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Abstract Background Despite the adverse effects of ambient fine particulate matter (PM2.5) on type 2 diabetes and the beneficial role of physical activity (PA), the influence of PM2.5 on the relationship between PA and type 2 diabetes remains unclear. Methods In this prospective study with 71,689 participants, PA was assessed by a questionnaire and was categorized into quartiles for volume and three groups for intensity. Long‐term PM2.5 exposure was calculated using 1‐km resolution satellite‐based PM2.5 estimates. PM2.5 exposure and PA's effect on type 2 diabetes were assessed by cohort‐stratified Cox proportional hazards models, individually and in combination. Results In 488,166 person‐years of follow‐up, 5487 incident type 2 diabetes cases were observed. The association between PA and type 2 diabetes was modified by PM2.5. Compared with the lowest quartile of PA volume, the highest quartile was associated with reduced type 2 diabetes risk in low PM2.5 stratification (≤65.02 µg/m3) other than in high PM2.5 stratification (>65.02 µg/m3), with the hazard ratio (HR) of 0.75 (95% confidence interval [CI]: 0.66–0.85) and 1.10 (95% CI: 0.99–1.22), respectively. Similar results were observed for PA intensity. High PM2.5 exposure combined with the highest PA levels increased the risk of type 2 diabetes the most (HR = 1.79, 95% CI: 1.59–2.01 for PA volume; HR = 1.82, 95% CI: 1.64–2.02 for PA intensity). Conclusion PA could reduce type 2 diabetes risk in low‐pollution areas, but high PM2.5 exposure may weaken or even reverse the protective effects of PA. Safety and health benefits of PA should be thoroughly assessed for long‐term polluted residents.

Abstract Background Cardiovascular disease (CVD) is a chronic disease with a serious prognosis, and obesity is a risk factor for CVD. Lipid accumulation product index (LAP) is a new indicator of obesity, waist circumference, and triglycerides were included in the formula, but its association with CVD is inconsistent. Therefore, this study researched the effect of LAP levels on CVD. Methods This prospective cohort study was based on the Kailuan cohort. A total of 95,981 participants who completed the first physical examination in 2006 and had no history of CVD or LAP absence were included. The participants were divided into four groups according to the LAP quartile (Q1 - Q4). Up until December 31, 2022, incidence density was calculated for each group. The hazard ratio (HR) and 95% confidence interval (CI) of CVD in each group were calculated by the Cox proportional hazards model. Results During a median follow-up period of 15.95 years, 9925 incident CVD events occurred (2123 myocardial infarction and 8096 stroke). There were differences in potential confounders among the four groups (P

Abstract Background Lipid-lowering drugs and antihypertensive drugs are commonly combined for cardiovascular disease (CVD). However, the relationship of combined medications with CVD remains controversial. We aimed to explore the associations of genetically proxied medications of lipid-lowering and antihypertensive drugs, either alone or both, with risk of CVD, other clinical and safety outcomes. Methods We divided 423,821 individuals in the UK Biobank into 4 groups via median genetic scores for targets of lipid-lowering drugs and antihypertensive drugs: lower low-density lipoprotein cholesterol (LDL-C) mediated by targets of statins or proprotein convertase subtilisin/kexin type 9 (PCSK9) inhibitors, lower systolic blood pressure (SBP) mediated by targets of β-blockers (BBs) or calcium channel blockers (CCBs), combined genetically lower LDL-C and SBP, and reference (genetically both higher LDL-C and SBP). Associations with risk of CVD and other clinical outcomes were explored among each group in factorial Mendelian randomization. Results Independent and additive effects were observed between genetically proxied medications of lipid-lowering and antihypertensive drugs with CVD (including coronary artery disease, stroke, and peripheral artery diseases) and other clinical outcomes (ischemic stroke, hemorrhagic stroke, heart failure, diabetes mellitus, chronic kidney disease, and dementia) (P > 0.05 for interaction in all outcomes). Take the effect of PCSK9 inhibitors and BBs on CVD for instance: compared with the reference, PCSK9 group had a 4% lower risk of CVD (odds ratio [OR], 0.96; 95%CI, 0.94–0.99), and a 3% lower risk was observed in BBs group (OR, 0.97; 95%CI, 0.94–0.99), while combined both were associated with a 6% additively lower risk (OR, 0.94; 95%CI, 0.92–0.97; P = 0.87 for interaction). Conclusions Genetically proxied medications of combined lipid-lowering and antihypertensive drugs have an independent and additive effects on CVD, other clinical and safety outcomes, with implications for CVD clinical practice, subsequent trials as well as drug development of polypills.

