Somatic and Germline Variants and Coronary Heart Disease in a Chinese Population.

Importance: The genetic basis of coronary heart disease (CHD) has expanded from a germline to somatic genome, including clonal hematopoiesis of indeterminate potential (CHIP). How CHIP confers CHD risk in East Asian individuals, especially those with small clones (variant allele fraction [VAF] 0.5%-2%) and different genetic backgrounds, was completely unknown. Objective: To investigate the CHIP profile in a general Chinese cohort by deep sequencing and further explore the association between CHIP and incident CHD considering germline predisposition. Design, Setting, and Participants: This cohort study used data from 3 prospective cohorts in the project Prediction for Atherosclerotic Cardiovascular Disease Risk in China. Participants without cardiovascular disease or cancer at baseline were enrolled in 2001 and 2008 and had a median follow-up of 12.17 years extending into 2021. Exposures: CHIP mutations were detected by targeted sequencing (mean depth, 916×). A predefined CHD polygenic risk score (PRS) comprising 531 variants was used to evaluate germline predisposition. Main Outcomes and Measures: The main outcome was first incident CHD. Results: Among 6181 participants, the median (IQR) age was 53.83 years (45.35-62.39 years); 3082 participants (49.9%) were female, and 3099 (50.1%) were male. A total of 1100 individuals (17.80%) harbored 1372 CHIP mutations at baseline. CHIP was independently associated with incident CHD (hazard ratio [HR], 1.42; 95% CI, 1.18-1.72; P = 2.82 × 10-4) and presented a risk gradient with increasing VAF (P = 3.98 × 10-3 for trend). Notably, individuals with small clones, nearly half of CHIP carriers, also demonstrated a higher CHD risk compared with non-CHIP carriers (HR, 1.33; 95% CI, 1.02-1.74; P = .03) and were 4 years younger than those with VAF of 2% or greater (median age, 58.52 vs 62.70 years). Heightened CHD risk was not observed among CHIP carriers with low PRS (HR, 1.02; 95% CI, 0.64-1.64; P = .92), while high PRS and CHIP jointly contributed a 2.23-fold increase in risk (95% CI, 1.51-3.29; P = 6.29 × 10-5) compared with non-CHIP carriers with low PRS. Interestingly, the diversity in CHIP-related CHD risk within each PRS group was substantially diminished when removing variants in the inflammatory pathway from the PRS. Conclusions: This study revealed that elevated CHD risk attributed to CHIP was nonnegligible even for small clones. Inflammation genes involved in CHD could aggravate or abrogate CHIP-related CHD risk.

Lifestyle improvement and the reduced risk of cardiovascular disease: the China-PAR project.

BACKGROUND: The benefits of healthy lifestyles are well recognized. However, the extent to which improving unhealthy lifestyles reduces cardiovascular disease (CVD) risk needs to be discussed. We evaluated the impact of lifestyle improvement on CVD incidence using data from the China-PAR project (Prediction for Atherosclerotic Cardiovascular Disease Risk in China). METHODS: A total of 12,588 participants free of CVD were followed up for three visits after the baseline examination. Changes in four lifestyle factors (LFs) (smoking, diet, physical activity, and alcohol consumption) were assessed through questionnaires from the baseline to the first follow-up visit. Cox proportional hazard models were used to estimate hazard ratios (HRs) and corresponding 95% confidence intervals (CIs). The risk advancement periods (RAPs: the age difference between exposed and unexposed participants reaching the same incident CVD risk) and population-attributable risk percentage (PAR%) were also calculated. RESULTS: A total of 909 incident CVD cases occurred over a median follow-up of 11.14 years. Compared with maintaining 0-1 healthy LFs, maintaining 3-4 healthy LFs was associated with a 40% risk reduction of incident CVD (HR = 0.60, 95% CI: 0.45-0.79) and delayed CVD risk by 6.31 years (RAP: -6.31 [-9.92, -2.70] years). The PAR% of maintaining 3-4 unhealthy LFs was 22.0% compared to maintaining 0-1 unhealthy LFs. Besides, compared with maintaining two healthy LFs, improving healthy LFs from 2 to 3-4 was associated with a 23% lower risk of CVD (HR = 0.77, 95% CI: 0.60-0.98). CONCLUSIONS: Long-term sustenance of healthy lifestyles or improving unhealthy lifestyles can reduce and delay CVD risk.

Cross-sectional study of household solid fuel use and renal function in older adults in China.

