Environmental perchlorate, thiocyanate, and nitrate exposures and bone mineral density: a national cross-sectional study in the US adults.

Associations of perchlorate, thiocyanate, and nitrate exposures with bone mineral density (BMD) in adults have not previously been studied. This study aimed to estimate the associations of individual and concurrent exposure of the three chemicals with adult BMD. Based on National Health and Nutrition Examination Survey (NHANES, 2011-2018), 1618 non-pregnant adults (age ≥ 20 years and 47.0% female) were included in this study. Survey-weighted linear regression models were used to estimate individual urinary perchlorate, thiocyanate, and nitrate concentrations with lumbar spine BMD and total BMD in adults. Then, weighted quantile sum (WQS) regression and Bayesian kernel machine regression (BKMR) models were conducted to evaluate associations of co-occurrence of the three chemicals with adult BMD. In all participants, nitrate exposure was inversely associated with lumbar spine BMD (ß = - 0.054, 95%CI: - 0.097, - 0.010). In stratification analyses, significant inverse associations were observed in female and participants older than 40 years old. In WQS regressions, significant negative associations of the weighted sum of the three chemicals with total and lumbar spine BMD (ß = - 0.014, 95%CI: - 0.021, - 0.007; ß = - 0.011, 95%CI: - 0.019, - 0.004, respectively) were found, and the dominant contributor was nitrate. In the BKMR models, non-linear dose-response associations of nitrate exposure with lumbar spine and total BMD were observed. These findings suggested that environmental perchlorate, thiocyanate, and nitrate exposure may reduce adult BMD and nitrate is the main contributor.

Corrigendum: Dietary intervention improves metabolic levels in patients with type 2 diabetes through the gut microbiota: a systematic review and meta-analysis.

[This corrects the article DOI: 10.3389/fnut.2023.1243095.].

Joint effects of phenol, chlorophenol pesticide, phthalate, and polycyclic aromatic hydrocarbon on bone mineral density: comparison of four statistical models.

Exposure to phenols, phthalates, pesticides, and polycyclic aromatic hydrocarbons (PAHs) can harm the skeleton. However, data about the joint effects of these chemicals' mixture on bone health are limited. The final analysis involved 6766 participants aged over 20 years recruited from the National Health and Nutrition Examination Survey. Generalized linear regression, weighted quantile sum (WQS) regression, Bayesian kernel machine regression (BKMR), and quantile g-computation (qgcomp) were performed to investigate the association of the urinary levels of chemicals (three phenols, two chlorophenol pesticides, nine phthalates, and six polycyclic aromatic hydrocarbon [PAH] metabolites) with bone mineral density (BMD) measurements and osteoporosis (OP) risk. Generalized linear regression identified that benzophenone-3, 2,4-dichlorophenol, mono-n-butyl phthalate, 1-napthol, 3-fluorene, 2-fluorene, and 1-phenanthrene were significantly associated with lower BMD and increased OP risk. The WQS index was negatively associated with total femur, femoral neck, and lumbar spine vertebra 1 (L1) BMD among all the participants, with corresponding ß (95% confidence interval) values of -0.028 g/cm2 (-0.040, -0.017), -0.015 g/cm2 (-0.025, -0.004), and -0.018 g/cm2 (-0.033, -0.003). In the BKMR analysis, the overall effect of the mixture was significantly associated with femoral neck BMD among males and OP risk among females. The qgcomp model found a significant association between co-exposure and L1 BMD among all the participants and among males. Our study presents compelling epidemiological evidence that co-exposure to phenols, chlorophenol pesticides, phthalates, and PAHs is associated with reduced BMD and elevated OP risk. It provides epidemiologic evidence for the detrimental effects of these chemicals on bone health.

Exposure to phenols, chlorophenol pesticides, phthalate and PAHs and mortality risk: A prospective study based on 6 rounds of NHANES.

