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.
Coronary heart disease(CHD) is a common chronic disease in clinic.This article explained the role of simultaneous treatment of heart and liver in angina pectoris of CHD from three aspects: physiology and pathology, Qi and blood, and emotions.Based on this theory, Professor HUANG Yongsheng′s understanding of this clinical complex disease was discussed, and the role of the liver in the course of coronary heart disease and angina pectoris was managed by using contingency method, that is, on the basis of strengthening spleen, supplementing Qi and nourishing kidney, the methods of softening liver, soothing liver, purging liver, warming liver and nourishing liver were applied respectively.Regulating liver method should be throughout the treatment of coronary heart disease.
目的:本研究旨在识别可能与动脉粥样硬化斑块破裂(APR)有关的关键免疫相关基因和潜在治疗药物.方法:下载GSE41571、GSE120521和E-MTAB-2055数据集并合并为一个数据集.提取免疫相关差异表达基因(DEIRGs),并构建DEIRGs的蛋白-蛋白相互作用(PPI)网络,利用分子复合物检测(MCODE)插件筛选关键hub基因.然后,利用cMap预测靶向DEIRGs治疗AS斑块破裂的候选化合物,并将其与hub基因进行了分子对接.同时,评价了hub基因的诊断效能,并开展hub基因的单基因基因集富集分析(GSEA).结果:共获得29个DEIRGs,筛选出 8 个 hub 基因(即 CD14、CSF1R、FCER1G、FCGR3A、HCST、ITGB2、S100A9 和 TYROBP).cMap 预测结果显示,9个候选化合物表现出了靶向DEIRGs治疗APR的潜在作用.8个hub基因在合并数据集中的曲线下面积(area under the curves,AUCs)均大于0.7,提示其具有良好的诊断APR的效能.单基因GSEA显示,8个hub基因高表达组共同富集到了 B细胞受体信号通路、趋化因子信号通路、NOD样受体信号通等16个信号通路.结论:本研究发现了 8个hub基因在APR的进展过程中起关键作用,9个候选化合物表现出了靶向DEIRGs治疗APR的潜在作用,结果为后续从免疫学角度探索APR的机制及治疗提供了新的思路和切入点.
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.
目的 单细胞RNA测序(scRNA-Seq)为深入探析不同细胞类型中单细胞与机体的关系提供了新的方法和思路.文中旨在利用scRNA-Seq筛选颈动脉粥样硬化(CAS)中巨噬细胞的特征基因.方法 从GEO数据库中下载单细胞测序数据集GSE159677,进行预处理、质控、降维聚类及注释,利用FindAllMarker函数筛选正常组和CAS组间的差异表达基因(DEGs)及CAS组巨噬细胞的特异性DEGs,将两者取交集获取共同DEGs,并利用clusterProfiler包对共同DEGs进行富集分析.其次,构建共同DEGs的蛋白互作网络,并筛选巨噬细胞的特征hub基因.然后,下载基因芯片数据集GSE43292,利用pROC包绘制巨噬细胞特征hub基因的受试者工作特征曲线,以评价其诊断效能;分别使用CIBERSORT和ssGSEA算法对所有样本中免疫细胞的浸润模式进行分析.采用Pearson法对GSE43292数据集中特征hub基因与CAS样本巨噬细胞的浸润模式进行相关性分析.结果 共筛选47个共同DEGs,主要涉及调控中性粒细胞介导的免疫反应、PPAR通路等生物学功能和通路.进一步利用cytoHubba插件共鉴定出5个巨噬细胞特征hub基因即CLU、CTSD、CTSB、CTSL、CTSZ.ROC分析显示,5个特征基因均表现出了良好的诊断CAS的效能.两种免疫细胞浸润算法的结果均提示,巨噬细胞在AS组织中的浸润比例较对照样本高.CIBERSORT算法结果显示,巨噬细胞含量的相对比例与CLU(r=-0.39,P=0.029)呈负相关性;与CTSD(r=0.83,P<0.001)、CTSB(r=0.76,P<0.001)、CTSL(r=0.85,P<0.001)、CTSZ(r=0.82,P<0.001)均表现出了明显的强正相关性(P<0.05).ssGSEA算法结果显示,巨噬细胞含量的相对比例与CLU呈一定的负相关性(P<0.05);与CTSD、CTSB、CTSL、CTSZ均表现出了明显的强正相关性.结论 CLU、CTSD、CTSB、CTSL、CTSZ为CAS的潜在巨噬细胞特征基因,可为后续探索CAS进展的免疫学机制、潜在临床诊断标志物的开发以及靶向巨噬细胞防治CAS提供了新的思路和切入点.
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.
单细胞测序技术近些年来发展迅猛,能够在单细胞水平上对基因组、转录组等遗传信息进行测序分析,使人们对多种疾病组织中细胞的分布状态、相互作用和细胞异质性方面有了更深入的了解.动脉粥样硬化(AS)是导致冠心病等心血管疾病的重要原因,单细胞测序技术已初步应用于AS的研究.文章就单细胞测序技术的发展和在AS中的应用以及AS的分子机制和单细胞测序技术存在的问题和可能的解决方法进行综述.
目的:观察中药热熨神阙穴联合耳穴埋豆治疗腹腔镜胆囊切除术后肠功能恢复的临床疗效.方法:将80例腹腔镜胆囊切除术后患者的肠功能恢复情况随机分为观察组和对照组各40例.对照组给予腹腔镜术后常规治疗护理,观察组在给予对照组治疗护理的基础上加用中药热熨神阙穴联合耳穴埋豆治疗.比较两组患者术后肠鸣音恢复时间,首次排气时间,首次排便时间和临床疗效.结果:观察组患者的肠鸣音恢复时间,首次排气时间,首次排便时间均早于对照组(P<0.05),观察组的临床疗效明显高于对照组.结论:中药热熨神阙穴联合耳穴埋豆可以显著提高腹腔镜胆囊切除术后患者的肠鸣音恢复时间,首次排气时间,首次排便时间和临床疗效.
目的:研究腹腔镜胆囊切除术患者肝、胆腧穴的红外热成像特征.方法:随机选取本院中西医结合外科普外组30例腹腔镜胆囊切除术患者作为观察组,选取同期同年龄段至本院健康体检中心无身体疾患者30例作为对照组,应用ATIR-M301型非制冷医用红外热成像仪对所有参与研究者进行肝、胆腧穴的检测.观察腹腔镜胆囊切除患者术前、术后和对照组的双侧肝俞、胆俞、日月穴、章门穴的红外温度进行比较分析.结果:对照组双侧肝俞、胆俞、日月穴、章门穴的红外温度比较,无统计学意义(P>0.05);观察组腹腔镜胆囊切除术前双侧肝俞、胆俞、章门穴的红外温度,比较无差异,但双侧日月穴的红外温度比较有差异(P<0.05),且呈现出右侧高于左侧的现象;观察组腹腔镜胆囊切除术后双侧肝俞、胆俞、章门穴的红外温度比较无差异,但双侧日月穴的红外温度比较有差异(P<0.05),且呈现出右侧高于左侧的现象.结论:特定穴能反应脏腑疾病演变的相关性及特异性;日月穴热成像的结果可作为临床胆囊相关疾病诊断和治疗的科学依据.