BackgroundFamilial hypercholesterolemia (FH) is a genetically inherited disorder caused by monogenic mutations or polygenic deleterious variants. Patients with FH innate with significantly elevated risks for coronary heart disease (CHD). FH prevalence based on genetic testing in Chinese CHD patients is missing. Whether classical index of coronary atherosclerosis severity can be used as indicators of FH needs to be explored. To investigate the FH prevalence in Chinese CHD patients and the association of SYNTAX I score with FH genotype.MethodsThe monogenic and polygenic FH related genes were genotyped in 400 consecutively enrolled CHD patients. The clinical characteristics and SYNTAX I scores were analyzed in a retrospective nested case-control study.ResultsThe prevalence of genetically confirmed FH in our CHD cohort was 8.75%. The cLDL-C level, SYNTAX I scores and incidences of triple vessel lesions in FH patients were significantly higher, while cLDL-C and SYNTAX I scores were independent risk factors for FH. Furthermore, cLDL-C levels of polygenic FH were significantly lower than monogenic FH, while their severity of coronary atherosclerosis was comparable.ConclusionsOur study revealed that the SYNTAX I score was an independent risk factor for FH. Besides, polygenic origin of FH should be taken into consideration for CHD patients suspected of FH.

Although previous observational studies have shown an association between venous thromboembolism (VTE) and atrial fibrillation (AF), the underlying causal relationship between them remains uncertain. This two-sample bidirectional Mendelian randomization (MR) analysis was performed to investigate the causal relationship between VTE and AF. The VTE dataset were obtained from FinnGen, including 9,176 cases and 209,616 controls. Meanwhile a genome-wide association study (GWAS) of 60,620 individuals with AF and 970,216 control subjects identified genetic variations associated with AF. The principal MR analytic approach used in this study is the inverse-variance weighting (IVW) method. Furthermore, we performed complementary MR analyses, including the MR-Egger, Weighted median (WM), and Weighted Mode. MR pleiotropy residual sum was applied to identify pleiotropy. The MR analysis showed suggestive causal associations between VTE and the risk of AF (p = 0.0245, OR [95

Background Familial hypercholesterolemia (FH) is a genetically inherited disorder caused by monogenic mutations or polygenic deleterious variants. Patients with FH innate with significantly elevated risks for coronary heart disease (CHD). FH prevalence based on genetic testing in Chinese CHD patients is missing. Whether classical index of coronary atherosclerosis severity can be used as indicators of FH needs to be explored. To investigate the FH prevalence in Chinese CHD patients and the association of SYNTAX I score with FH genotype. Methods The monogenic and polygenic FH related genes were genotyped in 400 consecutively enrolled CHD patients. The clinical characteristics and SYNTAX I scores were analyzed in a retrospective nested case-control study. Results The prevalence of genetically confirmed FH in our CHD cohort was 8.75%. The cLDL-C level, SYNTAX I scores and incidences of triple vessel lesions in FH patients were significantly higher, while cLDL-C and SYNTAX I scores were independent risk factors for FH. Furthermore, cLDL-C levels of polygenic FH were significantly lower than monogenic FH, while their severity of coronary atherosclerosis was comparable. Conclusions Our study revealed a genetically confirmed FH prevalence of 8.75% in a Chinese CHD cohort. Additionally, the SYNTAX I score was an independent risk factor for FH. Besides, polygenic origin of FH should be taken into consideration for CHD patients suspected of FH.

