目的系统评价我国老年人群认知衰弱风险预测模型,为护理人员选择或开发合适的老年人认知衰弱风险预测模型提供参考,并为老年人认知衰弱干预方案的制定提供依据。方法计算机系统检索Cochrane Library、Embase、PubMed、Web of Science、...目的系统评价我国老年人群认知衰弱风险预测模型,为护理人员选择或开发合适的老年人认知衰弱风险预测模型提供参考,并为老年人认知衰弱干预方案的制定提供依据。方法计算机系统检索Cochrane Library、Embase、PubMed、Web of Science、中国知网、万方数据及维普数据库发表的与主题相关的中国人群研究,检索时间为建库至2023年7月1日,根据纳入、排除标准筛选文献,2名研究者依据预测模型研究数据提取表和偏倚风险评估工具独立提取资料和评价质量。结果共纳入10篇文献,10个老年认知衰弱风险预测模型,总样本量为268~1182例,发生认知衰弱事件数为54~293例。1个模型未行内外部验证,2个模型仅行内部验证,3个模型仅行外部验证,4个模型行内外部验证,模型受试者工作特征曲线下面积为0.710~0.991,8篇研究对模型进行校准。多变量模型重复报告的独立预测因子包括年龄、运动习惯、抑郁、合并症及营养状况。纳入模型偏倚风险均为高风险,适用性评价均为好。结论我国老年人认知衰弱风险预测模型具有良好的区分度及适用性,但存在显著的方法学缺陷和高偏倚风险。未来研究应严格按照风险预测模型报告规范来开发和评估我国老年人群认知衰弱风险预测模型,并验证其在临床实践中的可行性。展开更多
OBJECTIVE To investigate whether aldo-keto reductases(AKRs)can act as a nitrore⁃ductase(NR)and bioactivate aristolochic acidⅠ(AA-Ⅰ)to produce AA-Ⅰ-DNA adducts.METHODS①Human-induced hepatocytes(hiHeps)and human bla...OBJECTIVE To investigate whether aldo-keto reductases(AKRs)can act as a nitrore⁃ductase(NR)and bioactivate aristolochic acidⅠ(AA-Ⅰ)to produce AA-Ⅰ-DNA adducts.METHODS①Human-induced hepatocytes(hiHeps)and human bladder RT4 cells were used as tool cells and treated with AA-Ⅰ0,0.5,1.0 and 2μmol·L^(-1)for 24 h.Cell viability was detected using the CCK-8 method,and the half maximal inhibition concentration(IC_(50))was calculated using the CCK-8 method and the level of DNA adduct production was calculated.②hiHeps and RT4 cells were treated with AKR inhibitor luteotin(0,5,10 and 25μmol·L^(-1))+AA-Ⅰ0.2 and 1.0μmol·L^(-1)for 24 h,respectively,and the levels of DNA adducts were detected by a liquid chromatography-tandem mass spectrometer(LC-MS/MS).③hiHeps cells were incubated with 80 nmol·L^(-1)small interfering RNAs(si-AKRs)for 48 h and treated with AA-Ⅰ1.0μmol·L^(-1)for 24 h.Real-time qualitative PCR(RT-qPCR)method was used to detect the mRNA expression of AKRs gene and LC-MS/MS technology was used to investigate the effect of specific AKR gene knockdown on DNA adduct levels.④500 nmol·L^(-1)human AKR recombinant proteins AKR1A1 and AA-Ⅰwere incubated in vitro under anaerobic conditions and the formation of AA-Ⅰ-DNA adducts was detected.RESULTS①The IC_(50)of AA-Ⅰto hiHeps and RT4 cells was 1.9 and 0.42μmol·L^(-1),respec⁃tively.The level of DNA adduct production of the two cell lines was significantly different(P<0.01).②Luteolin≥5μmol·L^(-1)significantly inhibited the production of AA-Ⅰ-DNA adducts in both cells(P<0.05),and there was a concentration-dependent effect in hiHeps cells(P<0.01,R=0.84).③In the AKR family,the knockdown of AKR1A1 gene up to 80%inhibited the generation of AA-Ⅰ-DNA adducts by 30%-40%.④The AA-Ⅰ-DNA adducts were detected in the incubation of recombinant protein AKR1A1 and AA-Ⅰunder anaerobic conditions in vitro,approximately 1 adduct per 107 nucleotides.CONCLU⁃SION AKR1A1 is involved in AA-Ⅰbioactivation,providing a reference for elucidation of the carcino⁃genic mechanism of AA-Ⅰ.展开更多
