The aim of the present study is to investigate how cytochrome P450 enzymes（CYP） 2C8-derived epoxyeicosatrienoic acids（EETs） regulate the nuclear factor erythroid 2-related factor 2（Nrf2） signaling pathway and pr...The aim of the present study is to investigate how cytochrome P450 enzymes（CYP） 2C8-derived epoxyeicosatrienoic acids（EETs） regulate the nuclear factor erythroid 2-related factor 2（Nrf2） signaling pathway and protect against oxidative stress-induced endothelial injuries in the development and progression of atherosclerosis. In this study,cultured human umbilical vein endothelial cells（HUVECs） were transfected with CYP2C8 or pretreated with exogenous EETs（1 μmol/L） before TNF-α（20 ng/m L） stimulation. Apoptosis and intracellular ROS production were determined by flow cytometry. The expression levels of ROS-associated NAD（P）H subunits gp91 and p47,the anti-oxidative enzyme catalase（CAT）,Nrf2,heme oxygenase-1（HO-1） and endothelial nitric oxide synthase（e NOS） were detected by Western blotting. The results showed that CYP2C8-derived EETs decreased apoptosis of HUVECs treated with TNF-α. Pretreatment with 11,12-EET also significantly blocked TNF-α-induced ROS production. In addition,11,12-EET decreased oxidative stress-induced apoptosis. Furthermore,the ability of 11,12-EET to protect cells against TNF-α-induced apoptosis via oxidative stress was abrogated by transient transfection with Nrf2-specific small interfering RNA（si RNA）. In conclusion,CYP2C8-derived EETs prevented TNF-α-induced HUVECs apoptosis via inhibition of oxidative stress associated with the Nrf2 signaling.展开更多
目的比较早期经皮冠状动脉介入(PCI)与延迟PCI策略对高危非ST段抬高型急性冠状动脉综合征(NSTE-ACS)12个月临床终点的影响。方法连续收集自2015年1月1日至2015年12月31日在武汉亚洲心脏病医院行PCI治疗的高危NSTE-ACS患者758例,并依据...目的比较早期经皮冠状动脉介入(PCI)与延迟PCI策略对高危非ST段抬高型急性冠状动脉综合征(NSTE-ACS)12个月临床终点的影响。方法连续收集自2015年1月1日至2015年12月31日在武汉亚洲心脏病医院行PCI治疗的高危NSTE-ACS患者758例,并依据介入治疗时间窗分为早期PCI组(确诊后24 h内PCI,185例)和延迟PCI组(确诊后超过24 h PCI,573例),主要终点是术后12个月主要不良心血管事件(MACE),包括全因死亡与再发非致死性心肌梗死。回顾性对比分析两组基线临床资料、冠状动脉影像特征、PCI相关数据以及主要终点。结果 711例(93.8%)患者完成12个月随访。早期PCI组主要终点MACE发生率与延迟PCI组比较差异无统计学意义(14.5%比11.2%,χ~2=1.289,P=0.256),全因死亡与再发非致死性心肌梗死两组比较,差异均无统计学意义(均P>0.05)。早期PCI组显著降低住院时间[(7.6±3.1)d比(10.7±3.8)d,t=2.489,P=0.014)]及减少医疗费用[(4.85±1.35)万元比(5.28±1.64)万元,t=2.132,P=0.038)]与延迟PCI组比较,差异均有统计学意义。结论早期介入干预不能降低高危NSTE-ACS患者PCI术后12个月MACE发生率,但能缩短住院时间,减少医疗费用。展开更多
The association between high-density lipoprotein cholesterol（HDL-C） and mortality in patients with acute aortic dissection（AAD） is unclear. From January 2007 to January 2014, a total of 928 consecutive AAD patient...The association between high-density lipoprotein cholesterol（HDL-C） and mortality in patients with acute aortic dissection（AAD） is unclear. From January 2007 to January 2014, a total of 928 consecutive AAD patients who were admitted within 48 h after the onset of symptoms were enrolled in the study. Patients were divided into two groups according to whether serum HDL-C level was below the normal lower limit or not. The Cox proportional hazard regression model was used to identify the predictive value of HDL-C for in-hospital mortality in patients with AAD. As compared with normal HDL-C group（n=585）, low HDL-C group（n=343） had lower levels of systolic blood pressure and hemoglobin and higher levels of leukocyte, alanine aminotransferase, blood glucose, blood urea nitrogen, creatinine and urea acid. Low HDL-C group had significantly higher in-hospital mortality than normal HDL-C group（21.6% vs. 12.6%, log-rank=10.869, P=0.001）. After adjustment for baseline variables including demographics and biologic data, the increased risk of in-hospital mortality in low HDL-C group was substantially attenuated and showed no significant difference（adjusted hazard ratio, 1.23; 95% confidence interval, 0.86–1.77; P=0.259）. Low HDL-C is strongly but not independently associated with in-hospital mortality in patients with AAD.展开更多
