BACKGROUND:Hypertension is one of the most challenging public health problems worldwide. Previous studies suggested that the Songling Xuemaikang capsule (SXC)-a Chinese herbal formula-was effective for essential hypertension. However, the efficacy of SXC monotherapy for hypertension remains unclear. We aimed to compare the blood pressure (BP)-lowering efficacy and safety of SXC versus losartan in patients with essential hypertension. METHODS:In this multicenter, randomized, double-blind, noninferiority trial in China, patients 18 to 65 years of age with mild essential hypertension were randomly allocated to receive either SXC or losartan for 8 weeks. The primary outcome was the change in sitting diastolic BP from baseline to 8 weeks, with a predefined noninferiority margin of -2.5 mm Hg. RESULTS:Of the 755 patients who entered a 2-week run-in period, 628 patients (327 women and 301 men; mean [SD] age, 52.6 [9.2] years) were randomly assigned to the SXC (n=314) or losartan (n=314) group. The primary analysis based on the intention-to-treat principle showed that the change in diastolic BP from baseline to 8 weeks was similar between the SXC and losartan groups (-7.9 [8.0] versus -8.1 [7.9]). The lower boundary of 95% CI (mean difference, -0.24 [95% CI, -1.51 to 1.03]) was above the margin of -2.5 mm Hg, showing noninferiority. Results were consistent with per-protocol analysis. SXC produced greater improvements in total hypertension symptom score (-5.7 [4.2] versus -5.0 [4.0]; P=0.020) and total cholesterol (-0.1 [1.0] versus 0.1 [1.2]; P=0.025). There were no differences between groups in the other BP and patient-reported outcomes. Incidence and severity of adverse events were similar between groups. CONCLUSIONS:SXC was well tolerated and demonstrated noninferior to losartan in BP lowering in patients with mild hypertension. SXC might be an alternative for mild hypertension, particularly for patients with a preference for natural medicine. REGISTRATION:URL: www.chictr.org.cn; Unique identifier: ChiCTR-IPR-16008108.

目的 观察理气活血滴丸治疗慢性稳定性心绞痛的有效性和安全性.方法 选取2016年4月在青岛大学附属医院综合内科就诊的慢性稳定性心绞痛患者204例,口服理气活血滴丸,每次10粒,每天3次,连服4周进行治疗.评估患者疗效、安全性和生活质量等指标.结果 服用4周末,心绞痛症状有效率91.66％,心电图疗效有效率65.69％,硝酸甘油停减率67.15％.共发生不良事件22例(10.78％),与药物可能有关的不良事件4例(1.96％).治疗4周末和筛选期相比,受试者生活质量有明显提高(P均<0.01).结论 理气活血滴丸治疗稳定性心绞痛有效可靠,安全性好,临床可继续推广应用.

目的 从卫生系统角度出发,基于中国医疗卫生实践环境,对理气活血滴丸和复方丹参滴丸治疗冠心病慢性稳定性心绞痛进行成本—效果分析(CEA)和成本—效用分析(CUA),系统评价理气活血滴丸临床短期和长期使用时的药物经济学价值.方法 根据既往Ⅱ/Ⅲ/Ⅳ期临床研究数据,CEA的结果比较两种药物治疗费用和健康产出的差异.CUA以质量调整生命年(QALYs)和增量成本效用比(ICUR)作为分析的主要结果,并对分析结果进行敏感性分析.结果 CEA中,与复方丹参滴丸组相比,理气活血滴丸组每月多花336元,心绞痛症状疗效指标、心电图改变有效率、硝酸甘油停减率和中医证候疗效分别提高16.80％、29.09％、9.79％和6.66％.CUA模拟1年的健康结果,与复方丹参滴丸组相比,理气活血滴丸组的ICUR为80355元/QALY.对于3倍人均GDP的成本效果阈值下(158400元),74.80％的情况下理气活血滴丸具有成本效用优势.结论 理气活血滴丸治疗冠心病可增加患者QALYs,提高患者的生存质量.在3倍人均GDP的阈值下,理气活血滴丸治疗冠心病是一种经济有效的治疗方法.

