeloid leukemia patients. CT63 plays an important role in promoting proliferation and inhibiting differentiation of K562 cells in vivo and in vitro. CT63 serves as a switch to regulate the balance between proliferation and differentiation of CML cells via the modulation of mitochondrial activity. Table and Figures | Reference | Related Articles | Metrics

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Mechanism of DUX-induced differentiation of mESC into extraembryonic endoderm HONG Lei, GUO Chuanliang, CAI Qin, LI Wanrui, ZENG Yitao, XUE Yan, ZENG Fanyi Journal of Shanghai Jiao Tong University (Medical Science)    2024, 44 (11): 1359-1369.   DOI: 10.3969/j.issn.1674-8115.2024.11.003 Abstract （254）   HTML （13）    PDF（pc） （3532KB）（1272）       Knowledge map    Save Objective ·To explore the effect of double homeobox (DUX) protein on the differentiation potential of mouse embryonic stem cells (mESCs) into extraembryonic endoderm (XEN) and the possible mechanism of its action. Methods ·Overexpression of DUX cell lines in mESCs was achieved by using a lentiviral system. The proportion of 2-cell-like cells (2CLCs) before and after DUX overexpression was detected by flow cytometry, and the expression of 2-cell stage-specific genes, Dux, zinc finger and SCAN domain containing 4c (Zscan4c), zinc finger protein 352 (Zfp352) and murine endogenous retrovirus-L polymerase (MERVL-pol), were detected by real-time quantitative reverse transcription polymerase chain reaction (RT-qPCR). RT-qPCR assay was used to detect the expression of pluripotency factors, nanog homeobox (Nanog), kruppel-like transcription factor 4 (Klf4), sex determining region Y-box 2 (Sox2), and octamer-binding transcription factor 4 (Oct4), in pluripotent state, as well as the expression of signature genes for different germ layers in the differentiated state [endodermal: GATA binding protein 4 (Gata4), GATA binding protein 6 (Gata6), and sex determining region Y-box 17 (Sox17); ectodermal: Nestin and tubulin beta 3 class Ⅲ (Tubb3); mesodermal: heart and neural crest derivatives expressed 1 (Hand1), myogenic differentiation 1 (Myod1), and kinase insert domain protein receptor (Flk1)]. Public RNA sequencing (RNA-seq) data were mined to further clarify the effect of DUX on the differentiation of mESCs into extraembryonic endoderm. Functional and pathway enrichment analyses of differentially expressed genes were performed using Gene Ontology (GO), Kyoto Encyclopedia of Genes and Genomes (KEGG), and gene set enrichment analysis (GSEA) to identify the signaling pathways regulated by DUX. Additionally, an in-depth analysis of existing chromatin immunoprecipitation sequencing (ChIP-seq) data was conducted to explore the potential target genes of DUX. Results ·Molecular biology experiments showed that overexpression of DUX could effectively maintain the pluripotency of mESCs, which was consistent with the analysis of public RNA-seq data. Differential gene analysis revealed that endodermal genes were specifically upregulated. After differentiation assay of mESCs, RT-qPCR assay experiments showed that mRNA expression of the XEN marker genes (Gata4, Gata6, Sox17) was significantly upregulated (P<0.001). In contrast, there was no specific change in mesodermal and ectodermal genes. GSEA enrichment analysis indicated that DUX might activate the retinoid metabolism signaling pathway, and the analysis of the ChIP-seq data further revealed the presence of a large number of known retinoic acid receptor motif in DUX-bound peaks, which could activate downstream target genes related to the development of the XEN. Conclusion ·DUX has a strong correlation with the retinoic acid signaling pathway and it is predicted to activate the retinoic acid signaling pathway, which could promote the tendency of mESCs toward XEN differentiation. Table and Figures | Reference | Related Articles | Metrics