BACKGROUND: Emerging evidence links outdoor air pollution and declined renal function but the relationship between household air pollution and renal function is not well understood. METHODS: Using cross-sectional data from the multi-provincial INTERMAP-China Prospective Study, we collected blood samples and questionnaire information on stove use and socio-demographic factors. We calculated estimated glomerular filtration rate (eGFR) from serum creatinine to assess renal function. Participants with eGFR <60 mL/min per 1.73 m2 were defined as having chronic kidney disease (CKD) in this analysis. Generalized estimating equations were used to estimate the association of household fuel with renal function and prevalent CKD in models adjusting for confounders. RESULTS: Among the 646 enrolled adults (40-79y; 56% female), one-third exclusively used clean fuel (gas and electric) cookstoves and 11% of northern China participants (n = 49 of 434) used only clean fuel heaters, whereas the rest used solid fuel. In multivariable models, use of solid fuel cookstoves was associated with 0.17 ml/min/1.73 m2 (95% CI: -0.30, 0.64) higher eGFR and 19% (0.86, 1.64) higher prevalence of CKD than exclusive clean fuel use. Greater intensity of solid fuel use was associated with 0.25 ml/min/1.73 m2 (-0.71, 0.21) lower eGFR per 5 stove-use years, though the confidence intervals included the null, while greater current intensity of indoor solid fuel use was associated with 1.02 (1.00, 1.04) higher prevalent CKD per 100 stove-use days per year. Larger associations between current solid fuel use and intensity of use with lower eGFR and prevalent CKD were observed among participants in southern China, those with hypertension or diabetes (eGFR only), and females (CKD only), through these groups had small sample sizes and some confidence intervals included the null. CONCLUSION: We found inconsistent evidence associating household solid fuel use and renal function in this cross-sectional study of peri-urban Chinese adults.

Metabolic Differences between Ex-Smokers and Nonsmokers: A Metabolomic Analysis.

The aim of this study was to compare changes in the metabolite levels of ex-smokers and nonsmokers using a metabolomics approach, accounting for the weight gain in ex-smokers. Volunteer ex-smokers and nonsmokers were recruited from two cohorts Shijingshan (174) and Xishan (78), respectively, at a 1 : 1 ratio for age and sex. Nontargeted metabolomics was performed on the volunteers' blood samples using liquid chromatography-mass spectrometry, and multivariate statistical analysis was performed using principal component analysis and orthogonal partial least squares discriminant analysis. Enrichment analysis was used to identify Kyoto Encyclopedia of Genes and Genomes (KEGG) pathways associated with differential metabolites and weighted gene co-expression network analysis and maximal correlation coefficient (MCC) algorithms were used to identify key metabolites. The results revealed no significant differences between the distribution of blood metabolite levels in the ex-smokers and nonsmokers. The biosynthesis of valine, leucine, and isoleucine was determined to be associated with differential metabolites, and five key metabolites were identified. Further analysis revealed differences in weight gain and regained metabolite levels in ex-smokers, and 10 differential metabolites were identified that may be associated with weight gain in ex-smokers. These findings suggest that quitting smoking restores metabolites to almost normal levels and results in weight gain. The identified key metabolites and metabolic pathways may also provide a basis for clinical studies.

Lifelong smoking status, weight gain, and subsequent risk of major adverse cardiovascular events: Long-term follow-up of a middle-aged Chinese population.

OBJECTIVE: The aim of this study was to explore the association of lifelong smoking status with risk of major adverse cardiovascular events (MACE) accounting for weight change in a Chinese cohort. METHODS: The cohort of the People's Republic of China-United States of America (PRC-USA) Collaborative Study of Cardiovascular and Cardiopulmonary Epidemiology was established in 1983 to 1984, resurveyed during 1987 to 1988 and 1993 to 1994, and followed up to 2005. A total of 5,849 participants who survived in 1993 to 1994 were classified into never smokers, long-term quitters, short-term quitters, short-term relapsers and new smokers, long-term relapsers and new smokers, and persistent smokers according to the information on lifelong smoking status collected in all three surveys. The associations of lifelong smoking status with MACE in the subsequent 10 years were explored with Cox proportional hazards models. RESULTS: During a median follow-up of 10.2 years, 694 participants had MACE. Compared with persistent smokers, the multivariable-adjusted hazard ratio of developing MACE was 0.83 (95% CI: 0.61-1.12) for short-term quitters, 0.75 (95% CI: 0.54-1.02) for long-term quitters, and 0.68 (95% CI: 0.54-0.85) for never smokers (ptrend = 0.001). In comparison, the hazard ratio was 1.03 (95% CI: 0.77-1.35) for long-term relapsers and new smokers and 0.78 (95% CI: 0.46-1.22) for short-term relapsers and new smokers (ptrend = 0.018). These associations were not significantly altered by further adjusting for weight change in the past 10 years. CONCLUSIONS: Lifelong smoking status is significantly associated with risk of MACE. As time duration increased, health benefit to quitters would become close to that of never smokers, and harms to relapsers and new smokers would become close to that of persistent smokers.

