Despite a wealth of research linking the triglyceride glucose index (TyG index) to metabolic diseases. However, little evidence links the TyG index to all-cause or CVD mortality in middle-aged and elderly individuals with type 2 diabetes (T2D). This study analyzed data from 2998 patients with T2D who participated in the National Health and Nutrition Examination Survey (NHANES) between 1999 and 2018. The TyG index and mortality in middle-aged and elderly T2D patients were investigated using Cox regression models. The nonlinear association between the TyG index and mortality can be understood with the help of a restricted cubic spline (RCS). During a median follow-up period of 82 months, 883 fatalities were observed from all causes and 265 from CVD. The TyG index was found to have a U-shaped relationship with all-cause and CVD mortality in T2D, with cutoffs of 8.95 and 9, respectively, according to the RCS. After controlling for other factors, an increase of 1 unit in the TyG index was related to an increase of 33% in all-cause mortality and 50% in CVD mortality when TyG was ≥ 8.95 and 9. When TyG < 8.95 and 9, with the change in the TyG index, the change in all-cause and CVD death was insignificant. Patients with T2D who are middle-aged or older, especially elderly patients, have higher TyG levels associated with increased mortality. In middle-aged and elderly patients with T2D, the TyG index may predict the probability of death from any cause and death from CVD.

Background: Contemporary treatments for functional dyspepsia have limitations. Herbal medicine has been suggested as adjunctive treatment. With growing scientific recognition and public interests, an in‐depth review of this is timely.Aims/Purpose: To evaluate the therapeutic potential and problems that may be associated with the adoption of herbal medicines in functional dyspepsia.Methods: We reviewed the treatment landscape of functional dyspepsia and assessed the scientific community's interest in herbal medicine. Preclinical pharmacological and clinical trial data were reviewed for several herbal medicines available in the market. Challenges associated with adoption of herbal medicine in mainstream medicine were critically evaluated.Results: We found that herbal medicines frequently comprise a combination of herbs with multiple reported pharmacological effects on gastrointestinal motility and secretory functions, as well as cytoprotective and psychotropic properties. We identified a number of commercially available herbal products that have undergone rigorous clinical trials, involving large numbers of well‐defined subjects, reporting both efficacy and safety for functional dyspepsia. Persisting concerns include lack of rigorous assessments for majority of products, toxicity, consistency of ingredients, dose standardizations, and quality control. We provide a quality framework for its evaluation.Conclusions: We commend herbal medicine as a viable future option in managing functional dyspepsia. An attractive appeal of herbal medicine is the prospect to simultaneously target multiple pathophysiological mechanisms. Wider adoption and acceptance of herbal medicines in treatment algorithms of functional dyspepsia will require the application of the scientific rigor expected of chemical therapies, to all stages of their development and evaluation.

The purpose of this study was to investigate how aerobic exercise affects oxidative stress (OS) in patients with chronic kidney disease (CKD). Retrieval dates range from the date the database was established to 19 July 2023, without languages being restricted. A meta-analysis and sensitivity analysis were conducted using RevMan 5.3 and Stata 16.0. The meta-analysis showed that, compared to usual activity or no exercise, aerobic exercise significantly reduced the oxidative markers malondialdehyde (MDA) (mean differences (MD) - 0.96 (95% CI -1.33, - 0.59); p < 0.00001), advanced oxidation protein product (AOPP) (MD - 3.49 (95% CI - 5.05, - 1.93); p < 0.00001), F2-isoprostanes (F2-iso) (MD - 11.02 (95% CI - 17.79, - 4.25); p = 0.001). Aerobic exercise also increased the antioxidant marker superoxide dismutase (SOD) in CKD patients (standardized mean differences (SMD) 1.30 (95% CI 0.56, 2.04); p = 0.0005). Subgroup analysis showed a significant increase in glutathione peroxidase (GPX) in patients aged ≥60 years (SMD 2.11 (95% CI 1.69, 2.54); p < 0.00001). The change in total antioxidant capacity (TAC) after aerobic exercise was insignificant in patients with CKD. The trial sequential analysis supported aerobic exercise's effectiveness in improving MDA, SOD, AOPP, and F2-iso in patients with CKD. The results of this review suggest that aerobic exercise improves OS indicators (MDA, SOD, AOPP, and F2-iso) in CKD patients compared to conventional treatment or no exercise and that the effects on GPX and TAC indicators need further confirmation. For better validation of benefits and exploration of the best aerobic exercise regimen to improve OS status with CKD, further studies with high methodological quality and large sample sizes are needed.