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Functional site analysis of mucin 1 in regulating the malignant characteristics of tumor cells GAO Kexing, LIAO Chunhua, LI Shengze, MA Shuangyu, HUANG Lei Journal of Shanghai Jiao Tong University (Medical Science)    2024, 44 (11): 1370-1382.   DOI: 10.3969/j.issn.1674-8115.2024.11.004 Abstract （219）   HTML （11）    PDF（pc） （8623KB）（925）       Knowledge map    Save Objective ·To identify the functional motifs of mucin 1 (MUC1) involved in regulating tumor cell proliferation, migration, and stemness maintenance. Methods ·Mutational characteristics of the MUC1 gene across different cancers were identified from The Cancer Genome Atlas (TCGA) database. Various MUC1 mutation sites were analyzed and localized, followed by ranking based on mutation frequency. Western blotting was used to screen high-frequency MUC1 mutants with stable protein expression. BT549 cell line with MUC1 knocked out and MCF-10A cell line were used to stably overexpress MUC1 wild-type (MUC1-WT) and mutants by using lentiviral technology. Immunofluorescence was used to detect the cellular localization of MUC1 mutants. Using MUC1-WT as a positive control and MUC1-AQA, a loss-of-function mutant, as a negative control, the biological functions of different MUC1 mutant cells were analyzed: cell proliferation ability was assessed by cell counting kit-8 (CCK-8) assay and colony formation assay; cell migration ability was evaluated by wound-healing and Transwell assays; cell stemness was examined by sphere formation assay. Structural localization of MUC1 mutants was analyzed by using PyMOL software, and molecular docking analysis was performed by using a protein docking software (ZDOCK Server). ·Results A total of 102 mutations located in the MUC1 coding region were identified in the TCGA database, among which five missense mutations (P418S, S251R, V359I, N271S, and N465H) exhibited higher frequencies and were located in the non-variable number of tandem repeats (non-VNTR) region. Further examination revealed that the MUC1-S251R, N271S, and V359I mutants could be stably expressed. The cellular localization assay indicated that these three mutants predominantly localized in the cytoplasm, but were also presented in the nucleus. The nuclear-to-cytoplasmic ratio showed minimal differences between MUC1-WT and the mutants. Analysis of the tumorigenic biological functions of the cells expressing different MUC1 mutants revealed that: ① High expression of MUC1-WT significantly enhanced the proliferation ability of both BT549 and MCF-10A cells; the proliferation of MUC1-AQA, S251R, and N271S mutant cells was decreased compared to MUC1-WT cells, while MUC1-V359I mutant cells exhibited a similar proliferative profile to MUC1-WT cells. ② The migration ability of MUC1-WT high-expressing cells was significantly enhanced, whereas MUC1-AQA cells demonstrated attenuated migration. In the BT549 cells, the migration ability of MUC1-S251R and V359I cells was similar to that of MUC1-WT cells, whereas MUC1-N271S cells showed reduced migration. In the MCF-10A cells, the migration ability of MUC1-N271S and MUC1-V359I cells was similar to that of MUC1-WT cells, whereas MUC1-S251R cells exhibited significantly decreased migration. ③ Stemness was enhanced in both cell types with high MUC1-WT expression, while MUC1-AQA cells lost stemness; the cells with MUC1-N271S, V359I and MUC1-WT showed comparable maintenance of stemness, whereas MUC1-S251R cells demonstrated compromised stemness. PyMOL software analysis unveiled that MUC1-N271S and V359I were located in or around the sperm protein-enterokinase-agarin (SEA) region, specifically in the loop region and the β-sheet, respectively. The molecular docking analysis revealed that the stability of the complex formed by MUC1-WT or V359I with the extracellular domain of epidermal growth factor receptor (EGFR) surpassed that of MUC1-N271S or S251R, indicating a stability hierarchy of V359I>WT>N271S>S251R. ·Conclusion MUC1 mutants exhibit diverse impacts on the biological functions of tumor cells, with their effects on proliferation correlating with the EGFR signaling pathway. MUC1-V359I is similar to MUC1-WT, indicating a negligible effect on tumor cell proliferation, migration, and stemness maintenance. Conversely, MUC1-S251 and N271 sites may be involved in the regulation of signaling pathways governing cell proliferation and migration and the MUC1-S251 site plays a critical role in maintaining cell stemness. Table and Figures | Reference | Related Articles | Metrics

