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Abstract Objective To investigate the association between total sleep duration variability and stroke in the middle-aged and elderly population in China. Methods Data were collected from the 2011, 2013, 2015, and 2018 surveys of the China Health and Retirement Longitudinal Study (CHARLS). A total of 3485 participants, who had not experienced a stroke until 2015 and completed the follow-up in 2018, were enrolled to analyze the relationship between total sleep duration variability and new stroke. Total sleep duration was calculated by summing self-reported nocturnal sleep duration and daytime napping. The variability was determined by calculating the standard deviation (SD) of total sleep duration across the first three waves. A binary logistic regression model was utilized to analyze this association. Results Of the 3485 participants, 183 (5.25%) sustained a stroke event. A dose-response relationship was observed, indicating an increased stroke risk of 0.2 per unit (hours) increase in total sleep duration variability [OR (95% CI): 1.20 (1.01–1.42)]. Upon stratification by sex groups, this increased risk was significant only in men [OR (95% CI): 1.44 (1.12–1.83)]. Conclusion Increased total sleep duration variability was associated with an increased risk of stroke in the middle-aged and elderly, independent of factors such as age, nocturnal sleep duration, napping habits, region of residence, hypertension, diabetes mellitus, dyslipidemia, BMI, smoking, drinking habits, and marital status. However, a more notable correlation was observed in males.

Astragaloside IV(AS-IV), the main active ingredient of Astragalus, has been used as a treatment for heart failure with favorable effects, but its molecular mechanism has not been fully elucidated. Network pharmacological analysis and molecular docking revealed that Heat shock transcription factor 1 (HSF1) is a potential target of AS-IV. We designed cellular and animal experiments to investigate the role and intrinsic molecular mechanisms of AS-IV in ameliorating pressure overload-induced heart failure. In cellular experiments, Myocardial microvascular endothelial cells (MMVECs) were cultured in isolation and stimulated by adding high and low concentrations of AS-IV, and a cell model with down-regulation of HSF1 expression was constructed by using siRNA technology. Changes in the expression of key molecules of HSF1/VEGF signaling pathway and differences in tube-forming ability were detected in different groups of cells using PCR, WB and tube-forming assay. In animal experiments, TAC technology was applied to establish a pressure overload-induced heart failure model in C57 mice, postoperative mice were ingested AS-IV by gavage, and adenoviral transfection technology was applied to construct a mouse model with down-regulation of HSF1 expression.Small animal ultrasound for cardiac function assessment, MASSON staining, CD31 immunohistochemistry, and Western blotting (WB) were performed on the mice. The results showed that AS-IV could promote the expression of key molecules of HSF1/VEGF signaling pathway, enhance the tube-forming ability of MMVECs, increase the density of myocardial capillaries, reduce myocardial fibrosis, and improve the cardiac function of mice with TAC.AS-IV could modulate the HSF1/VEGF signaling pathway to promote the angiogenesis and improve the pressure overload-induced heart failure.

BackgroundPrevious studies have demonstrated that repetitive transcranial magnetic stimulation (rTMS) can improve postural control in subacute and chronic ischemic stroke, but further research is needed to investigate the effect of rTMS on acute ischemic stroke.ObjectiveWe compared the therapeutic effects of rTMS plus conventional rehabilitation and conventional rehabilitation on postural control in patients with mild hemiparesis in acute ischemic stroke.MethodsEighty-six patients with acute ischemic stroke were randomly assigned to either the experimental group or the control group within 1–7 days of onset. Patients in both groups received conventional rehabilitation for 2 weeks. Patients in the experimental group received rTMS treatments lasting for 2 weeks. Before and after the 2-week treatment, patients were assessed based on the Timed up and Go (TUG) test, Dual-Task Walking (DTW) test, Functional Ambulation Category (FAC), Tinetti Performance Oriented Mobility Assessment (POMA), gait kinematic parameters, Barthel Index (BI), Mini-Mental State Examination (MMSE), Montreal Cognitive Assessment (MoCA), and National Institutes of Health Stroke Scale (NIHSS). Additionally, TUG and single-task gait velocity were assessed at 2 months after the start of treatment, and independent walking recovery was also followed up.ResultsAfter 2 weeks of treatment, compared to conventional rehabilitation, participants who underwent rTMS treatment plus conventional rehabilitation exhibited notable enhancements in TUG, FAC, POMA, and some gait parameters [single-task gait velocity, gait stride length, gait cadence, gait cycle]. Changes in cognitive function partially mediated the improvement in single-task gait velocity and gait stride length by rTMS plus conventional rehabilitation. Generalized Estimating Equation (GEE) analysis showed that the trend of improvement in single-task gait velocity over time was more pronounced in the experimental group than in the control group. The results of the Kaplan–Meier curve indicated a median gait recovery time of 90 days for patients in the experimental group and 100 days for the control group. Multifactorial Cox regression analyses showed that rTMS plus conventional rehabilitation promoted faster recovery of independent walking compared with conventional rehabilitation.ConclusionrTMS plus conventional rehabilitation outperformed conventional rehabilitation in improving postural control in patients with acute ischemic stroke. Improvements in cognitive function may serve as a mediating factor in the favorable treatment outcome of rTMS plus conventional rehabilitation for improving postural control.Clinical trial registrationhttps://www.chictr.org.cn, identifier ChiCTR1900026225.

