ABO and Rhesus blood groups and multiple health outcomes: an umbrella review of systematic reviews with meta-analyses of observational studies.

BACKGROUND: Numerous studies have been conducted to investigate the relationship between ABO and Rhesus (Rh) blood groups and various health outcomes. However, a comprehensive evaluation of the robustness of these associations is still lacking. METHODS: We searched PubMed, Web of Science, Embase, Scopus, Cochrane, and several regional databases from their inception until Feb 16, 2024, with the aim of identifying systematic reviews with meta-analyses of observational studies exploring associations between ABO and Rh blood groups and diverse health outcomes. For each association, we calculated the summary effect sizes, corresponding 95% confidence intervals, 95% prediction interval, heterogeneity, small-study effect, and evaluation of excess significance bias. The evidence was evaluated on a grading scale that ranged from convincing (Class I) to weak (Class IV). We assessed the certainty of evidence according to the Grading of Recommendations Assessment, Development, and Evaluation criteria (GRADE). We also evaluated the methodological quality of included studies using the A Measurement Tool to Assess Systematic Reviews (AMSTAR). AMSTAR contains 11 items, which were scored as high (8-11), moderate (4-7), and low (0-3) quality. We have gotten the registration for protocol on the PROSPERO database (CRD42023409547). RESULTS: The current umbrella review included 51 systematic reviews with meta-analysis articles with 270 associations. We re-calculated each association and found only one convincing evidence (Class I) for an association between blood group B and type 2 diabetes mellitus risk compared with the non-B blood group. It had a summary odds ratio of 1.28 (95% confidence interval: 1.17, 1.40), was supported by 6870 cases with small heterogeneity (I2 = 13%) and 95% prediction intervals excluding the null value, and without hints of small-study effects (P for Egger's test > 0.10, but the largest study effect was not more conservative than the summary effect size) or excess of significance (P < 0.10, but the value of observed less than expected). And the article was demonstrated with high methodological quality using AMSTAR (score = 9). According to AMSTAR, 18, 32, and 11 studies were categorized as high, moderate, and low quality, respectively. Nine statistically significant associations reached moderate quality based on GRADE. CONCLUSIONS: Our findings suggest a potential relationship between ABO and Rh blood groups and adverse health outcomes. Particularly the association between blood group B and type 2 diabetes mellitus risk.

Triglyceride-glucose index and health outcomes: an umbrella review of systematic reviews with meta-analyses of observational studies.

BACKGROUND: Numerous meta-analyses have explored the association between the triglyceride-glucose (TyG) index and diverse health outcomes, yet the comprehensive assessment of the scope, validity, and quality of this evidence remains incomplete. Our aim was to systematically review and synthesise existing meta-analyses of TyG index and health outcomes and to assess the quality of the evidence. METHODS: A thorough search of PubMed, EMBASE, and Web of Science databases was conducted from their inception through to 8 April 2024. We assessed the quality of reviews using A Measurement Tool to Assess Systematic Reviews (AMSTAR) and the certainty of the evidence using the Grading of Recommendations, Assessment, Development and Evaluation (GRADE) system. This study was registered with PROSPERO (CRD: 42024518587). RESULTS: Overall, a total of 95 associations from 29 meta-analyses were included, investigating associations between TyG index and 30 health outcomes. Of these, 83 (87.4%) associations were statistically significant (P < 0.05) according to the random effects model. Based on the AMSTAR tool, 16 (55.2%) meta-analyses were high quality and none was low quality. The certainty of the evidence, assessed by the GRADE framework, showed that 6 (6.3%) associations were supported by moderate-quality evidence. When compared with the lowest category of the TyG index, the risk of contrast-induced nephropathy (CIN) [relative risk (RR) = 2.25, 95%CI 1.82, 2.77], the risk of stroke in patients with diabetes mellitus (RR = 1.26, 95%CI 1.18, 1.33) or with acute coronary syndrome disease (RR = 1.56, 95%CI 1.06, 2.28), the prognosis of coronary artery disease (CAD)-non-fatal MI (RR = 2.02, 95%CI 1.32, 3.10), and the severity of CAD including coronary artery stenosis (RR = 3.49, 95%CI 1.71, 7.12) and multi-vessel CAD (RR = 2.33, 95%CI 1.59, 3.42) increased with high TyG index. CONCLUSION: We found that the TyG index was positively associated with many diseases including the risk of CIN and stroke, the prognosis of CAD, and the severity of CAD which were supported by moderate-quality evidence. TyG index might be useful to identify people at high-risk for developing these diseases.

