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).

[Release and supplement of carbon, nitrogen and phosphorus from jellyfish (Nemopilema nomurai) decomposition in seawater].

Abstract: Jellyfish bloom has been increasing in Chinese seas and decomposition after jellyfish bloom has great influences on marine ecological environment. We conducted the incubation of Nemopilema nomurai decomposing to evaluate its effect on carbon, nitrogen and phosphorus recycling of water column by simulated experiments. The results showed that the processes of jellyfish decomposing represented a fast release of biogenic elements, and the release of carbon, nitrogen and phosphorus reached the maximum at the beginning of jellyfish decomposing. The release of biogenic elements from jellyfish decomposition was dominated by dissolved matter, which had a much higher level than particulate matter. The highest net release rates of dissolved organic carbon and particulate organic carbon reached (103.77 ± 12.60) and (1.52 ± 0.37) mg · kg⁻¹ · h⁻¹, respectively. The dissolved nitrogen was dominated by NH4⁺-N during the whole incubation time, accounting for 69.6%-91.6% of total dissolved nitrogen, whereas the dissolved phosphorus was dominated by dissolved organic phosphorus during the initial stage of decomposition, being 63.9%-86.7% of total dissolved phosphorus and dominated by PO4³â»-P during the late stage of decomposition, being 50.4%-60.2%. On the contrary, the particulate nitrogen was mainly in particulate organic nitrogen, accounting for (88.6 ± 6.9) % of total particulate nitrogen, whereas the particulate phosphorus was mainly in particulate. inorganic phosphorus, accounting for (73.9 ±10.5) % of total particulate phosphorus. In addition, jellyfish decomposition decreased the C/N and increased the N/P of water column. These indicated that jellyfish decomposition could result in relative high carbon and nitrogen loads.

Jellyfish (Cyanea nozakii) decomposition and its potential influence on marine environments studied via simulation experiments.

A growing body of evidence suggests that the jellyfish population in Chinese seas is increasing, and decomposition of jellyfish strongly influences the marine ecosystem. This study investigated the change in water quality during Cyanea nozakii decomposition using simulation experiments. The results demonstrated that the amount of dissolved nutrients released by jellyfish was greater than the amount of particulate nutrients. NH4(+) was predominant in the dissolved matter, whereas the particulate matter was dominated by organic nitrogen and inorganic phosphorus. The high N/P ratios demonstrated that jellyfish decomposition may result in high nitrogen loads. The inorganic nutrients released by C. nozakii decomposition were important for primary production. Jellyfish decomposition caused decreases in the pH and oxygen consumption associated with acidification and hypoxia or anoxia; however, sediments partially mitigated the changes in the pH and oxygen. These results imply that jellyfish decomposition can result in potentially detrimental effects on marine environments.