Background: A gut-microbial metabolite, trimethylamine N-oxide (TMAO), has been associated with type 2 diabetes mellitus (T2DM). Few previous prospective studies have addressed associations between the changes in TMAO and T2DM incidence. Methods: Data were derived from a longitudinal cohort conducted from 2019 to 2021 in rural areas of Fuxin County, Liaoning Province, China, and 1515 diabetes-free participants aged above 35 years were included. The concentrations of serum TMAO and its precursors were measured at two time points, namely in 2019 and 2021. TMAO and TMAO changes (ΔTMAO) were separately tested in a logistic regression model. For further examination, the odds ratios (ORs) for T2DM were calculated according to a combination of TMAO levels and ΔTMAO levels. Results: During a median follow-up of 1.85 years, 81 incident cases of T2DM (5.35%) were identified. Baseline TMAO levels exhibited a nonlinear relationship, first decreasing and then increasing, and only at the highest quartile was it associated with the risk of T2DM. The OR for T2DM in the highest quartile of serum TMAO was 3.35 (95%CI: 1.55–7.26, p = 0.002), compared with the lowest quartile. As for its precursors, only choline level was associated with T2DM risk and the OR for T2DM in the Q3 and Q4 of serum choline was 3.37 (95%CI: 1.41–8.05, p = 0.006) and 4.72 (95%CI: 1.47–15.13, p = 0.009), respectively. When considering both baseline TMAO levels and ΔTMAO over time, participants with sustained high TMAO levels demonstrated a significantly increased risk of T2DM, with a multivariable-adjusted OR of 8.68 (95%CI: 1.97, 38.34). Conclusion: Both initial serum TMAO levels and long-term serum TMAO changes were collectively and significantly associated with the occurrence of subsequent T2DM events. Interventions aimed at normalizing TMAO levels, such as adopting a healthy dietary pattern, may be particularly beneficial in T2DM prevention.

Purpose: The study sought to summarize the evidence of pre-procedural atorvastatin therapy to improve the prognosis of acute coronary syndrome (ACS) patients undergoing percutaneous coronary intervention (PCI). Patients and methods: We searched PubMed and Embase from inception to July 2018 for randomized controlled trials that compared loading dose atorvastatin pretreatment with no or low dose for the prevention of cardiovascular events. The primary end points were all-cause mortality and myocardial infarction (MI) at 30 days. The secondary end point was 30-day major adverse cardiovascular events (MACE), a composite of all-cause mortality, MI, and revascularization. Results: Six trials with 4,991 individuals were included in our meta-analysis. High-dose atorvastatin preloading before PCI was associated with a 27% relative reduction in MI (OR: 0.73, 95% CI, 0.56–0.94, P=0.015). All-cause mortality was nonsignificantly reduced by early treatment with high-potency atorvastatin (OR: 0.94, 95% CI, 0.69–1.30, P=0.725). There was a 20% reduction in MACE in the group of patients treated with statin loading prior to PCI (OR: 0.80, 95% CI, 0.66–0.97, P=0.026). When stratified according to the diagnosis of ACS, the results of MACE were only significant for those ST-elevation myocardial infarction patients undergoing PCI (OR: 0.67, 95% CI, 0.48–0.94, P=0.022) and were not noted in the group of non-ST elevation ACS patients (OR: 0.65, 95% CI, 0.35–1.22, P=0.179). Conclusion: High-dose atorvastatin pretreatment leads to a significant reduction in MI and MACE at 30 days in ACS patients undergoing PCI, especially in ST-segment elevation MI.

