Journal of Shanghai Jiao Tong University (Medical Science)

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

2024, 44 (1): 1-12.
doi: 10.3969/j.issn.1674-8115.2024.01.001

Abstract ( 358 )

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Objective ·To establish a prognostic model for the overall survival (OS) of hepatocellular carcinoma (HCC) based on mitochondrial genes and clinical information. Methods ·The gene expression and the clinical data of 369 HCC patients and 50 controls with normal liver were downloaded from The Cancer Genome Atlas (TCGA) database. The nuclear-encoded mitochondrial genes (NEMGs) were obtained from the MitoCarta3.0 database. The "DESeq2" R package and univariate Cox analysis were used to select NEMGs [ubiquinol cytochrome C reductase hinge protein (UQCRH),ATP citrate lyase (ACLY),phosphoenolpyruvate carboxykinase 2 (PCK2), Bcl-2 homologous antagonist/killer1 (BAK1), Bcl-2-associated X protein (BAX) 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.

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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

2024, 44 (1): 13-22.
doi: 10.3969/j.issn.1674-8115.2024.01.002

Abstract ( 212 )

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

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Expression of adhesion G protein-coupled receptor F1 in pancreatic ductal adenocarcinoma and its mechanism of promoting cancer progression

CHEN Suyuan, Mutailifu Musitaba, LI Dongxue, ZHANG Zhigang

2024, 44 (1): 23-34.
doi: 10.3969/j.issn.1674-8115.2024.01.003

Abstract ( 240 )

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

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Effect of ceria nanoparticles on activity of DSS-induced colitis in mice by eliminating active oxygen species

LU Yuhan, SHI Yahong, LONG Manmei, WANG Zi, WU Yingwei

2024, 44 (1): 35-42.
doi: 10.3969/j.issn.1674-8115.2024.01.004

Abstract ( 337 )

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

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Application and accuracy assessment of a novel 3D-printed osteotomy guide in anterior maxillary segmental distraction osteogenesis

WAN Teng, JIANG Tengfei, ZHU Min, WANG Xudong

2024, 44 (1): 43-49.
doi: 10.3969/j.issn.1674-8115.2024.01.005

Abstract ( 207 )

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

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Relationship among maternal gut, vaginal microbiota and microbiota in meconium and vernix caseosa in newborns

MA Jinqian, FAN Pianpian, ZHENG Tao, ZHANG Lin, CHEN Yuanzhi, SHEN Jian, OUYANG Fengxiu

2024, 44 (1): 50-63.
doi: 10.3969/j.issn.1674-8115.2024.01.006

Abstract ( 224 )

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

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Clinicopathologic characteristics, gene mutation profile and prognostic analysis of thyroid diffuse large B-cell lymphoma

DU Zhishan, WANG Yue, SHI Ziyang, SHI Qing, YI Hongmei, DONG Lei, WANG Li, CHENG Shu, XU Pengpeng, ZHAO Weili

2024, 44 (1): 64-71.
doi: 10.3969/j.issn.1674-8115.2024.01.007

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

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Correlation between body compositions and cardiopulmonary fitness in patients with coronary heart disease

LI Yang, MA Jun, DU Yihong, XU Li, CHEN Hanfen, QIU Xunhan, JIANG Meng, PU Jun

2024, 44 (1): 72-78.
doi: 10.3969/j.issn.1674-8115.2024.01.008

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Objective ·To explore the correlation between body compositions and cardiovascular fitness (CRF) in patients with coronary heart disease (CHD). Methods ·The CHD patients (CHD group) who underwent elective percutaneous coronary intervention treatment at Renji Hospital, Shanghai Jiao Tong University School of Medicine from October 2022 to June 2023 as well as healthy people (control group) were selected. All the participants completed cardiopulmonary exercise testing (CPET) to determine CRF and bioelectrical impedance analysis (BIA) to determine body compositions on the same day. Results ·A total of 191 patients with coronary heart disease and 188 healthy individuals were included. There was no statistically significant difference in baseline characteristics between the two groups. Compared with the control group, the CRF indicators of the CHD group were significantly reduced (all P<0.05). In terms of body composition indicators, the trunk muscle mass (TMM) of the CHD group was significantly lower than that of the control group (P<0.01), and the trunk fat mass (TFM) was significantly higher than that of the control group (P<0.01). Correlation analysis showed that TMM (R=0.538), lower limbs muscle mass (LMM) (R=0.754), and lower limbs fat mass (LFM) (R=0.593) were positively correlated with peak oxygen uptake per kilogram of bodyweight (VO_2peak/kg) in the CHD group (all P<0.01), while TFM (R=-0.563) was negatively correlated with VO_2peak/kg (P<0.01). There was no statistically significant correlation between other body composition indicators and VO_2peak/kg. According to VO_2peak/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 VO_2peak/kg in the patients with CHD. The VO_2peak/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 VO_2peak/kg compared to the males. Conclusion ·The CRF of CHD patients is significantly lower than that of the healthy population, with higher TFM and lower TMM; in the CHD patients, CRF is negatively correlated with TFM and positively correlated with TMM, LMM, and LFM.