The atherogenic index of plasma (AIP), a novel composite lipid index, is closely linked to cardiovascular disease (CVD). However, lipid levels fluctuate dynamically, and it is unclear whether there are differences in the association of single-timescale, multiple-timescale, or AIP change trajectories with new-onset cardiovascular disease. Hence, the aim of this study was to investigate the correlation between different AIP parameters and the occurrence of CVD. Data were derived from the China Health and Retirement Longitudinal Study (CHARLS) conducted in 2011, 2015, 2018, and 2020, focusing on middle-aged and elderly populations aged over 45 years. Changes in AIP were classified into three groups using K-means cluster analysis: the low-level growth group (Class 1), the medium-level growth group (Class 2), and the high-level decline group (Class 3). Furthermore, participants were grouped based on tertiles (T) of cumulative AIP (Cum-AIP). Our multivariate logistic regression model integrated adjustments for potential confounders in order to investigate the association between Cum-AIP and the occurrence of CVD. Additionally, we employed restricted cubic spline (RCS) modeling to illustrate the dose-response relationship of baseline AIP, mean AIP, and Cum-AIP with CVD risk. During the 5-year follow-up period, 927 participants experienced the onset of CVD. After controlling for various potential confounding factors, it was observed that individuals in Class 2 demonstrated a notably heightened risk of CVD (OR = 1.23, 95% CI: 1.03, 1.46) and stroke (OR = 1.35, 95% CI: 1.02, 1.80) in comparison to those in Class 1. However, there was no significant difference in the risk of heart disease (OR = 1.21, 95% CI: 0.99, 1.48). In contrast, a noteworthy correlation was solely observed in the Class 3 group concerning the risk of stroke occurrence (OR = 1.60, 95% CI: 1.06, 2.42). The adjusted OR (95% CI) for CVD in the T2 and T3 groups were 1.21 (1.00, 1.46) and 1.30 (1.05, 1.62), respectively, compared to the T1 Cum-AIP group (P for trend = 0.017). Through the RCS model, we identified a positive and linear relationship between baseline AIP, mean AIP, and Cum-AIP with the incidence of CVD. However, the association between baseline AIP and CVD was weak. Sustained elevation of AIP is linked to a heightened risk of CVD in the general population. The elevated mean, and Cum-AIP levels are associated with a heightened risk of CVD. These findings indicate that AIP can serve as a valuable indicator of dyslipidemia, and continuous monitoring and early intervention targeting AIP may contribute to a further reduction in the incidence of CVD.

Viruses suppress immune recognition through diverse mechanisms. Epstein-Barr Virus (EBV) establishes latent infection in memory B-lymphocytes and B-cell malignancies where it impacts B-cell immune function. We show here that EBV primary infection of naïve B-cells results in a robust down-regulation of HLA genes. We found that the viral encoded transcriptional regulatory factor EBNA2 bound to multiple regulatory regions in the HLA locus. Conditional expression of EBNA2 correlated with the down regulation of HLA class II transcription. EBNA2 down-regulation of HLA transcription was found to be dependent on CIITA, the major transcriptional activator of HLA class II gene transcription. We identified a major EBNA2 binding site downstream of the CIITA gene and upstream of DEXI, a dexamethasone inducible gene that is oriented head-to-head with CIITA gene transcripts. CRISPR/Cas9 deletion of the EBNA2 site upstream of DEXI attenuated CIITA transcriptional repression. EBNA2 caused an increase in DEXI transcription and a graded change in histone modifications with activation mark H3K27ac near the DEXI locus, and a loss of activation marks at the CIITA locus. A prominent CTCF binding site between CIITA and DEXI enhancers was mutated and further diminished the effects of EBNA2 on CIITA. Analysis of HiC data indicate that DEXI and CIITA enhancers are situated in different chromosome topological associated domains (TADs). These findings suggest that EBNA2 down regulates HLA-II genes through the down regulation of CIITA, and that this down regulation is an indirect consequence of EBNA2 enhancer formation at a neighboring TAD. We propose that enhancer competition between these neighboring chromosome domains represents a novel mechanism for gene regulation demonstrated by EBNA2. We describe a novel transcriptional mechanism through which EBV encoded EBNA2 down-regulates HLA class II gene expression. EBNA2 is known to be a potent transcriptional activator and strengthens enhancer formation at many sites in B-lymphocytes. We show that EBNA2 binds to an enhancer element at the DEXI gene that competes with CIITA gene promoter, leading to the down regulation of CIITA transcription. As CIITA is the master regulator of HLA class II gene expression, these findings reveal a novel, highly indirect mechanism for EBNA2 down-regulation of HLA II gene transcription. Down regulation of HLA class II gene expression by EBNA2 is functionally important for the attenuation of T-cell recognition of EBV infected cells, and likely to contribute to EBV persistence and lymphomagenesis in vivo.

Numerous studies have affirmed a robust correlation between residual cholesterol (RC) and the occurrence of cardiovascular disease (CVD). However, the current body of literature fails to adequately address the link between alterations in RC and the occurrence of CVD. Existing studies have focused mainly on individual RC values. Hence, the primary objective of this study is to elucidate the association between the cumulative RC (Cum-RC) and the morbidity of CVD. The changes in RC were categorized into a high-level fast-growth group (Class 1) and a low-level slow-growth group (Class 2) by K-means cluster analysis. To investigate the relationship between combined exposure to multiple lipids and CVD risk, a weighted quantile sum (WQS) regression analysis was employed. This analysis involved the calculation of weights for total cholesterol (TC), low-density lipoprotein (LDL), and high-density lipoprotein (HDL), which were used to effectively elucidate the RC. Among the cohort of 5,372 research participants, a considerable proportion of 45.94% consisted of males, with a median age of 58. In the three years of follow-up, 669 participants (12.45%) had CVD. Logistic regression analysis revealed that Class 2 individuals had a significantly reduced risk of developing CVD compared to Class 1. The probability of having CVD increased by 13% for every 1-unit increase in the Cum-RC according to the analysis of continuous variables. The restricted cubic spline (RCS) analysis showed that Cum-RC and CVD risk were linearly related (P for nonlinearity = 0.679). The WQS regression results showed a nonsignificant trend toward an association between the WQS index and CVD incidence but an overall positive trend, with the greatest contribution from TC (weight = 0.652), followed by LDL (weight = 0.348). Cum-RC was positively and strongly related to CVD risk, suggesting that in addition to focusing on traditional lipid markers, early intervention in patients with increased RC may further reduce the incidence of CVD.