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BACKGROUND Previous studies indicated that selenium (Se) may play an important role in cardio-cerebrovascular disease. However, the relationship between circulating selenium and risk of first stroke remains inconclusive. OBJECTIVE We conducted a secondary analysis of the China Stroke Primary Prevention Trial (CSPPT), using a nested case-control design, and aimed to investigate the correlation between Se concentration and first stroke risk in adults with hypertension and examine the potential effect modifiers. METHODS In the CSPPT, a total of 20,702 adults with hypertension were randomly assigned to a double-blind, daily treatment with either 10 mg enalapril and 0.8 mg folic acid or 10 mg enalapril alone. A total of 618 first stroke cases and 618 controls matched for age, sex, treatment group, and study site were included in this study. RESULTS During a median follow-up duration of 4.5 years (IQR, 4.2-4.6 y), there was a significant inverse association between plasma Se and the risk of first stroke (per SD increment; adjusted OR: 0.81; 95% CI: 0.68, 0.96) and ischemic stroke (per SD increment; adjusted OR: 0.76; 95% CI: 0.62, 0.93). Furthermore, a stronger inverse association between plasma Se and first stroke was observed in participants with higher folate concentrations at baseline (≥ 7.7 (median), adjusted OR: 0.67; 95% CI: 0.54, 0.85, versus

While the received traditional predictors are still the mainstay in the diagnosis and prognosis of CVD events, increasing studies have focused on exploring the ancillary effect of biomarkers for the aspiring of precision. Under which circumstances, soluble ST2 (sST2), lipoprotein-associated phospholipase A2 (Lp-PLA2), myeloperoxidase (MPO), and procalcitonin (PCT) have recently emerged as promising markers in the field of both acute and chronic cardiovascular diseases. Existent clinical studies have demonstrated the significant associations between these markers with various CVD outcomes, which further verified the potentiality of markers in helping risk stratification and diagnostic and therapeutic work-up of patients. The current review article is aimed at illuminating the applicability of these four novels and often neglected cardiac biomarkers in common clinical scenarios, including acute myocardial infarction, acute heart failure, and chronic heart failure, especially in the emergency department. By thorough classification, combination, and discussion of biomarkers with clinical and instrumental evaluation, we hope the current study can provide insights into biomarkers and draw more attention to their importance.

Introduction The worldwide prevalence of diabetes has been increasing for decades; diabetes can lead to serious health problems and even death, but the effects of maintaining low fasting blood glucose (FBG) remain controversial. The purpose of this study was to investigate the relationship between FBG levels and all-cause mortality in a long-term follow-up cohort and to find a relatively safe range of FBG levels. Methods This study included 17,902 adults from a community-based cohort study in rural China who were prospectively followed from 2003 to 2018. Generalized estimating equations were used to evaluate the association between FBG and all-cause mortality, adjusting for pertinent covariates and auto-correlations among siblings. Results A total of 1053 (5.9%) deaths occurred during 15 years of follow-up. There was a significant U-shaped association between all-cause mortality and FBG. Compared with the reference group (FBG of 5.6 –

We aimed to evaluate the relationship of plasma Mg with the risk of new-onset hyperuricaemia and examine any possible effect modifiers in hypertensive patients. This is a post hoc analysis of the Uric acid (UA) Sub-study of the China Stroke Primary Prevention Trial (CSPPT). A total of 1685 participants were included in the present study. The main outcome was new-onset hyperuricaemia defined as a UA concentration ≥417 μmol/l in men or ≥357 μmol/l in women. The secondary outcome was a change in UA concentration defined as UA at the exit visit minus that at baseline. During a median follow-up duration of 4·3 years, new-onset hyperuricaemia occurred in 290 (17·2 %) participants. There was a significantly inverse relation of plasma Mg with the risk of new-onset hyperuricaemia (per sd increment; OR 0·85; 95 % CI 0·74, 0·99) and change in UA levels (per sd increment; β −3·96 μmol/l; 95 % CI −7·14, −0·79). Consistently, when plasma Mg was analysed as tertiles, a significantly lower risk of new-onset hyperuricaemia (OR 0·67; 95 % CI 0·48, 0·95) and less increase in UA levels (β −8·35 μmol/l; 95 % CI −16·12, −0·58) were found among participants in tertile 3 (≥885·5 μmol/l) compared with those in tertile 1 (

Background and aims Clarifying the association between 5-methyltetrahydrofolate and homocysteine and the effect pattern of methylene tetrahydrofolate reductase (MTHFR C677T) may contribute to the management of homocysteine and may serve as a significant reference for a randomized controlled trial of 5-methyltetrahydrofolate intervention. This study aimed to reveal the association between these two biochemical indices. Methods Study population was drawn from the baseline data of the China Stroke Primary Prevention Trial (CSPPT), including 2328 hypertensive participants. 5-methyltetrahydrofolate and homocysteine were determined by stable-isotope dilution liquid chromatography-tandem mass spectrometry and automatic clinical analyzers, respectively. MTHFR C677T polymorphisms were detected using TaqMan assay. Multiple linear regression was performed to evaluate the association between serum 5-methyltetrahydrofolate and homocysteine. Results There was a significant inverse association between 5-methyltetrahydrofolate and homocysteine when 5-methyltetrahydrofolate was ≤ 10 ng/mL, and this association was modified by MTHFR C677T (per 1-ng/mL increment; All: β = − 0.50, P β = − 0.14, P = 0.087; CT: β = − 0.20, P = 0.011; TT: β = − 1.19, P P for difference P for difference P for difference = 0.757). Conclusions Our data showed a non-linear association between serum homocysteine and 5-methyltetrahydrofolate among Chinese hypertensive adults, however, it could be inversely linearly fitted when serum 5-methyltetrahydrofolate was ≤ 10 ng/mL, and this association was modified by MTHFR C677T.

