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当代医学科学(英文)
当代医学科学(英文)

龚菲力；冯敢生

双月刊

2096-5230

jtmu@tjmu.edu.cn

027-83692514

430030

武汉市航空路13号同济医学院学报

当代医学科学(英文)/Journal Current Medical ScienceSCI
正式出版
收录年代

    LncRNA NPTN-IT1-201 Ameliorates Depressive-like Behavior by Targeting miR-142-5p and Regulating Inflammation and Apoptosis via BDNF

    Jun HEPeng XIEXiao-qiong ANDong-fen GUO...
    971-986页
    查看更多>>摘要：Objective:Long noncoding RNAs(lncRNAs)and microRNAs(miRNAs)are widely expressed in the brain and are associated with the development of neurological and neurodegenerative diseases.However,their roles and molecular mechanisms in major depressive disorder(MDD)remain largely unknown.This study aimed to identify lncRNAs and miRNAs involved in the development of MDD and elucidate their molecular mechanisms.Methods:Transcriptome and bioinformatic analyses were performed to identify miRNAs and lncRNAs related to MDD.C57 mice were subjected to chronic unpredictable mild stress(CUMS)to establish a depression model.Lentiviruses containing either lncRNA NPTN-IT1-201 or miR-142-5p were microinjected into the hippocampal region of these mice.Behavioral tests including the sucrose preference test(SPT),tail suspension test(TST),and forced swim test(FST)were conducted to evaluate depressive-like behaviors.Results:The results revealed that overexpression of lncRNA NPTN-IT1-201 or inhibition of miR-142-5p significantly ameliorated depressive-like behaviors in CUMS-treated mice.Dual-luciferase reporter assays confirmed interactions between miR-142-5p with both brain-derived neurotrophic factor(BDNF)and NPTN-IT1-201.ELISA analysis revealed significant alterations in relevant biomarkers in the blood samples of MDD patients compared to healthy controls.Histological analyses,including HE and Nissl staining,showed marked structural changes in brain tissues following CUMS treatment,which were partially reversed by lncRNA NPTN-IT1-201 overexpression or miR-142-5p inhibition.Immunofluorescence imaging demonstrated significant differences in the levels of BAX,Bcl2,p65,Iba1 among different treatment groups.TUNEL assays confirmed reduced apoptosis in brain tissues following these interventions.Western blotting showed the significant differences in BDNF,BAX,and Bc12 protein levels among different treatment groups.Conclusion:NPTN-IT1-201 regulates inflammation and apoptosis in MDD by targeting BDNF via miR-142-5p,making it a potential therapeutic target for MDD.
      原文链接:
    • NETL
    • NSTL
    • 万方数据

    Electroacupuncture Alleviates Memory Deficits in APP/PS1 Mice by Targeting Serotonergic Neurons in Dorsal Raphe Nucleus

    Chao-chao YUXiao-fei WANGJia WANGChu LI...
    987-1000页
    查看更多>>摘要：Objective:Alzheimer's disease(AD)has become a significant global concern,but effective drugs able to slow down AD progression is still lacked.Electroacupuncture(EA)has been demonstrated to ameliorate cognitive impairment in individuals with AD.However,the underlying mechanisms remains poorly understood.This study aimed at examining the neuroprotective properties of EA and its potential mechanism of action against AD.Methods:APP/PS1 transgenic mice were employed to evaluate the protective effects of EA on Shenshu(BL 23)and Baihui(GV 20).Chemogenetic manipulation was used to activate or inhibit serotonergic neurons within the dorsal raphe nucleus(DRN).Learning and memory abilities were assessed by the novel object recognition and Morris water maze tests.Golgi staining,western blot,and immunostaining were utilized to determine EA-induced neuroprotection.Results:EA at Shenshu(BL 23)and Baihui(GV 20)effectively ameliorated learning and memory impairments in APP/PS1 mice.EA attenuated dendritic spine loss,increased the expression levels of PSD95,synaptophysin,and brain-derived neurotrophic factor in hippocampus.Activation of serotonergic neurons within the DRN can ameliorate cognitive deficits in AD by activating glutamatergic neurons mediated by 5-HT1B.Chemogenetic inhibition of serotonergic neurons in the DRN reversed the effects of EA on synaptic plasticity and memory.Conclusion:EA can alleviate cognitive dysfunction in APP/PS1 mice by activating serotonergic neurons in the DRN.Further study is necessary to better understand how the serotonergic neurons-related neural circuits involves in EA-induced memory improvement in AD.
      原文链接:
    • NETL
    • NSTL
    • 万方数据

