Psychological stress to ovalbumin peptide-specific T-cell receptor transgenic mice impairs the suppressive ability of type 1 regulatory T cell.

Numerous diseases of the immune system can be traced back to the malfunctioning of the regulatory T cells. The aetiology is unclear. Psychological stress can cause disruption to the immune regulation. The synergistic effects of psychological stress and immune response on immune regulation have yet to be fully understood. The intention of this study is to analyse the interaction between psychological stress and immune responses and how it affects the functional status of type 1 regulatory T (Tr1) cells. In this study, ovalbumin peptide T-cell receptor transgenic mice were utilised. Mice were subjected to restraint stress to induce psychological stress. An airway allergy murine model was established, in which a mouse strain with RING finger protein 20 (Rnf20)-deficient CD4+ T cells were used. The results showed that concomitant exposure to restraint stress and immune response could exacerbate endoplasmic reticulum stress in Tr1 cells. Corticosterone was responsible for the elevated expression of X-box protein-1 (XBP1) in mouse Tr1 cells after exposure to both restraint stress and immune response. XBP1 mediated the effects of corticosterone on inducing Rnf20 in Tr1 cells. The reduction of the interleukin-10 expression in Tr1 cells was facilitated by Rnf20. Inhibition of Rnf20 alleviated experimental airway allergy by restoring the immune regulatory ability of Tr1 cells. In conclusion, the functions of Tr1 cells are negatively impacted by simultaneous exposure to psychological stress and immune response. Tr1 cells' immune suppressive functions can be restored by inhibiting Rnf20, which has the translational potential for the treatment of diseases of the immune system.

Visit to visit transition in TXNIP gene methylation and the risk of type 2 diabetes mellitus: a nested case-control study.

Our study aimed to investigate the association between the transition of the TXNIP gene methylation level and the risk of incident type 2 diabetes mellitus (T2DM). This study included 263 incident cases of T2DM and 263 matched non-T2DM participants. According to the methylation levels of five loci (CpG1-5; chr1:145441102-145442001) on the TXNIP gene, the participants were classified into four transition groups: maintained low, low to high, high to low, and maintained high methylation levels. Compared with individuals whose methylation level of CpG2-5 at the TXNIP gene was maintained low, individuals with maintained high methylation levels showed a 61-87% reduction in T2DM risk (66% for CpG2 [OR: 0.34, 95% CI: 0.14, 0.80]; 77% for CpG3 [OR: 0.23, 95% CI: 0.07, 0.78]; 87% for CpG4 [OR: 0.13, 95% CI: 0.03, 0.56]; and 61% for CpG5 [OR: 0.39, 95% CI: 0.16, 0.92]). Maintained high methylation levels of four loci of the TXNIP gene are associated with a reduction of T2DM incident risk in the current study. Our study suggests that preserving hypermethylation levels of the TXNIP gene may hold promise as a potential preventive measure against the onset of T2DM.

Association of traditional and novel obesity indicators with stroke risk: Findings from the Rural Chinese cohort study.

BACKGROUND AND AIMS: Few researchers have compared the effectiveness of traditional and novel obesity indicators in predicting stroke incidence. We aimed to evaluate the associations between six obesity indices and stroke risk, and to further identify the optimal indicator. METHODS AND RESULTS: A total of 14,539 individuals from the Rural Chinese Cohort Study were included in the analyses. We used the Cox proportional hazards regression models to evaluate the association between six obesity indices (including body mass index [BMI], waist circumference [WC], conicity index [C-index], lipid accumulation product [LAP], visceral adiposity index [VAI], and Chinese visceral adiposity index [CVAI]) and stroke risk. Receiver operating characteristic curves were employed to compare their predictive ability on stroke risk. During a median follow-up period of 11.13 years, a total of 1257 cases of stroke occurred. In the multiple-adjusted Cox regression model, WC, BMI, C-index, and CVAI were positively associated with ischemic stroke (P < 0.01) rather than hemorrhagic stroke risk. Dose-response analyses showed a linear correlation of WC, BMI, C-index, and LAP (Poverall <0.05, and Pnonlinear >0.05), but a non-linear correlation of CVAI (Poverall <0.05, and Pnonlinear <0.05) with the risk of ischemic stroke. CVAI demonstrates the highest areas under the curves (AUC: 0.661, 95% CI: 0.653-0.668), indicating a superior predictive ability for ischemic stroke occurrence compared to other five indices (P < 0.001). CONCLUSION: WC, BMI, C-index, LAP, and CVAI were all positively related to the risk of ischemic stroke, among which CVAI exhibited stronger predictive ability for ischemic stroke.

