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Journal of Shanghai Jiao Tong University (Medical Science) 2025 Vol.45

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Role of tumor necrosis factor-α in coronavirus disease 2019-associated kidney injury PANDIT Roshan, LU Junyao, HE Liheng, BAO Yujie, JI Ping, CHEN Yingying, XU Jie, WANG Ying Journal of Shanghai Jiao Tong University (Medical Science)    2025, 45 (1): 1-10.   DOI: 10.3969/j.issn.1674-8115.2025.01.001 Abstract （870）   HTML （46）    PDF（pc） （3324KB）（1466）       Knowledge map    Save Objective ·To identify relevant biomarkers for patients with coronavirus disease 2019-associated kidney injury (COVID-19-associated KI) and explore the mechanisms underlying the involvement of severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) proteins in infection-related KI by affecting the interactions between renal cells and macrophages. Methods ·A retrospective analysis was conducted on the clinical characteristics of COVID-19 patients with KI treated in Shanghai Ninth, People′s, hospital from December 2022 to February 2023. Serum levels of inflammatory factors and chemokines were measured by using enzyme- linked immunosorbent assay (ELISA). In vitro, human macrophage cell line THP-1 cells were stimulated with recombinant S1 subunit protein derived from SARS-CoV-2 spike protein. The cells and culture supernatants were collected to detect the levels of inflammatory factors and chemokines by using quantitative real-time PCR (qRT-PCR) and ELISA. Conditioned medium was prepared from the cell culture supernatants of S1-stimulated THP-1 cells and used to stimulate human renal epithelial cells (HK-2) in vitro to assess cytokine secretion. Antibody blocking experiments were performed to analyze the effects of the conditioned medium on the production of cytokines in HK-2 cells. Results ·Among 39 patients with COVID-19, 8 (20.50%) had creatinine levels above the reference interval, which indicated the occurrence of KI. The levels of peripheral tumor necrosis factor-α (TNF-α) in the COVID-19 patient with KI group [(18.33±8.20) pg/mL] were significantly higher than those in the non-KI group [(11.88±6.50) pg/mL] (P=0.015). In vitro assay has shown that S1-spike protein stimulation promoted the level of gene transcription and production of TNF-α, interleukin-1β (IL-1β) and chemokine C-X-C motif ligand 10 (CXCL10) in THP-1 macrophage cells (P<0.001). Furthermore, the conditioned medium from S1-stimulated THP-1 cells promoted the secretion of TNF-α, IL-1β and CXCL10 by HK-2 cells (P=0.005). When anti-TNF-α antibody (Infliximab) was used to block TNF-α in the culture supernatants from S1-stimulated THP-1 cells, the secretion level of TNF-α by HK-2 cells decreased dramatically (P<0.001). Conclusion ·TNF-α levels increase significantly in COVID-19 patients with KI, implying the significance of TNF-α in the occurrence of COVID-19-associated KI. In vitro experiments confirm that the S1 protein induces TNF-α secretion from THP-1 cells, leading to increased inflammatory responses in renal cells, which may contribute to the development of COVID-19-associated KI. Therefore, targeting TNF-α may become an alternative strategy to reduce the occurrence of COVID-19-associated KI. Table and Figures | Reference | Related Articles | Metrics

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Potential role of SUMO-specific proteases 1 in ferroptosis XIE Bin, BAI Meng, WU Yan, WO Lulu, HUANG Ying, ZHANG Jing Journal of Shanghai Jiao Tong University (Medical Science)    2025, 45 (1): 11-19.   DOI: 10.3969/j.issn.1674-8115.2025.01.002 Abstract （937）   HTML （37）    PDF（pc） （2842KB）（3269）       Knowledge map    Save Objective ·To explore the potential role of SUMO-specific protease 1 (SENP1) in ferroptosis. Methods ·The Cancer Genome Atlas (TCGA) database was used to analyze the correlation between the expression levels of SENP1 and the ferroptosis-related genes, acyl-CoA synthetase long chain family member 4 (ACSL4) and glutathione peroxidase 4 (GPX4). Ferroptosis in human fibrosarcoma HT1080 cells, murine fibrosarcoma MCA-205 cells, and human embryonic kidney 293T cells was induced by RAS-selective lethal 3 (RSL3). Quantitative real-time PCR (RT-qPCR) and Western blotting were used to detect the expression of SENP1. In 293T cells, immunoprecipitation-mass spectrometry was used to investigate the interacting proteins of SENP1 in the process of ferroptosis. The Flag-SENP1 plasmid was transiently transfected into 293T cells, and the overexpression efficiency of SENP1, along with the expression levels of ferroptosis-related genes ACSL4 and GPX4,was assessed by RT-qPCR and Western blotting. Results ·TCGA database analysis showed that the expression of SENP1 was positively correlated with ACSL4 and negatively correlated with GPX4 in most tumor tissues. RT-qPCR and Western blotting showed that the expression level of SENP1 was significantly down-regulated in RSL3-treated HT1080, MCA-205, and 293T cells. Immunoprecipitation-mass spectrometry showed that SENP1 enriched SUMO molecules in the process of ferroptosis. Western blotting showed that the level of ACSL4 protein increased after SENP1 overexpression, and there was no significant change in the level of GPX4 protein. RT-qPCR showed that after SENP1 overexpression, there was no significant change in the mRNA levels of ACSL4 and GPX4. Conclusion ·SENP1 gene expression is downregulated during ferroptosis, and may regulate the stability of ferroptosis-related protein ACSL4. Table and Figures | Reference | Related Articles | Metrics

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Inhibitory effect of rutin on the growth and metastasis of osteosarcoma in vitro and in vivo LI Xiang, WEI Ming, WU Wenxi, LUO Xiaoqin, YAO Biao, WU Siyu Journal of Shanghai Jiao Tong University (Medical Science)    2025, 45 (1): 20-28.   DOI: 10.3969/j.issn.1674-8115.2025.01.003 Abstract （708）   HTML （37）    PDF（pc） （7353KB）（1838）       Knowledge map    Save Objective ·To investigate the effects of rutin on proliferation, apoptosis, migration and invasion of osteosarcoma cells and its possible molecular mechanisms. Methods ·Human osteosarcoma MG63 and U2OS cells were treated with rutin at concentrations of 10, 20 and 40 μmol/L, respectively. The effects of rutin on proliferation, apoptosis, migration, and invasion of MG63 and U2OS cells were assessed by using CCK-8 assay, colony formation assay, flow cytometry, scratch closure assay, and Transwell assay. The expression levels of cell proliferation antigen Ki67, B-cell lymphoma-2 (Bcl-2), and Bcl-2 associated X protein (Bax) proteins were detected by Western blotting. Twelve BALB/c nude mice were subcutaneously injected with osteosarcoma MG63 cells to establish a subcutaneous transplant tumor model. The mice were randomly divided into two groups: a control group and a rutin 40 mg/kg group (6 mice in each group). The rutin 40 mg/kg group was intraperitoneally injected with rutin (40 mg/kg), and the control group was intraperitoneally injected with an equal volume of saline, once every other day for 4 weeks. The tumor volume was measured every week. After 4 weeks, the mice were euthanized, and the tumors were excised and weighed. Immunohistochemistry was used to detect the expression of Ki67 and vascular endothelial growth factor (VEGF) in tumor tissues. TUNEL was used to detect tumor cell apoptosis. Results ·Compared with MG63 and U2OS cells not treated with rutin, MG63 and U2OS cells treated with rutin at 20 and 40 μmol/L showed a significant decrease in proliferation rate, an increase in apoptotic rate, a decrease in migration and invasion abilities, a significant downregulation of Ki67 protein, and a significant increase in Bax/Bcl-2 ratio, with statistically significant differences (all P<0.05). In addition, rutin significantly inhibited the in vivo growth of osteosarcoma cells, reduced the expression of Ki67 and VEGF in tumor tissues, and promoted cell apoptosis (all P<0.05). Conclusion ·Rutin can inhibit the proliferation, migration, and invasion of osteosarcoma cells, and promote apoptosis. Table and Figures | Reference | Related Articles | Metrics

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Transcriptional regulatory network analysis of microglia in multiple sclerosis CAI Qiangwei, SUN Feng, WU Wenyu, SHAO Fuming, GAO Zhengliang, JIN Shengkai Journal of Shanghai Jiao Tong University (Medical Science)    2025, 45 (1): 29-41.   DOI: 10.3969/j.issn.1674-8115.2025.01.004 Abstract （816）   HTML （30）    PDF（pc） （8881KB）（9591）       Knowledge map    Save Objective ·To investigate the differential gene expression of microglia in the gray and white matter of multiple sclerosis (MS) using single-nucleus transcriptomic analysis, aiming to explore their roles in disease progression, and identify key transcriptional regulatory networks associated with the disease. Methods ·snRNA-seq data of frozen human brain tissue samples from MS patients and control individuals were obtained from the Gene Expression Omnibus (GEO) database. R language, along with R packages such as Seurat, was employed to identify cell types based on specific cell markers. Microglia were extracted from the identified cell populations and classified based on their anatomical origin, either gray matter or white matter. Dimensionality reduction and clustering techniques were utilized to identify distinct microglial subpopulations with differential characteristics. Differentially expressed genes (DEGs) between the MS and control groups at the subpopulation level were analyzed by using the Seurat package. Gene set enrichment analysis of Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) was conducted on the DEGs to further explore the biological significance of these differences. Monocle3 was used for pseudotime analysis to study dynamic changes in microglia subpopulations during disease progression. Single cell regulatory network inference and clustering (SCENIC) method was applied to analyze transcription factor (TF) regulatory networks, aiming to identify key transcription factors potentially involved in MS regulation. Results ·After quality control, a total of 149 062 nuclei were retained for analysis. Following dimensional reduction and clustering, 12 238 microglia were identified by using key markers, including DOCK8, CSF1R, P2RY12, and CD74. The results of GO and KEGG pathway analysis showed that in gray matter microglia, functions such as endocytosis, ion homeostasis, and lipid localization were downregulated during disease progression, while in white matter microglia, functions such as protein folding, cytoplasmic translation, and response to thermal stimuli were upregulated. SCENIC analysis revealed that the expression of transcription factors such as FLI1, MITF, and FOXP1 was upregulated in MS. Conclusion ·Microglia play a critical role in MS, with white matter microglia being more significantly impacted by MS than their gray matter counterparts. Transcription factors such as FLI1, MITF, and FOXP1 are identified as key regulators involved in disease modulation, with their associated transcriptional regulatory networks playing a central role in disease modulation. Table and Figures | Reference | Related Articles | Metrics

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Relationship between abdominal fat area and first-phase insulin secretion function of pancreatic β-cells in patients with type 2 diabetes LU Jiaping, LIU Xing, ZHANG Linshan, ZHAO Lin, ZHANG Min, LI Xiaoying, LIU Yuejun Journal of Shanghai Jiao Tong University (Medical Science)    2025, 45 (1): 42-50.   DOI: 10.3969/j.issn.1674-8115.2025.01.005 Abstract （808）   HTML （27）    PDF（pc） （2215KB）（2295）       Knowledge map    Save Objective ·To explore the relationship between abdominal fat area and the first-phase insulin secretion function of pancreatic β-cells in patients with type 2 diabetes, and to establish predictive models of nomogram. Methods ·From October 2020 to February 2024, a total of 120 patients with type 2 diabetes, who were hospitalized in the Department of Endocrinology, Zhongshan Hospital, Fudan University, and underwent the arginine stimulation test, were recruited for the study. Patients were categorized into an insulin secretion function-preserved group (i.e. preserved group) and a depleted group according to the results of the arginine stimulation test. General information and laboratory parameters were collected. Subcutaneous fat area (SFA) and visceral fat area (VFA) were non-invasively measured by abdominal fat detector. The variables were screened by univariate analysis, and multivariate Logistic regression was used to identify the influencing factors, followed by the establishment of predictive models of nomogram. The area under the receiver operating characteristic curve (ROC curve) and concordance index (C-index) were used to evaluate the predictive performance of the models. Results ·Seventy-four patients (61.7%) were assigned to the preserved group, and 46 patients (38.3%) to the depleted group. Patients in the depleted group had a longer diabetes duration, lower waist circumference, hip circumference, body mass index (BMI), uric acid, free triiodothyronine (FT3), adipose tissue insulin resistance (Adipo-IR), ankle brachial index (ABI), SFA and VFA, and higher brachial ankle pulse wave velocity (baPWV). Multivariate Logistic regression showed that SFA, VFA, FT3, baPWV, and ABI were independent risk factors for the depleted insulin secretion function. Nomogram models were constructed based on the above risk factors. Among them, the model comprising VFA, FT3, ABI, and baPWV showed the best predictive performance with a C-index of 0.81. Conclusion ·SFA and VFA are lower in patients with depleted first-phase insulin secretion function of pancreatic β-cells. The nomogram model, including SFA or VFA, can be used to predict first-phase insulin secretion function of pancreatic β-cells in patients with type 2 diabetes. Table and Figures | Reference | Related Articles | Metrics

