肾胺酶与心房颤动的相关性研究

目的:探讨肾胺酶在心房颤动(房颤)的发生及发展中的作用。方法:按照房颤与否将208例患者分为房颤组和对照组,每组各104例;按照房颤类型将房颤组分为持续性房颤组(n=68)与阵发性房颤组(n=36)。收集各组受试者的一般资料及静脉血,测定血浆肾胺酶、总儿茶酚胺浓度,比较两组肾胺酶及儿茶酚胺浓度的差异,分析其与房颤之间的相关性。结果:房颤组肾胺酶浓度低于对照组(P<0.05);阵发性房颤组与持续性房颤组肾胺酶浓度的差异无统计学意义(P>0.05)。房颤组与对照组之间及阵发性房颤组和持续性房颤组之间总儿茶酚胺浓度无统计学差异(P>0.05)。房颤组左房内径组大于对照组(P<0.05),持续性房颤组左房内径大于阵发性房颤组(P<0.05)。相关性分析显示,肾胺酶浓度与儿茶酚胺浓度负相关(r=-0.167,P<0.05)、与左房内径负相关(r=-0.212,P<0.05),但肾胺酶浓度与收缩压、舒张压、心率之间无相关性(P>0.05);总儿茶酚胺浓度与心率(r=0.176,P<0.05)、左房内径正相关(r=0.188,P<0.05),但总儿茶酚胺与收缩压、舒张压之间无相关性(P>0.05)。二元Logistic回归分析显示,肾胺酶是房颤发生的保护因素(OR<1,P<0.05)。结论:肾胺酶可能参与房颤的发生,并改善心脏重构。

成年小鼠心肌细胞腺病毒转染及缺氧/复氧诱导损伤模型的建立

目的 采用非Langendorff方法分离成年小鼠心肌细胞(adult mouse cardiomyocytes, AMCMs),并建立腺病毒转染及缺氧/复氧诱导细胞损伤模型,为应用AMCMs进行心肌缺血体外实验的研究提供便捷、实用、可操作性强的系统方法。方法 应用非Langendorff方法分离AMCMs,观察贴壁后2、24、48及72 h细胞的形态,计算存活率,并应用α-actinin免疫荧光染色观察AMCMs完整性;应用腺病毒转染AMCMs,观察并统计转染36、48 h后的转染效率;通过缺氧45 min/复氧24 h,进行碘化丙啶(propidium iodide, PI)染色,统计PI阳性细胞率以明确缺氧/复氧损伤模型的建立。结果 与AMCMs贴壁后2 h相比,贴壁后24和48 h的细胞存活率无显著下降,贴壁后72 h的细胞存活率显著下降;AMCMs细胞结构完整,可进行腺病毒转染,36和48 h转染效率分别可达82.07%±0.60%和82.84%±1.18%;缺氧/复氧诱导AMCMs可成功建立细胞损伤模型,PI染色阳性细胞达42.28%±3.10%。结论 本研究应用非Langendorff方法分离培养的AMCMs,细胞存活率高,并建立腺病毒转染和缺氧/复氧诱导细胞损伤模型,为体外建立AMCMs基因修饰、缺氧/复氧损伤模型提供了简单易行的系统方法。

血管内超声去肾交感神经术在高血压治疗中的研究进展

高血压是临床常见的慢性疾病之一,也是心脑血管疾病的重要危险因素之一。目前我国高血压诊疗存在患病率高、控制率低等特点,其核心疗法依然是药物治疗。但即使在充分药物治疗基础上,部分患者的血压仍难以长期且稳定地实现达标。血管内超声去肾交感神经术(RDN)是一种新型高血压器械治疗方法,其工作原理是在肾动脉四周通过超声能量对肾交感神经进行热消融,从而达到降压的目的。近年关于血管内超声RDN的临床试验不断增加,且均取得好的疗效。因此,深入研究血管内超声RDN在高血压治疗中的作用机制,可以为疾病的治疗提供新思路。