OBJECTIVES: Human exposure to various endocrine disrupting chemicals (EDCs) is widespread and long-lasting. The primary objective of this study was to prospectively evaluate the association of combined exposure of phenols, chlorophenol pesticides, phthalate and polycyclic aromatic hydrocarbons (PAHs) and mortality risk in a representative US population. METHODS: The data on urinary levels of phenols, chlorophenol pesticides, phthalates, and PAH metabolites, were collected from participants aged ≥20 years in six rounds of the National Health and Nutrition Examination Survey (NHANES) (2003-2014). NHANES-linked death records up to December 31, 2015 were used to ascertain mortality status and cause of death. Cox proportional hazards and competing risk models were mainly used for chemical and mortality risk association analysis. The weighted quantile sum (WQS) regression and the least absolute shrinkage and selection operator regression were employed to estimate the association between EDC co-exposure and mortality risk. RESULTS: High levels of mono-n-butyl phthalate, monobenzyl phthalate, and 1-napthol were significantly associated with increased risk of all cause, cardiovascular disease (CVD) and cancer mortality among all participants. WQS index was associated with the risks of all-cause (hazard ratio [HR] = 1.389, 95%CI: 1.155-1.669) and CVD mortality (HR = 1.925, 95%CI: 1.152-3.216). High co-exposure scores were associated with elevated all-cause (HR = 2.842, 95% CI: 1.2.094-3.858), CVD (HR = 1.855, 95% CI: 1.525-2.255), and cancer mortality risks (HR = 2.961, 95% CI: 1.468-5.972). The results of subgroup analysis, competing risk model, and sensitivity analysis were generally consistent with the findings from the main analyses, indicating the robustness of our findings. CONCLUSIONS: This study provided the first epidemiological evidence that co-exposure to EDC at fairly low levels contributed to elevated mortality risk among US adults. The underlying mechanisms for the effects of EDC co-exposure on human health are worthy of future exploration.

Composite dietary antioxidant intake and osteoporosis likelihood in premenopausal and postmenopausal women: a population-based study in the United States.

OBJECTIVE: Osteoporosis is a skeletal disease characterized by low bone mass, reduced bone strength, and increased fracture risk. We aimed to investigate the association between combined dietary antioxidant intake and the likelihood of osteoporosis in premenopausal and postmenopausal women, based on data from the National Health and Nutrition Examination Survey. METHODS: Nutrient intake data were obtained using two 24-hour recalls. Composite dietary antioxidant index (CDAI), which refers to the intake amounts of ß-carotene, vitamin A, vitamin C, vitamin E, selenium, zinc, copper, and iron, was then constructed. Prevalent osteoporosis was defined according to bone mineral density T scores of ≤ -2.5 and self-reports. Multiple logistic and Poisson regression models were used for association analyses. RESULTS: A total of 3,418 participants (1,157 premenopausal and 2,261 postmenopausal women) 40 years or older were included, 776 (22.70%) of whom had prevalent osteoporosis. In terms of individual nutrients, postmenopausal women in the highest CDAI quartiles for dietary ß-carotene, vitamin A, vitamin C, and iron intakes had a low likelihood of osteoporosis. Regarding the CDAI-osteoporosis association, postmenopausal women in the highest quartile were less likely to have osteoporosis (OR Q3 vs Q1 , 0.64; 95% CI, 0.43-0.96; OR Q4 vs Q1 , 0.56; 95% CI, 0.35-0.89; P for trend = 0.013), after controlling for covariates. CONCLUSIONS: CDAI was negatively associated with the likelihood of osteoporosis in postmenopausal women. Our findings suggest that the combined intake of antioxidant nutrients can help reduce the likelihood of osteoporosis in women.

Association between multiple vitamins and bone mineral density: a cross-sectional and population-based study in the NHANES from 2005 to 2006.

BACKGROUND: Bone mineral density (BMD) alterations in response to multivitamin exposure were rarely studied. Our study assessed the association of coexposure to six types of vitamins (i.e., vitamins B12, B9, C, D, A and E) with BMD measurements in adults in the US. METHODS: Data were collected from participants aged ≥ 20 years (n = 2757) in the U.S. National Health and Nutrition Examination Surveys (NHANES) from 2005 to 2006. Multiple linear regression, restricted cubic splines, principal component analysis (PCA) and weighted quantile sum (WQS) regression were performed for statistical analysis. RESULTS: The circulating levels of vitamins B12 and C were positively associated with BMDs, and an inverted L-shaped exposure relationship was observed between serum vitamin C and BMDs. PCA identified two principal components: one for 'water-soluble vitamins', including vitamins B12, B9 and C, and one for 'fat-soluble vitamins', including vitamins A, D and E. The former was positively associated with total femur (ß = 0.009, 95%CI: 0.004, 0.015) and femoral neck (ß = 0.007, 95%CI: 0.002, 0.013) BMDs, and the latter was negatively associated with BMDs with non-statistical significance. The WQS index constructed for the six vitamins was significantly related to total femur (ß = 0.010, 95%CI: 0.001, 0.018) and femoral neck (ß = 0.008, 95%CI: 0.001, 0.015) BMDs, and vitamins B12 and C weighted the most. The WQS index was inversely related to BMDs with non-statistical significance, and vitamins E and A weighted the most. CONCLUSION: Our findings suggested a positive association between water-soluble vitamin coexposure and BMD, and the association was mainly driven by vitamins B12 and C. Negative association between fat-soluble vitamin coexposure and BMD was indicated, mainly driven by vitamins E and A. An inverted L-shaped exposure relationship was found between vitamin C and BMD.