This study investigates the role of Cathepsin D (CTSD) in diabetic vascular complications, particularly its impact on the phenotypic transformation of vascular smooth muscle cells (VSMCs) induced by advanced glycation end-products (AGEs), and explores its potential molecular mechanisms. CTSD was overexpressed in VSMCs using lentiviral vectors. Various methods, including CCK-8, immunofluorescence, SA-β-Gal staining, EdU assay, scratch assay, cell cycle analysis, and Western blotting, were employed to assess VSMC viability, proliferation, migration, senescence, and apoptosis. Additionally, transcriptomic and metabolomic analyses were conducted to investigate the molecular mechanisms underlying CTSD overexpression in VSMCs. AGEs treatment significantly inhibited CTSD expression in VSMCs, leading to reduced cell viability, enhanced proliferation and migration, increased senescence, and apoptosis. In contrast, overexpression of CTSD effectively inhibited AGEs-induced VSMCs proliferation, migration, senescence, and apoptosis. Combined transcriptomic and metabolomic analyses suggested that CTSD may affect VSMCs phenotypic transformation by inhibiting the glycolysis pathway. This study highlights the critical role of CTSD in the phenotypic transformation of VSMCs induced by AGEs and provides a new perspective for cardiovascular and cerebrovascular disease treatment. CTSD may emerge as a novel therapeutic target, though its specific molecular mechanisms and clinical application prospects in VSMCs phenotypic transformation require further investigation.

Background: The new ACC/AHA hypertension guideline lower the definition of hypertension from 140/90 mmHg to 130/80 mmHg and eliminate the category of prehypertension thus increasing the prevalence of hypertension. A purpose of this study is to explore the applicability of the new guidelines in rural China. Methods: In total, 3229 participants aged ≥35 years and free of stroke at baseline were followed for up to 4.8 years during 2012 to 2017 in a rural community-based prospective cohort study of Xifeng County. The hazard ratio (HR) and 95% Confidence interval (CI) of different blood pressure (BP) levels for risk of incident stroke were analyzed by multivariable Cox proportional hazard models. Results: During the follow-up, 81 new strokes occurred among the 3229 participants. Compared with normal BP (Systolic BP (SBP)<120 mmHg and Diastolic BP (DBP)<80 mmHg), stage 2 hypertension (SBP ≥ 140 mmHg or DBP ≥ 90 mmHg) had approximately 2.1 greater risks for stroke (HR: 2.10, 95% CI: 1.13 to 3.91, P = 0.020). However, there was no significant association between elevated (SBP:120-129 mmHg and DBP<80 mmHg), stage1 hypertension (SBP:130-139 mmHg or DBP:80-89 mmHg) and stroke incidence (HR: 0.93, 95% CI: 0.33 to 2.61, P = 0.888; HR: 0.96, 95% CI: 0.46 to 2.02, P = 0.920, respectively). An increase of the SBP by 1-SD increases the risk for stroke by 56% (HR: 1.56, 95%CI: 1.29 to 1.88, P < 0.001). An increase of the SBP by 20 mmHg increases the risk for stroke by 51% (HR: 1.51, 95%CI: 1.27 to 1.80, P < 0.001). Conclusions: Compared with normal BP, the stage 2 hypertension based on 2017 ACC/AHA guideline significantly increases the risk of stroke incidence, but this association was not observed between elevated, stage1 hypertension and stroke incidence in Chinese rural adults.

This study investigated the relationship between trimethylamine N-oxide (TMAO), its precursors (choline, betaine, and carnitine), and the prevalence of hypertension in rural northeastern China. Conducted in 2019, the cross-sectional study involved 1,899 adults aged 35 and older, with serum levels of TMAO and its precursors quantified using high-performance liquid chromatography-mass spectrometry. Hypertension was defined according to blood pressure measurements or the use of antihypertensive medications, based on the 2018 Chinese Hypertension Guidelines. Logistic regression models were utilized to assess the associations between TMAO, its precursors, and hypertension, adjusting for potential confounders such as age, sex, smoking status, and physical activity. The results revealed a significant association between TMAO concentrations and the prevalence of hypertension. Participants in the highest quartile of TMAO (>7.75 μmol/L) exhibited a 36 % increased risk of hypertension (OR = 1.360, 95 % CI: 1.043-1.772, P = 0.023). Choline also showed a positive association with hypertension (OR = 1.426, 95 % CI: 1.092-1.863, P = 0.009), while no significant association was found for betaine. Conversely, carnitine was negatively associated with hypertension risk in the highest quartile. Subgroup analyses indicated that these associations varied by age, gender, and education level. Elevated serum levels of TMAO and choline were associated with an increased risk of hypertension. Modulating TMAO metabolism could aid in the prevention of hypertension in the future.