血清proBNP和Hcy在冠心病合并高血压中的研究进展

高血压是临床上极为常见的一种心血管疾病,且该类患者往往合并了冠心病,这直接导致了心血管事件的发生风险倍增。目前大量研究表明血清脑钠肽前体(proBNP)、同型半胱氨酸(Hcy)与冠心病合并高血压患者左心室几何构型和功能的异常密切相关。本文就血清proBNP和Hcy的概念、在冠心病和高血压诊断中的临床应用、与冠心病和高血压的关系、引起左心室几何构型及功能异常的机制、指导冠心病合并高血压的治疗进行综述,为预防左心室异常提供参考依据。

Rosmarinic acid improves tracheal smooth muscle responsiveness and lung pathological changes in ovalbumin-sensitized rats

Objective:To evaluate the effect of rosmarinic acid on tracheal smooth muscle responsiveness and lung pathological changes in ovalbumin-sensitized rats.Methods:Rats were randomly divided into six groups:the control group,the asthmatic group,and the asthmatic groups treated with dexamethasone(1 mg/kg;oral gavage)or three doses of rosmarinic acid(0.5,1,and 2 mg/kg;oral gavage).For induction of asthma,rats received intraperitoneal injections and inhalation of ovalbumin.After 21 days,bronchoalveolar lavage fluid and lung samples were collected for histopathological analyses.Moreover,total and differential white blood cell counts were determined.Results:The rosmarinic acid-treated group had significantly lower tracheal smooth muscle responses to methacholine than the asthmatic group.In addition,rosmarinic acid reduced white blood cell count and the percentages of eosinophils,monocytes,and neutrophils while increasing the percentage of lymphocytes.Ovalbumin-induced lung pathological changes were significantly improved by treatment with rosmarinic acid.Conclusions:Rosmarinic acid improves tracheal smooth muscle responsiveness and lung pathological changes in ovalbumin-sensitized rats.

From biomarker discovery to combined therapies:Advancing hepatocellular carcinoma treatment strategies

This editorial reviews advances in hepatocellular carcinoma(HCC)treatment,focusing on a triple therapy approach and biomarker discovery.Zhang et al discuss the synergistic potential of transarterial chemoembolization combined with tyrosine kinase inhibitors and PD-1 inhibitors.Meanwhile,Li et al identify protein tyrosine phosphatase non-receptor II(PTPN2)as a biomarker for poor prognosis and immune evasion in HCC.The studies highlight the importance of combined therapies and biomarkers in improving HCC treatment efficacy and patient outcomes,with PTPN2 emerging as a potential therapeutic target.This article supplements the aforementioned studies with more recent research advancements,focusing on the molecular mechanisms and clinical applications of biomarkers.

因地制宜——开拓中国特色心脏康复之路

面临国内外心血管疾病负担仍在持续增加的现状,亟需加强心血管疾病的预防和康复治疗。完全照搬西医的心脏康复模式及实施方案存在很多限制,也不符合我国国情特点。因此王承龙教授根据中国国情,继承陈可冀院士中西医结合学术思想,提出心血管患者心脏康复应围绕一个目标,坚持二项原则,制宜三张处方,规范四种行为,警戒五劳/六极/七伤,管理八点要素,因地制宜,因陋就简,安全有效,易于推广,符合国情,凸显中医药优势,开拓具有中国特色的“形神调和”心脏康复模式,助推我国心脏康复事业发展。

Effects of interventions on oxidative stress and inflammation of cardiovascular diseases

Excessive oxidative stress and low-grade chronic inflammation are major pathophysiological factors contributing to the development of cardiovascular diseases (CVD) such as hypertension, diabetes and atherosclerosis. Accumulating evidence suggests that a compromised antioxidant system can lead to excessive oxidative stress in cardiovascular related organs, resulting in cell damage and death. In addition, increased circulating levels of pro-inflammatory cytokines, such as tumor necrosis factor α, interleukin-6 and C-reactive protein, are closely related to morbidity and mortality of cardiovascular complications. Emerging evidence suggests that interventions including nutrition, pharmacology and exercise may activate expression of cellular anti-oxidant systems via the nuclear factor erythroid 2-related factor 2-Kelchlike ECH-associated protein 1 signaling pathway and play a role in preventing inflammatory processes in CVD. The focus of the present review is to summarize recent evidence showing the role of these anti-oxidant and anti-inflammatory interventions in cardiovascular disease. We believe that these findings may prompt new effective pathogenesis-oriented interventions, based on the exercise-induced protection from disease in the cardiovascular system, aimed at targeting oxidant stress and inflammation.