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Expression of MTA1 in preeclamptic placental tissue and its effects on trophoblast function GENG Yao, ZHANG Yang, ZHAO Jie, LI Wei, CAI Guoqing Journal of Shanghai Jiao Tong University (Medical Science)    2024, 44 (11): 1383-1390.   DOI: 10.3969/j.issn.1674-8115.2024.11.005 Abstract （211）   HTML （13）    PDF（pc） （3077KB）（430）       Knowledge map    Save Objective ·To investigate the expression of metastasis-associated protein 1 (MTA1) in placental tissues of preeclampsia (PE) patients and its impact on trophoblast cell function. Methods ·Placental specimens were collected from pregnant women with PE (PE group, 20 cases) patients and healthy pregnant women as controls (control group, 35 cases). Western blotting and immunofluorescent double staining were performed to analyze the expression changes of MTA1. The human first-trimester placental trophoblast cell line HTR8/SVneo was cultured, and the cell migration ability was assessed through wound healing assay. The cell invasion ability was detected using Transwell invasion assay. Under hypoxic conditions simulating the invasion of extravillous trophoblasts into the uterus, quantitative real-time polymerase chain reaction (qRT-PCR) was performed to analyze the mRNA expression of hypoxia-induced matrix metalloproteinases (MMP-2 and MMP-9), thus assessing their secretion levels. An extravillous trophoblast explant model was constructed to assess the overall villus outgrowth capacity of the explants. Immunohistochemistry (IHC) was performed to confirm the presence of the endothelial marker CD31 for placental angiogenesis analysis in mice. Fifteen Mta1-/- female mice and fifteen wild-type C57 female mice were mated with wild-type male C57 mice for fertility testing. Results ·Western blotting revealed significantly decreased expression of MTA1 protein in placental tissues of the PE group compared to the control group. Immunofluorescent double staining showed that MTA1 was mainly localized in the nuclei of trophoblast cells. The wound healing assay demonstrated that HTR8/SVneo with stable MTA1 knockdown exhibited weaker cell migration ability compared to the control group (P=0.002). The Transwell invasion assay demonstrated a marked decrease in invasiveness in MTA1-knockdown cells, significantly lower than the control group (P=0.015). Hypoxia-induced expression levels of matrix metalloproteinases MMP-2 and MMP-9 were significantly reduced (P=0.020, P=0.003). After MTA1 knockdown, the overall villus outgrowth capacity of the explants was decreased compared to the control group (P=0.003). IHC results showed that CD31 expression in the placenta of Mta1-/- female mice was significantly lower than that of wild-type female mice (P=0.004). The litter size of Mta1-/- female mice was significantly reduced (P=0.000). Conclusion ·The expression level of MTA1 is closely related to PE. Endogenous MTA1 may be involved in trophoblast invasion into the endometrium and villous capillary remodeling. Table and Figures | Reference | Related Articles | Metrics

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Nanoplastics aggravate severe asthma by inducing DNA damage of alveolar type Ⅱ epithelial cells SHI Zelun, WANG Qing, HE Wen, FU Weijia, WANG Yingwen, HAN Xiao, ZHANG Xiaobo Journal of Shanghai Jiao Tong University (Medical Science)    2024, 44 (11): 1391-1405.   DOI: 10.3969/j.issn.1674-8115.2024.11.006 Abstract （204）   HTML （6）    PDF（pc） （7132KB）（798）       Knowledge map    Save Objective ·To explore the effects and possible molecular mechanisms of nanoplastics (NPs) on severe asthma. Methods ·A mouse model of severe asthma was established by using house dust mite (HDM) and lipopolysaccharide (LPS) co-stimulation. Polystyrene nanoplastics (PS-NPs) were instilled into the severe asthma mice′s airways. Subsequently, bronchoalveolar lavage fluid (BALF) was collected and lung tissue sections were prepared. Flow cytometry, hematoxylin-eosin (H-E) staining, periodic acid-Schiff (PAS) staining, immunohistochemistry, and terminal dexynucleotidyl transferase-mediated dUTP nick-end labeling (TUNEL) staining, were used to observe the effects of PS-NPs on airway inflammation, mucus secretion, alveolar structure, and the proliferation and apoptosis of alveolar type Ⅱ epithelial cells (AT2 cells) in severe asthma mice. The CCK-8 assay and Annexin Ⅴ/PI double staining were performed to evaluate the effects of PS-NPs on the proliferation and apoptosis of the mouse AT2 cell line MLE-12. DNA damage in AT2 cells