目的分析程序性细胞死亡因子5(programmed cell death 5,PDCD5)、半胱天冬酶1(cysteinyl aspartate specific proteinase-1,Caspase-1)及分化簇64(cluster of differentiation 64,CD64)联合与甲型H1N1流行性感冒病毒性肺炎患者短期预后...目的分析程序性细胞死亡因子5(programmed cell death 5,PDCD5)、半胱天冬酶1(cysteinyl aspartate specific proteinase-1,Caspase-1)及分化簇64(cluster of differentiation 64,CD64)联合与甲型H1N1流行性感冒病毒性肺炎患者短期预后的相关性及预测价值,构建甲型H1N1流行性感冒病毒性肺炎患者短期不良预后的预测模型。方法选取2023年3月—2024年8月在上海市同仁医院确诊的甲型H1N1流行性感冒病毒性肺炎患者362例,并依据28 d内生存结局分为生存组259例与死亡组103例。收集比较2组入院时的临床特征资料,通过多因素Logistic回归分析确定甲型H1N1流行性感冒病毒性肺炎28 d死亡的独立危险因素,通过R 4.3.1绘制列线图模型。绘制受试者工作特征(receiver operating characteristic,ROC)曲线、校准曲线、临床决策曲线分析(decision curve analysis,DCA)评估列线图模型的预测效能及临床获益。结果死亡组年龄、体温、心率、呼吸频率、白细胞计数、中性粒细胞、C反应蛋白、乳酸脱氢酶、降钙素原、乳酸、血二氧化碳分压、血氧分压、吸入氧浓度、丙氨酸转氨酶、天冬氨酸转氨酶、尿素氮、血肌酐、PDCD5、Caspase-1、CD64、中性粒细胞与淋巴细胞比值(neutrophil-tolymphocyte ratio,NLR)、急性生理与慢性健康评分II(acute physiology and chronic health evaluationII,APACHEII)评分、序贯器官衰竭估计评分、临床肺部感染(clinical pulmonary infection score,CPIS)评分、机械通气高于生存组,收缩压、舒张压、淋巴细胞低于生存组,差异有统计学意义(P<0.05)。多因素Logistic回归分析显示,PDCD5(OR=1.02,95%CI:1.01~1.03)、Caspase-1(OR=1.03,95%CI:1.01~1.05)、CD64(OR=1.03,95%CI:1.01~1.05)、NLR(OR=1.23,95%CI:1.08~1.40)、APACHEII评分(OR=1.58,95%CI:1.24~2.02)、CPIS评分(OR=1.69,95%CI:1.29~2.22)、机械通气(OR=5.73,95%CI:2.97~11.08)均为甲型H1N1流行性感冒病毒性肺炎患者28 d死亡的独立相关因素(均P<0.05)。PDCD5、Caspase-1、CD64单项预测28 d死亡的曲线下面积(area under the curve,AUC)分别为0.723、0.704和0.639,三者联合预测模型的AUC为0.923。模型经Bootstrap法重抽样1000次内部验证后,C-index为0.903(95%CI:0.874~0.927)。校准曲线显示,预测概率与实际发生率拟合良好;DCA结果提示,当预测28 d死亡风险阈值概率在5%~62%范围内时,列线图模型可获得较高的净临床获益。结论基于PDCD5、Caspase-1、CD64构建甲型H1N1流行性感冒病毒性肺炎患者短期预后预测模型可对高危甲型H1N1流行性感冒病毒性肺炎患者进行早期预警。展开更多
BACKGROUND MicroRNAs play an important role in gastric cancer(GC)development following Helicobacter pylori(H.pylori)infection.Yet the exact mechanism is still not fully understood.Herein,we investigated the underlying...BACKGROUND MicroRNAs play an important role in gastric cancer(GC)development following Helicobacter pylori(H.pylori)infection.Yet the exact mechanism is still not fully understood.Herein,we investigated the underlying mechanisms of miR-136 during this process.AIM To investigate the role of miR-136 in H.pylori-induced GC progression.METHODS GC and gastric epithelial cells were infected with H.pylori and transfected with miR-136 mimic,inhibitor,mimic plus PDCD11(identified as miR-136 target),or miR-NC(control).Cell proliferation,migration,and invasion were assessed via cell counting kit-8 assay,colony formation,wound healing,and Transwell assays.Nuclear factor kappa-B(NF-κB)/miR-136/PDCD11 interactions were confirmed by luciferase and inhibition assays.For in vivo studies H.pylori-infected