Phospholipid remodeling and its derivatives are associated with COVID-19 severity.

BACKGROUND: Timely medical intervention in severe cases of coronavirus disease 2019 (COVID-19) and better understanding of the disease's pathogenesis are essential for reducing mortality, but early classification of severe cases and its progression is challenging. OBJECTIVE: We investigated the levels of circulating phospholipid metabolites and their relationship with COVID-19 severity, as well as the potential role of phospholipids in disease progression. METHODS: We performed nontargeted lipidomic analysis of plasma samples (n = 150) collected from COVID-19 patients (n = 46) with 3 levels of disease severity, healthy individuals, and subjects with metabolic disease. RESULTS: Phospholipid metabolism was significantly altered in COVID-19 patients. Results of a panel of phosphatidylcholine (PC) and lysophosphatidylcholine (LPC) and of phosphatidylethanolamine and lysophosphatidylethanolamine (LPE) ratios were significantly correlated with COVID-19 severity, in which 16 phospholipid ratios were shown to distinguish between patients with severe disease, mild disease, and healthy controls, 9 of which were at variance with those in subjects with metabolic disease. In particular, relatively lower ratios of circulating (PC16:1/22:6)/LPC 16:1 and (PE18:1/22:6)/LPE 18:1 were the most indicative of severe COVID-19. The elevation of levels of LPC 16:1 and LPE 18:1 contributed to the changes of related lipid ratios. An exploratory functional study of LPC 16:1 and LPE 18:1 demonstrated their ability in causing membrane perturbation, increased intracellular calcium, cytokines, and apoptosis in cellular models. CONCLUSION: Significant Lands cycle remodeling is present in patients with severe COVID-19, suggesting a potential utility of selective phospholipids with functional consequences in evaluating COVID-19's severity and pathogenesis.

Endoplasmic reticulum stress impairs the immune regulation property of macrophages in asthmatic patients.

The current study aims to characterize the counteraction of M2 cells in response to Endoplasmic reticulum (ER) stress. ER stress was detected in bronchoalveolar lavage fluids (BALF) Mϕs, which was at unresolved state in asthma patients. A positive correlation was detected between ER stress in Mϕs and lung functions/allergic mediators/Th2 cytokines in BALF or specific IgE in the serum. Levels of immune regulatory mediator in the BALF were negatively correlated to ER stress in BALF Mϕs. The ER stress state influenced the immune regulatory property of BALF Mϕ. Exposure to environmental pollutant, 3-metheyl-4-nitrophenol, exacerbated ER stress in Mϕ, which affected the Mϕ phenotyping. Exacerbation of ER stress suppressed the expression of IL-10 and programmed cell death protein-1 (PD-1) in Mϕs by increasing the expression of the ring finger protein 20 (Rnf20). Conditional inhibition of Rnf20 in Mϕs attenuated experimental airway allergy.

Identification and validation of DNA methylation-driven gene PCDHB4 as a novel tumor suppressor for glioblastoma diagnosis and prognosis.