Dietary intervention improves metabolic levels in patients with type 2 diabetes through the gut microbiota: a systematic review and meta-analysis.

Background: Poor dietary structure plays a pivotal role in the development and progression of type 2 diabetes and is closely associated with dysbiosis of the gut microbiota. Thus, the objective of this systematic review was to assess the impact of dietary interventions on improving gut microbiota and metabolic levels in patients with type 2 diabetes. Methods: We conducted a systematic review and meta-analysis following the PRISMA 2020 guidelines. Results: Twelve studies met the inclusion criteria. In comparison to baseline measurements, the high-fiber diet produced substantial reductions in FBG (mean difference -1.15 mmol/L; 95% CI, -2.24 to -0.05; I2 = 94%; P = 0.04), HbA1c (mean difference -0.99%; 95% CI, -1.93 to -0.03; I2 = 89%; P = 0.04), and total cholesterol (mean difference -0.95 mmol/L; 95% CI, -1.57 to -0.33; I2 = 77%; P = 0.003); the high-fat and low-carbohydrate diet led to a significant reduction in HbA1c (mean difference -0.98; 95% CI, -1.50 to -0.46; I2 = 0%; P = 0.0002). Within the experimental group (intervention diets), total cholesterol (mean difference -0.69 mmol/L; 95% CI, -1.27 to -0.10; I2 = 52%; P = 0.02) and LDL-C (mean difference -0.45 mmol/L; 95% CI, -0.68 to -0.22; I2 = 0%; P < 0.0001) experienced significant reductions in comparison to the control group (recommended diets for type 2 diabetes). However, no statistically significant differences emerged in the case of FBG, HbA1c, HOMA-IR, and HDL-C between the experimental and control groups. The high dietary fiber diet triggered an augmented presence of short-chain fatty acid-producing bacteria in the intestines of individuals with T2DM. In addition, the high-fat and low-carbohydrate diet resulted in a notable decrease in Bacteroides abundance while simultaneously increasing the relative abundance of Eubacterium. Compared to a specific dietary pattern, personalized diets appear to result in the production of a greater variety of beneficial bacteria in the gut, leading to more effective blood glucose control in T2D patients. Conclusion: Dietary interventions hold promise for enhancing metabolic profiles in individuals with T2D through modulation of the gut microbiota. Tailored dietary regimens appear to be more effective than standard diets in improving glucose metabolism. However, given the limited and highly heterogeneous nature of the current sample size, further well-designed and controlled intervention studies are warranted in the future.

Association between SEMA3A signaling pathway genes and BMD/OP risk: An epidemiological and experimental study.

Objective: This study aimed to explore the associations of genetic variants in the semaphorin 3A (SEMA3A) signaling pathway genes, including SEMA3A, NRP1, PLXNA1, PLXNA2 and PLXNA3 with osteoporosis (OP) risk and bone mineral density (BMD) in a Chinese Han older adult population. Study design and method: A two-stage design was adopted. Total of 47.8kb regions in the 5 genes were sequenced using targeted next-generation sequencing (NGS) technology in the discovery stage, and the discovered OP-related single nucleotide polymorphisms (SNPs) were further genotyped using improved multiple linkage detection reaction technique in the validation stage. Methods of ALP/TRAP staining, real-time fluorescent quantitative PCR, and cell proliferation and apoptosis assays were performed with MC3T3-E1 and RAW 264.7 cell lines to clarify biological effects of observed functional variants in cell lines responsible for bone mass remodeling. Results: Total of 400 postmenopausal women (211 OP cases) were involved in the discovery stage, where 6 common and 4 rare genetic variants were found to be associated with OP risk. In the validation stage among another 859 participants (417 women, 270 OP cases), the PLXNA2 rs2274446 T allele was associated with reduced OP risk and increased femoral neck (FN) BMD compared to the C allele. Moreover, significant associations of NRP1 rs2070296 with FN BMD/OP risk and of NRP1 rs180868035 with lumbar spine and FN BMDs were also observed in the combination dataset analysis. Compared to the osteoblasts/osteoclasts transfected with the wild-type NRP1 rs180868035, those transfected with the mutant-type had reduced mRNA expression of osteoblastic genes (i.e., ALP, RUNX2, SP7 and OCN), while elevated mRNA expression of osteoclastic genes (i.e., TRAP, NFATc1 and CTSK). Furthermore, mutant NRP1 rs180868035 transfection inhibited osteoblast proliferation and osteoclast apoptosis, while promoted osteoclast proliferation and osteoblast apoptosis in corresponding cell lines. Conclusion: Genetic variants located in NRP1 and PLXNA2 genes were associated with OP risk and BMD. The NRP1 rs180868035 affects bone metabolism by influencing osteoblasts and osteoclasts differentiation, proliferation and apoptosis.

