Dongfeng General Hospital

China has seen rapid socio-economic and epidemiolo-gical changes over the past several decades. Economicgrowth plus shifts in environment, lifestyles and diethave increased life expectancy, but they have also ledto a higher burden of chronic, non-communicablediseases. Stroke, coronary heart disease (CHD), cancerand diabetes account for 80% of the deaths and 70%of the disability-adjusted life-years lost in China.

BACKGROUND: Circulating metals from both the natural environment and pollution have been linked to cardiovascular disease. However, few prospective studies have investigated the associations between exposure to multiple metals and incident coronary heart disease (CHD). OBJECTIVES: We conducted a nested case-control study in the prospective Dongfeng-Tongji cohort, to investigate the prospective association between plasma metal concentrations and incident CHD. METHODS: A total of 1,621 incident CHD cases and 1,621 controls free of major cardiovascular disease at baseline and follow-up visits were matched on age ( 5 years) and sex. We measured baseline fasting plasma concentrations of 23 metals and used conditional logistic regression models to estimate odds ratios (ORs) of CHD for metal concentrations categorized according to quartiles in controls. RESULTS: Five metals (titanium, arsenic, selenium, aluminum, and barium) were significantly associated with CHD based on trend tests from singlemetal multivariable models adjusted for established cardiovascular risk factors. When all five were included in the same model, adjusted ORs for barium and aluminum were close to the null, whereas associations with titanium, arsenic, and selenium were similar to estimates from single-metal models, and ORs comparing extreme quartiles were 1.32 (95% CI: 1.03, 1.69; p-trend = 0:04), 1.78 (95% CI: 1.29, 2.46; p-trend = 0:001), and 0.67 (95% CI: 0.52, 0.85; p-trend = 0:001), respectively. CONCLUSIONS: Our study suggested that incident CHD was positively associated with plasma levels of titanium and arsenic, and inversely associated with selenium. Additional research is needed to confirm these findings in other populations.

Substantial progress has been made in identification of type 2 diabetes (T2D) risk loci in the past few years, but our understanding of the genetic basis of T2D in ethnically diverse populations remains limited. We performed a genome-wide association study and a replication study in Chinese Hans comprising 8,569 T2D case subjects and 8,923 control subjects in total, from which 10 single nucleotide polymorphisms were selected for further follow-up in a de novo replication sample of 3,410 T2D case and 3,412 control subjects and an in silico replication sample of 6,952 T2D case and 11,865 control subjects. Besides confirming seven established T2D loci (CDKAL1, CDKN2A/B, KCNQ1, CDC123, GLIS3, HNF1B, and DUSP9) at genome-wide significance, we identified two novel T2D loci, including G-protein-coupled receptor kinase 5 (GRK5) (rs10886471: P = 7.1 × 10(-9)) and RASGRP1 (rs7403531: P = 3.9 × 10(-9)), of which the association signal at GRK5 seems to be specific to East Asians. In nondiabetic individuals, the T2D risk-increasing allele of RASGRP1-rs7403531 was also associated with higher HbA(1c) and lower homeostasis model assessment of β-cell function (P = 0.03 and 0.0209, respectively), whereas the T2D risk-increasing allele of GRK5-rs10886471 was also associated with higher fasting insulin (P = 0.0169) but not with fasting glucose. Our findings not only provide new insights into the pathophysiology of T2D, but may also shed light on the ethnic differences in T2D susceptibility.