Background Cardiovascular health (CVH) status is associated with cardiovascular diseases (CVD). However, evidence for association of CVH change with risk of CVD is scarce. Methods and Results Seven metrics (smoking status, body mass index, physical activity, diet, total cholesterol, blood pressure, and fasting blood glucose) were used to evaluate the CVH status. Having 0 to 2, 3 to 4, and 5 to 7 ideal cardiovascular metrics were categorized as low, moderate, and high CVH status, respectively. Change in CVH status was assessed from 2006/2007 to 2010/2011. We calculated lifetime risk of CVD using a modified Kaplan–Meier method, and life expectancy was evaluated via the multistate lifetable method. There were 82 349 participants included in our analysis. At 35 years index age, the age‐adjusted incident rate and lifetime risk of CVD were increased with decreasing number of ideal CVH metrics. The direction of change in status of CVH was consistently associated with age‐adjusted incident rate and lifetime risk of CVD. At 35 years index age, improvement from low to moderate (37.6% [95% CI, 32.8%–42.4%]) or to high status (24.4% [95% CI, 12.7%–36.0%]) had lower lifetime risk of CVD compared with consistently low status (44.6% [95% CI, 40.8%–48.5%]). The improvement in CVH could prolong the years of life free from CVD. The pattern of incident rate and lifetime risk across change in CVH status was similar at 45 and 55 years index age. Conclusions Higher number of CVH metrics was associated with lower lifetime risk of CVD. The improvement of CVH status could reduce the lifetime risk of CVD and prolonged the year of life free from CVD.

Background: The association between plasma vitamin E levels and first stroke risk in men and women remains unclear.Objective: We aimed to examine the prospective association between plasma vitamin E and first stroke, and evaluate the effect modifiers for the association, among hypertensive patients.Design: The study sample was drawn from the China Stroke Primary Prevention Trial (CSPPT), which randomized a total of 20,702 hypertensive patients to a double-blind, daily treatment with either 10 mg enalapril and 0.8 mg folic acid or 10 mg enalapril alone. This nested case-control study, including 618 first stroke cases and 618 controls matched for age, sex, treatment group, and study site, was conducted after the completion of the CSPPT.Results: The median follow-up duration was 4.5 years. Among men, a significantly higher risk of first stroke (adjusted OR, 1.67; 95%CI: 1.01, 2.77) was found for those with plasma vitamin E ≥7.1 μg/mL (≥quartile 1) compared with those with plasma vitamin E < 7.1 μg/mL. Subgroup analyses further showed that the association between vitamin E (≥7.1 vs. P-interaction = 0.008). However, there was no significant association between plasma vitamin E and first stroke in women (P-interaction between sex and plasma vitamin E = 0.048).Conclusions: Among Chinese hypertensive patients, there was a statistically significant positive association between baseline plasma vitamin E and the risk of first stroke in men, but not in women.Clinical Trial Registration:https://clinicaltrials.gov/ct2/show/NCT00794885, Identifier: NCT00794885.

Composite rocks are easily encountered in a wide range of geotechnical construction projects. Understanding their mechanical properties and failure modes is very important to ensure project quality and safety. This study conducted a mechanical analysis to assess the stress distribution in composite rock with a horizontal interlayer and predicted the possible failure modes. Uniaxial compression tests were carried out on the composite rock samples to reveal their mechanical properties. It was concluded that a composite rock with a thick interlayer failed more easily than a composite rock with a thin interlayer. Four potential failure modes were related to the internal stress distribution under compression and the differences in deformation capacity and strength among the constituent components. The stress distribution derived from the mechanical analysis could explain the failure mechanism very well. These results verified the validity of the mechanical analysis results and improved understanding of the mechanical properties of composite rock with a horizontal interlayer.