Association between handgrip strength and depressive symptoms in patients undergoing hemodialysis: a cross-sectional study from a single Chinese center.

BACKGROUND: The relationship between handgrip strength (HGS) and depression in patients undergoing hemodialysis (HD) was unknown. Therefore, we aimed to clarify this association in a cohort of patients. METHODS: HGS was used as a representative indicator of muscle strength and was measured with a handheld dynamometer. Depressive symptoms were assessed with the self-reported Patient Health Questionnaire-9. A multivariable logistic regression model and restricted cubic spline analysis were used to assess the relationship between HGS and depression. RESULTS: The prevalence of depression in our study was 34% in 568 Chinese patients undergoing HD. Compared with patients in the lowest tertiles of absolute and weighted HGS, patients in the highest tertiles of HGS had an approximately 59% lower [odds ratio (OR) = 0.41, 95% confidence interval (CI) = 0.24-0.68; OR = 0.41, 95%CI = (0.24-0.69)] prevalence of depressive symptoms after multivariate adjustments. Besides, the risk of depression in hemodialysis patients decreased by 33% (OR = 0.67, 95%CI = 0.53-0.85) and 32% (OR = 0.68, 95%CI = 0.54-0.85) for each standard deviation increase in absolute HGS and weighted HGS, respectively. The prevalence of depressive symptoms decreased with both increasing absolute HGS and weighted HGS after multivariate adjustments (p for trend < 0.05). Furthermore, a linear dose-response relationship was observed between absolute HGS and weighted HGS and the prevalence of depressive symptoms (pnonlinearity>0.05). CONCLUSIONS: This study suggests that lower handgrip strength, a simple and modifiable parameter, is associated with a higher prevalence of depression in Chinese patients undergoing HD. Considering that depression is often unrecognized or underdiagnosed in HD patients, lowered muscle strength should be an important indicator and incentive for medical staff to screen for depression.

PM2.5 exposure and its interaction of oxidative balance score on ovarian cancer survival: A prospective cohort study.

Recent evidence advises particles with a diameter of 2.5 µm or less (PM2.5) might be a prognostic factor for ovarian cancer (OC) survival. The oxidative balance score (OBS) incorporates diet-lifestyle factors to estimate individuals' anti-oxidant exposure status which may be relevant to cancer prognosis. We aimed to investigate the roles of PM2.5, and OBS and their interaction in OC prognosis. 663 patients with OC were enrolled in the current study. Satellite-derived annual average exposures to PM2.5 based on patients' residential locations. The OBS was calculated based on 16 different diet-lifestyle components derived using an acknowledged self-reported questionnaire. The Cox regression model was performed to estimate the hazard ratios (HRs) and 95% confidence intervals (CIs) for overall survival (OS). We also assessed the effect of modification between PM2.5 and OS by OBS via interaction terms. During a median follow-up of 37.57 (interquartile:35.27-40.17) months, 123 patients died. Compared to low-concentration PM2.5 exposure, high PM2.5 during 1 year before diagnosis was associated with worse OC survival (HR= 1.19, 95% CI = 1.01-1.42). We observed an improved OS with the highest compared with the lowest OBS (HR = 0.46, 95% CI = 0.27-0.79, P for trend < 0.05). Notably, we also found an additive interaction between low OBS and high exposure to PM2.5, with the corresponding associations of PM2.5 being more pronounced among participants with lower OBS (HR = 1.42, 95% CI = 1.09-1.86). PM2.5 may blunt OC survival, but high OBS represented an antioxidative performance that could alleviate the adverse association of PM2.5 and OS.

A methodologic survey on use of the GRADE approach in evidence syntheses published in high-impact factor urology and nephrology journals.

BACKGROUND: To identify and describe the use of the Grading of Recommendations, Assessment, Development and Evaluation (GRADE) approach for rating the certainty of systematic reviews (SRs) evidence published in urology and nephrology journals. METHODS: SRs that were published in the top ten "urology and nephrology" journals with the highest impact factor according to the 2020 Journal Citation Reports (covering 2016-2020) were systematically searched and evaluated using the GRADE approach. RESULTS: A total of 445 SRs were researched. Sixty SRs of randomized control trials (RCTs) and/or non-randomized studies (NRSs) were evaluated using the GRADE approach. Forty-nine SRs (11%) rated the outcome-specific certainty of evidence (n = 29 in 2019-2020). We identified 811 certainty of evidence outcome ratings (n = 544 RCT ratings) as follows: very low (33.0%); low (32.1%); moderate (24.5%); and high (10.4%). Very low and high certainty of evidence ratings accounted for 55.0% and 0.4% of ratings in SRs of NRSs compared to 23.0% and 15.3% in SRs of RCTs. The certainty of evidence for RCTs and NRSs was downgraded most often for risk of bias and imprecision. CONCLUSIONS: We recommend increased emphasis on acceptance of the GRADE approach, as well as optimal use of the GRADE approach, in the synthesis of urinary tract evidence.

