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Background Limited studies have compared the association between various physical measurements and the risk of cancer or cardiovascular disease (CVD). We aim to explore the best‐individualized indicators of cancer and CVD risk assessment. Methods From May 2004 to December 2017, a community‐based cohort in China involving 100 280 participants were enrolled. BMI, height, body surface area (BSA), and body fat percentage (BFP) were compared in parallel about cancer and CVD risk with the multivariable‐adjusted Cox proportional hazard regression model. Results Within the follow‐up period, 3107 (3.10%) were diagnosed with cancer and 3721 (3.71%) had CVD. Per‐level increased (in tertile: T1, T2, and T3 level) BSA, height, and BFP was positively associated with the risk of overall cancer [HR (95% CI): 1.10 (1.05‐1.15), 1.12 (1.07‐1.18), and 1.10 (1.03‐1.16), respectively], whereas BMI was insignificant. Compared with the reference group (T2), the highest BSA level (T3) was positively associated with overall cancer incidence for both male [HR (95% CI): 1.28 (1.13‐1.45)] and female [HR (95% CI): 1.13 (1.00‐1.28)]. The BSA, height, and BFP also significantly associated with some site‐specific cancers including thyroid, stomach, breast, urinary system, and skin cancer. Meanwhile, BFP presented a strong positive association with overall CVD [HR (95% CI): 1.22 (1.15‐1.30) in trend] in both gender and associated with nearly all CVD subtypes especially the myocardial infarction and heart failure. Conclusion BSA, height, and BFP have more sensitivity in assessing cancer risk and BFP shows the largest hazard ratios for CVD incident. We provided valuable evidence for the application of height, BSA, and BFP in routine healthcare practice. These encouraging findings should be tested in more well‐defined studies for risk prediction., Body surface area, height, and body fat percentage has higher sensitivity in assessing cancer risk than BMI. Body fat percentage shows the largest hazard ratios in all cardiovascular events. BSA, height, and BFP have considerable application value in routine healthcare practice.

Background Although observational studies have shown an association between sex hormone-binding globulin (SHBG), testosterone (T) and cardiovascular diseases (CVD), controversy remains. In this study, we aim to explore the causal effects of SHBG and T on Coronary heart disease (CHD). Methods We used univariable, network and multivariable mendelian randomization (MR) analysis to investigate the causal effect of SHBG and T on CHD. We performed inverse variance weighted (IVW) MR as the primary analysis, with the robustness of this approach further tested by other methods in sensitivity analysis. The SHBG and T were collected from the UK Biobank data, about 180,000 men aged 40 to 69 years. CHD was collected from CARDIoGRAMplusC4D 1000 Genomes-based GWAS, which was a meta-analysis including 48 studies and involving 60,801 CHD cases and 123,504 controls. Results Using univariable MR-IVW, the results suggested that a one standard deviation (SD) increase in SHBG, the risk of CHD decreased by approximately 14% (OR (95% CI): 0.86(0.76,0.97)), and that a SD increase in total testosterone (TT), the risk also decreased, approximately 8% (OR (95% CI): 0.92(0.85,0.99)). Multivariable MR showed that both SHBG and TT had no direct causal effect with CHD (a SD increase in SHBG: OR (95% CI):0.75(0.57,1.00), P = 0.053; a SD increase in TT: OR (95% CI): 1.05(0.90,1.22), P = 0.53). In the network MR analysis, the results suggested that TT might act as mediator in the causal pathway from SHBG to CHD and account for 93% of the total effect of SHBG on CHD, and that SHBG might be a mediator in the causal pathway from TT to CHD and account for 67% of the total effect of TT on CHD. Conclusions Genetically predicted SHBG and TT were negatively correlated with CHD in both univariable and network MR, which may provide a causal explanation behind the observed conclusion. In addition, TT and SHBG had a bidirectional causal effect. Further work is required to disentangle the downstream effects of SHBG/TT on CHD and the molecular pathways involved, as the simultaneous regulation of SHBG and TT may make it a viable strategy for the prevention or treatment of CHD.