Abstract Background Population‐based epidemiological evidence regarding the association between fruit and vegetable intake and the incidence of hypertension is inconsistent. This prospective cohort study aimed to investigate the association between fruit and vegetable intake and the risk of new‐onset hypertension. Methods Based on the project of Prediction for Atherosclerotic Cardiovascular Disease Risk in China (China‐PAR), 58,981 Chinese adults without hypertension at baseline were included. Information on fruit and vegetable intake was collected using a food‐frequency questionnaire. Cox proportional hazards models were performed to estimate the hazard ratios (HRs) and 95% confidence intervals (CIs) of incident hypertension. Results During 640,795 person‐years of follow‐up, 21,008 new cases of hypertension were recorded. Compared with participants in the lowest quintile (Q1) of total fruit and vegetable (TFV) intake, the HRs (95% CIs) of incident hypertension were 0.90 (0.86–0.95), 0.85 (0.81–0.90), 0.82 (0.78–0.86), and 0.83 (0.78–0.88) for the Q2 to Q5 group (ptrend

The relationship of fine particulate matter (PM2.5) exposure and insulin resistance remains inclusive. Our study aimed to investigate this association in the project of Prediction for Atherosclerotic Cardiovascular Disease Risk in China (China-PAR). Specifically, we examined the associations between long-term PM2.5 exposure and three surrogate indicators of insulin resistance: the triglyceride-glucose index (TyG), TyG with waist circumference (TyG-WC) and metabolic score for insulin resistance (METS-IR). Additionally, we explored potential effect modification of dietary intake and components. Generalized estimating equations were used to evaluate the associations between PM2.5 and the indicators with an unbalanced repeated measurement design. Our analysis incorporated a total of 162,060 observations from 99,329 participants. Each 10 μg/m3 increment of PM2.5 was associated with an increase of 0.22 % [95 % confidence interval (CI): 0.20 %, 0.25 %], 1.60 % (95 % CI: 1.53 %, 1.67 %), and 2.05 % (95 % CI: 1.96 %, 2.14 %) in TyG, TyG-WC, and METS-IR, respectively. These associations were attenuated among participants with a healthy diet, particularly those with sufficient intake of fruit and vegetable, fish or tea (pinteraction

Abstract Background Dyslipidemia and inflammation are significant factors for the onset of cardiovascular diseases (CVD); however, studies regarding their interactions on the risk of CVD are scarce. This study aimed to assess the interaction of dyslipidemia and high-sensitivity C-reactive protein (hs-CRP) on CVD. Methods This prospective cohort enrolled 4,128 adults at baseline in 2009 and followed them up until May 2022 for collecting CVD events. Cox-proportional hazard regression analysis estimated the hazard ratios (HRs) and 95% confidence intervals (CIs) of the associations of increased hs-CRP (≥ 1 mg/L) and dyslipidemia with CVD. The additive interactions were explored using the relative excess risk of interaction (RERI) and the multiplicative interactions were assessed with HRs (95% CI) while the multiplicative interactions were assessed by the HRs (95% CI) of interaction terms. Results The HRs of the association between increased hs-CRP and CVD were 1.42 (95% CI: 1.14–1.79) and 1.17 (95% CI: 0.89–1.53) among subjects with normal lipid levels and subjects with dyslipidemia, respectively. Stratified analyses by hs-CRP levels showed that among participants with normal hs-CRP ( 2.10 g/L had a significant association with CVD [HR (95% CI): 1.69 (1.14–2.51)]. Interaction analyses showed that increased hs-CRP had multiplicative and additive interactions with LDL-C ≥ 160 mg/dL and non-HDL-C ≥ 190 mg/dL on the risk of CVD [HRs (95%CIs): 0.309 (0.153–0.621), and 0.505 (0.295–0.866); RERIs (95%CIs): -1.704 (-3.430-0.021 and − 0.694 (-1.476-0.089), respectively, all P

Abstract Background Familial hypercholesterolemia (FH) is underrecognized, and its association with coronary artery disease (CAD) remains limited, especially in China. We aimed to investigate the prevalence of FH and its relationship with CAD in a large Chinese cohort. Methods FH was defined using the Make Early Diagnosis to Prevent Early Death (MEDPED) criteria. The crude and age‐sex standardized prevalence of FH were calculated based on surveys of the Prediction for Atherosclerotic Cardiovascular Disease Risk in China (China‐PAR) project during 2007−2008. The associations of FH with incident CAD and its major subtypes were estimated with the cohort‐stratified multivariate Cox proportional hazard models based on the data from the baseline to the last follow‐up (2018−2020). Results Among 98,885 included participants, 190 participants were defined as FH. Crude and age−sex standardized prevalence and 95% confidence interval (CI) of FH were 0.19% (0.17%–0.22%) and 0.13% (0.10%–0.16%), respectively. The prevalence varied across age groups and peaked in the group of 60–

Abstract Background His-Purkinje system pacing (HPSP), including his-bundle pacing (HBP) and left bundle branch area pacing (LBBaP), imitates the natural conduction of the heart as an alternative to biventricular pacing (BVP) in cardiac resynchronization therapy (CRT). However, the feasibility and efficacy of HPSP were currently only evidenced by studies with a limited sample size, so this study aimed to provide a comprehensive assessment through a systematic review and meta-analysis. Methods In order to compare the clinical outcomes associated with HPSP and BVP in patients for CRT, PubMed, EMBASE, Cochrane Library and Web of Science database were searched from inception to April 10, 2023. Clinical outcomes of interest including QRS duration (QRSd), left ventricular (LV) function and New York Heart Association (NYHA) functional classification, pacing threshold, echocardiographic and clinical response, hospitalization rate of HF and all-cause mortality were also extracted and summarized for meta-analysis. Results A total of 13 studies (ten observational studies and three randomized studies) involving 1,121 patients were finally included. The patients were followed up for 6–27 months. Compared with BVP, CRT patients treated by HPSP presented shorter QRSd [mean difference (MD): -26.23 ms, 95% confidence interval (CI): -34.54 to -17.92, P

