Behavioral and ecotoxicology of sulfonamide metabolites in the aquatic environment.

Sulfonamides (SAs) are the first broad-spectrum synthetic antimicrobial agents used in human health and veterinary medicine. The majority of SAs entering human body is discharged into aquatic environment in the form of parent material or metabolites. The residues of SAs and their metabolites in the aquatic environment and the development of drug resistance can be serious threats to ecosystems and human health. We summarized recent advances in the research of SAs. The main metabolite types of SAs and the distribution characteristics of metabolites in different aquatic environments were introduced. The ecotoxicology of SAs metabolites, especially the distribution and hazards of sulfonamide resistance genes (sul-ARGs), were discussed with emphasis. Finally, the future research works were proposed. This paper could provide basic information for further research on SAs.

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).

The Correlation Between Urinary Sodium Excretion and Blood Pressure in Hospitalized Adult Patients with Hypertension.

INTRODUCTION: This study was designed to understand the baseline salt intake of adult patients with hypertension in Shanxi Province, and to analyze the correlation between urinary sodium excretion and blood pressure. METHODS: From June 2018 to December 2019, 16 hospitals with regional representativeness and experimental conditions in Shanxi Province were selected, and 643 eligible adult inpatients with primary hypertension were enrolled from these hospitals. The ages of patients ranged from 18 to 80 years. A 24-h ambulatory blood pressure monitoring was performed, and morning urine sodium concentration and 24-h urine sodium excretion were measured. The correlation between urinary sodium excretion and blood pressure in adult patients with hypertension was analyzed. RESULTS: The baseline salt intake of the adult patient participants with hypertension in Shanxi Province was 11.51 g/day. The average 24-h urinary sodium excretion of all observed subjects was 191.90 ± 98.18 mmol. The 24-h urinary sodium excretion and morning urinary sodium concentration were significantly positively correlated with systolic and diastolic blood pressure following adjustment of confounding factors, including gender, age, body weight, and smoking. CONCLUSION: The morning urine sodium concentration and 24-h urine sodium excretion were significantly positively correlated with blood pressure. High sodium excretion may be a risk factor for rhythm abnormalities in non-dipper pattern blood pressure. The control of urinary sodium concentration can thus be an important strategy for regulating abnormal blood pressure rhythm.

[Response of Bacteriohopanepolyols to Hypoxic Conditions in the Surface Sediments of the Yangtze Estuary and Its Adjacent Areas].

Bacteriohopanepolyols (BHPs), as a novel bacterial biomarker, show clear potential for tracking organic matter sources and environmental change. To evaluate BHPs as indicators of seasonal hypoxia in the Yangtze Estuary and its adjacent areas, the composition, distribution, and source of BHPs in surface sediments were analyzed using high-performance liquid chromatography-atmospheric pressure chemical ionization-mass spectrometry (HPLC-APCI-MS). A total of 12 BHPs were detected with a normalized TOC concentration of 3.79-269 µg·g-1. The BHPs present in the surface sediments were dominated by bacteriohopanetetrol (BHT), 2-methyl-BHT, amino-BHPs, and adenosylhopane and its homologues, accounting for 40%, 22%, 12%, and 4% of the total BHPs, respectively. Each of these components and their corresponding indices show clear spatial trends. Specifically, BHT showed an "offshore increase" trend, which was mainly attributed to marine autochthonous inputs; and soil marker BHPs including adenosylhopane, which were dominated by terrestrial sources, showed an "offshore decrease" trend. The Rsoil index indicated a similar spatial pattern to the soil marker BHPs, with the relative contribution of terrestrial organic matter decreasing from 61.5% in coastal waters to 1.66% in the open ocean. This suggests that the organic matter in the coastal waters was mainly derived from terrestrial sources while marine sources were dominant in the open ocean. BHT-Ⅱ, the BHT stereoisomer, was derived from anaerobic ammonium oxidizing bacteria. High BHT-Ⅱ ratios were consistent with seasonal hypoxic zones in the Yangtze Estuary and, furthermore, these ratios were significantly negatively correlated with dissolved oxygen (DO) concentrations in the bottom waters. These observations indicate that hypoxic environments are beneficial to BHT-Ⅱ production, implying that BHT-Ⅱ can be used as an indicator of marine hypoxia.