To test the causal effect of hip circumference adjusted for body mass index(HCadjBMI) and coronary heart disease(CHD) using a Mendelian randomization analysis.Based on genome-wide association study, the associations between the genetic instruments(IVs) and HCadjBMI were obtained from the GIANT consortium(n=211 114, European), the associations between IVs and CHD were derided from CARDIoGRAM consortium(n=86 995, European). The inverse-variance weighted method was used to estimate a pooled OR for the effect of a 1 cm higher HCadjBMI on CHD. Evidence of directional pleiotropy averaged across all variants was sought using MR-Egger regression.A total of 70 genetic variants that reached genome-wide significance and independent of each other were identified as IVs. A combined genetic variants expected to confer a lifetime exposure of per SD higher HCadjBMI was associated with a lower risk of CHD(OR=0. 831, 95%CI 0. 730-0. 946). MR-Egger regression intercept suggested that directional pleiotropy was unlikely to be biasing the result(intercept-0. 0012, P=0. 875). There was no specific single nucleotide polymorphism(SNP) detected by "leave one out" analysis.A genetic predisposition to higher HCadjBMI was associated with lower risk of CHD.

Background Prevention and control of cardiometabolic conditions and cardiovascular disease (CVD) in China may contribute to sustainable CVD reduction globally, given the fact that one-fifth of the worldwide population is in China. Knowing the distribution of behavioral risk factors (e.g., smoking and physical inactivity), especially at a national level in China, would be extremely relevant to the field of public health and CVD prevention. The objectives of this study were to investigate the nationwide prevalence of obesity, smoking, heavy drinking, and physical inactivity in Chinese adults, and further explore whether cardiometabolic conditions would modify the distribution of behavioral risk factors. Methods This population-based study is based on the China Health and Retirement Longitudinal Study (2011–2012), including 17,302 adults (≥45 years, mean age 59.67 years, female 51.66%) from 25 provinces in China. Data on demographics, lifestyle factors, health status and history of diseases were collected via structured interviews and laboratory tests. Smoking, heavy drinking, obesity, and physical inactivity were defined following standard guidelines. We performed descriptive analysis and logistic regressions in this study. Results The overall prevalence of heavy drinking, obesity, current smoking, and physical inactivity among middle-aged and older adults was 7.23% (95% confidence interval 6.53—7.29%), 11.53% (10.43—12.62%), 27.46% (26.30—28.62%), and 44.06% (41.19—46.92%), respectively. The prevalence varied between rural and urban areas as well as among geographic areas, with higher prevalence in the Northern and Northeastern regions. Heavy drinking and obesity were significantly associated with incident hypertension, diabetes, and high cholesterol; while current smoking was significantly associated with incident hypertension. Compared with healthy individuals, participants who self-reported a diagnosis of hypertension, high cholesterol, or diabetes were less likely to smoke currently and drink alcohol heavily, but more likely to be physically inactive and obese. Conclusions Among Chinese middle-aged and older adults, the prevalence of behavioral risk factors varies by geographic region. Further effort is required to improve physical activity and fitness for Chinese adults, especially those with cardiometabolic conditions.

Background Available data about the effects of circulating polyunsaturated fatty acids (PUFAs) on ischemic stroke (IS) and its main risk factors remains limited and conflicting. Therefore, we conducted Mendelian randomization (MR) to assess whether genetically predicted PUFA affected IS, lipids and blood pressure (BP). Methods Genetic instruments associated with IS were derived from ISGC Consortium (n = 29,633), with lipids were derived from GLGC(n = 188,577), with BP were derived from Neale Lab(n = 337,000). The inverse-variance weighted method was the main analysis to estimate the effect of exposure on outcome. Sensitivity analyses included principal components analysis, MR-Egger, weighted median, and weighted mode. Results Per SD increases in serum α-linolenic acid (ALA) were associated with lower IS risk, with odd ratio (OR) of 0.867(0.782,0.961), arachidonic acid (AA) were associated with higher IS risk (OR: 1.053(1.014,1.094)). Likewise, Per SD increases in ALA were associated with the lower-level low-density lipoprotein cholesterol(LDL-C), high-density lipoprotein cholesterol (HDL-C), total cholesterol (TC) (β:-0.122(− 0.144, − 0.101), − 0.159(− 0.182, − 0.135), − 0.148(− 0.171, − 0.126), respectively), AA were associated with the higher-level of LDL-C, HDL-C and TC (β:0.045(0.034,0.056), 0.059(0.050,0.067), 0.055(0.046,0.063), respectively). Linoleic acid (LA), eicosapentaenoic acid (EPA), docosahexaenoic acid (DHA) and docosapentaenoic acid (DPA) had little or no association with IS, lipids or BP at Bonferroni-corrected significance. Different analytic methods supported these findings. The intercept test of MR-Egger implied no pleiotropy. Conclusions High-level plasma ALA was protective for IS but AA was the opposite. LA, EPA, DHA, and DPA had no effects on IS.