Background:The efficacy of chronic heart failure (CHF) checklist management in reducing adverse outcomes of heart failure patients is still uncertain. This study explores whether CHF checklist management is more useful than usual care in reducing adverse health outcomes in the medium- and long-term among CHF patients.Methods:In our prospective study, 132 patients with CHF were randomly assigned to CHF management group and usual care group by random number method. Patients in CHF management group were conducted through CHF checklist by cardiologists and general practitioner. Patients assigned to usual care were treated by non-stationary medical group without checklist. All groups were followed up for 18 months.Results:There was no significant difference in overall mortality rate between management group and control group during 18 months (12.3% [8/65] vs. 11.7% [7/60], P = 0. 912]). The re-hospitalization rate of heart failure in management group (18.5% [12/65]) was significantly lower than that in usual care group (38.3% [23/60]) after 18 months of follow-up (P = 0.013). Median NT-proBNP level (632.3 ng/l vs. 1678 ng/l, p = 0.004) was lower in management group than that in usual care group. Cardiac ultrasonography was performed at 18 months between the management and usual care group. LVEDD (55.88±7.11 mm vs. 60.92±8.06 mm) and LVESD (43.25±8.42mm vs. 48.41± 9.02mm) were decreased (P<0.01). LVEF was increased (45.36±10.64% vs. 39.96 ±10.15%, P<0.01). The utilization rate of ACEI/ARB/ARNI, β-blocker were high in management group.Conclusion:CHF checklist management by cardiologists and general practitioners can significantly reduce the re-hospitalization and improve cardiac function. CHF management through heart failure checklist may improve prognosis in patients with CHF in the medium- and long-term.

目的 使用超声心动图评估沙库巴曲缬沙坦钠(angiotensin receptor-neprilysin inhibitor,ARNI)对心力衰竭患者左心室逆重构和舒张功能逆转的影响,并探讨沙库巴曲缬沙坦钠对舒张功能不全分级及早期心功能逆转的影响.方法 收集2019年1-12月于首都医科大学附属北京朝阳医院就诊的心力衰竭患者176例,服用沙库巴曲缬沙坦钠者归为ARNI治疗组79例、服用血管紧张素转化酶抑制剂或血管紧张素Ⅱ受体阻滞剂的归为对照组97例.ARNI治疗组与对照组均采用心力衰竭的常规治疗,通过比较两组患者基线超声心动图和用药后3个月超声心动图的各种参数和纽约心脏协会(New York Heart Association,NYHA)心力衰竭分级,探讨沙库巴曲缬沙坦钠对舒张功能不全分级的影响在心力衰竭患者早期心功能逆转中的作用.结果 两组入组前的临床基本情况和基线超声心动图结果均衡可比(P＞0.05).心脏超声左心室重构指标及左心室射血分数(left ventricular ejection fraction,LVEF)改善:用药后3个月,治疗组LVEF较对照组有所升高,但差异无显著性[(42.4±11.8)%比(39.2±9.7)%,t=2.803,P=0.08].但治疗组治疗前后LVEF的变化差值、左心室舒张末内径变化差值及左心室收缩末内径变化差值均较对照组差异有显著性(P＜0.05).心脏超声舒张功能指标及舒张功能障碍分级比较:用药后3个月,治疗组二尖瓣E峰和A峰比值、舒张早期二尖瓣血流速度与舒张早期二尖瓣环运动速度的比值较对照组有所降低(P＜0.05).治疗组舒张功能不全等级较对照组有所下降(χ2=7.518,P=0.023).治疗组较对照组舒张功能分级逆转率明显升高(40.5%比25%,χ2=4.557,P=0.033).治疗3个月后,治疗组较对照组NYHA分级逆转率明显升高(73.6%比43.5%,χ2=13.21,P=0.01).其中治疗组中,舒张功能分级逆转组和非逆转组NYHA改善的比较,分别为46.6%和 34.1%(χ2=2.498,P=0.041),差异有显著性.结论 通过心脏超声评价沙库巴曲缬沙坦钠对心力衰竭患者舒张功能不全分级的逆转,与治疗早期心功能NYHA分级的逆转相关,提示尽早启动ARNI治疗干预舒张功能不全,可能对患者临床结局获益更早.