Rational design of a large Stokes shift xanthene-benzothiozolium dyad for probing cysteine in mitochondria.

Xanthene-modified cyanine dyes are considered to be an effective means to extend the emission wavelength and improve the photo-stability of cyanine dyes. However, the fluorophores obtained by this strategy generally have narrow Stokes shifts, which severely limits their application in biological imaging. Herein, a reasonable design strategy is adopted to provide an effective strategy to commendably improve the Stokes shift of xanthene-benzothiozolium fluorophores via the simultaneous expansion of a molecular π-conjugated system and heteroatomic substitution. Combined with density functional theory calculation guidance, the O atom is replaced with the S atom in the xanthene moiety and a π-conjugated benzene ring is introduced in the benzothiozolium moiety. Surprisingly, the results of the spectroscopic experiment showed that the fluorescence emission wavelength of PhCy-OH was extended to 803 nm, and the Stokes shift was improved to 68 nm. PhCy-Cys can effectively distinguish Cys from homocysteine (Hcy) and glutathione (GSH) with an extremely low detection limit of 0.166 µM. Importantly, PhCy-Cys has the ability to image endogenous Cys in mitochondria, providing the potential for exploring the specific function and mechanism of Cys in regulating oxidative stress in mitochondria.

Adverse associations of sedentary behavior with cancer incidence and all-cause mortality: A prospective cohort study.

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 <6 h/day of sedentary time. Sedentary populations (≥10 h/day) developed cancer or died 4.09 years and 2.79 years earlier, respectively, at the index age of 50 years. Failure to achieve the recommended level of MVPA may further aggravate the adverse associations, with the highest cancer and mortality risks being observed among participants with both ≥10 h/day of sedentary time and <150 min/week of MVPA. Limitations of this study include the fact that physical activity information was obtained via questionnaire instead of objective measurement and that there were insufficient incident cases for the analysis of associations between sedentary behavior and site-specific cancers. CONCLUSION: Sedentary behavior was associated with an increased risk of cancer and all-cause mortality among Chinese adults, especially for those with ≥10 h/day of sedentary time. It is necessary to reduce sedentary time, in addition to increasing MVPA levels, for the prevention of cancer and premature death.

Determinants of personal exposure to PM2.5 and black carbon in Chinese adults: A repeated-measures study in villages using solid fuel energy.

Exposure to air pollution is a leading health risk factor. The variance components and contributions of indoor versus outdoor source determinants of personal exposure to air pollution are poorly understood, especially in settings of household solid fuel use. We conducted a panel study with up to 4 days of repeated measures of integrated gravimetric personal exposure to PM2.5 and black carbon in 787 men and women (ages 40-79) living in peri-urban villages in northern (Beijing and Shanxi) and southern (Guangxi) China. We simultaneously measured outdoor PM2.5 and collected questionnaire data on sociodemographic characteristics and indoor pollution sources including tobacco smoking and solid fuel stove use. We obtained over 2000 days of personal exposure monitoring which showed higher exposures in the heating season (geometric mean (GM): 108 versus 65 µg/m3 in the non-heating season for PM2.5) and among northern participants (GM: 90 versus 59 µg/m3 in southern China in the non-heating season for PM2.5). We used mixed-effects models to estimate within- and between-participant variance components and to assess the determinants of exposures. Within-participant variance in exposure dominated the total variability (68-95%). Outdoor PM2.5 was the dominant variable for explaining within-participant variance in exposure to PM2.5 (16%). Household fuel use (PM2.5: 8%; black carbon: 10%) and smoking status (PM2.5: 27%; black carbon: 5%) explained the most between-participant variance. Indoor sources (solid fuel stoves, tobacco smoking) were associated with 13-30% higher exposures to air pollution and each 10 µg/m3 increase in outdoor PM2.5 was associated with 6-8% higher exposure. Our findings indicate that repeated measurements of daily exposure are likely needed to capture longer-term exposures in settings of household solid fuel use, even within a single season, and that reducing air pollution from both outdoor and indoor sources is likely needed to achieve measurable reductions in exposures to air pollution.