OBJECTIVE: To investigate the associations of sleep duration, midday napping, sleep quality, and change in sleep duration with risk of incident stroke and stroke subtypes. METHODS: Among 31,750 participants aged 61.7 years on average at baseline from the Dongfeng-Tongji cohort, we used Cox regression models to estimate hazard ratios (HRs) and 95% confidence intervals (CIs) for incident stroke. RESULTS: Compared with sleeping 7 to <8 hours/night, those reporting longer sleep duration (≥9 hours/night) had a greater risk of total stroke (hazard ratio [HR] 1.23; 95% confidence interval [CI] 1.07-1.41), while shorter sleep (<6 hours/night) had no significant effect on stroke risk. The HR (95% CI) of total stroke was 1.25 (1.03-1.53) for midday napping >90 minutes vs 1-30 minutes. The results were similar for ischemic stroke. Compared with good sleep quality, those with poor sleep quality showed a 29%, 28%, and 56% higher risk of total, ischemic, and hemorrhagic stroke, respectively. Moreover, we observed significant joint effects of sleeping ≥9 hours/night and midday napping >90 minutes (HR 1.85; 95% CI 1.28-2.66), and sleeping ≥9 hours/night and poor sleep quality (HR 1.82; 95% CI 1.33-2.48) on risk of total stroke. Furthermore, compared with persistently sleeping 7-9 hours/night, those who persistently slept ≥9 hours/night or switched from 7 to 9 hours to ≥9 hours/night had a higher risk of total stroke. CONCLUSIONS: Long sleep duration, long midday napping, and poor sleep quality were independently and jointly associated with higher risks of incident stroke. Persistently long sleep duration or switch from average to long sleep duration increased the risk of stroke.

Scientific Reports 6: Article number: 24353; published online: 13 April 2016; updated: 31 May 2017. The original version of this Article contained errors in the order of the authors’ affiliations, and an additional affiliation for Chong Tian was omitted. The affiliations for all authors are listed as below:

Granulomatous lobular mastitis (GLM) is a rare and chronic benign inflammatory disease of the breast. Difficulties exist in the management of GLM for many front-line surgeons and medical specialists who care for patients with inflammatory disorders of the breast. This consensus is summarized to establish evidence-based recommendations for the management of GLM. Literature was reviewed using PubMed from January 1, 1971 to July 31, 2020. Sixty-six international experienced multidisciplinary experts from 11 countries or regions were invited to review the evidence. Levels of evidence were determined using the American College of Physicians grading system, and recommendations were discussed until consensus. Experts discussed and concluded 30 recommendations on historical definitions, etiology and predisposing factors, diagnosis criteria, treatment, clinical stages, relapse and recurrence of GLM. GLM was recommended as a widely accepted definition. In addition, this consensus introduced a new clinical stages and management algorithm for GLM to provide individual treatment strategies. In conclusion, diagnosis of GLM depends on a combination of history, clinical manifestations, imaging examinations, laboratory examinations and pathology. The approach to treatment of GLM should be applied according to the different clinical stage of GLM. This evidence-based consensus would be valuable to assist front-line surgeons and medical specialists in the optimal management of GLM.

