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Background: Little is known about the long-term risks of stroke and ischemic heart disease (IHD) in women who had a hysterectomy alone (HA) or with bilateral oophorectomy (HBO) for benign diseases, particularly in China where the burden of cardiovascular diseases (CVD) is high. We assessed mean levels of cardiovascular risk factors and relative risks of stroke and IHD in Chinese women who had a HA or HBO. Methods: A total of 302 510 women, aged 30 to 79 years were enrolled in the China Kadoorie Biobank from 2004 to 2008 and followed up for a mean of 9.8 years. The analysis involved premenopausal women without prior cardiovascular disease or cancer at enrollment. We calculated adjusted hazard ratios for incident cases of CVD and their pathological types (ischemic stroke, hemorrhagic stroke, and IHD) after HA and HBO. Analyses were stratified by age and region and adjusted for levels of education, household income, smoking status, alcohol consumption, physical activity, body mass index, systolic blood pressure, diabetes, self-reported health, and number of pregnancies. Results: Among 282 722 eligible women, 8478 had HA, and 1360 had HBO. Women who had HA had 9% higher risk of CVD after HA (hazard ratio, 1.09 [95% CI, 1.06–1.12]) and 19% higher risk of CVD after HBO (1.19 [95% CI, 1.12–1.26]) compared with women who did not. Both HA and HBO were associated with higher risks of ischemic stroke and IHD but not with hemorrhagic stroke. The relative risks of CVD associated with HA and HBO were more extreme at younger age of surgery. Conclusions: Women who had either HA or HBO have higher risks of ischemic stroke and IHD, and these risks should be evaluated when discussing these interventions. Additional screening for risk factors for CVD should be considered in women following HA and HBO operations, especially if such operations are performed at younger age.

Cancer-associated fibroblasts (CAFs) reconstitute cancer stemness. This study aims to investigate whether the loss of CAF-derived exosomal miR-34c-5p contributes to the maintenance of stem-like properties of laryngeal squamous cell carcinoma (LSCC).Exosomes from primarily cultured CAFs and paired normal fibroblasts (NFs) were collected and identified. The differential expression of exosomal miR-34c-5p between CAFs and NFs was detected by next-generation sequencing. In vitro and in vivo assays were performed to examine the effects of miR-34c-5p on the maintenance of stem-like properties.MiR-34c-5p expression is significantly reduced in CAF-derived exosomes. In vitro and in vivo assays revealed that exosomal miR-34c-5p can regulate the stem-like properties of LSCC cells, such as proliferation, invasion, sphere and plate colony formation, chemoresistance, tumorigenicity in nude mice, as well as the expression of cancer stem cell genes.Loss of miR-34c-5p in CAF-derived exosomes contributes to the maintenance of stem-like phenotypes of LSCC.

Background: Little is known about the effects of maintaining healthy sleep patterns on frailty transitions. Methods: Based on 23,847 Chinese adults aged 30–79 in a prospective cohort study, we examined the associations between sleep patterns and frailty transitions. Healthy sleep patterns included sleep duration at 7 or 8 h/d, without insomnia disorder, and no snoring. Participants who persisted with a healthy sleep pattern in both surveys were defined as maintaining a healthy sleep pattern and scored one point. We used 27 phenotypes to construct a frailty index and defined three statuses: robust, prefrail, and frail. Frailty transitions were defined as the change of frailty status between the 2 surveys: improved, worsened, and remained. Log-binomial regression was used to calculate the prevalence ratio (PR) to assess the effect of sleep patterns on frailty transitions. Results: During a median follow-up of 8.0 years among 23,847 adults, 45.5% of robust participants, and 10.8% of prefrail participants worsened their frailty status, while 18.6% of prefrail participants improved. Among robust participants at baseline, individuals who maintained sleep duration of 7 or 8 h/ds, without insomnia disorder, and no-snoring were less likely to worsen their frailty status; the corresponding PRs (95% CIs) were 0.92 (0.89–0.96), 0.76 (0.74–0.77), and 0.85 (0.82–0.88), respectively. Similar results were observed among prefrail participants maintaining healthy sleep patterns. Maintaining healthy sleep duration and without snoring, also raised the probability of improving the frailty status; the corresponding PRs were 1.09 (1.00–1.18) and 1.42 (1.31–1.54), respectively. Besides, a dose-response relationship was observed between constantly healthy sleep scores and the risk of frailty transitions (P for trend Conclusions: Maintaining a comprehensive healthy sleep pattern was positively associated with a lower risk of worsening frailty status and a higher probability of improving frailty status among Chinese adults.

Background The effect of the overall diet quality on cardiometabolic diseases has been well studied in the Western population. However, evidence is still in need regarding dietary patterns depicting unique Chinese dietary habits and their associations with cardiometabolic diseases. Methods A prospective cohort recruited around 0.5 million Chinese residents aged 30–79 years from 10 diverse survey sites during 2004–08. Dietary patterns were obtained using factor analysis based on the habitual consumption of 12 food groups collected at baseline. Among 477,465 eligible participants free of prior heart disease, stroke and cancer, linkages to multiple registries and health insurance database recorded 137,715 cardiovascular diseases (CVD) and 17,412 diabetes cases (among 451,846 non-diabetic participants) until 31 December 2017. Adjusted hazard ratios (HRs) were estimated to compare the risks of cardiometabolic diseases across quintiles of dietary pattern scores using the Cox regression. Results Two dietary patterns were derived: the traditional northern pattern, characterised by wheat, other staples, egg and dairy products; and the modern pattern, featured with fresh fruit, meat, poultry, fish, dairy products and soybean. Adherence to either dietary pattern was associated with lower risks of major cardiometabolic diseases in a dose-response relationship way. After multivariate adjustment, participants adhering to the traditional northern pattern the most had an 8% (95%CI: 5–11%) lower risk of CVD in comparison with those adhering the least. Corresponding risk reductions were 12% (11–32%) for haemorrhagic stroke (HS), 14% (8–19%) for ischaemic stroke (IS), and 15% (6–24%) for diabetes, respectively. When comparing extreme quintiles of the modern pattern, the adjusted HR of HS was 0.67 (95%CI: 0.59–0.77). Corresponding HRs were 0.89 (0.86–0.92) for CVD, 0.88 (0.77–0.99) for MCE, 0.85 (0.80–0.89) for IS, and 0.89 (0.81, 0.97) for diabetes. Conclusion Among Chinese adults, both traditional northern and modern dietary patterns were associated with lower risks of cardiovascular disease and diabetes beyond other risk factors.

Objectives To prospectively assess the association of metabolic health status and its transition with incident diabetes risk across BMI categories. Design Cohort study based on the China Kadoorie Biobank (CKB). Methods The CKB study enrolled 512 715 adults aged 30–79 years from ten diverse areas in China during 2004–2008. After exclusion, 432 763 participants were cross-classified by BMI categories and the metabolic status was followed up for incident diabetes disease. The changes in BMI and metabolic health status were defined from baseline to the second resurvey. Results Type 2 diabetes risk is higher for metabolically healthy obese (MHO) subjects than metabolically healthy normal weight (MHN) individuals (HR: 3.97, 95% CI: 3.64–3.66), and it is highest for those affected by metabolically unhealthy obese (MUO) (HR: 6.47, 95% CI: 6.17–6.79). About 15.26% of participants with MHN converted to metabolically healthy overweight or obesity (MHOO), whereas 48.40% of MHOO remained unconverted throughout the follow-up. In obese or overweight people, the conversion from metabolically healthy to unhealthy might increase the chances of developing diabetes as compared to those with a stable metabolic healthy state (HR: 3.70, 95% CI: 2.99–4.59), while those with persistent metabolic disorders are most likely to have diabetes (HR: 8.32, 95% CI: 7.08–9.78). Conclusions Metabolic healthy is a transient state, and individuals converted from metabolically healthy status to unhealthy phenotypes across all BMI categories might raise the risk of diabetes.

Background Both genetic and cardiovascular factors contribute to the risk of developing heart failure (HF), but whether idea cardiovascular health metrics (ICVHMs) offset the genetic association with incident HF remains unclear. Objectives To investigate the genetic association with incident HF as well as the modification effect of ICVHMs on such genetic association in Chinese and British populations. Methods An ICVHMs based on smoking, drinking, physical activity, diets, body mass index, waist circumference, blood pressure, blood glucose, and blood lipids, and a polygenic risk score (PRS) for HF were constructed in the China Kadoorie Biobank (CKB) of 96,014 participants and UK Biobank (UKB) of 335,782 participants which were free from HF and severe chronic diseases at baseline. Results During the median follow-up of 11.38 and 8.73 years, 1451 and 3169 incident HF events were documented in CKB and UKB, respectively. HF risk increased monotonically with the increase of PRS per standard deviation (CKB: hazard ratio [HR], 1.19; 95% confidence interval [CI], 1.07, 1.32; UKB: 1.07; 1.03, 1.11; P for trend < 0.001). Each point increase in ICVHMs was associated with 15% and 20% lower risk of incident HF in CKB (0.85; 0.81, 0.90) and UKB (0.80; 0.77, 0.82), respectively. Compared with unfavorable ICVHMs, favorable ICVHMs was associated with a lower HF risk, with 0.71 (0.44, 1.15), 0.41 (0.22, 0.77), and 0.48 (0.30, 0.77) in the low, intermediate, and high genetic risk in CKB and 0.34 (0.26, 0.44), 0.32 (0.25, 0.41), and 0.37 (0.28, 0.47) in UKB (P for multiplicative interaction > 0.05). Participants with low genetic risk and favorable ICVHMs, as compared with high genetic risk and unfavorable ICVHMs, had 56~72% lower risk of HF (CKB 0.44; 0.28, 0.70; UKB 0.28; 0.22, 0.37). No additive interaction between PRS and ICVHMs was observed (relative excess risk due to interaction was 0.05 [−0.22, 0.33] in CKB and 0.04 [−0.14, 0.22] in UKB). Conclusions In CKB and UKB, genetic risk and ICVHMs were independently associated with the risk of incident HF, which suggested that adherence to favorable cardiovascular health status was associated with a lower HF risk among participants with all gradients of genetic risk.

Objectives: It is crucial to elucidate the causal relevance of nutritional exposures (such as dietary patterns, food intake, macronutrients intake, circulating micronutrients), or biomarkers in non-communicable diseases (NCDs) in order to find effective strategies for NCD prevention. Classical observational studies have found evidence of associations between nutritional exposures and NCD development, but such studies are prone to confounding and other biases. This has direct relevance for translation research, as using unreliable evidence can lead to the failure of trials of nutritional interventions. Facilitated by the availability of large-scale genetic data, Mendelian randomization studies are increasingly used to ascertain the causal relevance of nutritional exposures and biomarkers for many NCDs. Methods: A narrative overview was conducted in order to demonstrate and describe the utility of Mendelian randomization studies, for individuals with little prior knowledge engaged in nutritional epidemiological research. Results: We provide an overview, rationale and basic description of the methods, as well as strengths and limitations of Mendelian randomization studies. We give selected examples from the contemporary nutritional literature where Mendelian randomization has provided useful evidence on the potential causal relevance of nutritional exposures. Conclusions: The selected exemplars demonstrate the importance of well-conducted Mendelian randomization studies as a robust tool to prioritize nutritional exposures for further investigation.