Pre-diagnostic dietary consumption of calcium and magnesium and calcium-to-magnesium intake ratio and ovarian cancer mortality: results from the ovarian cancer follow-up study (OOPS).

PURPOSE: Previous studies have indicated that dietary consumption of calcium (Ca), magnesium (Mg), and the Ca-to-Mg (Ca:Mg) ratio were associated with different health outcomes. However, no study has evaluated the association of pre-diagnostic Ca, Mg, and Ca:Mg ratio consumption with ovarian cancer (OC) survival. METHODS: The aforementioned associations were investigated in a cohort of 853 Chinese women diagnosed with OC between 2015 and 2020. A validated food frequency questionnaire was used to evaluate pre-diagnostic diet information. Deaths were recorded until March 31, 2021 via medical records and active follow-up. Cox proportional hazards model was applied to calculate the adjusted hazard ratios (HRs) and 95% confidence intervals (CIs). RESULTS: A total of 130 deaths were observed during a median follow-up of 37.2 months. After adjustment for potential confounders, pre-diagnostic Ca (HR< 600 vs. > 1000 = 1.45, 95% CI = 0.47-4.46, p for trend = 0.69) and Mg (HR< 250 vs. > 330 = 0.90, 95% CI = 0.39-2.08, p for trend = 0.77) intakes were found to be unrelated to OC survival, whereas a higher Ca:Mg intake ratio was significantly associated with worse survival (HR< 1.7 vs. > 2.5 = 2.72, 95% CI = 1.28-5.78, p for trend < 0.05). A significant result was also observed when treating the Ca:Mg ratio as a continuous variable (HR = 1.69, 95% CI = 1.12-2.55) for one-unit increment. CONCLUSION: Pre-diagnostic consumption of Ca and Mg was unrelated to OC survival, while a higher Ca:Mg intake ratio was strongly associated with worse survival among OC patients.

Ambient air pollution and COVID-19 risk: Evidence from 35 observational studies.

BACKGROUND AND AIMS: The coronavirus disease 2019 (COVID-19) pandemic is severely threatening and challenging public health worldwide. Epidemiological studies focused on the influence of outdoor air pollution (AP) on COVID-19 risk have produced inconsistent conclusions. We aimed to quantitatively explore this association using a meta-analysis. METHODS: We searched for studies related to outdoor AP and COVID-19 risk in the Embase, PubMed, and Web of Science databases. No language restriction was utilized. The search date entries were up to August 13, 2021. Pooled estimates and 95% confidence intervals (CIs) were obtained with random-/fixed-effects models. PROSPERO registration number: CRD42021244656. RESULTS: A total of 35 articles were eligible for the meta-analysis. For long-term exposure to AP, COVID-19 incidence was positively associated with 1 µg/m3 increase in nitrogen dioxide (NO2; effect size = 1.042, 95% CI 1.017-1.068), particulate matter with diameter <2.5 µm (PM2.5; effect size = 1.056, 95% CI 1.039-1.072), and sulfur dioxide (SO2; effect size = 1.071, 95% CI 1.002-1.145). The COVID-19 mortality was positively associated with 1 µg/m3 increase in nitrogen dioxide (NO2; effect size = 1.034, 95% CI 1.006-1.063), PM2.5 (effect size = 1.047, 95% CI 1.025-1.1071). For short-term exposure to air pollutants, COVID-19 incidence was positively associated with 1 unit increase in air quality index (effect size = 1.001, 95% CI 1.001-1.002), 1 µg/m3 increase NO2 (effect size = 1.014, 95% CI 1.011-1.016), particulate matter with diameter <10 µm (PM10; effect size = 1.005, 95% CI 1.003-1.008), PM2.5 (effect size = 1.003, 95% CI 1.002-1.004), and SO2 (effect size = 1.015, 95% CI 1.007-1.023). CONCLUSIONS: Outdoor air pollutants are detrimental factors to COVID-19 outcomes. Measurements beneficial to reducing pollutant levels might also reduce the burden of the pandemic.