•COVID-19 vaccination acceptance of health care workers (HCWs) was at moderate level.•Male HCWs, aged 30 years or older, with a history of prior influenza vaccination were more likely to get vaccinated against COVID-19.•No other meta-analysis has yet investigated intention to COVID-19 vaccination and associated factors among HCWs. ObjectivesTo gain insight into willingness and its influencing factors to vaccinate against COVID-19 among health care workers (HCWs), and provide a scientific basis for more reasonable epidemic prevention and control strategies.MethodsA comprehensive literature search was conducted in 4 English databases (PubMed, EMBASE, Web of Science and the Cochrane Library) and 4 Chinese databases (Chinese National Knowledge Infrastructure (CNKI), the Chongqing VIP Chinese Science (VIP), Wanfang Database and China Biomedical Literature Database (CBM)) to collect the related studies. Quality evaluation was carried out for papers meeting the inclusion criteria using 6 items from the Downs and Black assessment checklist. The STATA statistical software version 15.1 was hired to perform meta-analysis.ResultsNine records with a total of 24,952 subjects were included in this meta-analysis. The results of this meta-analysis revealed that the pooled effect value of COVID-19 vaccination willingness among HCWs using a random-effects model was 51% (95% confidence interval (CI) 0.41-0.62). Male, aged 30 years or older, having a history of prior influenza vaccination were facilitators for HCWs’ intention to vaccinate against COVID-19 (odds ratio (OR) 1.82, 95% CI 1.37-2.41, P = .000, I2 = 59.4%; OR 1.32, 95% CI 1.16-1.51, P = .000, I2 = 31.7%; OR 2.97, 95% CI 1.82-4.84, P = .000, I2 = 88.1%). The impact of occupation on HCWs’ intention to get vaccinated could not yet be definitively confirmed (OR 0.85, 95% CI 0.69-1.06, P = .160, I2 = 85.5%).ConclusionCOVID-19 vaccination acceptance of HCWs was at moderate level. Strengthening awareness of COVID-19 vaccine among HCWs, particularly female HCWs under 30 years who have no history of prior influenza vaccination, is crucial to eliminate concerns about vaccination and promote the application of COVID-19 vaccine in this population. To gain insight into willingness and its influencing factors to vaccinate against COVID-19 among health care workers (HCWs), and provide a scientific basis for more reasonable epidemic prevention and control strategies. A comprehensive literature search was conducted in 4 English databases (PubMed, EMBASE, Web of Science and the Cochrane Library) and 4 Chinese databases (Chinese National Knowledge Infrastructure (CNKI), the Chongqing VIP Chinese Science (VIP), Wanfang Database and China Biomedical Literature Database (CBM)) to collect the related studies. Quality evaluation was carried out for papers meeting the inclusion criteria using 6 items from the Downs and Black assessment checklist. The STATA statistical software version 15.1 was hired to perform meta-analysis. Nine records with a total of 24,952 subjects were included in this meta-analysis. The results of this meta-analysis revealed that the pooled effect value of COVID-19 vaccination willingness among HCWs using a random-effects model was 51% (95% confidence interval (CI) 0.41-0.62). Male, aged 30 years or older, having a history of prior influenza vaccination were facilitators for HCWs’ intention to vaccinate against COVID-19 (odds ratio (OR) 1.82, 95% CI 1.37-2.41, P = .000, I2 = 59.4%; OR 1.32, 95% CI 1.16-1.51, P = .000, I2 = 31.7%; OR 2.97, 95% CI 1.82-4.84, P = .000, I2 = 88.1%). The impact of occupation on HCWs’ intention to get vaccinated could not yet be definitively confirmed (OR 0.85, 95% CI 0.69-1.06, P = .160, I2 = 85.5%). COVID-19 vaccination acceptance of HCWs was at moderate level. Strengthening awareness of COVID-19 vaccine among HCWs, particularly female HCWs under 30 years who have no history of prior influenza vaccination, is crucial to eliminate concerns about vaccination and promote the application of COVID-19 vaccine in this population.

The upregulation of Th1 cells has been suggested to have an essential function in the development of atherosclerosis (AS). Recent studies indicate that miR-146a is a microRNA specifically and highly expressed in Th1-driven autoimmune disease. The aim of the study was to investigate the possible mechanisms of the miR-146a in the onset of acute coronary syndrome (ACS). The results showed that the expression of miR-146a in peripheral blood mononuclear cells (PBMCs) was significantly increased in patients with ACS. We showed that overexpression of miR-146a in PBMCs could significantly upregulate the function of Th1 cells. Furthermore, we showed that miR-146a treatment could modulate the Th1 differentiation through posttranscriptional enhancing the T-bet pathway in PBMCs. In addition, this study also provided evidence that miR-146a treatment in vitro could induce the protein expression of TNF-alpha, MCP-1, NF-kappaB p65, which are key pro-inflammatory cytokines and critical transcription factor in AS. In contrast, miR-146a inhibitor could attenuate these phenomena significantly. The results support the concept that miR-146a may be a novel regulatory factor in Th1 differentiation and a new therapeutic target for AS and ACS.