Introduction: Chronic relapsing ulcerative colitis (CRUC) is classified as an inflammatory bowel disease, and traditional Chinese medicine (TCM) has been recognized for its therapeutic benefits in treating CRUC. According to TCM principles, the prevailing syndromes in CRUC are yang deficiency and dampness stagnation (YDDS). The objective of this study is to establish a novel animal model of CRUC exhibiting the YDDS syndrome. Methods: Initially, the rats were administered hydrocortisone succinate sodium through subcutaneous injection, followed by the administration of senna folium granule solution. Subsequently, the rats underwent three cycles of dextran sulfate sodium solution ingestion. Results: Upon completion of the modeling process, it was observed that the disease activity index, colonic mucosal damage index score, colon weight/length ratio, colonic histopathology score, and tissue damage index scores of the model rats were elevated, while the colon length and spleen index exhibited a decrease compared to the control group. The pathological alterations in the model rats included the presence of shallow or deep ulcers and acute or chronic inflammation throughout the process of CRUC modeling. Additionally, our findings indicate a correlation between the proximity of the ulcer to the anal verge, the severity of the lesion, and the presence of precancerous glands, glandular disappearance, crypt abscesses, and tissue destruction. Furthermore, the expression levels of IL6, IL10, IFNG, and TNFA in the colon tissues were significantly elevated in the model rats compared to the control group. Notably, the end-stage lesions observed in CRUC exhibited greater severity when compared to those observed in cases of acute ulcerative colitis. Discussion: In conclusion, we have successfully developed a rat model of CRUC with YDDS syndrome, which can be utilized to investigate the effectiveness and underlying mechanisms of TCM in treating CRUC.

Abstract Background The effect of long‐standing prediabetes or its transition on incident cardiovascular disease (CVD) is unclear. This study aimed to evaluate the association of changes in fasting blood glucose (FBG) status with the risk of developing CVD. Methods This research included 12 145 Chinese adults aged 35–74 years and free from diabetes mellitus (DM) at baseline. Study participants were cross‐classified into six categories according to glucose at the first (1998–2001) and the second visit after 8 years: normal fasting glucose (NFG; 50–99 mg/dl), impaired FBG (IFG; 100–125 mg/dl), and DM. Cox proportional hazard regression model was used to estimate the hazard ratio (HR) and 95% confidence interval (CI) for CVD associated with transition of glucose status. Results During a median follow‐up of 5.5 years, 373 incident CVD cases occurred. Compared with participants remaining persistent NFG, a higher risk of developing CVD was identified among those remaining persistent IFG, progressing to DM from NFG or from IFG, with the multivariate‐adjusted HR (95% CI) of 1.792 (1.141, 2.816), 1.723 (1.122, 2.645) and 1.946 (1.120, 3.381), respectively. Furthermore, when stratified by glucose status at baseline, persistent IFG and progression from IFG to DM still increased CVD risk in comparison with reversion from IFG to NFG, with the multivariate‐adjusted HR (95% CI) of 1.594 (1.003, 2.532) and 1.913 (1.080, 3.389). Conclusions Participants with long‐standing IFG and progressing to DM had a higher risk of developing CVD. Further well‐designed studies are warranted to assess the association of other phenotypes or prediabetes duration with CVD.

Abstract Background Genetic variants within nearly 1000 loci are known to contribute to modulation of blood lipid levels. However, the biological pathways underlying these associations are frequently unknown, limiting understanding of these findings and hindering downstream translational efforts such as drug target discovery. Results To expand our understanding of the underlying biological pathways and mechanisms controlling blood lipid levels, we leverage a large multi-ancestry meta-analysis (N = 1,654,960) of blood lipids to prioritize putative causal genes for 2286 lipid associations using six gene prediction approaches. Using phenome-wide association (PheWAS) scans, we identify relationships of genetically predicted lipid levels to other diseases and conditions. We confirm known pleiotropic associations with cardiovascular phenotypes and determine novel associations, notably with cholelithiasis risk. We perform sex-stratified GWAS meta-analysis of lipid levels and show that 3–5% of autosomal lipid-associated loci demonstrate sex-biased effects. Finally, we report 21 novel lipid loci identified on the X chromosome. Many of the sex-biased autosomal and X chromosome lipid loci show pleiotropic associations with sex hormones, emphasizing the role of hormone regulation in lipid metabolism. Conclusions Taken together, our findings provide insights into the biological mechanisms through which associated variants lead to altered lipid levels and potentially cardiovascular disease risk.

