1.The Role and Mechanism of Aerobic Exercise in Enhancing Insulin Sensitivity by Reducing Circulating Glutamate
Xiao-Rui XING ; Qin SUN ; Huan-Yu WANG ; Ruo-Bing FAN ; Ru WANG
Progress in Biochemistry and Biophysics 2025;52(6):1373-1385
ObjectiveTo explore the role and potential mechanism of circulating glutamate in enhancing insulin sensitivity by aerobic exercise. This research may provide a novel strategy for preventing metabolic diseases through precise exercise interventions. MethodsTo investigate the effects of elevated circulating glutamate on insulin sensitivity and its potential mechanisms, 18 male C57BL/6 mice aged 6 to 8 weeks were randomly divided into 3 groups: a control group (C), a group receiving 500 mg/kg glutamate supplementation (M), and a group receiving 1 000 mg/kg glutamate supplementation (H). The intervention lasted for 12 weeks, with treatments administered 6 d per week. Following the intervention, an insulin tolerance test (ITT) and a glucose tolerance test (GTT) were conducted. Circulating glutamate levels were measured using a commercial kit, and the activity of the skeletal muscle InsR/IRS1/PI3K/AKT signaling pathway was analyzed via Western blot. To further investigate the role of circulating glutamate in enhancing insulin sensitivity through aerobic exercise, 30 male C57BL/6 mice were randomly assigned to 3 groups: a control group (CS), an exercise intervention group (ES), and an exercise combined with glutamate supplementation group (EG). The ES group underwent treadmill-based aerobic exercise, while the EG group received glutamate supplementation at a dosage of 1 000 mg/kg in addition to aerobic exercise. The intervention lasted for 10 weeks, with sessions occurring 6 d per week, and the same procedures were followed afterward. To further elucidate the mechanism by which glutamate modulates the InsR/IRS1/PI3K/AKT signaling pathway, C2C12 myotubes were initially subjected to graded glutamate treatment (0, 0.5, 1, 3, 5, 10 mmol/L) to determine the optimal concentration for cellular intervention. Subsequently, the cells were divided into 3 groups: a control group (C), a glutamate intervention group (G), and a glutamate combined with MK801 (an NMDA receptor antagonist) intervention group (GK). The G group was treated with 5 mmol/L glutamate, while the GK group received 50 μmol/L MK801 in addition to 5 mmol/L glutamate. After 24 h of intervention, the activity of the InsR/IRS1/PI3K/AKT signaling pathway was analyzed using Western blot. ResultsCompared to the mice in group C, the circulating glutamate levels, the area under curve (AUC) of ITT, and the AUC of GTT in the mice of group H were significantly increased. Additionally, the expression levels of p-InsRβ, IRS1, p-AKT, and p-mTOR proteins in skeletal muscle were significantly downregulated. Compared to the mice in group CS, the circulating glutamate levels, the AUC of ITT, and the AUC of GTT in the mice of group ES were significantly reduced. Additionally, the expression levels of p-InsRβ, IRS1, p-AKT, and p-mTOR proteins in skeletal muscle of group ES mice were significantly upregulated. There were no significant changes observed in the mice of group EG. Compared to the cells in group 0 mmol/L, the expression levels of p-InsRβ, p-IRS1, p-PI3K, and p-AKT proteins in cells of group 5 mmol/L were significantly downregulated. Compared to the cells in group C, the expression levels of p-InsRβ, p-IRS1, p-PI3K, and p-AKT proteins in the cells of group G were significantly downregulated. No significant changes were observed in the cells of group GK. ConclusionLong-term aerobic exercise can improve insulin sensitivity by lowering circulating levels of glutamate. This effect may be associated with the upregulation of the InsR/IRS1/AKT signaling pathway activity in skeletal muscle. Furthermore, glutamate can weaken the activity of the InsR/IRS1/PI3K/AKT signaling pathway in skeletal muscle, potentially by binding to NMDAR expressed in skeletal muscle.