Background: Immune checkpoint blockers (ICBs) are increasingly being used to treat patients with advanced hepatocellular carcinoma (HCC), but only a third of these patients are sensitive to ICBs. Emerging evidence suggests that ferroptosis could be a novel target for antitumor treatment, and combined treatment with ferroptosis inducers might enhance sensitivity to immunotherapy. However, there is a lack of information on the crosstalk between ferroptosis-related lncRNAs and anti-tumor immunity. Therefore, we aim to explore prognostic value of ferroptosis-related lncRNAs and clarify potential role in ICBs of HCC.Methods: We obtained mRNA and lncRNA expression data from two independent cohorts (TCGA and GEO database). Univariate Cox, the least absolute shrinkage and selection operator (Lasso) algorithm and multivariate Cox analysis were used to construct a lncRNA signature, which was evaluated using the area under the receiver operating characteristic curve (AUC) and Kaplan–Meier curves. Tumor-infiltrating cell (TIC) profiling and the tumor immune dysfunction and exclusion (TIDE) algorithm were used to validate the signature model and immunotherapy. Finally, we adopted RT-PCR assay to evaluate the differential expression of lncRNAs in HCC tissues in our hospital.Results: The ferroptosis-related lncRNA signature included five lncRNAs, most of which were positively correlated with clinical stage and grade. The signature could stratify patients into two risk groups, with the high-risk group associated with a shorter overall survival (OS, p < 0.05) in TCGA-LIHC and GSE76427. Besides, the AUCs of the 1-, 3-, and 5-years OS were 0.772, 0.707, and 0.666, respectively. Gene set enrichment analysis (GESA) of lncRNAs revealed enrichment of oncogenic and immune-related pathways. The TIC profiling indicated a close correlation between the signature and immune cells. Furthermore, the high-risk group had a better response to immunotherapy than low-risk group. RT-PCR demonstrated these five lncRNAs were upregulated in cancerous tissue than normal tissues.Conclusions: The ferroptosis-related lncRNA signature could accurately predict the OS of HCC patients and may serve as an independent clinical factor for patients’ outcomes. Ferroptosis-related lncRNAs may remodel the tumor microenvironment (TME) and affect the anti-cancer ability of ICBs, and therefore, could potentially act as an indicator for the response to immunotherapy in HCC.

Objective: The association between plasma magnesium and risk of incident cancer remains inconclusive in previous studies. We aimed to investigate the prospective relationship of baseline plasma magnesium concentrations with the risk of incident cancer and to examine possible effect modifiers. Methods: A nested case-control study with 228 incident cancer cases and 228 matched controls was conducted using data from the China Stroke Primary Prevention Trial (CSPPT), a randomized, double-blind, controlled trial, conducted from May 2008 to August 2013. Study outcomes included incident cancer and its subtypes. Results: When plasma magnesium concentrations were assessed as quartiles, a significantly higher incident risk of total cancer was found in participants in quartile 1 (Conclusions: Both low and high plasma magnesium concentrations were significantly associated with an increased incident risk of cancer, compared with the reference concentrations of 0.83 to

Objective The association between plasma selenium and new-onset diabetes in hypertensive adults is still unclear. We aimed to evaluate the relationship of baseline plasma selenium with new-onset diabetes and examine possible effect modifiers in a post-hoc analysis of the China Stroke Primary Prevention Trial (CSPPT). Methods A total of 2367 hypertensive, non-diabetic patients with plasma selenium measurements at baseline were included. The primary outcome was new-onset diabetes, defined as physician-diagnosed diabetes or use of glucose-lowering drugs during the follow-up period, or fasting glucose (FG) ≥126.0 mg/dL at the exit visit. Results At baseline, higher FG levels were found among participants with plasma selenium in quartile 4 (≥94.8 μg/L) (β, 1.64 mg/dL; 95%CI: 0.54, 2.73) compared to those in quartiles 1–3. During a median follow-up duration of 4.5 years, new-onset diabetes occurred in 270 (11.4%) participants. Graphic plot showed a positive association between baseline selenium levels and risk of new-onset diabetes. This was further confirmed by adjusted regression analyses; the odds ratios (OR) for new-onset diabetes comparing quartile 4 (≥94.8 μg/L) to quartiles 1–3 was 1.36 (95%CI: 1.01, 1.83). No clear trend was evident across quartiles 1–3. Conclusions Our data suggest that high plasma selenium (≥94.8 μg/L) was associated with increased risk of new-onset diabetes in hypertensive patients.

Evidence from epidemiologic studies on the association of circulating 25-hydroxyvitamin D [25(OH)D] concentrations with the incident risk of cancer has been inconsistent. We aimed to investigate the prospective relationship of baseline plasma 25(OH)D concentrations with the risk of cancer, and to examine possible effect modifiers.We employed a nested case-control study design, including 231 patients with incident cancer during a median 4.5 years of follow up, and 231 matched controls from the China Stroke Primary Prevention Trial (CSPPT).The prevalence of plasma 25(OH)D 15,20 and30 ng/mL was 23.6%, 47.4% and 85.5%, respectively. Overall, there was an inverse relation between risk of cancer and plasma 25(OH)D. The Odds ratios (95% CI) for participants in the second (15.1 to20.6 ng/mL), third (20.6 to26.4 ng/mL) and fourth quartiles (≥26.4 ng/mL) were 0.45 (95% CI: 0.25-0.80), 0.53 (95% CI: 0.27-1.06) and 0.55 (95% CI: 0.27-1.10), respectively, compared with those in quartile 1. Conversely, low 25(OH)D (15.1 ng/mL) concentrations were associated with increased risk of cancer (OR, 2.08; 95% CI: 1.20-3.59) compared to higher concentrations. These associations were consistent across subtypes of cancer. Several potential effect modifiers were identified, including plasma vitamin E concentrations and alcohol intake.Low plasma 25(OH)D concentrations (15.1 ng/mL) were associated with increased total cancer risk among Chinese hypertensive adults, compared to higher 25(OH)D concentrations. This finding and the possible effect modifiers warrant additional investigation.