Aberrant DNA methylation is a critical regulator of gene expression in the development and progression of glioblastoma (GBM). However, the impact of methylation-driven gene PCDHB4 changes on GBM occurrence and progression remains unclear. Therefore, this study aimed to identify the PCDHB4 gene for early diagnosis and prognostic evaluation and clarify its functional role in GBM. Methylation-driven gene PCDHB4 was selected for GBM using the multi-omics integration method based on publicly available data sets. The diagnostic capabilities of PCDHB4 methylation and 5-hydroxymethylcytosines were validated in tissue and blood cell-free DNA (cfDNA) samples, respectively. Combined survival analysis of PCDHB4 methylation and immune infiltration cells evaluated the prognostic predictive performance of GBM patients. We identified that the PCDHB4 gene achieved high discriminative capabilities for GBM and normal tissues with an area under the curve value of 0.941. PCDHB4 hypermethylation was observed in cfDNA blood samples from GBM patients. Compared with GBM patients with PCDHB4 hypermethylation level, patients with PCDHB4 hypomethylation level had significantly poorer overall survival (p = 0.035). In addition, GBM patients with PCDHB4 hypermethylation and high infiltration of CD4+ T cell activation level had a favorable survival (p = 0.026). Moreover, we demonstrated that mRNA expression of PCDHB4 was downregulated in GBM tissues and upregulated in GBM cell lines with PCDHB4 demethylation, and PCDHB4 overexpression inhibited GBM cell proliferation and migration. In summary, we discovered a novel methylation-driven gene PCDHB4 for the diagnosis and prognosis of GBM and demonstrated that PCDHB4 is a tumor suppressor in vitro experiments.

All-cause mortality risk with different metabolic abdominal obesity phenotypes: the Rural Chinese Cohort Study.

We aimed to investigate the association of metabolic obesity phenotypes with all-cause mortality risk in a rural Chinese population. This prospective cohort study enrolled 15 704 Chinese adults (38·86 % men) with a median age of 51·00 (interquartile range: 41·00-60·00) at baseline (2007-2008) and followed up during 2013-2014. Obesity was defined by waist circumference (WC: ≥ 90 cm for men and ≥ 80 cm for women) or waist-to-height ratio (WHtR: ≥ 0·5). The hazard ratio (HR) and 95 % CI for the risk of all-cause mortality related to metabolic obesity phenotypes were calculated using the Cox hazards regression model. During a median follow-up of 6·01 years, 864 deaths were identified. When obesity was defined by WC, the prevalence of participants with metabolically healthy non-obesity (MHNO), metabolically healthy obesity (MHO), metabolically unhealthy non-obesity (MUNO) and metabolically unhealthy obesity (MUO) at baseline was 12·12 %, 2·80 %, 41·93 % and 43·15 %, respectively. After adjusting for age, sex, alcohol drinking, smoking, physical activity and education, the risk of all-cause mortality was higher with both MUNO (HR = 1·20, 95 % CI 1·14, 1·26) and MUO (HR = 1·20, 95 % CI 1·13, 1·27) v. MHNO, but the risk was not statistically significant with MHO (HR = 0·99, 95 % CI 0·89, 1·10). This result remained consistent when stratified by sex. Defining obesity by WHtR gave similar results. MHO does not suggest a greater risk of all-cause mortality compared to MHNO, but participants with metabolic abnormality, with or without obesity, have a higher risk of all-cause mortality. These results should be cautiously interpreted as the representation of MHO is small.

Long-Term Exposure to Traffic Noise and Risk of Incident Cardiovascular Diseases: a Systematic Review and Dose-Response Meta-Analysis.

