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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 (\u0394SAQ-AF\u2009\u2265\u200920) (12.78% at Day 30, 95% confidence interval [CI] 5.86\u201319.71%, <jats:italic>P<\/jats:italic>\u2009=\u20090.0003, 13.82% at Day 60, 95% CI 6.82\u201320.82%, <jats:italic>P<\/jats:italic>\u2009=\u20090.0001 and 8.95% at Day 90, 95% CI 2.06\u201315.85%, <jats:italic>P<\/jats:italic>\u2009=\u20090.01). We also found that there were no significant differences in new-onset major vascular events (<jats:italic>P<\/jats:italic>\u2009=\u20090.8502) and serious adverse events (<jats:italic>P<\/jats:italic>\u2009=\u20090.9105) 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<jats:sub>summary<\/jats:sub> 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 (\u0394SAQ-AF, the change in SAQ-AF at Day 30 from baseline) calculated by WGCNA, was identified in the population with the best effect (\u0394SAQ-AF\u2009\u2265\u200940), 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 (<jats:italic>r<\/jats:italic><jats:sup>2<\/jats:sup>: 0.8204, <jats:italic>P<\/jats:italic>\u2009=\u20090.019) 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).<\/jats:p>","DOI":"10.1038\/s41392-021-00741-x","type":"journal-article","created":{"date-parts":[[2021,9,1]],"date-time":"2021-09-01T13:04:06Z","timestamp":1630501446000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":36,"title":["Detection of an anti-angina therapeutic module in the effective population treated by a multi-target drug Danhong injection: a randomized 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