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).

[Primary drug resistance of human immunodeficiency virus (HIV)among the treatment-naive individuals with HIV in China: a meta-analysis].

OBJECTIVE: To estimate the prevalence of antiretroviral drug resistance in treatment-naive individuals with human immunodeficiency virus (HIV) in China. METHODS: Five electronic databases [Chinese BioMedical Literature Database (CBM), Chinese Journal Full-text Database (CNKI), Chinese Science-Technology Journal Database (VIP), Wanfang Data, and PubMed] were searched for studies of HIV drug resistance in untreated individuals. Drug resistance data were abstracted then pooled using the random effect model. Subgroup analysis was done across sampling time, location, study population (mean age and infection status), and sample size. RESULTS: Seventy-six studies were included for our meta-analysis (46 in Chinese, 30 in English). The pooled rates of drug resistance to total, to non-nucleoside reverse transcriptase inhibitor (NNRTI), to nucleoside reverse transcriptase inhibitor (NRTI), and to protease inhibitor (PI) were 4.7% (95%CI:4.0%-5.4%), 2.3% (95%CI:1.8%-2.8%), 1.8% (95%CI:1.3%-2.3%), and 1.4% (95%CI: 1.1%-1.8%), respectively. All the rates before 2007 were higher than those for 2008 or later. Meanwhile, significant differences were found in the sample areas (P<0.05), in which, the rates in South-central and Southwest were both higher than 5%. The difference was complex between mean age and infection status subgroup, and we found the total prevalence in the group under 25 years and the newly infected, and confirmed group was lower than in the others. For sample size, all the rates in the group under 100 samples were higher than in the others, and the difference was significant (P<0.05). CONCLUSION: The prevalence of HIV primary drug resistance in China was 4.7%, which stayed low, but was also close to the line set by WHO. Enhanced surveillance for drug resistance is necessary in high epidemic areas including the South-central and Southwest China whose prevalence has crossed the line.