The aim of this study was to investigate whether intraplacental texture features from routine placental MRI can objectively and accurately predict invasive placentation. This retrospective study includes 99 pregnant women with pathologically confirmed placental invasion and 56 pregnant women with simple placenta previa. All participants underwent magnetic resonance imaging after 24 gestational weeks. The placenta was segmented in sagittal images from both turbo spin echo (TSE) and balanced turbo field echo (bTFE) sequences. Textural features were extracted from the both original and Laplacian of Gaussian (LoG)-filtered MRI images. An automated machine learning algorithm was applied to the extracted feature sets to obtain the optimal preprocessing steps, classification algorithm, and corresponding hyper-parameters. A gradient boosting classifier using all textual features from original and LoG-filtered TSE images and bTFE images identified by the automated machine learning algorithm achieved the optimal performance with sensitivity, specificity, accuracy, and area under ROC curve (AUC) of 100%, 88.5%, 95.2%, and 0.98 in the prediction of placental invasion. In addition, textural features that contributed to the prediction of placental invasion differ from the features significantly affected by normal placenta maturation. Quantifying intraplacental heterogeneity using LoG filtration and texture analysis highlights the different heterogeneous appearance caused by abnormal placentation relative to normal maturation. The predictive model derived from automated machine learning yielded good performance, indicating the proposed radiomic analysis pipeline can accurately predict placental invasion and facilitate clinical decision-making for pregnant women with suspicious placental invasion. • The intraplacental texture features have high efficiency in prediction of invasive placentation after 24 gestational weeks. • The features with dominated predictive power did not overlap with the features significantly affected by gestational age.

Associations between vitamin D and stroke remain inconsistent. One major risk factor for stroke is high blood glucose, but the role it plays in this association is not well studied.We aimed to evaluate the individual association between plasma 25-hydroxyvitamin D [25(OH)D] and risk of first stroke stratified by fasting blood glucose (FBG), and the joint associations between plasma 25(OH)D, glycemic status, and first stroke in hypertensive adults.This study was a nested, case-control design utilizing data from the China Stroke Primary Prevention Trial (CSPPT). This analysis included 591 first stroke cases (of which 475 were ischemic stroke, 114 were hemorrhagic stroke, and 2 were uncertain type) and 591 matched controls. The age range of the study population was 45-75 y. The normal FBG (NFG) group had FBG 5.6 mmol/L, and the impaired FBG (IFG) group had FBG ≥5.6 mmol/L and 7.0 mmol/L. Diabetes was defined as participants with FBG ≥7 mmol/L or who were receiving treatment with hypoglycemic agents. ORs (95% CIs) were calculated using unconditional logistic regression models.Multivariable adjusted models revealed an inverse association between quartiles of 25(OH)D and risk of first stroke among participants with NFG, but the opposite trend was observed for those with IFG or diabetes. The largest ORs (2) were observed among patients with diabetes, compared with the reference group of NFG and high 25(OH)D. Those with NFG and low 25(OH)D (OR = 1.73, 95% CI: 1.22 to 2.44) or those with IFG and high 25(OH)D (OR = 1.74, 95% CI: 1.14 to 2.67) both had a higher risk of total stroke. There was a significant interaction between 25(OH)D and a combined group of IFG and diabetes (P = 0.001). Similar results were observed for ischemic stroke.In a hypertensive population, the relation between plasma 25(OH)D and risk of first stroke was significantly modified by FBG. This trial was registered at https://www.clinicaltrials.gov as NCT00794885.

Background Dietary recommendations regarding egg intake remain controversial topic for public health. We hypothesized that there was a positive association between egg consumption and all-cause mortality. Methods To test this hypothesis, we enrolled 9885 adults from a community-based cohort in Anhui Province, China during 2003–05. Egg consumption was assessed by food questionnaire. Stratified analyses were performed for age, sex, body mass index (BMI), blood pressure, smoking, drinking and laboratory tests. Results After an average follow-up of 14.1 years, 9444 participants were included for analysis. A total of 814 deaths were recorded. Participants’ BMI and lipid profile had no significantly difference between three egg consumption groups. BMI was 21.6±2.7 of the whole population, especially BMI>24 was only 17.3%. A bivariate association of egg consumption >6/week with increased all-cause mortality was observed compared with ≤6/week (RR: 1.35, 95% CI: 1.05, 1.73, P = 0.018). A significant interaction was observed for BMI ≥ 21.2 kg/m2 vs. BMI Conclusions In this study, consuming >6 eggs/week increased risk of all-cause mortality, even among lean participants, especially who with BMI ≥ 21.2 kg/m2. Eggs are an easily accessible and constitute an affordable food source in underdeveloped regions. Consuming

