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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
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    Advancing the Battle against Cystic Fibrosis:Stem Cell and Gene Therapy Insights

    Disha D.ShahMehul R.ChorawalaAanshi J.PandyaNirjari Kothari...
    1155-1174页
    查看更多>>摘要：)Cystic fibrosis(CF)is a hereditary disorder characterized by mutations in the CFTR gene,leading to impaired chloride ion transport and subsequent thickening of mucus in various organs,particularly the lungs.Despite significant progress in CF management,current treatments focus mainly on symptom relief and do not address the underlying genetic defects.Stem cell and gene therapies present promising avenues for tackling CF at its root cause.Stem cells,including embryonic,induced pluripotent,mesenchymal,hematopoietic,and lung progenitor cells,offer regenerative potential by differentiating into specialized cells and modulating immune responses.Similarly,gene therapy aims to correct CFTR gene mutations by delivering functional copies of the gene into affected cells.Various approaches,such as viral and nonviral vectors,gene editing with CRISPR-Cas9,small interfering RNA(siRNA)therapy,and mRNA therapy,are being explored to achieve gene correction.Despite their potential,challenges such as safety concerns,ethical considerations,delivery system optimization,and long-term efficacy remain.This review provides a comprehensive overview of the current understanding of CF pathophysiology,the rationale for exploring stem cell and gene therapies,the types of therapies available,their mechanisms of action,and the challenges and future directions in the field.By addressing these challenges,stem cell and gene therapies hold promise for transforming CF management and improving the quality of life of affected individuals.
      原文链接:
    • NETL
    • NSTL
    • 万方数据

    Current Combinatorial Therapeutic Aspects:The Future Prospect for Glioblastoma Treatment

    Megha GautamReema Gabrani
    1175-1184页
    查看更多>>摘要：There are several types of brain tumors but glioblastoma(GBM)is one of the highly malignant tumors.A primary concern with GBM is that the treatment is inadequate.Even after giving many multi-stacked combinations of therapies to patients,inclusive of chemotherapy,radiation,and surgery,the median survival rate remains poor.Due to its heterogeneous nature,the use of selective therapy for specific targeting of tumor cells is of particular importance.Although many treatment alternatives which include surgery with adjuvant chemotherapy and radiotherapy are available,the prognosis of the disease is very poor.Combination therapy is becoming the foundation of modern antitumor therapy and it is continuously evolving and developing innovative drug regimens as evidenced by ongoing preclinical and clinical trials.In this review,we discuss the current treatment options and emerging therapeutic approaches for the treatment of GBM.The prospects for alternative glioblastoma therapy are also discussed.
      原文链接:
    • NETL
    • NSTL
    • 万方数据

    Acupuncture Treats Sepsis through Immune Modulation and Organ Protection

    Zi-xiao WANGRen-jie QINLing-ling YUArman Nurlan...
    1185-1192页
    查看更多>>摘要：Sepsis is a secondary condition resulting from severe systemic infections.It is a significant contributor to mortality in critically ill patients with rapid onset and severe symptoms.Acupuncture is a traditional Chinese medical treatment.Recent clinical studies have demonstrated that acupuncture,as an important synergistic therapy,has promising therapeutic effects in the treatment of sepsis.This paper reviews the mechanisms of immunomodulation and target organ protection associated with acupuncture and synergistic drug acupuncture in the treatment of sepsis.It also integrates existing studies to elucidate the modulation of the immune system and the protective effect of acupuncture on target organs.
      原文链接:
    • NETL
    • NSTL
    • 万方数据

    Trends in Bacterial Distribution and Antimicrobial Resistance in Intensive Care Units of Hubei Province,China:A Four-year Surveillance Study(2020-2023)