    Enhancing Orthopedic Knowledge Assessments:The Performance of Specialized Generative Language Model Optimization

    Hong ZHOUHong-lin WANGYu-yu DUANZi-neng YAN...
    1001-1005页
    查看更多>>摘要：Objective:This study aimed to evaluate and compare the effectiveness of knowledge base-optimized and unoptimized large language models(LLMs)in the field of orthopedics to explore optimization strategies for the application of LLMs in specific fields.Methods:This research constructed a specialized knowledge base using clinical guidelines from the American Academy of Orthopaedic Surgeons(AAOS)and authoritative orthopedic publications.A total of 30 orthopedic-related questions covering aspects such as anatomical knowledge,disease diagnosis,fracture classification,treatment options,and surgical techniques were input into both the knowledge base-optimized and unoptimized versions of the GPT-4,ChatGLM,and Spark LLM,with their generated responses recorded.The overall quality,accuracy,and comprehensiveness of these responses were evaluated by 3 experienced orthopedic surgeons.Results:Compared with their unoptimized LLMs,the optimized version of GPT-4 showed improvements of 15.3％in overall quality,12.5％in accuracy,and 12.8％in comprehensiveness;ChatGLM showed improvements of 24.8％,16.1％,and 19.6％,respectively;and Spark LLM showed improvements of 6.5％,14.5％,and 24.7％,respectively.Conclusion:The optimization of knowledge bases significantly enhances the quality,accuracy,and comprehensiveness of the responses provided by the 3 models in the orthopedic field.Therefore,knowledge base optimization is an effective method for improving the performance of LLMs in specific fields.
      原文链接:
    • NETL
    • NSTL
    • 万方数据

    Retrospective Analysis of Radiofrequency Ablation in Patients with Small Solitary Hepatocellular Carcinoma:Survival Outcomes and Development of a Machine Learning Prognostic Model

    Qi-fan HEYue XIONGYi-hui YUXiang-chao MENG...
    1006-1017页
    查看更多>>摘要：Background and Objective:The effectiveness of radiofrequency ablation(RFA)in improving long-term survival outcomes for patients with a solitary hepatocellular carcinoma(HCC)measuring 5 cm or less remains uncertain.This study was designed to elucidate the impact of RFA therapy on the survival outcomes of these patients and to construct a prognostic model for patients following RFA.Methods:This study was performed using the Surveillance,Epidemiology,and End Results(SEER)database from 2004 to 2017,focusing on patients diagnosed with a solitary HCC lesion ≤5 cm in size.We compared the overall survival(OS)and cancer-specific survival(CSS)rates of these patients with those of patients who received hepatectomy,radiotherapy,or chemotherapy or who were part of a blank control group.To enhance the reliability of our findings,we employed stabilized inverse probability treatment weighting(sIPTW)and stratified analyses.Additionally,we conducted a Cox regression analysis to identify prognostic factors.XGBoost models were developed to predict 1-,3-,and 5-year CSS.The XGBoost models were evaluated via receiver operating characteristic(ROC)curves,calibration plots,decision curve analysis(DCA)curves and so on.Results:Regardless of whether the data were unadjusted or adjusted for the use of sIPTWs,the 5-year OS(46.7％)and CSS(58.9％)rates were greater in the RFA group than in the radiotherapy(27.1％/35.8％),chemotherapy(32.9％/43.7％),and blank control(18.6％/30.7％)groups,but these rates were lower than those in the hepatectomy group(69.4％/78.9％).Stratified analysis based on age and cirrhosis status revealed that RFA and hepatectomy yielded similar OS and CSS outcomes for patients with cirrhosis aged over 65 years.Age,race,marital status,grade,cirrhosis status,tumor size,and AFP level were selected to construct the XGBoost models based on the training cohort.The areas under the curve(AUCs)for 1,3,and 5 years in the validation cohort were 0.88,0.81,and 0.79,respectively.Calibration plots further demonstrated the consistency between the predicted and actual values in both the training and validation cohorts.Conclusion:RFA can improve the survival of patients diagnosed with a solitary HCC lesion ≤5 cm.In certain clinical scenarios,RFA achieves survival outcomes comparable to those of hepatectomy.The XGBoost models developed in this study performed admirably in predicting the CSS of patients with solitary HCC tumors smaller than 5 cm following RFA.
      原文链接:
    • NETL
    • NSTL
    • 万方数据