caused by PS-NPs was detected by using anti-γ-H2A.X immunofluorescence staining. The expression of genes in the ATR/Chk1/p53 signaling pathway was detected by real-time fluorescent quantitative polymerase chain reaction (qPCR), Western blotting, Tyramide signal amplification (TSA) multiplex immunofluorescence staining, and immunofluorescence co-localization, respectively. The ATR-specific inhibitor Ceralasertib (AZD6738) was administrated to MLE-12 cells in combination with PS-NPs to evaluate the recovery effect on cell proliferation and apoptosis. Results ·Flow cytometry revealed that exposure to PS-NPs increased the total number of inflammatory cells and the number of each type of inflammatory cells in the BALF of mice with severe asthma, with a predominance of neutrophils. H-E and PAS staining showed significant increase in airway inflammatory cell infiltration and mucus secretion, as well as disruption of alveolar structure. In vitro, the CCK-8 assay demonstrated significant, dose-dependent inhibition of MLE-12 cell proliferation by PS-NPs. The Annexin V/PI double staining assay indicated a higher apoptosis rate of (56.20±3.84)% in PS-NP-exposed cells compared to (23.22±2.52)% in the control group. Immunofluorescence staining demonstrated that PS-NPs were phagocytosed by MLE-12 cells and localized around the nucleus. TUNEL staining confirmed enhanced apoptosis in AT2 cells in vivo. The immunofluorescence assay revealed that compared to the control group, the expression of the DNA damage marker γ-H2A.X increased in the experimental group. qPCR, Western blotting, and TSA multiplex staining results showed that PS-NP-induced elevated expression of mRNA and proteins was related to the ATR/Chk1/p53 pathway in MLE-12 cells. Moreover, immunofluorescence co-localization also confirmed the induction of ATR and p53 proteins in AT2 cells in vivo. The ATR-specific inhibitor Ceralasertib partially restored the PS-NP-induced inhibition of cell proliferation and enhancement of apoptosis in MLE-12 cells. Conclusion ·NPs exposure leads to DNA damage in AT2 cells, activating the ATR/Chk1/p53 signaling pathway and exacerbating airway inflammation and alveolar damage in mice with severe asthma. Table and Figures | Reference | Related Articles | Metrics

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Analysis of clinical and genetic characteristics of 18 pediatric patients with Barth syndrome ZHAN Tianliu, YAN Zihang, WU Jinjin, CHEN Hao, CHEN Lijun, CHEN Yiwei, FU Lijun Journal of Shanghai Jiao Tong University (Medical Science)    2024, 44 (11): 1406-1413.   DOI: 10.3969/j.issn.1674-8115.2024.11.007 Abstract （214）   HTML （25）    PDF（pc） （1638KB）（192）       Knowledge map    Save Objective ·To analyze the clinical and genetic characteristics of Chinese pediatric patients with Barth syndrome (BTHS) and provide data to support the prevention and treatment of BTHS. Methods ·Eighteen pediatric patients diagnosed with BTHS at Shanghai Children′s Medical Center, Shanghai Jiao Tong University School of Medicine, from January 2010 to November 2023, were included. Clinical data (age, birth weight, family history, electrocardiogram, echocardiogram, urine tandem mass spectrometry, complete blood count, blood biochemistry, and genetic test results) were collected to analyze the clinical characteristics, genetic findings, and prognoses of the patients. Results ·The study included 18 male patients with BTHS (including 2 monozygotic twins), consisting of one Yi ethnic and 17 Han Chinese patients. The median age at diagnosis was 3.0 (1.0, 5.6) months. Fifteen patients experienced decreased cardiac function at disease onset, with a left ventricular ejection fraction (LVEF) below 50%. Dilated cardiomyopathy (DCM) was observed in 15 patients, left ventricular non-compaction (LVNC) in 12 patients, and myocardial hypertrophy in 9 patients. During the diagnosis and follow-up, QTc interval prolongation occurred in 9 patients, ventricular arrhythmias in 2 patients, neutropenia in 9 patients, and monocytosis in 10 patients. Urine tandem mass spectrometry revealed 3-methylglutaconic aciduria (3-MGCA) in 8 of 13 tested patients. Fifteen types of TAZ gene mutation were identified in the 18 patients, including 5 novel mutations. Genetic testing of the parents of 16 patients indicated maternal inheritance in 15 