(247 words) Background and aims. The relationship between dynamic changes in metabolic syndrome (MetS) status and lifetime risk of cardiovascular disease (CVD) has not been reliably quantified. This study aimed to estimate lifetime risk of CVD and life expectancy with and without CVD according to dynamic MetS status. Methods and Results. Dynamic changes in MetS status were assessed: MetS-free, MetS-chronic, MetS-developed, and MetS-recovery groups. We used Modified Kaplan-Meier method to estimate lifetime risk and used multistate life table method to calculate life expectancy. Participants free of CVD at index ages 35 (n = 40 168), 45 (n = 33 569), and 55 (n = 18 546) years. At index age 35 years, we recorded 1341 CVD events during a median follow-up of 6.1 years. Lifetime risk of 33.9% (95% CI: 26.9%-41.0%) in MetS-recovery group was lower than that of 39.4% (95% CI: 36.1%-42.8%) in MetS-chronic group. Lifetime risk of 37.8% (95% CI: 30.6%-45.1%) in MetS-developed group was higher than that of 26.4% (95% CI: 22.7%-30.0%) in MetS-free group. At index age 35 years, life expectancy free of CVD for MetS-recovery group (44.1 years) was higher than that for MetS-chronic group (38.8 years). Life expectancy free of CVD for MetS-developed group (41.9 years) was lower than that for MetS-free group (46.7 years). Conclusions. Recovery from MetS was associated with decreased lifetime risk of CVD and a longer life expectancy free of CVD, whereas development of MetS was associated with increased lifetime risk of CVD and a shorter life expectancy free of CVD.

Owing to the structural replication of native extracellular matrix, nonwoven mats of electrospun nanofibers have great potential for use in wound healing. Herein, we report the design and fabrication of a sandwich wound dressing to balance its antimicrobial activity and biocompatibility. This success mainly relies on the incorporation of silver nanoparticles (AgNPs) into electrospun nanofibers, together with the rational design of a sandwich structure for the dressing. The bottom layer was composed of hydrophilic nanofibers made from a blend of polycaprolactone (PCL) and gelatin (Gel). The top layer consisted of hydrophobic PCL nanofibers. AgNP-loaded PCL/Gel nanofibers were sandwiched between the two layers. When compared with a commercial silver sulfadiazine dressing, the designed wound dressing showed competitive antimicrobial properties, lower cell toxicity, and accelerated wound closure for mouse skin injury. By balancing the biocompatibility of electrospun nanofibers and the broad-spectrum antibacterial activity of AgNPs within a sandwich structure, the novel multifunctional wound dressing could be valuable for effective wound healing and related applications.

Aims. - Evidence for the effects of metabolically healthy obese (MHO) status on heart failure (HF) is limited and ignores the dynamic change of metabolic health and obesity phenotypes. We aimed to investigate the associations of metabolic health and its transition with HF across body mass index (BMI) and waist circumference (WC) categories. Methods. - This prospective cohort study was conducted with 93,288 Chinese adults who were free of cardiovascular disease, cancer or HF at baseline (2006-2007). Metabolic health was defined as having no or only one abnormality in blood pressure, glucose, high-density lipoprotein cholesterol, or triglyceride levels. Participants were cross-classified at baseline by metabolic health and obesity (defined by BMI and WC criteria). Transitions in metabolic health status from 2006-2007 to 2010-2011 were considered. The hazard ratios (HRs) and 95% confidence intervals (CIs) for HF were assessed by Cox proportional hazards regression. Results. - During a mean ± standard deviation follow-up of 9.7 ± 1.5 years, 1,628 participants developed HF. Individuals with MHO (HR: 1.78, 95% CI: 1.45, 2.19 for BMI criteria; HR: 1.51, 95% CI: 1.30, 1.76 for WC criteria) had higher risk of HF than those with metabolically healthy normal weight (MH-NW). Individuals with initial MHO who shifted to metabolically unhealthy phenotype during follow-up had higher risk of HF compared with stable MH-NW individuals (HR 3.12; 95% CI: 2.01, 4.85 for BMI categories; HR 1.98; 95% CI: 1.42, 2.77 for WC categories). Even stable MHO individuals were at an increased risk of HF compared with stable MH-NW individuals (HR: 2.17; 95% CI: 1.39, 3.39 for BMI categories; HR: 1.33; 95% CI: 0.96, 1.85 for WC categories). Conclusions. - MHO phenotype is dynamic and its transition to metabolically unhealthy phenotype or even stable MHO is associated with increased risk of HF. Maintaining metabolic health may provide a clue for preventing HF.

Aims/hypothesis People with obesity and a normal metabolic profile are sometimes referred to as having ‘metabolically healthy obesity’ (MHO). However, whether this group of individuals are actually ‘healthy’ is uncertain. This study aims to examine the associations of MHO with a wide range of obesity-related outcomes. Methods This is a population-based prospective cohort study of 381,363 UK Biobank participants with a median follow-up of 11.2 years. MHO was defined as having a BMI ≥ 30 kg/m2 and at least four of the six metabolically healthy criteria. Outcomes included incident diabetes and incident and fatal atherosclerotic CVD (ASCVD), heart failure (HF) and respiratory diseases. Results Compared with people who were not obese at baseline, those with MHO had higher incident HF (HR 1.60; 95% CI 1.45, 1.75) and respiratory disease (HR 1.20; 95% CI 1.16, 1.25) rates, but not higher ASCVD. The associations of MHO were generally weaker for fatal outcomes and only significant for all-cause (HR 1.12; 95% CI 1.04, 1.21) and HF mortality rates (HR 1.44; 95% CI 1.09, 1.89). However, when compared with people who were metabolically healthy without obesity, participants with MHO had higher rates of incident diabetes (HR 4.32; 95% CI 3.83, 4.89), ASCVD (HR 1.18; 95% CI 1.10, 1.27), HF (HR 1.76; 95% CI 1.61, 1.92), respiratory diseases (HR 1.28; 95% CI 1.24, 1.33) and all-cause mortality (HR 1.22; 95% CI 1.14, 1.31). The results with a 5 year landmark analysis were similar. Conclusions/interpretation Weight management should be recommended to all people with obesity, irrespective of their metabolic status, to lower risk of diabetes, ASCVD, HF and respiratory diseases. The term ‘MHO’ should be avoided as it is misleading and different strategies for risk stratification should be explored. Graphical abstract

