Investigating the bi-directional association of rheumatoid arthritis and thyroid function: a methodological assessment of Mendelian randomization: Bi-directional association between rheumatoid arthritis and thyroid function.

OBJECTIVES: Rheumatoid arthritis (RA) and thyroid dysfunction are frequently observed in the same patient. However, whether they co-occur or exhibit a causal relationship remains uncertain. We aimed to systematically investigate the causal relationship between RA and thyroid function using a large sample and advanced methods. METHODS: Bi-directional two-sample Mendelian randomization (MR) analysis was performed based on RA and six thyroid function traits datasets in the European population. The robustness of the results was demonstrated using multiple MR methods and a series of sensitivity analyses. Multivariable MR using Bayesian model averaging (MR-BMA) was performed to adjust for possible competing risk factors. A sensitivity dataset, which included patients with seropositive RA and controls, was used to repeat the analyses. Furthermore, enrichment analysis was employed to discover the underlying mechanism between RA and thyroid functions. RESULTS: A significantly positive causal effect was identified for RA on autoimmune thyroid disease (AITD), as well as for AITD on RA (P < 0.001). Further sensitivity analyses showed consistent causal estimates from a variety of MR methods. After removing the outliers, MR-MBA results showed that RA and AITD were independent risk factors in their bi-directional causality, even in the presence of other competing risk factors (Padj < 0.05). Enrichment analysis showed immune cell activation and immune response play crucial roles in them. CONCLUSION: Our results illustrate the significant bi-directional causal effect of RA and AITD, which holds even in multiple competing risk factors. Clinical screening for thyroid dysfunction in RA patients deserves further attention, and vice versa.

Association between polycyclic aromatic hydrocarbons and infertility in U.S. women: National Health and Nutrition Examination Survey 2013-2016.

Although there is a body of research indicating the potential impact of polycyclic aromatic hydrocarbons (PAHs) exposure on male infertility, the understanding of how PAH might affect female infertility is still limited. This study aimed to evaluate associations of PAHs, both individually and as a mixture, with female infertility using multiple logistic regression, Bayesian kernel machine regression (BKMR), and quantile g-computation (QGC) models based on data from the National Health and Nutrition Examination Survey (NHANES) 2013-2016. The study included 729 female participants. Multiple logistic regression results indicated that there was a significant association between the third tertile of 2-hydroxy fluorene (2-OHFLU) and female infertility, and the OR was 2.84 (95% CI: 1.24-6.53, P value = 0.015) compared with the first tertile after adjusting for the potential covariates. The BKMR model revealed a positive overall trend between mixed PAH exposure and female infertility, particularly when the mixture was at or above the 55th percentile, where 2-hydroxynaphthalene (2-OHNAP) and 1-hydroxypyrene (1-OHPYR) were the primary influences of the mixture. The univariate exposure-response function indicated positive associations between individual PAH exposure, specifically 2-OHNAP, 2-OHFLU, and 1-OHPYR, and female infertility. The QGC model also indicated a positive trend between exposure to a mixture of PAHs and female infertility, although it did not reach statistical significance (OR = 1.33, 95%CI: 0.86-2.07), with 1-OHPYR having the greatest positive effect on the outcome. This study suggested that exposure to PAHs may be associated with female infertility and further research is needed to consolidate and confirm these findings.

Association of phthalate exposure with type 2 diabetes and the mediating effect of oxidative stress: A case-control and computational toxicology study.

