ABSTRACT
Background: Qiliqiangxin (QLQX) capsules are a commonly used proprietary Chinese medicine for the adjuvant treatment of chronic heart failure (CHF) in China. In recent years, several randomized controlled trials (RCTs) have reported on the efficacy and safety of QLQX combined with sacubitril/valsartan for CHF. Objective: The purpose of this study was to systematically analyze the clinical efficacy and safety of QLQX combined with sacubitril/valsartan in the management of CHF and to provide clinicians as well as scientists with optimal evidence-based medical evidence. Methods: We searched RCTs to evaluate the efficacy and safety of QLQX combined with sacubitril/valsartan in the treatment of CHF in the Wanfang Database, China National Knowledge Infrastructure, China Science and Technology Journal Database, PubMed, Embase, and Cochrane Library databases from their inception until January 8, 2022. RCTs on QLQX in combination with sacubitril/valsartan for CHF were included. The outcome measures considered were total effective rate, left ventricular ejection fraction (LVEF), left ventricular end-diastolic dimension (LVEDD), 6-minute walking distance (6-MWD), and adverse events. The quality of the included RCTs was assessed thereafter using the Cochrane risk of bias tool. RevMan 5.3 software was used to conduct the meta-analysis. Results: The meta-analysis included 17 trials involving 1427 CHF patients. The results indicated that with sacubitril/valsartan administration combined with QLQX treatment, the total effective rate (relative risk (RR) = 1.24; 95% confidence interval (CI) (1.17, 1.31); p < 0.01), LVEF (mean difference (MD) = 6.20; 95% CI (5.36, 7.05; p < 0.01)), and 6-MWD (MD = 55.87; 95% CI (40.66, 71.09); p < 0.01) of CHF patients were significantly increased, and the LVEDD value of CHF patients was noted to be significantly reduced (MD = -3.98; 95% CI (-4.47, -3.48); p < 0.01). Moreover, there was no increase in the number of adverse events during treatment (RR = 0.67; 95% CI (0.33, 1.34); p < 0.01). Conclusions: This study indicated that in CHF patients, on the basis of sacubitril/valsartan treatment, combination with QLQX can potentially enhance the total effective rate, improve LVEF and 6-MWD, and reduce LVEDD values, with good safety. However, considering the poor quality of the included studies, a multicenter, randomized, double-blind controlled study is needed for further confirmation.
ABSTRACT
Epilepsy is a common neurological disorder affecting people of all ages, races and ethnic backgrounds world-wide. Vitamin B6 supplementation has been widely used as an adjuvant for treating epilepsy. However, the adverse effects, including nausea and peripheral sensory neuropathy, caused by long-term and high-dose consumption of vitamin B6 have undermined the usefulness of vitamin B6 supplementation, justifying additional experimental scrutiny of vitamin B6-associated toxicity. In the current study, we found that the presence of pyridoxine, the inactive form of B6 vitamer included in most nutrient supplements, increased the mortality of the larvae displaying chemical-induced epilepsy. The expression of leptin-b, one zebrafish ortholog of human leptin, was significantly increased in the larvae displaying seizures. Increased leptin-b expression alleviated larval seizure-like behavior when exposed to epilepsy inducer, but also increased larval mortality in the presence of pyridoxine. Meanwhile, elevated adam17 and mmp13 mRNA level were found in the larvae simultaneously exposed to epilepsy-inducer and pyridoxine. Adding TNF-α inhibitor and mmp13 inhibitor effectively improved the survival of larvae injected with leptin-b mRNA and exposed to pyridoxine subsequently. We conclude that increased leptin-b and metalloprotease expression contributed, at least partly, to the pyridoxine-associated toxicity observed in larvae displaying seizures.