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Relationship between psychopathological symptoms and drug addiction, and mediating role of psychological distress in drug addicts GAO Yuyan, LI Wei, WANG Shuting, KISHIMOTO Tomoko, ZHANG Ruyuan Journal of Shanghai Jiao Tong University (Medical Science)    2025, 45 (1): 51-59.   DOI: 10.3969/j.issn.1674-8115.2025.01.006 Abstract （894）   HTML （38）    PDF（pc） （1934KB）（2407）       Knowledge map    Save Objective ·To identify different comorbidity types resulting from the spontaneous association of psychopathological symptoms among male drug addicts, explore the relationship between latent types and drug addiction, and examine the mediating role of psychological distress. Methods ·Four hundred and fifty male drug addicts, recruited by Yunnan First Compulsory Isolation Drug Rehabilitation Center according to the 2017 revised Drug Addiction Identification Method by the Ministry of Public Security, were enrolled as participants. The Symptom Checklist-90 (SCL-90), Craving Automated Scale for Substances (CAS-S), and Psychache Scale (PAS) were used to assess the severity of psychopathological symptoms, drug addiction, and psychological distress, respectively. Latent class analysis was employed to identify different types of psychopathological comorbidity that may exist in the participants, and the types were named based on the analysis results. Variance analysis was used to test differences in the severity of drug addiction and psychological distress among different latent types, and a mediation model was established to explore the mediating role of psychological distress between different latent types and drug addiction. Results ·Latent class analysis identified three types of psychopathology: high, medium, and low levels, with decreasing positive rates and numbers of comorbidity in each type based on the ten psychopathological symptoms included in the SCL-90. There were significant differences in the severity of psychological distress and drug addiction among the three types of participants. Psychopathological symptoms positively predicted the severity of psychological distress and drug addiction. Psychological distress completely mediated the relationship between medium levels of psychopathology and drug addiction, while partially mediating the relationship between high levels of psychopathology and drug addiction. Conclusion ·There are three types of psychopathological comorbidity among male drug addicts: high, medium, and low. Psychological distress plays a complete mediating role between medium levels of psychopathology and drug addiction, and a partial mediating role between high levels of psychopathology and drug addiction. Table and Figures | Reference | Related Articles | Metrics

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[18F]F-FMISO and [18F]F-FLT PET/CT dual-nuclide imaging for in vivo prediction of drug resistance in pancreatic cancer SUN Chenwei, HAI Wangxi, QU Qian, XI Yun Journal of Shanghai Jiao Tong University (Medical Science)    2025, 45 (1): 60-68.   DOI: 10.3969/j.issn.1674-8115.2025.01.007 Abstract （684）   HTML （21）    PDF（pc） （2304KB）（1080）       Knowledge map    Save Objective ·[18F]F-FMISO and [18F]F-FLT are specific PET imaging agents for detecting the hypoxia microenvironment and cell proliferation, respectively. This study aims to visualize and monitor the impact of drug resistance in pancreatic cancer on the hypoxia microenvironment and cell proliferation through [18F]F-FMISO and [18F]F-FLT PET/CT dual-nuclide imaging, with the goal of providing a theoretical basis for clinical application. Methods ·The CCK-8 assay was conducted to assess drug resistance in the PANC-1/R (PR) pancreatic cancer cell line compared to the parental PANC-1 (P) cell line. Subcutaneous xenograft models of pancreatic cancer were established by injecting male BALB/c nude mice with pancreatic cancer cells into the left axillary subcutaneous region. Subgroups were treated with gemcitabine (GEM) chemotherapy starting on day 18 (18D-G group) or day 12 (12D-G group) after inoculation of tumor cells. [18F] F-FMISO and [18F] F-FLT PET/CT imaging were performed before and after treatment to obtain semi-quantitative parameters (maximum standardized uptake value, SUVmax). ΔSUVmax was calculated by using the following equation: ΔSUVmax=(SUVmax of second imaging-SUVmax of first imaging)/ SUVmax of first imaging. Receiver operating characteristic (ROC) curves were used to determine the optimal threshold for the semi-quantitative parameters to assess pancreatic cancer drug resistance. Results ·The CCK-8 assay confirmed that the PR cells exhibited high resistance to GEM, with a resistance index of 4.24 (n=5). In vivo experiments showed that GEM chemotherapy significantly inhibited tumor growth and prolonged survival in the parental pancreatic cancer group (12D-G group, P=0.025), whereas GEM chemotherapy accelerated tumor growth and shortened survival (18D-G and 12D-G, P=0.025) in the drug-resistant pancreatic cancer group. In addition, in the non-chemotherapy group, ΔSUVmax-FLT might be negatively correlated with survival time, while in the chemotherapy group, both ΔSUVmax-FMISO and ΔSUVmax-FLT were negatively correlated with survival time (P=0.050, P=0.006). In the 18D-G and chemotherapy group, the second imaging showed significantly lower ΔSUVmax-FMISO and ΔSUVmax-FLT in P tumors compared to PR tumors (P=0.045, P=0.050). In the 12D-G and chemotherapy group, the second imaging showed slightly lower ΔSUVmax-FLT in P tumors compared to PR tumors (P=0.051). ROC analysis identified the optimal threshold for assessing pancreatic cancer drug resistance: when ΔSUVmax-FLT=0.45 in the non-chemotherapy group, the sensitivity and specificity were 100.00% and 50.00%, respectively; when ΔSUVmax-FMISO=0.37 and ΔSUVmax-FLT=0.36 in the chemotherapy group, the sensitivity and specificity were 100.00% and 83.33%, respectively. Conclusion ·[18F]F-FMISO and [18F]F-FLT PET/CT dual-nuclide imaging can be used to assess drug resistance in pancreatic cancer. The comparison of [18F]F-FMISO and [18F]F-FLT PET differences before and after chemotherapy provides the most accurate prediction of drug resistance and survival time. Table and Figures | Reference | Related Articles | Metrics

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Study on multi-parametric texture analysis for quantifying brain magnetic susceptibility in patients with Parkinson′s disease ZHAO Xinxin, PEI Mengchao Journal of Shanghai Jiao Tong University (Medical Science)    2025, 45 (1): 69-78.   DOI: 10.3969/j.issn.1674-8115.2025.01.008 Abstract （664）   HTML （23）    PDF（pc） （3237KB）（922）       Knowledge map    Save Objective ·To quantify brain iron content in Parkinson′s disease (PD) patients by using quantitative susceptibility mapping (QSM) based on phase linearity fitting. Combined with texture analysis methods, the magnetic susceptibility distribution characteristics of gray matter nuclei in PD patients were quantitatively analyzed with multiple parameters and dimensions, and the sensitivity of texture features was evaluated with clinical scoring. Methods ·Quantitative susceptibility images from 20 PD patients and 20 healthy controls (HC) were analyzed retrospectively. Regions of interest in basal ganglia were manually segmented, followed by three-dimensional texture analysis by using gray-level run-length matrix (GLRLM). One-way analysis of variance (ANOVA) was performed to compare differences between the two groups, and the bilateral Pearson linear correlation coefficient ( r) was calculated to evaluate the correlation between texture parameters and UPDRS-III clinical scores. Results ·The analysis of texture feature parameters showed that there were significant differences between the PD and HC groups in the gray matter nuclei. Among all the texture feature parameters of GLRLM, LngREnch showed significant differences between the PD group and the HC group in the five gray matter nuclei measured. The average magnetic susceptibility of gray matter nuclei and GLRLM texture parameters were sensitive in distinguishing PD from HC (AUC>0.5). The AUC values of RLNonUni, LngREnch, ShrtREmp, and Fraction were higher than that of the average magnetization susceptibiliyt. The correlation analysis showed that RLNonUni and GLevNonU in the caudate nucleus (CN), as well as GLevNonU in the red nucleus (RN), were significantly correlated with UPDRS-III scores, while no significant clinical correlations were found for the remaining parameters. Conclusion ·Compared to the mean magnetic susceptibility values, GLRLM texture parameters provide better differentiation between the PD and HC groups. Multiparameter texture analysis offers a novel approach to QSM-based quantitative assessment of brain iron content, which can provide additional multidimensional quantitative information for the non-invasive diagnosis of PD. Table and Figures | Reference | Related Articles | Metrics

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Optimization and evaluation of mouse model construction method for severe periodontitis WANG Jiaxuan, ZHANG Qianqian, SUI Baiyan, LIU Xin Journal of Shanghai Jiao Tong University (Medical Science)    2025, 45 (1): 79-86.   DOI: 10.3969/j.issn.1674-8115.2025.01.009 Abstract （1164）   HTML （42）    PDF（pc） （4215KB）（1932）       Knowledge map    Save Objective ·To investigate an optimal severe periodontitis mouse model by comparing two induction methods: simple ligature and ligature combined with injection of Porphyromonasgingivalis lipopolysaccharide (P.g. LPS). Methods ·Fifteen C57BL/6 mice were divided into three groups: a healthy control group, a simple ligature-induced periodontitis group, and a ligature combined with P.g. LPS injection-induced periodontitis group. After 14 d, the following evaluations were conducted: tooth mobility and probing depth under a stereomicroscope; alveolar bone resorption [bone volume fraction, bone mineral density, the distance from the cemento-enamel junction (CEJ) to the alveolar bone crest (ABC), and the area between CEJ and ABC] analyzed via micro computed tomography (Micro-CT) and stereomicroscopic examination. The serum levels of inflammatory cytokines interleukin-1β (IL-1β) and tumor necrosis factor-α (TNF-α) were assessed by enzyme-linked immunosorbent assay (ELISA). Results ·Compared with the simple ligature group, mice in the ligature with P.g. LPS injection group exhibited significantly increased tooth mobility [(2.20±0.45) vs (1.40±0.55)] and probing depth [(1.05±0.21) mm vs (0.58±0.39) mm], with statistically significant differences (P<0.05). The ligature with P.g. LPS injection group also demonstrated significantly reduced bone volume fraction [(16.44%±3.35%) vs (28.97%±7.90%)] and bone mineral density [(0.42±0.04) g/cm3vs (0.55±0.08) g/cm3], as well as increased distance from CEJ to ABC [(0.88±0.03) mm vs (0.74±0.12) mm] and area between CEJ and ABC [(0.34±0.01) mm2vs (0.30±0.02) mm2], all with statistically significant differences (all P<0.05). Additionally, serum levels of TNF-α and IL-1β were significantly elevated in the ligature with P.g. LPS injection group compared to the simple ligature group (both P<0.05). Conclusion ·The method of ligature combined with continuous P.g. LPS injection is more effective for constructing a severe periodontitis mouse model, making it suitable for studying the progression and treatment of severe periodontitis. Table and Figures | Reference | Related Articles | Metrics

