Background Myocardial ischemia-reperfusion injury (MIRI) constitutes a significant contributor to the increased incidence of post-ischemic heart failure. The primary mechanisms underlying MIRI involve oxidative stress and mitochondrial calcium overload in reperfused cardiomyocytes. Regulating the homeostasis of the mitochondrial-associated endoplasmic reticulum membranes (MAMs) to improve endoplasmic reticulum-mitochondrial communication is expected to treat MIRI, but there are currently no clear targeted drugs. The Shenfuyixin Granules (SFYX) exhibit capabilities in lowering reactive oxygen species levels, curtailing apoptosis, and improving mitochondrial performance in cardiomyocytes. However, its therapeutic role in MIRI remains unclear. Aim of the study This study aims to clarify the effect of SFYX on mitochondrial calcium overload after MIRI and elucidate its potential mechanism of action. Methods The rat MIRI model was established by short-time ligation of the left anterior descending coronary artery and reperfusion, and SXNI (3.275g/kg, 6.55g/kg, 13.1g/kg) was administered for treatment. Network pharmacology combined with molecular docking has revealed the specific molecular mechanism by which SFYX regulates mitochondrial calcium homeostasis in the myocardium. The improvement effect of SFYX on MIRI was evaluated by western blotting (WB), TUNEL staining, immunofluorescence staining, etc. A hypoxia/reoxygenation (H/R) model of myocardial cells was simultaneously established, MIRI was simulated in vitro, and the mechanism was verified using WB, fluorescent probes, mitochondrial function and other related tests. Results Network pharmacological analysis and molecular docking indicated that SFYX might improve MIRI by reducing mitochondrial calcium overload through the cGMP-PKG signaling pathway and calcium signaling pathway, and the key blood-entering components could stably bind to cGMP and PKG. In vivo experiments confirm that SFYX significantly attenuates myocardial injury associated with MIRI and alleviates levels of oxidative stress and apoptosis through the sGC/PKG pathway. In vitro experiments verify that SFYX regulates MAMs via the sGC/PKG signaling pathway, thereby stabilizing mitochondrial function, alleviating calcium overload and oxidative stress, and ultimately combating MIRI. Conclusion This study suggests that SFYX prophylactic administration can alleviate mitochondrial calcium overload by targeting MAMs through the sGC/PKG signaling axis and has a preventive effect on MIRI. These findings indicate that SFYX may become a potential drug for preventing MIRI in the future.
This multicenter observational analysis, based on prospectively collected data from a 1-year disease-management cohort, assessed secondary prevention status at enrollment and 1-year unplanned readmission among 2,896 patients with cardiovascular and cerebrovascular diseases in China. Patients included 1,061 with stable angina (CAD), 427 with myocardial infarction (MI), 1,141 with cerebral infarction (CI), and 267 with intracerebral hemorrhage (ICH), recruited from three regions between August 2020 and March 2021. Data on demographics, Traditional Chinese Medicine (TCM) syndromes, and medications were analyzed. Logistic regression was used to examine factors associated with blood pressure, lipid, and glucose target achievement, as well as 1-year readmission. Among 2,698 patients with available target-control data, the blood pressure target-achievement rate was 45.4
背景 目前我国冠心病合并高血压患病率和死亡率逐年攀升,严重威胁我国公共卫生安全,规范并总结中医组方治疗冠心病合并高血压的方案刻不容缓,以期为临床辨证论治冠心病合并高血压及共识和指南的制订提供数据来源。目的 基于隐结构模型结合关联规则探索冠心病合并高血压的组方及配伍规律。方法 本研究检索时间为建库至2024-05-31,系统性检索中国知网、维普中文期刊服务平台、万方数据知识服务平台、中国生物医学文献数据库,通过EndNote软件筛选出中药汤剂治疗冠心病合并高血压的最终文献。运用Microsoft Excel 2019导入规范化的数据并建立中药数据库,应用Lantern 5.0和Rstudio软件对高频中药进行隐结构模型和关联规则分析。结果 最终纳入中医处方122首,涉及中药104味,中药累计使用频次为1 390次,高频中药(使用率>4%)为丹参、川芎、牛膝、赤芍、郁金等,功效以活血化瘀、补虚为主。隐结构分析共获得19个隐变量、38个隐类、5个综合聚类模型、16个核心方剂,以方测证来推断出冠心病合并高血压证型以气虚血瘀证、气滞血瘀证、阴虚血瘀证和痰湿闭阻证为常见证型。关联规则分析获取43条强关联规则,支持度最高为牛膝-川芎,置信度最高为郁金-丹参。结论 冠心病合并高血压为本虚标实之证,核心病机以“瘀”为主,“虚”“痰”次之,与肝、心、脾三脏关系密切,当以活血补气、豁痰祛湿为治疗原则,随证结合滋阴健脾、理气疏肝治法。