    Functional Liver Imaging Score Derived from Gadoxetic Acid-enhanced MRI Predicts Cachexia and Prognosis in Hepatocellular Carcinoma Patients

    Xin-xiang LIBing LIUYu-fei ZHAOYang JIANG...
    1018-1025页
    查看更多>>摘要：Objective:Cachexia occurs in approximately half of hepatocellular carcinoma(HCC)patients as the disease progresses and is correlated with a poor prognosis.Therefore,early identification of HCC patients at risk of developing cachexia and their prognosis is crucial.This study investigated the functional liver imaging score(FLIS)derived from gadoxetic acid-enhanced magnetic resonance imaging(MRI)to identify cachexia in HCC patients and their prognosis.Methods:Pretreatment clinical and MRI data from 339 HCC patients who underwent gadoxetic acid-enhanced MRI scans were retrospectively collected.Patient weights were recorded for 6 months following the MRI scan to diagnose cachexia.The FLIS was calculated as the sum of the enhancement quality score,the excretion quality score,and the portal vein sign quality score.A Cox proportional hazards model was used to determine the significant factors affecting overall survival(OS).Multivariable logistic regression was then conducted to identify variables predicting cachexia in HCC patients,which were subsequently used to predict OS.Results:Cox regression analysis revealed a significant association between cachexia and worse OS.Both FLIS(0-4 vs.5-6 points)(OR,9.20;95％CI:4.68-18.10;P＜0.001)and α-fetoprotein＞100 ng/mL(OR,4.08;95％CI:2.13-7.83;P＜0.001)emerged as significant predictors of cachexia in patients with HCC.Furthermore,FLIS(0-4 vs.5-6 points)(HR,1.73;95％CI:1.19-2.51;P=0.004)was significantly associated with OS.Patients in the FLIS 0-4 points group had shorter OS than those in the FLIS 5-6 points group[20 months(95％CI,14.7-25.3)vs.43 months(95％CI,27.7-58.3);P=0.001].Conclusion:Cachexia was associated with worse OS.The functional liver imaging score emerged as a significant predictor of cachexia in HCC patients and their prognosis.
      原文链接:
    • NETL
    • NSTL
    • 万方数据

    Histological Risk Factors for Lymph Node Metastasis in pT1 Colorectal Cancer:Does Submucosal Invasion Depth Really Matter?

    Bing YUEMei JIARui XUGuang-yong CHEN...
    1026-1035页
    查看更多>>摘要：Objective:After endoscopic resection of colorectal cancer with submucosal invasion(pTl CRC),additional surgical treatment is recommended if deep submucosal invasion(DSI)is present.This study aimed to further elucidate the risk factors for lymph node metastasis(LNM)in patients with pTl CRC,especially the effect of DSI on LNM.Methods:Patients with pT1 CRC who underwent lymph node dissection were selected.The Chi-square test and multivariate logistic regression were used to analyze the relationship between clinicopathological characteristics and LNM.The submucosal invasion depth(SID)was measured via 4 methods and analyzed with 3 cut-off values.Results:Twenty-eight of the 239 patients presented with LNM(11.7％),and the independent risk factors for LNM included high histological grade(P=0.003),lymphovascular invasion(LVI)(P=0.004),intermediate to high budding(Bd 2/3)(P=0.008),and cancer gland rupture(CGR)(P=0.008).Moreover,the SID,width of submucosal invasion(WSI),and area of submucosal invasion(ASI)were not significantly different.When one,two,three or more risk factors were identified,the LNM rates were 1.1％(1/95),12.5％(7/56),and 48.8％(20/41),respectively.Conclusion:Indicators such as the SID,WSI,and ASI are not risk factors for LNM and are subjective in their measurement,which renders them relatively inconvenient to apply in clinical practice.In contrast,histological grade,LVI,tumor budding and CGR are relatively straightforward to identify and have been demonstrated to be statistically significant.It would be prudent to focus on these histological factors rather than subjective measurements.
      原文链接:
    • NETL
    • NSTL
    • 万方数据