Background: The trade-off between the benefits of regular physical activity (PA) and the potentially detrimental effects of augmented exposure to air pollution in highly polluted regions remains unclear. This study aimed to examine whether ambient fine particulate matter (PM2.5) exposure modified the impacts of PA volume and intensity on hypertension risk. Methods: We included 54,797 participants without hypertension at baseline in a nationwide cohort of the Prediction for Atherosclerotic Cardiovascular Disease Risk in China (China-PAR) project. PA volume and intensity were assessed by questionnaire, and high-resolution (1 km ×1 km) PM2.5 estimates were generated using a satellite-based model. Results: During 413,516 person-years of follow-up, 12,100 incident hypertension cases were identified. PM2.5 significantly modified the relationship between PA and hypertension incidence (pinteraction < 0.001). Increased PA volume was negatively associated with incident hypertension in the low PM2.5 stratum (

Abstract. Backgrounds:. Cardiovascular disease (CVD) remains the leading cause of deaths nationwide. However, little is understood about its temporal trend and corresponding influence on longevity improvements. We aimed to describe the updated tendency in CVD mortality and to quantify its impact on life expectancy (LE) increase in China. Methods:. All-cause mortality rates were calculated with population sizes from the National Bureau of Statistics and death counts from the National Health Commission. We estimated CVD mortality rates by allocating age- and sex-based mortality envelopes to each CVD subtype based on its proportion derived from the Disease Surveillance Points system. The probability of CVD premature deaths and LE were calculated with life tables and we adopted Arriaga's method to quantitate age- and cause-specific contributions to LE gains. Results:. During 2013 to 2018, the age-standardized mortality rate of CVD decreased from 289.69 (95% confidence interval [CI]: 289.03, 290.35)/100,000 to 272.37 (95%CI: 271.81, 272.94)/100,000, along with a decline in probability of CVD premature deaths from 9.05% (95%CI: 9.02%, 9.09%) to 8.13% (95%CI: 8.10%, 8.16%). The gap in CVD mortality across sexes expanded with more remarkable declines in females, especially for those aged 15 to 64 years. Among major subtypes, the probability of premature deaths from hemorrhage stroke declined fastest, while improvements of ischemic stroke and ischemic heart disease were limited, and there was an increase in stroke sequelae. LE in China reached 77.04 (95%CI: 76.96, 77.12) years in 2018 with an increase of 1.38 years from 2013. Of the total LE gains, 21.15% (0.29 years) were attributed to reductions of CVD mortality in the overall population, mostly driven by those aged >65 years. Conclusions:. The general process in reducing CVD mortality has contributed to longevity improvements in China. More attention should be paid to prevention and control of atherosclerotic CVD and stroke sequelae, especially for the elderly. Working-age males also deserve additional attention due to inadequate improvements.

Abstract Despite the recent development of using satellite remote sensing to predict surface NO2 levels in China, methods for estimating reliable historical NO2 exposure, especially before the establishment of NO2 monitoring network in 2013, are still rare. A gap‐filling model was first adopted to impute the missing NO2 column densities from satellite, then an ensemble machine learning model incorporating three base learners was developed to estimate the spatiotemporal pattern of monthly mean NO2 concentrations at 0.05° spatial resolution from 2005 to 2020 in China. Further, we applied the exposure data set with epidemiologically derived exposure response relations to estimate the annual NO2 associated mortality burdens in China. The coverage of satellite NO2 column densities increased from 46.9% to 100% after gap‐filling. The ensemble model predictions had good agreement with observations, and the sample‐based, temporal and spatial cross‐validation (CV) R2 were 0.88, 0.82, and 0.73, respectively. In addition, our model can provide accurate historical NO2 concentrations, with both by‐year CV R2 and external separate year validation R2 achieving 0.80. The estimated national NO2 levels showed a increasing trend during 2005–2011, then decreased gradually until 2020, especially in 2012–2015. The estimated annual mortality burden attributable to long‐term NO2 exposure ranged from 305 thousand to 416 thousand, and varied considerably across provinces in China. This satellite‐based ensemble model could provide reliable long‐term NO2 predictions at a high spatial resolution with complete coverage for environmental and epidemiological studies in China. Our results also highlighted the heavy disease burden by NO2 and call for more targeted policies to reduce the emission of nitrogen oxides in China.

Background: High sodium intake is an important risk factor for hypertension and cardiovascular disease. However, the association between gut microbiota composition and metabolomic profiles with dietary sodium intake and blood pressure (BP) is not well-understood. The metabolome, microbiome, and dietary salt intervention (MetaSalt) study aimed to investigate microbial and metabolomic profiles related to dietary sodium intake and BP regulation. Methods: This family-based intervention study was conducted in four communities across three provinces in rural northern China in 2019. Probands with untreated prehypertension or stage-1 hypertension were identified through community-based BP screening, and family members including siblings, offspring, spouses, and parents were subsequently included. All participants participated in a 3-day baseline examination with usual diet consumption, followed by a 10-day low-salt diet (3 g/d of salt or 51.3 mmol/d of sodium) and a 10-day high-salt diet (18 g/d of salt or 307.8 mmol/d of sodium). Differences in mean BP levels were compared according to the intervention phases using a paired Student's t-test. Results: A total of 528 participants were included in this study, with a mean age of 48.1 years, 36.7% of whom were male, 76.8% had a middle school (69.7%) or higher (7.1%) diploma, 23.4% had a history of smoking, and 24.4% were current drinkers. The mean arterial pressure at baseline was 97.2 ± 10.5 mm Hg for all participants, and significantly decreased during the low-salt intervention (93.8 ± 9.3, P