The association between whole blood viscosity (WBV) and metabolic syndrome (MetS) is still scarcely investigated in the population-based prospective cohort. We aim to explore the longitudinal effect of WBV on MetS, and to verify whether WBV measures can be used as early predictors for MetS. The longitudinal cohort consisted of 3,508 adults (2,350 males and 1,158 females) who visited the health check-up system twice. WBV were measured at four shear rate (200, 50, 10 and 1 s-1), and their values were classified into quartiles. Multivariate Cox models were used to estimate the adjusted hazard ratios (HRs) and 95% confidence intervals (CIs) in men and women, respectively. A total of 444 (12.66%) incident MetS were observed at follow-up period. The incidences of MetS significantly increased with increasing quartiles of WBVs at all of the shear rate in men. After adjusting for baseline age, smoking, obesity, hypertension, hyperglycemia, and hyperlipidemia status, all of the WBV measures were significantly associated with incident MetS in men, and the HRs showed clear increasing trend across the quartiles of baseline WBVs. There were no significant association between WBVs and incident MetS in women. These findings suggest that MetS has a hemodynamic basis, and WBVs could be used as independent early predictor for MetS in men.

Additional file 3. Software code for PCA.

Additional file 1: Supplementary Table 1. Geographic prevalence (95% confidence interval) of smoking, drinking, obesity and physical inactivity. Supplementary Fig. 1. Province-specific prevalence of current smoking, heavy drinking, physical inactivity and obesity by urban and rural areas. Supplementary Table 2. Association between behavioral risk factors and cardiometabolic conditions. Supplementary Table 3. Association between behavioral risk factors and cardiometabolic conditions among those without history of cardiovascular disease.

Chinese women in rural areas who are currently=55 years old have experienced extreme undernutrition during their childbearing age. Their specific experiences provided us with a natural quasiexperimental field for assessing the effects of consuming eggs to obtain nutrients during the childbearing period on preventing nonfatal coronary events (NCE) during the postmenopausal period in the framework of life course epidemiology.A population-based matched case-control design for NCE was conducted in Yiyuan County, Shandong Province, China. In this study, 462 women with NCE (cases; onset age=55 years) were included from the Active Surveillance System for Chronic Diseases, and 462 age-matched women without NCE and stroke (controls) from the same village were included. Conditional logistic model analysis was used to determine the association between egg intake and NCE during the postmenopausal period in 3 specific life-periods, namely age 18 to 49 years (childbearing period), age 50 years to NCE onset (perimenopausal and postmenopausal period), and age 18 years to NCE onset (total period).We found that=12 eggs vs. 0 egg intake per month under extreme undernutrition status during childbearing period exhibited a strong preventive effect against NCE during the postmenopausal period (OR=0.588, 95% CI=0.358-0.964). The window of protective effect was in the age 28 to 49 years, suggesting a critical period model of life course epidemiology.Egg intake under extreme undernutrition status during the childbearing period plays a critical role in preventing NCE during the postmenopausal period.