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Two-sample Mendelian randomization study on the causal association between air pollution and Alzheimer′s disease ZHANG Yingying, ZHANG Junyao, SONG Jiwei, WANG Shengjie, YAO Junyan Journal of Shanghai Jiao Tong University (Medical Science)    2025, 45 (1): 87-94.   DOI: 10.3969/j.issn.1674-8115.2025.01.010 Abstract （623）   HTML （15）    PDF（pc） （2532KB）（1866）       Knowledge map    Save Objective ·To explore the causal relationship between air pollution and the risk of Alzheimer′s disease (AD) by using two-sample Mendelian randomization (MR). Methods ·Based on the data from the genome-wide association study (GWAS), a two-sample MR analysis was conducted to evaluate the causal relationship between air pollution and the risk of AD. Air pollution indicators, including particulate matter 2.5 (PM2.5), particulate matter 2.5-10 (PM2.5-10), particulate matter 10 (PM10), nitrogen dioxide and nitrogen oxides, were used as exposure factors, and summarized data were aggregated from the UK Biobank database. The PM2.5 dataset included 423 796 cases, with correlation analysis conducted on 9 851 867 single nucleotide polymorphisms (SNPs); the PM2.5-10 dataset included 423 796 cases, with correlation analysis conducted on 9 851 867 SNPs; the PM10 dataset included 455 314 cases, with correlation analysis conducted on 9 851 867 SNPs; the nitrogen dioxide dataset included 456 380 cases, with correlation analysis conducted on 9 851 867 SNPs; the nitrogen oxides dataset included 456 380 cases, with correlation analysis conducted on 9 851 867 SNPs. AD was used as the outcome factor, and data were obtained from the International Genomics of Alzheimer′s Project (IGAP). The AD dataset included 25 580 cases and 48 466 controls, with correlation analysis of 7 067 513 SNPs. SNPs significantly associated with AD were used as instrumental variables. The main analysis was conducted by using the inverse variance weighted (IVW) method, and four methods including weighted median, MR-Egger regression, mode-based simple estimation and mode-based weighted estimation were used for quality control. Heterogeneity testing, gene pleiotropy testing and sensitivity analysis were conducted to assess the reliability of the study results. Results ·Heterogeneity testing indicated no evidence of heterogeneity among SNPs associated with air pollution indicators and AD (both IVW and MR-Egger results, P>0.05). Gene pleiotropy testing did not detect any pleiotropic effects (MR-Egger results, P>0.05). Sensitivity analysis confirmed the stability of the PM2.5 results. IVW analysis revealed a statistically significant association between PM2.5 and AD in European populations (P<0.001), while no statistically significant associations were observed between PM2.5-10 (P=0.664), PM10 (P=0.664), nitrogen dioxide (P=0.284), nitrogen oxides (P=0.567) and AD. Conclusion ·There is a significant causal relationship between PM2.5 exposure and the risk of AD, with PM2.5 exposure increasing the incidence of AD. However, no evidence has been found to suggest that PM2.5-10, PM10, nitrogen dioxide or nitrogen oxides cause an increased risk of AD. Table and Figures | Reference | Related Articles | Metrics

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Advances in the treatment of adrenoleukodystrophy LIU Xiaoli, CAO Li Journal of Shanghai Jiao Tong University (Medical Science)    2025, 45 (1): 95-100.   DOI: 10.3969/j.issn.1674-8115.2025.01.011 Abstract （1113）   HTML （79）    PDF（pc） （1348KB）（2610）       Knowledge map    Save Adrenoleukodystrophy (ALD) is an X-linked, potentially fatal peroxisome disease, characterized by three main clinical phenotypes: adrenomyeloneuropathy (AMN), cerebral adrenoleukodystrophy (CALD), and primary adrenal insufficiency. The clinical phenotypes of ALD are unpredictable, with no genotype-phenotype correlation, and disease progression cannot be predicted based on very long chain fatty acid (VLCFA) levels in plasma. Additionally, the phenotypes can exhibit significant variability. Currently, no definitive treatment for this disease exists, and treatment options vary depending on the specific phenotypes. For AMN, only symptomatic supportive treatment is available. However, early CALD can be stabilized through allogeneic hematopoietic stem cell transplantation (allo-HSCT) and transgenic autologous hematopoietic stem cell transplantation (trans-ASCT), and primary adrenal insufficiency can be treated through hormone replacement therapy. Allo-HSCT and trans-ASCT can prevent the progression of early CALD, but cannot reverse the changes of AMN or halt the progression of adrenal insufficiency. Furthermore, they cannot prevent neurological dysfunction or death in terminal CALD. In recent years, multiple clinical trials of drugs targeting ALD have demonstrated therapeutic potential for ALD. Trans-ASCT and gene editing therapy have also made breakthroughs in animal models and clinical trials, providing alternative options for ALD patients ineligible for allo-HSCT treatment. This paper reviews the latest therapeutic research results of ALD and provides a basis for clinical practice. Reference | Related Articles | Metrics

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Research progress in the clinical application of minimally invasive orthognathic surgery WANG Ruiyang, LIU Kai, WANG Xudong Journal of Shanghai Jiao Tong University (Medical Science)    2025, 45 (1): 101-106.   DOI: 10.3969/j.issn.1674-8115.2025.01.012 Abstract （907）   HTML （26）    PDF（pc） （1292KB）（2318）       Knowledge map    Save Orthognathic surgery is a procedure that involves cutting the deformed segments of the upper and lower jawbones and moving the dentoalveolar complex to a predetermined corrective position, aiming to establish a harmonious dental arch and occlusal relationship and improve facial appearance. With the rapid advancement of medical technology and the accumulation of clinical experience, minimally invasive orthognathic surgery, which uses endoscopy, piezoelectric bone scalpels, lasers, navigation systems, and robotic-assisted surgical devices, is gaining increasing attention due to its advantages of minimal trauma and high precision. However, the clinical application of minimally invasive orthognathic surgery has not yet been systematically explored. Given its significant role in advancing the field of orthognathic surgery, this paper aims to provide a comprehensive review of the latest progress in the clinical application of minimally invasive orthognathic surgery and offer an outlook on future directions, with the goal of providing valuable insights for future research and clinical practice. Reference | Related Articles | Metrics

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Research progress on the neuroinflammation mechanisms in bipolar disorder WANG Xiaohong, FANG Yiru Journal of Shanghai Jiao Tong University (Medical Science)    2025, 45 (1): 107-112.   DOI: 10.3969/j.issn.1674-8115.2025.01.013 Abstract （848）   HTML （34）    PDF（pc） （1288KB）（1911）       Knowledge map    Save Bipolar disorder (BD) is a chronic, recurrent mental illness characterized by extreme fluctuations in mood and state, clinically manifested as recurrent or alternating manic, depressive, and mixed episodes. The pathogenesis is complex and remains unknown, with neuroinflammation considered as a key factor in its development. In-depth research not only helps to understand the etiology, but also provides direction for the development of new therapeutic targets. This paper reviews recent studies on neuroinflammation in BD, discusses changes in peripheral and central inflammation and associated biomarkers, explores the underlying mechanisms of pathogenesis, and briefly describes the mechanisms and potential of mood stabilizers and new therapeutic drugs in anti-inflammatory effect, aiming to suggest possible future research directions. Reference | Related Articles | Metrics

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Research progress in the relationship between ultra-processed food intake and pregnancy outcomes MI Xiaoyang, DING Ying, CHEN Yijing, JIA Jie Journal of Shanghai Jiao Tong University (Medical Science)    2025, 45 (1): 113-121.   DOI: 10.3969/j.issn.1674-8115.2025.01.014 Abstract （954）   HTML （13）    PDF（pc） （1401KB）（2582）       Knowledge map    Save In recent years, the global consumption of ultra-processed foods (UPFs) has increased. UPFs are classified as the fourth group of food in the NOVA classification system: industrially formulated foods made entirely or mostly from substances extracted from foods (oils, fats, sugar, starch, proteins, etc), derivatives of food constituents (hydrogenated fats, modified starches, etc), or multiple food additives. Common manufacturing techniques include extrusion, moulding, and pre-frying. As high-energy-density foods, UPFs are typically characterized by high levels of sugar, fat, and salt, and low levels of dietary fiber, protein, vitamins, and minerals, resulting in low nutrient density. Studies have shown that a high intake of UPFs increases the risk of various chronic diseases. Nutrition during pregnancy is a crucial factor influencing pregnancy outcomes, and balanced and adequate nutrient intake is essential for the health of both the mother and child. Given that UPFs have limited nutritional density, high intake during pregnancy may be detrimental to maternal and infant health. However, the impact of consuming UPFs during pregnancy on maternal and infant health is not extensively studied. This article reviews the literature on the effects of UPFs on pregnancy outcomes, aiming to provide a foundation for further research and personalized dietary guidance. Table and Figures | Reference | Related Articles | Metrics

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A case report of relapsed and refractory multiple myeloma with multifocal extramedullary infiltration and pulmonary adenocarcinoma DU Fang, ZHOU Lingyun, CHEN Jiao, LIU Danbo, XIANG Hongxian, CHEN Haifei Journal of Shanghai Jiao Tong University (Medical Science)    2025, 45 (1): 122-128.   DOI: 10.3969/j.issn.1674-8115.2025.01.015 Abstract （593）   HTML （11）    PDF（pc） （9676KB）（1674）       Knowledge map    Save Multiple myeloma (MM) remains an incurable disease, with most patients experiencing multiple relapses before ultimately progressing to refractory stage. Extramedullary infiltration is a common manifestation of relapse. However, distinguishing synchronous multifocal extramedullary infiltration from secondary malignancies poses significant diagnostic challenges. This study presents a case of relapsed refractory MM with multifocal extramedullary infiltration, diagnosed as coexistence of multiple myeloma extramedullary infiltration and pulmonary adenocarcinoma through multidisciplinary team (MDT) collaboration. Such coexistence is exceedingly rare in clinical practice and introduces substantial complexity in diagnosis and treatment planning. Through a comprehensive case report and literature review, this paper explores the diagnostic and therapeutic approaches to managing multifocal extramedullary infiltration coexisting with secondary malignancies in MM, highlighting the pivotal role of MDT in achieving precise diagnosis and optimizing patient outcomes. Table and Figures | Reference | Related Articles | Metrics

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Analysis of epigenetic characteristics in colonic tumors of Apcmin/+via spatial ATAC-seq technology LIANG Lebin, CHEN Huifang, LAI Shujing, GU liang, SU Bing Journal of Shanghai Jiao Tong University (Medical Science)    2025, 45 (10): 1261-1270.   DOI: 10.3969/j.issn.1674-8115.2025.10.001 Abstract （273）   HTML （24）    PDF（pc） （5460KB）（648）       Knowledge map    Save Objective ·To investigate the spatial epigenetic characteristics of spontaneous colon tumors in Apcmin/+ mice. Methods ·A spatial assay for transposase-accessible chromatin with high-throughput sequencing (ATAC-seq) technology platform was established using an eight-month-old male Apcmin/+ mouse model with spontaneous colon tumors. One tumor from a mouse was harvested and embedded in OCT compound for serial cryosectioning; one tissue section was stained with hematoxylin-eosin (H-E) to observe its histological characteristics, while an adjacent section was processed using spatial ATAC-seq technology to generate spatially resolved DNA libraries, followed by sequencing to obtain spatial chromatin accessibility data. Another tumor from the same mouse was digested into a single-cell suspension, in which viable single cells were sorted by flow cytometry and processed for single-cell RNA sequencing. The results were integrated with spatial chromatin accessibility data to jointly analyze the epigenetic characteristics of the colon tumor microenvironment. Results ·A stable spatial ATAC-seq platform was successfully established, dividing the tumor into malignant, non-malignant, and malignant-non-malignant boundary regions. Transcription factors enriched in malignant regions included NK2 homeobox 5 (NKX2-5) and transcription factor 3 (TCF3). Analysis of transcription factor enrichment in the 3 regions revealed two distinct expression trends: one showing a gradual decrease from malignant to boundary to non-malignant regions, and the other exhibiting high expression in malignant and boundary regions but low expression in non-malignant regions. Gene analysis across regions revealed significant upregulation of hypoxia response, transforming growth factor (TGF), and Kirsten rat sarcoma viral oncogene homolog (KRAS) signaling pathways in malignant regions, with cell cycle-related functions markedly enhanced. Analysis of cell-cell interactions in the tumor microenvironment revealed significant differences in interaction strength: strong interactions within non-malignant regions, moderate interactions between boundary and non-malignant regions, and weak interactions between malignant and boundary regions as well as between malignant and non-malignant regions. Conclusion ·Colon tumors in Apcmin/+ mice exhibit high spatial heterogeneity; malignant regions were enriched with transcription factors including TCF3, and cell interactions between malignant regions and boundary/non-malignant regions were relatively weak. Table and Figures | Reference | Related Articles | Metrics