A lysosome-targeted fluorescent probe for the specific detection and imaging of formaldehyde in living cells.

We presented herien the rational design, synthesis, and photophysical property studies of the lysosome-targeted fluorescence FA probe NP-Lyso, an isopropyl group modified ortho-diaminonaphthalimide derivative. After the reaction of FA and ortho-phenylenediamine modified with the isopropyl group in NP-Lyso, the probe exhibited favorable features such as a large fluorescence enhancement, specific selectivity and high sensitivity for the detection of FA. More importantly, NP-Lyso could be used to detect and image endogenous FA in lysosomes. In light of these prominent properties, we envision that NP-Lyso will be an efficient optical imaging approach for investigating the biofunctions of FA in living systems.

Triglyceride to high-density lipoprotein cholesterol ratio and risk of atherosclerotic cardiovascular disease in a Chinese population.

BACKGROUND AND AIMS: Triglyceride (TG) to high-density lipoprotein cholesterol (HDL-C) ratio may play a role in predicting cardiovascular events. We aimed to prospectively explore the association between the TG/HDL-C ratio and atherosclerotic cardiovascular disease (ASCVD), ischemic stroke, as well as coronary heart disease (CHD) in a Chinese population. METHODS AND RESULTS: This prospective cohort study included 9368 participants from four Chinese populations in the People's Republic of China-United States of America (PRC-USA) Collaborative Study of Cardiovascular and Cardiopulmonary Epidemiology. Over a follow-up period of 20 years, 624 cases of ASCVD events including 458 ischemic stroke events and 166 CHD events were recorded. The relationship between the TG/HDL-C ratio and the endpoints was evaluated through multivariate Cox proportional hazard models adjusted for potential confounding variables, including age, sex, urban or rural residence, northern or southern China, occupational type, education, physical exercise, smoking status, drinking status, body mass index, hypertension, high low-density lipoprotein cholesterol, diabetes, and antihypertensive medication use at baseline. With the lowest TG/HDL-C tertile as the reference, the middle and highest tertiles had the hazard ratios (HRs) and 95% confidence intervals (CIs) of 1.13 (0.91, 1.40), 1.36 (1.10, 1.67) respectively for ASCVD (p for trend = 0.0028), and 1.19 (0.93, 1.54),1.47 (1.15, 1.87) respectively for ischemic stroke (p for trend = 0.0016). However, no significant association was found for CHD events. CONCLUSION: TG/HDL-C ratio was positively associated with the risk of ASCVD and ischemic stroke events in the Chinese population.

Chronic Effects of High Fine Particulate Matter Exposure on Lung Cancer in China.

Rationale: Limited cohort studies have evaluated chronic effects of high fine particulate matter (particulate matter with an aerodynamic diameter ≤2.5 µm [PM2.5]) exposure on lung cancer.Objectives: To investigate the response pattern of lung cancer associated with high PM2.5 exposure.Methods: A Chinese cohort of 118,551 participants was followed up from 1992 to 2015. By incorporating PM2.5 exposure at 1 km spatial resolution generated using the satellite-based model during 2000-2015, we estimated the association between lung cancer and time-weighted average PM2.5 concentration using Cox proportional hazard models.Measurements and Main Results: A total of 844 incident lung cancer cases were identified during 915,053 person-years of follow-up. Among them, 701 lung cancer deaths occurred later. The exposure-response curves for lung cancer associated with PM2.5 exposure were nonlinear, with steeper slopes at the higher concentrations. Adjusted for age, sex, geographical region, urbanization, education level, smoking status, alcohol consumption, work-related physical activity, and body mass index, participants exposed to the second-fifth quintiles of PM2.5 had higher risk for lung cancer incidence than those exposed to the first quintile, with hazard ratios of 1.44 (95% confidence interval [CI], 1.10-1.88), 1.49 (95% CI, 1.12-1.99), 2.08 (95% CI, 1.42-3.04), and 2.45 (95% CI, 1.83-3.29), respectively. The corresponding hazard ratios for lung cancer mortality were 1.83 (95% CI, 1.33-2.50), 1.80 (95% CI, 1.29-2.53), 2.50 (95% CI, 1.62-3.86), and 2.95 (95% CI, 2.09-4.17), respectively.Conclusions: We provide strong evidence that high PM2.5 exposure leads to an elevated risk of lung cancer incidence and mortality, highlighting that remarkable public health benefits could be obtained from the improvement of air quality in highly polluted regions.