Background: Rheumatoid arthritis (RA) is a chronic systemic autoimmune disorder characterized by inflammatory cell infiltration, leading to persistent synovitis and joint destruction. The pathogenesis of RA remains unclear. This study aims to explore the immune molecular mechanism of RA through bioinformatics analysis. Methods: Five microarray datasets and a high throughput sequencing dataset were downloaded. CIBERSORT algorithm was performed to evaluate immune cell infiltration in synovial tissues between RA and healthy control (HC). Wilcoxon test and Least Absolute Shrinkage and Selection Operator (LASSO) regression were conducted to identify the significantly different infiltrates of immune cells. Differentially expressed genes (DEGs) were screened by "Batch correction" and "RobustRankAggreg" methods. Functional correlation of DEGs were analyzed by Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG). Candidate biomarkers were identified by cytoHubba of Cytoscape, and their diagnostic effectiveness was predicted by Receiver Operator Characteristic Curve (ROC) analysis. The association of the identified biomarkers with infiltrating immune cells was explored using Spearman's rank correlation analysis in R software. Results: Ten significantly different types of immune cells between RA and HC were identified. A total of 202 DEGs were obtained by intersection of DEGs screened by two methods. The function of DEGs were significantly associated with immune cells. Five hub genes (CXCR4, CCL5, CD8A, CD247, and GZMA) were screened by R package "UpSet". CCL5+CXCR4 and GZMA+CD8A were verified to have the capability to diagnose RA and early RA with the most excellent specificity and sensitivity, respectively. The correlation between immune cells and biomarkers showed that CCL5 was positively correlated with M1 macrophages, CXCR4 was positively correlated with memory activated CD4+ T cells and follicular helper T (Tfh) cells, and GZMA was positively correlated with Tfh cells. Conclusions: CCL5, CXCR4, GZMA, and CD8A can be used as diagnostic biomarker for RA. GZMA-Tfh cells, CCL5-M1 macrophages, and CXCR4- memory activated CD4+ T cells/Tfh cells may participate in the occurrence and development of RA, especially GZMA-Tfh cells for the early pathogenesis of RA.

Human height is associated with risk of multiple diseases and is profoundly determined by an individual's genetic makeup and shows a high degree of ethnic heterogeneity. Large-scale genome-wide association (GWA) analyses of adult height in Europeans have identified nearly 180 genetic loci. A recent study showed high replicability of results from Europeans-based GWA studies in Asians; however, population-specific loci may exist due to distinct linkage disequilibrium patterns. We carried out a GWA meta-analysis in 93 926 individuals from East Asia. We identified 98 loci, including 17 novel and 81 previously reported loci, associated with height at P < 5 × 10(-8), together explaining 8.89% of phenotypic variance. Among the newly identified variants, 10 are commonly distributed (minor allele frequency, MAF > 5%) in Europeans, with comparable frequencies with in Asians, and 7 single-nucleotide polymorphisms are with low frequency (MAF < 5%) in Europeans. In addition, our data suggest that novel biological pathway such as the protein tyrosine phosphatase family is involved in regulation of height. The findings from this study considerably expand our knowledge of the genetic architecture of human height in Asians.

Background and Purpose- Circulating metals synchronously reflect multiple metal exposures from both natural and anthropogenic sources, which may be linked with the risk of stroke. However, there is a lack of prospective studies investigating the associations of multiple metal exposures with incident stroke. Methods- We performed a nested case-control study within the ongoing Dongfeng-Tongji cohort launched in 2008. A total of 1304 incident stroke cases (1035 ischemic strokes and 269 hemorrhagic strokes) were prospectively identified by December 31, 2016, and matched to incident identity sampled controls according to age (within 1 year), sex, and blood sampling date (within 1 month). We determined the concentrations of 24 plasma metals and assessed the associations of plasma multiple metal concentrations with incident stroke using conditional logistic regression and elastic net model. Results- The average follow-up was 6.1 years. After adjusting for established risk confounders, copper, molybdenum, and titanium were significantly associated with higher risk of ischemic stroke (odds ratios according to per interquartile range increase, 1.29 [95% CI, 1.13-1.46], 1.19 [95% CI, 1.05-1.35], and 1.30 [95% CI, 1.07-1.59]), whereas rubidium and selenium were associated with lower risk of hemorrhagic stroke (odds ratios according to per interquartile range increase, 0.66 [95% CI, 0.50-0.87] and 0.68 [95% CI, 0.51-0.91]). The predictive plasma metal scores based on multiple metal exposures were significantly associated with higher risk of ischemic and hemorrhagic stroke (adjusted odds ratios according to per interquartile range increase, 1.37 [95% CI, 1.20-1.56] and 1.53 [95% CI, 1.16-2.01]). Conclusions- Plasma copper, molybdenum, and titanium were associated with higher risk of ischemic stroke, whereas plasma rubidium and selenium were associated with lower risk of hemorrhagic stroke. These findings may have important public health implications given the ever-increasing burden of stroke worldwide.

