The triglyceride and glucose (TyG) index has been found to be significantly associated with a higher risk of mortality. However, there has been a lack of studies exploring the specific relationship between the TyG index and all-cause and cardiovascular mortality among middle-aged and elderly with hypertension. A total of 3,614 participants with hypertension were enrolled from the National Health and Nutrition Examination Survey. The TyG index was calculated using the formula log [fasting triglycerides (mg/dL) x fasting glucose (mg/dL)/2]. The Cox proportional hazard ratios were used to evaluate the association between the TyG index and the risk of mortality. Over a follow-up period of 7.87 years, 991 all-cause death and 189 cardiovascular deaths occurred. Compared with the reference quartile, the multivariate-adjusted hazard ratios and 95% confidence intervals were 1.28 (1.07-1.53; p = .006) in the fourth quartile for all-cause mortality and 0.63 (0.42-0.96; p = .031) in the second quartile for cardiovascular mortality. Dose-response analysis indicated an L-shaped relationship. The TyG index exhibited an L-shaped association with the risk of all-cause mortality among middle-aged and elderly with hypertension.

Background: Currently, there is little literature about the association between physical activity (PA) and the risk of ankylosing spondylitis (AS). The present study aimed to understand the causal relationships between PA and AS.Methods: We performed two-sample Mendelian randomization (MR) using publicly released genome-wide association studies summary statistics to estimate the causal associations of PA with AS risk. The inverse variance weighted (IVW) method was utilized as primary MR analysis. Furthermore, sensitivity, pleiotropy, and heterogeneity analyses were then conducted to assess the robustness of the findings of the present study.Results: Results of the IVW analysis suggested a protective relationship between accelerometer-based PA and AS (average acceleration, odds ratio [OR] = 0.9995, 95% CI, 0.9988–0.9999, P = 0.014). On the contrary, there was no causal relationship between accelerometer-based PA (acceleration fraction >425 mg; OR = 0.9981, 95% CI = 0.9936–1.0026, P = 0.402) and AS. Furthermore, there was no significant relationship between self-reported vigorous PA and AS (OR = 1.0005, 95% CI = 0.9875–1.0136, P = 0.943), or even between self-reported moderate-to-vigorous PA and AS (OR = 1.0000, 95% CI, 0.9947–1.0052; P = 0.990).Conclusions: The use of genetic approach in the present study revealed that total physical activity (TPA) has a protective relationship with AS risk. Furthermore, it was evident that vigorous PA or moderate-to-vigorous physical levels are not causally associated with AS. Therefore, the present study evidently supports the hypothesis that enhancing TPA rather than PA intensity is an effective prevention strategy for AS.

Leonurine, an active alkaloid extracted from Herba leonuri, is reported to have potent anti-inflammatory activity against rheumatoid arthritis (RA). However, the molecular mechanism of action of leonurine in RA remains poorly understood. In this study, we detected 3,425 mRNAs differentially expressed between CD4⁺ T cells of RA patients and those of healthy individuals using microarray raw data mining. Kyoto Encyclopedia of Genes and Genomes enrichment analysis revealed that transcriptional coactivator with PDZ-binding motif (TAZ) regulates a variety of biological processes including T-helper (Th)-17 cell development, and was thus selected for functional verification. In a naïve CD4⁺ T cell differentiation assay, we found that TAZ overexpression was associated with impaired balance between T regulatory (Treg) and Th17 cells in vitro. TAZ overexpression increased the levels of the pro-inflammatory cytokines interleukin (IL)-17, IL-1β, and tumor necrosis factor (TNF)-α and decreased that of the anti-inflammatory cytokine IL-10. Leonurine treatment had a direct recovery effect on the impaired balance and reduced the expression of TAZ and led to normalization of IL-17, IL-1β, and TNF-α and IL-10. Furthermore, IL-6 was found to promote the expression of TAZ and receptor activator of nuclear factor kappa-B ligand (RANKL), and RANK. Leonurine significantly inhibited TAZ-mediated expression of RANKL, and RANK and IL-6 in synovial fibroblasts. We conclude that the therapeutic effect of leonurine was through suppression of TAZ led to restoration of Treg/Th17 balance and suppression of synovial fibroblast action.