Xinkeshu for coronary heart disease complicated with anxiety or depression: A meta-analysis of randomized controlled trials.

ETHNOPHARMACOLOGICAL RELEVANCE: The incidence of coronary heart disease (CHD) complicated with anxiety or depression is increasing year by year. However, many anti-anxiety drugs or antidepressants have a certain degree of adverse reactions and are not easily accepted by patients. Xinkeshu (XKS), as a proprietary Chinese patent medicine with "psycho-cardiology" effect, is one of the commonly used drugs in the treatment of CHD complicated with anxiety or depression in China. AIM OF THE STUDY: To systematically evaluate the efficacy and safety of XKS for CHD complicated with anxiety or depression. METHODS: Nine different electronic databases were independently searched to include randomized controlled trials (RCTs) of XKS for CHD complicated with anxiety or depression published from inception to February 2022, and the methodological quality was evaluated using the bias risk assessment tool from Cochrane Handbook 5.0 and the modified Jadad scale. Meta-analysis was performed using RevMan 5.3 and Stata 16.0 software. The GRADE Profiler 3.6.1 and TSA 0.9.5.10 beta were adopted to evaluate the certainty and conclusiveness of the evidence. RESULTS: A total of 18 RCTs involving 1907 subjects were included. There were 956 subjects in the XKS group and 951 subjects in the control group. Baseline conditions were consistent and comparable between the groups. Compared with single-use western medicine (WM), XKS combined with WM significantly reduced scores of Hamilton Anxiety Scale (HAMA) [Mean difference (MD) = -7.60, 95% confidence interval (95% CI) (-10.37, -4.83), P < 0.000 01], Zung Self-rating Anxiety Scale (SAS) [MD = -10.05, 95% CI (-12.70, -7.41), P < 0.000 01], Hamilton Depression Scale (HAMD) [MD = -6.74, 95% CI (-11.58, -1.90), P = 0.006], and Zung Self-rating Depression Scale (SDS) [MD = -10.75, 95% CI (-17.05,-4.45), P = 0.000 8], as well as improved clinical effective rate [odds ratio (OR) = 4.24, 95% CI (2.47, 7.27), P < 0.000 01]. In terms of safety, 4 studies reported the adverse reactions in detail. The severity was mild and symptoms disappeared after treatment. CONCLUSION: Current evidence indicates that XKS may be effective and safe in the treatment of patients with CHD complicated with anxiety or depression. Since the quality of the literature included in this study was generally low, there is an urgent need for more RCTs with high quality, low bias risk and sufficient sample size to validate our conclusions.

Elevated serum uric acid is not an independent risk factor for the occurrence of Type 2 diabetic kidney disease in Chinese populations.

Previous studies suggested that increased serum uric acid (SUA) level is an independent risk factor for albuminuria in Type 2 diabetes (T2D) patients. However, the association between SUA and onset of Type 2 DKD (T2DKD) remained to be clarified. This was a cross-sectional clinical study in which 1210 Chinese T2D patients were enrolled. According to the urine albumin-to-creatinine ratio (UACR), the cohort was divided into normal-albuminuria (UACR < 30 mg/g), micro-albuminuria (UACR 30-300 mg/g) and macro-albuminuria (UACR > 300 mg/g). The micro- and macro-albuminuria groups were combined into albuminuria category. Results showed that T2D patients with macro-albuminuria have significantly higher SUA than the other 2 groups (P < .001). In the binary logistic regression model, the subjects with SUA higher than 420 µmol/L were associated with a 2-fold increase in the odds of albuminuria (odds ratio = 2.024, 95% confidence interval: 1.232-3.325, P = .005), as compared with those with SUA lower than 300 µmol/L. Moreover, the multinomial regression analysis revealed that the subjects with SUA higher than 420 µmol/L had about 3-fold increase in the odds of macro-albuminuria (odds ratio = 3.758, 95% confidence interval: 2.051-6.885, P < .001), as compared with those with SUA lower than 300 µmol/L. However, SUA was not significantly associated with the presence of micro-albuminuria. Although the SUAwas not independently risk factor for micro-albuminuria, it was closely correlated with the development of macro-albuminuria in Chinese T2DKD patients. Elevated SUA may be useful for predicting the occurrence of macro-albuminuria but not onset of micro-albuminuria at the early stage of T2DKD.

Prediction of the Potential Mechanism of Triptolide in Improving Diabetic Nephropathy by Utilizing A Network Pharmacology and Molecular Docking Approach.