目的观察并评价马方综合征(Marfan syndrome,MFS)并发A型主动脉夹层(type A aortic dissection,AAD)的手术疗效。方法回顾性分析2006年1月至2012年1月武汉亚洲心脏病医院收治44例MFS并发AAD患者的临床资料,其中男31例,女13例;年龄12～54...目的观察并评价马方综合征(Marfan syndrome,MFS)并发A型主动脉夹层(type A aortic dissection,AAD)的手术疗效。方法回顾性分析2006年1月至2012年1月武汉亚洲心脏病医院收治44例MFS并发AAD患者的临床资料,其中男31例,女13例;年龄12～54(33.0±9.8)岁。23例在AAD发病后不同疾病阶段施行外科手术治疗,均行Bentall手术;21例因经济或其它原因未采取手术治疗。采用含时变协变量的COX回归分析,分别以主要终点事件、主要+次要终点事件作为结局变量对相关因素进行分析,观察手术患者术后手术疗效和生活质量,并与未手术患者的随访资料进行对比。结果术后有1例手术患者死于多器官功能衰竭,其余22例手术均成功。随访43例,随访时间1～75个月。22例手术患者术后3年生存率为95.7%,随访期间生活质量良好。未行手术治疗的21例患者生存状况及生活质量较差,13例(61.9%)死亡,主要死亡原因:急性心脏压塞、主动脉夹层破裂、急性心肌梗死并发心源性休克等;发病后3年生存率仅为31.7%。采用含时变协变量COX回归模型分析校正手术时间不一产生影响后的结果显示,手术治疗患者与未手术治疗患者相比较,其临床疗效的差异有统计学意义(T_COV_的OR值=0.088,P=0.028),手术治疗死亡风险仅为非手术治疗的8.8%(P<0.05)。结论 MFS并发AAD预后凶险,应尽早外科手术,不论是急性期还是慢性期均可获益,疗效可靠,随访结果令人满意。展开更多
基金supported by National Nature Science Foundation of China(No.81170259)
文摘The aim of the present study is to investigate how cytochrome P450 enzymes（CYP） 2C8-derived epoxyeicosatrienoic acids（EETs） regulate the nuclear factor erythroid 2-related factor 2（Nrf2） signaling pathway and protect against oxidative stress-induced endothelial injuries in the development and progression of atherosclerosis. In this study,cultured human umbilical vein endothelial cells（HUVECs） were transfected with CYP2C8 or pretreated with exogenous EETs（1 μmol/L） before TNF-α（20 ng/m L） stimulation. Apoptosis and intracellular ROS production were determined by flow cytometry. The expression levels of ROS-associated NAD（P）H subunits gp91 and p47,the anti-oxidative enzyme catalase（CAT）,Nrf2,heme oxygenase-1（HO-1） and endothelial nitric oxide synthase（e NOS） were detected by Western blotting. The results showed that CYP2C8-derived EETs decreased apoptosis of HUVECs treated with TNF-α. Pretreatment with 11,12-EET also significantly blocked TNF-α-induced ROS production. In addition,11,12-EET decreased oxidative stress-induced apoptosis. Furthermore,the ability of 11,12-EET to protect cells against TNF-α-induced apoptosis via oxidative stress was abrogated by transient transfection with Nrf2-specific small interfering RNA（si RNA）. In conclusion,CYP2C8-derived EETs prevented TNF-α-induced HUVECs apoptosis via inhibition of oxidative stress associated with the Nrf2 signaling.
文摘目的比较早期经皮冠状动脉介入(PCI)与延迟PCI策略对高危非ST段抬高型急性冠状动脉综合征(NSTE-ACS)12个月临床终点的影响。方法连续收集自2015年1月1日至2015年12月31日在武汉亚洲心脏病医院行PCI治疗的高危NSTE-ACS患者758例,并依据介入治疗时间窗分为早期PCI组(确诊后24 h内PCI,185例)和延迟PCI组(确诊后超过24 h PCI,573例),主要终点是术后12个月主要不良心血管事件(MACE),包括全因死亡与再发非致死性心肌梗死。回顾性对比分析两组基线临床资料、冠状动脉影像特征、PCI相关数据以及主要终点。结果 711例(93.8%)患者完成12个月随访。早期PCI组主要终点MACE发生率与延迟PCI组比较差异无统计学意义(14.5%比11.2%,χ~2=1.289,P=0.256),全因死亡与再发非致死性心肌梗死两组比较,差异均无统计学意义(均P>0.05)。早期PCI组显著降低住院时间[(7.6±3.1)d比(10.7±3.8)d,t=2.489,P=0.014)]及减少医疗费用[(4.85±1.35)万元比(5.28±1.64)万元,t=2.132,P=0.038)]与延迟PCI组比较,差异均有统计学意义。结论早期介入干预不能降低高危NSTE-ACS患者PCI术后12个月MACE发生率,但能缩短住院时间,减少医疗费用。
基金supported by National Natural Science Foundation of China(No.81170259)
文摘The association between high-density lipoprotein cholesterol（HDL-C） and mortality in patients with acute aortic dissection（AAD） is unclear. From January 2007 to January 2014, a total of 928 consecutive AAD patients who were admitted within 48 h after the onset of symptoms were enrolled in the study. Patients were divided into two groups according to whether serum HDL-C level was below the normal lower limit or not. The Cox proportional hazard regression model was used to identify the predictive value of HDL-C for in-hospital mortality in patients with AAD. As compared with normal HDL-C group（n=585）, low HDL-C group（n=343） had lower levels of systolic blood pressure and hemoglobin and higher levels of leukocyte, alanine aminotransferase, blood glucose, blood urea nitrogen, creatinine and urea acid. Low HDL-C group had significantly higher in-hospital mortality than normal HDL-C group（21.6% vs. 12.6%, log-rank=10.869, P=0.001）. After adjustment for baseline variables including demographics and biologic data, the increased risk of in-hospital mortality in low HDL-C group was substantially attenuated and showed no significant difference（adjusted hazard ratio, 1.23; 95% confidence interval, 0.86–1.77; P=0.259）. Low HDL-C is strongly but not independently associated with in-hospital mortality in patients with AAD.