2.Risk factors associated with colorectal adenomatous polyps
Yujia TIAN ; Xianzhao YANG ; Rong XING ; Fenglei WANG ; Fuwen ZHANG ; Shuying RU
Journal of Chinese Physician 2025;27(3):411-416
Objective:To investigate the risk factors of colorectal adenomatous polyps.Methods:The clinical data of 395 patients who underwent colonoscopy in the Tongzhou branch, Tongzhou District, Dongzhimen Hospital Affiliated to Beijing University of Chinese Medicine from August 2017 to August 2021 were analyzed. According to the examination results, adenomatous polyps were divided into adenomatous polyps group (193 cases) and non-polyp group (202 cases). The risk factors of colorectal adenomatous polyps were screened by univariate analysis and multivariate logistic regression analysis.Results:The results of single factor analysis suggested that: body mass index (BMI), sex, age, proportion of blood type A, history of large intestine polyps, history of Helicobacter pylori (Hp) infection, history of alcohol consumption, history of smoking, proportion of heavy oil diet, history of oral calcium, history of oral statins, history of oral non-steroidal anti-inflammatory drugs, history of oral antibiotics, and high fat diet (pork, beef, and animal organs), high salt diet, love of pickled food, love of sweet food, love of greasy, good mood, anxiety, depression, impatience and irritability, history of hypertension, diabetes and hyperlipidemia were statistically significant in the adenomatous polyp group and the non-polyp group (all P<0.05). Factors with P<0.05 in the above single factor analysis were taken as independent variables, and the incidence of disease was taken as dependent variable for multi-factor logistic regression analysis. The results showed that BMI, age, blood type A, Hp infection history, drinking history, smoking history, oral non-steroidal anti-inflammatory drugs history, oral antibiotics history, high salt diet, good mood, hypertension were the influencing factors for the incidence of adenomatous polyps (all P<0.05). Conclusions:High BMI, old age, blood type A, history of Hp infection, smoking history, oral non-steroidal anti-inflammatory drug history, oral antibiotics history, high salt diet and hypertension are risk factors for the development of adenomatous polyps. Drinking alcohol and good mood can reduce the risk of colorectal adenomatous polyps. Therefore, targeted intervention measures can be formulated for high-risk patients to reduce the risk of colorectal adenomatous polyps.
3.Significance of Serum β2-Microglobulin for Survival and Relapse of Patients with Diffuse Large B-Cell Lymphoma in the Rituximab Era
Yu-Ze YANG ; Ya-Ru XU ; Mei ZHOU ; Wen-Yan XU ; Li-Qiang ZHOU ; Zhen-Xing GUO
Journal of Experimental Hematology 2025;33(4):1057-1062
Objective:To investigate the significance of serum β2-microglobulin(β2-MG)for survival and relapse of patients with diffuse large B-cell lymphoma(DLBCL)in the rituximab era.Methods:Clinical data of 92 patients with DLBCL admitted from December 2003 to July 2015 were retrospectively analyzed.The optimal cutoff value of β2-MG levels for predicting prognosis of the DLBCL patients was determined using receiver operating characteristic(ROC)curve.Kaplan-Meier analysis was used to estimate progression-free survival(PFS)and overall survival(OS).Cox logistic regression analysis was used to explore potential prognostic factors associated with survival.Binary logistic regression analysis was used to analyze the relationship between various factors and relapse.Results:The most discriminative cutoff value for β2-MG level was determined to be 2.25 mg/L by the ROC curve.Subgroup analysis showed that patients in the elevated β2-MG(>2.25 mg/L)group had significantly worse PFS(P=0.006)and a trend toward worse OS compared with those in the low β2-MG(≤2.25 mg/L)group(P=0.053).Univariate analysis showed that elevated β2-MG,age>60 years,Ann Arbor stage Ⅲ-Ⅳ,as well as IPI score ≥ 3 were associated with worse PFS.Binary logistic regression analysis showed that age>60 years and β2-M G>2.25 mg/L were potential influencing factors for relapse of DLBCL patients.Conclusion:Serum β2-MG might be an important predictor for the survival and relapse of DLBCL patients in the rituximab era.
