BACKGROUND The increased stroke risk associated with atrial fibrillation(AF)burden exceeding 5 min is a matter of debate.In addition,the potential linear or nonlinear relationship between AF burden and stroke risk has...BACKGROUND The increased stroke risk associated with atrial fibrillation(AF)burden exceeding 5 min is a matter of debate.In addition,the potential linear or nonlinear relationship between AF burden and stroke risk has been largely unexplored.AIM To determine the association between AF burden>5 min and the increased risk of stroke and explore the potential dose-response relationship between these two factors.METHODS Sixteen studies from six databases with 53141 subjects(mean age 65 years)were included.Fifteen studies were observational studies,and one was a randomized controlled trial study.The potential nonlinear dose-response association was characterized using a restricted cubic splines regression model.AF burden for each 1 h and 2 h was associated with an increased risk of stroke.Trial sequential analysis with a random-effect model was used to evaluate the robustness of the evidence from the included 16 studies.RESULTS AF burden>5 min was associated with an increased risk of clinical AF[adjusted risk ratio(RR)=4.18,95%confidence interval(CI):2.26-7.74].However,no association was found with an increased risk of all-cause mortality(adjusted RR=1.55,95%CI:0.87-2.75).Patients with AF burden>5 min had an increased risk of stroke(adjusted RR=2.49,95%CI:1.79-3.47).Moreover,a dose-response analysis showed that the increased stroke risk was paralleled by an increase in AF burden at a rate of 2.0%per hour(Pnonlinear=0.656,RR=1.02,95%CI:1.01-1.03).Trial sequential analysis provided robust evidence of the association between AF burden>5 min and an increased risk of stroke.CONCLUSION AF burden was a significant risk factor for clinical AF and future stroke.A significant linear association was documented between increased AF burden and risk of future stroke.展开更多
目的基于网络药理学结合谱效关系及分子对接,探讨五味甘露抗炎的物质基础及作用机制。方法利用中药系统药理学数据库与分析平台(TCMSP)、Genecards、Pubchem、UniProt、中国学术期刊全文数据库(CNKI)等数据库筛选五味甘露的活性成分及...目的基于网络药理学结合谱效关系及分子对接,探讨五味甘露抗炎的物质基础及作用机制。方法利用中药系统药理学数据库与分析平台(TCMSP)、Genecards、Pubchem、UniProt、中国学术期刊全文数据库(CNKI)等数据库筛选五味甘露的活性成分及抗炎的作用靶点,利用STRING数据库、Cytoscape3.7软件构建蛋白质-蛋白质相互作用(PPI)网络并筛选核心靶点,利用Metascape数据库进行基因本体(GO)及京都基因与基因组百科全书(KEGG)通路富集分析。将细胞炎症模型与高效液相色谱法相结合分析五味甘露不同极性部位的抗炎活性和药效成分。采用Discovery Studio Lib Dock软件将主要药效成分与核心靶点进行分子对接,并进行可视化分析。结果网络药理学分析共获取五味甘露抗炎成分125个,潜在抗炎靶点251个,得到核心靶点131个,包括肿瘤坏死因子(TNF)、白细胞介素-6(IL-6)、白细胞介素-1β(IL-1β)重要靶点。KEGG通路富集分析,共富集到20条相关通路,其中涉及基因较多的包括脂质与动脉粥样硬化和类风湿性关节炎(RA)等通路,诸多通路均涉及NOD样受体热蛋白结构域相关蛋白3(NLRP3)核心靶点。五味甘露的醋酸乙酯相能够抑制炎症相关的NLRP3、IL-1β、TNF的表达,且其中总黄酮含量最高,为(305.0±11.4)mg·g^(-1)。LC-MS图谱分析和分子对接实验显示醋酸乙酯相中山柰酚、杨梅素、异荭草素、异槲皮苷和黄芪苷等黄酮类物质的离子强度远远高于单味药材且其母核结构与NLRP3受体蛋白的7个氨基酸活性位点有显著的相互作用。结论五味甘露抗炎的主要物质为黄酮类,可通过抑制NLRP3炎症小体的活化起到抗炎作用。展开更多
基金Supported by National Natural Science Foundation of China,No.81673259Natural Science Foundation of Jiangsu Province,China,No.BK20161435.
