AbstractProprotein convertase subtilisin/kexin type 9 (PCSK9) increases plasma low‐density lipoprotein‐cholesterol (LDL‐C) by decreasing the expression of the LDL‐receptor on hepatic cells. Ongericimab (JS002) is a novel PCSK9 monoclonal antibody that exhibits a long‐acting LDL‐C lowering effect by exclusively inhibiting PCSK9 in pre‐clinical studies. Two randomized, double‐blind, placebo‐controlled trials were conducted to evaluate the safety, tolerability, efficacy, immunogenicity, pharmacokinetic, and pharmacodynamic profiles of ongericimab in healthy subjects and patients with hypercholesterolemia. Eighty‐four healthy subjects in the phase Ia study received a single dose of placebo or ongericimab (15–450 mg). Ninety patients with hypercholesterolemia in the phase Ib/II study received placebo or ongericimab 150 mg Q2W, 300 mg Q4W, or 450 mg Q4W for 12 weeks. Ongericimab exhibited non‐linear kinetics. The apparent clearance decreased as the dosage increased, with terminal elimination half‐life (t1/2) values of 4.5–6.5 days. Overall, ongericimab was well tolerated in both studies. A single dose of ongericimab reduced LDL‐C levels by 30%–73% in healthy subjects, and repeated doses of ongericimab reduced LDL‐C levels by 67%–80% in patients with hypercholesterolemia. At the end of the dosing interval in the phase Ib/II study, over 70% of patients' LDL‐C levels decreased by more than 50% from baseline. The results showed that ongericimab had a significant long‐acting LDL‐C lowering effect with good safety and potential for clinical application.

目的:评价高脂餐对中国健康受试者单次口服DDO-3055片药动学(PK)和药效学(PD)的影响.方法:采用随机、开放、两阶段双交叉试验设计.筛选合格的健康男性受试者14例,随机分成A,B两组,每组各7例受试者.试验分成2个阶段,第1阶段:A组受试者于d 1高脂餐后给药,B组受试者于d 1空腹给药.第2阶段:A组受试者于d 7空腹给药,B组受试者于d 7高脂餐后给药.两阶段均采用单次口服给药,给药剂量均为200 mg.受试者在每一阶段给药前60 min内和给药后0.5,1,1.5,2,2.5,3,4,6,8,12,24和48 h进行PK血样采集,在每一阶段给药前60 min内和给药后4,8,12,24和48 h进行PD血样采集.结果:入组的14例健康男性受试者均完成本研究.血浆中DDO-3055的峰浓度(Cmax),0-t时间的血药浓度-时间曲线下面积(AUC0-t),AUC0-∞的几何均值比(高脂餐/空腹)分别为77.9％,95.0％,95.0％,其比值的90％CI分别为67.6％ ～89.7％,85.9～105％,85.9％ ～105％.与空腹相比,高脂餐后血浆DDO-3055的Cmax降低22.1％,AUC0-t和AUC0-∞均降低5.0％.与空腹给药相比,高脂餐后血清平均内源性促红素(EPO)最大值与空腹给药相比略有增加,分别为15.015和14.739 mIU·mL-1;餐后平均EPO最大值较基线变化百分比与空腹给药相比有所增加,分别为92.976％和72.796％.本研究未发生不良事件、严重不良事件.结论:高脂餐饮食对健康男性受试者单次口服DDO-3055片的AUC0-t和AUC0-∞无影响,Cmax降低,说明食物对DDO-3055片的吸收速度有一定影响,但影响较弱.

目的 评价中国健康志愿者单次静脉注射低、中、高3个负荷剂量的盐酸尼非卡兰的安全性及QT间期等药效学指标的变化.方法 用随机双盲、安慰剂对照、剂量爬坡临床试验.低、中、高(0.15,0.30和0.50 mg·kg-1)3个剂量试验组,每组纳入14例受试者,每组中各有12名受试者给予试验药物,各组另外2名受试者给予安慰剂.根据体重计算给药量,药物溶于0.9％NaCl,配制为含2 mg·mL-1盐酸尼非卡兰的液体,注射泵5 min匀速注射给药.评价4组受试者给药前后QT间期、PR间期、QRS间期、RR间期、QTc间期指标的变化.结果 低、中、高剂量试验组和安慰剂组受试者用药后血压无明显变化,低剂量试验组心率较基线无明显变化,中、高剂量试验组心率较基线略有下降,部分时间点心率的平均值低于60次/分,均在给药后24 h回复至基线水平.低、中、高剂量试验组受试者均于给药结束即刻出现QT间期延长,静注结束后3 min达到峰值,分别为(450.33±22.25),(476.33±59.30)和(524.31±55.80)ms,QTc间期的变化趋势同QT间期.安慰剂组的QT间期、QTc间期均无明显变化.低、中、高剂量试验组及安慰剂组各时间点PR间期、QRS间期无明显变化.低、中、高剂量试验组受试者RR间期在负荷给药结束即刻至静注结束3 min出现延长,在静脉注射结束3 min至4 h稳定;RR间期在静脉结束后4～6 h较基线明显下降,6～10 h逐渐恢复至基线,10～12 h较基线下降.安慰剂组RR间期的变化趋势同试验组.低、中、高剂量试验组和安慰剂组受试者用药后均无不适主诉.本研究无严重不良事件.结论 在0.15～0.50 mg·kg-1剂量内,受试者单次静脉给予负荷剂量盐酸尼非卡兰的安全性好,盐酸尼非卡兰抗心律失常的药效学指标QT间期延长具有剂量依赖性.