目的 观察评价丹蒌片治疗稳定性心绞痛的经济性,为指导合理用药提供参考.方法 选取2015年11月-2017年12月期间,全国47家临床医院接受治疗的2243例稳定性心绞痛患者,其中暴露组1493例,非暴露组750例,非暴露组选择单纯西医常规治疗,暴露组在西医常规治疗基础上加用中成药丹蒌片.采用成本-效果和成本-效用分析方法,对暴露组西医常规治疗基础上加用中成药丹蒌片和非暴露组采用西医常规治疗稳定性心绞痛的经济性进行比较.结果 治疗稳定性心绞痛48周的治疗成本:暴露组为(4554.84±4585.24)元,非暴露组为(4531.06±5648.93)元,两队列间比较,差异有统计学意义(P<0.05);暴露组在西医常规治疗基础上加用中成药丹蒌片改善稳定性心绞痛患者生命质量的单位效用成本小于非暴露组西医常规治疗,且丹蒌片治疗多获得一个单位的质量调整生命年需比西医常规治疗多花费33165.74元,低于当前全国人均GDP的3倍.暴露组在西医常规治疗基础上加用丹蒌片治疗稳定性心绞痛,48周内主要心血管事件发生率小于非暴露组西医常规治疗,差异有统计学意义(P<0.05).西雅图心绞痛量表改善方面,暴露组西医常规治疗基础上加用中成药丹蒌片治疗稳定性心绞痛在改善活动能力、减少心绞痛发作次数、增强治疗满意度、提高疾病认识程度方面优于西医常规治疗,差异有统计学意义(P<0.05).中医证候改善方面,暴露组总有效率明显高于非暴露组,差异有统计学意义(P<0.05).暴露组西医常规治疗基础上加用丹蒌片治疗的效用权重系数在1年观察期内由0.8094增加至0.8709,增加0.0615,高于非暴露组西医常规治疗的0.0480(观察期内由0.8064增加至0.8544).结论 西医常规治疗基础上使用丹蒌片相对于西医常规治疗稳定型心绞痛效果占优,经济优势相对明显.

OBJECTIVE:´Three formulas and three medicines,' namely, Jinhua Qinggan Granule, Lianhua Qingwen Capsule, Xuebijing Injection, Qingfei Paidu Decoction, HuaShi BaiDu Formula, and XuanFei BaiDu Granule, were proven to be effective for coronavirus disease 2019 (COVID-19) treatment. The present study aimed to identify the active chemical constituents of this traditional Chinese medicine (TCM) and investigate their mechanisms through interleukin-6 (IL-6) integrating network pharmacological approaches. METHODS:We collected the compounds from all herbal ingredients of the previously mentioned TCM, but those that could down-regulate IL-6 were screened through the network pharmacology approach. Then, we modeled molecular docking to evaluate the binding affinity between compounds and IL-6. Furthermore, we analyzed the biological processes and pathways of compounds. Finally, we screened out the core genes of compounds through the construction of the protein-protein interaction network and the excavation of gene clusters of compounds. RESULTS:The network pharmacology research showed that TCM could decrease IL-6 using several compounds, such as quercetin, ursolic acid, luteolin, and rutin. Molecular docking results showed that the molecular binding affinity with IL-6 of all compounds except γ-aminobutyric acid was < -5.0 kJ/mol, indicating the potential of numerous active compounds in TCM to directly interact with IL-6, leading to an anti-inflammation effect. Finally, Cytoscape 3.7.2 was used to topologize the biological processes and pathways of compounds, revealing potential mechanisms for COVID-19 treatment. CONCLUSION:These results indicated the positive effect of TCM on the prevention and rehabilitation of COVID-19 in at-risk people. Quercetin, ursolic acid, luteolin, and rutin could inhibit COVID-19 by down-regulating IL-6.