Background: Previous studies have shown that Zhongfeng Xingnao Formula (ZXF) can effectively reduce the mortality of intracerebral hemorrhage (ICH), but the underlying mechanism of the treatment remained still unexplored. This study aimed to expound the potential mechanism of ZXF in the treatment of ICH through network pharmacology and molecular docking.Methods: The putative targets of ZXF were obtained from the TCMSP and Uniprot database, while the potential targets of ICH received from Drugbank, Genecards and OMIM database. Then through the Venn 2.1, the overlapping targets of disease and drug were gotten for the further study. The GO and KEGG enrichment analyses were performed by R version 4.0.2 software so that the signaling pathway was acquired to the subsequent analysis. Cytoscape was used to construct the drug-compound-target-pathway network and String was utilized for the protein-protein interaction network. What’s more, the interaction between compound and target was verified by the AutoDockTools and Autodock Vina. Results: There were a total of 166 ZXF-related targets and 1258 ICH-related targets obtained from the public databases. And 87 potential targets were both related to drug and disease. The GO enrichment analysis mainly involved receptor ligand activity, signaling receptor activator activity, and cytokine receptor binding, while the signaling pathway, such as Fluid shear stress and atherosclerosis, AGE-RAGE signaling pathway in diabetic complications, PI3K-Akt signaling pathway, were significantly enriched in the KEGG enrichment analysis. The molecular docking elucidated that the aloe-emodin, beta-sitosterol, quercetin could bound well to the top five targets sorted by degree value.Conclusions: ZXF treated ICH through multiple compounds, multiple targets, and multiple pathways. The underlying mechanism of the treatment may be promoting angiogenesis, anti-inflammatory, anti-oxidative stress, and reversing atherosclerosis, which is of great significance for the treatment of ICH.

Summary Background The relationship of osteoporosis and stroke is still not fully clarified. Apart from the well-known risk factors for stroke, bone mineral density (BMD) has gained more interest in recent years. Aim To further elucidate the relationship between BMD and stroke risk, a prospective cohort study in the Chinese rural population was conducted. Design Retrospective analysis of a family osteoporosis cohort. Methods Our subjects were selected from an osteoporosis cohort conducted in Anqing, China. All participants underwent a questionnaire assessment, clinical examinations and laboratory assessments. During the follow-up period, the number of people who had a stroke was recorded. Generalized estimating equation regression analysis was performed to determine the significance of the association between BMD and stroke. Results A total of 17868 people were included. A two-way interaction test of sex and BMD on stroke was significant (P = 0.002). There was a significant difference in BMD and stroke morbidity in the male group (P = 0.003). When BMD was assessed as quartiles and the lowest quartile was used as reference, a significantly lower risk for stroke was observed in Q2–4. Notably, no significant difference was observed in female participants with adjusted odds ratio (P > 0.05). The P-value for interaction was calculated. The body mass index (P = 0.014) and waist-to-hip ratio (P = 0.027) were found to be significantly associated with BMD and stroke risk in female participants. Conclusions In Chinese rural areas, total BMD may negatively correlated with stroke, especially in men.

Background According to the Global Burden of Disease Study 2017, smoking is one of the leading four risk factors contributing to deaths in China. We aimed to evaluate the associations of smoking with all-cause mortality in a Chinese rural population. Methods Male participants over age 45 (n = 5367) from a large familial aggregation study in rural China, were included in the current analyses. A total of 528 former smokers and 3849 current smokers accounted for 10 and 71.7% of the cohort, respectively. Generalized Estimating Equations were used to evaluate the association between baseline smoking status and mortality, adjusting for pertinent covariates. Results There were 579 recorded deaths during the 15-year follow-up. Current smokers (odds ratio [OR],1.60; 95% CI,1.23–2.08) had higher all-cause mortality risks than nonsmokers. Relative to nonsmokers, current smokers of more than 40 pack-years ([OR],1.85; 95% CI,1.33–2.56) had a higher all-cause mortality risk. Compared to nonsmokers, current smokers who started smoking before age 20 ([OR],1.91; 95% CI,1.43–2.54) had a higher all-cause mortality risk, and former smokers in the lower pack-year group who quit after age 41 (median) ([OR],3.19; 95% CI,1.83–5.56) also had a higher risk of death after adjustment. Furthermore, former smokers who were also former drinkers had the highest significant risk of mortality than never smokers or drinkers. (P for interaction = 0.034). Conclusions This study provides evidence that current smokers and former smokers have a higher mortality risk than nonsmokers and would benefit from cessation at a younger age.