Background This longitudinal study aims to characterize longitudinal body mass index (BMI) trajectories during young adulthood (20–40 years) and examine the impact of level‐independent BMI trajectories on hypertension risk. Methods and Results The cohort consisted of 3271 participants (1712 males and 1559 females) who had BMI and blood pressure (BP) repeatedly measured 4 to 11 times during 2004 to 2015 and information on incident hypertension. Four distinct trajectory groups were identified using latent class growth mixture model: low‐stable (n=1497), medium‐increasing (n=1421), high‐increasing (n=291), sharp‐increasing (n=62). Model‐estimated levels and linear slopes of BMI at each age point between ages 20 and 40 were calculated in 1‐year intervals using the latent class growth mixture model parameters and their first derivatives, respectively. Compared with the low‐stable group, the hazard ratios and 95% CI were 2.42 (1.88, 3.11), 4.25 (3.08, 5.87), 11.17 (7.60, 16.41) for the 3 increasing groups, respectively. After adjusting for covariates, the standardized odds ratios and 95% CI of model‐estimated BMI level for incident hypertension increased in 20 to 35 years, ranging from 0.80 (0.72–0.90) to 1.59 (1.44–1.75); then decreased gradually to 1.54 (1.42–1.68). The standardized odds ratios of level‐adjusted linear slopes increased from 1.22 (1.09–1.37) to 1.79 (1.59–2.01) at 20 to 24 years; then decreased rapidly to 1.12 (0.95–1.32). Conclusions These results indicate that the level‐independent BMI trajectories during young adulthood have significant impact on hypertension risk. Age between 20 and 30 years is a crucial period for incident hypertension, which has implications for early prevention., See Editorial Roush

Background and Objectives The existence of smokers who are resistant to smoking cessation interventions has attracted considerable interest in recent years. Given the paucity of data on that topic in rural China, we aimed to assess the prevalence and risk factors of hardcore smoking in rural China. Methods A cross-sectional study was conducted in 14 villages in Shandong, China. A total of 1,287 male daily smokers were face-to-face interviewed. A multiple logistic regression model was used to explore the associations of demographics, environment, knowledge and attitudes about smoking, and smoking behavior characteristics with hardcore smoking among daily male smokers. A general dominance analysis model was used to access the relative contribution of the determinants that were identified in the multiple logistic regression. Results Hardcore smokers constituted 32.9% (n = 423) of daily male smokers. Five determinants for hardcore smoking were identified in the multiple logistic regression. Dominance analysis showed higher level of smoking intensity was the most important determinant of hardcore smoking, followed by being a farmer, starting to smoke daily under the age of 20, younger age, having fewer smokers around. Discussion and Conclusions This study suggests that hardcore smokers account for a substantial proportion of daily male smokers and are distinct from other groups of daily smokers. Scientific Significance Specifically tailored tobacco-control efforts should be made to address the issues incurred by hardcore smokers. (Am J Addict 2016;25:628–633)

Background Previous studies examining temperature–disease associations of hand, foot and mouth disease (HFMD) mainly focused on a single city. The results demonstrated great heterogeneity. A multi-city study is necessary to better understand temperature risk on the childhood incidence of HFMD and the associated modified factors. Objective To assess the effect of ambient temperature on childhood HFMD incidence and explore the potential associated effect modifiers in the study area. Methods Daily morbidity data and meteorological variables of the 17 cities were collected for the period from 2007 to 2012. Distributed lag non-linear model (DLNM) was used to estimate city-specific effects of temperature on HFMD incidence. A multivariate meta-analysis was then applied to pool the estimated city-specific effect. Potential effect modifiers were included in the multivariate meta-regression as meta-predictors. Results A total of 504,017 childhood HFMD cases were included in the study. The high-incidence period of HFMD was detected in late spring and early summer (April to June). The temperature–disease associations of the 17 cities demonstrated great heterogeneity and the pooled exposure–response curve was an approximately inverted V-shape. Regional indicator, numbers of healthcare institution and annual household income were considered as associated modifiers. Conclusion Our findings can provide a practical reference for the early warning and intervention strategies of HFMD. Different temperature–disease associations among different regions should be considered when formulating and optimizing public health policy.