Network Meta-analysis was performed to compare the efficacy and safety of Chinese patent medicines in treating chronic pulmonary heart disease. CNKI, VIP, Wanfang, SinoMed, PubMed, Web of Science, EMbase, and Cochrane Library were searched for randomized controlled trial(RCT) of treating chronic pulmonary heart disease with Chinese patent medicines with the time interval from inception to December 2023. The Cochrane risk-of-bias tool was used for quality assessment of the included articles. RevMan 5.4 and Stata 17.0 were employed to establish the risk of bias map and perform the network Meta-analysis, respectively. Ultimately, a total of 95 RCTs involving 8 787 cases and 11 different Chinese patent medicines were included. Network Meta-analysis yielded the following results based on the surface under the cumulative ranking curve(SUCRA).(1)In terms of cardiac function improves clinical total effective rate, SUCRA the top three were Wenxin Granules + conventional western medicine, Tongxinluo Capsules + conventional western medicine, and Qishen Yiqi Dropping Pills + conventional western medicine.(2)For improving forced expiratory volume in the first se-cond(FEV1), SUCRA the top three were Danting Feixin Granules + conventional western medicine, Tongxinluo Capsules + conventional western medicine, and Bufei Huoxue Capsules + conventional western medicine.(3)Regarding increasing the FEV1/forced vital capacity(FVC%) value, SUCRA the top three were Qili Qiangxin Capsules + conventional western medicine, Shexiang Baoxin Pills + conventional western medicine, and Qishen Yiqi Dropping Pills + conventional western medicine.(4)In terms of increasing the partial pressure of oxygen(PaO_2), SUCRA the top three were Qili Qiangxin Capsules + conventional western medicine, Qishen Yiqi Dropping Pills + conventional western medicine, and Shexiang Baoxin Pills + conventional western medicine.(5)In terms of reducing the partial pressure of carbon dioxide(PaCO_2), SUCRA the top three were Tongxinluo Capsules + conventional western medicine, Qishen Yiqi Dropping Pills + conventional western medicine, and Shexiang Baoxin Pills + conventional western medicine.(6)In terms of increasing left ventricular ejection fraction(LVEF), SUCRA the top three were Bufei Huoxue Capsules + conventional western medicine, Qishen Yiqi Dropping Pills + conventional western medicine, and Shexiang Baoxin Pills + conventional western medicine.(7)In terms of decreasing brain natriu-retic peptide(BNP), SUCRA the top three were Compound Danshen Dropping Pills + conventional western medicine, Qili Qiangxin Capsules + conventional western medicine, and Tongxinluo Capsules + conventional western medicine.(8)In terms of improving the hematocrit level, SUCRA the top three were Qishen Yiqi Dropping Pills + conventional western medicine, Compound Danshen Dropping Pills + conventional western medicine, and Tongxinluo Capsules + conventional western medicine. In terms of safety, 26 RCTs reported adverse reactions, which primarily involved the circulatory and digestive systems. The combination of Chinese patent medicines with conventional western medicine has demonstrated enhanced therapeutic effects on chronic pulmonary heart disease. However, due to the varying quality and sample sizes of included studies and the absence of direct comparisons between Chinese patent medicines, the conclusions should be further validated by multicenter studies with larger sample sizes and higher methodological rigor.
Cardiovascular and cerebrovascular diseases (CVDs) present a significant challenge in the realm of chronic disease management in China. The objective of this study is to assess the efficacy of a health management model rooted in a three-tier prevention and control system for CVDs. From August 2020 to September 2020, this study enrolled 2033 CVDs patients from 105 villages across three townships in central China. All participants underwent a 12-month health management involving monitoring, risk assessment, health education, and interventions. The primary endpoint focused on recurrence and exacerbation, while secondary outcomes encompassed health economic indicators, awareness of prevention and control knowledge, risk factor, lifestyle behavior. Data analysis was conducted using generalized estimating equation models. After 1 year of follow-up, the odds of recurrence and exacerbation decreased significantly compared to the baseline [odds ratio (OR) 0.30, 95 https://www.chictr.org.cn/showproj.html?proj=52395 ).