An evaluation index system for regional mobile SARS-CoV-2 virus nucleic acid testing capacity in China: a modified Delphi consensus study.

BACKGROUND: Large-scale detection has great potential to bring benefits for containing the COVID-19 epidemic and supporting the government in reopening economic activities. Evaluating the true regional mobile severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) virus nucleic acid testing capacity is essential to improve the overall fighting performance against this epidemic and maintain economic development. However, such a tool is not available in this issue. We aimed to establish an evaluation index system for assessing the regional mobile SARS-CoV-2 virus nucleic acid testing capacity and provide suggestions for improving the capacity level. METHODS: The initial version of the evaluation index system was identified based on massive literature and expert interviews. The Delphi method questionnaire was designed and 30 experts were consulted in two rounds of questionnaire to select and revise indexes at all three levels. The Analytic Hierarchy Process method was used to calculate the weight of indexes at all three levels. RESULTS: The evaluation index system for assessing the regional mobile SARS-CoV-2 virus nucleic acid testing capacity, including 5 first-level indexes, 17 second-level indexes, and 90 third-level indexes. The response rates of questionnaires delivered in the two rounds of consultation were 100 and 96.7%. Furthermore, the authority coefficient of 30 experts was 0.71. Kendall's coordination coefficient differences were statistically significant (P < 0.001). The weighted values of capacity indexes were established at all levels according to the consistency test, demonstrating that 'Personnel team construction' (0.2046) came first amongst the five first-level indexes, followed by 'Laboratory performance building and maintenance' (0.2023), 'Emergency response guarantee' (0.1989), 'Information management system for nucleic acid testing resources' (0.1982) and 'Regional mobile nucleic acid testing emergency response system construction' (0.1959). CONCLUSION: The evaluation system for assessing the regional mobile SARS-CoV-2 virus nucleic acid testing capacity puts forward a specific, objective, and quantifiable evaluation criterion. The evaluation system can act as a tool for diversified subjects to find the weak links and loopholes. It also provides a measurable basis for authorities to improve nucleic acid testing capabilities.

Association Between Water Intake and Mortality Risk-Evidence From a National Prospective Study.

Background: Few studies have explored the association between water intake and mortality risk, and the findings were inconsistent. Objective: This study aimed to explore the water intake-mortality association, utilizing the data from the National Health and Nutrition Examination Survey (NHANES) and the 2015 public-linked mortality files released by the National Center for Health Statistics. Methods: We used the diet- and mortality-linked data of a total of 35,463 adults (17,234 men) aged ≥20 years in the NHANESs 1999-2014 to perform a prospective study. The multivariate-adjusted Cox proportional hazards model was used to explore the associations of the amount of water intake (expressed by total water, plain water, beverage, and food water) and water intake proportion (expressed by the percentage of each kind of water) with mortality risks due to all causes, malignant neoplasms/cancer, and heart disease. The restricted cubic spline plots were adopted to clarify the dose-response relationships among them. Results: With a median of 88 months (interquartile range: 49-136 months) follow-up, a total of 4,915 all-cause deaths occurred, including 1,073 and 861 deaths from malignant neoplasms/cancer and heart disease, respectively. The amount of water intake in either type was negatively associated with all-cause mortality risk. Additionally, the negative linear dose-response relationships of water intake and all-cause mortality risk were found for all types of water except for food water, which followed a non-linear pattern. Similarly, compared to the lowest quartile (beverage water intake: <676 g/day; food water intake: <532 g/day), beverage and food water intakes in the range of 1,033-1,524 and 1,612-3,802 g/day were associated with decreased malignant neoplasms/cancer mortality risk. A U-shaped dose-response relationship was found for beverage water intake and malignant neoplasms/cancer mortality risk and a negative linear dose-response relationship was found for food water intake and malignant neoplasms/cancer mortality risk. Coffee and/or tea consumption was/were negatively associated with mortality risks due to all causes and malignant neoplasms/cancer. No significant associations of water intake proportion and mortality risks were found. Conclusion: Our findings demonstrated that higher water intake is associated with lower mortality risks among the United States population.