Association of cardiovascular diseases with milk intake among general Chinese adults.

BACKGROUND: The association of milk intake with cardiovascular disease (CVD) and cause-specific mortality remained controversial and evidence among the Chinese population was limited. We aimed to study the relationship between milk intake and CVDs among general Chinese adults. METHODS: A total of 104,957 participants received questionnaire survey. Results of physical examination such as anthropometric measurements and biochemical tests during 2007 to 2008, demographic data and their information on milk intake were collected through standardized questionnaires. Cox proportional hazard regression models were used to calculate hazard ratios (HRs) and their corresponding 95% confidence intervals (CIs) of CVD incidence, cause-specific mortality and all-cause mortality related to milk intake. Restricted cubic splines (RCSs) were applied to examine dose-response associations. RESULTS: Among the 91,757 participants with a median follow-up period of 5.8 years, we documented 3877 CVD cases and 4091 all-cause deaths. Compared with participants who never consumed milk, the multivariate-adjusted HRs (95% CIs) of CVD incidence for 1 to 150 g/day, 151 to 299 g/day, and ≥300 g/day were 0.94 (0.86-1.03) (P > 0.05), 0.77 (0.66-0.89) (P < 0.05), and 0.59 (0.40-0.89) (P < 0.05), respectively; each 100 g increase of daily milk intake was associated with 11% lower risk of CVD incidence (HR, 0.89; 95% CI: 0.85-0.94; P < 0.001), and 11% lower risk of CVD mortality (HR, 0.89; 95% CI: 0.82-0.97; P = 0.008) after adjustment for age, sex, residential area, geographic region, education level, family history of CVD, smoking, alcohol drinking, physical activity level, body mass index, and healthy diet status (ideal or not). RCS analyses also showed a linear dose-response relationship with CVD (P for overall significance of the curve <0.001; P for non-linearity = 0.979; P for linearity <0.001) and stroke (P for overall significance of the curve = 0.010; P for non-linearity = 0.998; P for linearity = 0.002) incidence, and CVD mortality (P for overall significance of the curve = 0.045; P for non-linearity = 0.768; P for linearity = 0.014) within the current range of daily milk intake. CONCLUSIONS: Daily milk intake was associated with lower risk of CVD incidence and mortality in a linear inverse relationship. The findings provide new evidence for dietary recommendations in CVD prevention among Chinese adults and people with similar dietary pattern in other countries.

A lysosome-targeted near-infrared fluorescent probe for imaging endogenous cysteine (Cys) in living cells.

Cysteine (Cys) is one of the most important essential biothiols in lysosomes. Highly selective probes for specific detection and imaging of lysosomal Cys over other biological thiols are rare. Herein, we developed a lysosome-targeted near-infrared fluorescent probe SHCy-C based on a novel NIR-emitting thioxanthene-indolium dye. Due to the turn-on fluorescence response elicited by the intramolecular charge transfer (ICT) processes before and after the reaction with Cys, probe SHCy-C exhibits high selectivity and sensitivity (16 nM) for the detection of Cys. More importantly, probe SHCy-C is found to precisely target lysosomes and achieves the "turn-on" detection and imaging of endogenous Cys in lysosomes.

Association Between Serum Cotinine and Severe Abdominal Aortic Calcification in US Adults.

This study aims to explore the association between serum cotinine and severe abdominal aortic calcification (AAC) in the US adults. We examined 2840 participants with a weighted mean age of 57.4 years from the National Health and Nutrition Examination Survey 2013-2014. Serum cotinine was analyzed as the main exposure both continuously and categorically (tertiles). Abdominal aortic calcification detected with dual-energy X-ray absorptiometry was quantified using the Kauppila score system. Severe AAC was detected in 252 (8.9%) participants. The multivariable-adjusted odds ratios and 95% confidence intervals (CIs) of the middle and top cotinine categories were 1.14 (0.79-1.64) and 1.80 (1.21-2.68), respectively, P for trend = .004. Per unit increase in log-transformed serum cotinine was associated with 10% (95% CI: 6%-15%) higher odds of severe AAC when serum cotinine was analyzed as a continuous variable. The association was consistent across sex and ethnic groups. In conclusion, elevated serum cotinine level was associated with higher odds for severe AAC in a representative sample of US adults.