目的 对理气活血滴丸Ⅳ期临床研究中老年患者数据进行分析,系统评价理气活血滴丸在老年慢性稳定型心绞痛人群广泛使用条件下安全性和有效性.方法 2016年3月至2017年8月于上海长征医院等41家中心随机纳入慢性稳定型心绞痛患者2433例,其中老年患者1142例,口服理气活血滴丸,10粒/次,3/d,连服4周.进行老年患者有效性、安全性和生活质量等指标的分析.结果 服用4周后,老年患者心绞痛症状有效率71.50％,硝酸甘油停减率84.40％,心电图疗效有效率57.08％,共发生不良事件45例(3.95％).和筛选期相比,治疗4周后患者生活质量显著提高(P<0.001).结论 理气活血滴丸治疗老年慢性稳定型心绞痛疗效可靠,安全性好,患者生活质量明显提高,值得临床推广应用.

目的 研究理气活血滴丸在临床使用中的安全性和有效性.方法 选择2016年3月至2017年8月山东省交通医院冠心病慢性稳定型心绞痛患者185例,口服理气活血滴丸,每次10丸,每日3次,连服4周.4周后评估有效性、安全性和生活质量等指标.结果 心绞痛症状:总有效率,治疗2周为30.41％,治疗4周为69.18％;疼痛疗效的总有效率,治疗2周为20.40％,治疗4周为53.40％;发作次数疗效的总有效率,治疗2周为57.30％,治疗4周为70.90％;心绞痛持续时间疗效有效率,治疗2周为45.60％,治疗4周为73.80％.心电图疗效,服药4周为39.63％,硝酸甘油停减率治疗2周为70.00％,治疗4周为90.00％.共发生不良事件30例(16.22％),与药物可能有关不良事件17例(9.19％),治疗结束后所有不良事件均恢复正常.生活质量方面,治疗前和治疗4周后均有统计学意义(P<0.001).结论 理气活血滴丸可改善冠心病患者的临床症状,减少心绞痛的发作次数,改善心电图症状,并且具有较好的安全性,同时也可以改善生活质量.

目的 观察并比较丹参多酚酸盐对接受经皮冠状动脉介入术(PCI)的非ST段抬高型急性冠状动脉综合征(NSTE-ACS)患者的治疗效果、安全性和机制.方法 选取2018年7月—2019年6月上海中医药大学附属岳阳中西医结合医院心血管内科行PCI治疗的NSTE-ACS患者86例,随机数字表法分为对照组和观察组,各43例.对照组PCI术后给予冠心病二级预防治疗,观察组在对照组治疗基础上给予丹参多酚酸盐静脉滴注,均持续治疗14 d.比较治疗前后2组患者临床疗效、心功能、心肌损伤标志物、内皮功能标志物水平,以及心血管事件和药物不良反应.结果 观察组临床总有效率高于对照组(95.35％vs.83.72％,χ2/P=9.183/0.031);治疗后2组LVEF均升高,但观察组高于对照组(t/P=10.102/0.000),观察组左心室整体纵向应变优于对照组(t/P=8.847/<0.001);2组治疗后CK-MB、cTnI和BNP水平均较治疗前明显降低,但2组比较差异无统计学意义(P>0.05);治疗后观察组血清NO水平高于对照组(t/P=47.090/<0.001),而ET-1和VWF水平低于对照组(t/P=26.481/0.001,8.603/0.001);2组均无心血管不良事件和药物不良反应.结论 丹参多酚酸盐用于接受PCI治疗的NSTE-ACS患者,能够减少心绞痛发作,改善左心室收缩功能,其作用机制可能与改善血管内皮功能有关.