4.Prospective study on the association between lifestyles and the risk of type 2 diabetes in adult residents
Meng-ru HE ; Xiao-li XU ; Gen-ming ZHAO ; Xing LIU ; Hui-lin XU ; Dan-dan HE ; Yu-ping CHENG ; Yong-gen JIANG ; Qian PENG ; Jian-hua SHI ; Xiao-hua LIU
Fudan University Journal of Medical Sciences 2025;52(5):647-656,685
Objective To analyze the association between lifestyle and the risk of type 2 diabetes(T2D)among adult residents.Methods The data was sourced from the Shanghai Suburban Adult Cohort and Biobank.A total of 42 096 adult residents who had not developed T2D were recruited from four districts of Shanghai(Songjiang,Jiading,Minhang,and Xuhui)between 2016 and 2019.The follow-up ended on Feb 28,2023.A structured questionnaire was used to collect information on six lifestyle-related items,including smoking,alcohol consumption,BMI,waist circumference(WC),physical activity,and diet.The unhealthy lifestyle scores(UHLS)were calculated by counting the number of all the unhealthy lifestyle items,with a range of 0-6.New-onset T2D events diagnosed by physicians were obtained through the medical information system.Cox proportional hazards regression model and restricted cubic spline model were utilized to evaluate the association between unhealthy lifestyles and the risk of T2D incidence.Results About 28.1%of the participants led 4-6 unhealthy lifestyles.A total of 1 752 new T2D cases were identified during 218 513.4 person-years of follow-up.Analysis of single unhealthy lifestyle showed that abnormal WC(HR=1.5,95%CI:1.4-1.7)and abnormal BMI(HR=1.3,95%CI:1.2-1.5)were associated with an increased risk of T2D.Compared with individuals with a UHLS of 0-1,those with a UHLS of 3 and 4-6 had 30%(95%CI:1.1-1.6)and 50%(95%CI:1.2-1.8)higher risks of T2D,respectively.Each additional unhealthy lifestyle was associated with a 10%increase in T2D incidence risk(HR=1.1,95%CI:1.1-1.2).Conclusion The risk of T2D in adult residents increases with the cumulative number of unhealthy lifestyles.Adult residents with abnormal WC or BMI,or have three or more unhealthy lifestyles accumulated,will increase the risk of new-onset T2D.
5.Long noncoding RNA LINC01615 promotes malignant phenotypes of head and neck squamous cell carcinoma cells by up-regulating TEAD2 expres-sion
Bo WU ; Penghui ZHANG ; Ning GAO ; Huimin ZHANG ; Keyao XING ; Moyi QU ; Ru SONG
Chinese Journal of Pathophysiology 2025;41(10):1926-1937
AIM:To investigate the biological functions and molecular mechanisms of long noncoding RNA LINC01615 in head and neck squamous cell carcinoma(HNSCC)cells.METHODS:Transcriptome sequencing data from The Cancer Genome Atlas(TCGA)and Gene Expression Omnibus(GEO)databases were used to analyze the expres-sion level of LINC01615 in HNSCC cells and its correlation with patient survival.RT-qPCR was used to detect the expres-sion levels of LINC01615 in HNSCC and normal control cells.An siRNA-mediated LINC01615 knockdown HNSCC cell model was established,and high-content screening cell counting,ATP and CCK8 assays were performed to analyze cell proliferation.Transwell assays were conducted to assess cell migration and invasion.Bioinformatics analysis was em-ployed to predict potential target genes of LINC01615 and the biological processes and signaling pathways involved.RT-qPCR and Western blot were used to validate the regulatory effect of LINC01615 on the candidate target gene TEAD2.Transcriptome data from TCGA and GEO databases were analyzed to determine the expression pattern of TEAD2 in HN-SCC.Functional cell experiments were performed to investigate the impact of TEAD2 knockdown on HNSCC proliferation,migration,and invasion.Rescue experiments were conducted to examine whether LINC01615 influenced the malignant phenotypes(proliferation,migration,and invasion)of HNSCC cells by regulating TEAD2 expression.RESULTS:The expression levels of LINC01615 were significantly higher in HNSCC tissues and cells than those in normal control tissues and cells,respectively(P<0.01).Knockdown of LINC01615 significantly inhibited HNSCC proliferation,migration,and invasion(P<0.01).Bioinformatics analysis identified 134 candidate target genes of LINC01615,which were primarily en-riched in tumor-related biological processes and signaling pathways,including angiogenesis,regulation of endothelial cell proliferation,regulation of cell migration,HPV infection,Hippo signaling pathway,and PI3K-Akt signaling pathway.Knockdown of LINC01615 led to a significant decrease in TEAD2 expression in HNSCC cells(P<0.01).Functional cell studies demonstrated that TEAD2 knockdown suppressed HNSCC proliferation,migration,and invasion,whereas TEAD2 overexpression reversed the inhibitory effects of LINC01615 knockdown on these malignant phenotypes.CONCLUSION:LINC01615 is upregulated in HNSCC tissues and cells,functioning as an oncogene.Mechanistic studies reveal that LINC01615 promotes HNSCC proliferation,migration,and invasion by upregulating TEAD2,a key transcription factor in the Hippo signaling pathway.These findings may provide a novel potential biomarker for the clinical diagnosis and treat-ment of HNSCC.