Inflammation, lipid metabolism and cardiovascular risk in rheumatoid arthritis: A qualitative relationship?

Life expectancy in patients with rheumatoid arthritis(RA)is reduced compared to the general population owing to an increase in cardiovascular diseases(CVD)not fully explained by traditional cardiovascular risk factors.In recent years,interest has been focused on the alterations in lipid metabolism in relation to chronic inflammation as one of the possible mechanisms involvedin the pathogenesis of atherosclerosis of RA patients.Research regarding this issue has revealed quantitative alterations in lipoproteins during the acute-phase reaction,and has also demonstrated structural alterations in these lipoproteins which affect their functional abilities.Although many alterations in lipid metabolism have been described in this regard,these structural changes associated with inflammation are particularly important in high-density lipoproteins as they affect their cardioprotective functions.In this respect,excessive oxidation in low-density lipoprotein(LDL)and increased lipoprotein(a)with a predominance of smaller apolipoprotein(a)isoforms has also been reported.This article will discuss proinflammatory high-density lipoproteins(pi HDL),oxidized LDL and lipoprotein(a).Elevated concentrations of these lipoproteins with marked pro-atherogenic properties have been observed in RA patients,which could help to explain the increased cardiovascular risk of these patients.

Exercise and cardiovascular protection:Update and future

Cardiovascular disease(CVD)is a major cause of mortality and morbidity worldwide.In China,it is estimated that 330 million people are CVD patients.With the rapid aging of populations around the world,the number of CVD patients and death due to CVD are continuously rising.1 Exercise and physical activity have been recognized as economical and effective ways to enhance cardiovascular health and reduce CVD.Pathways mediating the cardiovascular benefits of exercise are promising therapeutic targets for CVD.

Synergisms of cardiovascular effects between iptakalim and amlodipine, hydrochlorothiazide or propranolol in anesthetized rats

The primary object of this fundamental research was to survey the synergistic cardiovascular effects of iptakalim, a novel ATP–sensitive potassium channel(KATP) opener, and clinical first-line antihypertensive drugs, such as calcium antagonists, thiazide diuretics and β receptor blockers by a 2×2 factorial-design experiment. It would provide a theoretical basis for the development of new combined antihypertensive therapy program after iptakalim is applied to the clinic. Amlodipine besylate, hydrochlorothiazide and propranolol were chosen as clinical first-line antihypertensive drugs. Blood pressure, heart rate(HR) and cardiac functions were observed in anesthetized normal rats by an eightchannel physiological recorder. The results showed that iptakalim monotherapy in a low dose could produce significant antihypertensive effect. There was no interaction between iptakalim and amlodipine on the maximal changes of systolic blood pressure(SBP), diastolic blood pressure(DBP), mean arterial blood pressure(MABP), the left ventricular systolic pressure(LVSP), and the left ventricular end-diastolic pressure(LVEDP)(P>0.05). However, the effects of combination iptakalim/amlodipine on the maximal changes of SBP, DBP, MABP, LVSP and LVEDP were more obvious than those of iptakalim or amlodipine monotherapy. And there was strong positive interaction between iptakalim and amlodipine on the maximal changes of HR(P>0.05). According to the maximal changes of DBP, MABP, LVSP and LVEDP(P<0.05) of combination iptakalim with hydrochlorothiazide, there was strong positive interaction between them. But there was no interaction between iptakalim and hydrochlorothiazide on the maximal drop of SBP and HR(P>0.05). According to the maximal drops of DBP, MABP of combination iptakalim with propranolol, there was strong positive interaction between them(P<0.05). But there was no interaction between iptakalim and propranolol on the maximal changes of SBP, LVSP,LVEDP and HR(P>0.05). In conclusion, it was the first time to study the effects of amlodipine, hydrochlorothiazide or propranolol, which had different mechanisms of action from iptakalim, on cardiovascular effects of iptakalim in anesthetized normal rats. This study proved that the combination of iptakalim with hydrochlorothiazide or propranolol respectively had significant synergism on lowering blood pressure, while the combination of iptakalim/amlodipine had additive action on lowering blood pressure. Meanwhile the antihypertensive effect was explicit, stable and long-lasting. Iptakalim thus appears suitable for the clinical treatment of hypertensive people who need two or more kinds of antihypertensive agents.

