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Detection of an anti-angina therapeutic module in the effective population treated by a multi-target drug Danhong injection: a randomized trial

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收录情况： ◇ SCIE ◇ 统计源期刊 ◇ CSCD-C ◇ 卓越：领军期刊

作者：
Jun Liu[1] * ; Dan-Dan Li[2] * ; Wei Dong[2] ; Yu-Qi Liu[2] ; Yang Wu[3] ; Da-Xuan Tang[3] ; Fu-Chun Zhang[4] ; Meng Qiu[4] ; Qi Hua[5] ; Jing-Yu He[5] ; Jun Li[6] ; Bai Du[6] ; Ting-Hai Du[7] ; Lin-Lin Niu[7] ; Xue-Jun Jiang[8] ; Bo Cui[8] ; Jiang-Bin Chen[8] ; Yang-Gan Wang[9] ; Hai-Rong Wang[9] ; Qin Yu[10] ; Jing He[10] ; Yi-Lin Mao[11] ; Xiao-Fang Bin[11] ; Yue Deng[12] ; Yu-Dan Tian[12] ; Qing-Hua Han[13] ; Da-Jin Liu[13] ; Li-Qin Duan[13] ; Ming-Jun Zhao[14] ; Cui-Ying Zhang[14] ; Hai-Ying Dai[15] ; Ze-Hua Li[15] ; Ying Xiao[15] ; You-Zhi Hu[16] ; Xiao-Yu Huang[16] ; Kun Xing[17] ; Xin Jiang[17] ; Chao-Feng Liu[18] ; Jing An[18] ; Feng-Chun Li[19] ; Tao Tao[19] ; Jin-Fa Jiang[20] ; Ying Yang[20] ; Yao-Rong Dong[21] ; Lei Zhang[21] ; Guang Fu[22] ; Ying Li[22] ; Shu-Wei Huang[23] ; Li-Ping Dou[23] ; Lan-Jun Sun[24] ; Ying-Qiang Zhao[24] ; Jie Li[24] ; Yun Xia[25] ; Jun Liu[25] ; Fan Liu[26] ; Wen-Jin He[26] ; Ying Li[26] ; Jian-Cong Tan[27] ; Yang Lin[27] ; Ya-Bin Zhou[28] ; Jian-Fei Yang[28] ; Guo-Qing Ma[29] ; Hui-Jun Chen[29] ; He-Ping Liu[30] ; Zong-Wu Liu[30] ; Jian-Xiong Liu[31] ; Xiao-Jia Luo[31] ; Xiao-Hong Bin[31] ; Ya-Nan Yu[1] ; Hai-Xia Dang[1,32] ; Bing Li[1,33] ; Fei Teng [34] ; Wang-Min Qiao[34] ; Xiao-Long Zhu[34] ; Bing-Wei Chen[35] ; Qi-Guang Chen[35] ; Chun-Ti Shen[36] ; Yong-Yan Wang[1] ; Yun-Dai Chen[2] ; Zhong Wang[1] ;
机构： [1]Institute of Basic Research in Clinical Medicine, China Academy of Chinese Medical Sciences, Beijing, China [2]Department of Cardiology, Chinese PLA General Hospital, Beijing,China [3]Department of Cardiology, Dongfang Hospital Affiliated to Beijing University of Chinese Medicine, Beijing, China [4]Department of Geratology, Peking University ThirdHospital, Beijing, China [5]Department of Cardiology, Xuan Wu Hospital, Capital Medical University, Beijing, China [6]Department of Cardiology, Guang’anmen Hospital, ChinaAcademy of Chinese Medical Sciences, Beijing, China [7]Department of Cardiology, First Affiliated Hospital of Henan University of Chinese Medicine, Zhengzhou, Henan, China [8]Department of Cardiology, Wuhan University Renmin Hospital, Wuhan, Hubei, China [9]Department of Cardiology, Wuhan University Zhongnan Hospital, Wuhan, Hubei, China [10]Affiliated Zhongshan Hospital of Dalian University, Dalian, Liaoning, China [11]Department of Cardiology, Second Affiliated Hospital to Hunan University of Chinese Medicine,Changsha, Hunan, China [12]Department of Cardiology, First Affiliated Hospital to Changchun University of Chinese Medicine, Changchun, Jilin, China [13]Department of Cardiology,First Affiliated Hospital to Shanxi Medical University, Taiyuan, Shanxi, China [14]Department of Cardiology, Affiliated Hospital of Shanxi University of Chinese Medicine, Xianyang,Shanxi, China [15]Department of Cardiology, Changsha Central Hospital, Changsha, Hunan, China [16]Department of Cardiology, Hubei Provincial Hospital of Traditional ChineseMedicine, Wuhan, Hubei, China [17]Department of Cardiology, Shanxi Provincial People’s Hospital, Xi’an, Shanxi, China [18]Department of Cardiology, Shanxi Province Hospital ofTraditional Chinese Medicine, Xi’an, Shanxi, China [19]Department of Cardiology, Xi’an City Hospital of Traditional Chinese Medicine, Xi’an, Shanxi, China [20]Department ofCardiology, Shanghai Tongji Hospital, Shanghai, China [21]Department of Cardiology, Shanghai Municipal Hospital of Traditional Chinese Medicine, Shanghai, China [22]Departmentof Cardiology, The First Hospital of Changsha, Changsha, Hunan, China [23]Department of Cardiology, Xinhua Hospital of Zhejiang Province, Hangzhou, Zhejiang, China [24]Department of Cardiology, Second Affiliated Hospital of Tianjin University of Traditional Chinese Medicine, Zengchan Dao, Tianjin, China [25]Department of Chinese medicine,Shanghai Tenth People’s Hospital, Shanghai, China [26]Department of Cardiology, Chongqing City Hospital of Traditional Chinese Medicine, Chongqing, China [27]Department ofCardiology, Third People’s Hospital of Chongqing, Chongqing, China [28]Department of Cardiology, First Affiliated Hospital of Heilongjiang University of Traditional ChineseMedicine, Harbin, Heilongjiang, China [29]Department of Cardiology, Second Affiliated Hospital of Heilongjiang University of Traditional Chinese Medicine, Harbin, Heilongjiang,China [30]Department of Cardiology, Jilin Province People’s Hospital, Changchun, Jilin, China [31]Department of Cardiology, Chengdu Second People’s Hospital, Chengdu, Sichuan,China [32]China Academy of Chinese Medical Sciences, Beijing, China [33]Institute of Chinese Meteria Medica, China Academy of Chinese Medical Sciences, Beijing, China [34]BeijingGenomics Institute (Shenzhen), Shenzhen, Guangdong, China [35]School of Public Health, Southeast University, Nanjing, Jiangsu, China [36]Changzhou Hospital of TraditionalChinese Medicine, Changzhou, Jiangsu, China
出处：
DOI： 10.1038/s41392-021-00741-x
ISSN：