6.Long noncoding RNA LINC01615 promotes malignant phenotypes of head and neck squamous cell carcinoma cells by up-regulating TEAD2 expres-sion
Bo WU ; Penghui ZHANG ; Ning GAO ; Huimin ZHANG ; Keyao XING ; Moyi QU ; Ru SONG
Chinese Journal of Pathophysiology 2025;41(10):1926-1937
AIM:To investigate the biological functions and molecular mechanisms of long noncoding RNA LINC01615 in head and neck squamous cell carcinoma(HNSCC)cells.METHODS:Transcriptome sequencing data from The Cancer Genome Atlas(TCGA)and Gene Expression Omnibus(GEO)databases were used to analyze the expres-sion level of LINC01615 in HNSCC cells and its correlation with patient survival.RT-qPCR was used to detect the expres-sion levels of LINC01615 in HNSCC and normal control cells.An siRNA-mediated LINC01615 knockdown HNSCC cell model was established,and high-content screening cell counting,ATP and CCK8 assays were performed to analyze cell proliferation.Transwell assays were conducted to assess cell migration and invasion.Bioinformatics analysis was em-ployed to predict potential target genes of LINC01615 and the biological processes and signaling pathways involved.RT-qPCR and Western blot were used to validate the regulatory effect of LINC01615 on the candidate target gene TEAD2.Transcriptome data from TCGA and GEO databases were analyzed to determine the expression pattern of TEAD2 in HN-SCC.Functional cell experiments were performed to investigate the impact of TEAD2 knockdown on HNSCC proliferation,migration,and invasion.Rescue experiments were conducted to examine whether LINC01615 influenced the malignant phenotypes(proliferation,migration,and invasion)of HNSCC cells by regulating TEAD2 expression.RESULTS:The expression levels of LINC01615 were significantly higher in HNSCC tissues and cells than those in normal control tissues and cells,respectively(P<0.01).Knockdown of LINC01615 significantly inhibited HNSCC proliferation,migration,and invasion(P<0.01).Bioinformatics analysis identified 134 candidate target genes of LINC01615,which were primarily en-riched in tumor-related biological processes and signaling pathways,including angiogenesis,regulation of endothelial cell proliferation,regulation of cell migration,HPV infection,Hippo signaling pathway,and PI3K-Akt signaling pathway.Knockdown of LINC01615 led to a significant decrease in TEAD2 expression in HNSCC cells(P<0.01).Functional cell studies demonstrated that TEAD2 knockdown suppressed HNSCC proliferation,migration,and invasion,whereas TEAD2 overexpression reversed the inhibitory effects of LINC01615 knockdown on these malignant phenotypes.CONCLUSION:LINC01615 is upregulated in HNSCC tissues and cells,functioning as an oncogene.Mechanistic studies reveal that LINC01615 promotes HNSCC proliferation,migration,and invasion by upregulating TEAD2,a key transcription factor in the Hippo signaling pathway.These findings may provide a novel potential biomarker for the clinical diagnosis and treat-ment of HNSCC.