Phthalic acid esters (PAEs) are widely used as plasticizers and have been suggested to engender adverse effects on glucose metabolism. However, epidemiological data regarding the PAE mixture on type 2 diabetes (T2DM), as well as the mediating role of oxidative stress are scarce. This case-control study enrolled 206 T2DM cases and 206 matched controls in Guangdong Province, southern China. The concentrations of eleven phthalate metabolites (mPAEs) and the oxidative stress biomarker 8-hydroxy-2'-deoxyguanosine (8-OHdG) in urine were determined. Additionally, biomarkers of T2DM in paired serum were measured to assess glycemic status and levels of insulin resistance. Significantly positive associations were observed for mono-(2-ethylhexyl) phthalate (MEHP) and Mono(2-ethyl-5-hydroxyhexyl) phthalate (MEHHP) with T2DM (P < 0.001). Restricted cubic spline modeling revealed a non-linear dose-response relationship between MEHHP and T2DM (Pnon-linear = 0.001). The Bayesian kernel machine regression and quantile g-computation analyses demonstrated a significant positive joint effect of PAE exposure on T2DM risk, with MEHHP being the most significant contributor. The mediation analysis revealed marginal evidence that oxidative stress mediated the association between the mPAEs mixture and T2DM, while 8-OHdG respectively mediated 26.88 % and 12.24 % of MEHP and MEHHP on T2DM risk individually (Pmediation < 0.05). Di(2-ethylhexyl) phthalate (DEHP, the parent compound for MEHP and MEHHP) was used to further examine the potential molecular mechanisms by in silico analysis. Oxidative stress may be crucial in the link between DEHP and T2DM, particularly in the reactive oxygen species metabolic process and glucose import/metabolism. Molecular simulation docking experiments further demonstrated the core role of Peroxisome Proliferator Activated Receptor alpha (PPARα) among the DEHP-induced T2DM. These findings suggest that PAE exposure can alter oxidative stress via PPARα, thereby increasing T2DM risk.

Association between serum 25-hydroxyvitamin D and vitamin D dietary supplementation and risk of all-cause and cardiovascular mortality among adults with hypertension.

BACKGROUND: The relationship between vitamin D status and mortality among adults with hypertension remains unclear. METHODS: This prospective cohort study involved a sample of 19,500 adults with hypertension who participated in the National Health and Nutrition Examination Survey (NHANES) from 2001 to 2018. We utilized a weighted COX proportional hazard model to assess the association between vitamin D status and mortality. This statistical model calculates hazard ratios (HR) and their corresponding 95% confidence intervals (95% CI). RESULTS: The study indicated that lower serum 25(OH)D concentration was associated with an increased risk of all-cause mortality among individuals with hypertension. Specially. Those with concentrations between 25.0 and 49.9 nmol/L (HR = 1.71, 95%CI = 1.22-2.40) and less than 25.0 nmol/L (HR = 1.97, 95%CI = 1.15-3.39) had higher hazard ratios for all-cause mortality. Individuals with hypertension who took vitamin D supplements had a lower risk of all-cause mortality, but not the risk of CVD mortality (HR 0.75, 95%CI 0.54-1.03), compared to those who did not supplement (HR = 0.76, 95%CI = 0.61-0.94). Subgroup analysis further revealed that vitamin D supplementation was associated with a reduced risk of all-cause mortality among individuals without diabetes (HR = 0.65, 95%CI = 0.52-0.81) and individuals without CVD (HR = 0.75, 95%CI = 0.58-0.97), and a decreased risk of CVD mortality among individuals without diabetes (HR = 0.63, 95%CI = 0.45-0.88) and without CVD (HR = 0.61, 95%CI = 0.40-0.92). Furthermore, higher-dose vitamin D supplementation was also associated with a greater reduction in all-cause mortality among hypertensive individuals, and there was the potential synergistic effect of combining normal-dose calcium and vitamin D supplementation, showing a superior effect on mortality compared to low-dose supplementation in adults with hypertension. CONCLUSIONS: This prospective cohort study demonstrated a significant association between lower serum 25 (OH)D concentration and increased all-cause mortality among adults with hypertension. Furthermore, the study found that vitamin D supplementation had a strong and significantly positive correlation with reduced all-cause and CVD mortality among hypertensive individuals without diabetes or CVD. This positive correlation suggests that vitamin D supplementation could potentially be an effective strategy to reduce the risk of mortality in this specific group of people.

Association between Psoriasis and Renal Functions: An Integration Study of Observational Study and Mendelian Randomization.