文摘目的系统评价我国老年人群认知衰弱风险预测模型,为护理人员选择或开发合适的老年人认知衰弱风险预测模型提供参考,并为老年人认知衰弱干预方案的制定提供依据。方法计算机系统检索Cochrane Library、Embase、PubMed、Web of Science、中国知网、万方数据及维普数据库发表的与主题相关的中国人群研究,检索时间为建库至2023年7月1日,根据纳入、排除标准筛选文献,2名研究者依据预测模型研究数据提取表和偏倚风险评估工具独立提取资料和评价质量。结果共纳入10篇文献,10个老年认知衰弱风险预测模型,总样本量为268~1182例,发生认知衰弱事件数为54~293例。1个模型未行内外部验证,2个模型仅行内部验证,3个模型仅行外部验证,4个模型行内外部验证,模型受试者工作特征曲线下面积为0.710~0.991,8篇研究对模型进行校准。多变量模型重复报告的独立预测因子包括年龄、运动习惯、抑郁、合并症及营养状况。纳入模型偏倚风险均为高风险,适用性评价均为好。结论我国老年人认知衰弱风险预测模型具有良好的区分度及适用性,但存在显著的方法学缺陷和高偏倚风险。未来研究应严格按照风险预测模型报告规范来开发和评估我国老年人群认知衰弱风险预测模型,并验证其在临床实践中的可行性。
文摘OBJECTIVE To investigate whether aldo-keto reductases(AKRs)can act as a nitrore⁃ductase(NR)and bioactivate aristolochic acidⅠ(AA-Ⅰ)to produce AA-Ⅰ-DNA adducts.METHODS①Human-induced hepatocytes(hiHeps)and human bladder RT4 cells were used as tool cells and treated with AA-Ⅰ0,0.5,1.0 and 2μmol·L^(-1)for 24 h.Cell viability was detected using the CCK-8 method,and the half maximal inhibition concentration(IC_(50))was calculated using the CCK-8 method and the level of DNA adduct production was calculated.②hiHeps and RT4 cells were treated with AKR inhibitor luteotin(0,5,10 and 25μmol·L^(-1))+AA-Ⅰ0.2 and 1.0μmol·L^(-1)for 24 h,respectively,and the levels of DNA adducts were detected by a liquid chromatography-tandem mass spectrometer(LC-MS/MS).③hiHeps cells were incubated with 80 nmol·L^(-1)small interfering RNAs(si-AKRs)for 48 h and treated with AA-Ⅰ1.0μmol·L^(-1)for 24 h.Real-time qualitative PCR(RT-qPCR)method was used to detect the mRNA expression of AKRs gene and LC-MS/MS technology was used to investigate the effect of specific AKR gene knockdown on DNA adduct levels.④500 nmol·L^(-1)human AKR recombinant proteins AKR1A1 and AA-Ⅰwere incubated in vitro under anaerobic conditions and the formation of AA-Ⅰ-DNA adducts was detected.RESULTS①The IC_(50)of AA-Ⅰto hiHeps and RT4 cells was 1.9 and 0.42μmol·L^(-1),respec⁃tively.The level of DNA adduct production of the two cell lines was significantly different(P<0.01).②Luteolin≥5μmol·L^(-1)significantly inhibited the production of AA-Ⅰ-DNA adducts in both cells(P<0.05),and there was a concentration-dependent effect in hiHeps cells(P<0.01,R=0.84).③In the AKR family,the knockdown of AKR1A1 gene up to 80%inhibited the generation of AA-Ⅰ-DNA adducts by 30%-40%.④The AA-Ⅰ-DNA adducts were detected in the incubation of recombinant protein AKR1A1 and AA-Ⅰunder anaerobic conditions in vitro,approximately 1 adduct per 107 nucleotides.CONCLU⁃SION AKR1A1 is involved in AA-Ⅰbioactivation,providing a reference for elucidation of the carcino⁃genic mechanism of AA-Ⅰ.