7.Exploring the sustainability of China's medical and health assistance and cooperation with Uganda
Ru-zhang JIANG ; Xiao-xing FU ; Jian JI ; Yi-hang LU ; Zhi-wei LENG
Chinese Journal of Health Policy 2025;18(2):69-75
Sustainability is a critical issue in China's medical and health assistance and cooperation with Africa.As China enters a new phase in this field,achieving sustainability presents both opportunities and challenges.Summarizing past successes and identifying barriers are of great practical significance for future development.This study examines the current state of China's medical and health assistance and cooperation with Uganda and finds that China has actively sought to integrate into local communities by collaborating with Ugandan medical institutions.However,several factors continue to constrain the sustainability of these efforts,including Uganda's fragmented public-private healthcare system heavily reliant on external aid,the personnel structure of Chinese medical teams,and linguistic and cultural barriers between China and Uganda.Based on official policy documents from both countries and field research findings,this study recommends supporting and assisting Uganda in establishing an independent healthcare system,with a particular focus on maternal and child health,youth health,and chronic disease management.Furthermore,strengthening cultural exchanges can contribute to the sustainable development of China-Uganda and broader China-Africa medical and health assistance and cooperation.
8.miR-142a-3p Reduces Autophagy in TCMK-1 Cells and Enhances Pyroptosis by Targeting ATG16L1
Xing ZHAO ; Fei YU ; Rui-Yang YUAN ; Ya-Ru YANG ; Jia-Yan LIU ; Hai-Mai DING ; Xue-Ming ZHANG
Chinese Journal of Biochemistry and Molecular Biology 2025;41(7):1031-1039
The incidence rate of kidney diseases in China has always remained high.At present,the clinical treat-ment mainly focuses on symptomatic treatment to delay the progression of the disease,and there is a lack of eco-nomical and effective treatment methods.MicroRNA plays an important regulatory role in the occurrence and devel-opment of diseases.This study aims to explore the role and regulatory mechanism of miR-142a-3p in adriamycin(ADR)-induced renal tubular epithelial cell(TCMK-1)injury,with a focus on its potential as a therapeutic target for ADR nephropathy.First,cell viability was assessed using the CCK-8 kit,and a mouse renal tubular epithelial cell model induced by ADR was established.Subsequently,alterations in miR-142a-3p and its target gene ATG16L1 mRNA levels were quantified using RT-qPCR.Western blotting was used to detect the protein levels of autophagy marker proteins and pyroptosis marker proteins.Monodansylcadaverin(MDC)staining was performed and the autophagy of cells was detected by flow cytometry.The results showed that the relative expression of miR-142a-3p in TCMK-1 cells induced by ADR was increased and the relative expression of its target gene ATG16L1 was decreased(P<0.0001).Western blotting results showed that the levels of p62(P<0.001)and pyroptosis-related proteins(P<0.001)were increased,while the protein levels of autophagy-related proteins were decreased(P<0.05).The flow cytometry results showed that there was no difference in the mean fluorescence intensity of autoph-agosomes between the ADR group and the autophagosome inhibitor group(3-MA group)(P>0.05),indicating that after ADR induction,cell autophagy was inhibited and pyroptosis was enhanced.When the expression of miR-142a-3p was inhibited by transfecting miR-142a-3p inhibitor,the relative expression level of the target gene ATG16L1 was restored(P<0.001).Western blotting showed that the protein level of p62(P<0.01)and pyropto-sis-related proteins(P<0.01)were decreased,and the protein level of autophagy-related proteins was restored(P<0.001).Flow cytometry results further indicated that cell autophagy was restored(P<0.0001).In conclusion,ADR targets A TG1 6L1 through miR-142a-3p to reduce the autophagy level of TCMK-1,and simultaneously activates GSDMD-mediated pyroptosis.
