Detection of an anti-angina therapeutic module in the effective population treated by a multi-target drug Danhong injection:a randomized trial
作者机构：Institute of Basic Research in Clinical MedicineChina Academy of Chinese Medical SciencesBeijingChina Department of CardiologyChinese PLA General HospitalBeijingChina Department of CardiologyDongfang Hospital Affiliated to Beijing University of Chinese MedicineBeijingChina Department of GeratologyPeking University Third HospitalBeijingChina Department of CardiologyXuan Wu HospitalCapital Medical UniversityBeijingChina Department of CardiologyGuang'anmen HospitalChina Academy of Chinese Medical SciencesBeijingChina Department of CardiologyFirst Affiliated Hospital of Henan University of Chinese MedicineZhengzhouHenanChina Department of CardiologyWuhan University Renmin HospitalWuhanHubeiChina Department of CardiologyWuhan University Zhongnan HospitalWuhanHubeiChina Affiliated Zhongshan Hospital of Dalian UniversityDalianLiaoningChina Department of CardiologySecond Affiliated Hospital to Hunan University of Chinese MedicineChangshaHunanChina Department of CardiologyFirst Affiliated Hospital to Changchun University of Chinese MedicineChangchunJilinChina Department of CardiologyFirst Affiliated Hospital to Shanxi Medical UniversityTaiyuanShanxiChina Department of CardiologyAffiliated Hospital of Shanxi University of Chinese MedicineXianyangShanxiChina Department of CardiologyChangsha Central HospitalChangshaHunanChina Department of CardiologyHubei Provincial Hospital of Traditional Chinese MedicineWuhanHubeiChina Department of CardiologyShanxi Provincial People's HospitalXi'anShanxiChina Department of CardiologyShanxi Province Hospital of Traditional Chinese MedicineXi'anShanxiChina Department of CardiologyXi'an City Hospital of Traditional Chinese MedicineXi'anShanxiChina Department of CardiologyShanghai Tongji HospitalShanghaiChina Department of CardiologyShanghai Municipal Hospital of Traditional Chinese MedicineShanghaiChina Department of CardiologyThe First Hospital of ChangshaChangshaHunanChina Department of CardiologyXinhua Hospital of Zhejiang ProvinceHangzhouZhejiangChina Department of CardiologySecond Affiliated Hospital of Tianjin University of Traditional Chinese MedicineZengchan DaoTianjinChina Department of Chinese medicineShanghai Tenth People's HospitalShanghaiChina Department of CardiologyChongqing City Hospital of Traditional Chinese MedicineChongqingChina Department of CardiologyThird People's Hospital of ChongqingChongqingChina Department of CardiologyFirst Affiliated Hospital of Heilongjiang University of Traditional Chinese MedicineHarbinHeilongjiangChina Department of CardiologySecond Affiliated Hospital of Heilongjiang University of Traditional Chinese MedicineHarbinHeilongjiangChina Department of CardiologyJilin Province People's HospitalChangchunJilinChina Department of CardiologyChengdu Second People's HospitalChengduSichuanChina China Academy of Chinese Medical SciencesBeijingChina Institute of Chinese Meteria MedicaChina Academy of Chinese Medical SciencesBeijingChina Beijing Genomics Institute(Shenzhen)ShenzhenGuangdongChina School of Public HealthSoutheast UniversityNanjingJiangsuChina Changzhou Hospital of Traditional Chinese MedicineChangzhouJiangsuChina
出 版 物：《Signal Transduction and Targeted Therapy》 (信号转导与靶向治疗（英文）)
年 卷 期：2021年第6卷第10期
页 面：3009-3018页
核心收录：
学科分类：0710[理学-生物学] 1002[医学-临床医学] 1001[医学-基础医学(可授医学、理学学位)] 100201[医学-内科学(含：心血管病、血液病、呼吸系病、消化系病、内分泌与代谢病、肾病、风湿病、传染病)] 10[医学]
基 金：funded by China National Science and Technology Major Project for"Significant New Drugs Development"(2011ZX09304-07) National Natural Science Foundation of China(81673833) China Fundamental Research Funds for the Central Public Welfare Research Institutes(ZZ0908029)
摘 要：It s a challenge for detecting the therapeutic targets of a polypharmacological drug from variations in the responsed networks in thedfferentiated populations with complex diseases,as stable coronary heart ***,in an adaptive,31-center,randomized,double-blind trial invoving 920 patients with moderate symptomatic stable angina treated by 14-day Danhong injection(DHI),a kind of polyphamacological drug with high quality control,or placebo(0.9%saline),with 76-day following-up,we firstly confrmed that DHl couldincrease the proportion of patients with clinically significant changes on angina-frequency assessed by Seattle Angina Questionnaire(ASAQ-AF220)(12.78%at Day 30,95%confidence interval[C]5.86-19.71%,P=0.0003,13.82%at Day 6C0,95%CI 6.82-20.82%,P=0.0001and 8.95%at Day 90,95%CI 2.06-15.85%,P=0.01).We also found that there were no significant differences in new-onset major vascularevents(P=0.8502)and serious adverse events(P=0.9105)between DHl and *** performing the RNA sequencing in 62 selectedpatients,we developed a systemic modular approach tp identfy differentilly expressed modules(DEMs)of DHI with the Z_(summay)valueless than 0 compared with the control group,calculated by weighted gene co-expression network analysis(WGCNA),and sketched out thebasic framework on a modular map with 25 functional modules targeted by ***,the effective therapeutic module(ETM),defined as the highest corelation value with the phenotype alteration(SAQ-AF,the change in SAQ-AF at Day 30 from baseline)calculatedby WGCNA,was identifed in the population with the best effect(ASAQ-AF240),which is related to anticoagulation and regulation ofcholesterol *** assessed the modular flexbility of this ETM using the global topological D value based on Euclidean distance,which is corelated with phenotype alteration(r^(2):0.8204,P=0.019)by linear *** study identified the ant-angina therapeuticmodule in the effective population treated by the multi-target
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