目的 探讨瑞舒伐他汀对晚期糖基化终产物修饰的低密度脂蛋白(AGE-LDL)刺激肥大细胞活化的影响及相关分子机制.方法 2019年6月—2020年12月于中国人民解放军海军军医大学中心实验室进行实验.以重组鼠白介素-3(rmIL-3)和重组鼠干细胞因子(rmSCF)体外诱导小鼠骨髓细胞向肥大细胞分化.收集细胞分为Con-trol组(加入PBS)、不同浓度AGE-LDL组(0.5、5、50μg/ml)、n-LDL组、LPS组、不同浓度瑞舒伐他汀组(1、10、50 mmol/L),用不同浓度的瑞舒伐他汀及AGE-LDL预处理分化成熟的肥大细胞,分别用RT-PCR及酶联免疫吸附试验(ELISA)检测肥大细胞中肿瘤坏死因子α(TNF-α)、白介素6(IL-6)和基质金属蛋白酶9(MMP-9)的基因表达和蛋白水平;采用Western-blot法检测瑞舒伐他汀及相关信号通路抑制剂对AGE-LDL刺激的丝裂原活化蛋白激酶(MAPK)通路的影响.结果 与Control组比较,AGE-LDL组可呈浓度依赖性地刺激肥大细胞分泌TNF-α、IL-6和MMP-9 mRNA表达,差异具有统计学意义(F=47.050、71.320、574.320,P均=0.000),其中50μg/ml亚组表达量最高,而非糖化低密度脂蛋白(n-LDL)组差异无统计学意义(P>0.05).瑞舒伐他汀能够呈浓度依赖性抑制上述指标mRNA表达(F=63.050、33.610、68.480,P均=0.000),并抑制TNF-α、IL-6、MMP-9分泌(t/P=28.190/0.000、19.900/0.000、19.550/0.000).AGE-LDL能够促进p38、ERK1/2、p65磷酸化(t/P=9.640/0.002、13.380/0.001、6.110/0.001),对JNK磷酸化则无影响(P>0.05);瑞舒伐他汀及ERK1/2抑制剂、NF-κB抑制剂能够下调相应信号通路磷酸化及炎性因子表达(瑞舒伐他汀组:t/P=4.470/0.004、6.330/0.001、3.640/0.011;PD98059组:t=14.500、12.670、18.180,P均=0.000;PDTC组:t=19.140、15.400、23.070,P均=0.000),而p38-MAPK抑制剂则无相应抑制作用(P>0.05).结论 瑞舒伐他汀能够抑制AGE-LDL刺激小鼠骨髓来源肥大细胞(mBMMCs)活化分泌炎性介质,其机制可能与抑制ERK1/2和NF-κB通路有关.

目的 观察青年急性心肌梗死病人发病节律模式,并探讨青年急性心肌梗死病人发病节律机制.方法 收集上海两所三级甲等医院2017年9月1日—2018年9月1日收治入院的青年及老年急性心肌梗死病人基本资料和临床信息,并收集青年心肌梗死病人和青年健康志愿者外周静脉血.回顾性探讨青年急性心肌梗死病人发病节律模式,并对参与者外周血的节律基因和纤溶酶原激活物抑制物-1(PAI-1)基因行实时荧光定量聚合酶链式反应(qPCR)检测.结果 入组病人中122例(37.20％)年龄≤45岁,206例(62.80％)年龄≥65岁.青年病人更易于上午发生心肌梗死(06:01～12:00),且在5月份发病率较老年病人高.上午发病的青年急性心肌梗死病人外周血中Clock、Bmal1和PAI-1的mRNA表达较青年健康志愿者明显升高.结论 青年病人较老年病人更易在上午和5月份罹患急性心肌梗死.而上午高发的原因可能与Clock、Bmal1和PAI-1等基因在上午的表达异常升高有关.此结果可为青年急性心肌梗死病人的时间治疗策略提供理论依据.

目的 本研究从社会角度出发,基于美国医疗环境,通过对理气活血滴丸和雷诺嗪治疗冠心病稳定型心绞痛进行成本-效果分析(Cost-Effectiveness Analysis,CEA),探讨二者长期临床应用的经济学优劣势,为理气活血滴丸在美国上市后的定价作为参考.方法 建立马尔可夫(Markov)药物经济学模型,以增量成本-效果比(Incremental Cost Effectiveness Ratios,ICER)和质量调整生命年(Quality-adjusted life years,QALYs)作为衡量指标,比较理气活血滴丸与雷诺嗪的健康产出,拟定理气活血滴丸在美国的上市后价格.结果 模拟理气活血滴丸和雷诺嗪持续1年治疗冠心病稳定型心绞痛患者的健康结果 ,理气活血滴丸组患者的平均QALYs值为0.797,高于雷诺嗪组的0.720.依据美国临床与经济评论研究所推荐的ICER阈值为50000～150000美元/QALY,理气活血滴丸在美国定价范围为135.8美元/盒到245美元/盒.结论 当理气活血滴丸在美国定价范围为135.8美元/盒到245美元/盒时,与雷诺嗪相比,具有成本效果优势.