Psoriasis is an autoimmune-mediated disease with several comorbidities in addition to typical skin lesions. Increasing evidence shows the relationships between psoriasis and renal functions, but the relationship and causality remain unclear. We aimed to investigate the associations and causality between psoriasis and four renal functions, including the estimated glomerular filtration rate (eGFR), blood urea nitrogen (BUN), urine albumin to creatinine ratio (UACR), and chronic kidney disease (CKD). For the population-based study, we analyzed the National Health and Nutrition Examination Survey (NHANES) data from five cycles (2003-2006 and 2009-2014) on psoriasis and renal functions. Subgroup analyses were conducted among different categories of participants. Meanwhile, a bidirectional two-sample Mendelian randomization (TSMR) study in European populations was also performed using summary-level genetic datasets. Causal effects were derived by conducting an inverse-variance weighted (MR-IVW) method. A series of pleiotropy-robust MR methods was employed to validate the robustness. Multivariable MR (MVMR) was conducted to complement the result when five competing risk factors were considered. A total of 20,244 participants were enrolled in the cross-sectional study, where 2.6% of them had psoriasis. In the fully adjusted model, participants with psoriasis had significantly lower eGFR (p = 0.025) compared with the healthy group. Individuals who are nonoverweight are more likely to be affected by psoriasis, leading to an elevation of BUN (Pint = 0.018). In the same line, TSMR showed a negative association between psoriasis and eGFR (p = 0.016), and sensitive analysis also consolidated the finding. No causality was identified between psoriasis and other renal functions, as well as the inverse causality (p > 0.05). The MVMR method further provided quite consistent results when adjusting five confounders (p = 0.042). We detected a significant negative effect of psoriasis on eGFR, with marginal association between BUN, UACR, and CKD. The adverse of psoriasis on the renal should merit further attention in clinical cares.

Anti-Toxoplasma gondii antibodies as a risk factor for the prevalence and severity of systemic lupus erythematosus.

BACKGROUND: Systemic lupus erythematosus (SLE) is a complex systemic autoimmune disease characterized by the presence of numerous autoantibodies. The interaction of infectious agents (viruses, bacteria and parasites) and a genetically susceptible host may be a key mechanism for SLE. Toxoplasma gondii is a widespread intracellular parasite that has been implicated in the pathogenesis of autoimmune diseases. However, the relationship between T. gondii infection and the increased risk of SLE in Chinese populations remains unclear. METHODS: The seroprevalence of T. gondii infection was assessed in 1771 serum samples collected from Chinese individuals (908 healthy controls and 863 SLE patients) from different regions of China using an enzyme-linked immunosorbent assay. Serum autoantibodies and clinical information were obtained and analysed. RESULTS: Our observations revealed a higher prevalence of anti-T. gondii antibodies (ATxA) immunoglobulin G (IgG) in serum samples from SLE patients (144/863, 16.7%) than in those from the healthy controls (53/917, 5.8%; P < 0.0001), indicating a 2.48-fold increased risk of SLE in the ATxA-IgG+ population, after adjustment for age and sex (95% confidence interval [CI] 1.70-3.62, P < 0.0001). ATxA-IgG+ SLE patients also showed a 1.75-fold higher risk of developing moderate and severe lupus symptoms (95% CI 1.14-2.70, P = 0.011) compared to ATxA-IgG- patients. Relative to ATxA-IgG- patients, ATxA-IgG+ patients were more likely to develop specific clinical symptoms, including discoid rash, oral ulcer, myalgia and alopecia. Seven antibodies, namely anti-ribosomal RNA protein (rRNP), anti-double stranded DNA (dsDNA), anti-cell membrane DNA (cmDNA), anti-scleroderma-70 (Scl-70), anti-cardiolipin (CL), anti-beta2-glycoprotein-I (B2GPI) and rheumatoid factor (RF), occurred more frequently in ATxA-IgG+ patients. When combined with anti-dsDNA and RF/anti-rRNP/anti-cmDNA/ESR, ATxA-IgG significantly increased the risk for severe lupus. CONCLUSIONS: Our results suggest that ATxA-IgG may be a significant risk factor for SLE prevalence and severity in Chinese populations.

The objectively measured walking speed and risk of hypertension in Chinese older adults: a prospective cohort study.

This study aims to investigate the longitudinal association between objectively measured walking speed and hypertension and to explore the potential effect modification of obesity on this association in Chinese older adults. The data from the Chinese Health and Retirement Prospective Cohort Study (CHARLS) during 2011-2015 was used. Walking speed was assessed by measuring the participants' usual gait in a 2.5 m course, and it was divided into four groups according to the quartiles (Q1, Q2, Q3, and Q4). A total of 2733 participants ≥60 years old were eligible for the analyses. After a follow-up of 4 years, 26.9% occurred hypertension. An inverse association was observed between walking speed and the risk of hypertension. There was an interaction between body mass index (BMI) and walking speed for the hypertension risk (P = 0.010). the association of walking speed with hypertension was stronger in overweight and obese participants (Q2, OR: 0.54, 95%CI = 0.34-0.85, P = 0.009; Q3, OR: 0.69, 95%CI = 0.44-1.08, P = 0.106; Q4, OR: 0.62, 95%CI = 0.39-0.98, P = 0.039). However, this association was not significant among lean ones. A similar trend was observed for systolic and diastolic blood pressure. In conclusion, higher walking speed was longitudinally associated with a lower risk of hypertension in Chinese older adults, especially among overweight and obese participants.