Hydrogen energy with clean, high–energy density, and renewable characteristics has been regarded as an ideal energy to solve the current energy crisis and environmental pollution problems. Water splitting driven by renewable resource–derived electricity and direct use of sunlight based on electrocatalytic and photocatalytic reactions are two promising ways for sustainable hydrogen production. The development and design of efficient electrocatalysts and photocatalysts for hydrogen production is one of the most challenging and demanding missions for today's scientists. In this review, the basic principle and performance evaluation parameters of electrocatalytic and photocatalytic hydrogen production are first introduced, followed by a comprehensive summary of the research progress in electrocatalysts and photocatalysts for hydrogen production from water splitting. Subsequently, special focus is put on the surface and interfacial regulation strategies of electrocatalysts and photocatalysts for improving their H2 production performances from water splitting, including morphology regulation, doping and surface defects, heterojunction construction, and cocatalyst modification. Finally, we also point out that the development of advanced electrocatalysts have the important positive effect for the design of efficient photocatalysts due to the similar nature between the electrocatalysts and cocatalysts in photocatalysis (the active sites that facilitate charge transfer and reduce the reaction energy barrier) during water splitting. We hope that this review article can give some inspirations and guidance for the design of efficient electrocatalytic and photocatalytic water splitting systems.

Background: Esophageal squamous cell carcinoma (ESCC) has been having a high mortality rate in China. Most patients are diagnosed in advanced stages, leading to the poor prognosis and low 5-year survival rate. Detection of precancerous lesions or early cancers is the key to improving this situation. Although previous studies have identified some risk factors for ESCC, they rarely paid attention to the premalignant esophageal lesions. We thus initiated a population-based screening study aiming to assess risk factors associated with esophageal precancerous lesions (EPLs) in a high risk Chinese population. Methods: From September 2013 to July 2015, we screened residents aged 40-69 years from 53 randomly selected communities in Feicheng, China (n = 5076). Each participant went through questionnaire interview, physical examination, endoscopy and biopsy. Using logistic regression, we compared participants with EPLs to that with normal esophageal mucosa for finding potential risk factors of EPLs. Results: A total of 570 participants were diagnosed with EPLs. We observed no association between EPLs and tobacco smoking or alcohol consumption in unadjusted or adjusted model. In the adjusted model, the OR (95% CI) was 1.84 (1.18-2.89) for people of drinking shallow-well water comparing to people who was drinking tap-water. In a comparison of participants with good oral health, the ESD/ESCC ORs (95% CI) for those with very poor or poor oral health, were 1.78 (1.28-2.49) and 1.58 (1.16-2.15) respectively. However, no statistical significance was observed after adjustment. Moreover, cereal straw heating (OR= 1.74, 95% CI: 0.90-3.36, P=0.099) may lead to increased risk of EPLs. Conclusion: In Feicheng population, tobacco smoking or alcohol consumption may not be risk factors of EPLs. Low-quality drinking water raised the EPLs risk. Bad house heating materials, such as cereal straw, may lead to high EPLs risk.

Background Estrogen may regulate gastrointestinal motor functions, but the mechanism(s) is not totally understood. Here, we investigated whether G protein-coupled estrogen receptor (GPER/GPR30) was involved in regulating colonic motor functions and explored the underlying physiological mechanisms. Methods Adult female C57BL/6 mice were used. The expression and localization of GPER were examined by RT-PCR, western blot, and immuno-labeling. The role of GPER in modulating colonic motor functions was assessed by the bead propulsion test in vivo and organ bath experiments in vitro. Key Results GPER was expressed in colonic myenteric neurons. The colonic transit time (CTT) in proestrus and estrus was significantly longer than that in diestrus. In vivo treatment with the selective GPER blocker G15 significantly shortened CTT in proestrus and estrus. In ovariectomized mice, acute estrogen supplementation increased CTT, which could be abolished by G15 co-administration. The GPER agonist G-1 caused a concentration-dependent inhibition of carbachol -induced circular muscle strips contraction, which was abolished by tetrodotoxin and the neuronal nitric oxide synthase (nNOS) inhibitor N-propyl-l-arginine. G-1 stimulated NO production in isolated longitudinal muscle myenteric plexus and cultured myenteric neurons, which was dependent on nNOS. Immunofluorescence labeling showed co-localization of GPER with nNOS in the myenteric plexus. Conclusions & Inferences We suggest that activation of GPER exerts an inhibitory effect on colonic motility by promoting NO release from myenteric nitrergic nerves. These results raise a possibility that GPER may be involved in mediating the inhibitory effect of estrogen on colonic motor functions, via a non-genomic, neurogenic mechanism.