Background: Although both environmental and genetic factors were linked to coronary artery disease (CAD), the extent to which the association of air pollution exposure with CAD can be influenced by genetic risk was not well understood. Methods: A total of 41,149 participants recruited from the project of Prediction for Atherosclerotic Cardiovascular Disease Risk in China (China-PAR) were included. Genetic risk scores of CAD were constructed based on 540 genetic variants. Long-term PM2.5 exposures were assessed by adopting satellite-based PM2.5 estimations at 1-km resolution. We used stratified Cox proportional hazards regression model to examine the impact of PM2.5 exposure and genetic risk on CAD risk, and further analyzed modification effect of genetic predisposition on association between PM2.5 exposure and CAD risk. Results: During a median of 13.01 years of follow-up, 1,373 incident CAD events were observed. Long-term PM2.5 exposure significantly increased CAD risk, and the hazard ratios (HRs) [95% confidence intervals (CIs)] were 1.27 (1.05–1.54) and 1.95 (1.57–2.42) among intermediate and high PM2.5 exposure groups compared to low PM2.5 exposure group. The relative risks of CAD were 40% (HR: 1.40, 95%CI: 1.18–1.66) and 133% (HR: 2.33, 95%CI: 1.94–2.79) higher among individuals at intermediate and high genetic risk than those at low genetic risk. Compared with individuals with both low genetic risk and low PM2.5 exposure, those with high genetic risk and high PM2.5 exposure had highest CAD risk, with HR of 4.37 (95%CI: 3.13–6.11). We observed significant multiplicative (P

Background: Inconsistent results have been reported in developed countries for relationships between sedentary behavior and cancer incidence and mortality, and evidence from the Chinese population is scarce. This study aimed to investigate such relationships in large Chinese population-based prospective cohorts and to explore the joint effect and interaction of sedentary behavior and moderate-to-vigorous physical activity (MVPA) on these relationships. Methods: We included 95,319 Chinese adults without cancer from 3 large cohorts and assessed their sedentary behavior and physical activity with a unified questionnaire. Cancer incidence and mortality were confirmed by interviewing participants or their proxies and checking hospital records and death certificates. Hazard ratios (HRs) and 95% confidence intervals (95%CIs) for cancer and mortality were estimated using Cox proportional hazards regression models. Results: During 559,002 person-years of follow-up, 2388 cancer events, 1571 cancer deaths, and 4562 all-cause deaths were recorded. Sedentary behavior was associated with increased risk of developing cancer and deaths in a dose–response manner. The multivariable-adjusted HRs (95%CIs) were the following: HR = 1.16, 95%CI: 1.01‒1.33; HR = 1.24, 95%CI: 1.04‒1.48; and HR = 1.15, 95%CI: 1.04‒1.28 for cancer incidence, cancer mortality, and all-cause mortality, respectively, for those having ≥10 h/day of sedentary time compared with those having

Several literatures have examined the risk of chronic respiratory diseases in association with short-term ambient PM2.5 exposure in China. However, little evidence has examined the chronic impacts of PM2.5 exposure on morbidity of chronic respiratory diseases in cohorts from high pollution countries. Our study aims to investigate the associations. Based on a retrospective cohort among adults in northern China, a Cox regression model with time-varying PM2.5 exposure and a concentration-response (C-R) curve model were performed to access the relationships between incidence of chronic respiratory diseases and long-term PM2.5 exposure during a mean follow-up time of 9.8 years. Individual annual average PM2.5 estimates were obtained from a satellite-based model with high resolution. The incident date of a chronic respiratory disease was identified according to self-reported physician diagnosis time and/or intake of medication for treatment. Among 38,047 urban subjects analyzed in all-cause chronic respiratory disease cohort, 482 developed new cases. In CB (38,369), asthma (38,783), and COPD (38,921) cohorts, the onsets were 276, 89, and 14, respectively. After multivariable adjustment, hazard ratio and 95% confidence interval for morbidity of all-cause chronic respiratory disease, CB, asthma, and COPD were 1.15 (1.01, 1.31), 1.20 (1.00, 1.42), 0.76 (0.55, 1.04), and 0.66 (0.29, 1.47) with each 10 μg/m3 increment in PM2.5, respectively. Stronger effect estimates were suggested in alcohol drinkers across stratified analyses. Additionally, the shape of C-R curve showed an increasing linear relationship before 75.00 μg/m3 concentrations of PM2.5 for new-onset all-cause chronic respiratory disease, and leveled off at higher levels. These findings indicated that long-term exposure to high-level PM2.5 increased the risks of incident chronic respiratory diseases in China. Further evidence of C-R curves is warranted to clarify the associations of adverse chronic respiratory outcomes involving air pollution.