Manganese, iron, copper, and selenium co-exposure and osteoporosis risk in Chinese adults.

BACKGROUND & AIMS: Previous experimental studies demonstrated that either deficient or excessive trace elements, such as manganese (Mn), iron (Fe), copper (Cu) and selenium (Se), are detrimental to bone health. Epidemiologic evidence for the effect of the four trace elements on osteoporosis (OP) risk remains inadequate. This cross-sectional study aimed to examine their associations with the OP risk among Chinese adults. METHODS: Concentrations of Mn, Fe, Cu, and Se were measured in plasma using an inductively coupled plasma mass spectrometer among 627 Chinese adults aged ≥ 50 years. Individual effect of the four elements on OP risk was analyzed by logistic regression and Bayesian Kernel Machine Regression (BKMR) models. The latter model was also adopted to examine the exposure-response relationships and joint effects of the four elements on OP risk. RESULTS: The median Mn, Fe, Cu, and Se levels were 4.78, 1026.63, 904.55, and 105.39 µg/L, respectively, in all participants. Inverse associations of Fe and Se levels with OP risk were observed in the logistic regression model. BKMR analysis revealed a U-shape pattern for the Fe-OP association, and a reduced OP risk in response to co-exposure of the four elements above the 50th percentiles but an elevated one in response to that below the 50th percentiles. Sex discrepancy existed in the findings. No interactions were found for the four elements affecting OP risk. CONCLUSIONS: Co-exposure to Mn, Fe, Cu, and Se was associated with improved bone density, where Fe contributed most to the beneficial effect. Further studies are needed to verify these findings and explore the underlying biological mechanism.

Multiple vitamin co-exposure and mortality risk: A prospective study.

BACKGROUND & AIMS: Existing epidemiological studies explored the associations of circulating vitamins and mortality focusing on individual vitamin effects, and controversial findings were obtained. The joint effects of multiple vitamin co-exposure are worth studying. The study aimed to elucidate the associations of circulating vitamins and the joint effects of these vitamins' co-exposure with all-cause and cause-specific mortality risks. METHODS: We prospectively evaluated the associations of the concentrations of six kinds of vitamins (A, D, E, C, B12 and B9) in serum with risks for all-cause and cause-specific mortalities among U.S. adults. Mortality status and cause of death were determined by NHANES-linked public available files dated up to 31 December 2015. An unsupervised K-means clustering method was used to cluster the participants into several vitamin co-exposure patterns. The Cox proportional hazards model was used for statistical analysis. RESULTS: A total of 1404 deaths occurred during a median of 10.9 years follow-up among 8295 participants. In multivariable adjustment, increasing levels of vitamin D were associated with reduced all-cause and cause-specific mortality risks. A J-shaped nonlinear exposure-response relationship was observed between all studied vitamins (except for vitamin D) and all-cause mortality risk. Four co-exposure patterns were generated based on the studied vitamins, as follows: low-level exposure (cluster 1), vitamin A/D exposure (cluster 2), water-soluble vitamin exposure (cluster 3) and high-level exposure (cluster 4). Compared with those in cluster 1, participants in cluster 2 had lower all-cause and cancer mortality risks, with hazard ratios (95% confidence intervals [CIs]) of 0.67 (0.53, 0.85) and 0.45 (0.29, 0.71), respectively. CONCLUSIONS: The findings in this study indicated that high circulating vitamin D levels were associated with reduced mortality risk among U.S. adults. Vitamin co-exposure at moderate levels appropriately contributed to low all-cause and cancer mortality risks. Our findings provided a novel perspective for exploring the joint health effects of multivitamin co-exposure. Future investigations are needed to further unravel the underlying mechanisms of possible vitamin interactions.