cases. The median follow-up period was 8.5 (2.6, 29.3) months, during which 12 patients died. The median age at death was 7.5 (6.0, 12.8) months. Causes of death included heart failure (7 cases, with 4 concurrent infections), sudden death (3 cases), ventricular fibrillation (1 case), and accidental death (1 case). Conclusion ·BTHS is a rare genetic disorder with multisystem involvement. Its primary clinical manifestations include cardiomyopathy and neutropenia. The condition typically presents early in life, with severe progression and poor prognosis. Prompt recognition, accurate diagnosis, and early intervention are essential for managing this disease. Table and Figures | Reference | Related Articles | Metrics

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Prediction of drug-drug interactions in clozapine combination therapy based on physiologically based pharmacokinetic model MOU Fan, HUANG Zhiwei, CHENG Yu, ZHAO Xue, LI Huafang, YU Shunying Journal of Shanghai Jiao Tong University (Medical Science)    2024, 44 (11): 1414-1421.   DOI: 10.3969/j.issn.1674-8115.2024.11.008 Abstract （226）   HTML （11）    PDF（pc） （3039KB）（289）       Knowledge map    Save Objective ·To develop physiologically based pharmacokinetic (PBPK) models specifically designed for the Chinese population by utilizing the combination of clozapine and fluvoxamine as a case, and predict the drug-drug interaction (DDI) associated with the combination medication of clozapine, ultimately optimizing the dosage of clozapine. Methods ·By obtaining the physicochemical parameters, absorption, distribution, metabolism, excretion (ADME)-related parameters, and physiologically relevant parameters of the Chinese population through literature and pharmacology-related databases, PBPK models for the clozapine and fluvoxamine were constructed by using PK-Sim? software. The models′ accuracy was evaluated by comparing predicted values of the area under the curve (AUC) and peak concentration (Cmax) to observed data, using the mean percentage error (MPE) and mean absolute percentage error (MAPE) as evaluation indicators. The models were validated against real-world plasma drug concentration data. Additionally, combining the inhibitory effect of fluvoxamine on clozapine, models for the combination therapy of clozapine and fluvoxamine were developed to predict the pharmacokinetic changes of clozapine. The presence of clinically significant DDI was determined by using the 90% confidence interval of the AUC ratio (AUCR) or Cmax ratio (CmaxR) as evaluation metrics, with a non-effect boundary set at 80%?125%. The pharmacokinetic changes of clozapine upon co-administration with fluvoxamine based on PBPK models were quantified, and a dosage optimization for clozapine was developed. Results ·The constructed model of clozapine and fluvoxamine was considered accurate if the absolute value of the MPE was ≤10% and the MAPE was <25% during validation, indicating that the predicted concentration-time curves were accurate. The PBPK model for the co-administration of clozapine and fluvoxamine was able to accurately predict pharmacokinetic parameters if the ratio of predicted AUC to observed AUC was within 1.25. The prediction of PBPK model for the co-administration showed that the 90% confidence intervals for AUCR and CmaxR of the combination therapy of clozapine and fluvoxamine were not entirely within the ineffective effect boundary, indicating a clinically significant DDI when these two drugs were used concomitantly. Moreover, the dose optimization according to the PBPK models indicated that when subjects were co-administered with clozapine and fluvoxamine, reducing the dose of clozapine to 50% of the original dose could maintain the exposure levels of clozapine consistent with monotherapy. Conclusion ·The established PBPK model can effectively simulate the impact of combination therapy on pharmacokinetic changes of clozapine, providing valuable insights for predicting potential DDI and optimizing dosage regimens. If clozapine needs to be co-administered with fluvoxamine during the treatment, clinicians should remain vigilant for clinically significant DDI and contemplate optimizing the dosage of clozapine accordingly. Table and Figures | Reference | Related Articles | Metrics

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