The long-term associations between multiple metals and incident diabetes are uncertain. We aimed to examine the relationship between plasma concentrations of 23 metals and the incidence of type 2 diabetes among Chinese senior adults. We quantified fasting plasma concentrations of 23 metals by inductively coupled plasma mass spectrometry among 1039 incident diabetes cases and 1039 controls (age and sex matched) nested in a prospective study, the Dongfeng-Tongji cohort. Both cases and controls were free of diabetes at baseline (2008–2010), incident diabetes were identified using the following criteria: fasting glucose ≥ 7.0 mmoL/l; or hemoglobin A1c (HbA1c) ≥ 6.5%; or self-reported physician diagnosis of diabetes or use of anti-diabetic medication during the follow-up visits in 2013. In the conditional logistic regression models, the multivariable adjusted ORs (95% CIs) of diabetes across quartiles (Q1–Q4) of metal concentrations were as follows: titanium, 1.00, 0.92, 1.31, 1.38 (1.00–1.91, Ptrend = 0.011); selenium, 1.00, 1.08, 1.45, 1.27 (0.93–1.74, Ptrend = 0.05); and antimony, 1.00, 0.79, 0.77, 0.60 (0.44–0.83, Ptrend = 0.002). Arsenic was significantly associated with diabetes in the crude model (ORs comparing extreme quartiles 1.30; 1.02–1.65; Ptrend = 0.006), but was not significant after adjustment for socio-demographic factors. No significant associations were found for other metals. In conclusion, titanium and selenium were positively while antimony was negatively associated with incident diabetes.

BACKGROUND AND AIMS: Research has increasingly suggested that gut flora plays an important role in the development of post-infectious irritable bowel syndrome (PI-IBS). Studies of the curative effect of probiotics for IBS have usually been positive but not always. However, the differences of treatment effects and mechanisms among probiotic stains, or mixture of them, are not clear. In this study, we compared the effects of different probiotics (Befidobacterium, Lactobacillus, Streptococcus or mixture of the three) on intestinal sensation, barrier function and intestinal immunity in PI-IBS mouse model. METHODS: PI-IBS model was induced by Trichinella spiralis infection in mice. Different probiotics were administered to mice after 8 weeks infection. Visceral sensitivity was measured by scores of abdominal withdrawal reflex (AWR) and the threshold intensity of colorectal distention. Colonic smooth muscle contractile response was assessed by contraction of the longitudinal muscle strips. Plasma diamine oxidase (DAO) and d-lactate were determined by an enzymatic spectrophotometry. Expression of tight junction proteins and cytokines in ileum were measured by Western blotting. RESULTS: Compared to control mice, PI-IBS mice treated either alone with Befidobacterium or Lactobacillus (but not Streptococcus), or the mixture of the three exhibited not only decreased AWR score and contractile response, but also reduced plasma DAO and D-lactate. These probiotic treatments also suppressed the expression of proinflammatory cytokine IL-6 and IL-17 and promoted the expression of major tight junction proteins claudin-1 and occludin. The mixture of the three probiotic strains performed better than the individual in up-regulating these tight junction proteins and suppressing IL-17 expression. CONCLUSIONS: Bifidobacterium and Lactobacillus, but not Streptococcus, alleviated visceral hypersensitivity and recovered intestinal barrier function as well as inflammation in PI-IBS mouse model, which correlated with an increase of major tight junction proteins. In addition, Mixture of three species was indicated to be superior to a single one.

BACKGROUND AND AIMS: It remains unclear whether extreme levels of blood urea nitrogen (BUN) and BUN to creatinine ratio (BUN/Cr) can increase future risk of stroke. We conducted this study to investigate the associations of BUN and BUN/Cr with incident stroke and its subtypes. METHODS: A total of 26,835 and 26,379 participants with a mean follow-up of 7.9 years were included to investigate the associations of BUN and BUN/Cr with incident stroke, respectively. Cox proportional hazard models were used to evaluate hazard ratios (HRs) and 95% confidence intervals (CIs) for incident stroke and its subtypes. RESULTS: Compared with participants in the third quintile of BUN, the adjusted HRs (95% CIs) for participants in the lowest quintile were 1.21 (1.04-1.40), 1.41 (1.18-1.68) and 1.36 (0.97-1.91) for total, ischemic and hemorrhagic stroke, respectively; while for those in the highest quintile, the corresponding HRs (95% CIs) were 1.16 (1.01-1.32), 1.30 (1.11-1.53), and 1.24 (0.90-1.71). The associations remained robust when restricting the analyses to participants within clinically normal range of BUN. For BUN/Cr, compared with participants in the third quintile, participants in the lowest quintile had significant higher risks of stroke (HRs [95% CIs] were 1.19 [1.04-1.37], 1.26 [1.07-1.48], and 1.22 [0.90-1.67] for total, ischemic and hemorrhagic stroke). CONCLUSIONS: Both high and low levels of BUN were associated with higher risks of total and ischemic stroke. Low level of BUN/Cr was associated with excess risks of total and ischemic stroke.