Serum total indoxyl sulfate levels and all-cause and cardiovascular mortality in maintenance hemodialysis patients: a prospective cohort study.

BACKGROUND: The association between serum total indoxyl sulfate (tIS), and cardiovascular disease (CVD) and all-cause mortality is a matter of debate. In the current study we sought to determine the association, if any, between serum tIS, and all-cause and CVD-associated mortality in patients on maintenance hemodialysis (MHD). METHODS: A prospective cohort study was conducted involving 500 MHD patients at Dalian Municipal Central Hospital from 31 December 2014 to 31 December 2020. Serum tIS levels were measured at baseline and classified as high (≥44.16 ng/ml) or low (< 44.16 ng/ml) according to the "X-tile" program. Besides, the associations between continuous serum tIS and outcomes were also explored. Predictors were tested for colinearity using variance inflation factor analysis. Hazard ratios (HRs) and 95% confidence intervals (CIs) were calculated using Cox proportional hazards regression models. Restricted cubic spline model was performed to assess dose-response relationships between tIS concentration and all-cause and CVD mortality. RESULTS: During a 58-month median follow-up period, 224 deaths (132 CVD deaths) were documented. After adjustment for potential confounders, the serum tIS level was positively associated with all-cause mortality (HR = 1.02, 95% = 1.01-1.03); however, we did not detect a significant association when tIS was a dichotomous variable. Compared with the MHD population with a serum tIS level < 44.16 ng/ml, the adjusted HR for CVD mortality among those with a serum tIS level ≥ 44.16 ng/ml was 1.76 (95% = 1.10-2.82). Furthermore, we also noted the same association when the serum tIS level was a continuous variable. CONCLUSION: The serum tIS level was associated with higher risk of all-cause and CVD mortality among MHD patients. Further prospective large-scale studies are required to confirm this finding.

Sulforaphane enhances the cisplatin sensitivity through regulating DNA repair and accumulation of intracellular cisplatin in ovarian cancer cells.

OBJECTIVES: Cisplatin is commonly applied as anticancer agent for various cancers, including ovarian cancer. Unfortunately, the drug resistance frequently occurred which obstructing the effect of cisplatin on tumors. The goal of our research was to investigate the reversal actions and the potential mechanisms of sulforaphane (SFN) on cisplatin resistance in ovarian carcinoma. METHODS: The A2780 and IGROV1 cells and their cisplatin resistance cells A2780/CP70 and IGROV1-R10 were used in this study. Cell viability was detected by CCK-8. The DNA repair was measured by comet assay. The cisplatin transporter proteins were measured with western blotting. The concentration of intracellular cisplatin was detected by HPLC. The luciferase activity assay was applied to determine the target site of miR-30a-3p on the 3'UTR of ERCC1 and ATP7A. A2780/CP70 and IGROV1-R10 xenograft mouse model were established to confirm the antineoplastic action of SFN combined with cisplatin. RESULTS: SFN reversed the resistance of A2780/CP70 and IGROV1-R10 ovarian carcinoma cells to cisplatin through inducing DNA damage and accumulation of intracellular cisplatin. SFN treatment notably increased miR-30a-3p expression, which was decreased in cisplatin-resistant cells. Moreover, overexpressed miR-30a-3p enhanced the sensitivity of A2780/CP70 and IGROV1-R10 cells to cisplatin treatment, and inhibiting miR-30a-3p activity abated the reversal actions of SFN on cisplatin resistance. The luciferase assay findings showed that miR-30a-3p binds to ERCC1 and ATP7A which are the key regulators for DNA repair and cisplatin transportation. CONCLUSIONS: Our findings indicated that SFN could enhance cisplatin sensitivity of ovarian carcinoma cells through up-regulating miR-30a-3p to induce DNA damage and accumulation of intracellular cisplatin.

Air pollution and metabolic syndrome risk: Evidence from nine observational studies.