Hand, foot and mouth disease (HFMD) has been a substantial burden throughout the Asia-Pacific countries over the past decades. For the purposes of disease prevention and climate change health impact assessment, it is important to understand the temperature–disease association for HFMD in different geographical locations. This study aims to assess the impact of temperature on HFMD incidence in an inland city and a coastal city and investigate the heterogeneity of temperature–disease associations. Daily morbidity data and meteorological variables of the study areas were collected for the period from 2007 to 2012. A total of 108,377 HFMD cases were included in this study. A distributed lag non-linear model (DLNM) with Poisson distribution was used to examine the nonlinear lagged effects of daily mean temperature on HFMD incidence. After controlling potential confounders, temperature showed significant association with HFMD incidence and the two cities demonstrated different impact modes ( I2= 96.1%, p &lt, 0.01). The results highlight the effect of temperature on HFMD incidence and the impact pattern may be modified by geographical localities. Our findings can be a practical reference for the early warning and intervention strategies of HFMD.

Objectives: The aim of this study was to quantify the relationship between meteorological factors and the occurrence of hand, foot, and mouth disease (HFMD) among children in Shandong Province, China, at a county level, using spatial panel data models. Methods: Descriptive analysis was applied to describe the epidemic characteristics of HFMD from January 2008 to December 2012, and then a global autocorrelation statistic (Moran's I) was used to detect the spatial autocorrelation of HFMD in each year. Finally, spatial panel data models were performed to explore the association between the incidence of HFMD and meteorological factors. Results: Moran's I at the county level were high, from 0.30 to 0.45 (p

Mumps presents a serious threat to public health in China. We conducted a descriptive analysis to identify the epidemiological characteristics of mumps in Shandong Province. Spatial autocorrelation and space-time scan analyses were utilized to detect spatial-temporal clusters. From 2005 to 2014, 115745 mumps cases were reported in Shandong, with an average male-to-female ratio of 1.94. Mumps occurred mostly in spring (32.17% of all reported cases) and in children aged 5 to 9 (40.79% of all reported cases). The Moran’s I test was significant and local indicators of spatial autocorrelation (LISA) analysis revealed significant spatial clusters with high incidence. The results showed that the mid-west of Shandong Province and some coastal regions (Qingdao City and Weihai City) were high-risk areas, particularly in the center of the Jining City and the junction of Dongying City, Binzhou City and Zibo City. The results could assist local and national public health agencies in formulating better public health strategic planning and resource allocation.

Background: Hyperuricemia (HUA) contributes to gout and many other diseases. Many hyperuricemia-related risk factors have been discovered, which provided the possibility for building the hyperuricemia prediction model. In this study we aimed to explore the incidence of hyperuricemia and develop hyperuricemia prediction models based on the routine biomarkers for both males and females in urban Han Chinese adults. Methods: A cohort of 58,542 members of the urban population (34,980 males and 23,562 females) aged 20–80 years old, free of hyperuricemia at baseline examination, was followed up for a median 2.5 years. The Cox proportional hazards regression model was used to develop gender-specific prediction models. Harrell’s C-statistics was used to evaluate the discrimination ability of the models, and the 10-fold cross-validation was used to validate the models. Results: In 7139 subjects (5585 males and 1554 females), hyperuricemia occurred during a median of 2.5 years of follow-up, leading to a total incidence density of 49.63/1000 person years (64.62/1000 person years for males and 27.12/1000 person years for females). The predictors of hyperuricemia were age, body mass index (BMI) systolic blood pressure, serum uric acid for males, and BMI, systolic blood pressure, serum uric acid, triglycerides for females. The models’ C statistics were 0.783 (95% confidence interval (CI), 0.779–0.786) for males and 0.784 (95% CI, 0.778–0.789) for females. After 10-fold cross-validation, the C statistics were still steady, with 0.782 for males and 0.783 for females. Conclusions: In this study, gender-specific prediction models for hyperuricemia for urban Han Chinese adults were developed and performed well.