Background Identification of novel risk factors is needed to further lower stroke risk. Data concerning the association between plasma retinol concentrations and the risk of stroke are limited. Objectives We aimed to evaluate the effect of plasma retinol on the risk of first stroke and to examine any possible effect modifiers in hypertensive patients. Methods The study sample population was drawn from the China Stroke Primary Prevention Trial (CSPPT), using a nested case-control design, including 620 cases with first stroke and 620 matched controls. In the CSPPT, a total of 20,702 hypertensive patients were randomly assigned to a double-blind, daily treatment with either 10 mg enalapril and 0.8 mg folic acid or 10 mg enalapril alone. The median treatment duration was 4.5 y. Results There was a significant inverse association between plasma retinol and the risk of first stroke (per 10-μg/dL increment; OR: 0.92; 95% CI: 0.86, 0.97) and first ischemic stroke (OR: 0.92; 95% CI: 0.86, 0.98). When retinol was assessed as quartiles, significantly lower risks of first stroke (OR: 0.64; 95% CI: 0.46, 0.88) and first ischemic stroke (OR: 0.67; 95% CI: 0.46, 0.96) were found in participants in quartiles 2-4 compared with those in quartile 1. Furthermore, a stronger inverse association between plasma retinol and first stroke was observed in participants with baseline total homocysteine (

Background and Purpose— We aimed to examine whether the efficacy of folic acid therapy in the primary prevention of stroke is jointly affected by smoking status and baseline folate levels in a male population in a post hoc analysis of the CSPPT (China Stroke Primary Prevention Trial). Methods— Eligible participants of the CSPPT were randomly assigned to a double-blind daily treatment of a combined enalapril 10-mg and folic acid 0.8-mg tablet or an enalapril 10-mg tablet alone. In total, 8384 male participants of the CSPPT were included in the current analyses. The primary outcome was first stroke. Results— The median treatment duration was 4.5 years. In the enalapril-alone group, the first stroke risk varied by baseline folate levels and smoking status (never versus ever). Specifically, there was an inverse association between folate levels and first stroke in never smokers ( P for linear trend=0.043). However, no such association was found in ever smokers. A test for interaction between baseline folate levels and smoking status on first stroke was significant ( P =0.045). In the total sample, folic acid therapy significantly reduced the risk of first stroke in never smokers with folate deficiency (hazard risk, 0.36; 95% confidence interval, 0.16–0.83) and in ever smokers with normal folate levels (hazard risk, 0.69; 95% confidence interval, 0.48–0.99). Conclusions— Baseline folate levels and smoking status can interactively affect the risk of first stroke. Our data suggest that compared with never smokers, ever smokers may require a higher dosage of folic acid to achieve a greater beneficial effect on stroke. Our findings need to be confirmed by future randomized trials. Clinical Trial Registration— URL: https://www.clinicaltrials.gov . Unique identifier: NCT00794885.

Background and Purpose— This study aimed to investigate the association between mean carotid intima-media thickness (cIMT) and the risk of first stroke and examine any possible effect modifiers in patients with hypertension. Methods— A total of 11 547 hypertensive participants without history of stroke from the CSPPT (China Stroke Primary Prevention Trial) were included in this analysis. The primary outcome was first stroke. Results— Over a median follow-up of 4.4 years, 726 first strokes were identified, of which 631 were ischemic, and 90 were hemorrhagic. A per SD increase in mean cIMT was positively associated with the risk of first stroke (hazard ratio [HR], 1.11 [95% CI, 1.03–1.20]), and first ischemic stroke (HR, 1.10 [95% CI, 1.01–1.20]). Moreover, when cIMT was categorized in quartiles, the higher risks of first stroke (HR, 1.31 [95% CI, 1.06–1.61]) and first hemorrhagic stroke (HR, 2.25 [95% CI, 1.11–4.58]) were found in participants in quartile 2 to 4 (≥0.66 mm), compared with those in quartile 1 (P -interaction=0.024) or diastolic blood pressure levels (≥90.7 [quintile 5] versus P -interaction=0.009). Conclusions— There was a significant positive association between baseline cIMT and the risk of first stroke in patients with hypertension. This association was even stronger among those with higher mean arterial pressure or diastolic blood pressure levels.

Tongxinluo (TXL) is a multifunctional traditional Chinese medicine and has been widely used in the treatment of cardiovascular and cerebrovascular diseases. Numerous studies demonstrate that TXL is a novel neuroprotective drug, however, the mechanisms are largely unknown.we aimed to demonstrate the protective effect of TXL on cerebral ischemia/reperfusion (I/R) injury and provide the evidence for the involvement of Connexin 43/Calpain II/ Bax/Caspase-3 pathway in TXL-mediated neuroprotection.Focal cerebral I/R injury were induced by transient middle cerebral artery occlusion (MCAO, for 90min) in adult male Sprague-Dawley rats. We estimated the effects of TXL on I/R injury including neurological deficit assessment and cerebral infarct volume measurement via TTC staining, and detected the protein expression of Connexin 43 (Cx43) by western blot. Furthermore, after the intracerebroventricular injection of carbenoxolone (CBX, the inhibitor of Cx43) at 30min before MCAO surgery, Calpain II, Bax and cleaved Caspased-3 immunoreactivity in ischemic penumbra region was detected by immunofluorescent staining, and cell apoptosis was detected by TUNEL staining.TXL treatment greatly improved neurological deficit and reduced the infarction volume compared to MCAO with buffer treatment (P