Repeated measurements of 21 urinary metabolites of volatile organic compounds and their associations with three selected oxidative stress biomarkers in 0-7-year-old healthy children from south and central China.

Human beings are extensively and concurrently exposed to multiple volatile organic compounds (VOCs, including some Class I human carcinogens), which may induce oxidative stress in human body. Data on urinary metabolites of VOCs (mVOCs) among young children are limited. No studies have examined their inter-day variability of mVOCs and their associations with oxidative stress biomarkers (OSBs) using repeated urine samples from children. In this study, we measured twenty one mVOCs and three OSBs [8-hydroxy-2'-deoxyguanosine (8-OHdG; for DNA), 8-hydroxyguanosine (8-OHG; for RNA], and 4-hydroxy nonenal mercapturic acid (HNEMA; for lipid)] in 390 urine samples of 130 children (three samples on three consecutive days provided by each participant) aged 0-7 years from September 2018 to January 2019 in Shenzhen, south China, and Wuhan, central China. HPMMA (3-hydroxypropyl-1-methyl mercapturic acid/N-Acetyl-S-(3-hydroxypropyl-1-methyl)-l-cysteine), 3HPMA (3-hydroxypropyl mercapturic acid/N-Acetyl-S-(3-hydroxypropyl)-l-cysteine), and ATCA (2-aminothiazoline-4-carboxylic acid) had higher specific gravity-adjusted median concentrations (1 383, 286, and 273 µg/L, respectively) than the others. Intraclass correlation coefficients of mVOCs ranged from 0.29 to 0.71. After false-discovery rate (FDR, defined as FDR q-value < 0.05) adjustment, linear mixed-effects models revealed that 14 mVOCs were positively associated with 8-OHdG (ß range: 0.09-0.37), 11 mVOCs were positively associated with 8-OHG (ß range: 0.08-0.30), and 11 mVOCs were positively associated with HNEMA (ß range: 0.21-0.70) in urine. Considering the weight of the mVOC index accounted for the associations, based on the weighted quantile sum regression model, parent compounds of DHBMA (3,4-dihydroxybutyl mercapturic acid/N-Acetyl-S-(3,4-dihydroxybutyl)-l-cysteine) and t,t-MA (trans,trans-muconic acid) should be listed as priority VOCs for management to mitigate health risks. For the first time, this study characterized the inter-day variability of urinary mVOCs and their associations with selected OSBs (8-OHdG, 8-OHG, and NHEMA) in young, healthy Chinese children.

Urinary parabens and their derivatives associated with oxidative stress biomarkers in children from South and Central China: Repeated measures.

Previous studies implied that elevated exposure to parabens may result in increased oxidative stress. However, the association between exposure to paraben derivatives and oxidative stress biomarkers in children has been rarely studied. This study examined the associations between exposure to paraben derivatives and oxidative stress biomarkers in Chinese children. Nine targeted compounds of parabens and their derivatives including methyl paraben (MeP), ethyl paraben (EtP), propyl paraben (PrP), butyl paraben (BuP), p-hydrox4ybenzoic acid (p-HB), 3,4-dihydroxy benzoic acid (3,4-DHB), benzoic acid, methyl 3,4-dihydroxybenzoate (rOH-MeP), and ethyl 3,4-dihydroxybenzoate (rOH-EtP) were detected in urine collected from 139 children from South and Central China. Additionally, 8-hydroxy-2'-deoxyguanosine (8-OHdG), 8-hydroxyguanosine (8-OHG), and 4-hydroxy-2-nonenal mercapturic acid (HNE-MA) were measured as oxidative stress biomarkers. All targeted compounds (except for BuP) were frequently detected in urine (detection frequencies ranged 80.8%-100%). Linear mixed effects model revealed that all targeted compounds (with detection frequencies >50%), except for EtP, were significantly associated with an increase in 8-OHdG. rOH-EtP was found to be significantly associated with 8-OHG (ß = 0.12; 95% confidence interval [95% CI]: 0.08, 0.16) positively. In addition, PrP and benzoic acid were associated with elevated levels of HNE-MA. Weighted quantile sum regression revealed that co-exposure to the targeted compounds was positively associated with 8-OHdG (ß = 0.17; 95% CI: 0.12, 0.22), 8-OHG (ß = 0.14; 95% CI: 0.10, 0.18), and HNE-MA (ß = 0.43; 95% CI: 0.27, 0.59); rOH-EtP and benzoic acid were the major contributors for the combined effects on oxidative stress of nucleic acids and lipid, respectively. Our findings provide new evidence for the effects of exposure to paraben derivatives on nucleic acid oxidative damage and lipid peroxidation in children.