BACKGROUND: Metabolomics studies in Caucasians have identified a number of novel metabolites in association with the risk of type 2 diabetes (T2D). However, few prospective metabolomic studies are available in Chinese populations. In the present study, we sought to identify novel metabolites consistently associated with incident T2D in two independent cohorts of Chinese adults. METHODS: We performed targeted metabolomics (52 metabolites) of fasting plasma samples by liquid chromatography-mass spectrometry in two prospective case-control studies nested within the Dongfeng-Tongji (DFTJ) cohort and Jiangsu Non-communicable Disease (JSNCD) cohort. After following for 4.61 ± 0.15 and 7.57 ± 1.13 years, respectively, 1039 and 520 eligible participants developed incident T2D in these two cohorts, and controls were 1:1 matched with cases by age (± 5 years) and sex. Multivariate conditional logistic regression models were constructed to identify metabolites associated with future T2D risk in both cohorts. RESULTS: ≤ 0.01). CONCLUSIONS: We confirmed the association of alanine, phenylalanine and tyrosine with future T2D risk and further identified palmitoylcarnitine as a novel metabolic marker of incident T2D in two prospective cohorts of Chinese adults. Our findings might provide new aetiological insight into the development of T2D.

STUDY OBJECTIVES: To analyze the independent and combined relations of sleep duration and midday napping with coronary heart diseases (CHD) incidence along with the underlying changes of cardiovascular disease (CVD) risk factors among Chinese adults. METHODS: We included 19,370 individuals aged 62.8 years at baseline from September 2008 to June 2010, and they were followed until October 2013. Cox proportional hazards models and general linear models were used for multivariate longitudinal analyses. RESULTS: Compared with sleeping 7- < 8 h/night, the hazard ratio (HR) of CHD incidence was 1.33 (95% CI = 1.10 to 1.62) for sleeping ≥ 10 h/night. The association was particularly evident among individuals who were normal weight and without diabetes. Similarly, the HR of incident CHD was 1.25 (95% CI = 1.05 to 1.49) for midday napping > 90 min compared with 1-30 min. When sleep duration and midday napping were combined, individuals having sleep duration ≥ 10 h and midday napping > 90 min were at a greater risk of CHD than those with sleeping 7- < 8 h and napping 1-30 min: the HR was 1.67 (95% CI = 1.04 to 2.66; P for trend = 0.017). In addition, longer sleep duration ≥ 10 h was significantly associated with increases in triglycerides and waist circumference, and a reduction in HDL-cholesterol; while longer midday napping > 90 min was related to increased waist circumference. CONCLUSIONS: Both longer sleep duration and midday napping were independently and jointly associated with a higher risk of CHD incidence, and altered lipid profile and waist circumference may partially explain the relationships.

Glucagon-like peptide-1 (GLP-1) is a 30-amino acid hormone secreted by L cells in the distal ileum, colon, and pancreatic α cells, which participates in blood sugar regulation by promoting insulin release, reducing glucagon levels, delaying gastric emptying, increasing satiety, and reducing appetite. GLP-1 specifically binds to the glucagon-like peptide-1 receptor (GLP-1R) in the body, directly stimulating the secretion of insulin by pancreatic β-cells, promoting proliferation and differentiation, and inhibiting cell apoptosis, thereby exerting a glycemic lowering effect. The glycemic regulating effect of GLP-1 and its analogues has been well studied in human and murine models in the circumstance of many diseases. Recent studies found that GLP-1 is able to modulate innate immune response in a number of inflammatory diseases. In the present review, we summarize the research progression of GLP-1 and its analogues in immunomodulation and related signal pathways.