Appendix: Deducing whether c-equivalence had same bias-reducing potential under logistic regression model. (DOCX 107Â kb)

Scenario 1 (Fig. 1a), simulation results of the bias and standard error of c-equivalence sets A 1 ≈ A 2 ≈ A 3 when varied across the log transformed odds ratio effect of Z on X and X on Y. (PDF 25 kb)

Scenario 4 (Figure 1d), simulation results of the bias and standard error of c-equivalence sets A 1 ≈ A 2 ≈ A 3 when varied across the log transformed odds ratio effect of Z on X and X on Y. (PDF 25 kb)

Scenario 2 (Fig. 1b), simulation results of the bias and standard error of c-equivalence sets A 1 ≈ A 2 ≈ A 3 when varied across the log transformed odds ratio effect of Z on T and X on Y. (PDF 25 kb)

Scenario 2 (Fig. 1b), simulation results of the bias and standard error of c-equivalence sets A 1 ≈ A 2 ≈ A 3 when varied across the log transformed odds ratio effect of Z on X and W on X. (PDF 25 kb)

Scenario 2 (Fig. 1b), simulation results of the bias and standard error of c-equivalence sets B 1 ≈ B 2 when varied across the log transformed odds ratio effect of Z on X and W on X. (PDF 19 kb)

Scenario 3 (Fig. 1c), simulation results of the bias and standard error of c-equivalence sets A 1 ≈ A 2 when varied across the log transformed odds ratio effect of T on Y, W on X and X on Y. (PDF 27 kb)

Scenario 3 (Fig. 1c), simulation results of the bias and standard error of c-equivalence sets C 1 ≈ C 2 ≈ C 3 when varied across the log transformed odds ratio effect of Z on X and W on V. (PDF 25 kb)

Scenario 3 (Fig. 1c), simulation results of the bias and standard error of c-equivalence sets A 1 ≈ A 2 when varied across the log transformed odds ratio effect of Z on X and W on V. (PDF 19 kb)

Scenario 2 (Fig. 1b), simulation results of the bias and standard error of c-equivalence sets B 1 ≈ B 2 when varied across the log transformed odds ratio effect of Z on T and X on Y. (PDF 19 kb)

The precise association between metabolic syndrome (MetS) and gallstone disease remains unclear in China. This study aimed to clarify the relationship between MetS and gallstone and evaluate whether counts of metabolic abnormalities had influence on gallstone disease. We fitted gender-specific generalized estimating equation (GEE) regression models with data from a large-scale longitudinal study over 6-year follow-up to elucidate the real association. This study included 18291 participants with 3 times repeated measures at least who were free from a prior history of gallstone disease and cholecystectomy. A total of 873 cases of gallstones occurred during 6-year follow-up. The incidence density of gallstone in the group of subjects with MetS was higher than the group without MetS (10.27 vs 5.79). The GEE analyses confirmed and clarified the association between MetS and gallstone disease in males (RR = 1.33, P = 0.0020), while this association was not significant in females (RR = 1.15, P = 0.4962). With numbers of metabolic syndrome components increasing, the risk of gallstone disease showed corresponding increasing in males. In conclusion, the associations of MetS and gallstone are different in males and in females. And the risk of gallstone disease increases with the number of components of MetS for males but not for females.

Previous metabolomics studies have revealed perturbed metabolic signatures in esophageal squamous cell carcinoma (ESCC) patients, however, most of these studies included mainly late-staged ESCC patients due to the difficulties of collecting the early-staged samples from asymptotic ESCC subjects. This study aims to explore the early-staged ESCC metabolic signatures and potential of serum metabolomics to diagnose ESCC at early stages. Serum samples of 97 ESCC patients (stage 0, 39 cases; stage I, 17 cases; stage II, 11 cases, stage III, 30 cases) and 105 healthy controls (HC) were enrolled and randomly separated into training data (77 ESCCs, 84 HCs) and validation data (20 ESCCs, 21 HCs). Untargeted metabolomics was performed to identify ESCC-related metabolic signatures. The global metabolomics profiles could clearly distinguish ESCC from HC in training data. 16 ascertained metabolites were found to be disturbed in the metabolic pathways characterized by dysregulated fatty acid biosynthesis, glycerophospholipid metabolism, choline metabolism in cancer and linoleic acid metabolism. The AUC value in validation data was 0.895, with sensitivity 85.0 % and specificity 90.5 %. Good diagnostic performances were also achieved for early stage ESCC, with the values of area under the curve (AUC) 0.881 for the ESCC patients in both stage 0 and I–II. In addition, six metabolites were found to discriminate ESCC stages. Among them, three biomarkers, dodecanoic acid, LysoPA(18:1), and LysoPC(14:0), exhibited clear trend for ESCC progression. These findings suggest serum metabolomics, performed in a minimally noninvasive and convenient manner, may possess great potential for early diagnosis of ESCC patients.