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Applications and challenges of generative artificial intelligence in psychiatry SONG Yijie, CHEN Tianzhen, ZHONG Na, ZHAO Min Journal of Shanghai Jiao Tong University (Medical Science)    2025, 45 (10): 1271-1278.   DOI: 10.3969/j.issn.1674-8115.2025.10.002 Abstract （375）   HTML （61）    PDF（pc） （1682KB）（1774）       Knowledge map    Save Mental disorders pose a significant challenge to global public health, profoundly affecting the quality of life of a vast number of individuals and imposing a heavy health burden on society. Nonetheless, there remains a substantial gap between the current societal capacity to provide prevention, diagnosis, and treatment for mental disorders and the existing demand for such services. In recent years, the development and application of artificial intelligence (AI) technologies have provided unprecedented opportunities to enhance mental healthcare services. As one of the fastest-growing fields of AI, generative AI has played a pivotal role in analyzing diverse forms of data, including medical image processing, protein structure prediction, clinical document generation, auxiliary diagnostic discrimination, and clinical decision support. These advancements have significantly strengthened capabilities in clinical diagnosis, data reconstruction, and adjunctive therapeutic interventions. This review highlights the potential applications of generative AI in advancing fundamental psychiatric research, identifying early risk factors for mental disorders, and assisting clinicians in diagnosis and treatment. Additionally, it addresses the challenges and limitations currently facing the application of generative AI to mental healthcare, including biases, privacy breaches, and insufficient interpretability. Finally, the review summarizes strategies to enhance AI's capacity to deliver mental health services, aiming to leverage new technologies to reduce the global burden of mental disorders and improve the quality of life of affected individuals. Table and Figures | Reference | Related Articles | Metrics

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Therapeutic effect of artesunate on spontaneous mouse models of Sjögren syndrome (NOD/Ltj mouse) LI Yanxiang, SHI Huan, YU Chuangqi Journal of Shanghai Jiao Tong University (Medical Science)    2025, 45 (10): 1279-1287.   DOI: 10.3969/j.issn.1674-8115.2025.10.003 Abstract （171）   HTML （7）    PDF（pc） （4649KB）（262）       Knowledge map    Save Objective ·To elevate the therapeutic effect of artesunate (ART) on NOD/Ltj mice (non-obese diabetic mice, the spontaneous models of Sjögren syndrome), and explore its potential impact on the distribution of B lymphocyte subsets. Methods ·ICR mice were used as the blank control group, and NOD/Ltj mice were randomly divided into disease and ART groups. NOD/Ltj mice and ICR mice were treated with ART (10 mg/ kg) or its vehicle (0.5%CMC) by oral gavage every other day for 4 weeks. Body weight, salivary flow rate, submandibular gland index, and spleen index were measured. Cytokines in plasma, including interleukin-6 (IL-6), interferon-γ (IFN-γ), and B-cell activating factor (BAFF) in serum, were detected by cytometric bead array (CBA). Hematoxylin-Eosin (H-E) staining of submandibular glands was used to observe the infiltration of lymphocyte. Flow cytometry was applied to analyze the distribution of B lymphocyte subsets in the spleen. The mRNA expression of Prdm1, Il-6r, Il-6, and Stat3 in spleen B lymphocytes was detected by RT-qPCR. The effect of ART on B cells was further detected by CCK-8 and Annexin V-FITC/PI staining by flow cytometry. Results ·Compared to the disease group, ART significantly improved the symptoms of Sjögren syndrome in NOD/Ltj mice. ART treatment also resulted in a reduction in the levels of BAFF, IL-6, and IFN-γ in the plasma (all P<0.05). Moreover, lymphocyte infiltration around the glandular ducts in the submandibular glands was greatly improved in the ART group compared with the disease group. Flow cytometry analysis revealed that the proportion of Naïve B cells in the ART group was significantly increased compared with the disease group, along with a significant reduction in the proportions of double-negative B cells, switched memory B cells, and plasmablasts (all P<0.05). The relative mRNA expression levels of Prdm1, Il-6r,and Stat3 in the ART group were significantly lower than those in the disease group (all P<0.05). The CCK8 assay results showed that after 6 h of treatment, with the extension of the culture time, cell proliferation in the ART group was significantly inhibited; after 24 h of treatment, the number of apoptotic cells in the ART group was significantly higher than that in the control group (P<0.001). Conclusion ·ART demonstrates therapeutic effects in NOD/Ltj mice, potentially through modulating the distribution of peripheral B lymphocyte subsets. It can inhibit the expression of Prdm1, thereby regulating the differentiation of B lymphocytes into plasma cells and plasmablasts. Table and Figures | Reference | Related Articles | Metrics

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Mechanistic study of OGT-promoted non-small cell lung cancer proliferation via the ERK signaling pathway ZHANG Xianzhou, DU Fenglin, WU Lei, REN Yizhe, ZHAO Mingna, LOU Jiatao Journal of Shanghai Jiao Tong University (Medical Science)    2025, 45 (10): 1288-1297.   DOI: 10.3969/j.issn.1674-8115.2025.10.004 Abstract （233）   HTML （7）    PDF（pc） （11210KB）（636）       Knowledge map    Save Objective ·To investigate the expression level of O-GlcNAc transferase (OGT) in non-small cell lung cancer (NSCLC) and its impact on lung cancer proliferation, as well as to explore the underlying mechanisms. Methods ·The expression of OGT in NSCLC tumors and adjacent normal tissues was detected by immunohistochemistry (IHC). The dataset (GSE31210) from the GEO database was analyzed to assess the correlation between OGT expression and NSCLC patient prognosis. siRNA transfection was performed to knock down OGT expression in H460 and H1299 cells, followed by total RNA extraction and transcriptome sequencing. Pathway enrichment analysis was conducted on differentially downregulated genes in the knockdown group compared with the control group, and Western blotting was used to validate the enrichment results. The effects of OGT knockdown on cell proliferation and colony formation in H460 and H1299 cells were evaluated using the cell counting kit-8 (CCK-8) assay and colony formation assay, respectively. The impact of overexpressing downstream genes was also examined. Stable OGT-knockdown cell lines were generated using shRNA and subcutaneously inoculated into nude mice to monitor tumor growth. Results ·IHC revealed that OGT expression was significantly upregulated in NSCLC tumor tissues compared to adjacent normal tissues. Patients with high OGT expression exhibited shorter survival times and poorer prognoses than those with low expression. Transcriptome sequencing demonstrated that genes downregulated after OGT knockdown were primarily enriched in the mitogen-activated protein kinase (MAPK) signaling pathway. Western blotting showed that total extracellular regulated protein kinase 1/2 (ERK1/2) levels remained unchanged in H460 and H1299 cells after OGT knockdown, while phosphorylated ERK1/2 (p-ERK1/2) and its downstream proto-oncogene JUNB protein were markedly reduced. Suppression of OGT expression attenuated the proliferation rate and colony formation capacity of H460 and H1299 cells, whereas JUNB overexpression rescued the proliferation defects induced by OGT knockdown. Notably, H460 cells with stable OGT knockdown formed significantly smaller tumors in nude mice. Conclusion ·OGT is highly expressed in NSCLC and correlates with poor prognosis. Knockdown of OGT inhibits NSCLC cell proliferation and clonogenicity in vitro, and tumor growth in vivo. Mechanistically, OGT appears to promote NSCLC progression by activating the ERK/JUNB signaling axis. Table and Figures | Reference | Related Articles | Metrics

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Role of "HA coat" in modulating stemness and endocrine resistance in ER+ breast cancer WU Shiyi, CHEN Si, LIU Bohan, LIU Yuting, LIU Yiwen, HE Yiqing, DU Yan, ZHANG Guoliang, GUO Qian, GAO Feng, YANG Cuixia Journal of Shanghai Jiao Tong University (Medical Science)    2025, 45 (10): 1298-1307.   DOI: 10.3969/j.issn.1674-8115.2025.10.005 Abstract （176）   HTML （3）    PDF（pc） （6706KB）（295）       Knowledge map    Save Objective ·To determine hyaluronan (HA) expression in the endocrine-resistant microenvironment of estrogen receptor-positive (ER+) breast cancer and elucidate its impact on the acquired resistance. Methods ·Chemiluminescent immunoassay was used to quantify HA levels in the culture supernatants of fulvestrant-resistant breast cancer cells. An immunofluorescence (IF) assay was performed to visualize the colocalization of CD44 and HA in MCF7/FulR cells. Using an established adaptive endocrine-resistant breast cancer mouse model, HA expression in resistant breast cancer tissues was assessed by immunohistochemistry (IHC) assay. Single-cell RNA sequencing (scRNA-seq) and RNA sequencing (RNA-seq) were conducted to examine transcriptomic profiles and alterations in HA-related genes in resistant breast cancer cells. Flow cytometry (FCM) was utilized to measure the proportion of CD44+CD24- cells in MCF7/FulR. The correlation between HA synthesis genes and cell stemness was investigated in clinical ER+ breast cancers from GEO data sets. Hyaluronidase (HAase) treatment was applied to remove the "HA coat", and RT-qPCR and Western blotting analysis were carried out to monitor changes in stemness-related molecules. CCK-8 assays, flow cytometry (FCM), and Hoechst 33258 staining were performed to determine changes in apoptosis and fulvestrant efficiency after HAase treatment. Results ·IF results revealed that compared with MCF7 cells, the "HA coat" on the surface of MCF7/FulR cells was significantly thickened. IHC demonstrated markedly increased HA retention in fulvestrant-resistant mouse breast cancer tissues. ScRNA-seq and RNA-seq analyses indicated elevated expression of stemness-related genes and HA synthesis-associated genes in fulvestrant-resistant breast cancer cells. Correlation analysis revealed a positive association between HA synthesis and cancer stemness in ER+ breast cancer. IF and RT-qPCR results demonstrated that removing the HA coating from the surface of MCF7/FulR cells led to a significant reduction in the expression of stemness-related molecules; concurrently, CCK-8 assays, FCM analysis, and Hoechst 33258 staining revealed that "HA coat" clearance reduced MCF7/FulR' tolerance to fulvestrant and increased apoptosis. Conclusion ·Endocrine-resistant breast cancer cells develop an enriched "HA coat", which promotes stemness in fulvestrant-resistant tumors. Disruption of this HA coat through HAase treatment effectively reduces cell stemness, induces apoptosis, and re-sensitizes breast cancer cells to fulvestrant. Table and Figures | Reference | Related Articles | Metrics

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Identification and mechanistic analysis of core genes associated with morphine tolerance in dorsal root ganglion: an integrative transcriptomics approach using WGCNA and machine learning algorithms YU Zhiyuan, DONG Haiping, GAO Nan, MA Ke Journal of Shanghai Jiao Tong University (Medical Science)    2025, 45 (10): 1308-1319.   DOI: 10.3969/j.issn.1674-8115.2025.10.006 Abstract （162）   HTML （3）    PDF（pc） （4609KB）（651）       Knowledge map    Save Objective ·To develop a multi-algorithm collaborative computational biology strategy for constructing a predictive model of the peripheral morphine tolerance network and for screening high-confidence candidate targets. Methods ·A murine model of morphine tolerance was established across multiple treatment time points. Bulk RNA sequencing was performed on harvested dorsal root ganglion (DRG) tissues. Using the expression matrix as a basis, a weighted gene co-expression network was constructed to identify co-expressed gene modules. Candidate genes were subsequently screened through the integration of differentially expressed genes (DEGs) with key weighted gene co-expression network modules. These candidates underwent functional annotation via Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analyses. A protein-protein interaction (PPI) network was established, and hub genes were systematically identified using the cytoHubba algorithm. Three distinct machine learning approaches, least absolute shrinkage and selection operator (LASSO) regression, support vector machine recursive feature elimination (SVM-RFE) model, and random forest (RF) model, were strategically integrated to screen characteristic signature genes. Finally, gene set enrichment analysis (GSEA) was implemented to functionally validate both the hub and signature genes. Results ·Weighted gene co-expression network analysis (WGCNA) identified 8 297 key module genes, of which 177 candidate genes overlapped with DEGs. These genes were significantly enriched in biological processes including ion channel regulation and vascular smooth muscle contraction. A combination of PPI network analysis and machine learning revealed four signature genes [actin γ2, smooth muscle (Actg2), centriolar coiled-coil protein 110 (Ccp110), neural cell adhesion molecule 2 (Ncam2), and selenium binding protein 1 (Selenbp1)] and six hub genes [actin α2, smooth muscle (Acta2), von Willebrand factor (Vwf) , cellular communication network factor 2 (Ccn2), integrin β4 (Itgb4), integrin α11 (Itga11), and TEK receptor tyrosine kinase (Tek)] closely associated with morphine tolerance. Conclusion ·In this study, we successfully constructed a multi-algorithm collaborative peripheral nerve regulation network prediction model for morphine tolerance, and screened out 10 core genes with high confidence. Table and Figures | Reference | Related Articles | Metrics