Fasting glucose and its association with 20-year all-cause and cause-specific mortality in Chinese general population.

OBJECTIVE: The aim of this study was to explore the relationship between fasting glucose levels and all-cause and cause-specific mortality in Chinese population. METHODS: The role of fasting blood glucose levels as a predictor of all-cause and cause-specific mortality was estimated in 9930 participants from four Chinese general populations with a 20-year follow-up. Multivariate Cox proportional hazard models were used to identify the relationship between fasting glucose and mortality. RESULTS: There were 1471 deaths after a median follow-up of 20.2 years (a total of 187,374 person-years), including 310 cardiovascular deaths, 581 cancer deaths, and 580 other-cause deaths. After adjustment for age, sex, urban or rural, northern or southern of China, types of work, education level, physical exercise, smoking status, drinking status, body mass index, systolic blood pressure, and serum total cholesterol at baseline, the hazard ratios (HRs) and 95% confidence intervals (CIs) for all-cause mortality in the fasting blood glucose categories of <60, 60-69, 70-79, 90-99, 100-109, 110-125, and ≥126 mg/dl were 1.38 (1.04-1.84), 1.20 (1.01-1.43), 1.18 (1.03-1.36), 1.18 (0.99-1.41), 1.48 (1.16-1.88), 1.17 (0.84-1.62), and 2.23 (1.72-2.90), respectively, in contrast to the reference group (80-89 mg/dl). The HRs and 95% CIs for cardiovascular disease mortality in these groups were 2.58 (1.44-4.61), 1.41 (0.95-2.10), 1.56 (1.15-2.11), 1.29 (0.88-1.89), 1.36 (0.78-2.37), 1.05 (0.52-2.11), and 2.73 (1.64-4.56), respectively. CONCLUSIONS: Both low and high fasting glucose were significantly associated with increased risk of all-cause and cardiovascular mortality in Chinese general population.

Predicting 10-Year and Lifetime Stroke Risk in Chinese Population.

Background and Purpose- Risk assessment is essential for the primary prevention of stroke. However, the current available tools derived from Chinese populations are insufficient for individualized 10-year and lifetime stroke risk prediction. Our study aims to develop and validate personalized 10-year and lifetime stroke risk equations incorporating 4 large Chinese cohorts. Methods- We used 2 prospective cohorts of 21 320 participants with similar survey protocols as the derivation cohort to develop sex-specific 10-year and lifetime stroke risk equations. Two other independent cohorts with 14 123 and 70 838 participants were used for external validation. In addition, the performance of the 10-year stroke risk equations among participants aged ≥55 years was compared with the new Framingham Stroke Risk Profile. Results- The sex-specific equations for predicting 10-year stroke risk had C statistics being 0.810 for men and 0.810 for women, with calibration χ2 being 15.0 (P=0.092) and 7.8 (P=0.550), respectively. The lifetime stroke risk equations also showed C statistics around 0.800 and calibration χ2 below 20 for both sexes. In the validation cohorts, we found good agreement between the observed and predicted stroke probabilities for both the 10-year and lifetime stroke risk equations. Further compared with the new Framingham Stroke Risk Profile, our 10-year stroke risk equations displayed better prediction capability. In addition, based on lifetime stroke risk assessment, 5.7% of study participants aged 35 to 49 years old were further reclassified as high risk, who were initially categorized as low 10-year risk. Conclusions- We developed a well-performed tool for predicting personalized 10-year and lifetime stroke risk among the Chinese adults, which will facilitate the further identification of high-risk individuals and community-based stroke prevention in China.

Long-term exposure to ambient fine particulate matter and incidence of diabetes in China: A cohort study.

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 <25 kg/m2. CONCLUSIONS: Our findings provided evidence for the association of long-term exposure to PM2.5 with diabetes incidence in China. A sustained improvement of air quality will benefit the reduction for diabetes epidemic in China.

Impact of healthy lifestyles on cancer risk in the Chinese population.