While noise pollution from transportation has become an important public health problem, the relationships between different sources of traffic noise and cardiovascular diseases (CVDs) remain inconclusive. A comprehensive meta-analysis was therefore conducted to quantitatively assess the effects of long-term exposure to road traffic, railway, and aircraft noise on CVDs and relevant subtypes. We systematically retrieved PubMed, Embase, and Web of Science for articles published before April 4, 2022. Summary relative risks (RRs) and 95% confidence intervals (CIs) were estimated by the fixed- or random-effects models. In total, 23 articles were included in our meta-analysis. The risk of CVDs increased by 2% (RR 1.020, 95% CI 1.006-1.035) and 1.6% (RR 1.016, 95% CI 1.000-1.032) for every 10 dB increment of road traffic and aircraft noise. For CVD subtypes, the risk increased by 3.4% (1.034, 1.026-1.043) for stroke and 5% (1.050, 1.006-1.096) for heart failure with each 10 dB increment of road traffic noise; the risk of atrial fibrillation increased by 1.1% (1.011, 1.002-1.021) with each 10 dB increment of railway noise; and the risk increased by 1% (1.010, 1.003-1.017) for myocardial infarction, 2.7% (1.027, 1.004-1.050) for atrial fibrillation, and 2.3% (1.023, 1.016-1.030) for heart failure with each 10 dB increment in aircraft noise. Further, effects from road traffic, railway, and aircraft noise all followed positive linear trends with CVDs. Long-term exposure to traffic noise is positively related to the incidence risk of cardiovascular events, especially road traffic noise which significantly increases the risk of CVDs, stroke, and heart failure.

Correlation of heavy metals' exposure with the prevalence of coronary heart disease among US adults: findings of the US NHANES from 2003 to 2018.

We sought to explore the association between heavy metal exposure and coronary heart disease (CHD) based on data from the US National Health and Nutrition Examination Survey (NHANES, 2003-2018). In the analyses, participants were all aged > 20 and had participated in heavy metal sub-tests with valid CHD status. The Mann-Kendall test was employed to assess the trends in heavy metals' exposure and the trends in CHD prevalence over 16 years. Spearman's rank correlation coefficient and a logistics regression (LR) model were used to estimate the association between heavy metals and CHD prevalence. 42,749 participants were included in our analyses, 1802 of whom had a CHD diagnosis. Total arsenic, dimethylarsonic acid, monomethylarsonic acid, barium, cadmium, lead, and antimony in urine, and cadmium, lead, and total mercury in blood all showed a substantial decreasing exposure level tendency over the 16 years (all Pfor trend < 0.05). CHD prevalence varied from 3.53 to 5.23% between 2003 and 2018. The correlation between 15 heavy metals and CHD ranges from - 0.238 to 0.910. There was also a significant positive correlation between total arsenic, monomethylarsonic acid, and thallium in urine and CHD by data release cycles (all P < 0.05). The cesium in urine showed a negative correlation with CHD (P < 0.05). We found that exposure trends of total arsenic, dimethylarsonic acid, monomethylarsonic acid, barium, cadmium, lead, and antimony in urine and blood decreased. CHD prevalence fluctuated, however. Moreover, total arsenic, monomethylarsonic acid, and thallium in urine all showed positive relationships with CHD, while cesium in urine showed a negative relationship with CHD.

Fried-food consumption and risk of overweight/obesity, type 2 diabetes mellitus, and hypertension in adults: a meta-analysis of observational studies.

Recent studies have reported conflicting associations of fried-food consumption and risk of overweight/obesity, type 2 diabetes mellitus (T2DM) and hypertension, and a meta-analysis is not available. We aimed to explore the association between fried-food consumption and risk of overweight/obesity, T2DM and hypertension in adults through a meta-analysis. We searched PubMed, EMBASE, and Web of Science for studies published up to 17 June 2020. Pooled relative risks (RRs) and 95% confidence intervals (CIs) were calculated by random-effects models. In comparing the highest to lowest fried-food intake, the pooled RRs (95% CIs) were 1.16 (1.07-1.25; I2 = 71.0%, Pheterogeneity < 0.001) for overweight/obesity (cohort: 1.19 [0.97-1.47], n = 2; cross-sectional: 1.14 [1.03-1.27], n = 9), 1.07 (0.90-1.27; 84.7%) for T2DM (cohort: 1.01 [0.89-1.15], n = 9; case-control: 2.33 [1.80-3.01], n = 1), and 1.20 (1.05-1.38; I2=91.8%) for hypertension (cohort: 1.06 [0.98-1.15], n = 8; cross-sectional: 2.16 [0.59-7.87], n = 3). Our meta-analysis indicates fried-food consumption is associated with increased risk of overweight/obesity and hypertension but not T2DM in adults, but the findings should be interpreted with caution due to high heterogeneity and unstable subgroup analyses of this meta-analysis. More studies are warranted to investigate the total fried-food consumption and these health outcomes.