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Inhibitory effect and mechanism of saikosaponin A on mouse myeloid-derived suppressor cells QIN Yahan, SHU Yating, PENG Meiyu Journal of Shanghai Jiao Tong University (Medical Science)    2025, 45 (10): 1320-1332.   DOI: 10.3969/j.issn.1674-8115.2025.10.007 Abstract （184）   HTML （7）    PDF（pc） （3545KB）（468）       Knowledge map    Save Objective ·To study the regulatory effect of saikosaponin A (SSA) on the differentiation, apoptosis, and immunosuppressive function of myeloid-derived suppressor cells (MDSCs) in mice, and to explore their molecular mechanism. Methods ·Recombinant mouse granulocyte-macrophage colony-stimulating factor (GM-CSF) was used to induce the differentiation of mouse bone marrow cells (BMCs) into MDSCs, or magnetic beads were used to sort MDSCs from tumor-bearing mice. After treating MDSCs with different concentrations (0, 2.5, 5.0 mg/L), flow cytometry (FCM) was used to detect the differentiation and apoptosis of MDSCs, as well as the expression levels of liver X receptor α (LXRα), arginase-1 (Arg-1), and reactive oxygen species (ROS). At the same time, the effects of MDSCs on the proliferation function of T cells, and the effects on the nuclear factor κB (NF-κB), and signal transducer and activator of transcription 1 (STAT1) signaling pathways were also detected. The mRNA levels of LXRα and Arg-1 were detected by quantitative real-time PCR (qPCR). Mice were given SSA by gavage (ig) or intraperitoneal injection (ip), and the mice were sacrificed after administration; and body mass, spleen weight, and spleen index were calculated. FCM was used to detect the proportion of immune cells in the spleen of mice. Results ·SSA could up-regulate the expression level of LXRα in MDSCs, reduce the differentiation of M-MDSCs, induce apoptosis of MDSCs, reduce the expression levels of Arg-1 and ROS in MDSCs, and reduce the inhibitory effect of MDSCs on T cell proliferation. SSA inhibited the phosphorylation levels of NF-κB and STAT1 in MDSCs. The mice treated with SSA by gavage or intraperitoneal injection showed no significant changes in body weight and spleen index. Both modes of administration can reduce the proportion of MDSCs and their subset M-MDSCs in mice, but had different degrees of regulatory effects on other immune cells. Conclusion ·SSA could regulate the differentiation and apoptosis of MDSCs, and inhibit their immunosuppressive function, which may be associated with the up-regulation of LXRα expression, and down-regulation of the NF-κB and STAT1 signaling pathways in MDSCs. Table and Figures | Reference | Related Articles | Metrics

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Mechanism of GRK subtypes modulating the unique binding properties of M1 acetylcholine receptor and transducers WEI Jiali, WANG Dongxue, WANG Shiqi, XU Jianrong, ZHAO Peishen, ZHAO Lanxue Journal of Shanghai Jiao Tong University (Medical Science)    2025, 45 (10): 1333-1341.   DOI: 10.3969/j.issn.1674-8115.2025.10.008 Abstract （186）   HTML （9）    PDF（pc） （2753KB）（338）       Knowledge map    Save Objective ·To investigate the mechanisms by which different subtypes of G protein-coupled receptor kinases (GRKs) regulate the biased signaling transduction mediated by the muscarinic acetylcholine receptor 1 (M1 receptor), focusing on their molecular effects in modulating the binding of the M1 receptor to the downstream heterotrimeric G protein (Gαq-Gβ1-Gγ2) and β-arrestin 2 (βarr2). Methods ·By establishing a highly sensitive protein interaction detection system based on bioluminescence resonance energy transfer (BRET), six M1 receptor agonists/allosteric modulators were selected to measure the dynamic interactions between the M1 receptor and four GRK subtypes (GRK2/3/5/6), βarr2, and the G protein under stimulation. All BRET data were statistically quantified using the area under the curve (AUC) of the time-response curves. First, concentration-effect curves were established by treatment with gradient concentrations of agonists/allosteric modulators and AUC fitting, to comprehensively analyze the differences in efficacy between each agonist/allosteric modulator and the endogenous agonist acetylcholine chloride (ACh) in promoting the interactions of M1 receptor with GRK3/5, βarr2, and the G protein; next, GRKs were divided into two groups based on subtypes: GRK2/3 and GRK5/6. The maximum AUC values for the interaction between the M1 receptor and the two GRK groups under high concentrations were calculated respectively, to further evaluate the regulatory propensity of different types of GRKs on the binding strength of the M1 receptor to βarr2 or the G protein. Results ·All six agonists/allosteric modulators effectively induced the association of the M1 receptor with GRK3, while simultaneousey inducing dissociation of the M1 receptor from GRK5. The allosteric modulator BQCA not only activated the M1 receptor alone and triggered its binding to downstream signaling proteins, but also, when co-treated with ACh, caused a significant leftward shift of the concentration-effect curves in the M1-G protein and M1-βarr2 systems, suggesting that its potentiation effect on ACh was mainly achieved by reducing the half-maximal effective concentration. A moderate positive correlation was observed between the maximum AUC values of M1-βarr2 and M1-G protein interactions induced by the seven groups of drug treatments (r =0.722, P=0.067). Further analysis showed that the ratio of the maximum AUC for M1-GRK2/3 interaction to that for M1-GRK5/6 interaction was also positively correlated with the ratio of the maximum AUC for M1-βarr2 interaction to that for M1-G protein interaction (r =0.760, P=0.047). Conclusion ·The M1 receptor may be pre-coupled with GRK5/6 under basal conditions, and they dissociate upon receptor activation, suggesting that GRK5/6 may be involved in M1 receptor inactivation or signal reprogramming. The relative efficiency of the M1 receptor's interaction with different GRK subtypes determines its preference for downstream signaling pathways. Table and Figures | Reference | Related Articles | Metrics

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Identification and evaluation of COL12A1 as a novel serological diagnostic marker in pancreatic ductal adenocarcinoma LIU Jia, REN Lingjie, SHI Minmin, TANG Xiaomei, MA Fangfang, QIN Jiejie Journal of Shanghai Jiao Tong University (Medical Science)    2025, 45 (10): 1342-1352.   DOI: 10.3969/j.issn.1674-8115.2025.10.009 Abstract （158）   HTML （3）    PDF（pc） （2853KB）（167）       Knowledge map    Save Objective ·To identify and evaluate novel and reliable non-invasive serological biomarkers for detecting pancreatic ductal adenocarcinoma (PDAC). Methods ·Sixty-seven PDAC patients (Ruijin cohort Ⅰ) were recruited at Pancreatic Center, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, from May 2018 to December 2019. Global proteome profiling of 67 PDAC tumor tissues and 67 matched adjacent normal tissues was performed using mass spectrum. Bioinformatics analysis on the proteomics data was conducted to identify new biomarkers, and receiver operating characteristic (ROC) curves and the area under the curve (AUC) were used to evaluate their value of detecting PDAC. The proteomic and mRNA sequencing data were further downloaded and analysed from the Clinical Proteomic Tumor Analysis Consortium (CPTAC) cohort for validation. In addition, the Ruijin Cohort Ⅱ, consisting of 47 PDAC patients and 75 healthy individuals, was recruited for a case-control study from June 2021 to June 2022. Enzyme-linked immunosorbent assay (ELISA) was used to detect the expression level of new biomarkers in the serum of patients and healthy individuals to evaluate the serological diagnostic values of them. Results ·Collagen type Ⅻ α1 chain (COL12A1) was identified as a candidate biomarker for PDAC diagnosis based on differential expression analysis on the proteomic data and was validated to be higher in tumor tissues than in adjacent normal tissues in the CPTAC cohort. In addition, COL12A1 protein levels were significantly higher in the sera of PDAC patients than in those of healthy controls, showing good diagnostic performance with an AUC of 0.82, a sensitivity of 81%, and a specificity of 83%. ROC analysis revealed that COL12A1 improved the performance of carbohydrate antigen 199 (CA199) in distinguishing PDAC patients from healthy individuals (AUCCA199=0.91 vs AUCCA199 +COL12A1=0.95, P<0.05). Furthermore, COL12A1 also showed excellent ability to distinguish early-stage PDAC patients (stage Ⅰ‒Ⅱ) from healthy individuals (AUCCOL12A1=0.83), and significantly improved the AUC of CA199 in early-stage PDAC patients (AUCCA199=0.92 vs AUCCA199+COL12A1=0.97, P<0.05). Conclusion ·COL12A1 is a potential serological diagnostic marker that complements CA199 in detecting early-stage PDAC. Table and Figures | Reference | Related Articles | Metrics

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A comparative study on the efficacy of two types of rotary nickel-titanium files in removing root canal fillings TAI Zhaowei, HU Zihang, TAN Chyiyann, PENG Weiwei, DU Rong Journal of Shanghai Jiao Tong University (Medical Science)    2025, 45 (10): 1353-1360.   DOI: 10.3969/j.issn.1674-8115.2025.10.010 Abstract （198）   HTML （4）    PDF（pc） （4188KB）（164）       Knowledge map    Save Objective ·To explore the efficacy of the XP-Endo Shaper (XPS) and Reciproc (RC) engine-driven nickel-titanium file systems in removing root canal fillings, and to provide evidence for clinical application. Methods ·The maxillary first permanent molars were obtained from patients who visited the Department of General Dentistry, Shanghai Ninth People's Hospital, Shanghai Jiao Tong University School of Medicine, between March and September 2022, which required tooth extraction due to periodontal disease. A total of 30 mesiobuccal or distobuccal root canals with moderate curvature were selected and randomly divided into the RC file group (control group, n=15) and the XPS file group (experimental group, n=15). All root canals were first negotiated and shaped using M3-PRO nickel-titanium files, followed by root canal obturation with bioceramic paste using the single-cone technique. Then, RC files (R25) were used in the control group, while XPS files were used in the experimental group to remove the root canal obturation. Cone Beam Computed Tomography (CBCT) scans were performed before and after the removal procedures. The time required for obturation removal, the percentage of residual obturation volume, the amount of apical debris extrusion, and the degree of instrument deformation were recorded. Independent-sample t-tests and chi-square test were used to compare the differences between the two groups. Results ·The XPS group required slightly more time (118.87±18.58) s than the RC group (107.93±14.79) s, but the difference between two groups was not statistically significant. The XPS group had a lower percentage of residual obturation volume (7.51±8.06)% compared to the RC group (15.02±14.63)%, but the difference was not statistically significant. The XPS group had significantly less apical debris extrusion (6.15±1.42) mg than the RC group (8.29±2.01) mg, with a statistically significant difference (P=0.002). Both groups exhibited varying degrees of instrument deformation, but yet no instrument separation occurred in either group. Conclusion ·The RC engine-driven nickel-titanium files were slightly more time-efficient in removing root canal fillings, whereas the XPS files achieved a higher canal cleanliness and produced less apical debris extrusion. As there was no significant difference in removal time, and considering the superior cleaning performance and reduced risk of postoperative complications, the XPS file system appears more suitable for removing root canal fillings in moderately curved root canals. Table and Figures | Reference | Related Articles | Metrics