BACKGROUND AND AIMS: Globally, the number of metabolic syndrome (MetS) cases has increased substantially over time. However, the association between air pollution (AP) and MetS risk has been contradictory in observational studies. This is the first reported meta-analysis quantitatively exploring the aforementioned association. METHODS: We searched PubMed, Embase, and Web of Science database entries up to September 14, 2020, and searches were updated up to December 6, 2020 to identify eligible articles on the AP-MetS risk association. No language restriction was imposed. Random-effects models were applied to estimate summary and subgroup effect sizes with 95% confidence intervals (CIs). PROSPERO registration number: CRD42020210431. RESULTS: Eight articles (nine studies) were eligible for the meta-analysis. Increased MetS prevalence was not found to be associated with particulate matter less than 1 µm (PM1), 2.5 µm (PM2.5), and 10 µm (PM10) in diameter or nitrogen dioxide (NO2), and the summary effect sizes were 1.33 (95% CI: 0.95-1.85), 1.34 (95% CI: 0.96-1.89), 1.18 (95% CI: 0.98-1.19), and 1.28 (95% CI: 0.89-1.82), respectively, based on cross-sectional studies. The summary results indicated no association between each 10 µg/m3 increase in PM2.5 and MetS incidence (effect size 2.78 [95% CI: 0.70-11.02]), based on cohort studies. Subgroup analysis demonstrated that MetS incidence in older men increased dramatically by 992% with each 10 µg/m3 increase in PM2.5. CONCLUSIONS: The evidence presented here suggests that although exposure to PM1, PM2.5, PM10, or NO2 was not found to have a significant association with the occurrence of MetS, the statistical significance of the relationship between exposure to PM1, PM2.5, or PM10 and MetS prevalence was approximately borderline. More studies on AP-MetS risk association in low-/middle-income countries, as well as on the association between other air pollutants and MetS risk, are warranted. A sufficient number of high-quality studies is required to perform a meaningful meta-analysis of the relationship between air pollutants and MetS.

Characterization of the Sperm Proteome and Reproductive Outcomes with in Vitro, Fertilization after a Reduction in Male Ejaculatory Abstinence Period.

Semen samples from men after a short ejaculatory abstinence show improved sperm quality and result in increased pregnancy rates, but the underlying mechanisms remain unclear. Herein, we report that ejaculates from short (1-3 h) compared with long (3-7 days) periods of abstinence showed increases in motile sperm count, sperm vitality, normal sperm morphology, acrosome reaction capacity, total antioxidant capacity, sperm mitochondrial membrane potential, high DNA stainability, and a decrease in the sperm DNA fragmentation index (p, < 0.05). Sperm proteomic analysis showed 322 differentially expressed proteins (minimal fold change of ±1.5 or greater and p, < 0.05), with 224 upregulated and 98 downregulated. These differentially expressed proteins are profoundly involved in specific cellular processes, such as motility and capacitation, oxidative stress, and metabolism. Interestingly, protein trimethyllysine modification was increased, and butyryllysine, propionyllysine, and malonyllysine modifications were decreased in ejaculates from a short versus, long abstinence (p, < 0.05). Finally, the rates of implantation, clinical pregnancy, and live births from in vitro, fertilization treatments were significantly increased in semen samples after a short abstinence. Our study provides preliminary mechanistic insights into improved sperm quality and pregnancy outcomes associated with spermatozoa retrieved after a short ejaculatory abstinence.

Infertility and ovarian cancer risk: Evidence from nine prospective cohort studies.

Epidemiological studies have investigated the relationship between infertility and the risk of ovarian cancer (OC); however, the results have been inconsistent. We therefore conducted the first meta-analysis to update and quantify the aforementioned association based on prospective cohort studies. Studies were identified by searching PubMed, EMBASE and Web of Science databases up to January 8, 2020. We extracted data from the studies and performed quality assessments. Summary relative risks (RRs) with 95% confidence intervals (CIs) were calculated using a random-effects model. Publication bias, and subgroup, meta-regression and sensitivity analyses were also conducted. Nine prospective cohort studies with a total of 10 383 OC cases and 6 278 830 participants were included in the present study. The summary RR of the association between infertility and the risk of OC was 1.51 (95% CI: 1.35-1.69), with low heterogeneity. Positive associations were observed in most subgroup analyses stratified by predefined factors, including region, duration of follow-up, study quality, causes of infertility, invasiveness of OC, infertility treatment status and adjustment of potential confounding parameters. No significant publication bias was detected. Our findings suggest that infertility in women were associated with an increased risk of OC.

The association between glycemic index, glycemic load, and metabolic syndrome: a systematic review and dose-response meta-analysis of observational studies.