BACKGROUND: Although cancer has become one of the leading health burdens, to the authors' knowledge, evidence regarding its relationship with a healthy lifestyle in the Chinese population remains limited. METHODS: The authors evaluated the association between clustering of healthy lifestyle factors and cancer risk using 3 prospective cohort studies with 101,208 Chinese adults from the general population. Hazard ratios (HRs) and corresponding 95% confidential intervals (95% CIs) related to healthy lifestyle factors were calculated using Cox proportional hazard models, and population-attributable risk percentages were estimated further. RESULTS: The results demonstrated that each additional healthy lifestyle factor was associated with a 6% (range, 3%-9%) lower risk of overall cancer. Compared with having none to 3 healthy lifestyle factors, HRs related to adherence to all 6 healthy lifestyle factors were 0.78 (95% CI, 0.60-1.02) and 0.82 (95% CI, 0.67-1.00), respectively, for men and women. It was estimated that approximately 18.4% and 2.3%, respectively, of overall cancer cases for men and women were attributable to nonadherence to all 6 healthy lifestyle factors. CONCLUSIONS: The results of the current study indicate that adherence to clustering of healthy lifestyle factors was associated with a reduced risk of cancer incidence among Chinese adults. Greater efforts urgently are needed to promote the adoption of multiple healthy lifestyle behaviors to reduce the increasing burden of cancer.

Urinary sodium excretion and risk of cardiovascular disease in the Chinese population: a prospective study.

The effect of dietary sodium (salt) on cardiovascular disease (CVD) has been debated for a long time. The present study aims to explore whether salt intake affects the risk of cardiovascular disease in the Chinese population. Data from a prospective cohort study that included 954 men and women aged 35-59 years at baseline from four urban and rural population samples in China were used. Each participant collected their overnight urine for three consecutive days during two seasons to estimate sodium intake. CVD events, including incidences of coronary heart disease (CHD), stroke, and death from CVD, and all-cause mortality were tested by Cox proportional hazards models. After a median of 18.6 years of follow-up, CVD events occurred in 81 (8.5%) participants, including 20 CHD and 64 stroke events. All-cause deaths occurred in 149 (15.6%) participants, including 31 CVD-related deaths, 56 cancer-related deaths and 62 other-cause deaths. The hazard ratios and 95% confidence intervals for CVD events in each of the sodium excretion tertiles were 1.00, 1.66 (0.79-3.47) and 3.04 (1.46-6.34), P for trend = 0.001. This trend was also found for stroke incidence (P for trend < 0.001). The cardiovascular mortality risk increased as the sodium excretion levels rose after adjusting for confounding factors (P for trend = 0.043). However, this trend was not significant after adjusting for the baseline systolic blood pressure and antihypertensive medication use (P for trend = 0.171). No significant associations were found between sodium excretion and all-cause, cancer-related or other-cause mortality. High urinary sodium excretion was independently associated with an increased risk of cardiovascular disease in the general Chinese population.

Cancer Cell Membrane-Biomimetic Nanoprobes with Two-Photon Excitation and Near-Infrared Emission for Intravital Tumor Fluorescence Imaging.

Biomimetic fluorescent nanoprobes capable of emitting near-infrared (NIR) fluorescence (λmax ≈ 720 nm) upon excitation of 800 nm light were developed. The key conjugated polymer enabled two-photon absorption and Förster resonance energy transfer (FRET) processes within the nanoprobes, which imparted the nanoprobes with ideal NIR-incoming-NIR-outgoing fluorescence features. The cancer cell membrane (CM) coating endowed these nanoprobes with perfect biocompatibility and highly specific targeting ability to homologous tumors. It was believed that CM encapsulation provided an additional protecting layer for the photoactive components residing in the core of nanoprobes for retaining their intrinsic fluorescing ability in the physiological milieu. The long-term structural integrity, excellent photostability (fluorescence decrease <10% upon 30 min illumination of 800 nm pulse laser), high NIR fluorescence quantum yield (∼20%), and long in vivo circulation time of the target nanoprobes were also confirmed. The ability of these feature-packed nanoprobes for circumventing the challenges of absorption and light scattering caused by cellular structures and tissues was definitely confirmed via in vivo and in vitro experiments. The superior performances of these nanoprobes in terms of fluorescence signaling as well as targeting specificity were verified in intravital fluorescence imaging on tumor-bearing model mice. Specifically, these nanoprobes unequivocally enabled high-resolution visualization of the fine heterogeneous architectures of intravital tumor tissue, which proclaims the great potential of this type of probe for high-contrast fluorescence detection of thick biological samples in practical applications.