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Short-axis cine cardiac magnetic resonance images-derived radiomics for hypertrophic cardiomyopathy and healthy control classification

LIU Qiming, LU Qifan, CHAI Yezi, JIANG Meng, PU Jun

2024, 44 (1): 79-86.
doi: 10.3969/j.issn.1674-8115.2024.01.009

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

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Alteration of cognitive function in overweight and obese adolescents and its relationship with serum FGF21 levels

HAN Rui, WU Qian, LIU Dan, CHENG Di, ZHANG Ying, NI Jiacheng, KANG Piao, CHEN Anran, YU Shujie, FANG Qichen, LI Huating

2024, 44 (1): 87-97.
doi: 10.3969/j.issn.1674-8115.2024.01.010

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Objective ·To evaluate the changes in cognitive function in overweight and obese adolescents, and explore the association between cognitive function and fibroblast growth factor 21 (FGF21). Methods ·A total of 175 adolescents from a senior high school in Shanghai were divided into normal weight group (n=50), overweight group (n=50) and obese group (n=75) based on their body mass index (BMI). General information, anthropometric data and laboratory testing indicators of the adolescents were collected and compared. The cognitive function of the three groups of adolescents was assessed by using the accuracy (ACC) and reaction time of Flanker task and n-back task. Enzyme-linked immunosorbent assay (ELISA) was used to detect the serum FGF21 level of the three groups of adolescents. Partial correlation analysis and multiple linear regression model were used to evaluate the correlation between cognitive task performance and anthropometric data and laboratory testing indicators. Results ·Compared with the normal weight group, systolic blood pressure, diastolic blood pressure, and the levels of fasting plasma glucose, glycosylated hemoglobin and triacylglycerol in the obese group were higher (all P<0.05). Under congruent or incongruent stimulus conditions in the Flanker task, there was no significant difference in ACC between any two groups; compared with the normal weight and overweight groups, the reaction time of the adolescents in the obese group was prolonged (all P<0.05). In the n-back task, there were no significant differences in ACC between any two groups, while the obese group had longer reaction time in the 1-back and 2-back tasks compared to the normal weight and overweight groups (all P<0.05). Compared with the normal weight group, serum FGF21 levels of the adolescents in the obese group were higher (P=0.000). Partial correlation analysis showed that the reaction time of the adolescents in Flanker and n-back tasks was correlated with their BMI, body fat mass, waist circumference, waist-to-hip ratio and FGF21 level (all P<0.05). Multiple linear regression analysis further confirmed that BMI was associated with prolonged reaction time in cognitive-related behavioral tasks in the adolescents (all P<0.05), and FGF21 level was associated with ACC in the 2-back task (P=0.000) and reaction time in the incongruent stimulus condition (P=0.048). Conclusion ·Overweight and obese adolescents have cognitive impairments, and BMI and serum FGF21 levels are associated with changes in their cognitive function.

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Establishment of discriminative models for predicting the infiltration degree of patients with lung adenocarcinoma based on clinical laboratory indicators

WANG Mengfei, YANG Shouzhi, QIAO Yongxia, HUANG Lin

2024, 44 (1): 98-107.
doi: 10.3969/j.issn.1674-8115.2024.01.011

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

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Effects of Astragali Radix on T lymphocyte subsets expression in peripheral blood of Hashimoto′s thyroiditis patients with normal thyroid function

LI Ziyun, ZHUANG Xinjuan, JI Ye, TIAN Hairong, YIN Jun

2024, 44 (1): 108-115.
doi: 10.3969/j.issn.1674-8115.2024.01.012

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

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Adjuvant strategies for patients with T1b invasion after endoscopic submucosal dissection for esophageal squamous cell carcinoma

ZHU Kaiyuan, SU Yuchen, LIU Zhichao, ZHANG Hong, LI Chunguang, ZHANG Jie, LI Zhigang

2024, 44 (1): 116-123.
doi: 10.3969/j.issn.1674-8115.2024.01.013

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

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Research progress in ceruloplasmin regulation of lipid metabolism homeostasis

JIANG Quanxin, CHEN Suzhen, LIU Junli

2024, 44 (1): 124-130.
doi: 10.3969/j.issn.1674-8115.2024.01.014

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

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Progress of olfactory changes in metabolic diseases and the mechanisms

WU Qian, LI Huating

2024, 44 (1): 131-136.
doi: 10.3969/j.issn.1674-8115.2024.01.015

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

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Research progress of m⁶A methylation modification in regulating tumor immunity

ZHOU Haixia, ZHANG Jing

2024, 44 (1): 137-144.
doi: 10.3969/j.issn.1674-8115.2024.01.016

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

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