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

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 (ΔSAQ-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 Zsummary 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 (ΔSAQ-AF, the change in SAQ-AF at Day 30 from baseline) calculated by WGCNA, was identified in the population with the best effect (ΔSAQ-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 (r2: 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).

[Study on relationship between the polymorphism of angiotensin converting enzyme gene and blood stasis syndrome in patients with coronary heart disease].

OBJECTIVE: To explore the relationship between the insertion/deletion (I/D) polymorphism of angiotensin converting enzyme (ACE), and blood stasis syndrome (BSS) in patients with coronary heart disease (CHD). METHODS: The ACE gene type in 48 patients of CHD of BSS type, 52 CHD patients of non-BSS type and 54 healthy subjects (control) was determined by PCR assay, also levels of endothelin (ET), angiotensin II (Ag II), and nitric oxide (NO) were determined. RESULTS: Occurrence of DD genotype and allele genotype of ACE gene was higher in patients of BSS than that in patients of non-BSS and control (P < 0.01). ET/NO level was higher in patients of BSS than that in control (P < 0.01). ET and Ag II levels in patients of BSS were significantly higher than those in patients of non-BSS (P < 0.05) and control (P < 0.01). Levels of ET/NO and Ag II in subjects with DD genotype in various groups were higher than those in subjects with Ag II or ID genotype, the highest level occurred in patients of BSS with DD genotype, when compared with the other two groups, the difference in Ag II was significant (P < 0.05 and P < 0.01), when compared with control, the difference in ET/NO was significant (P < 0.01). CONCLUSION: DD genotype of ACE gene may be the susceptible gene of CHD in patients of BSS type.