BACKGROUND: Exposure to metals/metalloids from both the natural environment and anthropogenic sources have a complex influence on human health. However, relatively few studies have explored the relations of exposure to multiple metals/metalloids with mortality. Therefore, this prospective study aims to examine the relations of multiple metal/metalloids exposures with all-cause and cardiovascular disease (CVD) mortality. METHODS: A total of 6155 participants within the Dongfeng-Tongji (DF-TJ) cohort were involved in this analysis, which were followed for mortality until December 31, 2018. We applied inductively coupled plasma mass spectrometry (ICP-MS) to measure baseline plasma concentrations of 23 metals. We utilized Cox regression models to calculate the hazard ratios (HRs) for all-cause and CVD mortality associated with metal concentrations. We proposed plasma metal score to assess the simultaneous exposure to multiple metals through summing each metal concentration weighted by the regression coefficients with all-cause mortality. RESULTS: During the follow-up (mean duration, 9.8 years), we ascertained 876 deaths, including 416 deaths of CVD (157 deaths of coronary heart disease and 259 deaths of stroke). In the multiple-metals model, after adjusting for potential confounders, plasma copper, molybdenum, and vanadium were positively associated with all-cause mortality, whereas manganese, selenium, and thallium were negatively associated with the risk of all-cause mortality, with adjusted HRs (95% Confidence Interval, CI) of the fourth quartiles were 1.73 (1.42-2.11, P-trend < 0.001) for copper, 1.33 (1.09-1.63, P-trend = 0.005) for molybdenum, 1.43 (1.16-1.77, P-trend < 0.001) for vanadium, 0.74 (0.58-0.94, P-trend = 0.005) for manganese, 0.68 (0.56-0.83, P-trend < 0.001) for selenium, and 0.74 (0.59-0.92, P-trend = 0.002) for thallium, respectively. Positive associations were observed between plasma copper, molybdenum, vanadium concentrations and CVD mortality, whereas negative associations were found for plasma selenium and thallium concentrations with CVD mortality in the multiple-metals model. Compared with the first quartiles, the HRs of fourth quartiles were 1.94 (1.45-2.58, P-trend < 0.001) for copper, 1.72 (1.26-2.35, P-trend < 0.001) for molybdenum, 1.81 (1.32-2.47, P-trend < 0.001) for vanadium, 0.67 (0.50-0.89, P-trend = 0.003) for selenium, and 0.58 (0.41-0.81, P-trend < 0.001) for thallium, respectively. The plasma metal score was significantly associated with higher risks of all-cause and CVD death in dose-response fashions. When compared with the first quartiles of plasma metal score, the HRs of fourth quartiles were 2.16 (1.76-2.64; P-trend < 0.001) for all-cause mortality and 3.00 (2.24-4.02; P-trend < 0.001) for CVD mortality. CONCLUSIONS: The study indicated that several plasma metals/metalloids were key determinants and predictors of all-cause and CVD death in the Chinese population. Our findings highlighted the importance to comprehensively assess and monitor multiple metals/metalloids exposures.

BACKGROUND: Uric acid (UA) is a complex phenotype influenced by both genetic and environmental factors as well as their interactions. Current genome-wide association studies (GWASs) have identified a variety of genetic determinants of UA in Europeans; however, such studies in Asians, especially in Chinese populations remain limited. METHODS: A two-stage GWAS was performed to identify single nucleotide polymorphisms (SNPs) that were associated with serum uric acid (UA) in a Chinese population of 12,281 participants (GWAS discovery stage included 1452 participants from the Dongfeng-Tongji cohort (DFTJ-cohort) and 1999 participants from the Fangchenggang Area Male Health and Examination Survey (FAMHES). The validation stage included another independent 8830 individuals from the DFTJ-cohort). Affymetrix Genome-Wide Human SNP Array 6.0 chips and Illumina Omni-Express platform were used for genotyping for DFTJ-cohort and FAMHES, respectively. Gene-environment interactions on serum UA levels were further explored in 10,282 participants from the DFTJ-cohort. RESULTS: Briefly, we identified two previously reported UA loci of SLC2A9 (rs11722228, combined P = 8.98 × 10-31) and ABCG2 (rs2231142, combined P = 3.34 × 10-42). The two independent SNPs rs11722228 and rs2231142 explained 1.03% and 1.09% of the total variation of UA levels, respectively. Heterogeneity was observed across different populations. More importantly, both independent SNPs rs11722228 and rs2231142 were nominally significantly interacted with gender on serum UA levels (P for interaction = 4.0 × 10-2 and 2.0 × 10-2, respectively). The minor allele (T) for rs11722228 in SLC2A9 has greater influence in elevating serum UA levels in females compared to males and the minor allele (T) of rs2231142 in ABCG2 had stronger effects on serum UA levels in males than that in females. CONCLUSIONS: Two genetic loci (SLC2A9 and ABCG2) were confirmed to be associated with serum UA concentration. These findings strongly support the evidence that SLC2A9 and ABCG2 function in UA metabolism across human populations. Furthermore, we observed these associations are modified by gender.