9.Risk factors associated with colorectal adenomatous polyps
Yujia TIAN ; Xianzhao YANG ; Rong XING ; Fenglei WANG ; Fuwen ZHANG ; Shuying RU
Journal of Chinese Physician 2025;27(3):411-416
Objective:To investigate the risk factors of colorectal adenomatous polyps.Methods:The clinical data of 395 patients who underwent colonoscopy in the Tongzhou branch, Tongzhou District, Dongzhimen Hospital Affiliated to Beijing University of Chinese Medicine from August 2017 to August 2021 were analyzed. According to the examination results, adenomatous polyps were divided into adenomatous polyps group (193 cases) and non-polyp group (202 cases). The risk factors of colorectal adenomatous polyps were screened by univariate analysis and multivariate logistic regression analysis.Results:The results of single factor analysis suggested that: body mass index (BMI), sex, age, proportion of blood type A, history of large intestine polyps, history of Helicobacter pylori (Hp) infection, history of alcohol consumption, history of smoking, proportion of heavy oil diet, history of oral calcium, history of oral statins, history of oral non-steroidal anti-inflammatory drugs, history of oral antibiotics, and high fat diet (pork, beef, and animal organs), high salt diet, love of pickled food, love of sweet food, love of greasy, good mood, anxiety, depression, impatience and irritability, history of hypertension, diabetes and hyperlipidemia were statistically significant in the adenomatous polyp group and the non-polyp group (all P<0.05). Factors with P<0.05 in the above single factor analysis were taken as independent variables, and the incidence of disease was taken as dependent variable for multi-factor logistic regression analysis. The results showed that BMI, age, blood type A, Hp infection history, drinking history, smoking history, oral non-steroidal anti-inflammatory drugs history, oral antibiotics history, high salt diet, good mood, hypertension were the influencing factors for the incidence of adenomatous polyps (all P<0.05). Conclusions:High BMI, old age, blood type A, history of Hp infection, smoking history, oral non-steroidal anti-inflammatory drug history, oral antibiotics history, high salt diet and hypertension are risk factors for the development of adenomatous polyps. Drinking alcohol and good mood can reduce the risk of colorectal adenomatous polyps. Therefore, targeted intervention measures can be formulated for high-risk patients to reduce the risk of colorectal adenomatous polyps.
10.Integrated Optical and Magnetic Navigation for Simplified Percutaneous Transforaminal Endoscopic Lumbar Discectomy: A Novel Approach
Xing-Chen YAO ; Jun-Peng LIU ; Xin-Ru DU ; Li GUAN ; Yong HAI ; Jincai YANG ; Aixing PAN
Neurospine 2025;22(1):297-307
Objective:
This study aims to evaluate the clinical benefits of the integrated optical and magnetic surgical navigation system in assisting transforaminal endoscopic lumbar discectomy (TELD) for the treatment of lumbar disc herniation (LDH).
Methods:
A retrospective analysis was conducted on patients who underwent TELD for LDH at Beijing Chaoyang Hospital, Capital Medical University from November 2022 to December 2023. Patients treated with the integrated optical and magnetic surgical navigation system were defined as the navigation-guided TELD (Ng-TELD) group (30 cases), while those treated with the conventional x-ray fluoroscopy method were defined as the control group (31 cases). Record and compare baseline characteristics, surgical parameters, efficacy indicators, and adverse events between the 2 patient groups.
Results:
The average follow-up duration for the 61 patients was 11.8 months. Postoperatively, both groups exhibited significant relief from back and leg pain, which continued to improve over time. At the final follow-up, patients’ lumbar function and quality of life had significantly improved compared to preoperative levels (p < 0.05). The Ng-TELD group had significantly shorter total operation time (58.43 ± 12.37 minutes vs. 83.23 ± 25.90 minutes), catheter placement time (5.83 ± 1.09 minutes vs. 15.94 ± 3.00 minutes), decompression time (47.17 ± 11.98 minutes vs. 67.29 ± 24.23 minutes), and fewer intraoperative fluoroscopies (3.20 ± 1.45 vs. 16.58 ± 4.25) compared to the control group (p < 0.05). There were no significant differences between the groups in terms of efficacy evaluation indicators and hospital stay. At the final follow-up, the excellent and good rate of surgical outcomes assessed by the MacNab criteria was 98.4%, and the overall adverse event rate was 8.2%, with no statistically significant differences between the groups (p > 0.05).
Conclusion
This study demonstrates that the integrated optical and magnetic surgical navigation system can reduce the complexity of TELD, shorten operation time, and minimize radiation exposure for the surgeon, highlighting its promising clinical potential.

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