Integrative Analysis of LGR5/6 Gene Variants, Gut Microbiota Composition and Osteoporosis Risk in Elderly Population.

Objective: This study aimed to explore the relationships between the common variants of R-spondin/Wnt signaling genes, gut microbiota composition, and osteoporosis (OP) risk in elderly Chinese Han population. Design: Dual-energy X-ray absorptiometry was used to obtain the OP-associated measurements at multiple skeleton sites among all 1,168 participants. Genotyping data was obtained by using the next-generation sequencing in the discovery stage (n = 400, 228 OP patients) and SNPscan technology in the replication stage (n = 768, 356 OP patients). Bioinformatic analysis was performed to provide more evidence for the genotype-OP associations. The 16S ribosomal RNA gene high-throughput sequencing technology was adopted to explore OP-associated gut microbiota variations. Results: The genetic variants of rs10920362 in the LGR6 gene (P-FDR = 1.19 × 10-6) and rs11178860 in the LGR5 gene (P-FDR = 1.51 × 10-4) were found to associate with OP risk significantly. Several microbial taxa were associated with the BMDs and T-scores at multiple skeleton sites. The associations between rs10920362 and BMD-associated microbiota maintained significance after adjusting confounders. The rs10920362 CT/TT genotype associated with a decreased relative abundance of Actinobacteria (ß = -1.32, P < 0.001), Bifidobacteriaceae (ß = -1.70, P < 0.001), and Bifidobacterium (ß = -1.70, P < 0.001) compared to the CC genotype. Conclusion: Our findings suggested that the variants loci of LGR6 may be associate with OP pathogenesis via gut microbiota modifications. The relationship between host genetics and gut microbiome provides new perspectives about OP prevention and treatment.

Associations of multiple metals with bone mineral density: A population-based study in US adults.

Epidemiologic studies focus on combined effects of multiple metals on bone mineral density (BMD) are scarce. Therefore, this study was conducted to examine associations of multiple metals exposure with BMD. Data of adults aged ≥20 years (n = 2545) from the US National Health and Nutrition Examination Survey (NHANES, 2011-2016) were collected and analyzed. Concentrations of metals were measured in blood (cadmium [Cd], lead [Pb], mercury [Hg], and manganese [Mn]) and serum (copper [Cu], selenium [Se], and zinc [Zn]) using inductively coupled plasma mass spectrometry and inductively coupled plasma dynamic reaction cell mass spectrometry, respectively. The weighted quantile sum (WQS) and Bayesian kernel machine regression (BKMR) models were performed to determine the joint effects of multiple metals exposure on lumbar and total BMD. The linear regression analyses showed Pb was negatively associated with BMDs. The WQS regression analyses revealed that the WQS index was inversely related to lumbar (ß = -0.022, 95% CI: -0.036, -0.008) and total BMD (ß = -0.015, 95% CI: -0.024, -0.006), and Se, Mn, and Pb were the main contributors for the combined effects. Additionally, nonlinear dose-response relationships between Pb, Mn, and Se and BMD, as well as a synergistic interaction of Pb and Mn, were found in the BKMR analyses. Our findings suggested co-exposure to Cd, Pb, Hg, Mn, Cu, Se, and Zn (above their 50th percentiles) was associated with reduced BMD, and Pb, Mn, and Se were the main contributors driving the overall effects.

High-Throughput Absolute Quantification Sequencing Revealed Osteoporosis-Related Gut Microbiota Alterations in Han Chinese Elderly.