A Quickly Organized Response to a COVID-19 Positive Case Comeback After Clearance for over 2 Months in Shenzhen, China.

BACKGROUND: The ongoing coronavirus disease 2019 (COVID-19) pandemic has spread quickly throughout the world. So far, there are no standard measures in terms of quick and effective control of new COVID-19 positive patient comeback after COVID-19 clearance for a certain time. Here, we report a quickly organized response from Luohu Hospital Group to a COVID-19 positive case comeback after clearance for over 2 months in Shenzhen, China. METHODS: After 2 months with no new COVID-19 cases in Shenzhen, on August 14, 2020, a supermarket employee living in the Luohu district of Shenzhen was tested positive in a nearby city. She has no any symptoms and signs, with unremarkable laboratory testing and radiological image, so she was soon diagnosed as asymptomatic COVID-19 positive case. Rapid contact tracing revealed that three of her relatives in Shenzhen were infected with COVID-19 and all of them were diagnosed as asymptomatic COVID-19 positive cases. To ensure residents' safety, Luohu hospital group (LHG) mounted a rapid organized response focusing on four measures: local environment management and residents' health monitoring, guidance for resumption of work, education and psychological counseling, and management of patients with fever in outpatient clinics. RESULTS: The LHG being structured as a people-centered, integrated organization responded to residents' medical and psychological needs rapidly, provided 6-hour results for COVID-19 testing, and recleared the city of COVID-19, as evidenced by the processing of 459,381 community samples within 15 days, with universally negative results beyond the originally identified case and her three close relatives. CONCLUSIONS: A quick and effective response from local organization to a new comeback COVID-19 positive case after clearance for a certain time is necessary in terms of ensuring the physical and psychological health of residents, as well as guarantying normal social work.

Chinese visceral adiposity index: A reliable indicator of visceral fat function associated with risk of type 2 diabetes.

BACKGROUND: The evidence of the association between Chinese visceral adiposity index (CVAI) and risk of type 2 diabetes mellitus (T2DM) is limited. We explored the association of CVAI with T2DM and directly compared with the predictive power of CVAI with other visceral obesity indices (visceral adiposity index, waist to height ratio, waist circumference and body mass index) based on a large prospective study. METHODS: We conducted a population-based study of 12 237 Chinese participants. Cox proportional-hazards models were used to estimate hazard ratios (HRs) and 95% confidence intervals (CIs) for the association between CVAI and T2DM. RESULTS: During follow-up (median: 6.01 years), the incidence of T2DM was 3.29, 7.34, 12.37 and 23.72 per 1000 person-years for quartiles 1, 2, 3 and 4 of CVAI, respectively. The risk of T2DM was increased with quartiles 2, 3 and 4 vs quartile 1 of CVAI (HR 2.12 [95% CI 1.50-3.00], 2.94 [2.10-4.13] and 5.01 [3.57-7.04], Ptrend < 0.001). Per-SD increase in CVAI was associated with a 72% increased risk of T2DM (HR 1.72 [95% CI 1.56-1.88]). Sensitivity analyses did not alter the association. The area under receiver operating characteristic curve was significantly higher for CVAI than other visceral obesity indices (all P <.001). Similar results were observed in stratified analyses by sex. CONCLUSIONS: Our findings show a positive association between CVAI and risk of T2DM. CVAI has the best performance in predicting incident T2DM, so the index might be a reliable and applicable indicator identifying people at high risk of T2DM.