    Sui GAOCui JIAN
    1193-1201页
    查看更多>>摘要：Objective:To investigate the distribution characteristics of common bacteria and changes in antimicrobial resistance in intensive care unit(ICU)patients in 58 hospitals in Hubei Province from 2020-2023.Method:The antimicrobial agents for antimicrobial susceptibility tests was selected based on the 2022 China Antimicrobial Resistance surveillance system(CARSS)technical scheme,and the specific experimental operation was based on the requirements of the CLSI M02 and M07 documents.The commercial instruments were used following the manufacturer's instructions.The interpretation of antimicrobial susceptibility test results was based on the 2023 CLSI Ml00 standard.Results:There were 15 585,19 258,23 423 and 22 395 clinical isolates in the ICU from 2020 to 2023,respectively.Among them,gram-positive bacteria accounted for 20.5％(3190/15 585),21.2％(4089/19 258),21.6％(5067/23 423)and 21.6％(4 831/22 395),respectively.Gram-negative bacteria accounted for 79.5％(12 395/15585),78.8％(15 169/19 258),78.4％(18 356/23 423)and 78.4％(17 564/22 395)of the bacteria,respectively.The top 5 isolates of gram-positive bacteria were Staphylococcus aureus,Enterococcus faecium,Streptococcus pneumoniae,Enterococcus faecalis,Staphylococcus epidermidis and gram-negative bacteria were Klebsiella pneumoniae,Acinetobacter baumannii,Escherichia coli,Pseudomonas aeruginosa and Stenotrophomonas maltophil,respectively,but the proportions and rankings of the isolates in different years slightly differed.The detection rate of methicillin-resistant S.aureus(MRSA)decreased from 44.4％in 2020 to 36％in 2023,and that of methicillin-resistant coagulase-negative Staphylococcus(MRCNS)decreased from 79.8％in 2020 to 73.8％in 2022 and increased to 78.4％in 2023.The detection rates of both vancomycin-resistant E.faecium and E.faecalis were lower than 1％.The detection rate of carbapenem-resistant P.aeruginosa(CRPA)decreased from 25％in 2020 to 19.7％in 2022 and increased slightly to 20.6％in 2023.The detection rate of carbapenem-resistant A.baumannii(CRAB)decreased from 81.9％in 2020 to 79.7％in 2022 and increased to 82.9％in 2023.The detection rate of third-generation cephalosporin-resistant E.coli decreased from 59.8％in 2020 to 53.1％in 2022 and increased to 52.5％in 2023.The detection rate of fluoroquinolone-resistant E.coli decreased from 62.7％in 2020 to 50.2％in 2022 and increased slightly to 51.0％in 2023.The detection rate of carbapenem-resistant E.coli(CRECO)decreased from 3.3％in 2020 to 1.8％in 2022 and slightly increased to 2.1％in 2023.The detection rate of third-generation cephalosporin-resistant K.pneumoniae decreased from 34.3％in 2020 to 26.3％in 2022 and then increased to 32.4％in 2023.The detection rate of carbapenem-resistant K.pneumoniae(CRKPN)increased from 17.9％to 19.4％in 2020,decreased to 13.2％in 2022,and rose sharply to 20.4％in 2023.Conclusion:MRSA showed a continuous downwards trend from 2020 to 2023,while the detection rates of MRCNS and most multidrug-resistant gram-negative bacteria continuously decreased from 2020 to 2022 but tended to increase in 2023.Therefore,it is still necessary to strengthen the monitoring of bacterial resistance and rational application of antibiotics and actively and effectively control nosocomial infections.
      原文链接:
    • NETL
    • NSTL
    • 万方数据

    Rates,Risk Factors,and Outcomes of Nonvariceal Upper Gastrointestinal Bleeding in Patients Hospitalized for CO VID-19 in the United States

    Mohammad AldiabatWesam AleyadehTaimur MuzammilKemi Adewuyi...
    1202-1209页
    查看更多>>摘要：Objective:This study aimed to investigate the incidence and predictors of non-variceal upper gastrointestinal bleeding(NVUGIB)in hospitalized patients with coronavirus disease 2019(COVID-19),as well as the inpatient outcomes associated with this complication.Methods:This was an analysis of the National Inpatient Sample Database from January to December 2020.Adult COVID-19 patients were categorized into two groups based on NVUGIB development during hospitalization.Multivariate logistic analysis was performed to identify predictors and outcomes associated with NVUGIB in hospitalized COVID-19 patients in the US,after adjusting for age,sex,race,and Charlson Comorbidity Index(CCI)score,using Stata/BE 17.0.Results:Among 1 050 045 hospitalized patients,1.87％developed NVUGIB.Asian Americans had the highest risk,followed by Native Americans,Hispanics,and African Americans,with odds ratios(ORs)of 1.70,1.59,1.40,and 1.14,respectively.Patients with higher CCI scores were also at greater risk(with ORs of 1.47,2.09,and 3.45 for CCI scores of 1,2,and 3,respectively).COVID-19 patients with NVUGIB had a higher risk of inpatient mortality(OR=3.84),acute kidney injury(OR=3.12),hypovolemic shock(OR=13.7),blood transfusion(OR=7.02),and in-hospital cardiac arrest(OR=4.02).Conclusion:NVUGIB occurred in 1.87％of hospitalized COVID-19 patients and was associated with a threefold increase in mortality.Further research is necessary to identify strategies for reducing its incidence in COVID-19 patients with multiple risk factors.
      原文链接:
    • NETL
    • NSTL
    • 万方数据

    Intraperitoneal and Extraperitoneal Pringle Hepatic Hilar Occlusion in Laparoscopic Liver Resection:A Prospective Randomized Controlled Study

