目的探究血清microRNA-21(miR-21)、microRNA-193a-3p(miR-193a-3p)水平与结直肠癌患者手术预后的关系。方法回顾性分析2020年1月—2022年1月苏州大学附属第一医院收治112例结直肠癌患者的病历资料。患者均接受结直肠癌根治术,术后随访1...目的探究血清microRNA-21(miR-21)、microRNA-193a-3p(miR-193a-3p)水平与结直肠癌患者手术预后的关系。方法回顾性分析2020年1月—2022年1月苏州大学附属第一医院收治112例结直肠癌患者的病历资料。患者均接受结直肠癌根治术,术后随访16个月,记录患者的预后生存结局,多因素逐步Logistic回归分析结直肠癌患者手术预后的影响因素,评估血清miR-21、miR-193a-3p对结直肠癌患者预后的预测效能。结果112例结直肠癌患者死亡22例,病死率为19.64%;生存90例,生存率为80.36%。死亡组术前血清miR-21 mRNA相对表达量、临床分期Ⅲ期占比、淋巴结转移率均高于生存组(P<0.05),血清miR-193a-3p m RNA相对表达量低于生存组(P<0.05)。多因素逐步Logistic回归分析结果显示,临床分期Ⅲ期[OR=3.777(95%CI:1.399,10.194)]、淋巴结转移[OR=5.099(95%CI:1.715,15.156)]、miR-21表达升高[OR=4.889(95%CI:1.645,14.533)]、miR-193a-3p表达降低[OR=4.402(95%CI:1.481,13.084)]均是直肠癌患者预后的影响因素(P<0.05)。受试者工作特性曲线分析结果显示,血清miR-21、miR-193a-3p单一及联合预测结直肠癌预后的敏感性分别为69.04%(95%CI:0.487,0.813)、72.73%(95%CI:0.495,0.884)、86.36%(95%CI:0.640,0.964),特异性分别为62.22%(95%CI:0.513,0.720)、68.89%(95%CI:0.581,0.780)、90.00%(95%CI:0.814,0.950),曲线下面积分别为0.782、0.731和0.901。结论结直肠癌患者术前miR-21、miR-193a-3p表达与术后预后密切相关,且在结直肠癌患者的预后结局中表现出良好的预测效能。展开更多
BACKGROUND Diabetic kidney disease(DKD),characterized by increased urinary microalbumin levels and decreased renal function,is the primary cause of end-stage renal di-sease.Its pathological mechanisms are complicated ...BACKGROUND Diabetic kidney disease(DKD),characterized by increased urinary microalbumin levels and decreased renal function,is the primary cause of end-stage renal di-sease.Its pathological mechanisms are complicated and multifactorial;Therefore,sensitive and specific biomarkers are needed.Urinary exosome originate from diverse renal cells in nephron segments and partially mirror the pathological changes in the kidney.The microRNAs(miRNAs)in urinary exosome are remark-ably stable and highly tissue-specific for the kidney.METHODS Type 2 diabetic mellitus(T2DM)patients were recruited from the Second Hospital of Hebei Medical University and were divided into two groups:DM,diabetic pa-tients without albuminuria[urinary albumin to creatinine ratio(UACR)<30 mg/g]and DKD,diabetic patients with albuminuria(UACR≥30 mg/g).Healthy subjects were the normal control(NC)group.Urinary exosomal miR-145-5p,miR-27a-3p,and miR-29c-3p,were detected using real-time quantitative polymerase chain reaction.The correlation between exosomal miRNAs and the clinical in-dexes was evaluated.The diagnostic values of exosomal miR-145-5p and miR-27a-3p in DKD were determined using receiver operating characteristic(ROC)analysis.Biological functions of miR-145-5p were investigated by performing RESULTS Urinary exosomal expression of miR-145-5p and miR-27a-3p was more upregulated in the DKD group than in the DM group(miR-145-5p:4.54±1.45 vs 1.95±0.93,P<0.001;miR-27a-3p:2.33±0.79 vs 1.71±0.76,P<0.05)and the NC group(miR-145-5p:4.54±1.45 vs 1.55±0.83,P<0.001;miR-27a-3p:2.33±0.79 vs 1.10±0.51,P<0.001).The exosomal miR-145-5p and miR-27a-3p positively correlated with albuminuria and serum creatinine and negatively correlated with the estimated glomerular filtration rate.miR-27a-3p was also closely related to blood glucose,gly-cosylated hemoglobin A1c,and low-density lipoprotein cholesterol.ROC analysis revealed that miR-145-5p had a better area under the curve of 0.88[95%confidence interval(CI):0.784-0.985,P<0.0001]in diagnosing DKD than miR-27a-3p with 0.71(95%CI:0.547-0.871,P=0.0239).Bioinformatics analysis revealed that the target genes of miR-145-5p were located in the actin filament,cytoskeleton,and extracellular exosome and were involved in the pathological processes of DKD,including apoptosis,inflammation,and fibrosis.CONCLUSION Urinary exosomal miR-145-5p and miR-27a-3p may serve as novel noninvasive diagnostic biomarkers or promising therapeutic targets for DKD.展开更多