The efficacy and safety of different Chinese patent medicines in the treatment of coronary heart disease complicated with heart failure were evaluated by network Meta-analysis. The randomized controlled trial(RCT) of Chinese patent medicines for coronary heart disease complicated with heart failure was retrieved from CNKI, Wanfang, VIP, SinoMed, PubMed, Web of Science, EMbase, and Cochrane Library with the time interval from inception to July 5, 2023. The quality of the included RCT was evaluated by the Cochrane's risk of bias assessment tool, and a network Meta-analysis was performed in Stata 16.0. Finally, a total of 82 RCTs were included, involving 9 298 patients and 11 Chinese patent medicines. Network Meta-analysis yielded the following results based on the surface under the cumulative ranking curve(SUCRA).(1)In terms of improving the clinical response rate, the top three interventions were Qishen Yiqi Dripping Pills + conventional western medicine, Zhenyuan Capsules + conventional western medicine, and Tongxinluo Capsules + conventional western medicine.(2) In terms of increasing left ventricular ejection fraction(LVEF), the top three interventions were Shexiang Baoxin Pills + conventional western medicine, Compound Danshen Dripping Pills + conventional western medicine, and Tongxinluo Capsules + conventional western medicine.(3) In terms of reducing left ventricular end-diastolic diameter(LVEDD), the top three interventions were Shexiang Tongxin Dripping Pills + conventional western medicine, Tongxinluo Capsules + conventional western medicine, and Shexiang Baoxin Pills + conventional western medicine.(4) In terms of reducing N-terminal pro-brain natriuretic peptide(NT-proBNP), the top three interventions were Shexiang Baoxin Pills + conventional western medicine, Qi-shen Yiqi Dripping Pills + conventional western medicine, and Compound Danshen Dripping Pills + conventional western medicine.(5) In terms of reducing hyper-sensitive C-reactive protein(hs-CRP), the top three interventions were Naoxintong Capsules + conventional western medicine, Shexiang Baoxin Pills + conventional western medicine, and Compound Danshen Dripping Pills + conventional western medicine.(6) In terms of increasing the distance of the six-minute walking trail(6MWT), the top three interventions were Zhen-yuan Capsules + conventional western medicine, Qili Qiangxin Capsules + conventional western medicine, and Qishen Yiqi Dripping Pills + conventional western medicine. The results showed that Chinese patent medicines combined with conventional western medicine can effectively improve the clinical response rate, LVEF, and 6MWT and reduce LVEDD, NT-proBNP, and hs-CRP. However, due to the overall low quality of the articles included and the few articles of some Chinese patent medicines, direct comparison between diffe-rent Chinese patent medicines remains to be carried out and the results need to be further verified.
心肌梗死具有高病死率、高复发率以及并发症多等特点,已成为亟待解决的重大公共卫生问题.国内外研究显示健康监测是控制心血管疾病切实可行的方法.运用中医学理论指导并结合现代医学技术对心梗后患者的健康进行动态监测,有利于改善患者的预后,降低心血管事件发生,这也符合"健康中国"的要求.本文对心肌梗死中医健康监测的文献进行系统回顾和梳理,发现对心梗后患者监测气虚血瘀证、气滞血瘀证、阳气亏虚证;厚腻苔、青紫舌象;脾虚、痰湿、气郁体质;嗜食油腻、紧张焦虑、睡眠不足等不良生活方式以及寒冷多变的气候时令,能够对疾病发生、严重程度、死亡率以及心血管主要不良事件具有预警作用,这为心肌梗死中医慢病管理提供新的思路与方法.
Objective:To explore the correlation between differential immune-related genes(DIRGs)and immune cells in the progression of atherosclerosis(AS)and general rule of Chinese medicine for intervening DIRGs.Methods:Firstly,GSE28829 data set was obtained from GEO database,and immune-related genes were downloaded from ImmPort database and MSigDB database.Secondly,differentially expressed genes between early AS plaques(EAP)and advanced AS plaques(AAP)of GSE28829 were screened by limma package,and their intersections with immune-related genes were known as DIRGs.clusterProfiler package was used to enrich the DIRGs.Protein interaction network of DIRGs was constructed and Hub genes were screened.Then,the infiltration patterns of 22 kinds of immune cells were analyzed by CIBERSORT to screen differential immune cells,and the correlation between them and Hub genes were analyzed by Pearson method.Finally,Coremine Medical database was used to predict Chinese herbs for in-tervening DIRGs,the property and flavor of Chinese herbs were collected.Results:Total 63 DIRGs were obtained,and 10 Hub genes(CD86,TLR2,TYROBP,CCR1,ITGB2,CCL2,CCL4,CSF1R,CXCR4,CTSS)were screened out.Enrichment analysis results showed that the molecular functions,biological processes and signaling pathways of DIRGs were closely related to immune regulation.Analysis of immune cell infiltration showed that proportions of regulatory T cells,activated dendritic cells and resting mast cells in EAP were increased.Proportions of memory B cells,γδ T cells,M0 macrophages and M2 macrophages were increased in AAP.Correla-tion analysis showed that CD86 was positively correlated with M2 macrophages in EAP.In AAP,CD86,CTSS,CXCR4,CSF1R,ITGB2 and TYROBP were positively correlated with M0 macrophages,while CCL4 and CCL2 were negatively correlated with resting mast cells.Results of frequency showed that Chinese herbs for intervening DIRGs mainly distributed to liver and lung meridians,and their property and taste were cold and bitter.Conclusion:This study found that in the progression of AS,10 DIRGs were the most important,and 7 kinds of immune cells were dysregulated,among which CD86,CTSS,CXCR4,CSF1R,ITGB2,TYROBP,CCL4 and CCL2 were correlated with resting mast cells,M0 and M1 macrophages.At the same time,immune mechanism of AS progression was closely related to liver meridian,lung meridian,bitter,sweet,cold and warm.The results can provide reference and ideas for Chinese herbs clinical prescription to treat AS and further exploratory the immunological mechanism of AS progression.