BGC-823 cells were injected into nude mice.Reverse transcription PCR,western blot,immunohistochemistry,and immunofluorescent staining assay were used to assess mRNA and protein expression.RESULTS miR-136 expression was significantly upregulated while PDCD11 expression was significantly downregulated in early GC tissues and GC cells infected with H.pylori compared with non-infected tissues or cells(all P<0.01).miR-136 overexpression induced by H.pylori could promote the proliferation and migration of infected GC cells and induce the growth of H.pylori-positive GC tumors in mice while its inhibition could reverse this effect.Mechanistically,upregulation of miR-136 suppressed PDCD11 through NF-κB activation induced by H.pylori infection.CONCLUSION miR-136 is a novel diagnostic biomarker and therapeutic target in H.pylori-associated early-stage gastric carcinogenesis and acts through the NF-κB-miR-136-PDCD11 pathway.展开更多
本研究观察程序性细胞死亡5基因(programmed cell death 5,PDCD5)重组腺病毒转染K562细胞后对化疗药物依托泊甙的增敏作用。利用AdMaxTM腺病毒载体包装系统,通过同源重组方法构建Ad-PDCD5重组腺病毒及对照腺病毒Ad-null及Ad-eGFP;用不...本研究观察程序性细胞死亡5基因(programmed cell death 5,PDCD5)重组腺病毒转染K562细胞后对化疗药物依托泊甙的增敏作用。利用AdMaxTM腺病毒载体包装系统,通过同源重组方法构建Ad-PDCD5重组腺病毒及对照腺病毒Ad-null及Ad-eGFP;用不同感染复数将Ad-eGFP、Ad-null或Ad-PDCD5转染人白血病细胞系,实时定量PCR检测PDCD5mRNA的相对表达水平;利用MTT法及Annexin-V-FITC/PI双染色流式细胞术观察依托泊甙对转染后K562细胞增殖与凋亡的影响。结果表明:Ad-eGFP腺病毒对白血病细胞系K562、Jurkat及CEM的转染效率可达60%-86%。Ad-PDCD5重组腺病毒能梯度增加K562细胞PDCD5 mRNA的相对表达水平,腺病毒介导的PDCD5基因转移促进依托泊甙诱导的K562细胞凋亡。结论:PDCD5重组腺病毒可能成为化疗药物的增敏剂。展开更多
文摘目的分析程序性细胞死亡因子5(programmed cell death 5,PDCD5)、半胱天冬酶1(cysteinyl aspartate specific proteinase-1,Caspase-1)及分化簇64(cluster of differentiation 64,CD64)联合与甲型H1N1流行性感冒病毒性肺炎患者短期预后的相关性及预测价值,构建甲型H1N1流行性感冒病毒性肺炎患者短期不良预后的预测模型。方法选取2023年3月—2024年8月在上海市同仁医院确诊的甲型H1N1流行性感冒病毒性肺炎患者362例,并依据28 d内生存结局分为生存组259例与死亡组103例。收集比较2组入院时的临床特征资料,通过多因素Logistic回归分析确定甲型H1N1流行性感冒病毒性肺炎28 d死亡的独立危险因素,通过R 4.3.1绘制列线图模型。绘制受试者工作特征(receiver operating characteristic,ROC)曲线、校准曲线、临床决策曲线分析(decision curve analysis,DCA)评估列线图模型的预测效能及临床获益。结果死亡组年龄、体温、心率、呼吸频率、白细胞计数、中性粒细胞、C反应蛋白、乳酸脱氢酶、降钙素原、乳酸、血二氧化碳分压、血氧分压、吸入氧浓度、丙氨酸转氨酶、天冬氨酸转氨酶、尿素氮、血肌酐、PDCD5、Caspase-1、CD64、中性粒细胞与淋巴细胞比值(neutrophil-tolymphocyte ratio,NLR)、急性生理与慢性健康评分II(acute physiology and chronic health evaluationII,APACHEII)评分、序贯器官衰竭估计评分、临床肺部感染(clinical pulmonary infection score,CPIS)评分、机械通气高于生存组,收缩压、舒张压、淋巴细胞低于生存组,差异有统计学意义(P<0.05)。多因素Logistic回归分析显示,PDCD5(OR=1.02,95%CI:1.01~1.03)、Caspase-1(OR=1.03,95%CI:1.01~1.05)、CD64(OR=1.03,95%CI:1.01~1.05)、NLR(OR=1.23,95%CI:1.08~1.40)、APACHEII评分(OR=1.58,95%CI:1.24~2.02)、CPIS评分(OR=1.69,95%CI:1.29~2.22)、机械通气(OR=5.73,95%CI:2.97~11.08)均为甲型H1N1流行性感冒病毒性肺炎患者28 d死亡的独立相关因素(均P<0.05)。PDCD5、Caspase-1、CD64单项预测28 d死亡的曲线下面积(area under the curve,AUC)分别为0.723、0.704和0.639,三者联合预测模型的AUC为0.923。模型经Bootstrap法重抽样1000次内部验证后,C-index为0.903(95%CI:0.874~0.927)。校准曲线显示,预测概率与实际发生率拟合良好;DCA结果提示,当预测28 d死亡风险阈值概率在5%~62%范围内时,列线图模型可获得较高的净临床获益。结论基于PDCD5、Caspase-1、CD64构建甲型H1N1流行性感冒病毒性肺炎患者短期预后预测模型可对高危甲型H1N1流行性感冒病毒性肺炎患者进行早期预警。