Objectives The white blood cell (WBC) count is a simple and convenient marker of inflammation for use in medical practice; however, its association with non-alcoholic fatty liver disease (NAFLD) has not been determined. We examined the relationship between WBC and NAFLD to provide a convenient and useful marker for the prediction of NAFLD. Setting A longitudinal cohort participating in a large health check-up programme for the Chinese population was selected and followed up from 2005 to 2011. Participants A total of 21 307 male and female participants without NAFLD who underwent health check-ups at least twice between 2005 and 2011 were included in this study. 15 201 participants (7286 men and 7915 women) were eligible for inclusion. Results The baseline distribution of age, WBC, body mass index (BMI), systolic blood pressure (SBP), diastolic blood pressure (DBP), fasting plasma glucose (FPG), total cholesterol (TC), triglyceride (TG), high-density lipoprotein cholesterol (HDL-C), low-density lipoprotein cholesterol (LDL-C), serum total protein (TP), albumin (ALB) and globin (GLO) and the prevalence of males, hypertension, hyperglycaemia, smoking and regular exercise were significantly different between the incident NAFLD and non-NAFLD groups (p

Background An increasing trend of the incidence of mumps has been observed in a few developing countries in recent years, presenting a major threat to children's health. A few studies have examined the relationship between meteorological factors and mumps with inconsistent findings. Methods The daily data of meteorological variables and mumps from 2009 to 2013 were obtained from Jining, a temperate inland city of China. A generalized additive model was used to quantify the association between meteorological factors and mumps based on the exposure-response relationship. Results A total of 8520 mumps cases were included in this study. We found a nonlinear relationship of daily mean temperature, sunshine duration and relative humidity with mumps, with an approximately linear association for mean temperature above 4 °C (excess risk (ER) for 1 °C increase was 2.72%, 95% confidence interval (CI): 2.38%, 3.05% on the current day), for relative humidity above 54%, the ER for 1% increase was − 1.86% (95% CI: − 2.06%, − 1.65%) at lag day 14; and for sunshine duration higher than 5 h/d, the ER for per 1 h/d increase was12.91% (95% CI: 11.38%, 14.47%) at lag day 1. While we found linear effects for daily wind speed (ER: 2.98%, 95% CI: 2.71%, 3.26% at lag day 13). Conclusions This study suggests that meteorological factors might be important predictors of incidence of mumps, and should be considered in its control and prevention.

The type I error rates of the seven methods without correlation and interaction under (β 1 = 0, β 2 = 0, β 3 = 0). Table S2. The type I error rates of the SBS and LASSO without correlation and interaction under (β 1 = log(1.3), β 2 = log(1.5)). Table S3. The type I error rates of the SBS and LASSO without main effects and interaction (β 1 = 0, β 2 = 0, β 3 = 0). (DOCX 24 kb)

The power of the seven methods when the summation of the main effects of the two causal SNPs were fixed as log(2.8), interaction effect at β 3 = 0 and the correlation at 0.5 for type II co-association. (PDF 3 kb)

The power of the seven methods under different sample sizes with two main effects and fixed interaction effect (β 1 = log(1.3), β 2 = log(1.5), β 3 = log(1.5)) for type I co-association. (PDF 3 kb)

The power of the seven methods under different co-association levels with no main effect (β 1 = 0, β 2 = 0). Note: figure a for Type I co-association with different interaction effects; figure b for Type II co-association with different causal SNP pairs; figure c for Type III co-association given fixed correlation 0.3 and different interaction effects; figure d for Type III co-association given fixed interaction effect β 3 = log(1.3) and different causal SNP pairs. (PDF 7 kb)