高甘油三酯对人主动脉平滑肌细胞凋亡和炎症因子的影响

目的:探讨高甘油三酯(HTG)对人主动脉平滑肌细胞(HASMC)凋亡和炎症因子白细胞介素6(IL-6)和肿瘤坏死因子α(TNF-α)的影响。方法:不同浓度的甘油三酯(TG)干预HASMC 24 h,采用四甲基偶氮唑蓝(MTT)法检测细胞抑制率;流式细胞仪检测细胞凋亡;Western blot检测B细胞淋巴瘤/白血病-2(Bcl-2)、半胱氨酸天冬氨酸蛋白酶-3(Caspase-3)蛋白的表达水平;酶联免疫吸附试验(ELISA)检测IL-6和TNF-α的水平。结果:与对照组相比,TG 2.5 mmol/L和5 mmol/L组凋亡率增加(P<0.05),且TG 5 mmol/L组凋亡率高于2.5 mmol/L组(P<0.05),而TG 1 mmol/L组凋亡率差异无统计学意义(P>0.05);TG处理细胞后,2.5 mmol/L和5 mmol/L组中Bcl-2蛋白表达降低(P<0.05),Caspase-3蛋白表达均升高(P<0.05),2.5 mmol/L和5 mmol/L组中IL-6和TNF-α浓度均升高(P<0.05),呈浓度依赖性。结论:中高浓度TG可促进HASMC凋亡,促使炎症因子IL-6和TNF-α的产生增加。

The association of cardiovascular mortality with a first-degree family member history of different cardiovascular diseases

OBJECTIVE To investigate which history of cardiovascular disease[coronary heart disease(CHD),stroke,or peripheral arterial disease]in a first-degree family member predicts cardiovascular mortality.METHODS We studied a prospective cohort(the Lipid Research Clinics Prevalence Study)from ten primary care centers across North America.The primary outcome was cardiovascular mortality,assessed using Cox survival models.RESULTS There were 8,646 participants(mean age:47.4±12.1 years,46%women,52%of participants with hyperlipidemia)who were followed up for a mean duration of 19.4±4.9 years.There were 1,851 deaths(21%),including 852 cardiovascular deaths.A paternal,maternal or sibling history of premature CHD(before 60 years)was present in 26%of participants,of stroke in 27%of participants,and of peripheral arterial disease in 24%of participants.After adjusting for risk factors(age,sex,systolic blood pressure,diastolic blood pressure,body mass index,smoking,fasting glucose,low-density lipoprotein cholesterol and triglycerides),only a paternal history of premature or any CHD,a maternal history of diabetes mellitus or premature or any CHD,and a sibling history of premature CHD,hypertension,or hyperlipidemia were individually predictive of cardiovascular mortality.After adjusting for risk factors and the mentioned familial factors,only paternal and maternal histories of CHD,espe-cially before 60 years,remained predictive of cardiovascular mortality,with a somewhat higher association for a maternal history[adjusted hazard ratio(aHR)=1.99,95%CI:1.36−2.92,P<0.001 for maternal history of premature CHD;aHR=1.52,95%CI:1.10−2.10,P=0.011 for paternal history of premature CHD].Family history of stroke or peripheral arterial disease did not predict cardiovascular mortality.Parental history of premature CHD predicted cardiovascular mortality independently of baseline age(<60 years and≥60 years),hypertension,or hyperlipidemia and carried more important prognostic value in men rather than wo-men.CONCLUSIONS In this study,a parental history of CHD,especially before 60 years,best predicted cardiovascular mortality.This finding could help more accurately identify high-risk patients who would benefit from preventive strategies.