Objective To analyze the application of calcium channel blockers in patients of coronary heart disease in Peking Fuwai Hos-pital, to provide evidence for clinical rational use. Methods By extracting 146 coronary heart disease patients treated in Peking Fuwai Hospital, the situation of drug use were recorded and investigated. Results The utilization ratio of calcium channel blockers in coronary heart disease in hospital is 42. 47%, which is lower than other secondary prevention drugs in the same row. The influencing factors in-clude complication of cardiac failure or old myocardial infarction. Diltiazem and amlodipine have higher usage rate. Conclusion The ap-plication of calcium channel blockers in Peking Fuwai Hospital is basically rational, but the indications of calcium channel blockers are not explicit and the adverse effects are excessively scrupled in some patients, which need strengthening the training for clinicians to reasonable use of calcium channel blockers.

Berberine is an isoquinoline alkaloid isolated fromCoptis chinensis, and it is applied widely in clinic as a traditional anti-inflammatory and antibacterial drug for a long time. In recent years, it has been discovered that berberine still has lipid-regulating effects. Berberine plays the role of lipid-regulating by adjusting the structure of intestinal flora, influencing the synthesis and metabolism of bile acid, up-regulating the expression of low density lipoprotein receptor (LDLR), activating the expression of visceral adipose tissue related genes, elevating the expression of adiponectin, activating AMP-activated protein kinase (AMPK) pathways, and improving insulin resistance. This paper mainly summarizes the lipid-regulating function of berberine and its mechanisms of action.

Background: Left ventricular thrombus (LVT) is reported to be a common complication in acute myocardial infarction (AMI) patients. And it has the potential to cause systemic embolism. This retrospective study was to present the current situation of LVT in clinical practice, as well as to evaluate the clinical characteristics and the risk factors of LVT after AMI. Methods: LVT cases (n = 96) were identified from 13,732 AMI (non-ST elevation myocardial infarction was excluded) patients in Fuwai Hospital's electronic medical records system from January 2003 to January 2013. The controls (n = 192) were gender- and age-matched AMI patients without LVT during this period. A conditional logistic regression (fitted by the Cox model) was performed to identify the independent risk factors. Results: The incidence of LVT after AMI was 0.7%. Univariate analysis indicated that the anterior myocardial infarction (especially extensive anterior myocardial infarction), lower left ventricular ejection fraction (LVEF), LVEF ⩽40%, severe regional wall motion abnormalities (RWMA), pericardial effusion, and left ventricular aneurysm were all related to LVT after AMI. The independent risk factors obtained from the conditional logistic regression analysis were lower LVEF (odds ratio (OR) = 0.891, 95% confidence interval (CI): 0.828–0.960), extensive anterior myocardial infarction (OR = 6.403, 95% CI: 1.769–23.169), severe RWMA (OR = 7.348, 95% CI: 1.323–40.819), and left ventricular aneurysm (OR = 6.955, 95% CI: 1.673–28.921). Conclusions: This study indicated that lower LVEF, extensive anterior myocardial infarction, severe RWMA, and left ventricular aneurysm were independent risk factors of LVT after AMI. It also suggested that further efforts are needed for the LVT diagnosis after AMI in clinical practice.