Importance: Although numerous studies have separately investigated the associations of changes in weight or waist circumference with mortality risk, few studies have examined the associations of concurrent changes in these 2 anthropometric parameters with all-cause mortality. Objective: To assess the associations of changes in body weight, waist circumference, or both, combined with all-cause mortality. Design, Setting, and Participants: This cohort study used data from 2 longitudinal cohort studies in Dongfeng-Tongji and Kailuan, China. Participants included 58 132 adults (aged 40 years and older) with measures of weight and waist circumference at baseline and follow-up visit. Statistical analysis was performed from June 2020 to September 2021. Exposures: Changes in weight and waist circumference between 2 visits (2008-2010 to 2013 in the Dongfeng-Tongji cohort, and 2006-2007 to 2010-2011 in the Kailuan study). Stable weight was defined as change in weight within 2.5 kg between the 2 visits and stable waist circumference was defined as changes within 3.0 cm. Changes were categorized as loss, stable, or gain for weight and waist circumference separately, and created a 9-category variable to represent the joint changes. Main Outcomes and Measures: All-cause mortality from follow-up visit (2013 in Dongfeng-Tongji cohort and 2010-2011 in Kailuan study) until December 31, 2018. Cox proportional hazard regression models were used to estimate the associations with adjustment for potential confounders. Results were obtained in the 2 cohorts separately and pooled via fixed-effect meta-analysis. Results: A total of 10 951 participants in the Dongfeng-Tongji cohort (median [IQR] age, 62 [56-66] years; 4203 [38.4%] men) and 47 181 participants in the Kailuan study (median [IQR] age, 51 [46-58] years; 36 663 [77.7%] men) were included in the analysis. During 426 072 person-years of follow-up, 4028 deaths (523 in the Dongfeng-Tongji cohort and 3505 in the Kailuan study) were documented. When changes in weight and waist circumference were examined separately, U-shape associations were found: both gain and loss in weight (weight loss: pooled hazard ratio [HR], 1.33; 95% CI, 1.23-1.43; weight gain: HR, 1.10; 95% CI, 1.02-1.19) or waist circumference (waist circumference loss: HR, 1.14; 95% CI, 1.05-1.24; waist circumference gain: HR, 1.11; 95% CI, 1.03-1.21) were associated with higher mortality risk compared with stable weight or waist group. When changes in weight and waist circumference were jointly assessed, compared with participants with stable weight and waist circumference (16.9% of the total population [9828 of 58 132] with 508 deaths), participants with different combinations of weight and waist circumference change all had higher mortality risks except for those with stable weight but significant loss in waist. Notably, those who lost weight but gained waist circumference (6.4% of the total population [3698 of 58 132] with 308 deaths) had the highest risk of all-cause mortality (HR, 1.69; 95% CI, 1.46-1.96; absolute rate difference per 100 000 person-years in the Dongfeng-Tongji cohort: 414; 95% CI, 116-819; and in the Kailuan study: 333; 95% CI, 195-492) among the joint subgroups. Conclusions and Relevance: In this cohort study, weight loss with concurrent waist circumference gain was associated with a higher mortality risk in middle-aged and older Chinese adults. This study's findings suggest the importance of evaluating the changes in both body weight and waist circumference when assessing their associations with mortality.