Serum perfluoroalkyl substances and growth and development in US adolescents: a nationally representative cross-sectional study.

Per- and polyfluoroalkyl substances (PFAS), synthetic organic chemicals, have been discovered in the blood of both humans and animals throughout the world. This has raised widespread concerns about its toxicity, especially for growing children and adolescents. Most research on growth and development to date has concentrated on children at birth and during the first two years, while few studies have analyzed weight, height, and Body Mass Index (BMI) changes in children later in life. The present study aims to assess the association between serum PFAS levels and growth and development in adolescents. Through multiple linear regression, we explored the relationship between serum PFAS levels and weight, height, and BMI in adolescents (aged 12 to 19 years) participating in the 2015-2018 National Health and Nutrition Examination Survey (NHANES). After covariate adjustment, serum perfluorooctane sulfonic acid (PFOS) was associated with decreased weight-for-age z-score in females (tertile 2 of PFOS: ß = - 0.22, 95% CI: -0.68, 0.23; tertile 3 of PFOS: ß = - 0.78, 95% CI: -1.20, - 0.36; P for trend = 0.009), while serum perfluorononanoic acid (PFNA) was associated with decreased weight-for-age z-score in males (tertile 2 of PFNA: ß = 0.09, 95% CI: -0.40, 0.58; tertile 3 of PFNA: ß = - 0.44, 95% CI: -0.86, - 0.03; P for trend = 0.018).In addition, serum PFOS was associated with decreased BMI z-score in all participants (tertile 2 of PFOS: ß = - 0.15, 95% CI: -0.46, 0.16; tertile 3 of PFOS: ß = - 0.63, 95% CI: -1.06, - 0.20; P for trend = 0.013). CONCLUSION: Our findings indicate a negative association between serum PFAS levels and weight, and BMI among adolescents, and we observed that the negative association was sex-specific in weight. WHAT IS KNOWN: • Wide exposure to PFAS has led to concerns about its adverse effects, especially for children during their growth and development. • So far, much research has evaluated the effects of prenatal PFAS exposures on children, and the current results are mixed, with some research showing that there are sex differences. WHAT IS NEW: • This study investigated the relationship between serum PFAS levels and height and weight in adolescents and is a good addition to current research. • Our study found that exposure to PFAS negatively affects adolescent growth and development and that this effect is sex-specific.

Five Tibetan patent medicines orally for ischemic stroke: A systematic review and meta-analysis of randomized controlled trials.

ETHNOPHARMACOLOGICAL RELEVANCE: Tibetan Patent Medicines (TPMs) have unique advantages in the treatment of ischemic stroke (IS) with the features of multi-component, multi-channel, and multi-target. In China, five TPMs mainly consisting of precious medicinal materials such as gold, pearls, and agate are widely utilized to treat IS and have achieved good results according to the current clinical practice. AIM OF THE STUDY: To systematically evaluate the efficacy and safety of the five TPMs orally in treating IS and provide a reference for future clinical application and research. MATERIALS AND METHODS: We searched the following 24 databases up to December 11, 2022: China National Knowledge Infrastructure (CNKI), Wanfang database, China Science and Technology Journal Database, Chinese Biomedical Database (CBM), PubMed, Embase, Web of Science, MEDLINE, Scopus, the Cochrane Library, ScienceDirect, etc. Comprehensive searches for randomized controlled trials (RCTs) of the five TPMs for IS were conducted. Outcome measures included clinical effective rate, neurological impairment score, activities of daily living (ADL), hematologic indices, and adverse events (AEs). The meta-regression, subgroup analyses, and sensitivity analyses were conducted to explore the sources of heterogeneity. We assessed the evidence grade of outcomes via the GRADE system. TSA software was used for trial sequential analyses of the clinical effective rate, neurological impairment score, and ADL. RESULTS: 17 RCTs (1603 patients) met our criteria. Compared with the control groups, the five TPMs showed greater improvement in clinical effective rate (RR = 1.23, 95% CI 1.17 to 1.29, P < 0.00001), neurological impairment score (SMD = -1.71, 95% CI -2.31 to -1.10, P < 0.00001), ADL (SMD = 1.97, 95% CI 1.26 to 2.68, P < 0.00001), hematocrit (MD = -1.56, 95% CI -2.83 to -0.29, P = 0.02), and hypersensitive-c-reactive-protein (MD = -2.96, 95% CI -3.30 to -2.61, P < 0.00001). AEs were reported in four RCTs and there was no statistical difference between groups (RD = -0.00, 95% CI -0.04 to 0.03, P = 0.82). The quality of evidence of the outcomes was rated as low to very low according to the GRADE system. The results of TSA provided firm evidence for the significant effect of the five TPMs on clinical effective rate, neurological impairment score, and ADL. CONCLUSIONS: This review showed that the five TPMs were beneficial in improving clinical effective rate, neurological impairment scores, and ADL. However, no definite conclusions for hematologic indices and AEs were drawn due to insufficient studies. Further high-quality clinical trials are required to confirm these findings.