目的 本研究对理气活血滴丸IV期临床研究中伴有介入治疗史的患者数据进行分析,系统评价理气活血滴丸对伴有介入治疗史的冠心病慢性稳定性心绞痛人群广泛使用条件下有效性和安全性.方法 2016年3月至2017年8月在上海长征医院等全国41家中心随机纳入冠心病慢性稳定性心绞痛患者2433例,其中伴有介入治疗史患者1173例.口服理气活血滴丸,每次10粒,每日3次,连服4周.对伴有介入史患者的有效性、安全性及生活质量等指标的评价.结果 服药4周后,伴有介入史患者心绞痛症状有效率68.42％,硝酸甘油停减率85.70％,心电图疗效有效率60.70％.合并介入史患者新发生不良事件58例.和筛选期相比,治疗4周后患者生活质量显著提高(P<0.001).结论 理气活血滴丸治疗伴有介入治疗史的冠心病稳定性心绞痛人群疗效可靠,安全性好,患者生活质量明显提高,值得临床推广使用.

"Three formulas and three medicines," which include Jinhua Qinggan granule, Lianhua Qingwen capsule/granule, Xuebijing injection, Qingfei Paidu decoction, HuaShiBaiDu formula, and XuanFeiBaiDu granule, have been proven to be effective in curbing coronavirus disease 2019 (COVID-19), according to the State Administration of Traditional Chinese Medicine. The aims of this study were to identify the active components of "Three formulas and three medicines" that can be used to treat COVID-19, determine their mechanism of action via angiotensin-converting enzyme 2 (ACE2) by integrating network pharmacological approaches, and confirm the most effective components for COVID-19 treatment or prevention. We investigated all the compounds present in the aforementioned herbal ingredients. Compounds that could downregulate the transcription factors (TFs) of ACE2 and upregulate miRNAs of ACE2 were screened via a network pharmacology approach. Hepatocyte nuclear factor 4 alpha (HNF4A), peroxisome proliferator-activated receptor gamma (PPARG), hsa-miR-2113, and hsa-miR-421 were found to regulate ACE2. Several compounds, such as quercetin, decreased ACE2 expression by regulating the aforementioned TFs or miRNAs. After comparison with the compounds present in Glycyrrhiza Radix et Rhizoma, quercetin, glabridin, and gallic acid present in the herbal formulas and medicines were found to alter ACE2 expression. Gene ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analysis were used to search for possible molecular mechanisms of these compounds. In conclusion, traditional Chinese medicine (TCM) plays a pivotal role in the prevention and treatment of COVID-19. Quercetin, glabridin, and gallic acid, the active components of recommended TCM formulas and medicines, can inhibit COVID-19 by downregulating ACE2.

目的 确证理气活血滴丸治疗冠心病慢性稳定性心绞痛人群的有效性和安全性.方法 2016年3月至2017年8月我院入组慢性稳定性心绞痛患者254例,服用理气活血滴丸,口服10粒/次,每天3次,连服28 d.定期评估有效性、安全性和生活质量等指标.结果 心绞痛症状的总有效率,服药2周后18.70％,4周后50.84％;心绞痛疼痛疗效的有效率,服药2周后11.00％,4周后23.30％;心绞痛发作次数疗效有效率,服药2周后,28.20％,4周后66.90％;心绞痛持续时间疗效有效率,服药2周后33.2％,4周后56.50％;服药4周后心电图疗效26.81％,硝酸甘油停减率61.76％.服药4周后的各项疗效指标均优于服药前和服药2周后.共发生不良事件13例(5.14％),与药物可能有关的不良事件4例(1.58％).治疗4周后和筛选期相比,患者生活质量有明显提高(P<0.001).结论 理气活血滴丸治疗冠心病稳定性心绞痛疗效可靠,安全性好,值得临床推广应用.

冠状动脉微循环障碍严重影响着人类健康,因心绞痛行冠状动脉造影检查的患者中非阻塞性冠心病较为常见.冠状动脉微循环障碍可能与非阻塞性冠心病患者心绞痛的发生密切相关,然而微血管性心绞痛与冠状动脉微循环障碍的关系尚不明确.本文就冠状动脉微循环障碍的主要危险因素(如糖尿病、炎症反应、衰老、性别等)、发病机制(内皮细胞功能紊乱、平滑肌细胞功能障碍等)和治疗手段的研究进展作一综述.