Aims The potential difference in the impacts of lifestyle factors (LFs) on progression from healthy to first cardiometabolic disease (FCMD), subsequently to cardiometabolic multimorbidity (CMM), and further to death is unclear. Methods and results We used data from the China Kadoorie Biobank of 461 047 adults aged 30–79 free of heart disease, stroke, and diabetes at baseline. Cardiometabolic multimorbidity was defined as the coexistence of two or three CMDs, including ischaemic heart disease (IHD), stroke, and type 2 diabetes (T2D). We used multi-state model to analyse the impacts of high-risk LFs (current smoking or quitting because of illness, current excessive alcohol drinking or quitting, poor diet, physical inactivity, and unhealthy body shape) on the progression of CMD. During a median follow-up of 11.2 years, 87 687 participants developed at least one CMD, 14 164 developed CMM, and 17 541 died afterwards. Five high-risk LFs played crucial but different roles in all transitions from healthy to FCMD, to CMM, and then to death. The hazard ratios (95% confidence intervals) per one-factor increase were 1.20 (1.19, 1.21) and 1.14 (1.11, 1.16) for transitions from healthy to FCMD, and from FCMD to CMM, and 1.21 (1.19, 1.23), 1.12 (1.10, 1.15), and 1.10 (1.06, 1.15) for mortality risk from healthy, FCMD, and CMM, respectively. When we further divided FCMDs into IHD, ischaemic stroke, haemorrhagic stroke, and T2D, we found that LFs played different roles in disease-specific transitions even within the same transition stage. Conclusion Assuming causality exists, our findings emphasize the significance of integrating comprehensive lifestyle interventions into both health management and CMD management.

Background: The consumption of legumes is promoted as part of a healthy diet in many countries but associations of total and types of legume consumption with type 2 diabetes (T2D) are not well established. Analyses across diverse populations are lacking despite the availability of unpublished legume consumption data in prospective cohort studies. Objective: To examine the prospective associations of total and types of legume intake with the risk of incident T2D. Methods: Meta-analyses of associations between total legume, pulse, and soy consumption and T2D were conducted using a federated approach without physical data-pooling. Prospective cohorts were included if legume exposure and T2D outcome data were available and the cohort investigators agreed to participate. We estimated incidence rate ratios (IRRs) and CIs of associations using individual participant data including ≤42,473 incident cases among 807,785 adults without diabetes in 27 cohorts across the Americas, Eastern Mediterranean, Europe, and Western Pacific. Random-effects meta-analysis was used to combine effect estimates and estimate heterogeneity. Results: Median total legume intake ranged from 0-140 g/d across cohorts. We observed a weak positive association between total legume consumption and T2D (IRR = 1.02, 95% CI: 1.01 to 1.04) per 20 g/d higher intake, with moderately high heterogeneity (I2 = 74%). Analysis by region showed no evidence of associations in the Americas, Eastern Mediterranean, and Western Pacific. The positive association in Europe (IRR = 1.05, 95% CI: 1.01 to 1.10, I2 = 82%) was mainly driven by studies from Germany, UK, and Sweden. No evidence of associations was observed for the consumption of pulses or soy. Conclusions: These findings suggest no evidence of an association of legume intakes with T2D in several world regions. The positive association observed in some European studies warrants further investigation relating to overall dietary contexts in which legumes are consumed, including accompanying foods which may be positively associated with T2D. Funding for the InterConnect project was provided by the European Union Seventh Framework Programme (FP7/2007-2013) under grant agreement no. 602068. Additionally, investigators acknowledge funding from the following agencies: NJW, NGF, FI, and MP acknowledge funding from the Medical Research Council Epidemiology Unit (MC_UU_12015/1 and MC_UU_12015/5); NJW and NGF acknowledge support from National Institute of Health Research (NIHR) Biomedical Research Centre Cambridge: Nutrition, Diet, and Lifestyle Research Theme (IS-BRC-1215-20014). TB acknowledges funding from EUCAN-Connect under the European Union's Horizon 2020 research and innovation programme (grant agreement no. 824989). MBR and MAMG acknowledge funding from the Spanish Government Instituto de Salud Carlos III and the European Regional Development Fund (FEDER) (PI17/01795). JK acknowledges funding from the Korea Centers for Disease Control and Prevention, Ministry for Health and Welfare, Republic of Korea (4845-301 and 4851-302), and the Collaborative Genome Program for Fostering New Post-Genome Industry of the National Research Foundation (NRF) funded by the Ministry of Science and ICT (NRF-2017M3C9A6047623). RM acknowledges funding from the Tehran University of Medical Sciences (grant number: 81/15), Cancer Research UK (grant number: C20/A5860), the Intramural Research Program of the U.S. National Cancer Institute, NIH, and the International Agency for Research on Cancer. LB acknowledges that the Cohort of Swedish Men (COSM) and the Swedish Mammography Cohort (SMC) are part of the Swedish Infrastructure for Medical Population-Based Life-Course and Environmental Research (SIMPLER), which receives funding from the Swedish Research Council (2017-00644). BD is an investigator of the Brazilian National Health Technology Assessment Institute and SC received a fellowship from Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq), the Brazilian National Council for Scientific and Technological Development Fund (FEDER) (PI17/01795). The Zutphen Elderly Study was funded by The Netherlands Prevention Foundation, The Hague, The Netherlands and the National Institute of Aging, Bethesda, MD, USA. The funding sources did not participate in the design or conduct of the study; collection, management, analysis, or interpretation of the data; or preparation, review, or approval of the manuscript.

Background Acute respiratory infections have been associated with a transient increase in cardiovascular risk. However, whether such an association persists beyond 1 month and the potential modifying effect of cardiovascular risk factors on such an association are less well established. Methods The China Kadoorie Biobank enrolled 512 726 participants aged 30–79 years from 10 areas across China during 2004–2008. By the end of 2017, a total of 5444 participants with new-onset ischaemic heart disease (IHD) and 4846 with ischaemic stroke (IS) who also had at least a record of hospitalization for pneumonia during follow-up were included. We used a self-controlled case-series method and calculated the age- and season-adjusted relative incidences (RIs) and 95% confidence intervals (CIs) for ischaemic cardiovascular disease (CVD) after pneumonia. Results The risk of ischaemic CVD increased during days 1–3 after pneumonia hospitalization, with an RI (95% CI) of 4.24 (2.92–6.15) for IHD and 1.85 (1.02–3.35) for IS. The risk gradually reduced with longer duration since pneumonia hospitalization but remained elevated until days 92–365 for IHD (1.23, 1.12–1.35) and days 29–91 for IS (1.25, 1.05–1.48). Pre-existing cardiovascular risk factors amplified the associations between pneumonia and ischaemic CVD risks, such as chronic obstructive pulmonary disease for both IHD and IS, and diabetes and smoking for IHD (all Pinteraction Conclusion Among middle-aged and older Chinese adults, pneumonia hospitalization was associated with both short- and long-term increases in ischaemic CVD risk for ≤1 year.

Alcohol drinking is associated with increased risks of several site‐specific cancers, but its role in many other cancers remains inconclusive. Evidence is more limited from China, where cancer rates, drinking patterns and alcohol tolerability differ importantly from Western populations. The prospective China Kadoorie Biobank recruited >512 000 adults aged 30 to 79 years from 10 diverse areas during 2004 to 2008, recording alcohol consumption patterns by a standardised questionnaire. Self‐reported alcohol consumption was estimated as grams of pure alcohol per week based on beverage type, amount consumed per occasion and drinking frequency. After 10 years of follow‐up, 26 961 individuals developed cancer. Cox regression was used to estimate adjusted hazard ratios (HRs) and 95% confidence intervals (CIs) relating alcohol consumption to incidence of site‐specific cancers. Overall, 33% (n = 69 734) of men drank alcohol regularly (ie, ≥weekly) at baseline. Among male current regular drinkers, alcohol intake showed positive dose‐response associations with risks of cancers in the oesophagus (655 events; HR = 1.98 [95%CI 1.79‐2.18], per 280 g/wk), mouth and throat (236; 1.74 [1.48‐2.05]), liver (573; 1.52 [1.31‐1.76]), colon‐rectum (575; 1.19 [1.00‐1.43]), gallbladder (107; 1.60 [1.16‐2.22]) and lung (1017; 1.25 [1.10‐1.42]), similarly among never‐ and ever‐regular smokers. After adjustment for total alcohol intake, there were greater risks of oesophageal cancer in daily drinkers than nondaily drinkers and of liver cancer when drinking without meals. The risks of oesophageal cancer and lung cancer were greater in men reporting flushing after drinking than not. In this male population, alcohol drinking accounted for 7% of cancer cases. Among women, only 2% drank regularly, with no clear associations between alcohol consumption and cancer risk. Among Chinese men, alcohol drinking is associated with increased risks of cancer at multiple sites, with certain drinking patterns (eg, daily, drinking without meals) and low alcohol tolerance further exacerbating the risks., What's new? A comprehensive assessment of the role of alcohol in cancer aetiology is needed in China, where cancer rates, drinking patterns, and alcohol tolerability differ from those in the West. In this large prospective study, regular alcohol drinkers had increased risks of cancers in several sites previously considered to be alcohol‐related (i.e., oesophagus, mouth and throat, liver and colon‐rectum) as well as in the lung and gallbladder. Certain drinking patterns (e.g., drinking daily or without meals) and low alcohol tolerance further exacerbated the risks. The findings suggest that lowering population‐levels of alcohol consumption is an important strategy for cancer prevention.

Associations of circulating metabolic biomarkers with type 2 diabetes (T2D) and their added value for risk prediction are uncertain among Chinese adults. A case-cohort study included 882 T2D cases diagnosed during 8-years’ follow-up and a subcohort of 789 participants. NMR-metabolomic profiling quantified 225 plasma biomarkers in stored samples taken at recruitment into the study. Cox regression yielded adjusted hazard ratios (HRs) for T2D associated with individual biomarkers, with a set of biomarkers incorporated into an established T2D risk prediction model to assess improvement in discriminatory ability. Mean baseline BMI (SD) was higher in T2D cases than in the subcohort (25.7 [3.6] vs. 23.9 [3.6] kg/m2). Overall, 163 biomarkers were significantly and independently associated with T2D at false discovery rate (FDR) controlled p p p p p

Background: Existing limited evidence suggests that smoking and tea consumption may be associated with a lower risk of Parkinson’s disease (PD). However, less is known about the independent and joint roles of these two habits, which are often clustered among Chinese, on PD risk. Objective: To prospectively examine the independent and joint association of tea consumption and smoking with the risk of PD. Methods: The China Kadoorie Biobank (CKB) study recruited 512,725 participants aged 30 to 79 years from ten areas across China since 2004. Information on smoking and tea consumption was collected at baseline, and PD cases were ascertained by linkage to the national health insurance system and death registry. Cox proportional hazards models were used to estimate the multivariable-adjusted hazard ratios (HRs) and corresponding 95%confidence intervals (CIs). Results: During a median of 10.8 years of follow-up, 922 PD cases were recorded. Compared with participants who never consumed tea, the HR (95%CI) for daily consumers was 0.68 (0.55, 0.84). Compared with participants who never or occasionally smoked, the HR (95%CI) for current smokers was 0.66 (0.53, 0.82). Those who had a clustering habit of smoking and tea consumption had a 38%(HR = 0.62; 95%CI: 0.49, 0.79) lower PD risk than those who consumed none. However, there were no statistically significant multiplicative or additive interaction for tea consumption and smoking on PD risk. Conclusion: We found that smoking and daily tea consumption were independently inversely associated with the risk of PD.