BackgroundCurrent evidences suggest that Proprotein Convertase Subtilisin/kexin Type 9 inhibitors (PCSK9i) exhibit a protective influence on acute coronary syndrome (ACS). Nevertheless, further investigation is required to comprehend the impact and mechanisms of these pharmaceutical agents on inflammatory factors and arterial stiffness (AS) in patients with ACS. Consequently, the objective of this study is to ascertain the influence of PCSK9i on arterial stiffness in ACS patients and elucidate the underlying mechanisms behind their actions.MethodsThis study employed Mendelian randomization (MR) analysis to examine the association between genetic prediction of PCSK9 inhibition and arterial stiffness. Data of 71 patients with ACS were retrospectively collected, including PCSK9i group (n = 36, PCSK9 inhibitors combined with statins) and control group (n = 35, statins only). Blood lipid levels, inflammatory markers and pulse wave velocity (PWV) data were collected before treatment and at 1 and 6 months after treatment for analysis. Additionally, cell experiments were conducted to investigate the impact of PCSK9i on osteogenesis of vascular smooth muscle cells (VSMCs), utilizing western blot (WB), enzyme-linked immunosorbent assay (ELISA), and calcification index measurements.ResultsThe results of the MR analysis suggest that genetic prediction of PCSK9 inhibition has potential to reduce the PWV. Following treatment of statins combined with PCSK9 inhibitors for 1 and 6 months, the PCSK9i group exhibited significantly lower levels of total cholesterol (TC), low-density lipoprotein cholesterol (LDL-C), C-reactive protein (CRP), interleukin-6 (IL-6), fibrinogen (FIB) and procalcitonin (PCT) compared to the control group (p

BackgroundThere are no specific clinical medications that target cardiac fibrosis in heart failure (HF). Recent studies have shown that tyrosine kinase inhibitors (TKIs) may benefit fibrosis in various organs. However, there is limited research on their application in cardiac fibrosis. Axitinib, an FDA-approved tyrosine kinase inhibitor, was used to evaluate its effects on cardiac fibrosis and function in pressure overload-induced heart failure.MethodsTo build a pharmacological network, the pharmacological targets of axitinib were first retrieved from databases and coupled with key heart failure gene molecules for analysis and prediction. To validate the results outlined above, 8-week-old male C57BL/6 J mice were orally administrated of axitinib (30 mg/kg) daily for 8 weeks after Transverse Aortic Constriction (TAC) surgery. Mouse cardiomyocytes and cardiac fibroblasts were used as cell lines to test the function and mechanism of axitinib.ResultsWe found that the pharmacological targets of axitinib could form a pharmacological network with key genes involved in heart failure. The VEGFA-KDR pathway was found to be closely related to the differential gene expression of human heart-derived primary cardiomyocyte cell lines treated with axitinib, based on analysis of the publicly available dataset. The outcomes of animal experiments demonstrated that axitinib therapy greatly reduced cardiac fibrosis and improved TAC-induced cardiac dysfunction. Further research has shown that the expression of transforming growth factor-β(TGF-β) and other fibrosis genes was significantly reduced in vivo and in vitro.ConclusionOur study provides evidence for the repurposing of axitinib to combat cardiac fibrosis, and offers new insights into the treatment of patients with HF.