Objective: Accumulative evidence suggests that gut microbiota play an important role in bone remodeling and hence bone health maintenance. This study aimed to explore the association of gut microbiota with the risk of osteoporosis and to identify potential disease-related taxa, which may be promising targets in osteoporosis prevention and treatment in the future. Methods: Absolute quantification 16S ribosomal RNA gene sequencing was used to detect absolute and relative abundances of gut microbiota in 44 patients with osteoporosis and 64 controls. In combination with one of our previous studies, a total of 175 samples were involved in the relative abundance analysis. Results: Compared with the controls, the patients with osteoporosis had higher absolute and relative abundances of Bacteroidetes phylum, and Bacteroides and Eisenbergiella genera. The absolute abundances of Clostridium_XlVa, Coprococcus, Lactobacillus, and Eggerthella genera increased, and that of the Veillonella genus decreased in the osteoporosis group. As for relative abundance, that of the Parabacteroides and Flavonifractor genera increased, whereas that of the Raoultella genus decreased in the osteoporosis group. Controlling for potential confounders, the associations of Clostridium_XlVa, Coprococcus, and Veillonella genera with the risk of osteoporosis did not maintain significance. Ridge regression analysis suggested that Bacteroides is associated with reduced bone mineral density (BMD) and T-score at lumbar spines, and Anaerovorax is associated with increased BMD at the femoral neck. Functional predictions revealed that 10 Kyoto Encyclopedia of Genes and Genomes pathways were enriched in the osteoporosis group. Conclusions: Gut microbiota compositions may contribute to the risk of osteoporosis. Several specific taxa and functional pathways are identified to associate with reduced bone density, thus providing epidemiologic evidence for the potential role of aberrant gut microbiota in osteoporosis pathogenesis.

The association between maternal and foetal REN gene polymorphisms and preeclampsia/eclampsia: A hybrid design study.

OBJECTIVES: Preeclampsia (PE)/eclampsia (E) is an important cause of foetal and maternal morbidity and mortality, and its aetiology is poorly understood. Good evidence suggests that renin (REN) might be associated with PE/E. The risk of PE/E is determined by both maternal and foetal genes, but most previous studies have focused on maternal contributions. This study aimed to explore the association of maternal and foetal REN polymorphisms with PE/E in pregnant Han Chinese women. METHODS: A case-parents/mother-control study including 347 PE/E patients with their partners and offspring and 700 control mothers with their offspring was conducted. A log-linear model was used to investigate the association between maternal and foetal REN SNPs and PE/E simultaneously, as well as the interaction of REN SNPs and environmental factors on PE/E. RESULTS: The foetal REN rs5707 AC genotype in combination with a pre-pregnancy BMI ≥ 24 kg/m2 was significantly associated with an increased risk of PE/E, with an OR of 2.75 (95%CI = 1.50-5.06). Maternal and foetal rs5707 were significantly associated with an increased risk of PE/E under the recessive model (AA + AC/CC). In haplotype analyses, foetal CCT (in the order of rs2368564, rs5707, rs5705) and TAT genotypes were positively associated with the risk of PE/E. There was no significant association between maternal and foetal REN SNP genotypes and PE/E in the transmission disequilibrium test (TDT) and log-linear model analysis. CONCLUSIONS: Findings from this study indicate that foetal rs5707 polymorphisms may play a significant role in PE/E development, especially among overweight or obese pregnant women in China.

The effect of a web-based training for improving primary health care providers' knowledge about diabetes mellitus management in rural China: A pre-post intervention study.

BACKGROUND: The performance of primary health care providers regarding DM management is poor in rural China, and effective training methods for providers are urgently needed. This study aimed to evaluate the effect of web-based training for improving knowledge about DM management among primary health care providers in rural China and to further compare the effects of the training effect between primary health care providers with different backgrounds. METHODS: A pre-post intervention study was conducted from April to August 2014. In this study, a total of 901 primary health care workers were recruited from six counties in Hubei province. To evaluate the effect of the web-based training, the knowledge achievement of participants was measured with multiple choice questions (MCQ) at baseline, at the end of two weeks of training and at three months after training. A mixed linear model (MLM) was used to measure group differences in the mean scores at baseline and follow-up. RESULTS: After the web-based training, the knowledge scores of the village doctors increased from 73.58 at baseline to 89.98 at posttest and to 84.57 three months after the training. For township health workers, we observed an upward trend in scores from 78.87 at the pre-test to 91.72 at the second test, and at the three months after the training, the scores increased to 94.91. For village doctors, greater knowledge achievement was observed between the scores at baseline and after two weeks of training(adjusted difference: 3.55, P = 0.03) compared to that observed for the township health workers, while decreased their knowledge achievement between baseline and the third-test compared with that of township health workers (adjusted difference: 5.05, P = 0.01). CONCLUSIONS: This study suggested that web-based training was an effective method for improving the knowledge of primary health care providers about management of DM in remote areas. Compared with the effect of the training on village doctors, the training had a poor short-term effect on township health workers but a better long-term effect.