Background Previous studies of primarily Western populations have reported contrasting associations of dairy consumption with certain cancers, including a positive association with prostate cancer and inverse associations with colorectal and premenopausal breast cancers. However, there are limited data from China where cancer rates and levels of dairy consumption differ importantly from those in Western populations. Methods The prospective China Kadoorie Biobank study recruited ~0.5 million adults from ten diverse (five urban, five rural) areas across China during 2004–2008. Consumption frequency of major food groups, including dairy products, was collected at baseline and subsequent resurveys, using a validated interviewer-administered laptop-based food frequency questionnaire. To quantify the linear association of dairy intake and cancer risk and to account for regression dilution bias, the mean usual consumption amount for each baseline group was estimated via combining the consumption level at both baseline and the second resurvey. During a mean follow-up of 10.8 (SD 2.0) years, 29,277 incident cancer cases were recorded among the 510,146 participants who were free of cancer at baseline. Cox regression analyses for incident cancers associated with usual dairy intake were stratified by age-at-risk, sex and region and adjusted for cancer family history, education, income, alcohol intake, smoking, physical activity, soy and fresh fruit intake, and body mass index. Results Overall, 20.4% of participants reported consuming dairy products (mainly milk) regularly (i.e. ≥1 day/week), with the estimated mean consumption of 80.8 g/day among regular consumers and of 37.9 g/day among all participants. There were significant positive associations of dairy consumption with risks of total and certain site-specific cancers, with adjusted HRs per 50 g/day usual consumption being 1.07 (95% CI 1.04–1.10), 1.12 (1.02–1.22), 1.19 (1.01–1.41) and 1.17 (1.07–1.29) for total cancer, liver cancer (n = 3191), female breast cancer (n = 2582) and lymphoma (n=915), respectively. However, the association with lymphoma was not statistically significant after correcting for multiple testing. No significant associations were observed for colorectal cancer (n = 3350, 1.08 [1.00–1.17]) or other site-specific cancers. Conclusion Among Chinese adults who had relatively lower dairy consumption than Western populations, higher dairy intake was associated with higher risks of liver cancer, female breast cancer and, possibly, lymphoma.

Background Tobacco smoking is estimated to account for more than 1 million annual deaths in China, and the epidemic continues to increase in men. Large nationwide prospective studies linked to different health records can help to periodically assess disease burden attributed to smoking. We aimed to examine associations of smoking with incidence of and mortality from an extensive range of diseases in China. Methods We analysed data from the prospective China Kadoorie Biobank, which recruited 512 726 adults aged 30–79 years, of whom 210 201 were men and 302 525 were women. Participants who had no major disabilities were identified through local residential records in 100–150 administrative units, which were randomly selected by use of multistage cluster sampling, from each of the ten diverse study areas of China. They were invited and recruited between June 25, 2004, and July 15, 2008. Upon study entry, trained health workers administered a questionnaire assessing detailed smoking behaviours and other key characteristics (eg, sociodemographics, lifestyle, and medical history). Participants were followed up via electronic record linkages to death and disease registries and health insurance databases, from baseline to Jan 1, 2018. During a median 11-year follow-up (IQR 10–12), 285 542 (55·7%) participants were ever hospitalised, 48 869 (9·5%) died, and 5252 (1·0%) were lost to follow-up during the age-at-risk of 35–84 years. Cox regression yielded hazard ratios (HRs) associating smoking with disease incidence and mortality, adjusting for multiple testing. Findings At baseline, 74·3% of men and 3·2% of women (overall 32·4%) ever smoked regularly. During follow-up, 1 137 603 International Classification of Diseases, 10th revision (ICD-10)-coded incident events occurred, involving 476 distinct conditions and 85 causes of death, each with at least 100 cases. Compared with never-regular smokers, ever-regular smokers had significantly higher risks for nine of 18 ICD-10 chapters examined at age-at-risk of 35–84 years. For individual conditions, smokers had significantly higher risks of 56 diseases (50 for men and 24 for women) and 22 causes of death (17 for men and nine for women). Among men, ever-regular smokers had an HR of 1·09 (95% CI 1·08–1·11) for any disease incidence when compared with never-regular smokers, and significantly more episodes and longer duration of hospitalisation, particularly those due to cancer and respiratory diseases. For overall mortality, the HRs were greater in men from urban areas than in men from rural areas (1·50 [1·42–1·58] vs 1·25 [1·20–1·30]). Among men from urban areas who began smoking at younger than 18 years, the HRs were 2·06 (1·89–2·24) for overall mortality and 1·32 (1·27–1·37) for any disease incidence. In this population, 19·6% of male (24·3% of men residing in urban settings and 16·2% of men residing in rural settings) and 2·8% of female deaths were attributed to ever-regular smoking. Interpretation Among Chinese adults, smoking was associated with higher risks of morbidity and mortality from a wide range of diseases. Among men, the future smoking-attributed disease burden will increase further, highlighting a pressing need for reducing consumption through widespread cessation and uptake prevention. Funding British Heart Foundation, Cancer Research UK, Chinese Ministry of Science and Technology, Kadoorie Charitable Foundation, UK Medical Research Council, National Natural Science Foundation of China, Wellcome Trust.

RNA-binding proteins (RBPs) have been suggested as important prognostic indicators in different human cancers. This study was designed to search the prognostic value of RBPs of laryngeal squamous cell carcinoma (LSCC). Differentially expressed RBPs (DERBPs) were screened via The Cancer Genome Atlas (TCGA). Bioinformatics methods were used to identify prognostic DERBPs. Expression profiling of training cohort were calculated to develop a transcriptomic signature, which was validated by three independent cohorts (TCGA cohort, GSE65858 cohort and GSE27020 cohort). We identified DERBPs and a set of signatures (GTPBP3, KHDRBS3 and RBM38) were confirmed as prognosis-related hub DERBPs in LSCC, which was also tested and verified by bioinformatics method and molecular biology experiment. The role of immune cell infiltration and drug resistance between subgroups was explored. Furthermore, the risk score based on transcriptomic signature was turned out to be an independent prognostic indicator for LSCC. Finally, a nomogram for further clinical application was established. Our study demonstrated that the transcriptomic signature we constructed could serve as a novel therapeutic target and biomarker for LSCC from the perspective of RBPs.

The evidence about the association between dietary patterns and the incidence of chronic obstructive pulmonary disease (COPD) among Chinese adults is limited. In the present study, we analyzed the prospective data of 421,426 participants aged 30–79 years from the China Kadoorie Biobank. Factor analysis with a principal component method was employed to identify dietary patterns. Cox proportional hazard regression models were performed to explore the association between dietary patterns and incident COPD. Two dietary patterns were identified: the traditional northern dietary pattern was characterized by a low intake of rice and a high intake of wheat and other staple foods, while the balanced dietary pattern was characterized by a high intake of fresh fruit and protein-rich foods (soybean, meat, poultry, fish, eggs, and dairy products). During a median follow-up of 11.13 years, 5542 men and 5750 women developed COPD. After adjustments for potential confounders, the balanced dietary pattern was associated with a lower risk of COPD (p for trend

This study aimed to describe the characteristics and lifestyle differences of spicy food consumption in 0.5 million adults. Participants were recruited from 2004 to 2008 in the baseline research of the CKB study. Higher frequency and stronger pungency degree in spicy food positively correlated with preference for salty taste, eating snacks/deep-fried foods, tea/alcohol drinking and tobacco smoking. Among weekly tea/alcohol drinkers and current regular smokers, participants with a higher frequency of spicy food consumption or preference for stronger pungency degree were more likely to prefer strong tea, drink alcohol exceed the healthy amount, drink alcohol in the morning every day, smoke ≥ 40 cigarettes per day, consume a larger amount of tea leaves, alcohol and cigarettes each day, and start habitual tea/alcohol drinking or smoking at an earlier age. Differences existed in lifestyle factors related to major chronic diseases according to spicy food consumption frequency and pungency degree among the Chinese population.

It is well known that alcohol consumption is associated with type 2 diabetes mellitus. However, the association of age at initiation of alcohol consumption and duration of alcohol drinking with type 2 diabetes mellitus among Chinese adults is not fully understood. This study was based on data from the China Kadoorie Biobank, which included 512,712 participants aged 30–79 years who were living in China in 2004–2008. A Cox proportional hazards model was used to estimate the association of AAI and drinking duration with type 2 diabetes. After adjustment for potential covariates, ages at alcohol initiation (AAIs) of 18.1–29.0 years, 29.1–39.0 years, and >39.0 years were associated with 22% (95% confidence interval (CI): 14, 30), 25% (95% CI: 17, 33), and 32% (95% CI: 24, 39) lower hazards of type 2 diabetes compared with abstaining, respectively. Drinking durations of 30.0 years were associated with 18% (95% CI: 4, 33) and 20% (95% CI: 3, 40) higher hazards of type 2 diabetes, compared with AAI 18.1–29.0 years and drinking duration

ObjectiveThere is limited prospective evidence on the association of physical activity with hepatobiliary cancer subtypes and other major hepatobiliary diseases, especially in China. We aimed to quantify the associations with risk of these diseases.MethodsThe study population involved 460 937 participants of the prospective China Kadoorie Biobank aged 30–79 years from 10 diverse areas in China without history of cancer or hepatobiliary disease at baseline. Cox regression was used to estimate adjusted hazard ratios (HRs) for each disease associated with self-reported total and domain-specific physical activity (occupational and non-occupational, ie, leisure time, household and commuting).ResultsDuring ~10 years of follow-up, 22 012 incident cases of hepatobiliary diseases were recorded. The overall mean (SD) total physical activity was 21.2 (13.9) metabolic equivalent of task (MET)-hours/day, with 62% from occupational activity. Total physical activity was inversely associated with hospitalised non-alcoholic fatty liver disease (HR comparing top vs bottom quintile: 0.62, 95% confidence interval (CI) 0.53 to 0.72), viral hepatitis (0.73, 95% CI 0.62 to 0.87), cirrhosis (0.76, 95% CI 0.66 to 0.88) and liver cancer (0.81, 95% CI 0.71 to 0.93), as well as gallstone disease (0.86, 95% CI 0.81 to 0.90), gallbladder cancer (0.51, 95% CI 0.32 to 0.80) and biliary tract cancer (0.55, 95% CI 0.38 to 0.78). The associations for occupational physical activity were similar to those for total physical activity, but for non-occupational physical activity they differed by disease subtype. For leisure-time physical activity, there was an inverse association with liver cancer and an inverse trend for gallstone disease (HR comparing ≥7.5 MET-hours/day with none: 0.83, 95% CI 0.75 to 0.91 and 0.82, 95% CI 0.66 to 1.01).ConclusionAmong Chinese adults, high total physical activity, particularly occupational physical activity, was inversely associated with risk of major hepatobiliary cancers and diseases, including non-alcoholic fatty liver disease, cirrhosis and certain types of cancer.