目的 原发性高血压是常见的心血管疾病之一,但其发病机制尚未完全阐明.高血压是心脑血管疾病的独立危险因素,对高血压的有效管理可以降低心、脑血管事件的发生率.尽管目前可供选择的降压药物有多种,仍有部分难治性高血压患者当使用≥3种不同机制的足量降压药物,且其中至少有一种为利尿剂,血压控制仍不达标.研究表明焦虑、抑郁可能是此类患者血压难以控制的关键因素.在降压治疗基础上联合抗焦虑、抗抑郁治疗,可达到事半功倍的效果[1].近年来,焦虑、抑郁与高血压的关系已引起广泛关注,高血压可诱发焦虑、抑郁,而焦虑抑郁也会促发并加重高血压,使原有的降压药物疗效欠佳,形成难治性高血压.本文主要对高血压伴焦虑和抑郁的研究进展做一综述,为临床诊治提供参考.

自2011-08至2014-08，阜外心血管病医院牵头开展完成了对在常规治疗基础上联合托伐普坦片治疗非低容量性、非急性低钠血症的有效性、安全性的随机、双盲、安慰剂对照、多中心临床研究。全国共有40家医疗研究单位参与，共入组心衰、肝硬化和抗利尿激素分泌异常综合征（SIADH）患者242例，其中慢性心衰（CHF）79例。所有患者保持原来的基本常规治疗（试验期间无口服或静脉含钠处方），试验期间给予7天药物治疗（起始剂量15 mg/d，根据情况逐渐增至60 mg/d）及2次药后随访，主要评价低钠血症患者血钠浓度、尿量及需要限液情况、及水肿相关症状和体征的改变，并进行安全性评价。试验数据的初步分析结果显示，托伐普坦组及安慰剂组组间前4天日均血钠浓度较基线分别升高为（5.52±3.63）mmol/L和（0.51±2.38）mmol/L（P<0.0001）；前7天的日均血钠浓度较基线升高分别为（6.40±3.79） mmol/L和（1.22±2.27）mmol/L（P<0.0001）。组间在第4天及第7天血钠升高至正常的患者比例分别为76.92% vs 28.08%（P<0.0001），80.56% vs 31.87%（P<0.0001）；达到正常值时间分别为（2.15±1.31）天 vs（3.27±2.16）天（P=0.0011）；托伐普坦组24小时尿量在用药7天内均有明显增加，且日增加量均高于安慰剂组（P<0.0001）。试验表明，托伐普坦15~60 mg 的剂量是安全可以耐受的，试验过程中常见的不良事件，有口干、口渴、尿频、血钠升高、头晕等。共有9例次严重不良事件，其中托伐普坦组为3例；安慰剂组为6例，组间无明显差异。试验期间（2013年）由于国外一项大规模临床试验表明，常染色体显性遗传型多囊肾病（ADPKD）患者大剂量（60 mg，bid），且30天的长期应用托伐普坦易引发药物相关的肝损害，因此美国FDA在2013年发表了对托伐普坦用药的安全警告，指出托伐普坦在临床上用药不能超过30天，且由于其潜在的致肝损伤的风险，不能大剂量长时间用于肝病患者。

目的：分析血栓弹力图（TEG）在冠心病患者凝血检测中的临床应用，以提高临床实践和认识。

目的：研究表明，冠心病患者血浆高密度脂蛋白（HDL）组成的改变可能与冠心病风险相关。本研究拟探讨HDL组分中载脂蛋白A1（apoA1）和血浆淀粉样蛋白A（SAA）与冠心病风险的关系，及二者在冠心病诊断中的价值。

T-type calcium channel is a kind of low voltage calcium channel, widely distributed throughout the body and participates in many physiological activities. Now increasing attention has been focused on the blockers of the T-type calcium channel. It has not only the function of lowing blood pressure like traditional calcium channel blockers, but also some pharmacological activities such as inhibiting cardiac muscle autorhythmicity, anti-cardiovascular remodeling, renal protective action, and resistance to the sympathetic nervous. This paper summarizes the pharmacological activities, drug interaction, and side effects of T-type calcium channel blockers, which helps to understand the application status of the T type calcium channel blockers in clinical practice, and explore and develop new use value of T-type calcium channel blockers.