Heart‘omicsin’AGEing (HOMAGE):design,research objectives and characteristics of the common database

Heart failure is common in older people and its prevalence is increasing.The Heart ＇omics＇ in AGEing（HOMAGE） project aims to provide a biomarker approach that will improve the early diagnosis of heart failure.A large clinical database,based on（1） prospective population studies or（2） cross-sectional,prospective studies or randomized controlled trials（RCTs） of patients at risk for or with overt cardiovascular disease will be constructed to determine most promising ＇omics＇-based biomarkers to identify the risk of developing heart failure and/or comorbidities.Population studies,patient cohorts and RCTs are eligible for inclusion in the common database,if they received ethical approval to obtain and share data and have baseline information on cardiovascular risk factors.Currently,the HOMAGE database includes 43,065 subjects,from 20 studies in eight European countries,including healthy subjects from three population studies in France,Belgium and Italy（n = 7,124）,patients with heart failure（n = 4,312） from four cohorts in the UK,Spain and Switzerland and patients at high risk for cardiovascular disease（n = 31,629） in 13 cohorts.It is anticipated that more partners will join the consortium and enlarge the pooled data.This large merged database will be a useful resource with which to identify candidate biomarkers that play a role in the mechanism underlying the onset and progression of heart failure.

可穿戴设备支持心房颤动人群筛查与管理研究进展

心房颤动(简称房颤)是当代心血管领域亟须攻克的两大“堡垒”之一,而传统的房颤筛查存在“检测时未发病、发病时未检测”的局限,导致房颤管理存在检测率低、规范管理率低等不足。可穿戴设备为房颤早期发现和科学管理创造了技术条件,其在房颤筛查中的可行性、高灵敏度和特异度逐步得到验证。本文基于国内外相关文献,对可穿戴设备在房颤人群筛查与管理中的流行特征、应用现状、局限及前景等进行综述,以期为可穿戴设备用于房颤的筛查与管理提供理论依据。

CTRP9对冷刺激诱导的小鼠棕色脂肪组织脂质代谢的影响

目的 探究过表达C1q/肿瘤坏死因子相关蛋白9(CTRP9)对冷刺激诱导后小鼠棕色脂肪脂质代谢相关基因和蛋白的表达调控。方法 C57BL6J雄性小鼠分为对照组(Ad-GFP组)、实验组(Ad-CTRP9组),分别注射Ad-GFP、Ad-CTRP9腺病毒。两组小鼠经普通饮食饲喂7 d后再置于4℃环境中冷刺激10 h,利用Real-time PCR和Western blot技术检测棕色脂肪标志性基因和蛋白表达。结果 在冷刺激诱导下过表达CRTP9,棕色脂肪中碘化甲状腺原氨酸脱碘酶2(Dio2)的mRNA水平升高(P<0.01),棕色脂肪细胞标志基因(UCP-1、PGC-1α、PRDM16和ARβ3)、脂质合成与分解相关基因(PPARγ、HSL和ATGL)表达水平无显著性差异。Western blot结果显示,与Ad-GFP组相比,经冷刺激诱导后Ad-CTRP9组解偶联蛋白1(UCP-1)蛋白表达升高,而脂肪分解相关蛋白脂肪三酰甘油脂肪酶(ATGL)表达下降(P<0.05)。结论 在寒冷环境下,过表达CTRP9促进UCP-1蛋白在棕色脂肪组织中蓄积,上调甲状腺激素信号相关基因Dio2表达,并抑制三酰甘油水解以维持体温恒定。

Piezo1在运动调节免疫中的作用及分子机制研究进展

科学运动有益于身体健康。然而,在运动过程中,机体感受运动刺激的响应靶点和具体分子机制尚未完全阐明。运动传感器Piezo被证实能够响应多种机械力刺激,如触觉、痛觉、听觉,并在身体生理或病理调控中发挥关键作用。Piezo1通道在响应运动产生的机械刺激时被激活,其主要通过Ca^(2+)调节下游信号通路。总结Piezo1通道与运动调节免疫的相关研究发现,在运动促进肌肉骨骼免疫、增强机体抵抗力和调节慢性心血管疾病及其炎症免疫过程中均存在Piezo1的调控作用。重点归纳并评述了Piezo1在运动调控肌骨和慢性心血管疾病免疫反应过程中的调控机制,旨在为临床预防和治疗肌骨和心血管相关慢性疾病提供新的思路。