Summary Background Stroke is a leading cause of death and disability worldwide. Despite considerable improvements in diagnosis and treatment, little is known about the short-term and long-term prognosis after a first stroke in low-income and middle-income countries, including China. We aimed to assess the short-term and long-term risk of recurrent stroke and mortality after a first stroke for each of the major pathological stroke types. Methods This population-based cohort study included adults aged 35–74 years without disability who were recruited to the China Kadoorie Biobank (CKB). A baseline survey was conducted in ten geographical areas (five urban, five rural) in China, and participants had clinical measurements recorded. Participants were followed up by monitoring death registries and by electronic linkage to health registries and health insurance claims databases, with follow-up until Jan 1, 2017. Participants were excluded from analyses if they had a previous history of stroke, transient ischaemic attack, or ischaemic heart disease at baseline. All incidences of fatal and non-fatal stroke during the study period were recorded by type (ischaemic stroke, intracerebral haemorrhage, subarachnoid haemorrhage, and unspecified type). Primary outcome measures were 28-day mortality, recurrent stroke, major vascular events (recurrent stroke, myocardial infarction, or vascular death), vascular mortality, and all-cause mortality. Findings Of 512 715 individuals in the CKB, 489 586 participants without previous ischaemic heart disease and stroke at recruitment were included, of whom 45 732 (42 073 [92%] confirmed by brain imaging) had a stroke during the study period. The mean age was 59·3 years (SD 9·8) for participants who had a stroke (54% women) and 50·8 years (10·3) for participants with no stroke (60% women). 36 588 (80%) of the incident cases of stroke were ischaemic stroke, 7440 (16%) were intracerebral haemorrhage, 702 (2%) were subarachnoid haemorrhage, and 1002 (2%) were an unspecified stroke type. 28-day mortality was 3% (95% CI 3–4) for ischaemic stroke, 47% (46–48)for intracerebral haemorrhage, 19% (17–22; 52% for rural areas and 32% for urban areas) subarachnoid haemorrhage, and 24% (22–27) for unspecified stroke. Among participants who survived stroke at 28 days, 41% (41–42) had recurrent stroke at 5 years (ischaemic stroke 41% [41–42], intracerebral haemorrhage 44% [42–46], subarachnoid haemorrhage 22% [18–27], unspecified stroke type 40% [35–44]) and mortality at 5 years was 17% ([17–18] ischaemic stroke 16% [15–16], intracerebral haemorrhage 28% [26–29], subarachnoid haemorrhage 16% [12–20], unspecified stroke type 15% [12–19]). After a first ischaemic stroke, 91% of recurrent strokes were also ischaemic stroke; after an intracerebral haemorrhage, 56% of recurrent strokes were intracerebral haemorrhage, and 41% of recurrent strokes were ischaemic stroke. Interpretation After a first stroke, the risk of recurrence or death within 5 years was high among this population of Chinese adults. Urgent improvements to secondary prevention of stroke in China are needed to reduce these risks. Funding Wellcome Trust, Medical Research Council, British Heart Foundation, Cancer Research UK, Kadoorie Charitable Foundation, Chinese Ministry of Science and Technology, National Natural Science Foundation of China. Copyright © 2020 The Author(s). Published by Elsevier Ltd. This is an Open Access article under the CC BY 4.0 license.

Aims/hypothesis Previous evidence linking red meat consumption with diabetes risk mainly came from western countries, with little evidence from China, where patterns of meat consumption are different. Moreover, global evidence remains inconclusive about the associations of poultry and fish consumption with diabetes. Therefore we investigated the associations of red meat, poultry and fish intake with incidence of diabetes in a Chinese population. Methods The prospective China Kadoorie Biobank recruited ~512,000 adults (59% women, mean age 51 years) from ten rural and urban areas across China in 2004–2008. At the baseline survey, a validated interviewer-administered laptop-based questionnaire was used to collect information on the consumption frequency of major food groups including red meat, poultry, fish, fresh fruit and several others. During ~9 years of follow-up, 14,931 incidences of new-onset diabetes were recorded among 461,036 participants who had no prior diabetes, cardiovascular diseases or cancer at baseline. Cox regression analyses were performed to calculate adjusted HRs for incident diabetes associated with red meat, poultry and fish intake. Results At baseline, 47.0%, 1.3% and 8.9% of participants reported a regular consumption (i.e. ≥4 days/week) of red meat, poultry and fish, respectively. After adjusting for adiposity and other potential confounders, each 50 g/day increase in red meat and fish intake was associated with 11% (HR 1.11 [95% CI 1.04, 1.20]) and 6% (HR 1.06 [95% CI 1.00, 1.13]) higher risk of incident diabetes, respectively. For both, the associations were more pronounced among men and women from urban areas, with an HR (95% CI) of 1.42 (1.15, 1.74) and 1.18 (1.03, 1.36), respectively, per 50 g/day red meat intake and 1.15 (1.02, 1.30) and 1.11 (1.01, 1.23), respectively, per 50 g/day fish intake. There was no significant association between diabetes and poultry intake, either overall (HR 0.96 [95% CI 0.83, 1.12] per 50 g/day intake) or in specific population subgroups. Conclusions/interpretation In Chinese adults, both red meat and fish, but not poultry, intake were positively associated with diabetes risk, particularly among urban participants. Our findings add new evidence linking red meat and fish intake with cardiometabolic diseases. Data availability Details of how to access the China Kadoorie Biobank data and rules of China Kadoorie Biobank data release are available from www.ckbiobank.org/site/Data+Access.

Background: Cooking practice has transitioned from use of solid fuels to use of clean fuels, with addition of better ventilation facilities. However, the change in mortality risk associated with such a transition remains unclear. Methods: The China Kadoorie Biobank (CKB) Study enrolled participants (aged 30–79 years) from ten areas across China; we chose to study participants from five urban areas where transition from use of solid fuels to clean fuels for cooking was prevalent. Participants who reported regular cooking (weekly or more frequently) at baseline were categorised as persistent clean fuel users, previous solid fuel users, or persistent solid fuel users, according to self-reported fuel use histories. All-cause and cardiopulmonary mortality were identified through linkage to China's Disease Surveillance Point system and local mortality records. Findings: Between June 24, 2004, and July 15, 2008, 226 186 participants living in five urban areas of China were enrolled in the CKB Study. Among 171 677 participants who reported cooking regularly (weekly or more frequently), 75 785 (44%) were persistent clean fuel users, 80 511 (47%) were previous solid fuel users, and 15 381 (9%) were persistent solid fuel users. During a mean of 9·8 (SD 1·7) years of follow-up, 10 831 deaths were documented, including 3819 cardiovascular deaths and 761 respiratory deaths. Compared with persistent clean fuel users, persistent solid fuel users had significantly higher risks of all-cause mortality (hazard ratio [HR] 1·19, 95% CI 1·10–1·28), cardiovascular mortality (1·24, 1·10–1·39), and respiratory mortality (1·43, 1·10–1·85). The excess risk of all-cause and cardiopulmonary mortality fell by more than 60% in 5 years after cessation of solid fuel use and continued to decrease afterwards. Use of ventilation was associated with lower all-cause mortality risk, even among persistent clean fuel users (HR 0·78, 0·69–0·89). Interpretation: Solid fuel use for cooking is associated with a higher risk of mortality, and cessation of solid fuel use cuts excess mortality risks swiftly and substantially within 5 years. Ventilation use also lowers the risk of mortality, even among people who persistently use clean fuels. It is of prime importance for both policy makers and the public to accelerate the transition from solid fuels to clean fuels and promote efficient ventilation to minimise further adverse health effects.

Background: This study aimed to identify lipid metabolism-related dietary patterns with reduced rank regression (RRR) among Chinese adults and examine their associations with incident diabetes. Methods: We derived lipid metabolism-related dietary patterns using an RRR with 21 food groups as predictors as well as total cholesterol, low-density lipoprotein (LDL) cholesterol, high-density lipoprotein (HDL) cholesterol, triglycerides, body mass index (BMI), and waist circumference from the responses of 17,318 participants from the second resurvey of the China Kadoorie Biobank (CKB). The dietary scores were calculated for the entire cohort. We followed up 479,207 participants for diabetes incidence from the baseline and used multivariable Cox regression models to estimate the hazard ratios (HRs) and 95% confidence intervals (CIs). Results: Two lipid metabolism-related dietary patterns were extracted. The dietary pattern—characterized by high intakes of fish, poultry, and other staples as well as fresh fruit and vegetables—was correlated with a higher BMI, waist circumference, and LDL cholesterol. Participants in the highest quintile (Q5) had a 44% increased risk of diabetes incidence when compared with those in the lowest quintile (Q1) (HR = 1.44; 95% CI: 1.31–1.59). Conclusions: A dietary pattern characterized by high intakes of both animal and plant foods was related to obesity and dyslipidemia and could increase the risk of diabetes incidence.

Previous research found tobacco smoking and solid fuel use for cooking to increase the risk of chronic liver disease mortality, but previous cohort studies have not investigated their independent and joint associations with liver cancer incidence in contemporary China. The China Kadoorie Biobank (CKB) study recruited 0.5 million adults aged 30 to 79 years from 10 areas across China during 2004 to 2008. Participants reported detailed smoking and fuel use information at baseline. After an 11.1-year median follow-up via electronic record linkage, we recorded 2997 liver cancer cases. Overall, 29.4% participants were current smokers. Among those who cooked at least once per month, 48.8% always used solid fuels (ie, coal or wood) for cooking. Tobacco smoking and solid fuel use for cooking were independently associated with increased risks of liver cancer, with hazard ratios (95% confidence intervals [CIs]) of 1.28 (1.15-1.42) and 1.25 (1.03-1.52), respectively. The more cigarettes consumed each day, the earlier the age of starting smoking or the longer duration of solid fuels exposure, the higher the risk (P

Involuntary smoking was a major public health problem for women in China. Previous studies mainly focused on secondhand smoke (SHS), which referred to direct exposure to smoke from burning cigarettes. Little evidence existed about the relationship between thirdhand smoke (THS), the residual tobacco smoke remaining in the environment after tobacco had been smoked, and cervical cancer. The China Kadoorie Biobank (CKB) study recruited 0.3 million female participants from 10 areas across China during 2004-2008. After an 11.2-year median follow-up, we documented 1094 cervical cancer cases. Multivariable Cox regression yielded adjusted hazard ratios (HRs) and 95% confidence intervals (CIs) for the associations of SHS and THS with cervical cancer incidence, respectively and jointly. Overall, 60.3% reported weekly SHS exposure, and 83.2% had been exposed to THS. Daily SHS exposure and THS exposure at the enrollment were associated with elevated risks of cervical cancer incidence, with adjusted HRs (95% CI) of 1.22 (1.06,1.42) and 1.24 (1.03,1.49), respectively. The longer the exposure duration, the higher the risks (P for trend = 0.006, 0.035, respectively). Compared with those who were neither exposed to SHS nor THS, those exposed to both SHS and THS had the highest risk, with adjusted HRs (95% CI) of 1.29 (1.05,1.58). Area of residence, breastfeeding duration and heating fuel types are potential effect modifiers. Among Chinese females, both SHS and THS were associated with higher risks of cervical cancer incidence, and a dose-response relationship was found between the exposure duration and cervical cancer risk. Our findings reinforce the need for proactive strategies for tobacco control, to protect women health.