Decabromodiphenyl ethane (DBDPE) is a major alternative to BDE-209 owing to its lower toxicity. However, the mass production and increased consumption of DBDPE in recent years have raised concerns related to its adverse health effects. However, the effect and mechanism of DBDPE on cardiotoxicity have rarely been studied. In the present study, we investigated the impacts of DBDPE on the cardiovascular system in male SD rats and then explored the underlying mechanisms to explain the cardiotoxicity of DBDPE using AC16 cells. Under in vivo conditions, male rats were administered with an oral dosage of DBDPE at 0, 5, 50, and 500 mg/kg/day for 28 days, respectively. Histopathological analysis demonstrated that DBDPE induced cardiomyocyte injury and fibrosis, and ultrastructural observation revealed that DBDPE could induce mitochondria damage and dissolution. DBDPE could thus decrease the level of MYH6 and increase the level of SERCA2, which are the two key proteins involved in the maintenance of homeostasis during myocardial contractile and diastolic processes. Furthermore, DBDPE could increase the serum levels of glucose and low-density lipoprotein but decrease the content of high-density lipoprotein. In addition, DBDPE could activate the PI3K/AKT/GLUT2 and PPARγ/RXRα signaling pathways in AC16 cells. In addition, DBDPE decreased the UCP2 level and ATP synthesis in mitochondria both under in vitro and in vivo conditions, consequently leading to apoptosis via the Cytochrome C/Caspase-9/Caspase-3 pathway. Bisulfite sequencing PCR (BSP) identified the hypermethylation status of fat mass and obesity-associated gene (FTO). 5-aza exerted the opposite effects on the PI3K/AKT/GLUT2, PPARγ/RXRα, and Cytochrome C/Caspase-9/Caspase-3 signaling pathways induced by DBDPE in AC16 cells. In addition, the DBDPE-treated altered levels of UCP2, ATP, and apoptosis were also found to be significantly reversed by 5-aza in AC16 cells. These results suggested that FTO hypermethylation played a regulative role in the pathological process of DBDPE-induced glycolipid metabolism disorder, thereby contributing to the dysfunction of myocardial contraction and relaxation through cardiomyocytes fibrosis and apoptosis via the mitochondrial-mediated apoptotic pathway resulting from mitochondrial dysfunction.

Objective: To evaluate the impact of the integrated care in Luohu, China on the hypertension management. Methods: Hypertensive patients aged 35–74 years were recruited by the cluster-randomized sampling method from Luohu district which adopted integrated care and another district that remained original routine care during October 2018~January 2020, with 1353 and 583 patients from integrated and routine care communities, respectively. Health information, knowledge, attitude, and practice (KAP) towards cardiovascular diseases, pharmaceutical expenditure on hypertension and its comorbidities, and healthcare-related satisfaction were collected by questionnaires, with the expenditure additionally verified by hospitals’ billing records database. Continuous and categorical variables were compared by Wilcoxon test and Chi-square test, respectively. The age-standardized hypertension control rate was calculated by direct standardization. Results: The standardized hypertension management rate in the integrated care communities (45.75%) was significantly higher than that in routine care communities (14.07%) (P < 0.0001), while the age-standardized hypertension control rates were similar (integrated care: 50.3%, routine care: 52.65%, P = 0.518). The pharmaceutical expenditure on hypertension and its comorbidities in the integrated care communities was Ұ264.23 ± 357.38/month/person, lower than that in the routine care communities (Ұ354.56 ± 430.59/month/person). Patients in the integrated care had higher KAP scores (73.48 ± 11.54), compared with routine care (68.89 ± 15.51) (P < 0.0001). Moreover, the integrated care communities had higher satisfaction rates towards the convenience of dual referral (90.15% vs. 77.99%) and service quality (95.18% vs. 87.81%) than routine care communities (P < 0.0001). Conclusion: The practice of the integrated care in Luohu has substantially improved the hypertension management and the healthcare-related satisfaction while with relatively low pharmaceutical expenditure. The investigation of long-term impact of the integrated care on hypertension control and management is warranted.

Obesity is a leading contributor to colorectal cancer (CRC) risk, but the metabolic mechanisms linking obesity to CRC are not fully understood. We leveraged untargeted metabolomics data from two 1:1 matched, nested case–control studies for CRC, including 223 pairs from the US Prostate, Lung, Colorectal, and Ovarian (PLCO) Cancer Screening Trial and 190 pairs from a prospective Chinese cohort. We explored serum metabolites related to body mass index (BMI), constructed a metabolomic signature of obesity, and examined the association between the signature and CRC risk. In total, 72 of 278 named metabolites were correlated with BMI after multiple testing corrections (p FDR < 0.05). The metabolomic signature was calculated by including 39 metabolites that were independently associated with BMI. There was a linear positive association between the signature and CRC risk in both cohorts (p for linear < 0.05). Per 1-SD increment of the signature was associated with 38% (95% CI: 9–75%) and 28% (95% CI: 2–62%) higher risks of CRC in the US and Chinese cohorts, respectively. In conclusion, we identified a metabolomic signature for obesity and demonstrated the association between the signature and CRC risk. The findings offer new insights into the underlying mechanisms of CRC, which is critical for improved CRC prevention.