目的探究寻常性银屑病患者血清微小RNA(microRNA,miR)-133a-3p,蛋白酪氨酸磷酸酶非受体型22(protein tyrosine phosphatase non-receptor type 22,PTPN22)水平表达与疾病严重程度的相关性。方法收集沧州市人民医院2022年1~6月收治的寻...目的探究寻常性银屑病患者血清微小RNA(microRNA,miR)-133a-3p,蛋白酪氨酸磷酸酶非受体型22(protein tyrosine phosphatase non-receptor type 22,PTPN22)水平表达与疾病严重程度的相关性。方法收集沧州市人民医院2022年1~6月收治的寻常性银屑病患者86例作为观察组,根据皮损面积和严重程度将其分为进展期组(n=41)和静止期组(n=45),同期选取整形外科体检健康者86例作为对照组。采用实时荧光定量PCR(real time fluorescent quantitative PCR,qRT-PCR)法检测患者血清miR-133a-3p和PTPN22相对表达水平;Target Scan Human网站预测PTPN22与miR-133a-3p的靶向关系;运用Spearman法分析寻常性银屑病患者血清miR-133a-3p,PTPN22表达水平与银屑病皮损面积及严重程度指数(the psoriasis area and severity index score,PASI)评分的相关性;行Logistic回归分析寻常性银屑病患者严重度的影响因素。结果与对照组相比,观察组血清miR-133a-3p(1.85±0.46 vs 1.05±0.21)表达水平明显升高,PTPN22 mRNA(0.76±0.13 vs 1.02±0.18)表达水平明显降低,差异具有统计学意义(t=14.671,10.859,均P<0.05);与静止期组比较,进展期组血清miR-133a-3p(2.05±0.52 vs 1.67±0.41)表达水平明显升高,PTPN22 mRNA(0.66±0.11 vs 0.85±0.15)表达水平明显降低,差异具有统计学意义(t=3.780,6.643,均P<0.05)。Target Scan Human网站预测,miR-133a-3p与PTPN22可能存在靶向关系。Spearman分析显示,寻常性银屑病患者血清miR-133a-3p与PASI评分呈正相关性(r=0.469,P<0.05),而血清PTPN22 mRNA水平与PASI评分呈负相关性(r=-0.508,P<0.05);血清miR-133a-3p[OR(95%CI)=2.884(1.261~6.595)]是寻常性银屑病患者严重度的独立危险因素,而PTPN22[OR(95%CI)=0.562(0.367~0.860)]是独立保护因素(均P<0.05)。结论寻常性银屑病患者血清miR-133a-3p表达水平明显升高,PTPN22表达水平明显降低,两者与PASI评分紧密相关,且在一定程度上可反映银屑病患者的严重程度。展开更多
Objective Little is known about the role of microRNA-29a-3p(miR-29a-3p)in inflammation-related pyroptosis,especially in drug-induced acute liver failure(DIALF).This study aimed to identify the relationship between miR...Objective Little is known about the role of microRNA-29a-3p(miR-29a-3p)in inflammation-related pyroptosis,especially in drug-induced acute liver failure(DIALF).This study aimed to identify the relationship between miR-29a-3p and inflammation-related pyroptosis in DIALF and confirm its underlying mechanisms.Methods Thioacetamide(TAA)-and acetaminophen(APAP)-induced ALF mouse models were established,and human samples were collected.The expression levels of miR-29a-3p and inflammation and pyroptosis markers were measured by quantitative real-time polymerase chain reaction(qRT-PCR),Western blotting,or immunochemical staining in miR-29a-3p knock-in transgenic mouse(MIR29A(KI/KI))DIALF models.In addition,RNA sequencing was conducted to explore the mechanisms.Results MiR-29a-3p levels were decreased in TAA-and APAP-induced DIALF models.MiR-29a-3p prevented DIALF caused by TAA and APAP.RNA sequencing and further experiments showed that the protective effect of miR-29a-3p on DIALF was mainly achieved through inhibition of inflammation-related pyroptosis,and the inhibition was dependent on activation of the PI3K/AKT pathway.In addition,miR-29a-3p levels were reduced,and pyroptosis was activated in both peripheral blood mononuclear cells and liver tissues of DIALF patients.Conclusion The study supports the idea that miR-29a-3p inhibits pyroptosis by activating the PI3K/AKT pathway to prevent DIALF.MiR-29a-3p may be a promising therapeutic target for DIALF.展开更多