    Key Genes Involved in the Beneficial Mechanism of Hyperbaric Oxygen for Glioblastoma and Predictive Indicators of Hyperbaric Oxygen Prolonging Survival in Glioblastoma Patients

    Zi-qi RENRen-dong WANGCong WANGXiao-hui REN...
    1036-1046页
    查看更多>>摘要：Objective:The prognosis of glioblastoma is poor,and therapy-resistance is largely attributed to intratumor hypoxia.Hyperbaric oxygen(HBO)effectively alleviates hypoxia.However,the sole role of HBO in glioblastoma remains controversial.We previously reported that HBO can promote apoptosis,shorten protrusions,and delay growth of glioblastoma,but the molecular mechanism is unclear.We aimed to test candidate genes in HBO-exposed glioblastoma cells and to analyze their correlation with the survival of glioblastoma patients.Methods:Glioblastoma cell lines exposed to repetitive HBO or normobaric air(NBA)were collected for RNA isolation and microarray data analysis.GO analysis,KEGG pathway analysis and survival analysis of the differentially expressed genes(DEGs)were performed.Results:HBO not only inhibited hypoxia-inducing genes including CA9,FGF11,PPFIA4,TCAF2 and SLC2A12,but also regulated vascularization by downregulating the expression of COL1 Al,COL8A1,COL12A1,RHOJ and FILIP 1L,ultimately attenuated hypoxic microenvironment of glioblastoma.HBO attenuated inflammatory microenvironment by reducing the expression of NLRP2,CARD8,MYD88 and CD 180.HBO prevented metastasis by downregulating the expression of NTM,CXCL12,CXCL13,CXCR4,CXCR5,CDC42,IGFBP3,IGFBP5,GPC6,MMP19,ADAMTS1,EFEMP1,PTBP3,NF1 and PDCD1.HBO upregulated the expression of BAK1,PPIF,DDIT3,TP53I11 and FAS,whereas downregulated the expression of MDM4 and SIVA1,thus promoting apoptosis.HBO upregulated the expression of CDC25A,MCM2,PCNA,RFC33,DSCC1 and CDC14A,whereas downregulated the expression of ASNS,CDK6,CDKN1B,PTBP3 and MAD2L1,thus inhibiting cell cycle progression.Among these DEGs,17 indicator-genes of HBO prolonging survival were detected.Conclusions:HBO is beneficial for glioblastoma.Glioblastoma patients with these predictive indicators may prolong survival with HBO therapy.These potential therapeutic targets especially COL1 Al,ADAMTS1 and PTBP3 deserve further validation.
      原文链接:
    • NETL
    • NSTL
    • 万方数据

    Gene Expression Profile Identifies LncRNA AL355974.3 As a Potential Glioma Biomarker