A microtiter plate assay is described for detecting cells bearing Fc receptors for IgE (Fcϵ receptors) and for assaying IgE-binding molecules. Cells are bound specifically to IgE-coated wells of microtiter plates, and the bound cells are enumerated in a quantitative colorimetric assay. IgE-binding molecules and monoclonal antibodies are assayed as inhibitors of the IgE-dependent cell binding. Major advantages of the plate assay compared to rosetting assays are its ability to accomodate many test samples for replicates and titrattions and the ease with which results are read out. The versatility of the assay is discussed with respect to detecting other immunoglobulin Fc receptor-bearing cells.

BACKGROUND There is scarce data on the long-term mortality and associated prognostic factors in patients with dilated cardiomyopathy (DCM). The study aimed to investigate the all-cause mortality up to 15 years (mean 7.9 ± 5.7 years) in such patients, and the independent prognostic factors influencing their long-term mortality. METHODS One hundred and sixty-six consecutive patients with DCM were prospectively enrolled from 2002 to 2003. The mean age of patients was 59.5 ± 10.4 years, and approximately 57% were male. They were followed up by telephone or outpatient visit at least every three months until 2019 or all-cause death occurred. Predictors of mortality were identified using multivariate logistic regression analysis. RESULTSDuring the 15 years of follow-up, five patients were lost to follow-up, and the complete data records of 161 patients were included in the analysis. Patients were treated with angiotensin-converting-enzyme inhibitors (ACEI) or angiotensin-receptor blocker (ARB), β-blockers, mineralocorticoid receptor antagonist (MRA), diuretics and digitalis from 2002 to 2004, and maintained at the maximum tolerated doses between 2004 and 2019. Our safety targets to maintain heart rate and blood pressure at 60-80 beats/min and 90-120/60-80 mmHg, respectively. All-cause mortality in the first five years was 55.9%. The independent risk factors for the 5-year mortality were age ≥ 70 years old (OR = 5.45, P = 0.006), systolic blood pressure (SBP) > 120 mmHg (OR = 3.63, P = 0.004), 6-minute walk distance (6MWD) < 450 m (OR = 3.84, P = 0.001). 15-year all-cause mortality was 65.8%. The independent risk factors for 15-year mortality were age ≥ 70 years old (OR = 16.07, P = 0.009), LVEF ≤ 35% (OR = 5.69, P = 0.003), and SBP > 120 mmHg (OR = 9.56, P < 0.001). CONCLUSIONSThis study was the first to demonstrate the 15-year survival rate of 34% in DCM patients. The DCM patients’ first five-year all-cause mortality decreased significantly after continuous standardized treatment and intensive management. The mortality then plateaued in the following 10 years. Age ≥ 70 years, LVEF ≤ 35%, and SBP > 120 mmHg were independent predictors of 15-year all-cause mortality.

Resumo Fundamento: A fração de ejeção (FE) tem sido utilizada em análises fenotípicas e na tomada de decisões sobre o tratamento de insuficiência cardíaca (IC). Assim, a FE tornou-se parte fundamental da prática clínica diária. Objetivo: Este estudo tem como objetivo investigar características, preditores e desfechos associados a alterações da FE em pacientes com diferentes tipos de IC grave. Métodos: Foram incluídos neste estudo 626 pacientes com IC grave e classe III–IV da New York Heart Association (NYHA). Os pacientes foram classificados em três grupos de acordo com as alterações da FE, ou seja, FE aumentada (FE-A), definida como aumento da FE ≥10%, FE diminuída (FE-D), definida como diminuição da FE ≥10%, e FE estável (FE-E), definida como alteração da FE <10%. Valores p inferiores a 0,05 foram considerados significativos. Resultados: Dos 377 pacientes com IC grave, 23,3% apresentaram FE-A, 59,5% apresentaram FE-E e 17,2% apresentaram FE-D. Os resultados mostraram ainda 68,2% de insuficiência cardíaca com fração de ejeção reduzida (ICFEr) no grupo FE-A e 64,6% de insuficiência cardíaca com fração de ejeção preservada (ICFEp) no grupo FE-D. Os preditores de FE-A identificados foram faixa etária mais jovem, ausência de diabetes e fração de ejeção do ventrículo esquerdo (FEVE) menor. Já os preditores de FE-D encontrados foram ausência de fibrilação atrial, baixos níveis de ácido úrico e maior FEVE. Em um seguimento mediano de 40 meses, 44,8% dos pacientes foram vítimas de morte por todas as causas. Conclusão: Na IC grave, a ICFEr apresentou maior percentual no grupo FE-A e a ICFEp foi mais comum no grupo FE-D.