Living alone and the risk of depressive symptoms: a cross-sectional and cohort analysis based on the China Health and Retirement Longitudinal Study.

BACKGROUND: There were a few studies that examined the longitudinal association between living alone and depressive symptoms, and the vast majority of them were conducted in patients with certain diseases, such as heart failure, cancer, and glaucoma. This study aimed to examine the association between living alone and depressive symptoms in a large representative older Chinese population. METHODS: The China Health and Retirement Longitudinal Study (CHARLS) data from 2015 to 2018 were used. Living alone was defined as participants who did not live with others ever or more than 11 months in the past year at baseline. Depressive symptoms were measured using the 10-item Center for Epidemiological Studies-Depression Scale (CES-D10). The multivariate logistic regression was used to estimate the relationship between living alone and depressive symptoms. RESULTS: There were 5,311 and 2,696 participants ≥ 60 years old included in the cross-sectional and cohort analysis, respectively. The risk of depressive symptoms in participants who lived alone was significantly higher than those who lived with others in both cross-sectional (OR:1.33; 95%CI:1.14,1.54) and cohort analysis (OR:1.23; 95%CI:0.97,1.55). There was a significant interaction between financial support and living alone (Pinteraction = 0.008) on the risk of depressive symptoms. Stratified analyses showed that, compared to those who lived with others, the risk of depressive symptoms in participants who lived alone increased by 83% (OR:1.83; 95%CI:1.26,2.65) in participants receiving lower financial support. However, we did not find statistically significant associations in participants with medium (OR:1.10; 95%CI: 0.74,1.63) and higher financial support (OR: 0.87; 95%CI: 0.53,1.41). CONCLUSION: Living alone was associated with a higher risk of depressive symptoms in the Chinese older population, and this association was moderated by the receipt of financial support. Living alone may be an effective and easy predictor for early identification of high-risk populations of depression in the older population.

The potential DNA methylation markers of cardiovascular disease in patients with type 2 diabetes.

BACKGROUND: DNA methylation is associated with cardiovascular (CV) disease. However, in type 2 diabetes (T2D) patients, the role of gene methylation in the development of CV disease is under-studied. We aimed to identify the CV disease-related DNA methylation loci in patients with T2D and to explore the potential pathways underlying the development of CV disease using a two-stage design. METHODS: The participants were from the Jinan Diabetes Cohort Study (JNDCS), an ongoing longitudinal study designed to evaluate the development of CV risk in patients with T2D. In the discovery cohort, 10 diabetic patients with CV events at baseline were randomly selected as the case group, and another 10 diabetic patients without CV events were matched for sex, age, smoking status, and body mass index as the control group. In 1438 T2D patients without CV disease at baseline, 210 patients with CV events were identified after a mean 6.5-year follow-up. Of whom, 100 patients who experienced CV events during the follow-up were randomly selected as cases, and 100 patients who did not have CV events were randomly selected as the control group in the validation cohort. Reduced representation bisulfite sequencing and Targeted Bisulfite Sequencing were used to measure the methylation profiles in the discovery and validation cohort, respectively. RESULTS: In the discover cohort, 127 DMRs related to CV disease were identified in T2D patients. Further, we validated 23 DMRs mapped to 25 genes, of them, 4 genes (ARSG, PNPLA6, NEFL, and CRYGEP) for the first time were reported. There was evidence that the addition of DNA methylation data improved the prediction performance of CV disease in T2D patients. Pathway analysis identified some significant signaling pathways involved in CV comorbidities, T2D, and inflammation. CONCLUSIONS: In this study, we identified 23 DMRs mapped to 25 genes associated with CV disease in T2D patients, of them, 4 DMRs for the first time were reported. DNA methylation testing may help identify a high CV-risk population in T2D patients.

Association of polycyclic aromatic hydrocarbon internal exposure and urinary iodine concentration with thyroid volume in children.

