OBJECTIVE To explore the antipost-traumatic-stress-disorder(PTSD) effects and its probable mechanism of YQA14,a dopamine D3 receptor antagonist.METHODS Two PTSD animal models,the rat single prolonged stress(SPS) model...OBJECTIVE To explore the antipost-traumatic-stress-disorder(PTSD) effects and its probable mechanism of YQA14,a dopamine D3 receptor antagonist.METHODS Two PTSD animal models,the rat single prolonged stress(SPS) model and the mouse pre-shock model,were used in this experiment.In the SPS model,adult male Sprague-Dawley(SD) rats were randomly divided into control group,model group,positive group and YQA14 groups with different dosages.In the mouse pre-chock model,dopamine D3 receptor knockout(KO) and wild type(WT) mice were randomly divided into control group,model group,positive group and YQA14 group.After the establishment of animal models,the saline,sertraline(ig) and YQA14(ip)were administered to the animals in the control,model,positive control and test groups respectively.The open field test(OFT) was used to evaluate the locomotor activity while the contextual freezing(CF) measurement and elevated plus maze(EPM) test were used to evaluate the PTSD-like behaviors.RESULTS In the rat SPS model,neither SPS nor drug treatment affected the locomotor activity in rats.However,SPS rats showed significant PTSD-like behaviors with enhanced freezing time in CF(P<0.01) and decreased percentage of entries into open arms and time spent in open arms in EPM(P<0.05,P<0.01).Moreover,compared with the model group,the repeated administration of YQA14(3.125,6.25 and 12.5 mg·kg-1)significantly reduced the freezing time(P<0.01)and increased the percentages of entries into open arms and time spent in open arms(P<0.05).In the mouse pre-shock model,when both model groups showed significant higher freezing time compared with the respective control groups(P<0.05,P<0.01),YQA14 selectively alleviated the freezing time on WT mice(P<0.05) while had no effect on KO mice.In the EPM tests,the WT mice model group showed a significant reduction in the percentage of entries into open arms and time spent in open arms(P<0.05) while D3 R KO mice model group didn′ t show any reduction,compared with respective control groups.Furthermore,daily administration of YQA14 at 12.5 mg·kg-1 both significantly reduced the percentages of entries into and time spent in open arms(P<0.05) but not D3 R KO mice.None of the locomotor activity were significantly affected.CONCLUSION YQA14 could significantly alleviate the PTSD-like behaviors in rodents and the effects were mediated by the blockade of brain D3 receptors.展开更多
目的:通过meta分析全面评估认知行为疗法(CBT)在治疗创伤后应激障碍(PTSD)的效果。方法:系统检索PubMed、Web of Science、PsycINFO、中国知网(CNKI)、万方数据库、维普数据库,筛选相关随机对照试验(RCTs),以标准化评定量表评估PTSD症...目的:通过meta分析全面评估认知行为疗法(CBT)在治疗创伤后应激障碍(PTSD)的效果。方法:系统检索PubMed、Web of Science、PsycINFO、中国知网(CNKI)、万方数据库、维普数据库,筛选相关随机对照试验(RCTs),以标准化评定量表评估PTSD症状的减轻程度为主要结局指标。对纳入的研究进行了数据提取、质量评估和meta分析,检索时限为2005年1月-2024年10月。Meta分析采用Review Manager Software 5.4完成。结果:共纳入21项研究(总样本量1 683例)。Meta分析结果显示,CBT在减轻PTSD症状方面显著优于对照组,(SMD=-0.25,95%CI:-0.43~-0.06,P<0.05)。亚组分析探讨了研究区域、样本量和创伤来源等因素对结果的影响,为CBT在不同情境下的应用提供了参考。结论:CBT在缓解成年人PTSD症状方面具有良好疗效。展开更多
目的:创伤后癫痫(post-traumatic epilepsy,PTE)是创伤性脑损伤(traumatic brain injury,TBI)的常见并发症,严重影响患者预后,早期预测PTE风险对临床管理至关重要,相比成人,儿童PTE相关研究较少,且缺乏临床公认的高预测效能模型。本研...目的:创伤后癫痫(post-traumatic epilepsy,PTE)是创伤性脑损伤(traumatic brain injury,TBI)的常见并发症,严重影响患者预后,早期预测PTE风险对临床管理至关重要,相比成人,儿童PTE相关研究较少,且缺乏临床公认的高预测效能模型。本研究旨在构建并验证适用于儿童TBI患者的PTE风险预测列线图模型。方法:系统检索中国知网、万方、中国生物医学文献数据库、维普、Pubmed、Embase和Web of Science数据库中关于儿童PTE危险因素的研究,检索时限为建库至2024年10月。采用Stata 15.0软件进行Meta分析,根据Meta分析结果提取合并效应量具有显著性的风险因素。回顾性收集2019年1月—2023年12月南京医科大学附属儿童医院外科重症监护病房(surgical intensive care unit,SICU)收治的262例TBI患儿,按7∶3比例随机划分为训练队列和内部验证队列,基于Meta分析筛选的危险因素,利用R软件构建多因素Logistic回归模型并绘制列线图。采用受试者工作特征(receiver operating characteristic,ROC)曲线下面积(area under the curve,AUC)评价模型区分度,Hosmer-Lemeshow检验评估校准度,运用决策曲线分析(decision curve analysis,DCA)评估临床实用性。结果:共纳入13项研究,涉及1371819例TBI患儿。Meta分析显示,中国TBI儿童中PTE的发病率为19%(95%CI:17%~20%)。结合Meta分析筛选结果和临床经验,最终纳入8个危险因素构建模型:格拉斯哥昏迷量表(Glasgow coma scale,GCS)评分、开放性脑损伤、早期痫性发作、意识丧失以及异常颅脑影像学表现(颅内血肿、脑挫伤、硬膜下出血、蛛网膜下腔出血),预测模型在训练队列和内部验证队列的AUC分别为0.801(95%CI:0.735~0.867,P<0.05)和0.831(95%CI:0.728~0.934,P<0.05)。Hosmer-Lemeshow拟合优度检验示模型拟合良好(训练队列:P=0.079;验证队列:P=0.082)。DCA显示该模型具有较高临床净获益。结论:本研究基于Meta分析构建的儿童PTE风险预测模型具有良好的区分度、校准度和临床实用性,可作为TBI儿童发生PTE风险评估的有效工具。展开更多
基金National Key Research and DevelopmentProgram of China (2016YFC0800907)MedicalInnovation Program (16CXZ033)+2 种基金National KeyBasic Research Program (2015CB553504)National Natural Science Foundation of China(8157340581373385).