Background: Active commuting as a contributor to daily physical activity is beneficial for cardiovascular health, but leads to more chances of exposure to ambient air pollution. This study aimed to investigate associations between active commuting to work with cardiovascular disease (CVD), mortality and life expectancy among general Chinese adults, and to further evaluate the modification effect of fine particulate matter (PM2.5) exposure on these associations. Methods: We included 76,176 Chinese adults without CVD from three large cohorts of the Prediction for Atherosclerotic Cardiovascular Disease Risk in China project. Information about commuting mode and physical activity were collected by unified questionnaire. Satellite-based PM2.5 concentrations at 1-km spatial resolution was used for estimating PM2.5 exposure of participants. Hazard ratios (HRs) and 95% confidence intervals (CIs) for CVD incidence, mortality and all-cause mortality were estimated using Cox proportional hazards regression models. Multiplicative interaction term of commuting mode and PM2.5 level was tested to investigate potential effect modification. Results: During 448,499 person-years of follow-up, 2230 CVD events and 2777 all-cause deaths were recorded. Compared with the non-active commuters, the multivariable-adjusted HRs (95% CIs) of CVD incidence and all-cause mortality were 0.95(0.85–1.05) and 0.79(0.72–0.87) for walking commuters, respectively. Corresponding HRs (95% CIs) for cycling commuters were 0.71(0.62–0.82) and 0.67(0.59–0.76). Active commuters over 45 years old were estimated to have more CVD-free years and life expectancy than non-active commuters under lower PM2.5 concentration. However, these beneficial effects of active commuting were alleviated or counteracted by long-term exposure to high PM2.5 concentration. Significant multiplicative interaction of commuting mode and PM2.5 level was showed in all-cause mortality, with the lowest risk observed in cycling participants exposed to lower level of PM2.5. Conclusions: Active commuting was associated with lower risk of CVD, all-cause mortality, and longer life expectancy among Chinese adults under ambient settings with lower PM2.5 level. It will be valuable to encourage active commuting among adults and develop stringent strategies on ambient PM2.5 pollution control for prevention of CVD and prolongation of life expectancy.

Background: Decline in pulmonary function contributes to increasing cardiovascular disease (CVD) risk. Although adverse effects of short-term exposure to fine particulate matter (PM2.5) on pulmonary function have been recognized in healthy people or patients with respiratory disease, these results were not well illustrated among people with elevated CVD risk. Materials and methods: A panel study was conducted in three Chinese cities with three repeated visits among populations at intermediate to high-risk of CVD, defined as treated hypertension patients or those with blood pressure ≥ 130/80 mmHg, who met any of the three conditions including abdominal obesity, dyslipidemia, and diabetes mellitus. Individualized PM2.5 exposure and pulmonary function were measured during each seasonal visit. Linear mixed-effect models were applied to analyze the associations of PM2.5 concentrations with pulmonary function indicators, including forced expiratory volume in 1 s (FEV1), FEV1/forced vital capacity (FVC), maximal mid-expiratory flow (MMF), and peak expiratory flow (PEF). Results: Short-term PM2.5 exposure was significantly associated with decreased pulmonary function and an increment of 10 μg/m3 in PM2.5 concentrations during lag 12–24 hour was associated with declines of 41.7 ml/s (95% confidence interval [CI]: 7.7–75.7), 0.35% (95% CI: 0.01, 0.69), and 20.9 ml/s (95% CI: 0.5–41.3) for PEF, FEV1/FVC, and MMF, respectively. Results from stratified and sensitivity analyses were generally similar with the overall findings, while the adverse effects of PM2.5 on pulmonary functions were more pronounced in those who were physically inactive. Conclusions: This study first identified short-term exposure to PM2.5 was associated with impaired pulmonary function and physical activity might attenuate the adverse effects of PM2.5 among populations at intermediate to high-risk of CVD. These findings provide new robust evidence on health effects of air pollution and call for effective prevention measures among people at CVD risk.

The aim of this study was to evaluate the association between fruit intake and stroke risk considering the genetic predisposition. We used data from 34,871 participants from the project of Prediction for Atherosclerotic Cardiovascular Disease Risk in China (China-PAR project) from 2007 to 2020. A polygenic risk score comprising 534 genetic variants associated with stroke and its related factors was constructed to categorize individuals into low, intermediate, and high genetic risk groups. The associations of genetic and fruit intake with incident stroke were assessed by the Cox proportional hazard regression. We documented 2586 incident strokes during a median follow-up of 11.2 years. Compared with fruit intake < 200 g/week, similar relative risk reductions in stroke with adherence to fruit intake > 100 g/day across the genetic risk categories were observed (28–32%), but the absolute risk reductions were relatively larger in the highest genetic risk group (p for trend = 0.03). In comparison to those with a fruit intake < 200 g/week, those with a fruit intake >100 g/day in the low, intermediate, and high genetic risk groups had an average of 1.45 (95% CI, 0.61–2.31), 2.12 (1.63–2.59), and 2.19 (1.13–3.22) additional stroke-free years at aged 35, respectively. Our findings suggest that individuals with a high genetic risk could gain more absolute risk reductions and stroke-free years than those with a low genetic risk from increasing fruit intake for the stroke primary prevention.

Background: Diabetes caused substantial economic and health burden worldwide. However, the associations between air pollution and diabetes incidence were rarely reported in the developing countries, especially in China with relatively high PM2.5 concentrations. Objectives: A cohort-based study was conducted to assess the diabetes incidence associated with long-term exposure to ambient PM2.5. Methods: We collected individual health data and risk factors from the project of Prediction for Atherosclerotic Cardiovascular Disease Risk in China (China-PAR Project) from 15 provinces over China. Diabetes was defined as fasting glucose levels ≥7.0 mmol/L at the follow-ups and/or the use of insulin or oral hypoglycemic agents and/or diagnosed medical history of diabetes during 2004 to 2015. Individual-level PM2.5 exposures were estimated from satellite-based PM2.5 concentrations (10 km spatial resolution) during the study period. Cox proportional hazards models with random intercepts of each cohort and region were employed to estimate the diabetes incidence attributable to PM2.5, after the adjustment for age, gender, body mass index, smoking status, education, work-related physical activity level, hypertension, urbanicity, county-level averaged years of education, and long-term levels of temperature and relative humidity. Results: A total of 88,397 subjects were analyzed with 580,928 person-years of follow-up after 2004, among which 6439 new cases of diabetes were observed. The mean age of the subjects was 51.7 years at baseline. For an increase of 10 μg/m3 in long-term PM2.5 exposure, the multivariable-adjusted percent increase in the diabetes incidence was estimated to be 15.66% (95% confidence interval: 6.42%, 25.70%). The adverse effects of PM2.5 were larger among females, rural subjects, non-smokers, normotensives, subjects younger than 65 years and subjects with body mass index