BACKGROUND: Triptolide (TP) is a major active component of colquhounia root tablet, which has been long been used in China to treat diabetic nephropathy (DN) due to its marked anti­inflammatory, antiproteinuric, and podocyte­protective effects. METHODS: This study investigated the anti-proteinuria activity and related signaling cascade of TP in DN by utilizing a network pharmacology and molecular docking approach. RESULTS: From the GeneCard, DisGeNET, and National Center for Biotechnology Information Gene databases, 1458 DN targets were obtained and input together with 303 TP targets into Venny2.1.0 for mapping and comparing. In total, 113 common targets of TP and DN were obtained, of which 7 targets were found to play an important role through theoretical inhibitory constant analysis. The common targets were further analyzed by Kyoto Encyclopedia of Genes and Genomes to identify the pathways related to the therapeutic effect of TP on DN. Among them, the seven targets were found to play key roles in six signaling pathways. The molecular docking results also showed TP had good binding ability to the seven targets. CONCLUSIONS: Analysis of the common targets and key pathways showed that TP can improve DN via its anti-nephritis, anti-renal fibrosis, antioxidant, and podocyte-protective effects, which might elucidate the mechanism by which TP improves renal function and reduces proteinuria in DN.

The occurrence of hypogonadotropic hypogonadism in Chinese men with type 2 diabetes.

CONTEXT: The previous studies showed that hypogonadotropic hypogonadism (HH) occurred commonly in men with type 2 diabetes. However, since all the cohorts tested were from American and European studies, the occurrence of HH/nongonadal illness (NGI) in Chinese populations is unclear. OBJECTIVE: The study aimed to explore the occurrence of HH/NGI in Chinese men with type 2 diabetes. Furthermore, the correlative factors and predictors of hypogonadism were investigated. DESIGN: We conducted a cross-sectional study of 637 Chinese men with type 2 diabetes aged 20-75 years in our clinic. The prevalence of HH/NGI was investigated by measuring serum total testosterone (TT), sex hormone-binding globulin (SHBG), luteinizing hormone (LH) and follicle-stimulating hormone (FSH) in the enrolled subjects. Free testosterone (FT) was calculated by using SHBG and TT levels and hypogonadism was defined as TT lower than 10.4 nmol/L and calculated FT (cFT) lower than 0.225 nmol/L. The LH cut-off value for defining HH/NGI was 9.4 mIU/ml. RESULTS: The results suggested that 31.9% of male Chinese type 2 diabetes patients had hypogonadism and 26.5% of subjects in our cohort were determined as HH/NGI. The occurrence of hypogonadism was markedly correlated with body mass index (BMI). There was a significant association between TT, cFT and SHBG levels with BMI. TT levels are inversely correlated with BMI and homeostasis model assessment-estimated insulin resistance (HOMA-IR) while positively related with SHBG. The cFT levels were inversely correlated with age, LH, FSH, BMI and HOMA-IR. Multiple regression analysis suggested that SHBG, BMI and HOMA-IR were significant predictors of TT and cFT. CONCLUSION: Our present study offered the first evidence that the occurrence of HH/NGI in Chinese male type 2 diabetes was 26.5%. TT and cFT were significantly correlated with BMI, SHBG and HOMA-IR in Chinese men with type 2 diabetes.

Frutescone O from Baeckea frutescens Blocked TLR4-Mediated Myd88/NF-κB and MAPK Signaling Pathways in LPS Induced RAW264.7 Macrophages.

Frutescone O was isolated from the aerial parts of Baeckea frutescens L., which was commonly used as a folk medicinal material for treating anti-inflammatory disease in South East Asia. This study aimed to investigate the anti-inflammatory activity and related signaling cascade of Frutescone O (Fru) in LPS induced RAW264.7 cells. The anti-inflammation activity of Frutescone O was determined according to the inhibitory effects on the secretion of nitric oxide (NO), expression of inducible NO synthase, and pro-inflammatory cytokines. The regulation of Myeloid differentiation factor 88 (Myd88), inhibition of NF-κB, and MAPK pathways were further investigated for molecular mechanisms. Fru significantly decreased the expression of iNOS and the production of NO in LPS-stimulated RAW264.7 cells. It also dose-dependently suppressed LPS induced expression of IL-1ß, IL-6, and TNF-α. Furthermore, Fru remarkably inhibited the upregulation of NF-κB (p50) expression in the nucleus and the phosphorylation ratio of p38, JNK, ERK, and Myd88 signaling protein. The molecular docking and cellular thermal shift assay (CETSA) results indicated that Fru participated in a robust and stable interaction with the active site of TLR4-MD2. Thus, Fru suppressed the LPS induced inflammation in RAW264.7 cells by blocking the TLR4 mediated signal transduction through the NF-κB and MAPK signaling pathways and inhibiting the Myd88 and iNOS expression.