Dose-response association between adult height and all-cause mortality: a systematic review and meta-analysis of cohort studies.

BACKGROUND: We conducted a systematic review and meta-analysis from published cohort studies to examine the association of adult height and all-cause mortality and to further explore the dose-response association. METHODS: PubMed, The Cochrane Library, The Ovid, CNKI, CQVIP and Wanfang databases were searched for articles published from database inception to 6 February 2018. We used the DerSimonian-Laird random-effects model to estimate the quantitative association between adult height and all-cause mortality and the restricted cubic splines to model the dose-response association. RESULTS: We included 15 articles, with 1 533 438 death events and 2 854 543 study participants. For each 5-cm height increase below the average, the risk of all-cause mortality was reduced by 7% [relative risk (RR) = 0.93, 95% confidence interval (CI), 0.89-0.97] for men and 5% (RR = 0.95, 95% CI, 0.90-0.99) for women. All-cause mortality had a U-shaped association with adult height, the lowest risk occurring at 174 cm for men and 158 cm for women (both Pnonlinearity < 0.001). Relative to the shortest adult height (147 cm for men and 137 cm for women), men at 174 cm had a 47% lower likelihood of all-cause mortality and women at 158 cm a 33% lower risk of all-cause mortality. CONCLUSIONS: Our study suggests that the relation between adult height and all-cause mortality is approximately U-shaped in both men and women.

Thrombospondin-4 (TSP4) gene-modified bone marrow stromal cells (BMSCs) promote the effect of therapeutic angiogenesis in critical limb ischemia (CLI) of diabetic rats.

Critical limb ischemia (CLI) is the leading cause of lower limb amputation. Traditional treatments for CLI have limitations. Studies have shown that thrombospondin-4 (TSP4) can promote the growth of neovascularization. In this study, we observed the angiogenesis efficiency of TSP4-overexpressing BMSC transplantation in CLI treatment. The recombinant FT106-tsp4-gfp lentiviral vector plasmid was constructed and transfected into 293FT cells. Primary BMSCs were successfully infected with the tsp4 virus, and TSP4 overexpression was confirmed before TSP4-BMSCs infusion. A rat CLI model was established, and 60 CLI rats were randomly divided into the CLI, BMSC + CLI and TSP4-BMSC + CLI groups. The effect of TSP4-BMSC on angiogenesis was detected by the motor function, immunohistochemistry and immunofluorescence staining assays. Neovascular density was detected by digital subtraction angiography (DSA). Our results demonstrated that TSP4-BMSCs improved the motor function score of the CLI rats and increased MMP2, MMP9, Ang-1, VEGF and vWF protein expression in tissue of the ischaemic area. Meanwhile, new blood vessels can be observed around the ischemic area after TSP4-BMSCs treatment. Our data illustrate that TSP4-BMSCs can promote the recovery of motor function in diabetic hind limb ischaemic rats. TSP4-BMSCs have better therapeutic effects than BMSCs.

Metabolically healthy general and abdominal obesity are associated with increased risk of hypertension.

Metabolically healthy obesity refers to a subset of obese people with a normal metabolic profile. We aimed to explore the association between metabolically healthy and obesity status and risk of hypertension among Chinese adults from The Rural Chinese Cohort Study. This prospective cohort study enrolled 9137 Chinese adults without hypertension, type 2 diabetes or treatment for lipid abnormality at baseline (2007-2008) and followed up during 2013-2014. Modified Poisson regression models were used to examine the risk of hypertension by different metabolically healthy and obesity status, estimating relative risks (RR) and 95 % CI. During 6 years of follow-up, we identified 1734 new hypertension cases (721 men). After adjusting for age, sex, smoking and other confounding factors, risk of hypertension was increased with metabolically healthy general obesity (MHGO) defined by BMI (RR 1·75, 95 % CI 1·02, 3·00) and metabolically healthy abdominal obesity (MHAO) defined by waist circumference (RR 1·51, 95 % CI 1·12, 2·04) as compared with metabolically healthy non-obesity. The associations between metabolically healthy and obesity status and hypertension outcome were consistent after stratifying by sex, age, smoking, alcohol drinking and physical activity. Both MHGO and MHAO were associated with increased risk of hypertension. Obesity control programmes should be implemented to prevent or delay the development of hypertension in rural China.