目的 研究慢性心力衰竭(CHF)患者的生存率、死亡原因及与预后相关的影响因素等,为CHF提供一定的流行病学参考.方法 入选2009年9月—2010年5月确诊的295例CHF患者.采用电话咨询、预约来院、到户走访等每年随访1次,应用寿命表、Kaplan-Meier法分析生存率,采用Cox比例风险模型分析与预后相关的影响因素,并观察基础用药变化情况.结果 (1)患者随访1~117个月,平均81个月,随访期死亡136例,脱落62例,完成随访97例;(2)CHF患者1、5、9年的累积生存率分别为90.4%、65.0%、51.1%,中位生存时间约为114个月;(3)CHF死亡前三位原因是CHF急性加重(86.02%)、心脏猝死(5.14%)、急性心肌梗死(3.67%);(4)无心梗病史、无合并症、纽约心脏病协会(NYHA)分级Ⅱ级的CHF患者远、近期累积生存率均较高,射血分数≥35%的CHF患者远期生存率较高,差异均有统计学意义(P<0.05);(5)NYHA分级Ⅲ级、有合并症、未规范药物治疗、射血分数<35%、左心室舒张末期内径>55 mm、右心房内径>41 mm、体重指数≤24 kg/m2、血清白蛋白<40 g/L、血清总胆红素>17.1 μmol/L、尿素氮>7.14 mmol/L与CHF患者的死亡风险有关,差异均有统计学意义(P<0.05);(6)与随访前比较,β受体阻滞剂、螺内酯、利尿剂、肾素-血管紧张素系统阻滞剂使用比例增长均超过10%.结论 本研究中CHF患者近10年生存率较既往研究有所升高,NYHA分级、合并症数量、规范药物治疗、射血分数、左心室舒张末期内径等是影响CHF患者预后的预测因素.
目的 采用数据挖掘技术探讨中医药治疗高血压伴焦虑、抑郁状态的用药规律,为临床治疗高血压伴焦虑、抑郁状态提供依据.方法 检索中国知网、万方、维普等数据库,收集中药治疗高血压伴焦虑、抑郁状态的临床研究,整理数据并建立数据库.运用Rstudio、R version4.1.3、Excel等统计软件对药物进行统计分析,探讨该病中医药用药规律.结果 获得中药处方101首,涉及中药170味,使用频次为1237次,单次使用频次>15次的中药有31味,高频药物有柴胡、茯苓、当归、白芍、钩藤、栀子等;药物功效以补虚药、安神药、清热药、平肝息风为主;药物四气以寒、温平为主,五味以甘、苦、辛为主,归经以肝、心、脾为主;关联规则分析获得常用药物组合19组;聚类分析获得6类药物组合.结论 中医药治疗高血压伴焦虑、抑郁状态多以补虚药、安神药为主,四气五味以寒、温及甘、苦为主,当归、茯苓-白术,天麻-钩藤为治疗高血压伴焦虑、抑郁状态的核心药对,聚类分析得出核心方剂为逍遥散与天麻钩藤饮.