Little is known about the incidence rates and importance of major modifiable risk factors for hip and major osteoporotic fractures in low- and middle-income countries. We estimated the age- and sex-specific incidence of hip, major osteoporotic, and any fractures and their associated risk factors in Chinese adults.This was a prospective study of 512,715 adults, aged 30-79 years, recruited from 10 diverse areas in China from 2004 to 2008 and followed up for 10 years. Age- and sex-specific incidence rates were estimated, and Cox regression was used to yield adjusted hazard ratios (HRs) and population attributable fractions for risk factors.The incidence rates of hip fracture in Chinese adults were 5.1 (95% confidence interval [CI] 5.0-5.3) per 10,000 person-years; they were higher in women than in men and increased by two- to threefold per 10-year older age. Among men, five risk factors for hip fracture, including low education (HR = 1.23; 95% CI 1.04-1.45), regular smoker (1.22, 1.03-1.45), lower weight (1.59, 1.34-1.88), alcohol drinker (1.18, 1.02-1.36), and prior fracture (1.62, 1.33-1.98), accounted for 44.3% of hip fractures. Among women, lower weight (1.30, 1.15-1.46), low physical activity (1.22, 1.10-1.35), diabetes (1.62, 1.41-1.86), prior fracture (1.54, 1.33-1.77), and self-rated poor health (1.29, 1.13-1.47) accounted for 24.9% of hip fractures. Associations of risk factors with major osteoporotic or any fractures were weaker than those with hip fractures.The age- and sex-specific incidence rates of hip fracture in Chinese adults were comparable with those in Western populations. Five potentially modifiable factors accounted for half of the hip fractures in men and one quarter in women.

Two genetic variants that alter alcohol metabolism, ALDH2-rs671 and ADH1B-rs1229984, can modify oesophageal cancer risk associated with alcohol consumption in East Asians, but their associations with other cancers remain uncertain. ALDH2-rs671 G>A and ADH1B-rs1229984 G>A were genotyped in 150,722 adults, enrolled from ten areas in China during 2004-2008. After 11 years’ follow-up, 9339 individuals developed cancer. Cox regression was used to estimate hazard ratios (HRs) for site-specific cancers associated with these genotypes, and their potential interactions with alcohol consumption. Overall, the A-allele frequency was 0.21 for ALDH2-rs671 and 0.69 for ADH1B-rs1229984, with A-alleles strongly associated with lower alcohol consumption. Among men, ALDH2- rs671 AA genotype was associated with HR of 0.69 (95% CI: 0.53-0.90) for IARC alcohol related cancers (n=1900), compared with GG genotype. For ADH1B-rs1229984, the HRs of AG and AA versus GG genotype were 0.80 (0.69-0.93) and 0.75 (0.64-0.87) for IARC alcohol-related cancers, 0.61 (0.39-0.96) and 0.61 (0.39-0.94) for head and neck cancer (n=196), and 0.68 (0.53-0.88) and 0.60 (0.46-0.78) for oesophageal cancer (n=546). There were no significant associations of these genotypes with risks of liver (n=651), colorectal (n=556), stomach (n=725) or lung (n=1135) cancers. Among male drinkers, the risks associated with higher alcohol consumption were greater among ALDH2-rs671 AG than GG carriers for head and neck, oesophageal, and lung cancers (p-interaction

IntroductionWe examined the associations between long-term usual random plasma glucose (RPG) levels and cause-specific mortality risks among adults without known diabetes in China.Research design and methodsThe China Kadoorie Biobank recruited 512,891 adults (59% women) aged 30–79 from 10 regions of China during 2004–2008. At baseline survey, and subsequent resurveys of a random subset of survivors, participants were interviewed and measurements collected, including on-site RPG testing. Cause of death was ascertained via linkage to local mortality registries. Cox regression yielded adjusted HR for all-cause and cause-specific mortality associated with usual levels of RPG.ResultsDuring median 11 years’ follow-up, 37,214 deaths occurred among 452,993 participants without prior diagnosed diabetes or other chronic diseases. There were positive log-linear relationships between RPG and all-cause, cardiovascular disease (CVD) (n=14,209) and chronic kidney disease (CKD) (n=432) mortality down to usual RPG levels of at least 5.1 mmol/L. At RPG ConclusionsAmong Chinese adults without diabetes, higher RPG levels were associated with higher mortality risks from several major diseases, with no evidence of apparent thresholds below the cut-points for diabetes diagnosis.

Lower consumption of whole grains is associated with higher risks of diabetes and coronary heart disease in Western populations, but evidence is still limited for stroke. Moreover, little is known in China, where the rates of cardiometabolic diseases are high and the grain types consumed are different from those in Western countries.To examine the associations between coarse-grain (e.g., millet, corn, and sorghum) consumption and incident cardiometabolic diseases among Chinese adults.The prospective China Kadoorie Biobank enrolled0.5 million adults aged 30-79 years from 10 urban and rural areas during 2004-2008. At baseline, consumption frequencies (in 5 categories from "never" to "daily") of 12 major food groups, including coarse grains, were collected using a validated FFQ. After a median of 11 years of follow-up, 17,149 cases of diabetes, 29,876 ischemic strokes, 6097 hemorrhagic strokes, and 6704 major coronary events were recorded among 461,047 participants without a prevalence of major chronic diseases at baseline. Cox regression analyses were used to yield adjusted HRs for each disease associated with coarse-grain consumption.Overall, 13.8% of participants reported regularly consuming (i.e., ≥4 days/week, regular consumers) and 29.4% reported never or rarely consuming coarse grains (i.e., nonconsumers) at baseline. Compared with nonconsumers, regular consumers had lower risks of diabetes (adjusted HR, 0.88; 95% CI, 0.78-0.98) and ischemic stroke (adjusted HR, 0.86; 95% CI, 0.81-0.93), but not hemorrhagic stroke (adjusted HR, 0.96; 95% CI, 0.76-1.20) or major coronary events (adjusted HR, 0.95; 95% CI, 0.81-1.12). For diabetes and ischemic stroke, each 100 g/day increase in the usual intake of coarse grains was associated with 14% (adjusted HR, 0.86; 95% CI, 0.76-0.97) and 13% (adjusted HR, 0.87; 95% CI, 0.81-0.94) lower risks, respectively, with similar results in various subgroups.In Chinese adults, higher coarse-grain consumption is associated with lower risks of diabetes and ischemic stroke, supporting the promotion of coarse-grain consumption in China.

Background:Identifying environmentally responsive genetic loci where DNA methylation is associated with coronary heart disease (CHD) may reveal novel pathways or therapeutic targets for CHD. We conducted the first prospective epigenome-wide analysis of DNA methylation in relation to incident CHD in the Asian population.Methods:We did a nested case-control study comprising incident CHD cases and 1:1 matched controls who were identified from the 10 year follow-up of the China Kadoorie Biobank. Methylation level of baseline blood leukocyte DNA was measured by Infinium Methylation EPIC BeadChip. We performed the single cytosine-phosphate-guanine (CpG) site association analysis and network approach to identify CHD-associated CpG sites and co-methylation gene module.Results:After quality control, 982 participants (mean age 50.1 years) were retained. Methylation level at 25 CpG sites across the genome was associated with incident CHD (genome-wide false discovery rate [FDR] < 0.05 or module-specific FDR < 0.01). One SD increase in methylation level of identified CpGs was associated with differences in CHD risk, ranging from a 47 % decrease to a 118 % increase. Mediation analyses revealed 28.5 % of the excessed CHD risk associated with smoking was mediated by methylation level at the promoter region of ANKS1A gene (P for mediation effect = 0.036). Methylation level at the promoter region of SNX30 was associated with blood pressure and subsequent risk of CHD, with the mediating proportion to be 7.7 % (P = 0.003) via systolic blood pressure and 6.4 % (P = 0.006) via diastolic blood pressure. Network analysis revealed a co-methylation module associated with CHD.Conclusions:We identified novel blood methylation alterations associated with incident CHD in the Asian population and provided evidence of the possible role of epigenetic regulations in the smoking- and blood pressure-related pathways to CHD risk.Funding:This work was supported by National Natural Science Foundation of China (81390544 and 91846303). The CKB baseline survey and the first re-survey were supported by a grant from the Kadoorie Charitable Foundation in Hong Kong. The long-term follow-up is supported by grants from the UK Wellcome Trust (202922/Z/16/Z, 088158/Z/09/Z, 104085/Z/14/Z), grant (2016YFC0900500, 2016YFC0900501, 2016YFC0900504, 2016YFC1303904) from the National Key R&D Program of China, and Chinese Ministry of Science and Technology (2011BAI09B01).

Background:Few studies have assessed the role of individual plasma cholesterol levels in the association between egg consumption and the risk of cardiovascular diseases. This research aims to simultaneously explore the associations of self-reported egg consumption with plasma metabolic markers and these markers with the risk of cardiovascular disease (CVD).Methods:Totally 4778 participants (3401 CVD cases subdivided into subtypes and 1377 controls) aged 30–79 were selected based on the China Kadoorie Biobank. Targeted nuclear magnetic resonance was used to quantify 225 metabolites in baseline plasma samples. Linear regression was conducted to assess associations between self-reported egg consumption and metabolic markers, which were further compared with associations between metabolic markers and CVD risk.Results:Egg consumption was associated with 24 out of 225 markers, including positive associations for apolipoprotein A1, acetate, mean HDL diameter, and lipid profiles of very large and large HDL, and inverse associations for total cholesterol and cholesterol esters in small VLDL. Among these 24 markers, 14 were associated with CVD risk. In general, the associations of egg consumption with metabolic markers and of these markers with CVD risk showed opposite patterns.Conclusions:In the Chinese population, egg consumption is associated with several metabolic markers, which may partially explain the protective effect of moderate egg consumption on CVD.Funding:This work was supported by the National Natural Science Foundation of China (81973125, 81941018, 91846303, 91843302). The CKB baseline survey and the first re-survey were supported by a grant from the Kadoorie Charitable Foundation in Hong Kong. The long-term follow-up is supported by grants (2016YFC0900500, 2016YFC0900501, 2016YFC0900504, 2016YFC1303904) from the National Key R&D Program of China, National Natural Science Foundation of China (81390540, 81390541, 81390544), and Chinese Ministry of Science and Technology (2011BAI09B01). The funders had no role in the study design, data collection, data analysis and interpretation, writing of the report, or the decision to submit the article for publication.