PURPOSE: The association of glycemic index (GI) and glycemic load (GL) with metabolic syndrome (MetS) is controversial. Therefore, we conducted this first systematic review and dose-response meta-analysis of observational studies to quantify these associations. METHODS: We searched PubMed, EMBASE, Web of Science, and the Cochrane Library for relevant studies up to 1 April 2019. Summary odds ratios (OR) and 95% confidence intervals (CI) were calculated by a random-effects model. This study was registered with PROSPERO (CRD42019131788). RESULTS: We included eight high-quality (n = 5) or medium-quality (n = 3) cross-sectional studies in the final meta-analysis, comprising 6058 MetS events and 28,998 participants. The summary ORs of MetS for the highest versus lowest categories were 1.23 (95% CI 1.10-1.38, I2 = 0, tau2 = 0, n = 5) for dietary GI, 1.06 (95% CI 0.89-1.25, I2 = 36.2%, tau2 = 0.0151, n = 6) for dietary GL. The summary OR was 1.12 (95% CI 1.00-1.26, I2 = 0, tau2 = 0, n = 3) per 5 GI units, 0.96 (95% CI 0.83-1.10, I2 = 33.4%, tau2 = 0.0059, n = 2) per 20 GL units. CONCLUSIONS: Dietary GI was positively associated with the prevalence of MetS. However, no significant association was found between dietary GL and the prevalence of MetS. Further studies with prospective design are needed to establish potential causal relationship between dietary GI and the MetS.

Maternal preconception and first trimester exposure to PM10 and the risk of oral clefts in offspring: a population-based, case-control study.

BACKGROUND: Current literature describes limited and controversial evidence on the associations between maternal preconception and first trimester exposure to particulate matter with a diameter ≤10 µm (PM10) and the risk of oral cleft (OC). METHODS: We conducted a case-control study involving 3086 OC cases and 7950 controls, registered in the Maternal and Child Health Certificate Registry in Liaoning Province between 2010 and 2015. PM10 concentrations were obtained from the Environment Protection Bureau. The exposure windows included the 3 months before pregnancy, the first trimester and the individual months. Unconditional logistic regression model was performed to estimate the OR and 95% CI for the association between PM10 exposure and the risk of OC, cleft lip only (CLO), cleft palate only (CPO), and cleft lip and palate (CLP). RESULTS: Maternal PM10 exposure was positively associated with an increased risk for OC during the 3 months preconception (per 10 µg/m3 increment: OR=1.04, 95% CI 1.01 to 1.07; highest vs lowest quartile: OR=1.23, 95% CI 1.04 to 1.45) and the first trimester (per 10 µg/m3 increment: OR=1.05, 95% CI 1.02 to 1.08; highest vs lowest quartile: OR=1.37, 95% CI 1.15 to 1.64). Analyses based on individual months presented similar positive associations, particularly in the second month of pregnancy (OR=1.77, 95% CI 1.51 to 2.09) for highest versus lowest quartile. In the subtype analysis, stronger associations were observed for CLO, whereas there was negligible evidence for CPO and CLP. Sensitivity analyses using propensity score matching generated similar findings. CONCLUSIONS: Our study provides evidence that PM10 exposure during the 3 months preconception and the first trimester increases the risk of OC.

Association between maternal exposure to PM10 and polydactyly and syndactyly: A population-based case-control study in Liaoning province, China.

BACKGROUND: The number of studies on air pollution with birth defects as the primary outcome has increased dramatically over the past two decades, but the potential role of specific air pollutants in congenital limb anomalies remains unclear. OBJECTIVES: To evaluate associations between preconception and first-trimester PM10 exposure and polydactyly and syndactyly in a population-based case-control study. METHODS: Polydactyly cases (n = 2605), syndactyly cases (n = 595), and controls without any birth defects (n = 7950) born between 2010 and 2015 were selected from the Maternal and Child Health Certificate Registry of Liaoning Province. The monthly mean PM10 concentrations were obtained from 75 air monitoring stations, and the exposure assessment was based on the mean concentration of all stations in mother's residential city. A multivariable logistic regression model was constructed to calculate adjusted odds ratios (aORs) and 95% confidence intervals (CIs). RESULTS: PM10 exposure was positively associated with the risks of polydactyly (preconception: aORT3 vs. T1 = 1.95, 95% CI 1.56-2.45, aOR = 1.06, 95% CI 1.01-1.10 [per 10-µg/m3 increment]; first-trimester: aORT3 vs. T1 = 2.51, 95% CI 2.00-3.15) and syndactyly (preconception: aORT3 vs. T1 = 2.86, 95% CI 1.98-4.13, aOR = 1.11, 95% CI 1.03-1.20 [per 10-µg/m3 increment]; first-trimester: aORT3 vs. T1 = 3.10, 95% CI 2.11-4.56). Analyses based on single month exposure windows basically showed similar positive associations. Additionally, these findings were robust in sensitivity analyses and broadly consistent across subgroups. CONCLUSION: Our study suggest that preconception and first-trimester PM10 exposures are related to increased risks of polydactyly and syndactyly.