Thyroid volume was proposed as a factor for malignancy in evaluating thyroid nodules. Previous studies have demonstrated the endocrine disrupting effect of polycyclic aromatic hydrocarbons (PAHs), but studies on the association between internal exposure of PAHs and thyroid volume are still scarce. In this work, we evaluated the association of polycyclic aromatic hydrocarbon internal exposure and urinary iodine concentration with thyroid volume in 590 school-age children without thyroid disease in Guangzhou, China. Urinary hydroxylated polycyclic aromatic hydrocarbons (OH-PAHs), urinary iodine concentrations, and thyroid volumes were measured. The mean concentrations of urinary iodine and ΣOH-PAHs were 271.1 µg/L and 3.27 µg/L, respectively, and the mean thyroid volume was 2.4 mL. The associations of urinary iodine and OH-PAH concentrations with thyroid volume were investigated by multivariable linear regression and the Bayesian kernel machine regression models. Urinary ΣOH-PAHs were observed to be significantly positively associated with thyroid volume in multivariable linear regression models. The increase in each unit in the log-transformed concentration of ΣOH-PAHs caused 3.88% change in thyroid volume. The Bayesian kernel machine regression model demonstrated a positive joint effect of increased urinary ΣOH-PAHs on thyroid volume. Moreover, urinary ΣOH-PAHs were statistically significant linked to urinary iodine, and iodine mediated the relationship between urinary OH-PAHs and thyroid volume with the mediated proportions of 15.2.

Temporal Trends in the Incidence and Mortality of Major Reproductive-Related Cancers in Women in Guangzhou From 2010 to 2020: A Joinpoint and Age-Period-Cohort Study.

Objective: To understand the temporal trends of cancer incidence and mortality in women in Guangzhou during the past 11 years and provide clues for future research. Methods: Data were obtained from the Guangzhou Cancer and Death Registry. Average annual percentage changes (AAPCs) in age-standardized incidence rates (ASIRs) and age-standardized mortality rates (ASMRs) were obtained by joinpoint regression. The age-period-cohort (APC) model was generated to quantify the effects of age, period, and cohort. Results: The ASIRs for cervical (AAPC = -4.3%) and ovarian (AAPC = -3.2%) cancers showed a downward trend during 2010-2020, and that for uterine cancer showed an upward trend. The ASMRs of breast (APC = 5.0%) and cervical (APC = 8.8%) cancers increased. The APC model highlights different age, period, and birth cohort effects depending on the cancer site. Conclusion: The ASIRs for cervical and ovarian cancers among women in Guangzhou showed a decreasing trend during the period. The APC model showed mortality for 4 cancers increased with age. Incidence and mortality decreased with increasing birth cohort. Annual reproductive cancer screening is recommended for women of appropriate age to reduce the disease burden.

Association between co-exposure of polycyclic aromatic hydrocarbons and chronic obstructive pulmonary disease among the US adults: results from the 2013-2016 National Health and Nutrition Examination Survey.

Although existing epidemiological studies have reported the relationship between single polycyclic aromatic hydrocarbon (PAH) exposure and chronic obstructive pulmonary disease (COPD), little is known about the impact of PAH mixture exposure on COPD. Therefore, we aimed to evaluate the associations of single and mixed exposures to PAHs with COPD in US adults using data from NHANES 2013-2016 by fitting three statistical methods, including multiple logistic regression, Bayesian kernel machine regression (BKMR), and quantile-based g-computation (qgcomp) models. This study included 1836 participants aged 40 and older. Multiple logistic regression showed that 2-FLU, 1-PHE, 1-PYR, and 2&3-PHE increased the risk of COPD after adjusting for all covariates. The BKMR model identified positive trends between PAH mixture and the risk of COPD in all adults and males when all PAHs were at or above their 55th percentile compared to all PAHs at their 50th percentile. The qgcomp model suggested that PAH co-exposure increased the risk of COPD (OR:1.44, 95%CI:1.09, 1.90) when each quartile increased in PAH mixture concentration, with 2-FLU having the highest weight. The combined impact also be observed in men. In conclusion, PAHs co-exposure was associated with a higher risk of COPD, especially in males, with the positive impact of 2-FLU being the most important.

Association of urinary iodine concentration with prediabetes/diabetes in adults: Analysis of the NHANES 2005-2016.