Background Little is known about the effects of lifestyle modification on biological aging in population-based studies of middle-aged and older adults. Method We examined the individual and joint associations of multiple lifestyle factors with accelerated biological aging measured by change in frailty index (FI) over 8 years in a prospective study of Chinese adults. Data were obtained on 24 813 participants in the China Kadoorie Biobank on lifestyle factors and frailty status at baseline and at 8 years after baseline. Adherence to healthy lifestyle factors included nonsmoking or quitting smoking for reasons other than illness, avoidance of heavy alcohol consumption, daily intake of fruit and vegetables, being physically active, body mass index of 18.5–23.9 kg/m2, and waist-to-hip ratio of Results Overall, 8 760 (35.3%) individuals had a worsening frailty status. In multivariable-adjusted logistic regression analyses, adherence to healthy lifestyle was associated with a lower risk of worsening frailty status. Compared with robust participants maintaining 0–1 healthy lifestyle factors, the corresponding odds ratios (95% CIs) were 0.93 (0.83–1.03), 0.75 (0.67–0.84), 0.68 (0.60–0.77), and 0.55 (0.46–0.65) for robust participants with 2, 3, 4, and 5–6 healthy lifestyle factors. The decreased risk of frailty status worsening by adherence to healthy lifestyle factors was similar in both middle-aged and older adults, and in both robust and prefrail participants at baseline. Conclusions Adherence to a healthy lifestyle may attenuate the rate of change in biological aging in middle-aged and older Chinese adults.

Existing evidence on the associations of urinary element profiles with related food intake and cardiometabolic diseases has been limited in China.To examine the associations of urinary toxic metals and other elements with food intakes and with the prevalence of cardiometabolic diseases.Inductively coupled plasma mass spectrometry was used to measure the concentrations of cadmium (Cd), arsenic (As), nickel (Ni), aluminum (Al), copper (Cu), and 16 other elements in spot urine samples collected from 19,380 adults in 10 geographically diverse areas of China during 2013-2014. The levels of creatinine-corrected elements were used to analyze their correlations with self-reported dietary intake and associations with prevalent diabetes (n = 1862), stroke (n = 1322) and ischemic heart disease (IHD) (n = 1690).Overall, the mean (SD) age was 59.2 (10.1) years with a mean BMI of 24.2 (3.5) kg/mIn China, the urinary levels of several toxic metals were significantly associated with the consumption of specific food groups and the risk of cardiometabolic diseases including diabetes and stroke.

Background Evidence from epidemiological studies remains inconsistent or limited about the associations of tea consumption with incident diabetes and risk of diabetic complications and death among patients with diabetes. Objectives We aimed to investigate the associations of tea consumption with long-term risk of developing type 2 diabetes (T2D) and risks of diabetic complications and death among patients with diabetes. Methods This study included 482,425 diabetes-free participants and 30,300 patients with diabetes aged 30–79 y at study enrollment from the China Kadoorie Biobank. Tea consumption information was collected at baseline by interviewer-administered questionnaires. Incidences of diabetes, diabetic complications, and death were identified by linkages to the National Health Insurance system, disease registries, and death registries. Cox proportional hazard regression models were used to estimate HRs and 95% CIs. Results The mean ± SD age of participants free of diabetes was 51.2 ± 10.5 y and 41% were male. The mean ± SD age of patients with diabetes was 58.2 ± 9.6 y and 39% were male. Of all daily tea consumers, 85.8% preferred green tea. In the diabetes-free population, 17,434 participants developed incident T2D during 11.1 y of follow-up. Compared with participants who never consumed tea in the past year, the HR (95% CI) of T2D for daily consumers was 0.92 (0.88, 0.97). In patients with diabetes, we identified 6572 deaths, 12,677 diabetic macrovascular cases, and 2441 diabetic microvascular cases during follow-up. Compared with patients who never consumed tea in the past year, the HRs (95% CIs) of all-cause mortality and risk of microvascular complications for daily consumers were 0.90 (0.83, 0.97) and 0.88 (0.78, 1.00), respectively. Tea consumption was not associated with risk of macrovascular complications among patients with diabetes. With regard to tea consumed, the inverse associations between daily tea consumption and risks of T2D and all-cause mortality in patients with diabetes were only observed among daily green tea drinkers. Conclusions In Chinese adults, daily green tea consumption was associated with a lower risk of incident T2D and a lower risk of all-cause mortality in patients with diabetes, but the associations for other types of tea were less clear. In addition, daily tea consumption was associated with a lower risk of diabetic microvascular complications, but not macrovascular complications.

Background Early life development plays a key role in adult type 2 diabetes mellitus (T2DM), but the extent to which can be attenuated by lifestyle is unknown. Objectives To investigate the independent relevance of genetic predisposition to low birth weight and childhood obesity for T2DM, and their attenuation by adherence to a healthy lifestyle in adulthood. Methods Genetic risk scores (GRSs) were estimated for birth weight and childhood body mass index (BMI) with genetic risk categories according to their quintiles in 90,029 and 321,225 participants from China Kadoorie Biobank (CKB) (mean age, 53.0 years) and UK Biobank (UKB) (56.1 years). Healthy lifestyle scores were defined on non-current smoking, moderate alcohol consumption, healthy diet, regular physical activity, non-obesity, categorized into healthy (4∼5 factors), intermediate (2∼3 factors) and unhealthy (0∼1 factor) lifestyle. Results GRSs for low birth weight and childhood BMI were associated with higher T2DM risks. Healthy lifestyle was related to lower T2DM risk, and there was an additive interaction with increasing childhood BMI GRS and decreasing healthy lifestyle factors on T2DM risk, while no additive interaction was observed for birth weight. Participants with a healthy compared with an unhealthy lifestyle had a 68% (hazard ratio: 0.32; 95%CI: 0.22, 0.47) and 77% (0.23; 0.19, 0.28) lower T2DM risk among participants at high genetic risk (lowest quintile) of low birth weight in CKB and UKB. Among participants with high genetic risk (highest quintile) of childhood obesity, compared with unhealthy lifestyle, adherence to a healthy lifestyle was associated with a 69% (0.31; 0.22, 0.46) and 80% (0.20; 0.17, 0.25) lower risk in CKB and UKB. Conclusions Genetic predisposition to low birth weight and childhood obesity were associated with higher risk of adult T2DM and these excess risks were attenuated by adherence to a healthy lifestyle in adulthood, particularly among those at high genetic risk of childhood obesity.

A few prospective studies have suggested that tea, alcohol, and fruit consumption may reduce the risk of kidney stones. However, little is known whether such associations and their combined effect persist in Chinese adults, for whom the popular tea and alcohol drinks are different from those investigated in the aforementioned studies. The present study included 502,621 participants from the China Kadoorie Biobank (CKB). Information about tea, alcohol, and fruit consumption was self-reported at baseline. The first documented cases of kidney stones during follow-up were collected through linkage with the national health insurance system. Cox regression was used to calculate the hazard ratio (HR) and 95% confidence interval (CI). During a median of 11.1 years of follow-up, we collected 12,407 cases of kidney stones. After multivariable adjustment, tea, alcohol, and fruit consumption were found to be negatively associated with kidney stone risk, but the linear trend was only found in tea and fruit consumption. Compared with non-tea consumers, the HR (95% CI) for participants who drank ≥7 cups of tea per day was 0.73 (0.65–0.83). Compared with non-alcohol consumers, the HR (95% CI) was 0.79 (0.72–0.87) for participants who drank pure alcohol of 30.0–59.9 g per day but had no further decrease with a higher intake of alcohol. Compared with less-than-weekly consumers, the HR (95% CI) for daily fruit consumers was 0.81 (0.75–0.87). Even for those who did not drink alcohol excessively, increasing tea and fruit consumption could also independently reduce the stone risk. Among Chinese adults, tea, alcohol, and fruit consumption was associated with a lower risk of kidney stones.

BackgroundThe relationship between educational attainment and ischaemic heart disease (IHD) is limited in evidence in middle-income countries like China. Exploring lifestyle-related mediators, which might be not universal between socioeconomic status and health outcomes in diverse regions, can contribute to interventions targeted at the Chinese to narrow the educational gap in IHD.MethodsBased on the China Kadoorie Biobank of 489 594 participants aged 30–79 years who did not have heart disease or stroke at baseline, this study examined the association of educational attainment with IHD. Total IHD cases were further divided into acute myocardial infarction (AMI) cases and non-AMI cases. The Cox proportional hazard model was performed to estimate the HRs and 95% CIs for mortality and incidence of IHD. Logistic regression was used to estimate the ORs and 95% CIs for case fatality.ResultsDuring the median follow-up period of 11.1 years, this study documented 45 946 (6668) incident IHD (AMI) cases and 5948 (3689) deaths altogether. Lower educational attainment was associated with increased risk of incident AMI as well as death and fatality of total IHD including its subtypes (ptrend trend DiscussionInterventions targeting unhealthy lifestyles are ideal ways to narrow the educational gap in IHD while solving ‘upstream’ causes of health behaviours might be the most fundamental ones.

Background: Epidemiological evidence on the association of soy intake with breast cancer risk is still inconsistent due to different soy intake levels across previous studies and small number of breast cancer cases. We aimed to investigate this issue by analyzing data from the China Kadoorie Biobank (CKB) study and doing a dose-response meta-analysis to integrate existing evidence. Methods: The CKB study included over 300,000 women aged 30 to 79 from 10 regions across China enrolled between 2004 and 2008, and followed-up for breast cancer events until 31 December 2016. Information on soy intake was collected from baseline, two resurveys and twelve 24-hour dietary recalls. We also searched for relevant prospective cohort studies to do a dose-response meta-analysis. Findings: The mean soy intake was 9.4 mg/day soy isoflavones among CKB women. During 10 years of follow-up, 2,289 women developed breast cancers. The multivariable-adjusted relative risk was 0.98 (95% confidence interval [CI]: 0.80 to 1.20) for the fourth (19.1 mg/day) versus the first (4.5 mg/day) soy isoflavone intake quartile. Meta-analysis of prospective studies found that each 10 mg/day increment in soy isoflavone intake was associated with a 3% (95%CI: 1% to 5%) reduced risk of breast cancer. Interpretation: Soy intake at around 20 mg/day of soy isoflavones was not associated with breast cancer risk among Chinese women. Women might need to consume soy at an amount of i‚³ 35 mg/day soy isoflavones to get benefits (reduced risk by 10%) in preventing breast cancer. Funding: National Natural Science Foundation of China and National Key Research and Development Program. Declaration of Interest: All authors declare: no financial relationships with any organizations that might have an interest in the submitted work in the previous three years; no other relationships or activities that could appear to have influenced the submitted work. Ethical Approval: The Ethical Review Committee of the Chinese Center for Disease Control and Prevention (Beijing, China) and the Oxford Tropical Research Ethics Committee, University of Oxford (UK) approved the study.