This study aims to explore the medication rule of traditional Chinese medicine(TCM) for heart failure after myocardial infarction via data mining. To be specific, articles on the treatment of the disease with Chinese medicine were retrieved from CNKI, Wanfang, VIP, and SinoMed and related information was collected. A database was created with Microsoft Excel 2019, and SPSS Clementine 12.0 and IBM SPSS Statistics 23.0 were applied for association rules analysis, cluster analysis, and factor analysis. Finally, a total of 81 TCM prescriptions were screened out, involving 91 medicinals with cumulative use frequency of 740. The main syndromes were Qi deficiency and blood stasis, Yang Qi deficiency and blood stasis together with retained morbid fluid, deficiency of both Qi and Yin and blood stasis. The medicinals with high-frequency were Astragali Radix, Salviae Miltiorrhizae Radix et Rhizoma, Ginseng Radix et Rhizoma, Poria, and Aconiti Lateralis Radix Praeparata. The effects of the medicinals were tonifying deficiency, activating blood and resolving stasis, and promoting urination and draining dampness. The association rules analysis yielded "Astragali Radix-Salviae Miltiorrhizae Radix et Rhizoma" "Astragali Radix-Aconiti Lateralis Radix Praeparata-Salviae Miltiorrhizae Radix et Rhizoma" "Aconiti Lateralis Radix Praeparata-Ginseng Radix et Rhizoma-Salviae Miltiorrhizae Radix et Rhizoma-Astragali Radix" combinations. Cluster analysis yielded 6 basic formulas for heart failure after myocardial infarction. Factor analysis extracted a total of 8 common factors. Heart failure after myocardial infarction is characterized by the syndrome of deficiency in nature and excess in superficiality. The core pathogenesis is "deficiency" "stasis" "retained morbid fluid", particularly "deficiency". This disease is closely related to the heart, lung, and spleen. The basic treatment principle is replenishing Qi and activating blood, and warming Yang, excreting water, and nourishing yin should also be emphasized. The common basic prescriptions, such as Siwu Decoction, Shengmai Powder, Xuefu Zhuyu Decoction, Linggui Zhugan Decoction, and Shenfu Decoction, have been discovered. This study provided data for clinical medication and drug development for heart failure after myocardial infarction.
目的:系统评价养心氏片治疗冠心病经皮冠状动脉介入术(percutaneous coronary intervention,PCI)术后的有效性.方法:检索国内外6个数据库(中国知网、中国生物医学文献数据库、万方数据库、维普中文科技期刊数据库、循证医学数据库、PubMed),时间从建库起至2020年11月,收集养心氏片治疗冠心病PC1术后的随机对照研究.筛选文献、提取资料并评价纳入研究的偏倚风险后,采用RevMan 5.3软件进行Meta分析,并按照GRADE标准进行证据质量评价.结果:纳入6项符合标准的研究,纳入研究对象共504例.Meta分析显示:相对于对照组,养心氏片试验组能显著改善心绞痛疗效[RR=1.42,95%CI(1.21,1.66),P<0.0001],对中医证候[RR=1.57,95%CI(0.89,2.78),P=0.12]及6分钟步行距离(6-MWT)[MD=32.33,95%CI(-1.83,66.49),P=0.06]无影响,对主要心血管不良事件(major adverse cardio-vascular events,MACE)发生率、西雅图心绞痛量表(seattle angina questionnaiire,SAQ)进行描述性分析,提示养心氏片可降低MACE发生率、提高SAQ积分,差异有统计学意义(P<0.05).GRADE证据评级显示结局指标的证据质量评级为极低级.结论:常规西药治疗加用养心 氏片可以降低冠心病PCI术后MACE发生率,提高治疗有效率,减少心绞痛症状,提高生活质量.
目的:利用生物信息学和机器学习筛选心肌梗死后心室重构(VRpMI)中的关键基因,并探索其对VRp-MI的诊断价值.方法:从GEO数据库分别下载GSE132143中健康人和VRpMI患者心室组织的测序数据,猪心肌梗死后6个月梗死区和梗死远端区组织的测序数据,GSE775中小鼠心肌梗死后48 h、8周及正常小鼠心室组织的表达谱数据.基于健康人和VRpMI患者心室组织的测序数据,利用edgeR包和加权基因共表达网络分析筛选重要差异表达基因(DEG);通过LASSO算法和SVM-RFE算法筛选关键基因,并利用自身数据和猪、小鼠数据分析关键基因诊断VRpMI的价值;最后,对关键基因开展单基因的基因集富集分析.结果:共获得355个重要DEG,从中筛选出1个关键基因即神经元正五聚蛋白2(NPTX2).NPTX2在自身数据和小鼠、猪验证数据中的AUC(95%CI)分别为0.996(0.984~1.000)、0.972(0.895~1.000)和0.963(0.882~1.000).单基因的基因集富集分析显示,NPTX2富集于心肌收缩、鞘脂类代谢、细胞凋亡、谷胱甘肽代谢等19个信号通路.结论:NPTX2可能为诊断VRpMI的潜在生物标志物.
