Herb-Drug Interaction: Effects of Relinqing® Granule on the Pharmacokinetics of Ciprofloxacin, Sulfamethoxazole, and Trimethoprim in Rats

Relinqing granule (RLQ) is the best-selling Chinese patent drug for treatment of urinary system diseases. In this study, the effects of RLQ on the pharmacokinetics of ciprofloxacin, sulfamethoxazole, and trimethoprim in SD rats were investigated. Rats were randomly divided into control group 1, control group 2, RLQ group 1, and RLQ group 2. RLQ group 1 and RLQ group 2 were treated orally with RLQ for 7 days, and rats were treated with the same volume of water in control group 1 and control group 2. Then, RLQ group 1 and control group 1 were given intragastrically ciprofloxacin on day 8, while RLQ group 2 and control group 2 were given intragastrically sulfamethoxazole and trimethoprim on day 8. Blood samples were collected and determined. There was no significant influence of pharmacokinetic parameters of trimethoprim on two groups. But some pharmacokinetic parameters of ciprofloxacin and sulfamethoxazole in RLQ pretreated rats were evidently altered (P < 0.05), which indicated that absorption of ciprofloxacin and sulfamethoxazole in RLQ pretreated rats was significantly affected. It indicated the coadministration of RLQ would have an influence on the efficacy of ciprofloxacin and sulfamethoxazole, and the doses of ciprofloxacin tablet and compound sulfamethoxazole tablet need adjustment

Application of toxicology data reliability assessment method, a toxicological data reliability evaluation tool, in the neurotoxic hazard assessment of glutamate acid and its salts

Objective This paper aims to evaluate data reliability of the neurotoxic hazard assessment of glutamate and its salts and provide recommendations, as well as to improve toxicology data reliability assessment method (TRAM) via trial application. Methods TRAM was used to evaluate the reliability of 60 articles which were selected by the method of systematic review documentation retrieval. The evaluation was based on types of toxicological data involved in each paper (laboratory animal data or human data) and they were scored by reliability criteria. The quality percentage was obtained via calculations to judge reliability categories and give recommendations. It’s necessary to note that the evaluation of each paper was independently completed by two persons in related fields. Results After three rounds of evaluation, the reliability of 12 articles were evaluated as "high" and recommended for priority use. The reliability of 43 articles was rated as "moderate" and can be used. The reliability of 5 articles was evaluated as "low" and not recommended to use. Conclusion TRAM takes both reporting quality and methodological quality into consideration, especially including human data reliability evaluation method which is absent in the other toxicology data reliability assessment tools. TRAM is more suitable for food safety risk assessment. It provides a better objective and scientific guarantee for hazard identification and risk assessment

Causal associations of genetically predicted gut microbiota and blood metabolites with inflammatory states and risk of infections: a Mendelian randomization analysis

BackgroundInflammation serves as a key pathologic mediator in the progression of infections and various diseases, involving significant alterations in the gut microbiome and metabolism. This study aims to probe into the potential causal relationships between gut microbial taxa and human blood metabolites with various serum inflammatory markers (CRP, SAA1, IL-6, TNF-α, WBC, and GlycA) and the risks of seven common infections (gastrointestinal infections, dysentery, pneumonia, bacterial pneumonia, bronchopneumonia and lung abscess, pneumococcal pneumonia, and urinary tract infections).MethodsTwo-sample Mendelian randomization (MR) analysis was performed using inverse variance weighted (IVW), maximum likelihood, MR-Egger, weighted median, and MR-PRESSO.ResultsAfter adding other MR models and sensitivity analyses, genus Roseburia was simultaneously associated adversely with CRP (Beta IVW = −0.040) and SAA1 (Beta IVW = −0.280), and family Bifidobacteriaceae was negatively associated with both CRP (Beta IVW = −0.034) and pneumonia risk (Beta IVW = −0.391). After correction by FDR, only glutaroyl carnitine remained significantly associated with elevated CRP levels (Beta IVW = 0.112). Additionally, threonine (Beta IVW = 0.200) and 1-heptadecanoylglycerophosphocholine (Beta IVW = −0.246) were found to be significantly associated with WBC levels. Three metabolites showed similar causal effects on different inflammatory markers or infectious phenotypes, stearidonate (18:4n3) was negatively related to SAA1 and urinary tract infections, and 5-oxoproline contributed to elevated IL-6 and SAA1 levels. In addition, 7-methylguanine showed a positive correlation with dysentery and bacterial pneumonia.ConclusionThis study provides novel evidence confirming the causal effects of the gut microbiome and the plasma metabolite profile on inflammation and the risk of infection. These potential molecular alterations may aid in the development of new targets for the intervention and management of disorders associated with inflammation and infections

Low-mass dark matter search results from full exposure of PandaX-I experiment

We report the results of a weakly-interacting massive particle (WIMP) dark matter search using the full 80.1\;live-day exposure of the first stage of the PandaX experiment (PandaX-I) located in the China Jin-Ping Underground Laboratory. The PandaX-I detector has been optimized for detecting low-mass WIMPs, achieving a photon detection efficiency of 9.6\%. With a fiducial liquid xenon target mass of 54.0\,kg, no significant excess event were found above the expected background. A profile likelihood analysis confirms our earlier finding that the PandaX-I data disfavor all positive low-mass WIMP signals reported in the literature under standard assumptions. A stringent bound on the low mass WIMP is set at WIMP mass below 10\,GeV/c$^2$, demonstrating that liquid xenon detectors can be competitive for low-mass WIMP searches.Comment: v3 as accepted by PRD. Minor update in the text in response to referee comments. Separating Fig. 11(a) and (b) into Fig. 11 and Fig. 12. Legend tweak in Fig. 9(b) and 9(c) as suggested by referee, as well as a missing legend for CRESST-II legend in Fig. 12 (now Fig. 13). Same version as submitted to PR