基金Supported by the National Natural Science Foundation of China,No.82470593General Project of the Development Fund of the Affiliated Hospital of Xuzhou Medical University,No.XYFM202334.
文摘BACKGROUND MicroRNAs play an important role in gastric cancer(GC)development following Helicobacter pylori(H.pylori)infection.Yet the exact mechanism is still not fully understood.Herein,we investigated the underlying mechanisms of miR-136 during this process.AIM To investigate the role of miR-136 in H.pylori-induced GC progression.METHODS GC and gastric epithelial cells were infected with H.pylori and transfected with miR-136 mimic,inhibitor,mimic plus PDCD11(identified as miR-136 target),or miR-NC(control).Cell proliferation,migration,and invasion were assessed via cell counting kit-8 assay,colony formation,wound healing,and Transwell assays.Nuclear factor kappa-B(NF-κB)/miR-136/PDCD11 interactions were confirmed by luciferase and inhibition assays.For in vivo studies H.pylori-infected BGC-823 cells were injected into nude mice.Reverse transcription PCR,western blot,immunohistochemistry,and immunofluorescent staining assay were used to assess mRNA and protein expression.RESULTS miR-136 expression was significantly upregulated while PDCD11 expression was significantly downregulated in early GC tissues and GC cells infected with H.pylori compared with non-infected tissues or cells(all P<0.01).miR-136 overexpression induced by H.pylori could promote the proliferation and migration of infected GC cells and induce the growth of H.pylori-positive GC tumors in mice while its inhibition could reverse this effect.Mechanistically,upregulation of miR-136 suppressed PDCD11 through NF-κB activation induced by H.pylori infection.CONCLUSION miR-136 is a novel diagnostic biomarker and therapeutic target in H.pylori-associated early-stage gastric carcinogenesis and acts through the NF-κB-miR-136-PDCD11 pathway.
文摘本研究观察程序性细胞死亡5基因(programmed cell death 5,PDCD5)重组腺病毒转染K562细胞后对化疗药物依托泊甙的增敏作用。利用AdMaxTM腺病毒载体包装系统,通过同源重组方法构建Ad-PDCD5重组腺病毒及对照腺病毒Ad-null及Ad-eGFP;用不同感染复数将Ad-eGFP、Ad-null或Ad-PDCD5转染人白血病细胞系,实时定量PCR检测PDCD5mRNA的相对表达水平;利用MTT法及Annexin-V-FITC/PI双染色流式细胞术观察依托泊甙对转染后K562细胞增殖与凋亡的影响。结果表明:Ad-eGFP腺病毒对白血病细胞系K562、Jurkat及CEM的转染效率可达60%-86%。Ad-PDCD5重组腺病毒能梯度增加K562细胞PDCD5 mRNA的相对表达水平,腺病毒介导的PDCD5基因转移促进依托泊甙诱导的K562细胞凋亡。结论:PDCD5重组腺病毒可能成为化疗药物的增敏剂。