目的:通过网络药理学及分子对接技术探讨基于"心肝同治"理论的宣痹通瘀方治疗冠状动脉粥样硬化性心脏病(coronary atherosclerotic heart disease,CHD)的作用机制.方法:通过TCMSP数据库获得药物活性成分及靶点,利用Uniprot及Swiss Target Prediction数据库补充部分活性成分的预测靶点,利用PharmGKB、OMIM及DisGeNET数据库获得CHD和非酒精性脂肪肝(nonalcoholic fatty liver disease,NAFLD)靶点,利用韦恩软件获得药物和疾病交集靶点并导入STRING数据库进行蛋白互作,利用Cytoscape软件构建"中药-成分-交集靶点"网络图和蛋白互作图,利用eFP数据库进行基因定位,运用Autodock vina软件对核心靶点与其对应成分进行分子对接,最后运用R软件对交集靶点进行GO功能富集和KEGG富集分析.结果:宣痹通瘀方有718个化合物64个候选活性成分591个靶点及与疾病共同靶点130个,根据eFP数据库基因定位显示,心脏存在41个特异性/相对高表达的靶点,肝脏存在62个特异性/相对高表达的靶点,共有18个表达量相近的靶点,9个不表达靶点;分子对接表明RAC-α丝氨酸/苏氨酸蛋白激酶(RAC-alpha serine/threonine-protein kinase,AKT1)、肿瘤坏死因子(tumor necrosis factor,TNF)、磷脂酰肌醇-3-激酶催化亚基α(phosphoinositide 3 kinase catalytic alpha polypeptide,PIK3CA)、转录因子p65(transcription factor p65,RELA)、细胞肿瘤抗原p53(cellular tumor antigen p53,TP53)与其对应成分有较好的结合能力.最后,GO功能及KEGG富集分析表明,主要涉及的生物过程有调节脂多糖的反应、类固醇代谢、转录因子活性、氧化应激反应及脂质代谢等,参与的信号途径有脂酰肌醇3-激酶(phosphoinositide 3-kinase,PI3K)/蛋白激酶B(protein kinase B,AKT)、缺氧诱导因子(hypoxia inducible factor-1,HIF)-1及丝裂原活化蛋白激酶(mitogen activated protein kinase,MAPK)等.结论:通过网络药理学及分子对接可知,宣痹通瘀方治疗疾病具有多组分、多脏腑、多靶点、多途径的特点,亦初步揭示了其"心肝同治"理论的内涵,为进一步深入实验研究奠定了基础.
在分析国内外心血管病健康管理现状的基础上,提出有必要开展基于家庭-社区/乡村医师-三级医院防控体系的心血管病中医健康管理.在心血管病中医健康管理指南的研制过程中,建议充分了解基层心血管病中医健康管理工作中的临床问题,注重临床问题的构建;按照心血管病-中医健康监测/风险评估/干预模式检索证据,进行证据评价后按照心血管病-中医健康监测/风险评估、心血管病-中医证型-干预模式合并证据,同时结合基层医疗现状调研结果形成适用于基层心血管病患者健康管理的推荐意见;突出包括中药、中医适宜技术、中医康复调摄方案在内的中医干预方案,区分家庭、社区/乡村医师、三级医院的功能定位,形成以"患者为核心、社区/乡村医师为执行主体、三级医院专科医师为主导"的心血管病中医健康管理体系.
目的 ·基于基因表达数据库(gene expression omnibus,GEO)运用生物信息学分析筛选与小鼠心肌缺血再灌注损伤(myocardium ischemia-reperfusion injury,MIRI)相关的潜在枢纽(hub)基因.方法 ·从GEO数据库中获取小鼠MIRI数据集GSE61592、GSE83472和GSE160516.利用limma包筛选各数据集中差异表达基因(differentially expressed genes,DEGs),再用稳健排序整合(robust rank aggregation,RRA)方法筛选稳健DEGs.构建稳健DEGs的蛋白质-蛋白质相互作用(protein-protein interaction,PPI)网络,并筛选PPI网络中的子模块和hub基因,利用clusterProfiler包对稳健DEGs、最重要子模块基因和hub基因进行基因本体论(gene ontology,GO)和京都基因与基因组百科全书(Kyoto Encyclopedia of Genes and Genomes,KEGG)通路富集分析.将18只6~8周龄的C57BL/6 J雄性小鼠随机分为假手术(sham)组和MIRI组,每组9只,通过结扎冠状动脉左前降支,缺血30 min再灌注24 h,来构建MIRI模型.采用反转录-定量聚合酶链反应(reverse transcription-quantitative polymerase chain reaction,RT-qPCR)检测hub基因mRNA的表达情况.结果 ·RRA法在3个数据集中共鉴定出294个稳健DEGs.在PPI网络中,共筛选14个子模块,其中模块1最重要;共发现17个关键基因.GO和KEGG分析显示,稳健DEGs、模块1中的基因和hub基因主要涉及调控炎性细胞的迁移、趋化因子和细胞因子及其受体活性、Toll样受体等生物学功能和通路.RT-qPCR结果显示,与sham组相比,MIRI组小鼠心肌中趋化因子(C-C基序)配体4[chemokine (C-C motif) ligand 4,Ccl4]、Ccl6、Ccl7、趋化因子(C-X-C基序)受体4[chemokine (C-X-C motif) receptor 4,Cxcr4]、趋化因子(C-C基序)受体2[chemokine (C-C motif) receptor 2,Ccr2]、信号调节蛋白β1(signal-regulatory protein β l,Sirpb1)、低亲和力免疫球蛋白γ Fc区受体Ⅱb(low affinity immunoglobulin gamma Fe region receptor Ⅱb,Fcgr2b)、白细胞表面抗原Cd53(leukocyte surface antigen CD53,Cd53)、花生四烯酸5-脂氧合酶激活蛋白(arachidonate 5-1ipoxygenase activating protein,Alox5ap)、髓样分化初级反应基因88(myeloid differentiation primary response gene 88,Myd88、巨噬细胞清道夫受体1(macrophage scavenger receptor 1,Msr1)、基质金属肽酶14 (matrix metallopeptidase 14,Mmp14)、髓样细胞上表达的触发受体2(triggering receptor expressed on myeloid cells 2,Trem2)、桩蛋白(leupaxin,Lpxn)的mRNA表达上调,而低亲和力免疫球蛋白γ Fc区受体Ⅲ(low affinity immunoglobulin gamma Fc region receptor Ⅲ,Fcgr3)、补体C1q亚组分亚单位B(complementC1q subcomponent subunitB,C1qb)、去整合素和含金属蛋白酶结构域蛋白(a disintegrin and metalloproteinase domain-containing protein 8,Adam8)的mRNA表达未见差异.回顾文献,17个hub基因中Trem2、Lpxn、Cd53、Alox5ap、Sirpb1、Fcgr2b这6个基因未见报道参与MIRI.结论 ·该研究挖掘出小鼠MIRI相关的6个潜在hub基因,可为进一步探讨MIRI的分子机制和治疗靶点提供新的思路和切入点.