Sugar and artificially sweetened beverages and risk of obesity, type 2 diabetes mellitus, hypertension, and all-cause mortality: a dose-response meta-analysis of prospective cohort studies.

Although consumption of sugar-sweetened beverages (SSBs) and artificially sweetened beverages (ASBs) has increasingly been linked with obesity, type 2 diabetes mellitus, hypertension, and all-cause mortality, evidence remains conflicted and dose-response meta-analyses of the associations are lacking. We conducted an updated meta-analysis to synthesize the knowledge about their associations and to explore their dose-response relations. We comprehensively searched PubMed, EMBASE, Web of Science, and Open Grey up to September 2019 for prospective cohort studies investigating the associations in adults. Summary relative risks (RRs) and 95% confidence intervals (CIs) were estimated for the dose-response association. Restricted cubic splines were used to evaluate linear/non-linear relations. We included 39 articles in the meta-analysis. For each 250-mL/d increase in SSB and ASB intake, the risk increased by 12% (RR = 1.12, 95% CI 1.05-1.19, I2 = 67.7%) and 21% (RR = 1.21, 95% CI 1.09-1.35, I2 = 47.2%) for obesity, 19% (RR = 1.19, 95% CI 1.13-1.25, I2 = 82.4%) and 15% (RR = 1.15, 95% CI 1.05-1.26, I2 = 92.6%) for T2DM, 10% (RR = 1.10, 95% CI 1.06-1.14, I2 = 58.4%) and 8% (RR = 1.08, 95% CI 1.06-1.10, I2 = 24.3%) for hypertension, and 4% (RR = 1.04, 95% CI 1.01-1.07, I2 = 58.0%) and 6% (RR = 1.06, 95% CI 1.02-1.10, I2 = 80.8%) for all-cause mortality. For SSBs, restricted cubic splines showed linear associations with risk of obesity (Pnon-linearity = 0.359), T2DM (Pnon-linearity = 0.706), hypertension (Pnon-linearity = 0.510) and all-cause mortality (Pnon-linearity = 0.259). For ASBs, we found linear associations with risk of obesity (Pnon-linearity = 0.299) and T2DM (Pnon-linearity = 0.847) and non-linear associations with hypertension (Pnon-linearity = 0.019) and all-cause mortality (Pnon-linearity = 0.048). Increased consumption of SSBs and ASBs is associated with risk of obesity, T2DM, hypertension, and all-cause mortality. However, the results should be interpreted cautiously because the present analyses were based on only cohort but not intervention studies.

Race- and sex-specific association between alcohol consumption and hypertension in 22 cohort studies: A systematic review and meta-analysis.