IntroductionPrevious studies in mostly Western populations have yielded conflicting findings on the association of vitamin B12 with diabetes risk, in part due to differences in study design and population characteristics. This study sought to examine the vitamin B12–diabetes association in Chinese adults with hypertension by both cross-sectional and longitudinal analyses.Research design and methodsThis report included a total of 16 699 participants from the China Stroke Primary Prevention Trial, with pertinent baseline and follow-up data. Diabetes mellitus was defined as either physician-diagnosed diabetes, use of glucose-lowering drugs, or fasting blood glucose (FBG) ≥7.0 mmol/L. New-onset diabetes was defined as any new case of onset diabetes during the follow-up period or FBG ≥7.0 mmol/L at the exit visit.ResultsAt baseline, there were 1872 (11.2%) patients with diabetes; less than 1.5% had clinical vitamin B12 deficiency (12 levels and FBG levels (β=0.18, 95% CI 0.15 to 0.21) and diabetes (OR=1.16, 95% CI 1.10 to 1.21). However, longitudinal analyses showed no association between baseline vitamin B12 and new-onset diabetes or changes in FBG levels. Among a subset of the sample (n=4366) with both baseline and exit vitamin B12 measurements, we found a positive association between an increase in vitamin B12 and an increase in FBG.ConclusionsIn this large Chinese population of patients with hypertension mostly sufficient with vitamin B12, parallel cross-sectional and longitudinal analyses provided new insight into the conflicting findings of previous studies, and these results underscore the need for future studies to consider both baseline vitamin B12 and its longitudinal trajectory in order to better elucidate the role of vitamin B12 in the development of diabetes. Such findings would have important clinical and public health implications.

BACKGROUND Previous studies indicated that trace elements may play an important role in cardiovascular diseases. However, data concerning the association between blood copper and the risk of stroke are limited. OBJECTIVE The aim of this study was to evaluate the association between plasma copper and the risk of first stroke, and examine any possible effect modifiers in hypertensive patients. METHODS We conducted a nested case-control study, using data from the China Stroke Primary Prevention Trial. Hypertension is defined as systolic blood pressure ≥ 140 mm Hg or diastolic blood pressure ≥ 90 mm Hg, or taking antihypertensive medication. A total of 618 first stroke cases and 618 controls matched for age, sex, treatment group, and study site were included in this study. The crude and adjusted risks of first stroke were estimated by ORs and 95% CIs using conditional logistic regression, without or with adjusting for pertinent covariates, respectively. RESULTS There were significant positive associations of plasma copper with risk of first stroke (per SD increment-OR: 1.20; 95% CI: 1.03, 1.39) and first ischemic stroke (OR: 1.26; 95% CI: 1.07, 1.50). When plasma copper was categorized in quartiles, significantly higher risks of first stroke (OR: 1.72; 95% CI: 1.12, 2.65) and first ischemic stroke (OR: 1.91; 95% CI: 1.18, 3.11) were found in participants in quartile 4 (≥ 117.0 μg/dL) than in those in quartile 1 (

Both increased arterial stiffness and higher total homocysteine (tHcy) are associated with an elevated risk for cardiovascular disease. However, the relationship between tHcy and arterial stiffness is still inconclusive. The authors aimed to test the relationship of tHcy with carotid‐femoral pulse wave velocity (cfPWV) and examine the possible effect modifiers in adults. A study was conducted from July to September 2016 in Jiangsu Province, China. A total of 16 644 participants were enrolled in the final analysis. Increased arterial stiffness is defined as a cfPWV ≥10 m/s. Overall, there was a positive association between tHcy and cfPWV levels (per 5‐μmol/L tHcy increase: β = 0.10; 95% confidence interval [CI], 0.08–0.13) and increased arterial stiffness (per 5‐μmol/L tHcy increase: odds ratio, 1.11; 95% CI, 1.07–1.14). Compared with participants with tHcy

Background: Subcortical ischemic vascular dementia (SIVD) has been proposed as the most frequent subtype of vascular cognitive impairment. The aim of this study was to evaluate the psychometric properties of the Chinese (Cantonese) Montreal Cognitive Assessment (CC- MoCA) in patients with SIVD in the Guangdong Province of China. Methods: 71 SIVD patients and 60 matched controls were recruited for the CC-MoCA, Mini Mental State Examination and executive clock drawing tasks. Receiver-operating characteristic curve analyses were performed to determine optimal sensitivity and specificity of the CC-MoCA total score in differentiating mild vascular dementia (VaD) patients from moderate VaD patients and controls. Results: The mean CC-MoCA scores of the controls, and mild and moderate VaD patients were 25.2 ± 3.8, 16.4 ± 3.7, and 10.0 ± 5.1, respectively. In our study, the optimal cutoff value for the CC-MoCA to be able to differentiate patients with mild VaD from controls is 21/22, and 13/14 to differentiate mild VaD from moderate VaD. Conclusion: The CC-MoCA is a useful cognitive screening instrument in SIVD patients.