    Liang HEWei-xiang LIDa-chen ZHOUYong WANG...
    1210-1216页
    查看更多>>摘要：Objective:This prospective randomized controlled study was conducted to evaluate the safety and efficacy of the Pringle hepatic hilar occlusion with a bulldog clamp in laparoscopic liver resection.Methods:From March 1,2020 to July 31,2021,80 patients were enrolled,including 40 undergoing intraperitoneal Pringle maneuver(IPM)and 40 extraperitoneal Pringle maneuver(EPM).The observation indices included basic preoperative clinical characteristics and intraoperative and postoperative liver function indices.Results:There were no significant differences in the basic characteristics or types of hepatectomy,intraoperative blood loss,intraoperative blood transfusion,or hepatectomy time between the IPM and EPM groups.However,the blocking and operation time in the IPM group was shorter than that in the EPM group.There were no significant differences in alanine aminotransferase(ALT)or aspartate aminotransferase(AST)levels on the first day after surgery or in total bilirubin(TBIL)or albumin(ALB)levels on the first,third,or fifth days after surgery.However,C-reactive protein(CRP)levels on the first and third days,ALT and AST levels on the third and fifth days were lower,and hospital stay after surgery was shorter in the IPM group than in the EPM group.Conclusion:IPM using bulldog clamps is simple,safe,and effective.The inflammatory reaction is less severe,the degree of liver function injury is lower,and recovery is faster.
      原文链接:
    • NETL
    • NSTL
    • 万方数据

    Cell Cycle-related LncRNA-based Prognostic Model for Hepatocellular Carcinoma:Integrating Immune Microenvironment and Treatment Response

    Lin CHENGuo-zhi WUTao WUHao-hu SHANG...
    1217-1231页
    查看更多>>摘要：Objective:Hepatocellular carcinoma(HCC)presents substantial genetic and phenotypic diversity,making it challenging to predict patient outcomes.There is a clear need for novel biomarkers to better identify high-risk individuals.Long non-coding RNAs(lncRNAs)are known to play key roles in cell cycle regulation and genomic stability,and their dysregulation has been closely linked to HCC progression.Developing a prognostic model based on cell cycle-related lncRNAs could open up new possibilities for immunotherapy in HCC patients.Methods:Transcriptomic data and clinical samples were obtained from the TCGA-HCC dataset.Cell cycle-related gene sets were sourced from existing studies,and coexpression analysis identified relevant lncRNAs(correlation coefficient＞0.4,P＜0.001).Univariate analysis identified prognostic lncRNAs,which were then used in a LASSO regression model to create a risk score.This model was validated via cross-validation.HCC samples were classified on the basis of their risk scores.Correlations between the risk score and tumor mutational burden(TMB),tumor immune infiltration,immune checkpoint gene expression,and immunotherapy response were evaluated via R packages and various methods(TIMER,CIBERSORT,CIBERSORT-ABS,QUANTISEQ,MCP-COUNTER,XCELL,and EPIC).Results:Four cell cycle-related lncRNAs(AC009549.1,AC090018.2,PKD1P6-NPIPP1,and TMCC1-AS1)were significantly upregulated in HCC.These lncRNAs were used to create a risk score(risk score=0.492×AC009549.1+1.390×AC090018.2+1.622×PKD1P6-NPIPP1+0.858×TMCC1-AS1).This risk score had superior predictive value compared to traditional clinical factors(AUC=0.738).A nomogram was developed to illustrate the 1-year,3-year,and 5-year overall survival(OS)rates for individual HCC patients.Significant differences in TMB,immune response,immune cell infiltration,immune checkpoint gene expression,and drug responsiveness were observed between the high-risk and low-risk groups.Conclusion:The risk score model we developed enhances the prognostication of HCC patients by identifying those at high risk for poor outcomes.This model could lead to new immunotherapy strategies for HCC patients.
      原文链接:
    • NETL
    • NSTL
    • 万方数据

    LncRNA H19 Activates the RAS-MAPK Signaling Pathway via miR-140-5p/SOS1 Axis in Malignant Liver Tumors

    Ya-qun YUShu-qun LIJun WENGBo LI...
    1232-1240页
    查看更多>>摘要：Objective:To study the influences of LncRNA H19(H19)on malignant liver tumor cells and elucidate the underlying molecular mechanisms.Methods:H19 expression in liver tumor tissues,matched normal liver tissues,human liver malignant tumor cell lines and the human hepatocyte line LO2 was assessed via quantitative RT-PCR.Cell viability analysis and Matrigel invasion analysis were performed to evaluate the effects of H19 on cell proliferation and invasion.Luciferase reporter analysis was carried out to assess the interaction between miR-140-5p and SOS Ras/Rac guanine nucleotide exchange factor 1(SOS1).The influence of H19 on the Ras-MAPK signalling pathway was evaluated by detecting key protein levels via active Ras pull-down analysis and Western blot analysis.Results:H19 expression was lower in liver cancer samples than in matched normal liver tissue samples.H19 overexpression enhanced the proliferation and invasion of HepG2 and SMMC-7721 cells.H19 overexpression increased the level of activated Ras.The expression levels of phosphorylated Raf,phosphorylated ERK and phosphorylated MEK were increased by H19 overexpression.H19 knockdown had the opposite effect.Treatment with a MAPK inhibitor significantly reversed the influence of H19 overexpression on liver malignant tumor cell growth and invasion.The MAPK activator reversed the opposing effects of H19 silencing.H19 overexpression increased the protein level of SOS1,and miR-140-5p directly targeted SOS1.Conclusion:H19 can activate the Ras-MAPK signalling pathway via the miR-140-5p/SOS1 axis in malignant liver tumour cells.
      原文链接:
    • NETL
    • NSTL
    • 万方数据