Background Myocardial ischemia-reperfusion injury (MIRI) has become a thorny and unsolved clinical problem. The pathological mechanisms of MIRI are intricate and unclear, so it is of great significance to explore potential hub genes and search for some natural products that exhibit potential therapeutic efficacy on MIRI via targeting the hub genes. Methods First, the differential expression genes (DEGs) from GSE58486, GSE108940, and GSE115568 were screened and integrated via a robust rank aggregation algorithm. Then, the hub genes were identified and verified by the functional experiment of the MIRI mice. Finally, natural products with protective effects against MIRI were retrieved, and molecular docking simulations between hub genes and natural products were performed. Results 230 integrated DEGs and 9 hub genes were identified. After verification, Emr1, Tyrobp, Itgb2, Fcgr2b, Cybb, and Fcer1g might be the most significant genes during MIRI. A total of 75 natural products were discovered. Most of them (especially araloside C, glycyrrhizic acid, ophiopogonin D, polyphyllin I, and punicalagin) showed good ability to bind the hub genes. Conclusions Emr1, Tyrobp, Itgb2, Fcgr2b, Cybb, and Fcer1g might be critical in the pathological process of MIRI, and the natural products (araloside C, glycyrrhizic acid, ophiopogonin D, polyphyllin I, and punicalagin) targeting these hub genes exhibited potential therapeutic efficacy on MIRI. Our findings provided new insights to explore the mechanism and treatments for MIRI and revealed new therapeutic targets for natural products with protective properties against MIRI.
Objective To summarize the medication rules of Chinese herbs to treat heart failure with preserved ejection fraction (HFPEF) based on data mining and to provide references for clinical utilization. Methods The China National Knowledge Infrastructure (CNKI), Wanfang database (Wanfang), VIP database (VIP), Chinese Biomedical Literature (CBM), PubMed, Embase, and Cochrane Library databases were searched from inception to October 2021 to identify relevant literature on treating HFPEF with Chinese herbs. Microsoft Excel 2019 was used to set up a database, and then, association rule analysis and hierarchical cluster analysis were performed by using apriori algorithm and hclust function respectively in R-Studio (Version 4.0.3). Results A total of 182 qualified papers were included, involving a total of 92 prescriptions, 130 Chinese herbs, and 872 individual herbs prescribed, with an average of 9.5 herbs per prescription. The six most frequently prescribed herbs were Astragali Radix (Huangqi), Salviae Miltiorrhizae Radix Et Rhizoma (Danshen), Poria (Fuling), Glycyrrhizae Radix Et Rhizoma (Gancao), Cinnamomi Ramulus (Guizhi), and Ginseng Radix Et Rhizoma (Renshen). There were 35 herbs used more than 5 times, involving 11 efficacy categories. The top three categories were deficiency-tonifying herbs, blood-activating and stasis-removing herbs, and dampness-draining diuretic herbs. The most commonly used herbs were mainly warm and sweet. The primary meridian tropisms were Lung Meridian, Heart Meridian and Spleen Meridian. Association rule analysis yielded 26 association rules, such as Astragali Radix (Huangqi) & Salviae Miltiorrhizae Radix Et Rhizoma (Danshen), Poria (Fuling), Cinnamomi Ramulus (Guizhi) & Atractylodis Macrocephalae Rhizoma (Baizhu). Hierarchical cluster analysis yielded four herb classes, and their functions were mainly qi-replenishing and yang-warming, blood-activating and diuresis-inducing. Conclusions HFPEF is the syndrome of root vacuity and tip repletion, and its core pathogenesis is "deficiency", "stasis", and "water", with "deficiency" being the most principal, which is closely related to Xin (heart), Fei (Lung), and Pi (Spleen). The treatment of this disease occurs by improving qi, warming yang, activating blood and inducing diuresis. Astragali Radix (Huangqi) with Salviae Miltiorrhizae Radix Et Rhizoma (Danshen) is the basic combination of herbs applied.