摘要：
It's a challenge for detecting the therapeutic targets of a polypharmacological drug from variations in the responsed networks in the differentiated populations with complex diseases, as stable coronary heart disease. Here, in an adaptive, 31-center, randomized, double-blind trial involving 920 patients with moderate symptomatic stable angina treated by 14-day Danhong injection(DHI), a kind of polypharmacological drug with high quality control, or placebo (0.9% saline), with 76-day following-up, we firstly confirmed that DHI could increase the proportion of patients with clinically significant changes on angina-frequency assessed by Seattle Angina Questionnaire (Delta SAQ-AF >= 20) (12.78% at Day 30, 95% confidence interval [CI] 5.86-19.71%, P = 0.0003, 13.82% at Day 60, 95% CI 6.82-20.82%, P = 0.0001 and 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 vascular events (P = 0.8502) and serious adverse events (P = 0.9105) between DHI and placebo. After performing the RNA sequencing in 62 selected patients, we developed a systemic modular approach to identify differentially expressed modules (DEMs) of DHI with the Z(summary) value less than 0 compared with the control group, calculated by weighted gene co-expression network analysis (WGCNA), and sketched out the basic framework on a modular map with 25 functional modules targeted by DHI. Furthermore, the effective therapeutic module (ETM), defined as the highest correlation value with the phenotype alteration (Delta SAQ-AF, the change in SAQ-AF at Day 30 from baseline) calculated by WGCNA, was identified in the population with the best effect (Delta SAQ-AF >= 40), which is related to anticoagulation and regulation of cholesterol metabolism. We assessed the modular flexibility of this ETM using the global topological D value based on Euclidean distance, which is correlated with phenotype alteration (r(2): 0.8204, P = 0.019) by linear regression. Our study identified the anti-angina therapeutic module in the effective population treated by the multi-target drug. Modular methods facilitate the discovery of network pharmacological mechanisms and the advancement of precision medicine. (ClinicalTrials.gov identifier: NCT01681316).

基金：
China National Science and Technology Major Project for “Significant New Drugs Development” (2011ZX09304-07), National Natural Science Foundation of China (81673833), and China Fundamental Research Funds for the Central Public Welfare Research Institutes (ZZ0908029).
语种：
外文
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PubmedID：
中科院(CAS)分区：
出版当年[2020]版：
大类 | 1 区 医学
小类 | 1 区 生化与分子生物学 1 区 细胞生物学
最新[2025]版：
大类 | 1 区 医学
小类 | 1 区 生化与分子生物学 1 区 细胞生物学
JCR分区：
出版当年[2019]版：
Q1 CELL BIOLOGY Q1 BIOCHEMISTRY & MOLECULAR BIOLOGY
最新[2023]版：
Q1 BIOCHEMISTRY & MOLECULAR BIOLOGY Q1 CELL BIOLOGY

影响因子： 最新[2023版] 最新五年平均 出版当年[2019版] 出版当年五年平均 出版前一年[2018版] 出版后一年[2020版]

第一作者：
第一作者机构： [1]Institute of Basic Research in Clinical Medicine, China Academy of Chinese Medical Sciences, Beijing, China
共同第一作者：
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推荐引用方式(GB/T 7714)：
Jun Liu,Dan-Dan Li,Wei Dong,et al.Detection of an anti-angina therapeutic module in the effective population treated by a multi-target drug Danhong injection: a randomized trial[J].SIGNAL TRANSDUCTION AND TARGETED THERAPY.2021,6(1):doi:10.1038/s41392-021-00741-x.
APA：
Jun Liu,Dan-Dan Li,Wei Dong,Yu-Qi Liu,Yang Wu...&Zhong Wang.(2021).Detection of an anti-angina therapeutic module in the effective population treated by a multi-target drug Danhong injection: a randomized trial.SIGNAL TRANSDUCTION AND TARGETED THERAPY,6,(1)
MLA：
Jun Liu,et al."Detection of an anti-angina therapeutic module in the effective population treated by a multi-target drug Danhong injection: a randomized trial".SIGNAL TRANSDUCTION AND TARGETED THERAPY 6..1(2021)

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