Relationship between legume consumption and metabolic syndrome: A systematic review and meta-analysis of observational studies.

AIMS: The prevalence of metabolic syndrome (MetS) has been increasing in recent years. Investigation of whether consumption of legumes as a part of healthy diet could reduce the odds of MetS has led to inconsistent conclusions. Here, we performed the first meta-analysis of observational studies to analyze the association between legume consumption and prevalence of MetS. DATA SYNTHESIS: PubMed, EMBASE, and Web of Science databases were searched to identify observational studies up to June 1, 2019. We extracted data from the studies included and performed quality assessments. Summary odds ratios (ORs) with 95% confidence intervals (CIs) were calculated using a random-effects model. Publication bias and subgroup and sensitivity analyses were also performed. We finally included four cross-sectional studies, two cohort studies, and one case-control study involving 56,028 participants. The summary OR revealed no statistically significant association between legume consumption and odds of MetS (OR = 0.93, 95% CI = 0.76-1.12, I2 = 73.5%). Subgroup analysis of study characteristics and adjustment for confounding along with sensitivity analyses revealed no statistically significant differences. No evidence of publication bias was detected. CONCLUSION: Legume consumption is not associated with the odds of MetS. These findings require validation in well-designed cohort studies and randomized clinical trials with accurate measurement of legume intake and strict control of confounders. REGISTRATION: This study was registered with the International Prospective Register of Systematic Reviews (registration number: CRD42019131777).

Higher Levels of High-Sensitivity C-Reactive Protein Is Positively Associated with the Incidence of Hyperuricemia in Chinese Population: A Report from the China Health and Retirement Longitudinal Study.

PURPOSE: The aim of the present cohort study was to explore the longitudinal association between high-sensitivity C-reactive protein (CRP) and hyperuricemia in Chinese population. Furthermore, we conducted subgroup analyses to explore this association according to age, sex, and body mass index. METHODS: A total of 5,419 healthy participants were enrolled in the final cohort analysis. The high-sensitivity CRP level was measured by immunoturbidimetric assay. Hyperuricemia was defined as serum uric acid ≥7.0 mg/dL (416 µmol/L) in men and ≥6.0 mg/dL (357 µmol/L) in women. Multivariate logistic regression was used to analyze the association. RESULTS: During the 4 years follow-up, 474 participants developed hyperuricemia. Compared with participants in the lowest tertile of high-sensitivity CRP, the multivariate-adjusted odds ratio (OR) (95% confidence interval [CI]) for incident hyperuricemia in the highest tertile was 1.36 (1.02, 1.82). In the subgroup analyses, high-sensitivity CRP was positively associated with the incidence of hyperuricemia after multivariate adjustments (P for trend = 0.04) in women. Compared with the women in the lowest tertile of high-sensitivity CRP, the multivariate-adjusted OR (95% CI) in the highest tertile was 1.69 (1.10, 2.66). No statistically significant association was found in other subgroups. CONCLUSIONS: The findings of this prospective cohort study suggest that higher level of high-sensitivity CRP is an independent risk factor for hyperuricemia in Chinese, especially in women.

Carbohydrate intake and risk of metabolic syndrome: A dose-response meta-analysis of observational studies.

BACKGROUND AND AIMS: Epidemiological association studies have reported inconsistent findings on the relationship between carbohydrate intake and risk of metabolic syndrome (MetS). Therefore, we aimed to conduct the first dose-response meta-analysis to investigate this effect. METHODS AND RESULTS: A systematic search in PubMed and Web of Science databases from their inception to June 01, 2019, together with relevant literature scrutiny, was performed to identify related studies for inclusion into the meta-analysis. We calculated the odds ratios (ORs) with 95% confidence intervals (CIs) using a random effects model. Furthermore, subgroup, sensitivity, heterogeneity, and publication bias analyses were performed. This meta-analysis included 14 cross-sectional and four cohort studies, totaling 284,638 participants and 69,554 MetS cases. The highest versus the lowest carbohydrate intake values were associated with an increased risk of MetS (OR: 1.253, 95% CI: 1.147-1.368), with moderate heterogeneity (I2 = 54.5%). Using dose-response analysis, we found a linear association between carbohydrate consumption and MetS risk with a corresponding OR of 1.026 (95% CI, 1.004-1.048) and with significant heterogeneity (I2 = 82.0%) at 5% energy intake from carbohydrates. We have found similar results using subgroup analyses for major study characteristics and adjustment for confounders. Sensitivity analysis further enhanced the robustness of the results, and no publication bias was detected. CONCLUSION: Carbohydrate intake is associated with an increased risk of developing MetS. Therefore, additional large prospective cohort studies are warranted to confirm our findings.