BACKGROUND:Ejection fraction (EF) has been used in phenotype analyses and to make treatment decisions regarding heart failure (HF). Thus, EF has become a fundamental part of daily clinical practice. OBJECTIVE:This study aims to investigate the characteristics, predictors, and outcomes associated with EF changes in patients with different types of severe HF. METHODS:A total of 626 severe HF patients with New York Heart Association (NYHA) class III-IV were enrolled in this study. The patients were classified into three groups according to EF changes, namely, increased EF (EF-I), defined as an EF increase ≥10%, decreased EF (EF-D), defined as an EF decrease ≥10%, and stable EF (EF-S), defined as an EF change <10%. A p-value lower than 0.05 was considered significant. RESULTS:Out of 377 severe HF patients, 23.3% presented EF-I, 59.5% presented EF-S, and 17.2% presented EF-D. The results further showed 68.2% of heart failure with reduced ejection fraction (HFrEF) in the EF-I group and 64.6% of heart failure with preserved ejection fraction (HFpEF) in the EF-D group. The predictors of EF-I included younger age, absence of diabetes, and lower left ventricular ejection fraction (LVEF). The predictors of EF-D were absence of atrial fibrillation, lower uric acid level, and higher LVEF. Within a median follow-up of 40 months, 44.8% of patients suffered from all-cause death. CONCLUSION:In severe HF, HFrEF presented the highest percentage in the EF-I group, and HFpEF was most common in the EF-D group.

目的:分析不同性别重症心力衰竭(心衰)患者的临床特点及预后影响因素.方法:入选我院2011年1月至2016年12月因心衰住院的NYHA心功能分级Ⅲ～Ⅳ级患者848例,记录患者的一般临床资料及用药情况,实验室指标和超声心动图参数.通过电话或门诊进行随访,记录发生全因死亡时间.比较不同性别重症心衰患者临床特点,Cox回归分析全因死亡影响因素.结果:(1)基线资料:中位随访时间41(1 d,93个月)个月,失访56例,纳入分析792例.其中女性290例,男性502例.NYHA心功能分级Ⅲ级400例,Ⅳ级392例;射血分数降低的心衰(HFrEF)361例(45.6％),射血分数中间值的心衰(HFmrEF)145例(18.3％),射血分数保留的心衰(HFpEF)286例(36.1％).(2)在重症心衰患者中,男性以HFrEF为主,NYHA心功能分级Ⅳ级多见;女性以HFpEF为主,NYHA心功能分级Ⅲ级多见,两者基础疾病以冠心病最多见.与男性患者相比,女性患者瓣膜病比例高,年龄大,多伴有糖尿病、心房颤动病史,左心室射血分数(LVEF)高,肌酐清除率(Ccr)低(P均<0.05).NYHA心功能分级Ⅳ级患者N末端B型利钠肽原(NT-proBNP)水平显著高于NYHA心功能分级Ⅲ级患者(P均<0.05).(3)不同类型重症心衰患者亚组比较显示,各类型心衰基础疾病均以冠心病为主,占55％左右.HFpEF女性患者多,年龄最大,心房颤动比例最高,NT-proBNP值最低;HFrEF男性患者为主,心房颤动比例最低,NT-proBNP最高.三种类型心衰全因死亡率相似.(4)患者全因死亡共345例(43.6％),其中男性215例(42.9％),女性130例(44.8％),预后相似.年龄、NYHA心功能分级Ⅳ级、冠心病病史、血红蛋白、血尿酸、血钠、NT-proBNP≥3300 ng/L、服用血管紧张素转换酶抑制剂(ACEI)/血管紧张素Ⅱ受体拮抗剂(ARB)类药物、男性是重症心衰患者全因死亡的独立影响因素.结论:重症心衰患者男性以HFrEF及NYHA心功能分级Ⅳ级为主,年龄低,而女性以高龄、HFpEF为主,NYHA心功能Ⅲ级多,两者预后相似.年龄、NYHA心功能分级Ⅳ级、冠心病病史、血红蛋白、血尿酸、血钠、NT-proBNP≥3300 ng/L、服用ACEI/ARB类药物、男性是重症心衰患者全因死亡的独立影响因素.