OBJECTIVEThe aim of this study was to explore the correlation between muscle RAS oncogene homolog (MRAS) gene polymorphism and the onset risk of atherosclerosis (AS).PATIENTS AND METHODSA total of 135 AS patients diagnosed and treated in our hospital from November 2017 to October 2018 were randomly enrolled in the observation group. Meanwhile, 150 healthy adults were selected as control group. Venous blood was withdrawn from all the subjects, and DNAs were extracted. MRAS gene loci rs9818870 and rs3755751 were analyzed by the multiplex SNaPshot method, and their correlations with the onset risk of AS were explored.RESULTSNo statistically significant differences in the frequencies at gene loci were observed between the two groups (p>0.05). Subjects with genotype TT at rs9818870 exhibited significantly higher risk of AS (p=0.041<0.05). The recessive model of rs9818870 (GG + AG/AA) in AS patients with coronary heart disease was correlated with AS (p=0.048<0.05). Similarly, the dominant model of rs3755751 (TT/TC+CC) in those with hypertension was associated with AS (p=0.027<0.05).CONCLUSIONSMRAS gene is correlated with the onset of AS to a certain degree.

目的 系统阐明理气活血滴丸在冠心病慢性稳定型心绞痛人群广泛使用条件下的安全性和有效性.方法 2016年3月-2017年8月在上海长征医院等全国41家中心随机纳入冠心病慢性稳定型心绞痛病人2433例,口服理气活血滴丸,每次10粒,每日3次,连服4周进行治疗,评估疗效、安全性和生活质量等指标.结果 服用4周后,心绞痛症状总有效率为72.45％,硝酸甘油停减率为88.80％,心电图疗效总有效率为52.53％.共发生不良事件494例(20.27％),与药物可能有关的不良事件123例(5.06％).治疗4周后和筛选期相比,病人生活质量显著提高(P＜0.001).结论 理气活血滴九治疗冠心病稳定型心绞痛有效可靠,安全性好.

"坏胆固醇"是冠心病的"导火索" 现代医学研究成果显示:导致中风和冠心病发生的"导火索"是动脉粥样硬化,80％的缺血性中风患者的心脏冠状动脉存在动脉粥样硬化斑块,40％的患者冠状动脉狭窄超过50％.也就是说,动脉粥样硬化也是冠心病和中风发生的主要病理基础,而"坏胆固醇"(低密度脂蛋白胆固醇)水平的升高会导致动脉粥样硬化.

BACKGROUND To explore the protective effects of Shexiang Tongxin Dropping Pill (STP) in improving peripheral microvascular dysfunction in mice and to explore the involved mechanism. MATERIAL AND METHODS A peripheral microvascular dysfunction model was established by combined myocardial infarction (MI) and lipopolysaccharide (LPS) injection in mice. Then, the mice were randomized into a model group (n=10) or an STP group (n=10), which were treated with normal saline and STP, respectively. The cremaster muscle microvascular blood flow velocity and numbers of leukocytes adherent to the venular wall were evaluated before and after drug intervention. We assessed the expression of adhesion molecule CD11b and related transcript factor FOXO1 in leukocytes, cystathionine-γ-lyase (CSE) mRNA expression in the cremaster muscle, and mitochondrial DNA copy numbers. RESULTS Compared with those of control mice, the cremaster microvascular blood flow velocity, cremaster CSE expression, and mitochondrial DNA copy number in mice from the model group were significantly lower and leukocyte adhesion and CD11b and FOXO1 expression were significantly higher. Intervention with STP could significantly increase the cremaster microvascular flow velocity (0.480±0.010 mm/s vs. 0.075±0.005 mm/s), mRNA expression of cremaster CSE, and mitochondrial DNA copy number, but it inhibited leukocyte adhesion and decreased leukocyte CD11b and FOXO1 expression. CONCLUSIONS STP significantly improved peripheral microcirculation, in which increased CSE expression might be the underlying mechanism.