BACKGROUND AND AIMS: The alcohol-hypertension relation has been well documented, but whether women have protective effect or race and type of beverage consumed affect the association remain unclear. To quantify the relation between total or beverage-specific alcohol consumption and incident hypertension by considering the effect of sex and race. METHODS AND RESULTS: Articles were identified in PubMed and Embase databases with no restriction on publication date. Pooled relative risks (RRs) and 95% confidence intervals (CIs) were calculated by random effects models. Restricted cubic splines were used to model the dose-response association. This study involved 22 articles (31 studies) and included 414,477 participants. The hypertension risk was different among liquor, wine, and beer at 5.1-10 g/d of ethanol consumption (P-across subgroups = 0.002). The hypertension risk differed between men (RR: 1.14, 95% CI: 1.07, 1.20) and women (RR: 0.98, 95% CI: 0.89, 1.06) at 10 g/d (P-across subgroups = 0.005). We found a linear alcohol-hypertension association among white (P-linearity = 0.017), black people (P-linearity = 0.035), and Asians (P-linearity<0.001). With 10 g/d increment of consumption, the RRs for hypertension were 1.06 (95% CI: 1.04, 1.08), 1.14 (95% CI: 1.01, 1.28), and 1.06 (95% CI: 1.01, 1.10) for Asians, black, and white people, respectively. CONCLUSION: Sex modifies the alcohol-hypertension association at low level of alcohol consumption and we did not find evidence of a protective effect of alcohol consumption among women. Black people may have higher hypertension risk than Asians and white people at the same ethanol consumption.

Dietary iron intake and risk of death due to cardiovascular diseases: A systematic review and dose-response meta-analysis of prospective cohort studies.

BACKGROUND AND OBJECTIVES: Many studies have investigated the association between dietary iron intake and death due to cardiovascular disease (CVD), but the results were inconsistent. We performed a dose-response meta- analysis to quantitatively assess the risk of CVD mortality with dietary intake of iron (total iron, heme iron, and non-heme iron). METHODS AND STUDY DESIGN: PubMed and Embase databases were searched for articles published up to February 21, 2019. Prospective cohort studies were included if reporting relative risks (RRs) and 95% confidence intervals (CIs) for risk of CVD mortality associated with dietary iron intake. Restricted cubic splines were used to model the dose-response association. RESULTS: We included eight articles (19 studies including 720,427 participants [46,045 deaths due to CVD]) in the meta-analysis. When comparing the highest versus lowest level of dietary heme iron intake, the pooled RR for CVD mortality was 1.19 (95% CI, 1.01-1.39). With a 1-mg/day increase in dietary heme iron intake, the pooled RR for death due to CVD, stroke, coronary heart disease, and myocardial infarction were 1.25 (95% CI, 1.17-1.33), 1.17 (1.04-1.32), 1.25 (0.70-2.22), and 1.17 (0.55-2.50) respectively. The association between dietary iron intake and CVD mortality was linear (pnonlinearity> 0.05). CONCLUSIONS: Higher dietary intake of heme iron was associated with a greater risk of CVD mortality. Reducing consumption of heme iron may help to prevent premature death due to CVD.

Birth weight and risk of type 2 diabetes: A dose-response meta-analysis of cohort studies.

The association between birth weight and type 2 diabetes mellitus has been debated for several decades. The objective of this systematic review and meta-analysis was to quantitatively clarify the association between birth weight and risk of type 2 diabetes mellitus based on cohort studies. We searched PubMed, Web of Science, and Embase databases for cohort study articles on the association between birth weight and risk of type 2 diabetes mellitus published up to 1 March 2018. Random effects of generalized least square regression models were used to estimate relative risk (RR). Restricted cubic splines were conducted to model the dose-response relationship. We included 21 studies (19 articles) involving 1 041 879 individuals and 35 699 cases of type 2 diabetes mellitus, with follow-up ranged from 6 to 47 years. We identified significant decreasing trend for the highest versus lowest category of birth weight for the association with type 2 diabetes mellitus risk: The risk was reduced by 35% (RR, 0.65; 95% confidence interval [CI], 0.53-0.81) and by 12% (RR 0.88; 95% CI, 0.85-0.91) per 500-g increment in birth weight. Our results showed a dose-response relationship between birth weight and diabetes risk, which was nonlinear (Pnonlinearity  < 0.001) and L-shaped. With increasing birth weight (<5000 g), the risk of type 2 diabetes mellitus decreased substantially. The association between birth weight and type 2 diabetes mellitus was curvilinear and L-shaped.