BACKGROUND & AIMS: Iodine is required for synthesizing thyroid hormones and regulating human metabolism. Iodine deficiency can lead to thyroid function abnormalities, which are closely associated with disturbances in glucose-insulin homeostasis. Research on the relationship between iodine and diabetes/prediabetes in adults was sparse and inconsistent. We assessed trends in urinary iodine concentration (UIC) and diabetes/prediabetes prevalence and focused on the association between iodine and diabetes/prediabetes among U.S. adults. METHODS: We analyzed the National Health and Nutrition Examination Survey (NHANES) data from the 2005-2016 cycles. Linear regression was employed to evaluate UIC and prediabetes/diabetes prevalence trends over time. Both multiple logistic regression and restricted cubic splines (RCS) were performed to evaluate the association of UIC with diabetes/prediabetes. RESULTS: A distinctly declining trend in median UIC and a significant increase in diabetes prevalence in U.S. adults from 2005 to 2016 were observed. The fourth quartile of UIC was associated with a 30% lower risk for prediabetes, compared with the first quartile (OR=0.70, 95% CI: 0.56-0.86, Ptrend=0.001). However, UIC was not significantly associated with the prevalence of diabetes. The RCS model suggested a significant nonlinear relationship between UIC and the risk of diabetes (P for nonlinearity =0.0147). Stratification analysis showed that the negative associations of UIC with the risk of prediabetes were more pronounced in participants who were men, aged 46-65, overweight, light alcohol drinkers, and nonactive smokers. CONCLUSIONS: Overall, the adults' median UIC in the U.S. population was a declining trend. However, diabetes prevalence increased significantly from 2005 to 2016. Higher UIC was associated with a lower risk of prediabetes.

Association between phthalates and sleep problems in the U.S. adult females from NHANES 2011-2014.

There is little research on the relationship between phthalates exposure and sleep problems in adult females, with existing studies only assessing the association between exposure to individual phthalates with sleep problems. We aimed to analyse the relationship between phthalates and sleep problems in 1366 US females aged 20 years and older from the 2011-2014 National Health and Nutrition Examination Survey (NHANES) by age stratification. Multivariate logistic regression showed that the fourth quartile of MECPP increased the risk of sleep problems in females aged 20-39 compared with the reference quartile (OR: 1.87, 95% CI: 1.14, 3.08). The WQS index was significantly associated with the sleep problems in females aged 20-39. In the BKMR, a positive overall trend between the mixture and sleep problems in females aged 20-39. In this study, we concluded that phthalates might increase the risk of sleep problems in females aged 20-39.

The Association between Prenatal Per- and Polyfluoroalkyl Substances Exposure and Neurobehavioral Problems in Offspring: A Meta-Analysis.

Exposure to per- and polyfluoroalkyl substances (PFAS) during pregnancy has been suggested to be associated with neurobehavioral problems in offspring. However, current epidemiological studies on the association between prenatal PFAS exposure and neurobehavioral problems among offspring, especially attention deficit/hyperactivity disorder (ADHD) and autism spectrum disorder (ASD), are inconsistent. Therefore, we aimed to study the relationship between PFAS exposure during pregnancy and ADHD and ASD in offspring based on meta-analyses. Online databases, including PubMed, EMBASE, and Web of Science, were searched comprehensively for eligible studies conducted before July 2021. Eleven studies (up to 8493 participants) were included in this analysis. The pooled results demonstrated that exposure to perfluorooctanoate (PFOA) was positively associated with ADHD in the highest quartile group. Negative associations were observed between perfluorooctane sulfonate (PFOS) and ADHD/ASD, including between perfluorononanoate (PFNA) and ASD. There were no associations found between total PFAS concentration groups and neurobehavioral problems. The trial sequential analyses showed unstable results. Our findings indicated that PFOA and PFOS exposure during pregnancy might be associated with ADHD in offspring and that prenatal PFOS and PFNA exposure might be associated with ASD in offspring. According to the limited evidence obtained for most associations, additional studies are required to validate these findings.

Association between blood metal exposures and hyperuricemia in the U.S. general adult: A subgroup analysis from NHANES.