目的:基于生物信息学分析和网络药理学探讨黄连解毒汤(HLJDD)延缓或抑制动脉粥样硬化(AS)由稳定斑块到破裂过程的作用机制.方法:从GEO和ArrayExpress数据库中获取含有人颈AS稳定和破裂斑块的数据集;利用limma包和wilcoxTest筛选差异表达基因(DEGs),再用稳健排序整合(RRA)方法筛选稳健DEGs,并进行富集分析.利用TCMSP和Swiss Target Prediction数据库筛选HLJDD的活性成分及其作用靶点,并与稳健DEGs取交集,获取HLJDD-AS交集DEGs.对交集DEGs进行功能富集分析,并构建蛋白互作(PPI)网络,筛选PPI网络中的子模块和Hub基因.利用Autodock Vina软件将Hub基因与其所对应HLJDD的活性成分进行分子对接.结果:RRA法共鉴定出864个稳健DEGs,其功能主要涉及中性粒细胞的脱颗粒、活化、炎症反应、趋化因子信号通路、PPAR信号通路、细胞黏附分子等.筛选出HLJDD有84个活性成分、928个作用靶点,获得HLJDD-AS交集DEGs有42个.GO和KEGG分析显示,交集DEGs主要涉及胶原蛋白的分解代谢、组织重构、中性粒细胞的脱颗粒、活化、PPAR信号通路、补体与凝血级联反应等.在PPI网络中,共筛选2个子模块,7个Hub基因.分子对接结果显示,7个Hub基因与其对应HLJDD的活性成分表现出了良好的亲和力.结论:本研究揭示了以清热解毒为治则的HLJDD有效抑制或延缓AS斑块破裂的作用机制,为中医从毒论治AS易损斑块提供一定的科学依据.
目的:探讨冠心病心力衰竭气虚血瘀证严重程度与心功能指标、能量代谢指标、凝血功能指标、炎性因子指标之间的相关性,为冠心病心力衰竭气虚血瘀证的生物学基础研究提供科学依据.方法:连续收集200例冠心病心力衰竭气虚血瘀证患者作为研究组,根据气虚血瘀证评分划为轻、中、重3组,并纳入40例同期健康体检者作为对照组,完成各组心功能指标、能量代谢指标、凝血相关指标及炎性因子等生物学指标的采集.比较各组指标,采用Spearman分析差异指标与气虚血瘀证严重程度的相关性,同时使用有序Logistic回归分析气虚血瘀证严重程度的风险因素.结果:冠心病心力衰竭气虚血瘀证患者存在能量代谢、凝血功能、炎性因子及心功能相关指标的差异,气虚血瘀证轻、中、重3组间N末端B型利钠肽原(NT-ProBNP),6分钟步行试验(6MWT),心肌型-脂肪酸结合蛋白(H-FABP),凝血酶原时间(PT),活化部分凝血活酶时间(APTT),肿瘤坏死因子-α(TNF-α),一氧化氮(NO)水平差异具有统计学意义(P<0.05);气虚血瘀证严重程度与NT-proBNP(r=0.144),PT(r=0.173),APTT(r=0.144)水平呈正相关,与6MWT(r=-0.287)水平呈负相关;6MWT[比值比(OR) =0.995,95%置信区间(CI)0.991~0.998),P<0.01],APTT(OR=1.088,95%CI 1.021~1.157,P<0.01)指标是冠心病心力衰竭气虚血瘀证严重程度的独立影响因素.结论:冠心病心力衰竭气虚血瘀证严重程度与NT-ProBNP,6MWT,H-FABP,PT,APTT,TNF-α,NO指标密切相关,且6MWT,APTT指标可作为独立影响因素,用于评估冠心病心力衰竭气虚血瘀证患者的严重程度.