The α5 subunit-containing gamma-amino butyric acid type A receptors(α5 GABAARs) are a distinct subpopulation that are specifically distributed in the mammalian hippocampus and also mediate tonic inhibitory currents ...The α5 subunit-containing gamma-amino butyric acid type A receptors(α5 GABAARs) are a distinct subpopulation that are specifically distributed in the mammalian hippocampus and also mediate tonic inhibitory currents in hippocampal neurons. These tonic currents can be enhanced by low-dose isoflurane, which is associated with learning and memory impairment. Inverse agonists of α5 GABAARs, such as L-655,708, are able to reverse the short-term memory deficit caused by low-dose isoflurane in young animals. However, whether these negative allosteric modulators have the same effects on aged rats remains unclear. In the present study, we mainly investigated the effects of L-655,708 on low-dose(1.3%) isoflurane-induced learning and memory impairment in elderly rats. Young(3-month-old) and aged(24-month-old) Wistar rats were randomly assigned to receive L-655,708 0.5 hour before or 23.5 hours after 1.3% isoflurane anesthesia.The Morris Water Maze tests demonstrated that L-655,708 injected before or after anesthesia could reverse the memory deficit in young rats. But in aged rats, application of L-655,708 only before anesthesia showed similar effects. Reverse transcription-polymerase chain reaction showed that low-dose isoflurane decreased the mRNA expression of α5 GABAARs in aging hippocampal neurons but increased that in young animals. These findings indicate that L-655,708 prevented but could not reverse 1.3% isoflurane-induced spatial learning and memory impairment in aged Wistar rats. All experimental procedures and protocols were approved by the Experimental Animal Ethics Committee of Academy of Military Medical Science of China(approval No. NBCDSER-IACUC-2015128) in December 2015.展开更多
目的系统评价国内外现有的老年轻度认知障碍(MCI)风险预测模型的偏倚风险、适用性。方法计算机检索中国知网、万方数据知识服务平台、中国生物医学文献数据库、PubMed、Cochrane Library、Web of Science、Embase中关于老年MCI风险预测...目的系统评价国内外现有的老年轻度认知障碍(MCI)风险预测模型的偏倚风险、适用性。方法计算机检索中国知网、万方数据知识服务平台、中国生物医学文献数据库、PubMed、Cochrane Library、Web of Science、Embase中关于老年MCI风险预测模型的研究,检索时限为建库至2024-05-31。剔除重复文献后,由两位研究人员严格按照文献纳入与排除标准独立进行文献筛选;对于最终纳入的文献,由两位研究人员根据系统评价的批判性评估和数据提取清单(CHARMS)进行资料提取;由两位研究人员使用预测模型偏倚风险评估工具(PROBAST)评估纳入模型的偏倚风险和适用性。结果最终纳入文献14篇,共构建了21个老年MCI风险预测模型,本研究仅选择各文献中性能表现最佳的模型。14个模型的候选预测变量数为4~42个,每个自变量的事件数(EPV)为2.5~195.5;在建模方法方面,主要采用Logistic回归分析、Cox回归分析;在模型性能评估结果方面,12个模型的AUC为0.676~0.96;在模型校准方法方面,11个模型未进行校准;在模型验证方法方面,8个模型未进行验证。14个模型的整体偏倚风险均为高风险,整体适用性均为低风险。结论现有的老年MCI风险预测模型多数具备一定的区分能力,整体适用性较好,但其校准度尚不明确,整体偏倚风险较高。展开更多
文摘The α5 subunit-containing gamma-amino butyric acid type A receptors(α5 GABAARs) are a distinct subpopulation that are specifically distributed in the mammalian hippocampus and also mediate tonic inhibitory currents in hippocampal neurons. These tonic currents can be enhanced by low-dose isoflurane, which is associated with learning and memory impairment. Inverse agonists of α5 GABAARs, such as L-655,708, are able to reverse the short-term memory deficit caused by low-dose isoflurane in young animals. However, whether these negative allosteric modulators have the same effects on aged rats remains unclear. In the present study, we mainly investigated the effects of L-655,708 on low-dose(1.3%) isoflurane-induced learning and memory impairment in elderly rats. Young(3-month-old) and aged(24-month-old) Wistar rats were randomly assigned to receive L-655,708 0.5 hour before or 23.5 hours after 1.3% isoflurane anesthesia.The Morris Water Maze tests demonstrated that L-655,708 injected before or after anesthesia could reverse the memory deficit in young rats. But in aged rats, application of L-655,708 only before anesthesia showed similar effects. Reverse transcription-polymerase chain reaction showed that low-dose isoflurane decreased the mRNA expression of α5 GABAARs in aging hippocampal neurons but increased that in young animals. These findings indicate that L-655,708 prevented but could not reverse 1.3% isoflurane-induced spatial learning and memory impairment in aged Wistar rats. All experimental procedures and protocols were approved by the Experimental Animal Ethics Committee of Academy of Military Medical Science of China(approval No. NBCDSER-IACUC-2015128) in December 2015.
文摘目的系统评价国内外现有的老年轻度认知障碍(MCI)风险预测模型的偏倚风险、适用性。方法计算机检索中国知网、万方数据知识服务平台、中国生物医学文献数据库、PubMed、Cochrane Library、Web of Science、Embase中关于老年MCI风险预测模型的研究,检索时限为建库至2024-05-31。剔除重复文献后,由两位研究人员严格按照文献纳入与排除标准独立进行文献筛选;对于最终纳入的文献,由两位研究人员根据系统评价的批判性评估和数据提取清单(CHARMS)进行资料提取;由两位研究人员使用预测模型偏倚风险评估工具(PROBAST)评估纳入模型的偏倚风险和适用性。结果最终纳入文献14篇,共构建了21个老年MCI风险预测模型,本研究仅选择各文献中性能表现最佳的模型。14个模型的候选预测变量数为4~42个,每个自变量的事件数(EPV)为2.5~195.5;在建模方法方面,主要采用Logistic回归分析、Cox回归分析;在模型性能评估结果方面,12个模型的AUC为0.676~0.96;在模型校准方法方面,11个模型未进行校准;在模型验证方法方面,8个模型未进行验证。14个模型的整体偏倚风险均为高风险,整体适用性均为低风险。结论现有的老年MCI风险预测模型多数具备一定的区分能力,整体适用性较好,但其校准度尚不明确,整体偏倚风险较高。