BACKGROUND: The relationship between metal exposure and hyperuricemia is still controversial, especially in certain population groups. METHODS: This cross-sectional study included adults from NHANES 2011-2016. Seven metals, including Pb, Cd, Hg, Mn, Se, Cu, and Zn, were detected in blood by ICP‒MS. Multivariable logistic regression, LASSO, and BKMR models were used to assess the effects of single and mixed metal exposures and hyperuricemia. Moreover, this association was analyzed by sex, BMI, and age. RESULTS: A total of 4074 individuals were included in our final analysis, and 825 (20.3%) people were classified as having hyperuricemia. In logistic regression, Pb (Q4: OR [95% CI]: 1.50 [1.00, 2.24]) was associated with hyperuricemia after adjusting for all covariates. LASSO penalized regression analysis further indicated positive associations of lead and zinc with hyperuricemia. In BKMR analysis, U-shaped dose‒response curves were generated for Se, Mn, Cu, and Zn when fixing the other metals in the 50th percentile. A significant positive trend was found between mixed metal exposure and hyperuricemia, in which blood Se, Zn, and Cd had the highest PIP (PIP = 0.651, 0.549, and 0.530, respectively). In weighted logistic regression, subgroup analyses revealed a significant association between Pb and hyperuricemia among the non-overweight group. Significant positive trends between mixed metals and hyperuricemia were found in the male and non-overweight groups in the BKMR models. CONCLUSION: Our study suggests that a higher concentration of mixed metal might increase the risk of hyperuricemia in U.S. adults. Males and people with a BMI under 25 are more likely to be affected.

Relationship between phthalates exposures and hyperuricemia in U.S. general population, a multi-cycle study of NHANES 2007-2016.

BACKGROUND: Phthalates exposure might cause kidney damage and a potential risk for hyperuricemia. However, direct evidence on phthalates and hyperuricemia is somewhat limited. OBJECTIVE: To examine associations between 10 phthalates metabolites and hyperuricemia in a large-scale representative of the U.S. METHODS: A cross-sectional study of 6865 participants aged over 20 from NHANES 2007-2016 was performed. All participants had complete data on ten phthalate metabolites (MECPP, MnBP, MEHHP, MEOHP, MiBP, cx-MiNP, MCOP, MCPP, MEP, MBzP), hyperuricemia, and covariates. We used multivariable logistics regression, restricted cubic splines (RCS) model, and Bayesian kernel machine regression (BKMR) models to assess single, nonlinear, and mixed relationships between phthalate metabolites and hyperuricemia. As a complement, we also assessed the relationship between phthalate metabolites and serum uric acid (SUA) levels. RESULTS: The multivariable logistics regression showed that MECPP, MEOHP, MEHHP, MBzP, and MiBP were generally positively associated with hyperuricemia (PFDR < 0.05), especially in MiBP (Q3 (OR (95 %): 1.31 (1.02, 1.68)) and Q4 (OR (95 %): 1.68 (1.27, 2.24)), compared to Q1). All ten phthalate metabolites had a linear dose-response relationship with hyperuricemia in the RCS model (P for non-linear >0.05). BKMR showed that mixed phthalate metabolites were associated with a higher risk of hyperuricemia, with MBzP contributing the most (groupPIP = 0.999, condPIP = 1.000). We observed the consistent results between phthalate metabolites and SUA levels in three statistical models. The relationship between phthalate metabolites and hyperuricemia remained in the sensitivity analysis. CONCLUSIONS: The present study suggests that exposure to phthalates, individually or jointly, might increase the risk of hyperuricemia. Since hyperuricemia influences on the quality of life, more explorations are needed to confirm these findings.

Associations of single and multiple organophosphate pesticide exposure with female infertility in the USA: data from the 2015-2018 National Health and Nutrition Examination Survey.

Substantial evidence has shown that organophosphate pesticide (OPP) exposure altered the reproductive system functions, such as prolonged menstrual cycles, sexual hormone imbalance, and changes in ovarian weight. However, the association of OPP exposure with female infertility is unclear. We explored the relationships of four single OPP metabolites and their mixed exposure with self-reported infertility among women aged 20-50 in the USA using the data from two cycles (2015-2016 and 2017-2018) of the National Health and Nutrition Examination Survey (NHANES) by multiple logistic regression, Bayesian kernel machine regression (BKMR), and quantile g-computation (QGC). Eventually, 659 females were included in our study. Among these females, 77 participants were ever infertile. Multiple logistic regression showed that the odds ratios (ORs) in the second and third tertiles of dimethylphosphate (DMP) for female infertility were 2.53 (95% confidence interval (95%CI): 1.20-5.32, P value = 0.016) and 2.96 (95%CI: 1.18-7.47, P value = 0.023) compared to the lowest tertile after adjusting for all covariates (P for trend = 0.022). A significantly positive association between the mixed OPP metabolites and infertility was observed in the BKMR model, in which DMP had the highest posterior inclusion probability (PIP = 0.741). The QGC model showed similar results, in which OPP metabolite mixtures increased the risk of female infertility, with DMP as a significantly positive contributor to the outcome. This study revealed the potential harm of OPP mixtures for female infertility in the USA, and DMP played the most critical role in female infertility risk among all OPP metabolites.