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Online risk calculator and nomogram prediction model for urinary incontinence after robot-assisted laparoscopic radical prostatectomy DUN Yiting, ZHAO Jing, FENG Chengling, LI Xingjian, CUI Di, HAN Bangmin Journal of Shanghai Jiao Tong University (Medical Science)    2025, 45 (10): 1361-1371.   DOI: 10.3969/j.issn.1674-8115.2025.10.011 Abstract （254）   HTML （9）    PDF（pc） （4344KB）（398）       Knowledge map    Save Objective ·To develop a nomogram prediction model and an online risk calculator, and to predict the continence of patients after robot-assisted laparoscopic radical prostatectomy (RARP). Methods ·A total of 604 prostate cancer patients who underwent RARP and had preoperative prostate magnetic resonance imaging at the Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine from September 2022 to December 2024 were analyzed and included. All patients were randomly resampled and divided into a training set (n=420) and a validation set (n=184) at a ratio of 7∶3. The patients' continence was followed up every month from the first month after the operation. The least absolute shrinkage and selection operator (LASSO) model was applied to screen the features. A Logistic multivariate regression analysis was used to establish a prediction model integrating the features selected from the LASSO analysis. The receiver operator characteristic (ROC) curve was drawn to predict the recovery of continence in patients after RARP, and the areas under the curve were compared by the DeLong test to evaluate the discrimination of the model. Calibration curves and decision curve analysis (DCA) were used to evaluate the calibration and clinical utility the model. Results ·According to the postoperative continence follow-up data of the patients, the continence rate of the patients at 3 months after the operation was 58.28% (352/604). The length of the membranous urethra, the thickness of the right levator ani muscle, and blood loss were identified as independent predictors of early postoperative (3-month) incontinence by Logistic multivariate regression analysis of the training set. The area under the ROC curve was calculated as 0.976 (0.954, 0.998) for the training set and 0.977 (0.945, 1.000) for the validation set, demonstrating good discrimination of this model. No significant difference between the ROC curves of the training set and the validation set was confirmed by the DeLong test (P=0.949). A good goodness of fit of this model was demonstrated by the Hosmer-Lemeshow test (P=0.179). The clinical utility of the nomogram prediction model was indicated by the DCA plot. This nomogram prediction model was incorporated into an online calculator (https://yitingd.shinyapps.io/DynNomapp). Conclusion ·This study developed and validated a nomogram prediction model that can effectively predict the early continence of patients after RARP. The length of the membranous urethra, the thickness of the right levator ani muscle, and the intraoperative blood loss are significant independent predictors of early postoperative incontinence. Table and Figures | Reference | Related Articles | Metrics

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Relationship between non-renin-dependent aldosterone and left ventricular hypertrophy in essential hypertension CHANG Guili, LIU Changyuan, LI Mingchun, HU Zhe, CHEN Jing, CAO Qun'an, CHU Shaoli, CHEN Xin Journal of Shanghai Jiao Tong University (Medical Science)    2025, 45 (10): 1372-1377.   DOI: 10.3969/j.issn.1674-8115.2025.10.012 Abstract （163）   HTML （2）    PDF（pc） （1302KB）（203）       Knowledge map    Save Objective ·To analyze the influencing factors of left ventricular mass index (LVMI) in patients with essential hypertension, and explore the relationship between aldosterone levels and left ventricular hypertrophy (LVH). Methods ·A total of 155 patients with essential hypertension, hospitalized in the Hypertension Department of the Northern Campus of Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, from January 2013 to December 2019, and excluded from primary aldosteronism by saline load test (post-saline suppression plasma aldosterone <60 pg/mL), were enrolled. General clinical data (age, gender, smoking status, duration of hypertension, etc.), physical examination data (blood pressure and body mass index), blood biochemistry (renal function, electrolytes, fasting blood glucose, and lipids), urinary sodium, and relevant hormones (basal and activated aldosterone, basal and activated renin, urinary aldosterone, post-saline suppression aldosterone, etc.) were collected. LVMI was evaluated by echocardiography. Pearson correlation analysis was used to assess the linear association between LVMI and each variable. Binary Logistic regression models were applied to screen independent risk factors for LVH. Multiple linear regression models were used to assess the impact of variables on LVMI. Results ·The mean age of the 155 patients was (46.85±11.08) years, with 51.6% being male. Pearson correlation analysis showed that LVMI was significantly positively correlated with post-saline suppression aldosterone (r=0.334, P<0.001), age (r=0.184, P=0.032), duration of hypertension (r=0.241, P=0.005), systolic blood pressure (r=0.280, P=0.001), and pulse pressure (r=0.339, P<0.001). No significant correlations were found with diastolic blood pressure, body mass index, fasting blood glucose, total cholesterol, low-density lipoprotein cholesterol, triglyceride, high-density lipoprotein cholesterol, urinary sodium, basal aldosterone, activated aldosterone, or urinary aldosterone. After adjusting for confounders, including gender, smoking history, age, duration of hypertension, body mass index, pulse pressure, systolic blood pressure, fasting blood glucose, and total cholesterol, binary Logistic regression showed that each 1 pg/mL increase in post-saline suppression aldosterone was associated with a 5.1% increased risk of LVH (OR=1.051, 95%CI 1.016‒1.088, P=0.004). Multiple linear regression identified suppressed aldosterone (β=0.359, P<0.001), duration of hypertension (β=0.168, P=0.046), and pulse pressure (β=0.226, P=0.008) as independent influencing factors for LVMI. Conclusion ·Suppressed aldosterone is an independent influencing factor for LVH in patients with essential hypertension. Table and Figures | Reference | Related Articles | Metrics

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Progress of impaired memory suppression in patients with depressive disorders GENG Menglu, LI Chunbo Journal of Shanghai Jiao Tong University (Medical Science)    2025, 45 (10): 1378-1382.   DOI: 10.3969/j.issn.1674-8115.2025.10.013 Abstract （227）   HTML （16）    PDF（pc） （1166KB）（688）       Knowledge map    Save The intentional suppression of memory retrieval to achieve directed forgetting is a crucial adaptive function for individuals. In psychotherapy theory, such active forgetting is often associated with trauma, where in individuals actively exclude trauma-related negative memories from awareness to reduce unpleasant emotional experiences. Based on the "go/no-go" task paradigm, researchers developed the "think/no-think" (TNT) paradigm, and through this paradigm, they have revealed that individuals can achieve active forgetting by suppressing the retrieval of previously encoded memories. Patients with depressive disorders often exhibit cognitive processing biases toward negative information. Compared to healthy populations, they demonstrate impaired memory retrieval suppression in TNT tasks, especially for negative memories. This deficit in retrieval suppression makes negative memories more susceptible to reactivation, triggering negative emotions and perpetuating a vicious cycle. Relevant neuroimaging results show that during memory retrieval suppression, the lateral prefrontal lobe exerts top-down control through relevant regions to modulate memory processing of hippocampus, thereby blocking intentional recall. Abnormalities in the prefrontal-hippocampal inhibitory pathway and hyperactivation of the amygdala in depressed individuals may be the underlying neural mechanisms for their impaired suppression of negative memory retrieval.This article provides a review focusing on the negative memory bias exhibited in depressed individuals in the TNT task and the exploration of its underlying mechanisms. It summarizes relevant research findings with the aim of offering references for the development of precise psychotherapies and novel approaches targeting the improvement of specific symptom clusters. Reference | Related Articles | Metrics

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Research progress on ferroptosis of placental cells in recurrent spontaneous abortion LI Guanghui, FENG Xiaoling Journal of Shanghai Jiao Tong University (Medical Science)    2025, 45 (10): 1383-1389.   DOI: 10.3969/j.issn.1674-8115.2025.10.014 Abstract （188）   HTML （13）    PDF（pc） （2624KB）（160）       Knowledge map    Save Recurrent spontaneous abortion (RSA) is a pregnancy complication with a complex etiology that seriously threatens the fertility and physical and mental health of women of childbearing age. As the main component of the maternal-fetal interface, the placenta plays a central role in maternal and fetal health during pregnancy, and its dysfunction is closely associated with the development of RSA. Iron homeostasis is essential for supporting maternal needs, placental function, and fetal development. In recent years, ferroptosis, a novel form of cell death triggered by iron overload and the accumulation of lipid peroxides, has garnered increasing attention regarding its regulatory mechanisms in the physiological and pathological processes of the female reproductive system. Ferroptosis has been confirmed to correlate with placental pathology and to influence the pathogenesis of RSA. The placenta plays a crucial role in regulating iron transport. This paper systematically reviewed the mechanisms of ferroptosis in placental cells and its involvement in the pathogenesis of RSA by affecting trophoblast cell function, causing decidualization disorders, inducing angiogenesis defects, and the potential of ferroptosis-related molecules in the treatment of RSA was analyzed, with the aim of providing research directions for improving the pregnancy outcomes in patients with RSA. Table and Figures | Reference | Related Articles | Metrics

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Advances in the treatment of pediatric B-cell acute lymphoblastic leukemia with high-risk cytogenetics TANG Junqian, LI Benshang Journal of Shanghai Jiao Tong University (Medical Science)    2025, 45 (10): 1390-1399.   DOI: 10.3969/j.issn.1674-8115.2025.10.015 Abstract （275）   HTML （10）    PDF（pc） （1362KB）（405）       Knowledge map    Save B-cell acute lymphoblastic leukemia (B-ALL) is one of the most common pediatric malignancies, characterized by highly heterogeneous genetic alterations. The precise identification of high-risk genetic abnormalities, such as BCR-ABL1, KMT2A rearrangement, and TCF3-HLF, plays a crucial role in risk stratification, the formulation of chemotherapy regimens, and the selection of individualized therapies. High-risk cytogenetics can profoundly impact the trajectory of disease progression and therapeutic outcomes. Regarding therapy, the refinement of treatment strategies through precise molecular classification and risk stratification has catalyzed a gradual paradigm shift in clinical practice. This transition moves away from the traditional reliance on conventional chemotherapy agents toward individualized pharmacotherapy and disease management strategies based on prognostic risk stratification. In recent years, immunotherapy has achieved significant progress in leukemia treatment. Chimeric antigen receptor T-cell (CAR-T) therapy and monoclonal antibodies have emerged as novel therapies for patients with relapsed/refractory (R/R) B-ALL harboring high-risk cytogenetic features. These innovations have significantly improved the prognosis for this patient population. Currently, new clinical trials are continuously advancing. Emerging targeted therapies and cell therapies represented by CAR-T cells have become hot spots of current research and have demonstrated remarkable development potential. This review synthesizes recent therapeutic advances across pediatric B-cell acute lymphoblastic leukemia subtypes harboring high-risk genetic abnormalities, with a focused emphasis on the evolving role of immunotherapy. By critically integrating current evidence, we aim to outline rational strategies for developing safer and more effective therapies that can meaningfully improve clinical outcomes in these high-risk children and adolescents. Table and Figures | Reference | Related Articles | Metrics

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Diagnosis and treatment analysis of two cases of severe fever with thrombocytopenia syndrome complicated with hemophagocytic lymphohistiocytosis QIAO Liang, ZHANG Tingjuan, FENG Yuan, YANG Lei, QIAN Jun, ZHOU Jingdong Journal of Shanghai Jiao Tong University (Medical Science)    2025, 45 (10): 1400-1406.   DOI: 10.3969/j.issn.1674-8115.2025.10.016 Abstract （174）   HTML （2）    PDF（pc） （2064KB）（301）       Knowledge map    Save Case 1, a 69-year-old male patient, was admitted to our hospital due to "dizziness, fatigue, nausea, diarrhea, and oral bleeding for 10 d", with a recent history of field farming work. The patient exhibited leukopenia, thrombocytopenia, and clinical manifestations of multi-organ dysfunction, including coagulation dysfunction, liver function abnormalities, gastrointestinal disorders, myocardial injury, and respiratory failure. Bone marrow aspiration smear revealed hemophagocytosis, and out-of-hospital testing for the severe fever with thrombocytopenia syndrome bunyavirus was positive. The patient was diagnosed with severe fever with thrombocytopenia syndrome (SFTS) complicated by hemophagocytic lymphohistiocytosis (HLH). After diagnosis, glucocorticoid combined with ribavirin treatment was initiated. However, the patient still died, which may be related to factors such as delayed medical consultation, advanced age, and poor control of viral replication. Case 2, a 73-year-old male patient, was admitted to our hospital due to "fatigue for 1 week", with a recent history of field farming work. The patient also presented with leukopenia and thrombocytopenia, combined with liver and coagulation function abnormalities. Bone marrow aspiration smear showed hemophagocytosis, and the patient was highly suspected of SFTS with HLH. We empirically initiated preemptive treatment with favipiravir for antiviral therapy, combined with glucocorticoid for anti-inflammation, to early inhibit novel bunyavirus replication and cytokine storm. Subsequent testing reported the severe fever with thrombocytopenia syndrome bunyavirus nucleic acid quantification as 2.69×10³ 50% tissue culture infective dose (TCID50)/mL, confirming the diagnosis of SFTS with HLH. The patient's clinical symptoms and various indicators generally improved. Review of these two similar cases suggests that early empirical preemptive use of favipiravir to control viral replication in clinical practice may improve the treatment and prognosis of patients with SFTS complicated by HLH. Table and Figures | Reference | Related Articles | Metrics