文摘BACKGROUND The increased stroke risk associated with atrial fibrillation(AF)burden exceeding 5 min is a matter of debate.In addition,the potential linear or nonlinear relationship between AF burden and stroke risk has been largely unexplored.AIM To determine the association between AF burden>5 min and the increased risk of stroke and explore the potential dose-response relationship between these two factors.METHODS Sixteen studies from six databases with 53141 subjects(mean age 65 years)were included.Fifteen studies were observational studies,and one was a randomized controlled trial study.The potential nonlinear dose-response association was characterized using a restricted cubic splines regression model.AF burden for each 1 h and 2 h was associated with an increased risk of stroke.Trial sequential analysis with a random-effect model was used to evaluate the robustness of the evidence from the included 16 studies.RESULTS AF burden>5 min was associated with an increased risk of clinical AF[adjusted risk ratio(RR)=4.18,95%confidence interval(CI):2.26-7.74].However,no association was found with an increased risk of all-cause mortality(adjusted RR=1.55,95%CI:0.87-2.75).Patients with AF burden>5 min had an increased risk of stroke(adjusted RR=2.49,95%CI:1.79-3.47).Moreover,a dose-response analysis showed that the increased stroke risk was paralleled by an increase in AF burden at a rate of 2.0%per hour(Pnonlinear=0.656,RR=1.02,95%CI:1.01-1.03).Trial sequential analysis provided robust evidence of the association between AF burden>5 min and an increased risk of stroke.CONCLUSION AF burden was a significant risk factor for clinical AF and future stroke.A significant linear association was documented between increased AF burden and risk of future stroke.
文摘目的基于网络药理学结合谱效关系及分子对接,探讨五味甘露抗炎的物质基础及作用机制。方法利用中药系统药理学数据库与分析平台(TCMSP)、Genecards、Pubchem、UniProt、中国学术期刊全文数据库(CNKI)等数据库筛选五味甘露的活性成分及抗炎的作用靶点,利用STRING数据库、Cytoscape3.7软件构建蛋白质-蛋白质相互作用(PPI)网络并筛选核心靶点,利用Metascape数据库进行基因本体(GO)及京都基因与基因组百科全书(KEGG)通路富集分析。将细胞炎症模型与高效液相色谱法相结合分析五味甘露不同极性部位的抗炎活性和药效成分。采用Discovery Studio Lib Dock软件将主要药效成分与核心靶点进行分子对接,并进行可视化分析。结果网络药理学分析共获取五味甘露抗炎成分125个,潜在抗炎靶点251个,得到核心靶点131个,包括肿瘤坏死因子(TNF)、白细胞介素-6(IL-6)、白细胞介素-1β(IL-1β)重要靶点。KEGG通路富集分析,共富集到20条相关通路,其中涉及基因较多的包括脂质与动脉粥样硬化和类风湿性关节炎(RA)等通路,诸多通路均涉及NOD样受体热蛋白结构域相关蛋白3(NLRP3)核心靶点。五味甘露的醋酸乙酯相能够抑制炎症相关的NLRP3、IL-1β、TNF的表达,且其中总黄酮含量最高,为(305.0±11.4)mg·g^(-1)。LC-MS图谱分析和分子对接实验显示醋酸乙酯相中山柰酚、杨梅素、异荭草素、异槲皮苷和黄芪苷等黄酮类物质的离子强度远远高于单味药材且其母核结构与NLRP3受体蛋白的7个氨基酸活性位点有显著的相互作用。结论五味甘露抗炎的主要物质为黄酮类,可通过抑制NLRP3炎症小体的活化起到抗炎作用。