    Jianpi Huoxue Decoction Ameliorates Alcohol-associated Liver Disease by Improving Intestinal Barrier Function in Rats

    Xin WANGDong-sheng YAOLin XUDong-ming YAN...
    1241-1248页
    查看更多>>摘要：Objective:Jianpi huoxue decoction(JHD),a Chinese herbal formula,is commonly used for treating alcohol-associated liver disease(ALD).This study aimed to investigate the mechanism by which JHD affects intestinal barrier function in ALD rats.Methods:The Sprague-Dawley rats were randomly divided into three groups:control group,model group and JHD group.They were pair-fed a modified Lieber-DeCarli liquid diet containing alcohol(model group,n=10;JHD group,n=10)or isocaloric maltose dextrin(control group,n=10)for 6 weeks.After 3 weeks of feeding,the mice in the JHD group were given JHD(10 mL/kg/day)by gavage for 3 weeks,and those in the control and model groups received equal amounts of double-distilled water for the same period of time.Afterwards,all the rats were given lipopolysaccharide(LPS)by gavage and sacrificed 3.5 h later.LPS levels were measured in the portal blood to evaluate gut leakage.Transmission electron microscopy(TEM)was used to observe ultrastructural changes in the intestinal tract.Adherens junction(AJ)and tight junction(TJ)proteins were detected by Western blotting,immunofluorescence or immunohistochemistry.Results:JHD ameliorated Lieber-DeCarli liquid diet-induced hepatic steatosis,inflammation and LPS expression.It improved pathological changes in the liver and alleviated intestinal ultrastructure injury.Moreover,it significantly enhanced the integrity of tight junctions by increasing the expression of zonula occludens-1(ZO-1)and occludin.It suppressed the activation of myosin light chain(MLC)phosphorylation.Conclusion:JHD improves intestinal barrier function and reduces gut leakiness in ALD rats.
      原文链接:
    • NETL
    • NSTL
    • 万方数据

    Contribution of ECT2 to Tubulointerstitial Fibrosis in the Progression of Chronic Kidney Disease

    Kai-xin SONGHua SU
    1249-1258页
    查看更多>>摘要：Objective:Chronic kidney disease(CKD)is a complex disorder resulting from a combination of various environmental and genetic factors.Considerable efforts have been dedicated to elucidating its etiological mechanisms.Nevertheless,the pathogenic mechanism of CKD remains poorly understood,which hinders the development of effective therapeutic strategies.In this study,we aimed to identify novel mediators that could contribute to the development of CKD.Methods:The ClinVar,STRING,MEME Suite,TRRUST,bedtools,GEO,and R Studio databases and software were used to analyze their common features and investigate potential CKD disease genes.Transcriptomic analysis,immunohistochemistry,qRT-PCR,and Western blotting were utilized to further validate the role of ECT2 in kidney fibrosis.Results:In total,26 CKD disease genes were obtained from the ClinVar database,and the STRING,MEME Suite,TRRUST,bedtools,and GEO databases and software were used to analyze their common properties and explore potential CKD disease genes.Epithelial cell transforming sequence 2(ECT2),cyclin B 1,caspase 7 and collagen alpha-1(Ⅳ)were identified as potential candidates for CKD progression.Weighted correlation network analysis(WGCNA)subsequently revealed the relationships between potential genes and CKD.The results of the transcriptomic analysis further confirmed that ECT2 expression was greater in the kidney tissue of CKD patients than in that of healthy controls.Next,immunohistochemistry and Western blotting demonstrated that ECT2 was predominantly expressed in the renal tubules of a unilateral ureteral obstruction(UUO)mouse model.Consistently,in vitro experiments revealed that ECT2 was upregulated in TGF-β1-treated HK-2 cells.Moreover,ECT2 overexpression or knockdown in HK-2 cells altered the intensity of fibrosis markers.Conclusion:ECT2 significantly affects the development and progression of CKD,particularly in association with tubulointerstitial fibrosis.
      原文链接:
    • NETL
    • NSTL
    • 万方数据