Objective: This study aimed to find echocardiographic parameters that can predict short- and long-term adverse cardiovascular events in patients with AMI. Methods: A total of 126 patients with AMI admitted to our hospital from July to December 2012 were enrolled in this study. All patients underwent echocardiographic examination within 12 hours after admission and received regular follow-ups until December 2018. The primary endpoint was a composite of the major adverse cardiovascular events (MACEs). Results: In the first year of this study, a primary endpoint occurred in 35 patients and the predictor derived from the echocardiography of 1-year primary endpoint was LVEF<40% (OR: 9.000, 95% CI 3.242-24.987, p<0.0001) and the area under the curve (AUC) for the predictor was 0.676 (95% CI 0.561-0.790, p=0.002). For the total 5 years, 57 patients underwent primary endpoint. The results of the 5-year primary endpoint were: E/E'>15 (OR: 4.094, 95% CI 1.726-9.710, P=0.001), the wall motion score index was (WMSI)>1.5 (OR: 12.791, 95% CI 1.511-108.312, P=0.019), and the AUC was 0.691 (95% CI 0.595-0.787 P<0.0001). Conclusion: LVEF is correlated with a short-term outcome (1-year), and WMSI and E/E' can predict a long-term outcome (5-year) in patients with acute myocardial infarction.

The authors have requested that this preprint be removed from Research Square.

BACKGROUND:Coronary plaque burden (CPB) is an important prognostic factor in patients with unstable angina pectoris (UAP). Our current study aims to investigate the relationships between peripheral reactive hyperemia index (RHI) with CPB and prognosis in patients with UAP complicated with type 2 diabetes mellitus (T2DM).METHODS:The clinical data of 187 UAP-T2DM patients who were treated in our center from June 2017 to January 2019 were retrospectively collected. RHI, CPB, and other clinical features were measured. The patients were followed up for 18 months and then divided into an adverse cardiovascular event (ACE) group (n=71, with ACEs) and a control group (n=116, without ACEs). The differences in RHI, CPB, and other clinical features between these two groups were compared, and the potential correlation between RHI and CPB was analyzed.RESULTS:Compared with the control group, the ACE group had significantly lower RHI (1.21±0.32 vs. 1.59±0.35, P=0.000) and left ventricular ejection fraction (LVEF) (42.92%±7.78% vs. 48.90%±6.76%, P=0.000) and a significantly higher left ventricular myocardial mass index (2.67±0.87 vs. 2.27±0.49 mg/g, P=0.000), carotid intima-media thickness (1.65±0.34 vs. 1.51±0.32 mm, P=0.000), number of coronary plaques (3.98±0.53 vs. 3.32±0.38, P=0.000), non-calcified plaque volume (32.89±12.56 vs. 22.58±9.97 mm3, P=0.000), calcified plaque volume (4.89±1.29 vs. 3.88±1.05 mm3, P=0.000), non-calcified plaque burden (5.70%±1.60% vs. 3.18%±1.08%, P=0.000), and calcified plaque burden (0.90%±0.22% vs. 0.65%±0.19%, P=0.000). Pearson linear correlation analysis showed that peripheral RHI was negatively correlated with plaque number, non-calcified plaque volume, calcified plaque volume, non-calcified plaque burden, and calcified plaque burden in patients with UAP complicated with T2DM (all P<0.05).CONCLUSIONS:Decreased peripheral RHI is associated with ACEs and CPB in patients with UAP complicated with T2DM.