文摘OBJECTIVE To explore the antipost-traumatic-stress-disorder(PTSD) effects and its probable mechanism of YQA14,a dopamine D3 receptor antagonist.METHODS Two PTSD animal models,the rat single prolonged stress(SPS) model and the mouse pre-shock model,were used in this experiment.In the SPS model,adult male Sprague-Dawley(SD) rats were randomly divided into control group,model group,positive group and YQA14 groups with different dosages.In the mouse pre-chock model,dopamine D3 receptor knockout(KO) and wild type(WT) mice were randomly divided into control group,model group,positive group and YQA14 group.After the establishment of animal models,the saline,sertraline(ig) and YQA14(ip)were administered to the animals in the control,model,positive control and test groups respectively.The open field test(OFT) was used to evaluate the locomotor activity while the contextual freezing(CF) measurement and elevated plus maze(EPM) test were used to evaluate the PTSD-like behaviors.RESULTS In the rat SPS model,neither SPS nor drug treatment affected the locomotor activity in rats.However,SPS rats showed significant PTSD-like behaviors with enhanced freezing time in CF(P<0.01) and decreased percentage of entries into open arms and time spent in open arms in EPM(P<0.05,P<0.01).Moreover,compared with the model group,the repeated administration of YQA14(3.125,6.25 and 12.5 mg·kg-1)significantly reduced the freezing time(P<0.01)and increased the percentages of entries into open arms and time spent in open arms(P<0.05).In the mouse pre-shock model,when both model groups showed significant higher freezing time compared with the respective control groups(P<0.05,P<0.01),YQA14 selectively alleviated the freezing time on WT mice(P<0.05) while had no effect on KO mice.In the EPM tests,the WT mice model group showed a significant reduction in the percentage of entries into open arms and time spent in open arms(P<0.05) while D3 R KO mice model group didn′ t show any reduction,compared with respective control groups.Furthermore,daily administration of YQA14 at 12.5 mg·kg-1 both significantly reduced the percentages of entries into and time spent in open arms(P<0.05) but not D3 R KO mice.None of the locomotor activity were significantly affected.CONCLUSION YQA14 could significantly alleviate the PTSD-like behaviors in rodents and the effects were mediated by the blockade of brain D3 receptors.
文摘目的:创伤后癫痫(post-traumatic epilepsy,PTE)是创伤性脑损伤(traumatic brain injury,TBI)的常见并发症,严重影响患者预后,早期预测PTE风险对临床管理至关重要,相比成人,儿童PTE相关研究较少,且缺乏临床公认的高预测效能模型。本研究旨在构建并验证适用于儿童TBI患者的PTE风险预测列线图模型。方法:系统检索中国知网、万方、中国生物医学文献数据库、维普、Pubmed、Embase和Web of Science数据库中关于儿童PTE危险因素的研究,检索时限为建库至2024年10月。采用Stata 15.0软件进行Meta分析,根据Meta分析结果提取合并效应量具有显著性的风险因素。回顾性收集2019年1月—2023年12月南京医科大学附属儿童医院外科重症监护病房(surgical intensive care unit,SICU)收治的262例TBI患儿,按7∶3比例随机划分为训练队列和内部验证队列,基于Meta分析筛选的危险因素,利用R软件构建多因素Logistic回归模型并绘制列线图。采用受试者工作特征(receiver operating characteristic,ROC)曲线下面积(area under the curve,AUC)评价模型区分度,Hosmer-Lemeshow检验评估校准度,运用决策曲线分析(decision curve analysis,DCA)评估临床实用性。结果:共纳入13项研究,涉及1371819例TBI患儿。Meta分析显示,中国TBI儿童中PTE的发病率为19%(95%CI:17%~20%)。结合Meta分析筛选结果和临床经验,最终纳入8个危险因素构建模型:格拉斯哥昏迷量表(Glasgow coma scale,GCS)评分、开放性脑损伤、早期痫性发作、意识丧失以及异常颅脑影像学表现(颅内血肿、脑挫伤、硬膜下出血、蛛网膜下腔出血),预测模型在训练队列和内部验证队列的AUC分别为0.801(95%CI:0.735~0.867,P<0.05)和0.831(95%CI:0.728~0.934,P<0.05)。Hosmer-Lemeshow拟合优度检验示模型拟合良好(训练队列:P=0.079;验证队列:P=0.082)。DCA显示该模型具有较高临床净获益。结论:本研究基于Meta分析构建的儿童PTE风险预测模型具有良好的区分度、校准度和临床实用性,可作为TBI儿童发生PTE风险评估的有效工具。