Effectiveness and safety of Ginkgo biloba extract (GBE50) in the treatment of dizziness caused by cerebral arteriosclerosis: a multi-center, double-blind, randomized controlled trial.

OBJECTIVE: To evaluate the effectiveness and safety of Ginkgo biloba extract (GBE50) in the treatment of dizziness caused by cerebral arteriosclerosis. METHODS: This was a multi-center, double-blind, double-dummy, positive-controlled, parallel randomized controlled clinical trial with 1? allocation. We recruited 404 patients with dizziness caused by cerebral arteriosclerosis (blood stasis symptom pattern) in 10 hospitals in China. GBE50 group received GBE50 and Naoxinqing tablet (NXQ) of mimetic agent, control group received NXQ and GBE50 of mimetic agent. The main outcome was Traditional Chinese Medicine (TCM) symptom pattern score of blood stasis after 6 weeks. The secondary outcomes were changes in the dizziness handicap inventory (DHI) score, vertigo visual analogue scale (VAS) score, the university of California vertigo questionnaire (UCLA-DQ) score and single-item symptom score of TCM from baseline to 2, 4 and 6 weeks. Safety indicators included the incidence of adverse events, severe adverse events and laboratory examination including blood routine, liver function, renal function, and so forth. RESULTS: The total effective rate of TCM symptom pattern score in the GBE50 group after 6 weeks of treatment was higher than that in the control group, the difference in rate was statistically significant (92.67% vs 83.07%, P = 0.004). Compared with the control group, there was no difference in the incidence of adverse reactions (9.95% vs 14.85%, P = 0.136). CONCLUSION: The treatment of dizziness caused by cerebral arteriosclerosis with GBE50 is effective, safe and reliable.

Modular Lipid Nanoparticle Platform Technology for siRNA and Lipophilic Prodrug Delivery.

Successfully employing small interfering RNA (siRNA) therapeutics requires the use of nanotechnology for efficient intracellular delivery. Lipid nanoparticles (LNPs) have enabled the approval of various nucleic acid therapeutics. A major advantage of LNPs is the interchangeability of its building blocks and RNA payload, which allow it to be a highly modular system. In addition, drug derivatization approaches can be used to synthesize lipophilic small molecule prodrugs that stably incorporate in LNPs. This provides ample opportunities to develop combination therapies by co-encapsulating multiple therapeutic agents in a single formulation. Here, it is described how the modular LNP platform is applied for combined gene silencing and chemotherapy to induce additive anticancer effects. It is shown that various lipophilic taxane prodrug derivatives and siRNA against the androgen receptor, a prostate cancer driver, can be efficiently and stably co-encapsulated in LNPs without compromising physicochemical properties or gene-silencing ability. Moreover, it is demonstrated that the combination therapy induces additive therapeutic effects in vitro. Using a double-radiolabeling approach, the pharmacokinetic properties and biodistribution of LNPs and prodrugs following systemic administration in tumor-bearing mice are quantitatively determined. These results indicate that co-encapsulating siRNA and lipophilic prodrugs into LNPs is an attractive and straightforward plug-and-play approach for combination therapy development.