目的 探讨老年重症射血分数保留心力衰竭(HFpEF)患者临床特点并对其预后因素进行分析.方法 入选2011-2016年北京朝阳医院住院的纽约心脏协会(NYHA)心功能分级Ⅲ～Ⅳ级重症HFpEF患者308例,记录患者一般资料、生化指标、超声心电图等参数.按年龄分为＜75岁组和≥75岁组.采用Kaplan-Meier生存曲线及Cox回归对患者预后及其影响因素进行分析.结果(1)共纳入分析286例,NYHA Ⅲ级171例,Ⅳ级115例,平均年龄71.3岁,死亡131例.≥75岁组142例,死亡80例,＜75岁组144例,死亡51例.(2)≥75岁组女性多见;伴随高血压、糖尿病、卒中等疾病多;糖化血红蛋白、老年营养风险指数(GNRI)＜92比例高于＜75岁组;白蛋白、血红蛋白、肌酐清除率、左室舒张末期内径(LVEDD)及地高辛和β受体阻滞剂使用率明显低于＜75岁组.≥75岁组死亡率明显高于＜75岁组,P＜0.001.(3)Cox多因素回归分析显示≥75岁组NT-proBNP、未服用血管紧张素转换酶抑制剂(ACEI)或血管紧张素受体拮抗剂(ARB)、左室肥厚是其预后的独立危险因素.结论 老年重症HFpEF患者一般状况差,伴随疾病多,死亡率高,预后差.NT-proBNP、未服用ACEI/ARB类药物、左室肥厚是其预后的独立危险因素.

The hallmark of atherogenesis is characterized as endothelial dysfunction and subsequent macrophage activation. Although our previous study has demonstrated that endothelin-1 (ET-1) plays an important role in atherogenesis, the underlying mechanism remains deeply investigation. Enhanced atherosclerotic plaques were observed in endothelium-specific ET-1 overexpression ApoE(-/-) mice (eET-1/ApoE(-/-)) concomitant with increased secretion of pro-inflammatory adhesion molecules and cytokines. The conditional media used for culturing human umbilical vein endothelial cells (HUVECs) with AdET-1 infection and subjected to OX-LDL stimulation, was collected and utilized for bone marrow-derived macrophages (BMDMs) culturing. RT-PCR analysis showed increased genes expression related to classical M1 macrophages but decreased alternative activated M2 macrophages genes expression in macrophage culturing with the conditional media. Furthermore, consistent regulations of macrophage polarization were observed using isolated exosomes from the conditional media. More importantly, we noticed that miR-33 was enriched in the exosomes derived by HUVECs with AdET-1 infection, while bioinformatics analysis further indicated that miR-33 directly targeted NR4A and miR-33/NR4A axis was required for the effect of endothelial-specific ET-1 overexpression on pro-inflammatory macrophage activation. By contrast, such effects could be reversed by ET-1 knockdown. Taken together, our study indicated that the exosomes derived by HUVECs with AdET-1 infection can transfer miR-33 to macrophages and subsequently promote pro-inflammatory macrophage activation by directly targeting to NR4A. These evidences clearly revealed that miR-33/NR4A axis was the important mechanism underlying the effect of ET-1 on macrophage activation and indicated that ET-1 may act as a promising target for atherosclerosis management.