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Expression of long noncoding RNA LINC00467 and its mechanism in affecting lung adenocarcinoma progression GUO Linyan, ZHANG Hailong, ZHENG Chao, LEI Ming Journal of Shanghai Jiao Tong University (Medical Science)    2025, 45 (11): 1407-1420.   DOI: 10.3969/j.issn.1674-8115.2025.11.001 Abstract （198）   HTML （31）    PDF（pc） （54055KB）（154）       Knowledge map    Save Objective ·To investigate the expression of long noncoding RNA (lncRNA) LINC00467 in lung adenocarcinoma (LUAD) and its impact on the poor prognosis of patients, as well as its functional role and underlying molecular mechanisms in the occurrence and development of LUAD. Methods ·First, tumor sample data from The Cancer Genome Atlas (TCGA) database were utilized to analyze the expression levels of LINC00467 in LUAD tissues and its correlation with patient survival. Second, a stable LINC00467-knockdown LUAD cell line was established, and the effects of LINC00467 on LUAD cell proliferation, colony formation, migration, and tumorigenicity were assessed through cell phenotypic experiments (including live-cell imaging for cell proliferation analysis, plate colony formation assays, and wound healing assays) and nude mouse tumor formation experiments. Furthermore, RNA sequencing (RNA-seq), differentially expressed genes (DEGs) analysis, and hallmark gene sets enrichment analysis were performed to identify signaling pathways regulated by LINC00467, and Western blotting was used to validate its impact on tumor cell pathways. Finally, RNA pull-down combined with mass spectrometry and co-immunoprecipitation (co-IP) assays were conducted to filter and identify LINC00467-interacting proteins. Results ·Analysis of tumor sample data from the TCGA database showed that LINC00467 was highly expressed in LUAD, and its expression level was negatively correlated with overall survival in LUAD patients (P=0.004). Cell phenotypic experiments and nude mouse tumor formation experiments demonstrated that LINC00467 knockdown significantly inhibited the proliferation, colony formation, migration and in vivo tumorigenesis of LUAD cells (all P<0.05). RNA-seq, DEGs analysis, hallmark gene sets enrichment analysis, and Western blotting indicated that knockdown of LINC00467 suppressed the activation of nuclear factor kappa-B (NF-κB) signaling pathway. RNA pull-down combined with mass spectrometry and co-IP assays demonstrated that LINC00467 interacted with casein kinase 2 alpha 2 (CSNK2A2) and promoted the phosphorylation of NF-κB p65. Conclusion ·High expression of LINC00467 in LUAD tissues is negatively correlated with patient prognosis. LINC00467 can interact with CSNK2A2, promote the phosphorylation of NF-κB p65, activate the NF-κB pathway, and enhance LUAD proliferation, colony formation, migration, and in vivo tumorigenesis. Table and Figures | Reference | Related Articles | Metrics

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Three-dimensional imaging of cochlear nerve fibers based on multi-scale resolution CHENG Yaqiong, DU Yiwei, LIU Sidi, JING Dian, WU Hao Journal of Shanghai Jiao Tong University (Medical Science)    2025, 45 (11): 1421-1431.   DOI: 10.3969/j.issn.1674-8115.2025.11.002 Abstract （175）   HTML （25）    PDF（pc） （25678KB）（179）       Knowledge map    Save Objective ·To establish a standardized research platform for comprehensive imaging of the cochlea and its surrounding tissues through multi-scale resolution three-dimensional (3D) imaging, thereby enabling 3D visualization and analysis of the cochlea under physiological conditions. Methods ·The cochlea or combined cochlea and whole brain samples were obtained from 8‒12-week-old thymus cell antigen 1 (Thy1) -driven yellow fluorescent transgenic mice (Thy1-YFP-16 mice) after cardiac perfusion. Tissue clearing was performed using PEGASOS, followed by direct imaging of the cochlea and surrounding tissues through their entire depth using a laser confocal microscope with 4× and 10× objectives. For individual cochlear samples, whole tissue immunofluorescence staining was performed in combination with a neurofilament-200 (NF200) antibody and propidium iodide (PI) fluorescent dye, in the process of tissue clearing and embedding using PEGASOS and TESOS techniques. The entire cochlea was then subjected to serial sectioning with a paraffin microtome, and each section was imaged using a laser confocal microscope equipped with a 63× oil immersion objective. 3D reconstruction was performed using ImageJ for image stitching, followed by image processing, single-nerve-fiber tracking, and length measurement conducted in Imaris software. Fiber path curvature was calculated using MATLAB, and statistical analyses were performed with GraphPad Prism. Results ·Transparent cochlear and surrounding tissue samples were successfully prepared using tissue clearing techniques. The cochlea and its surrounding tissues were directly imaged by low- and medium-magnification objectives on the confocal microscope, which reconstructed the 3D morphology of the cochlea and delineated its spatial relationship with adjacent structures such as the vestibular nerve. Serial sectioning and imaging with a high-magnification objective enabled 3D imaging of the entire cochlear sample at single-cell resolution. This approach revealed the overall pathway of THY1+ fibers within the cochlea, extending from the hair cell region to the modiolus. Single nerve fiber tracing revealed distinct trajectory characteristics of the cochlear efferent nervous system and auditory nerve fibers near the spiral ganglion. Conclusion ·The PEGASOS and TESOS techniques enable multi-scale resolution 3D imaging of the cochlea and its surrounding tissues as an integrated whole. When combined with whole-tissue immunofluorescence staining, this methodology can be used to delineate the 3D spatial relationships between the cochlea and adjacent tissues, as well as between cells and nerve fibers within the cochlea itself. Furthermore, it allows for the tracing of individual nerve fiber pathways. Table and Figures | Reference | Related Articles | Metrics

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Review of CAR-T cell therapy for autoimmune diseases WANG Xueyi, LI Benshang Journal of Shanghai Jiao Tong University (Medical Science)    2025, 45 (11): 1432-1442.   DOI: 10.3969/j.issn.1674-8115.2025.11.003 Abstract （238）   HTML （13）    PDF（pc） （1941KB）（249）       Knowledge map    Save Chimeric antigen receptor T cell (CAR-T) therapy, which involves genetically engineering T cells to specifically recognize and efficiently eliminate target cells, has achieved groundbreaking success in treating hematological malignancies such as B-cell lymphoma and leukemia. Driven by its unique mechanism of action, research into extending its applications to other disease areas is actively underway. In particular, CAR-T therapy has shown significant potential in treating autoimmune diseases (AIDs), attracting considerable attention. Current conventional treatments for AIDs, including glucocorticoids, immunosuppressants, and biologics, are often associated with limitations such as limited efficacy, short duration of remission, and long-term toxicity. In contrast, CAR-T therapy has emerged as a highly promising treatment strategy for AIDs, owing to its advantages of precise targeting and the capacity to induce sustained, drug-free remission. This article reviews recent preclinical and clinical advances in CAR-T therapy for various AIDs, demonstrating its feasibility in eradicating pathogenic B cells and reestablishing immune tolerance. It also examines the major challenges confronting this treatment approach, including adverse effects, limited persistence, and treatment resistance in some patients. Furthermore, strategies to address these challenges are discussed, focusing on the optimization of the chimeric antigen receptor (CAR) structure, the exploration of novel specific targets, and the development of universal CAR-T products. Finally, future research directions are outlined, with the aim of providing a rational foundation for the further development and refinement of CAR-T therapy for AIDs. Table and Figures | Reference | Related Articles | Metrics

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LINC01123 promotes proliferation and glycolysis of gastric cancer via binding to ENO1 ZHANG Shuqiong, KE Xing, ZHAO Xinghe, CHEN Xiaocui, ZHENG Haodong, CHEN Hui, SHEN Lisong, YANG Junyao Journal of Shanghai Jiao Tong University (Medical Science)    2025, 45 (11): 1443-1457.   DOI: 10.3969/j.issn.1674-8115.2025.11.004 Abstract （126）   HTML （13）    PDF（pc） （130835KB）（134）       Knowledge map    Save Objective ·To investigate the expression and tumor-promoting mechanism of the long non-coding RNA (lncRNA) LINC01123 in gastric cancer and evaluate its potential as a novel diagnostic biomarker and therapeutic target. Methods ·Differential expression analysis of lncRNAs between gastric cancer and normal tissues was performed based on The Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO) datasets (GSE95667, GSE99416) by using R software. LINC01123 was identified as the candidate of interest. Its expression was validated in gastric cancer cell lines and clinical tissue samples by using qRT-PCR. The biological effects of LINC01123 on cell proliferation and metastasis were evaluated in vitro through gene overexpression and knockdown by utilizing CCK-8, colony formation, wound healing, and Transwell migration and invasion assays. In vivo, a subcutaneous xenograft tumor model in nude mice was established to assess the effect of LINC01123 on tumor growth. ATP and lactate production were measured to evaluate the role of LINC01123 in glycolysis. Transcriptome sequencing and Gene Set Enrichment Analysis (GSEA) were conducted to explore related pathways. RNA pull-down combined with mass spectrometry was used to identify proteins interacting with LINC01123. The binding region was predicted using the catRAPID database and validated by constructing α-enolase (ENO1) protein truncation mutants and performing RNA immunoprecipitation (RIP) assays. Functional interaction studies were carried out to determine whether ENO1 mediates the oncogenic effect of LINC01123. Results ·LINC01123 was upregulated in gastric cancer tissues and cell lines and was associated with poor patient prognosis (P=0.021). Functional assays demonstrated that LINC01123 promoted proliferation, migration, invasion, and glycolysis of gastric cancer cells such as MKN-45 in vitro, and enhanced tumor growth in vivo (all P<0.05). Mechanistically, LINC01123 was predominantly localized in the cytoplasm and bound to the 97‒237 amino acid region of ENO1 protein. Further studies showed that ENO1 knockdown in LINC01123-overexpressing cells partially reversed the proliferative and migratory effects of LINC01123 (all P<0.05) , indicating that ENO1 upregulation enhances the tumor-promoting function of LINC01123. Conclusion ·LINC01123 is highly expressed in gastric cancer and promotes tumor progression by binding to ENO1 protein and enhancing proliferation, migration, invasion, and glycolysis. LINC01123 holds promise as a novel diagnostic and prognostic biomarker and a potential therapeutic target for gastric cancer. Table and Figures | Reference | Related Articles | Metrics

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N-glycosylation of Cav3.2 channel in DRG neurons of myelinated A-fiber contributes to diabetic mechanical allodynia LIAO Chenlong, LI Shuo, XU Xin, ZHANG Yue, ZHANG Wenchuan Journal of Shanghai Jiao Tong University (Medical Science)    2025, 45 (11): 1458-1465.   DOI: 10.3969/j.issn.1674-8115.2025.11.005 Abstract （109）   HTML （8）    PDF（pc） （7927KB）（93）       Knowledge map    Save Objective ·To investigate the association of Cav3.2 channel N-glycosylation in myelinated A-fiber dorsal root ganglion (DRG) neurons with diabetic mechanical allodynia (MA). Methods ·Diabetic rat models were induced by a single intraperitoneal injection of streptozotocin. Pain behavior assessments, including evaluations of MA and thermal hyperalgesia (TH), were conducted on a weekly basis. Diabetic rats exhibiting TH were subsequently categorized into two subcategories based on the onset of mechanical allodynia by the third week. The impact of N-glycosylation on both the expression of Cav3.2 channels in DRG neurons and pain behaviors was investigated through sequential administration of neuraminidase (NEU) and TTA-P2, a selective blocker of T-type calcium channels, after C-unmyelinated fiber blockage by the application of resiniferatoxin (RTX). The extent of Cav3.2 N-glycosylation was quantitatively compared between diabetic rats with and without MA by analyzing the N-terminal fragment of Cav3.2 following de-glycosylation. Results ·Higher levels of Cav3.2 expression in myelinated A-fiber DRG neurons were observed in diabetic rats with MA compared to those without MA (P<0.001). NEU-induced de-glycosylation led to a reduction in Cav3.2 expression across all groups, with diabetic rats with MA maintaining higher levels of the Cav3.2 expression than those without MA (P<0.05). It was observed that RTX eliminated only TH and not MA, whereas NEU had a restorative effect on both TH and MA, similar to TTA-P2. Diabetic rats with MA exhibited increased expression of N-terminal fragments compared to those without MA (P<0.001). Conclusion ·N-glycosylation of the Cav3.2 channel within DRG neurons of myelinated A-fiber is a contributing factor to diabetic MA. Table and Figures | Reference | Related Articles | Metrics