文摘目的探究血清microRNA-21(miR-21)、microRNA-193a-3p(miR-193a-3p)水平与结直肠癌患者手术预后的关系。方法回顾性分析2020年1月—2022年1月苏州大学附属第一医院收治112例结直肠癌患者的病历资料。患者均接受结直肠癌根治术,术后随访16个月,记录患者的预后生存结局,多因素逐步Logistic回归分析结直肠癌患者手术预后的影响因素,评估血清miR-21、miR-193a-3p对结直肠癌患者预后的预测效能。结果112例结直肠癌患者死亡22例,病死率为19.64%;生存90例,生存率为80.36%。死亡组术前血清miR-21 mRNA相对表达量、临床分期Ⅲ期占比、淋巴结转移率均高于生存组(P<0.05),血清miR-193a-3p m RNA相对表达量低于生存组(P<0.05)。多因素逐步Logistic回归分析结果显示,临床分期Ⅲ期[OR=3.777(95%CI:1.399,10.194)]、淋巴结转移[OR=5.099(95%CI:1.715,15.156)]、miR-21表达升高[OR=4.889(95%CI:1.645,14.533)]、miR-193a-3p表达降低[OR=4.402(95%CI:1.481,13.084)]均是直肠癌患者预后的影响因素(P<0.05)。受试者工作特性曲线分析结果显示,血清miR-21、miR-193a-3p单一及联合预测结直肠癌预后的敏感性分别为69.04%(95%CI:0.487,0.813)、72.73%(95%CI:0.495,0.884)、86.36%(95%CI:0.640,0.964),特异性分别为62.22%(95%CI:0.513,0.720)、68.89%(95%CI:0.581,0.780)、90.00%(95%CI:0.814,0.950),曲线下面积分别为0.782、0.731和0.901。结论结直肠癌患者术前miR-21、miR-193a-3p表达与术后预后密切相关,且在结直肠癌患者的预后结局中表现出良好的预测效能。
基金Supported by the Nature Science Foundation of Hebei Province,No.H2023104011.
文摘BACKGROUND Diabetic kidney disease(DKD),characterized by increased urinary microalbumin levels and decreased renal function,is the primary cause of end-stage renal di-sease.Its pathological mechanisms are complicated and multifactorial;Therefore,sensitive and specific biomarkers are needed.Urinary exosome originate from diverse renal cells in nephron segments and partially mirror the pathological changes in the kidney.The microRNAs(miRNAs)in urinary exosome are remark-ably stable and highly tissue-specific for the kidney.METHODS Type 2 diabetic mellitus(T2DM)patients were recruited from the Second Hospital of Hebei Medical University and were divided into two groups:DM,diabetic pa-tients without albuminuria[urinary albumin to creatinine ratio(UACR)<30 mg/g]and DKD,diabetic patients with albuminuria(UACR≥30 mg/g).Healthy subjects were the normal control(NC)group.Urinary exosomal miR-145-5p,miR-27a-3p,and miR-29c-3p,were detected using real-time quantitative polymerase chain reaction.The correlation between exosomal miRNAs and the clinical in-dexes was evaluated.The diagnostic values of exosomal miR-145-5p and miR-27a-3p in DKD were determined using receiver operating characteristic(ROC)analysis.Biological functions of miR-145-5p were investigated by performing RESULTS Urinary exosomal expression of miR-145-5p and miR-27a-3p was more upregulated in the DKD group than in the DM group(miR-145-5p:4.54±1.45 vs 1.95±0.93,P<0.001;miR-27a-3p:2.33±0.79 vs 1.71±0.76,P<0.05)and the NC group(miR-145-5p:4.54±1.45 vs 1.55±0.83,P<0.001;miR-27a-3p:2.33±0.79 vs 1.10±0.51,P<0.001).The exosomal miR-145-5p and miR-27a-3p positively correlated with albuminuria and serum creatinine and negatively correlated with the estimated glomerular filtration rate.miR-27a-3p was also closely related to blood glucose,gly-cosylated hemoglobin A1c,and low-density lipoprotein cholesterol.ROC analysis revealed that miR-145-5p had a better area under the curve of 0.88[95%confidence interval(CI):0.784-0.985,P<0.0001]in diagnosing DKD than miR-27a-3p with 0.71(95%CI:0.547-0.871,P=0.0239).Bioinformatics analysis revealed that the target genes of miR-145-5p were located in the actin filament,cytoskeleton,and extracellular exosome and were involved in the pathological processes of DKD,including apoptosis,inflammation,and fibrosis.CONCLUSION Urinary exosomal miR-145-5p and miR-27a-3p may serve as novel noninvasive diagnostic biomarkers or promising therapeutic targets for DKD.