他汀联合曲美他嗪对冠状动脉粥样硬化性心脏病炎性因子水平调控及改善心室重构的Meta分析

目的:系统评价他汀联合曲美他嗪对冠状动脉粥样硬化性心脏病基于inflammasomes/免疫损伤应答学说的炎性因子水平调控及心室重构的改善。方法:计算机检索EMbase、The Cochrane Library、Web of Science、Medline、Pubmed、万方数据(WanFang Data)、中国知网(CNKI)、中国生物医学文献服务系统(CBM)、维普数据库(VIP)共9个数据库,检索时限均为建库至2021年6月7日。人工检索所有纳入研究的参考文献,根据Cochrane系统评价方法,筛选关于阿托伐他汀联合曲美他嗪及常规治疗(抗血小板、控制血压、利尿、扩张冠脉等)对比应用曲美他嗪或他汀类药物联合常规治疗冠状动脉粥样硬化性心脏病患者的中、英文随机对照试验(RCT),并进行纳入文献资料的提取和质量评价,运用RevMan5.4软件进行Meta分析。结局指标包括炎性因子指标:CRP(C反应蛋白)、IL-6(白介素6)、肿瘤坏死因子α(TNF-α),以及心室重构相关结局指标:左室舒张末期内径(LVEDD)、左室收缩末期内径(LVESD)。结果:最终纳入随机对照试验12项,共计1120例冠心病患者。Meta分析结果:(1)炎性因子方面:他汀联合曲美他嗪组较对照组(单纯应用他汀类药物或曲美他嗪)可显著降低冠心病患者血液CRP[n=770,SMD=-2.70,95%CI(-2.55,--1.40),P<-0.00001]、TNF-α[n=678,SMD=-2.25,95%CI(-3.39,-1.12),P<-0.0001]、IL-6[n=770,SMD=-2.10,95%CI(-3.10,-1.10),P<0.00001]三种炎性因子的表达程度。(2)心室重构方面:他汀联合曲美他嗪组和对照组(单纯应用他汀类药物或曲美他嗪)相比,更能明显降低治疗前冠心病患者的左室收缩末期内径[n=626,SMD=-1.55,95%CI(-2.10,-0.99),P<-0.00001]及左室舒张末期内径[n=626,SMD=-1.18,95%CI[-1.56,-0.80),P<-0.00001]。结论:他汀联合曲美他嗪和对照组相比更能明显降低炎性因子水平,并改善冠心病患者的心室重构。

早发冠心病发病机制相关基因多态性研究进展

早发冠心病是指发病年龄男性≤55岁、女性≤65岁,发生于青年的冠心病,多伴有家族史,遗传因素的影响更为重要。随着基因检测技术的进步,人们试图从基因多态性的角度揭示早发冠心病的发生,为其预防和治疗提供依据。目前对早发冠心病致病基因的寻找大多集中在内皮损伤、炎性反应、脂质代谢异常、血栓形成等主要发病机制,现基于国内外研究进展,拟从发病机制的角度论述多种类型的基因多态性与早发冠心病风险之间的关系。

Beyond cardiomyocytes:Cellular diversity in the heart's response to exercise

Cardiomyocytes comprise~70%to 85%of the total volume of the adult mammalian heart but only about 25%to 35%of its total number of cells.Advances in single cell and single nuclei RNA sequencing have greatly facilitated investigation into and increased appreciation of the potential functions of non-cardiomyocytes in the heart.While much of this work has focused on the relationship between non-cardiomyocytes,disease,and the heart's response to pathological stress,it will also be important to understand the roles that these cells play in the healthy heart,cardiac homeostasis,and the response to physiological stress such as exercise.The present review summarizes recent research highlighting dynamic changes in non-cardiomyocytes in response to the physiological stress of exercise.Of particular interest are changes in fibrotic pathways,the cardiac vasculature,and immune or inflammatory cells.In many instances,limited data are available about how specific lineages change in response to exercise or whether the changes observed are functionally important,underscoring the need for further research.