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CD10+ neutrophils promote CD8+ T-cell depletion in mucosal malignant melanoma through the SELPG-SELL pathway HAO Meiling, MA Yanni, MA Xuhui, ZHANG Yanjie, ZENG Hanlin, CHEN Shanshuang Journal of Shanghai Jiao Tong University (Medical Science)    2025, 45 (11): 1466-1479.   DOI: 10.3969/j.issn.1674-8115.2025.11.006 Abstract （168）   HTML （5）    PDF（pc） （5132KB）（138）       Knowledge map    Save Objective ·To compare the immune microenvironment of mucosal malignant melanoma (MM) and cutaneous malignant melanoma (CM) using single-cell transcriptome analysis system, and to elucidate the key regulatory mechanism of CD8+ T cell depletion in MM. Methods ·A total of 36 531 cells from three treatment-naïve MM surgical specimens and three CM samples were subjected to single-cell RNA sequencing. Data pre-processing included batch correction, strict quality control (based on mitochondrial gene ratio and gene number screening), unsupervised clustering, and cell-type annotation (using established marker genes). Differential gene analysis (Wilcoxon test), gene set enrichment analysis [based on Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) databases], cell-cell interaction network analysis, and prognostic association analysis using. The Cancer Genome Atlas (TCGA) were used to comprehensively analyse the heterogeneity of MM and CM tumour immune microenvironment. Results ·Compared with CM, the expression of cytotoxicity-related genes (GZMB, IFNG, etc.) in CD8+ T cells in MM was reduced (P<0.001), while the depletion markers (PDCD1, LAG3, etc.) were significantly up-regulated (P<0.001). The proportion of depleted CD8+ T cell subsets increased by nearly 6 times (CM: 3.38% vs MM: 19.26%, P<0.010), and the terminal depletion score was higher. In addition, the level of neutrophil infiltration in the MM microenvironment was significantly higher than that in CM (CM: 1.6% vs MM: 34.1%, P=0.009), and single-cell analysis further divided it into five subgroups. Among them, the CD10+ neutrophil subset (accounting for 23.52% of MM neutrophils) highly expressed pro-inflammatory molecules (S100A8/A9) and immunosuppressive molecules (MME/CD10, CD55), and the characteristic scores of myeloid-derived suppressor cells (MDSCs) in this subset were significantly higher than those of other subgroups. TCGA and MM cohort analyses further confirmed that the highly expressed genes of this subset were independently associated with poor prognosis (P=0.049), suggesting that this subset was involved in tumour immunosuppressive effects. Mechanistically, CD10+ neutrophils interacted with depleted CD8+ T cells through the SELPLG-SELL ligand-receptor pair, driving T-cell inactivation. Conclusion ·Single-cell transcriptome sequencing was performed on MM clinical samples, and the single-cell immunomes of MM and CM were systematically compared, suggesting that CD10+ neutrophils in MM induce CD8+ T-cell terminal depletion through the SELPLG-SELL pathway. The molecular mechanism of MM immunotherapy tolerance was elucidated, providing a new strategy for targeting neutrophil-T cell interaction. Table and Figures | Reference | Related Articles | Metrics

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Research on the impact of in vivo liver transfection of carboxylesterase 1f gene on acute liver failure BIAN Shu, YU Qian, ZHANG Yuting, LI Dingjia, ZHANG Qiaoting, LIU Liangming Journal of Shanghai Jiao Tong University (Medical Science)    2025, 45 (11): 1480-1489.   DOI: 10.3969/j.issn.1674-8115.2025.11.007 Abstract （89）   HTML （7）    PDF（pc） （42324KB）（92）       Knowledge map    Save Objective ·To explore the effects of in vivo gene transfection of Carboxylesterase 1f (Ces1f) on mice with acute liver failure (ALF) induced by lipopolysaccharide (LPS) in combination with D - galactosamine (D - GalN), as well as its impact on the expression of hepatic endocannabinoid (EC) and their specific receptors, cannabinoid receptor 1 (Cb1r) and cannabinoid receptor 2 (Cb2r). Methods ·Twenty male C57BL/6J mice were randomly divided into four groups (n=5 per group): the blank control group, the Ces1f over expression group, the ALF model group (LPS/D-GalN), and the Ces1f over expression ALF model group. Recombinant adeno-associated virus 8 (rAAV8) containing the Ces1f sequence was injected via the tail vein, while the control group received an injection of the empty viral vector. Three weeks after virus injection, an ALF animal model was established by intraperitoneal injection of LPS+D-GalN. Immunofluorescence was used to observe the transfection efficiency of Ces1f in the mouse liver. Quantitative real-time polymerase chain reaction (qPCR) and Western blotting were employed to determine the expression levels of CES1F, CB1R, and CB2R in mouse liver tissue. Hematoxylin-eosin (H-E) staining was used to observe the pathological changes in the mouse liver tissue. The enzyme-linked immunosorbent assay (ELISA) was utilized to detect the levels of serum alanine aminotransferase (ALT), aspartate aminotransferase (AST), interleukin-1β (IL-1β), tumor necrosis factor-α (TNF-α), arachidonoylethanolamide (AEA), and 2-arachidonoylglycerol (2-AG). Results ·The AAV8 virus had high transfection efficiency and significant hepatotropism in the mouse liver. Compared with the control group, the ALF model group showed decreased mRNA (P<0.001) and protein expression levels of Ces1f and Cb2r (P=0.039, P=0.012). The pathological injury score of liver tissue, the levels of serum ALT, AST, IL-1β, and TNF-α, as well as the levels of Il-1β mRNA, Tnf-α mRNA, AEA, 2-AG, Cb1r mRNA, and CB1R protein in liver tissue were significantly increased (P<0.001). Compared with the ALF model group, the Ces1f over expression ALF model group had significantly increased Ces1f mRNA (P<0.001) and CES1F protein (P=0.002) expression levels, decreased serum AST level (P=0.011), significantly decreased pathological injury scores of liver tissue (P=0.001), decreased levels of serum ALT, IL-1β, and TNF-α, and decreased levels of Il-1β mRNA, Tnf-α mRNA, AEA, and 2-AG in liver tissue (P<0.001). The levels of Cb1r mRNA (P=0.024) and CB1R protein (P=0.027) were also decreased. Conclusion ·Liver-targeted Ces1f gene transfection exerts a protective effect in the ALF mouse model induced by LPS/D-GalN. This protective effect may be achieved by downregulating the levels of hepatic endocannabinoids AEA and 2 - AG and inhibiting the expression of CB1R. Table and Figures | Reference | Related Articles | Metrics

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Clinical value and transcriptional regulatory mechanism of ABCA7 in colorectal cancer SUN Ruizhuang, QIAO Kunpeng, LI Pu, XU Xiaolian, MENG Jun Journal of Shanghai Jiao Tong University (Medical Science)    2025, 45 (11): 1490-1501.   DOI: 10.3969/j.issn.1674-8115.2025.11.008 Abstract （155）   HTML （11）    PDF（pc） （10308KB）（164）       Knowledge map    Save Objective ·To investigate the prognostic value of the ATP-binding cassette subfamily A member 7 (ABCA7) gene in colorectal cancer (CRC) and provide a novel molecular marker for the precise diagnosis and personalized treatment of CRC. Methods ·Single-cell transcriptome data of CRC were retrieved from the Tumor Immune Single-cell Hub (TISCH). Spatial transcriptome data of sample GSM8594571 (based on the 10x Genomics Visium platform) were downloaded from the Gene Expression Omnibus (GEO) database. Transcriptome data from the TCGA-COAD and TCGA-READ projects were extracted from The Cancer Genome Atlas (TCGA) database. Using a multi-omics integration analysis strategy, single-cell transcriptome data were employed to analyze the expression patterns of ABCA7 in different cell subpopulations and were combined with spatial transcriptome data to explore its spatial distribution characteristics in tumor and adjacent tissues. The Cox Proportional Hazards Model (Cox) was used to evaluate the prognostic value of ABCA7. The effect of ABCA7 on CRC cell proliferation was verified using Clustered Regularly Interspaced Short Palindromic Repeats (CRISPR) knockout technology combined with the CERES algorithm. The transcriptional regulatory network between ABCA7 and the transcription factors zinc finger BTB domain-containing protein 33 (ZBTB33) and Nuclear factor-κB-repressing factor (NKRF) was constructed using chromatin immunoprecipitation sequencing (ChIP-seq) data from the Cistrome database and Pearson correlation analysis. Results ·The analysis revealed that ABCA7 was significantly overexpressed in CRC malignant cells, with further upregulation particularly in tumor tissues with high Ki-67 expression. Moreover, the mRNA expression of ABCA7 in tumor tissues was significantly higher than that in normal tissues (P<0.05), showing certain diagnostic efficacy [area under the curve (AUC) of the receiver operating characteristic (ROC) curve=0.686]. Knockout of ABCA7 significantly inhibited the proliferative capacity of CRC cell lines (e.g., C75, CL11). Patients in the ABCA7 high-expression group had significantly shorter overall survival (OS), disease-specific survival (DSS), and progression-free interval (PFI) (all P<0.05). Epigenetic analysis showed that ZBTB33 and NKRF could directly bind to the regulatory region of the ABCA7 gene, forming a ZBTB33/NKRF-ABCA7 transcriptional regulatory axis, and all three were significantly upregulated in CRC (P<0.05). Conclusion ·ABCA7 is highly expressed in CRC and associated with poor prognosis. The ZBTB33/NKRF-ABCA7 regulatory axis may be a key mechanism driving CRC progression. Table and Figures | Reference | Related Articles | Metrics

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Effect of automatic tube current modulation on radiation dose and image quality of robotic-assisted hip CT HU Jie, YANG Xianfeng Journal of Shanghai Jiao Tong University (Medical Science)    2025, 45 (11): 1502-1506.   DOI: 10.3969/j.issn.1674-8115.2025.11.009 Abstract （90）   HTML （3）    PDF（pc） （2630KB）（111）       Knowledge map    Save Objective ·To evaluate the feasibility of automatic tube current modulation (ATCM) in reducing radiation dose during preoperative CT imaging for robotic-assisted hip arthroplasty and to assess its impact on image quality. Methods ·A total of 106 patients undergoing CT scans for robotic-assisted hip arthroplasty at Nanjing Drum Tower Hospital (from November 2021 to October 2024) were prospectively enrolled. Participants were randomly divided into Group A (n=56) and Group B (n=50).The patients in Group A underwent ATCM scanning, and the patients in Group B underwent partial fixed tube current scanning for hip imaging. Radiation dose parameters included volume CT dose index (CTDIvol) and dose-length product (DLP). Image quality was evaluated using signal-to-noise ratio (SNR), contrast-to-noise ratio (CNR), and objective noise. Age, gender, body mass index (BMI), scan length, CTDIvol, DLP, SNR, CNR,noise,and image qualification rate were compared between the two groups. Results ·No statistically significant differences were observed between the two groups in baseline characteristics (gender, age, and BMI), scan length, image qualification rate, SNR, CNR, or objective noise (all P>0.05). However, Group A demonstrated significantly lower CTDIvol and DLP compared to Group B (both P<0.001). Conclusion ·The use of ATCM in preoperative CT imaging for robotic-assisted hip surgery significantly reduces radiation dose while maintaining image quality sufficient for 3D modeling requirements. Table and Figures | Reference | Related Articles | Metrics

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