目的：研究急性心肌梗死（AMI）患者并发左心室血栓（LVT）形成的临床特征及危险因素。

目的：评价以CYP2C19基因型或血小板功能表现型两种不同的分组方式，对冠状动脉支架置入术后持续服用氯吡格雷的患者临床预后及安全性的预测价值。

PurposeThe aim of this study was to assess the efficacy and safety of ivabradine (Iva) noninferiority to atenolol (Aten) in Chinese patients with chronic stable angina pectoris.MethodsIn this double-blind, double-dummy trial, patients with symptomatic angina pectoris and positive exercise tolerance test were randomized into the Iva [5 or 7.5mg bis in die (BID)] or Aten group (12.5 or 25mg BID) according to computer-generated random numbers for 12weeks.ResultsOne hundred and sixty-eight patients were randomized to the Iva group and 166 to the Aten group. In a full analysis set, increases in the total exercise duration (TED) were 54.3120.1seconds with Iva 5mg and 58.8 +/- 114.7seconds with Aten 12.5mg at the fourth week, and at the 12th week, TED improved by 84.1 +/- 130.5seconds with Iva and 77.8 +/- 126.6seconds with Aten (95%CI: -21.4-34.1seconds, p=0.0011 for noninferiority). The analysis of per protocol set yielded similar results (95%CI: -31.4-33.0seconds, p=0.0131 for noninferiority). Heart rate was reduced in both groups at rest and during peak exercise. There were small, nonsignificant differences in the number of adverse events between the two groups (66 in Iva and 73 in Aten, p>0.05). Nine patients (5.42%) were reported to develop phosphenes/luminous phenomena and blurred vision in the Iva group (p=0.0035).ConclusionsIva is effective in reducing heart rates and improving exercise capacity and noninferior to Aten in Chinese patients with chronic stable angina pectoris. Iva is well tolerated and safe. Copyright (c) 2014 John Wiley & Sons, Ltd.

Objective: To explore the impact for plasma levels of ferritin(FT) and transferrin(TRF) to the risk levels of coronary artery disease(CAD).Methods: Our research included 2 groups, CAD group, n=321 patients and Control group, n=290 healthy subjects. The fasting venous blood was taken from everybody, plasma FT level was detected by electro-chemiluminescence assay and TRF was examined by immune turbidimetric method. The results were compared between 2 groups. Results: Compared with Control group, CAD group had significantly increased plasma FT(236.7 ±174.8) ng/ml vs(207.8 ± 136.9) ng/ml, P=0.032 and decreased TRF(230.5 ±38.1) mg/dl vs(261.6 ± 42.3) mg/dl, P0.001. Multivariate logistic regression analysis presented that plasma FT was not related to CAD, P=0.646 and FRT was related to the risk of CHD(OR: 0.98, 95% CI 0.97-0.99), P0.001. The area under ROC curve for CAD diagnosis showed that FT had no diagnostic value(P=0.145, 95%CI 0.417-0.756), while TRF had medium diagnostic value(P0.001, 95%CI 0.673-0.756), the best cut-off point was TRF≤ 243.5 mg/dl, with the sensitivity of 82.4% and specificity of 47.6%. Conclusion: Our work implies that for CAD related FT and TRF study, plasma level of TRF is more valuable.

目的：研究表明血浆高密度脂蛋白（HDL）的异常修饰可影响其抗动脉粥样硬化的功能。本研究拟利用同位素标记相对和绝对定量技术（iTRAQ）对冠心病患者血浆HDL组分中的4种常见修饰情况加以鉴定和分析。

Background Alteration in the protein composition of high-density lipoprotein (HDL) has been proposed as a mechanism for the development of coronary heart disease (CHD). In HDL, an increase in serum amyloid A protein (SAA) accompanying the decrease in apolipoprotein A-I (apoA-I) has been found during the acute inflammation period. However, whether this phenomenon persists in CHD patients, a disease related to inflammation, is unknown. The purpose of the present study was to explore the relationship between SAA and apoA-I in HDL isolated from CHD patients. Methods Overall, 98 patients with confirmed stable CHD and 90 control subjects matched for age and gender were enrolled in this case-control study. Potassium bromide (KBr) density gradient ultracentrifugation was used to isolate HDL from plasma. The levels of SAA and apoA-I in the HDL samples were detected by enzyme-linked immunosorbent assay kits. Pearson's correlation and general linear models were used in the analysis. Results Compared with controls, patients with CHD had a significant decrease in the amount of apoA-I ((14.21±8.44) μg/ml vs. (10.95±5.95) μg/ml, P =0.003) in HDL and a significant increase in the amount of log SAA (1.21±0.46 vs. 1.51±0.55, P <0.00001). Differences were independent of age, body mass index (BMI), HDL cholesterol (HDL-C), and other factors. An independently and statistically significant positive correlation between log SAA and apoA-I in HDL was observed only in the CHD group (β =2.0, P =0.026). In the general linear model, changes in log(SAA), age, age2, gender, BMI and HDL-C could explain a statistically significant 43% of the variance in apoA-I. Conclusions This study provides direct evidence for the first time that there was an independent positive correlation between log SAA and apoA-I in the HDL of CHD patients, indicating the alteration of protein composition in HDL. However, the question of whether this alteration in HDL is associated with impairment of HDL functions requires further research.