Background Adherence to a healthy lifestyle is associated with substantially lower risks of mortality from all causes, cardiovascular diseases, and cancer in white populations. However, little is known about the health benefits among non-white populations. Also, no previous studies have focused on respiratory disease mortality in both white and non-white populations. We assessed the relationships between a combination of healthy lifestyle factors and multiple death outcomes in Chinese adults. Methods This study included 487,198 adults aged 30–79 years from the China Kadoorie Biobank without heart disease, stroke, and cancer at study enrolment. We defined five healthy lifestyle factors as never smoking or smoking cessation not due to illness; non-daily drinking or moderate alcohol drinking; median or higher level of physical activity; a diet rich in vegetables, fruits, legumes and fish, and limited in red meat; a body mass index of 18.5 to 27.9 kg/m2 and a waist circumference Results During a median follow-up of 10.2 years (IQR 9.2–11.1), we documented 37,845 deaths. After multivariable adjustment, the number of healthy lifestyle factors exhibited almost inverse linear relationships with the risks of all-cause and cause-specific mortality. Compared with participants without any healthy factors, the hazard ratio of participants with five healthy factors was 0.32 [95% confidence interval (CI): 0.28, 0.37] for all-cause mortality. The corresponding HRs in specific cause of death were 0.42 (95% CI: 0.26, 0.67) for ischaemic heart disease, 0.21 (95% CI: 0.09, 0.49) for ischaemic stroke, 0.37 (95% CI: 0.22, 0.60) for haemorrhage stroke, 0.36 (95% CI: 0.29, 0.45) for cancer, 0.26 (95% CI: 0.14, 0.48) for respiratory diseases, and 0.29 (95% CI: 0.22, 0.39) for other causes. Theoretically, 38.5% (95% CI: 33.0, 43.8%) of all-cause mortality was attributable to nonadherence to a healthy lifestyle, and the proportions of preventable deaths through lifestyle modification ranged from 26.9 to 47.9% for cause-specific mortality. Conclusions Adherence to a healthy lifestyle was associated with substantially lower risks of all-cause, cardiovascular, respiratory, and cancer mortality in Chinese adults. Promotion of a healthy lifestyle may considerably reduce the burden of non-communicable diseases in China.

BackgroundsIn contrast to developed countries, breast cancer in China is characterized by a rapidly escalating incidence rate in the past two decades, lower survival rate, and vast geographic variation. However, there is no validated risk prediction model in China to aid early detection yet.MethodsA large nationwide prospective cohort, China Kadoorie Biobank (CKB), was used to evaluate relative and attributable risks of invasive breast cancer. A total of 300,824 women free of any prior cancer were recruited during 2004–2008 and followed up to Dec 31, 2016. Cox models were used to identify breast cancer risk factors and build a relative risk model. Absolute risks were calculated by incorporating national age- and residence-specific breast cancer incidence and non-breast cancer mortality rates. We used an independent large prospective cohort, Shanghai Women’s Health Study (SWHS), with 73,203 women to externally validate the calibration and discriminating accuracy.ResultsDuring a median of 10.2 years of follow-up in the CKB, 2287 cases were observed. The final model included age, residence area, education, BMI, height, family history of overall cancer, parity, and age at menarche. The model was well-calibrated in both the CKB and the SWHS, yielding expected/observed (E/O) ratios of 1.01 (95% confidence interval (CI), 0.94–1.09) and 0.94 (95% CI, 0.89–0.99), respectively. After eliminating the effect of age and residence, the model maintained moderate but comparable discriminating accuracy compared with those of some previous externally validated models. The adjusted areas under the receiver operating curve (AUC) were 0.634 (95% CI, 0.608–0.661) and 0.585 (95% CI, 0.564–0.605) in the CKB and the SWHS, respectively.ConclusionsBased only on non-laboratory predictors, our model has a good calibration and moderate discriminating capacity. The model may serve as a useful tool to raise individuals’ awareness and aid risk-stratified screening and prevention strategies.

Background Alcohol consumption is an important risk factor for hepatic neoplastic and non-neoplastic diseases. Questions remain, however, about the relevance to disease risk of drinking patterns and alcohol tolerability, which differ appreciably between Chinese and Western populations. Methods The prospective China Kadoorie Biobank included 512,715 adults (41% men) aged 30–79 years recruited from ten areas during 2004–2008, recording alcohol intake, drinking patterns, and other characteristics. After median 10 years’ follow-up, 2531 incident liver cancer, 2040 liver cirrhosis, 260 alcoholic liver disease (ALD), and 1262 non-alcoholic fatty liver disease (NAFLD) cases were recorded among 492,643 participants without prior cancer or chronic liver disease at baseline. Cox regression was used to estimate adjusted hazard ratios (HR) relating alcohol intake and drinking patterns to each disease. Results Overall, 33% of men and 2% of women drank alcohol regularly (i.e. at least weekly) at baseline. Among male current regular drinkers, alcohol consumption showed positive dose-response associations with risks of several major chronic liver diseases, with HRs per 280 g/week (i.e. around four drinks/day) higher usual alcohol intake of 1.44 (95% CI 1.23–1.69) for liver cancer (n = 547), 1.83 (1.60–2.09) for liver cirrhosis (n = 388), 2.01 (1.77–2.28) for ALD (n = 200), 1.71 (1.35–2.16) for NAFLD (n = 198), and 1.52 (1.40–1.64) for total liver disease (n = 1775). The association with ALD appeared stronger among men reporting flushing (i.e., with low alcohol tolerance). After adjustment for the total amount of weekly alcohol consumption, daily drinkers had significantly increased risk of ALD (2.15, 1.40–3.31) compared with non-daily drinkers, and drinking without meals was associated with significantly greater risks of liver cancer (1.32, 1.01–1.72), liver cirrhosis (1.37, 1.02–1.85), and ALD (1.60, 1.09–2.33) compared with drinking with meals. Female current regular drinkers had significantly higher risk of ALD, but not other liver diseases, than female abstainers. Conclusions In Chinese men, alcohol intake was associated with significantly increased risks of several major chronic liver diseases, and certain drinking patterns (e.g. drinking daily, drinking without meals) may further exacerbate the disease risks.

Adherence to healthy lifestyles is associated with reduced risk of coronary heart disease (CHD), but uncertainty persists about the underlying lipid pathway. In a case–control study of 4681 participants nested in the prospective China Kadoorie Biobank, 61 lipidomic markers in baseline plasma were measured by targeted nuclear magnetic resonance spectroscopy. Baseline lifestyles included smoking, alcohol consumption, dietary habit, physical activity, and adiposity levels. Genetic instrument was used to mimic the lipid-lowering effect of statins. We found that 35 lipid metabolites showed statistically significant mediation effects in the pathway from healthy lifestyles to CHD reduction, including very low-density lipoprotein (VLDL) particles and their cholesterol, large-sized high-density lipoprotein (HDL) particle and its cholesterol, and triglyceride in almost all lipoprotein subfractions. The statins genetic score was associated with reduced intermediate- and low-density lipoprotein, but weak or no association with VLDL and HDL. Lifestyle interventions and statins may improve different components of the lipid profile.

Background and aims Observational studies have associated resting heart rate with incident diabetes. Whether the associations are causal remains unclear. We aimed to examine the shape and strength of the associations and assessed the causal relevance of such associations in Chinese adults. Methods and results The China Kadoorie Biobank enrolled 512,891 adults in China. Cox proportional hazard regression models was conducted to estimate hazard ratios (HRs) for the associations of resting heart rate with type 2 diabetes and total diabetes. Among 92,724 participants, 36 single-nucleotide polymorphisms (SNPs) related to resting heart rate were used to construct genetic risk score. We used Mendelian randomization analyses to make the causal inferences. During a median follow-up of 9 years, 7872 incident type 2 diabetes and 13,349 incident total diabetes were documented. After regression dilution bias adjustment, each 10 bpm higher heart rate was associated with about a 26% higher risk of type 2 diabetes (HR, 1.26 [95% CI, 1.23, 1.29]) and 23% higher risk of total diabetes (HR, 1.23 [95% CI, 1.20, 1.26]). Instrumental variable analyses showed participants at top quintile compared with those at bottom quintile had 30% higher risk for type 2 diabetes (HR, 1.30 [95% CI, 1.17, 1.43]), and 10% higher risk for total diabetes (HR, 1.10 [95% CI, 1.02, 1.20]). Conclusions This study provides evidence that resting heart rate is an important risk factor for diabetes risk. The results suggest that novel treatment approaches targeting reduction of high heart rate for incidence of diabetes may be worth further investigation.

Background Previous case–control studies have reported positive associations of spicy food consumption with risks of certain gastrointestinal-tract (GI) cancers. However, there is no prospective evidence on such associations, particularly from China, where there are high incidence rates of GI cancers and spicy food is widely consumed. Methods The prospective China Kadoorie Biobank study recruited >512 000 adults aged 30–79 years from 10 areas in China during 2004–2008; 2350 oesophageal, 3350 stomach and 3061 colorectal incident cancer cases were recorded by 1 January 2017, after a median of 10.1 years of follow-up. Cox regression yielded adjusted hazard ratios (HRs) for each cancer associated with spicy food intake. Results Overall, 30% of participants reported daily spicy food consumption at baseline. Spicy food consumption was inversely associated with oesophageal cancer risk, with adjusted HRs of 1.00, 0.88, 0.76, 0.84 and 0.81 for those who never/rarely consumed (reference) and consumed monthly, 1–2 days/week, 3–5 days/week and 6–7 days/week, respectively (ptrend Conclusion In Chinese adults, higher spicy food consumption was associated with lower risks of certain GI cancers, particularly among individuals who never smoked or drank alcohol regularly.