背景 对于慢性心力衰竭患者给予积极治疗和良好的管理可避免心力衰竭加重.目前国内外没有统一、公众认可的心力衰竭管理模式.本课题拟应用心力衰竭清单方式对慢性心力衰竭患者进行统一的管理,旨在为我国探索社区管理模式提供参考.目的 应用心力衰竭清单对慢性心力衰竭患者进行社区管理,并评价此方法的效果,希望通过此研究探索一种简单易行的慢性心力衰竭社区管理模式并可进行推广.方法 选取2016-06-30至2017-06-30于首都医科大学附属北京朝阳医院心脏中心住院且明确诊断为慢性心力衰竭的患者200例.采用随机数字法将其分为管理组100例和对照组100例,管理组由全科团队采用心力衰竭清单对患者进行全方位管理,随访1次/月;对照组不应用心力衰竭清单,由全科团队进行常规门诊管理,随访1次/月,仅记录相关资料但不特别干预.查阅患者电子病例系统收集基线资料.随访6个月后,比较两组患者N末端脑钠肽前体(NT-proBNP)及心功能指标左心室射血分数(LVEF)、左心室舒张末期内径(LVEDD)、左心室收缩末期内径(LVESD)、慢性心力衰竭标准化药物使用率及心力衰竭再住院率和死亡率.结果 共176例患者完成随访,其中管理组89例,对照组87例.管理后,管理组NT-proBNP、心功能分级、LVEDD、LVESD均低于对照组,LVEF高于对照组(P<0.05).管理组管理后血管紧张素转化酶抑制剂(ACEI)/血管紧张素Ⅱ受体拮抗剂(ARB)使用率高于管理前,螺内酯使用率低于管理前(P<0.05).管理后两组β-受体阻滞剂、螺内酯使用率比较,差异无统计学意义(P>0.05);管理组ACEI/ARB使用率高于对照组(P<0.05).管理组心力衰竭再住院率〔11.2％(10/89)〕低于对照组〔29.9％(26/87)〕(χ2=9.404,P=0.002).两组死亡率比较,差异无统计学意义〔9.0％(8/89)与11.5％(10/87),χ2=0.301,P=0.583〕.结论 全科医生应用心力衰竭清单管理慢性心力衰竭患者能明显提高管理效果,提示心力衰竭清单是一种简单易行的慢性心力衰竭社区管理模式.

目的:探讨微小RNA-214-5p(miR-214-5p)靶向p21活化蛋白激酶4(PAK4)对缺血再灌注(I/R)大鼠的心肌损伤和免疫反应的作用.方法:将健康雄性SD大鼠随机分为假手术(sham)组、I/R组、Ad-Scramble组和Ad-miR-214组(n=9).在大鼠左心室前壁6个不同的位点注入腺病毒;4 d后,缝合左前部下行冠状动脉构建I/R模型.RT-qPCR检测miR-214的表达水平,HE染色观察心肌损伤,ELISA检测心肌损伤标志物(CK-MB、Mb和cTnI)和炎症因子(IL-6、IL-1β和TNF-α)的水平,流式细胞术检测心肌细胞凋亡率,试剂盒检测MDA含量和SOD活性,基因软件预测靶基因并通过双萤光素酶报告验证,Western blot检测caspase-3、caspase-9、Bcl-2、Bax、PAK4、p-Akt和p-mTOR表达水平.结果:miR-214在I/R大鼠心肌细胞中低表达(P<0.01);miR-214-5p过表达减轻I/R大鼠心肌损伤程度,下调CK-MB、Mb和cTnI表达,降低心肌细胞凋亡率,上调Bcl-2表达,下调Bax、caspase-3和caspase-9表达,提高SOD活性,降低MDA、IL-6、IL-1β和TNF-α的含量(P<0.01);miR-214-5p与PAK4在3'-UTR存在结合位点,miR-214-5p过表达上调PAK4、p-Akt和p-mTOR表达(P<0.01).结论:miR-214-5p过表达靶向PAK4减轻I/R大鼠的心肌损伤,并抑制心肌细胞凋亡、氧化应激反应和炎症反应,同时激活PI3K/Akt/mTOR通路.