Selective serotonin reuptake inhibitor use during early pregnancy and congenital malformations: a systematic review and meta-analysis of cohort studies of more than 9 million births.

BACKGROUND: In 2005, the FDA cautioned that exposure to paroxetine, a selective serotonin reuptake inhibitor (SSRI), during the first trimester of pregnancy may increase the risk of cardiac malformations. Since then, the association between maternal use of SSRIs during pregnancy and congenital malformations in infants has been the subject of much discussion and controversy. The aim of this study is to systematically review the associations between SSRIs use during early pregnancy and the risk of congenital malformations, with particular attention to the potential confounding by indication. METHODS: The study protocol was registered with PROSPERO (CRD42018088358). Cohort studies on congenital malformations in infants born to mothers with first-trimester exposure to SSRIs were identified via PubMed, Embase, Web of Science, and the Cochrane Library databases through 17 January 2018. Random-effects models were used to calculate summary relative risks (RRs). RESULTS: Twenty-nine cohort studies including 9,085,954 births were identified. Overall, use of SSRIs was associated with an increased risk of overall major congenital anomalies (MCAs, RR 1.11, 95% CI 1.03 to 1.19) and congenital heart defects (CHD, RR 1.24, 95% CI 1.11 to 1.37). No significantly increased risk was observed when restricted to women with a psychiatric diagnosis (MCAs, RR 1.04, 95% CI 0.95 to 1.13; CHD, RR 1.06, 95% CI 0.90 to 1.26). Similar significant associations were observed using maternal citalopram exposure (MCAs, RR 1.20, 95% CI 1.09 to 1.31; CHD, RR 1.24, 95% CI 1.02 to 1.51), fluoxetine (MCAs, RR 1.17, 95% CI 1.07 to 1.28; CHD, 1.30, 95% CI 1.12 to 1.53), and paroxetine (MCAs, RR 1.18, 95% CI 1.05 to 1.32; CHD, RR 1.17, 95% CI 0.97 to 1.41) and analyses restricted to using women with a psychiatric diagnosis were not statistically significant. Sertraline was associated with septal defects (RR 2.69, 95% CI 1.76 to 4.10), atrial septal defects (RR 2.07, 95% CI 1.26 to 3.39), and respiratory system defects (RR 2.65, 95% CI 1.32 to 5.32). CONCLUSIONS: The evidence suggests a generally small risk of congenital malformations and argues against a substantial teratogenic effect of SSRIs. Caution is advisable in making decisions about whether to continue or stop treatment with SSRIs during pregnancy.

Hyperhomocysteinemia in polycystic ovary syndrome: decreased betaine-homocysteine methyltransferase and cystathionine ß-synthase-mediated homocysteine metabolism.

RESEARCH QUESTION: What are the metabolic characteristics of homocysteine in polycystic ovary syndrome (PCOS)? DESIGN: Homocysteine concentrations were determined in serum samples from non-obese and obese control subjects and PCOS patients. Homocysteine metabolism was studied in a rat model of PCOS established using dehydroepiandrosterone (DHEA) or DHEA in combination with a high-fat diet (HFD). RESULTS: It was shown that (i) serum homocysteine concentrations were greater in PCOS patients than in control subjects in the obese group (P < 0.05) and serum homocysteine concentrations were significantly higher in the obese group than in the non-obese group, regardless of PCOS status (both P < 0.05); (ii) serum homocysteine concentrations were significantly increased in DHEA + HFD-induced rats compared with controls (P < 0.05); (iii) when compared with the control group, mRNA concentrations of homocysteine metabolic enzymes Bhmt and Cbs were significantly reduced in the liver tissues of DHEA + HFD-induced rats (both P < 0.0001); (iv) when compared with the control group, there was a significant decrease in the methylation concentrations of the Cbs (P < 0.05) and Bhmt (P < 0.05 and P < 0.0001) promoter in the DHEA + HFD group. The methylation patterns, together with previous data, indicate that hypomethylated promoter-mediated transcriptional activation of Bhmt and Cbs might be a defence mechanism against PCOS-related hyperhomocysteinemia. CONCLUSIONS: These findings indicate that decreased liver Bhmt and Cbs-mediated homocysteine metabolism might have a role in hyperhomocysteinemia in PCOS and provides further evidence for a potential role of decreased liver function in PCOS.