Graphical abstract Averaged 24-hour variation of fine particulate matter (PM2.5) concentrations (µg/m3) recorded in the personal, kitchen, living room, and ambient monitors across the three study sites in the warm and cool season., Highlights • We collected detailed fuel use, time-activity, and air pollution data from 477 Chinese adults. • Mix of solid and clean fuels was common for cooking or heating in rural areas. • Real-time PM2.5 data at personal, household, and ambient environments are presented. • PM2.5 levels in rural areas with solid fuel use were 2–3 times higher than in urban areas. • Personal, household and ambient PM2.5 levels were 2–3 times higher in the cool season., Background Previous studies of the health impact of ambient and household air pollution (AAP/HAP) have chiefly relied on self-reported and/or address-based exposure modelling data. We assessed the feasibility of collecting and integrating detailed personal exposure data in different settings and seasons. Methods/design We recruited 477 participants (mean age 58 years, 72% women) from three (two rural [Gansu/Henan] and one urban [Suzhou]) study areas in the China Kadoorie Biobank, based on their previously reported fuel use patterns. A time-resolved monitor (PATS+CO) was used to measure continuously for 120-hour the concentration of fine particulate matter (PM2.5) at personal and household (kitchen and living room) levels in warm (May-September 2017) and cool (November 2017–January 2018) seasons, along with questionnaires on participants’ characteristics (e.g. socio-demographic, and fuel use) and time-activity (48-hour). Parallel local ambient monitoring of particulate matter (PM1, PM2.5 and PM10) and gaseous pollutants (CO, ozone, nitrogen oxides) was conducted using regularly-calibrated devices. The air pollution exposure data were compared by study sites and seasons. Findings Overall 76% reported cooking at least weekly (regular-cooks), and 48% (urban 1%, rural 65%) used solid fuels (wood/coal) for cooking. Winter heating was more common in rural sites than in urban site (74–91% vs 17% daily), and mainly involved solid fuels. Mixed use of clean and solid fuels was common for cooking in rural areas (38%) but not for heating (0%). Overall, the measured mean PM2.5 levels were 2–3 fold higher in the cool than warm season, and in rural (e.g. kitchen: Gansuwarm_season = 142.3 µg/m3; Gansucool_season = 508.1 µg/m3; Henanwarm_season = 77.5 µg/m3; Henancool_season = 222.3 µg/m3) than urban sites (Suzhouwarm_season = 41.6 µg/m3; Suzhoucool_season = 81.6 µg/m3). The levels recorded tended to be the highest in kitchens, followed by personal, living room and outdoor. Time-resolved data show prominent peaks consistently recorded in the kitchen at typical cooking times, and sustained elevated PM2.5 levels (> 100 µg/m3) were observed in rural areas where use of solid fuels for heating was common. Discussion Personal air pollution exposure can be readily assessed using a low-cost time-resolved monitor in different settings, which, in combination with other personal and health outcome data, will enable reliable assessment of the long-term health effects of HAP/AAP exposures in general populations.

Background Sepsis represents a major worldwide healthcare burden. However, how body-mass index (BMI) is related to the long-term risk of sepsis-related mortality in low- and middle-income countries remains uncertain. Methods We examined the associations of sepsis-related mortality with both baseline BMI and waist circumference (WC) using data from China Kadoorie Biobank, a prospective cohort recruited during 2004–2008 and followed up to December 2016. After excluding participants with chronic obstructive pulmonary disease, tuberculosis, cancer, heart disease, and stroke, and omitting the first 3 years of follow-up, 440,763 participants remained for analysis. Results During a median follow-up of 10.0 years, 1957 sepsis-related deaths (3,134,870 person-years) were included for analysis. Compared with reference BMI of 22.5 to 2, the multivariable-adjusted hazard ratios (HRs) for sepsis-related mortality were 2.42 (95% CIs 2.07–2.84) for BMI of 2. Further adjustment for WC led to slightly augmentation of the effect size for the lower BMI groups and null association in the obese group. In the association analysis between WC and sepsis-related mortality, compared with the middle quintile group, only the highest quintile group showed an increased risk of sepsis-related mortality after adjusted for BMI (HR = 1.54; 95% CI 1.28–1.84). Conclusions Underweight, lower normal weight, and abdominal obesity are associated with increased future risk of sepsis-related mortality over 10 years in the Chinese population. The double burden of underweight and obesity indicates a heavy sepsis burden faced by low- and middle-income countries.

Background Over 3.5 billion individuals worldwide are exposed to household air pollution from solid fuel use. There is limited evidence from cohort studies on associations of solid fuel use with risks of major eye diseases, which cause substantial disease and economic burden globally. Methods and findings The China Kadoorie Biobank recruited 512,715 adults aged 30 to 79 years from 10 areas across China during 2004 to 2008. Cooking frequency and primary fuel types in the 3 most recent residences were assessed by a questionnaire. During median (IQR) 10.1 (9.2 to 11.1) years of follow-up, electronic linkages to national health insurance databases identified 4,877 incident conjunctiva disorders, 13,408 cataracts, 1,583 disorders of sclera, cornea, iris, and ciliary body (DSCIC), and 1,534 cases of glaucoma. Logistic regression yielded odds ratios (ORs) for each disease associated with long-term use of solid fuels (i.e., coal or wood) compared to clean fuels (i.e., gas or electricity) for cooking, with adjustment for age at baseline, birth cohort, sex, study area, education, occupation, alcohol intake, smoking, environmental tobacco smoke, cookstove ventilation, heating fuel exposure, body mass index, prevalent diabetes, self-reported general health, and length of recall period. After excluding participants with missing or unreliable exposure data, 486,532 participants (mean baseline age 52.0 [SD 10.7] years; 59.1% women) were analysed. Overall, 71% of participants cooked regularly throughout the recall period, of whom 48% used solid fuels consistently. Compared with clean fuel users, solid fuel users had adjusted ORs of 1.32 (1.07 to 1.37, p < 0.001) for conjunctiva disorders, 1.17 (1.08 to 1.26, p < 0.001) for cataracts, 1.35 (1.10 to 1.66, p = 0.0046) for DSCIC, and 0.95 (0.76 to 1.18, p = 0.62) for glaucoma. Switching from solid to clean fuels was associated with smaller elevated risks (over long-term clean fuel users) than nonswitching, with adjusted ORs of 1.21 (1.07 to 1.37, p < 0.001), 1.05 (0.98 to 1.12, p = 0.17), and 1.21 (0.97 to 1.50, p = 0.088) for conjunctiva disorders, cataracts, and DSCIC, respectively. The adjusted ORs for the eye diseases were broadly similar in solid fuel users regardless of ventilation status. The main limitations of this study include the lack of baseline eye disease assessment, the use of self-reported cooking frequency and fuel types for exposure assessment, the risk of bias from delayed diagnosis (particularly for cataracts), and potential residual confounding from unmeasured factors (e.g., sunlight exposure). Conclusions Among Chinese adults, long-term solid fuel use for cooking was associated with higher risks of not only conjunctiva disorders but also cataracts and other more severe eye diseases. Switching to clean fuels appeared to mitigate the risks, underscoring the global health importance of promoting universal access to clean fuels., Ka Hung Chan and co-workers study associations between use of solid fuel for cooking and eye disorders in China., Author summary Why was this study done? Household air pollution from solid fuel use has been linked to higher risks of cataracts and a range of acute eye symptoms, but most previous studies used relatively crude exposure assessment methods and cross-sectional or case–control designs and were relatively small. The relationships of long-term solid fuel use with common eye diseases other than cataracts, including conjunctiva disorders, keratitis, and glaucoma, are poorly understood. What did the researchers do and find? We analysed data from 486,532 adults aged 30 to 79 years recruited from 10 areas of China into the China Kadoorie Biobank during 2004 to 2008 to assess the associations of self-reported long-term solid fuel use for cooking with risks of conjunctivitis, cataracts, disorders of sclera, cornea, iris and ciliary body (DSCIC), and glaucoma during approximately 10-year follow-up. Multivariable logistic regression was used to estimate odds ratios comparing long-term clean fuels and solid fuels users, as well as those who had switched from solid to clean fuels prior to the initial baseline survey. Long-term solid fuel use was associated with 32%, 17%, and 35% higher risks of conjunctiva disorders, cataracts, and DSCIC, respectively, but not associated with glaucoma. Individuals who had switched from solid to clean fuels appeared to have smaller risks than those who used solid fuels persistently. What do these findings mean? To our knowledge, this is one of the first cohort studies on the relationships between long-term solid fuel use and risks of multiple common eye diseases. Our findings support a significant association between solid fuel use and cataracts, but the strength of association appeared to be considerably weaker compared to that observed in previous studies; the associations with conjunctiva disorders and DSCIC indicate that solid fuel use may have more extensive harm on eye health, which should be further investigated.

Limited convincing evidence is available of the relationship between habitual snoring and cardiovascular diseases (CVDs).Is habitual snoring associated with total CVD and CVD subtypes in different age groups of Chinese adults?The China Kadoorie Biobank study enrolled more than 0.5 million adults aged 30 to 79 years from 10 regions in China. Snoring status and other baseline characteristics were collected from 2004 to 2008, using an interviewer-administered laptop-based questionnaire. The current analysis included 489,583 participants without stroke or coronary heart disease at baseline. Cox proportional hazards models were used to calculate the adjusted hazard ratios (HRs) and 95% CIs of cardiovascular diseases (CVDs) for habitual snoring vs nonhabitual snoring.During a median follow-up of 9.6 years, 130,935 participants developed CVDs. Associations between habitual snoring and CVDs varied with age. Among participants aged younger than 50 years at baseline, habitual snoring was associated with an increased risk of total CVD (HR, 1.11; 95% CI, 1.07-1.14) after adjustment for known CVD risk factors, including systolic BP. The corresponding HRs (95% CIs) for ischemic heart disease, ischemic stroke, and hemorrhagic stroke were 1.18 (1.12-1.24), 1.12 (1.05-1.19), and 1.05 (0.92-1.19), respectively. However, such associations in adults aged 50 to 64 years were much weaker, and no statistically significant association was observed among individuals aged ≥65 years. Age-specific risk estimates were generally similar across sex and obesity subgroups.Habitual snoring was associated with increased risks of total CVD, ischemic heart disease, ischemic stroke, but not hemorrhagic stroke in Chinese, and these associations were mainly limited to those aged 50 years. Clinicians in China are encouraged to identify snoring, particularly in younger adults.

Summary In a Chinese population from both urban and rural areas, weight loss of ≥ 5 kg from early adulthood to midlife was associated with a higher risk of hip fracture and lower BMD in later life. Introduction This study investigates the association of the long-term weight loss from young adulthood through the middle ages with the subsequent 10-year risk of hospitalized fracture and calcaneus bone mineral density (BMD). Methods China Kadoorie Biobank (CKB) was established during 2004–2008 in ten areas across China. Weight at age 25 years was self-reported at baseline, and weight at baseline and resurvey was measured by the calibrated equipment. Outcomes were hospitalized fracture during follow-up and calcaneus BMD measured at resurvey. Analysis for fracture risk included 411,812 participants who were free of fracture in the last 5 years before baseline, cancer, or stroke at any time before baseline. Analysis for BMD included 21,453 participants who participated in the resurvey of 2013–2014 with the same exclusion criteria as above. Results The mean age was 50.8 at baseline and 58.4 at resurvey. Median weight change from age 25 to baseline was 4.4 kg, with 20.7% losing weight and 58.5% gaining weight. During a median follow-up of 10.1 years, we documented 13,065 cases of first diagnosed fracture hospitalizations, including 1222 hip fracture. Compared with participants whose weight was stable (± 2.4 kg), the adjusted hazard ratios (95% CIs) for those with weight loss of ≥ 5.0 kg from age 25 to baseline was 1.39 (1.17 to 1.66) for hip fracture. Weight loss was not associated with fracture risk at other sites. Those with weight loss from age 25 to resurvey had the lowest BMD measures, with β (95% CIs) of − 4.52 (− 5.08 to − 3.96) for broadband ultrasound attenuation (BUA), − 4.83 (− 6.98, − 2.67) for speed of sound (SOS), and − 4.36 (− 5.22, − 3.49) for stiffness index (SI). Conclusions Weight loss from early adulthood to midlife was associated with a higher risk of hip fracture and lower BMD in later life.