A number of studies have suggested that autoantibodies against β1-adrenoreceptors (β1R-AAbs) have an important role in pathophysiological processes of heart failure. The aim of the present study was to determine whether β1R-AAbs are implicated in cardiac dysfunction following acute myocardial infarction (AMI) and their association with prognosis. A total of 33 cases with systolic heart failure (SHF), 49 with diastolic heart failure (DHF) and 44 with normal heart function following AMI were recruited. β1R-AAbs were detected by ELISA and major adverse cardiac events (MACEs) were recorded during the 5-year follow-up. The positive rate of β1R-AAbs in the SHF group (45.5%) was significantly higher compared with that in the DHF (22.4%; P<0.05) and normal (15.9%; P<0.05) groups. The area under the receiver operating characteristics curve for the diagnosis of SHF was 0.630 (95% CI: 0.514-0.747, P=0.026). During a median follow-up period of 51.0±15.4 months, the positive rate of β1R-AAbs in the MACEs group was significantly higher compared with that in the non-MACEs group (P<0.05). Multivariate logistic regression analysis indicated that the left ventricular ejection fraction and diabetes were independent predictors of 5-year MACEs following AMI, whereas β1R-AAbs were not. Kaplan-Meier analysis revealed that the cumulative MACEs-free survival rate was the lowest in the SHF group, followed by the DHF and normal groups (P<0.05). Therefore, β1R-AAbs were indicated to be of value for early diagnosis of SHF after AMI but not as independent predictors for the prognosis of patients with AMI.

BACKGROUND Atherosclerosis is a chronic inflammatory disease triggered by endothelial dysfunction and exaggerated by macrophage infiltration. Although endothelin-1 (ET-1) plays an important role in vascular inflammation and reactive oxygen species production, the individual effect of ET-1 in atherogenesis remains unclear. METHODS AND RESULTS ET-1 expression was increased in mouse atherosclerotic plaques and human umbilical vein endothelial cells (HUVECs) administrated by oxidized low-density lipoprotein stimulation. Moreover, the immunofluorescence co-staining showed upregulated ET-1 expression in endothelial cells. Real-time polymerase chain reaction demonstrated that ET-1 overexpression promoted adhesion molecules and chemokines secretion in HUVECs. Following this intervention, the migration of macrophages and the pro-inflammatory cytokines were increased. More importantly, the endothelial dysfunction regulated by ET-1 and subsequently the effect on macrophage activation were mediated by ETA receptor and largely reversed by protein kinase C (PKC) inhibitor. Eight-week-old male ApoE(-/-) mice and eET-1/ApoE(-/-) mice were fed with high-fat diet for 12 weeks. eET-1/ApoE(-/-) significantly increased atherosclerotic lesions in the whole aorta and aortic sinus, which accompanied by the induction of inflammatory cytokines and macrophages infiltration. CONCLUSIONS ET-1 accelerates atherogenesis by promoting adhesion molecules and chemokines, as well as subsequent macrophage activation. Collected, these evidence suggest that ET-1 might be a potential target for the treatment of atherogenesis.

目的:总结重症射血分数中间值心力衰竭(HFmrEF)患者死亡情况并对其影响因素进行分析.方法:于2011～2016年连续入选NYHA心功能分级Ⅲ～Ⅳ级重症HFmrEF患者113例,进行电话或门诊随访,并记录其发生全因死亡的原因及时间,并采用Cox回归对影响患者全因死亡的因素进行分析.结果:中位随访41个月期间,失访2例,死亡率46.8％(52/111).Cox多因素回归分析显示,冠心病(HR=2.74,P=0.005)、糖尿病(HR=1.84,P=0.041)、既往心力衰竭病史(HR=2.28,P=0.005)、N末端B型利钠肽原(NT-proBNP)>3400 pg/ml(HR=3.56,P<0.001)、未服用血管紧张素转换酶抑制剂(ACEI)/血管紧张素Ⅱ受体拮抗剂(ARB)类药物(HR=2.18,P=0.006)是影响患者全因死亡的因素;影响预后因素的ROC曲线AUC为0.876(95％CI:0.812～0.941,P<0.001),提示这些因素可以较好地预测患者全因死亡发生情况.结论:重症HFmrEF患者预后差,冠心病、糖尿病、既往心力衰竭病史、NT-proBNP>3400 pg/ml、未服用ACEI/ARB类药物是影响患者死亡的危险因素.