Background: The concentration-response relationship between mortality and long-term exposure to fine particulate matter (PM2.5) has not been fully elucidated, especially at high levels of PM2.5 concentrations. Objective: We aimed to evaluate chronic effects of ambient PM2.5 exposure on deaths among Chinese adults in high-exposure settings. Methods: Participants of the Prediction for Atherosclerotic cardiovascular disease Risk in China (China-PAR) project were included from four prospective cohorts among Chinese adults aged ≥18 years old. The overall follow-up rate of the four cohorts was 93.4% until the recent follow-up survey that ended in 2015. The average of satellite-based PM2.5 concentrations during 2000–2015 at 1-km spatial resolution was assigned to each participant according to individual residence addresses. Based on the pooled analysis of individual data from the four cohorts, a Cox proportional hazards model was used to estimate the hazard ratio (HR) and corresponding 95% confidence intervals (95% CIs) for the association of PM2.5 exposure with mortality after multivariate adjustment. Results: A total of 116,821 participants were eligible in the final analysis. During a mean of 7.7 years of follow-up, 6,395 non-accidental deaths and 2,507 cardio-metabolic deaths occurred. The mean of PM2.5 concentration was 64.9 μg/m3 ranging from 31.2 μg/m3 to 97.0 μg/m3. For each 10 μg/m3 increment in PM2.5, the HR was 1.11 (95% CI: 1.08–1.14) for non-accidental mortality and 1.22 (95% CI: 1.16–1.27) for cardio-metabolic mortality. In addition, a weak exponential curve for the concentration-response association between mortality and PM2.5 was observed among Chinese adults. Conclusions: Our study provided important evidence of the long-term effects of PM2.5 exposure on deaths among Chinese adults. The findings expand our knowledge on concentration-response relationship in high-exposure environments, which is essential to address the urgent challenge of reducing the disease burden attributable to PM2.5 exposure in rapidly industrializing countries such as China. Keywords: Satellite-based PM2.5, Long-term exposure, Cohort study, Mortality, Concentration-response relationship

INMAP is a spindle protein that plays essential role for mitosis, by ensuring spindle and centromere integrality. The aim of this study was to investigate the relevant functions of INMAP for genomic stability and its functional pathway. We overexpressed INMAP in HeLa cells, resulting in growth inhibition in monolayer cell cultures, anchorage-independent growth in soft agar and xenograft growth in nude mice. In this system caused micronuclei (MNi) formation, chromosome distortion and γH2AX expression upregulation, suggesting DNA damage induction and genomic stability impairment. As a tumour biochemical marker, lactate dehydrogenase (LDH) isoenzymes were detected to evaluate cell metabolic activity, the results confirming that total activity of LDH, as well as that of its LDH5 isoform, is significantly decreased in INMAP-overexpressing HeLa cells. The levels of p53 and p21 were upregulated, and however, that of PCNA and Bcl-2, downregulated. Indirect immunofluorescence (IIF) and coimmunoprecipitation (CoIP) analyses revealed the interaction between INMAP and p21. These results suggest that INMAP might function through p53/p21 pathways.

We evaluated the potentiality of plasma microRNAs (miRNAs, or miRs) that were considered as novel biomarkers for acute coronary syndrome (ACS), including acute myocardial infarction (AMI) and unstable angina (UA).We initially identified plasma miR-122, -140-3p, -144, -720, -1225-3p, -2861, and -3149 as candidate miRNAs associated with AMI (≥2 fold and P < 0.05) by comparing expression differences of miRNAs among AMI, non-coronary heart disease (non-CHD) and stable angina (SA) groups, using miRNA microarrays (n = 8 independent arrays in each group). Those seven plasma miRNAs were further examined with qRT-PCR analyses in two replications including 111 and 428 patients separately, and the results demonstrated that plasma miR-122, -140-3p, -720, -2861, and -3149 were elevated in the ACS group vs. the non-ACS (non-CHD + SA) group (P < 0.01). The area under the receiver operating characteristic curve (AUC) of the five miRNAs for ACS classification was 0.838, 0.818, 0.865, 0.852, and 0.670, respectively (all P < 0.001), while the values reached 0.843 and 0.925 when simultaneously with miR-122 and -3149 or with miR-122, -2861, and -3149 together (all P < 0.001). In plasma of pigs after coronary ligation, miR-122 was increased from 180 min to 240 min and miR-3149 was augmented from 30 min to 240 min compared with the sham pigs (all P < 0.05).Plasma miR-122, -140-3p, -720, -2861, and -3149 were associated with and potentially novel biomarkers for ACS.