文摘目的探究寻常性银屑病患者血清微小RNA(microRNA,miR)-133a-3p,蛋白酪氨酸磷酸酶非受体型22(protein tyrosine phosphatase non-receptor type 22,PTPN22)水平表达与疾病严重程度的相关性。方法收集沧州市人民医院2022年1~6月收治的寻常性银屑病患者86例作为观察组,根据皮损面积和严重程度将其分为进展期组(n=41)和静止期组(n=45),同期选取整形外科体检健康者86例作为对照组。采用实时荧光定量PCR(real time fluorescent quantitative PCR,qRT-PCR)法检测患者血清miR-133a-3p和PTPN22相对表达水平;Target Scan Human网站预测PTPN22与miR-133a-3p的靶向关系;运用Spearman法分析寻常性银屑病患者血清miR-133a-3p,PTPN22表达水平与银屑病皮损面积及严重程度指数(the psoriasis area and severity index score,PASI)评分的相关性;行Logistic回归分析寻常性银屑病患者严重度的影响因素。结果与对照组相比,观察组血清miR-133a-3p(1.85±0.46 vs 1.05±0.21)表达水平明显升高,PTPN22 mRNA(0.76±0.13 vs 1.02±0.18)表达水平明显降低,差异具有统计学意义(t=14.671,10.859,均P<0.05);与静止期组比较,进展期组血清miR-133a-3p(2.05±0.52 vs 1.67±0.41)表达水平明显升高,PTPN22 mRNA(0.66±0.11 vs 0.85±0.15)表达水平明显降低,差异具有统计学意义(t=3.780,6.643,均P<0.05)。Target Scan Human网站预测,miR-133a-3p与PTPN22可能存在靶向关系。Spearman分析显示,寻常性银屑病患者血清miR-133a-3p与PASI评分呈正相关性(r=0.469,P<0.05),而血清PTPN22 mRNA水平与PASI评分呈负相关性(r=-0.508,P<0.05);血清miR-133a-3p[OR(95%CI)=2.884(1.261~6.595)]是寻常性银屑病患者严重度的独立危险因素,而PTPN22[OR(95%CI)=0.562(0.367~0.860)]是独立保护因素(均P<0.05)。结论寻常性银屑病患者血清miR-133a-3p表达水平明显升高,PTPN22表达水平明显降低,两者与PASI评分紧密相关,且在一定程度上可反映银屑病患者的严重程度。
基金This project was supported by grants from the National Science and Technology Major Project(No.2014ZX10005001 and No.2018ZX10302204-001)Chen Xiaoping Development Foundation(No.CXPJJH12000002-2020032).
文摘Objective Little is known about the role of microRNA-29a-3p(miR-29a-3p)in inflammation-related pyroptosis,especially in drug-induced acute liver failure(DIALF).This study aimed to identify the relationship between miR-29a-3p and inflammation-related pyroptosis in DIALF and confirm its underlying mechanisms.Methods Thioacetamide(TAA)-and acetaminophen(APAP)-induced ALF mouse models were established,and human samples were collected.The expression levels of miR-29a-3p and inflammation and pyroptosis markers were measured by quantitative real-time polymerase chain reaction(qRT-PCR),Western blotting,or immunochemical staining in miR-29a-3p knock-in transgenic mouse(MIR29A(KI/KI))DIALF models.In addition,RNA sequencing was conducted to explore the mechanisms.Results MiR-29a-3p levels were decreased in TAA-and APAP-induced DIALF models.MiR-29a-3p prevented DIALF caused by TAA and APAP.RNA sequencing and further experiments showed that the protective effect of miR-29a-3p on DIALF was mainly achieved through inhibition of inflammation-related pyroptosis,and the inhibition was dependent on activation of the PI3K/AKT pathway.In addition,miR-29a-3p levels were reduced,and pyroptosis was activated in both peripheral blood mononuclear cells and liver tissues of DIALF patients.Conclusion The study supports the idea that miR-29a-3p inhibits pyroptosis by activating the PI3K/AKT pathway to prevent DIALF.MiR-29a-3p may be a promising therapeutic target for DIALF.