Association between Perfluoroalkyl and Polyfluoroalkyl Substances and Women's Infertility, NHANES 2013-2016.

Perfluoroalkyl and polyfluoroalkyl substances (PFASs) are widely used in consumer products. However, the role of PFAS in infertility is still poorly understood. A total of 788 women from the 2013-2016 nationally representative NHANES were included to explore the association between PFAS exposure and self-reported infertility. Six PFAS, including PFDE, PFNA, PFHxS, n-PFOA, n-PFOS, and Sm-PFOS, were detected by online SPE-HPLC-TIS-MS/MS. We used the generalized linear regression model (GLM), generalized additive models (GAM), and Bayesian kernel machine regression (BKMR) to assess the single effects, non-linear relationships, and mixed effects on women's infertility, respectively. The prevalence of self-reported infertility was 15.54% in this study. In GLM, n-PFOA showed a negative association with self-reported infertility in women for the Q3 (OR: 0.396, 95% CI: 0.119, 0.788) and Q4 (OR: 0.380, 95% CI: 0.172-0.842) compared with Q1 (p for trend = 0.013). A negative trend was also observed in n-PFOS and ∑PFOS (p for trend < 0.05). In GAM, a non-linear relationship was revealed in Sm-PFOS, which exhibits a U-shaped relationship. The BKMR model indicated that there might be a joint effect between PFAS and women's infertility, to which PFNA contributed the highest effect (PIP = 0.435). Moreover, age stratification analysis showed a different dose-response curve in under and above 35 years old. Women under the age of 35 have a more noticeable U-shaped relationship with infertility. Therefore, the relatively low level of mixed PFAS exposure was negatively associated with self-reported infertility in women in general, and the impact of PFAS on infertility may vary among women of different age groups. Further studies are needed to determine the etiological relationship.

Predictive value of baseline metabolic tumor volume for non-small-cell lung cancer patients treated with immune checkpoint inhibitors: A meta-analysis.

Background: Immune checkpoint inhibitors (ICIs) have emerged as a promising treatment option for advanced non-small-cell lung cancer (NSCLC) patients, highlighting the need for biomarkers to identify responders and predict the outcome of ICIs. The purpose of this study was to evaluate the predictive value of baseline standardized uptake value (SUV), metabolic tumor volume (MTV) and total lesion glycolysis (TLG) derived from 18F-FDG-PET/CT in advanced NSCLC patients receiving ICIs. Methods: PubMed and Web of Science databases were searched from January 1st, 2011 to July 18th, 2022, utilizing the search terms "non-small-cell lung cancer", "PET/CT", "standardized uptake value", "metabolic tumor volume", " total lesion glycolysis", and "immune checkpoint inhibitors". Studies that analyzed the association between PET/CT parameters and objective response, immune-related adverse events (irAEs) and prognosis of NSCLC patients treated with ICIs were included. We extracted the hazard ratio (HR) with a 95% confidence interval (CI) for progression-free survival (PFS) and overall survival (OS). We performed a meta-analysis of HR using Review Manager v.5.4.1. Results: Sixteen studies were included for review and thirteen for meta-analysis covering 770 patients. As for objective response and irAEs after ICIs, more studies with consistent assessment methods are needed to determine their relationship with MTV. In the meta-analysis, low SUVmax corresponded to poor PFS with a pooled HR of 0.74 (95% CI, 0.57-0.96, P=0.02). And a high level of baseline MTV level was related to shorter PFS (HR=1.45, 95% CI, 1.11-1.89, P<0.01) and OS (HR, 2.72; 95% CI, 1.97-3.73, P<0.01) especially when the cut-off value was set between 50-100 cm3. SUVmean and TLG were not associated with the prognosis of NSCLC patients receiving ICIs. Conclusions: High level of baseline MTV corresponded to shorter PFS and OS, especially when the cut-off value was set between 50-100 cm3. MTV is a potential predictive value for the outcome of ICIs in NSCLC patients.