    Hao-tian LUYu-yang CHENYong-jia YUXing-sheng LIAO...
    1047-1057页
    查看更多>>摘要：Objective:Glioma is a central nervous system tumor arising from glial cells.Despite significant advances in diagnosis and treatment,most patients with high-grade gliomas have a poor prognosis.Many studies have shown that long noncoding RNAs(lncRNAs)may play important roles in the development,progression and treatment of many tumors,including gliomas.Molecularly targeted therapy may be a new direction for the adjuvant treatment of glioma.Therefore,we hope that by studying differentially expressed lncRNAs(DElncRNAs)in glioma,we can discover lncRNAs that can serve as biomarkers for glioma and provide better therapeutic modalities for glioma patients.Methods:First,the expression of lncRNAs in 5 normal brain(NB)tissues and 10 glioma tissues was examined by RNA sequencing(RNA-seq).Next,we performed Kaplan-Meier analysis of data from The Cancer Genome Atlas(TCGA)database to assess the prognostic value of these variables.Finally,functional analysis of the DElncRNAs was performed by means of Gene Ontology(GO)enrichment and Kyoto Encyclopedia of Genes and Genomes(KEGG)pathway analysis.Results:RNA sequencing analysis revealed 85 upregulated miRNAs and 71 downregulated lncRNAs in low-grade glioma(LGG)and 50 upregulated lncRNAs and 70 downregulated lncRNAs in glioblastoma(GBM).Among them,AL355974.3 was the most upregulated lncRNA.LINC00632 was the most downregulated lncRNA.Second,LGG patients with higher AL355974.3 expression had worse overall survival according to Kaplan-Meier analysis of the TCGA database.Finally,bioinformatics analysis revealed that the target genes of these DElncRNAs were enriched in various biological processes and signaling pathways,such as cell metabolic and developmental processes.Conclusion:Our findings provide evidence that AL355974.3 may be a new biomarker for glioma.
      原文链接:
    • NETL
    • NSTL
    • 万方数据

    Autocrine IL-8 Contributes to Propionibacterium Acnes-induced Proliferation and Differentiation of HaCaT Cells via AKT/FOXO1/Autophagy

    Xiu-qin YUJin-zhu MAOShu-yun YANGLu WANG...
    1058-1065页
    查看更多>>摘要：Objective:Proprionibacterium acnes(P.acnes)-induced inflammatory responses,proliferation and differentiation of keratinocytes contribute to the progression of acne vulgaris(AV).P.acnes was found to enhance the production of interleukin-8(IL-8)by keratinocytes.This study aimed to investigate the role of IL-8 in P.acnes-induced proliferation and differentiation of keratinocytes and the underlying mechanism.Methods:The P.acnes-stimulated HaCaT cell(a human keratinocyte cell line)model was established.Western blotting and immunofluorescence were performed to detect the expression of the IL-8 receptors C-X-C motif chemokine receptor 1(CXCR1)and C-X-C motif chemokine receptor 2(CXCR2)on HaCaT cells.Cell counting kit-8(CCK-8)assay,5-ethynyl-20-deoxyuridine(EdU)assay and Western blotting were performed to examine the effects of IL-8/CXCR2 axis on the proliferation and differentiation of HaCaT cells treated with P.acnes,the IL-8 neutralizing antibody,the CXCR2 antagonist(SB225002),or the CXCR1/CXCR2 antagonist(G31P).Western blotting,nuclear and cytoplasmic separation,CCK-8 assay,and EdU assay were employed to determine the downstream pathway of CXCR2 after P.acnes-stimulated HaCaT cells were treated with the CXCR2 antagonist,the protein kinase B(AKT)antagonist(AZD5363),or the constitutively active forkhead box O1(FOXO1)mutant.Finally,autophagy markers were measured in HaCaT cells following the transfection of the FOXO1 mutant or treatment with the autophagy inhibitor 3-methyladenine(3-MA).Results:The expression levels of CXCR1 and CXCR2 were significantly increased on the membrane of HaCaT cells following P.acnes stimulation.The IL-8/CXCR2 axis predominantly promoted the proliferation and differentiation of P.acnes-induced HaCaT cells by activating AKT/FOXO1/autophagy signaling.In brief,IL-8 bound to its receptor CXCR2 on the membrane of keratinocytes to activate the AKT/FOXO1 axis.Subsequently,phosphorylated FOXO1 facilitated autophagy to promote the proliferation and differentiation of P.acnes-induced keratinocytes.Conclusion:This study demonstrated the novel autocrine effect of IL-8 on the proliferation and differentiation of P acnes-induced keratinocytes,suggesting a potential therapeutic target for AV.
      原文链接:
    • NETL
    • NSTL
    • 万方数据

    Standardizing R-E-NSM Surgical Protocols:A Critical Appraisal for Breast Cancer Patients

    Wen-qin WANGXiang-zhi LIYong-mei WANG
    1066-1067页
      原文链接:
    • NETL
    • NSTL
    • 万方数据