Associating phthalate exposure during pregnancy with preschooler's FMI, ABSI and BRI trajectories via putative mechanism pathways.

Phthalates are well-known obesogens, but a few studies have explored their impacts on the childhood fat mass index (FMI), body shape index (ABSI) and body roundness index (BRI). Information from 2950 participants recruited in the Ma'anshan Birth Cohort was analyzed. The relationships between six maternal phthalate metabolites and their mixture and childhood FMI, ABSI and BRI were investigated. FMI, ABSI and BRI in children aged 3.5 y, 4.0 y, 4.5 y, 5.0 y, 5.5 y and 6.0 y were calculated. The latent class trajectory modeling categorized the FMI trajectories into "rapidly increasing FMI" (4.71%) and "stable FMI" (95.29%) groups; ABSI trajectories were categorized as "decreasing ABSI" (32.74%), "stable ABSI" (46.55%), "slowly increasing ABSI" (13.26%), "moderately increasing ABSI" (5.27%) and "rapidly increasing ABSI" (2.18%) groups; BRI trajectories were categorized as "increasing BRI" (2.82%), "stable BRI" (19.85%), and "decreasing BRI" (77.34%) groups. Prenatal MEP exposure was associated with repeated measurements of FMI (ß = 0.111, 95% CI = 0.002-0.221), ABSI (ß = 0.145, 95% CI = 0.023-0.268) and BRI (ß = 0.046, 95% CI = -0.005-0.097). Compared with each stable trajectory group, prenatal MEP (OR = 0.650, 95% CI = 0.502-0.844) and MBP (OR = 0.717, 95% CI = 0.984-1.015) were linked to a decreased risk of "decreasing BRI" in children; there was a negative relationship between MBP and the "decreasing ABSI" group (OR = 0.667, 95% CI = 0.487-0.914), and MEP increased the risks of "slowly increasing ABSI" (OR = 1.668, 95% CI = 1.210-2.299) and "rapidly increasing ABSI" (OR = 2.522, 95% CI = 1.266-5.024) in children. Phthalate mixture during pregnancy showed significant relationships with all anthropometric indicator trajectories, with MEP and MBP always being of the largest importance. In conclusion, this study suggested that prenatal phthalate coexposure increased the childhood probability of being in higher ABSI and BRI trajectory groups. That is, children were more likely to be obese when they were exposed to higher levels of some phthalate metabolites and their mixture. The low-molecular weight phthalates, including MEP and MBP, contributed the greatest weights.

[Network Meta-analysis of Chinese medicine injection combined with conventional western medicine in treatment of stable angina pectoris].

This study aimed to systematically evaluate the efficacy and safety of different Chinese medicine injections combined with conventional western medicine for stable angina pectoris. PubMed, Cochrane Library, EMbase, Web of Science, CNKI, Wanfang, VIP, and SinoMed were searched to collect randomized controlled trial(RCT) of Chinese medicine injection combined with conventio-nal western medicine in the treatment of stable angina pectoris from the inception of the databases to July 8, 2022. Two researchers independently screened the literature, extracted the data, and evaluated the risk of bias of the included studies. Stata 15.1 was used for network Meta-analysis. A total of 52 RCTs were included, involving 4 828 patients treated by 9 Chinese medicine injections(Danhong Injection, Salvia Miltiorrhiza Polyphenol Hydrochloride Injection, Tanshinone Sodium Ⅱ_A Sulfonate Injection, Salvia Miltiorrhiza Ligustrazine Injection, Dazhu Hongjingtian Injection, Puerarin Injection, Safflower Yellow Pigment Injection, Shenmai Injection and Xuesaitong Injection). The network Meta-analysis showed that:(1)in terms of improving the efficacy of angina pectoris, the surface under the cumulative ranking curve(SUCRA) followed the order of conventional western medicine combined with Salvia Miltiorrhiza Ligustrazine Injection>Tanshinone Sodium Ⅱ_A Sulfonate Injection>Danhong Injection>Salvia Miltiorrhiza Polyphenol Hydrochloride Injection>Xuesaitong Injection>Shenmai Injection>Puerarin Injection>Safflower Yellow Pigment Injection>Dazhu Hongjingtian Injection;(2)in terms of improving the efficacy of electrocardiogram(ECG), SUCRA followed the order of conventional western medicine combined with Salvia Miltiorrhiza Ligustrazine Injection>Puerarin Injection>Danhong Injection>Salvia Miltiorrhiza Polyphenol Hydrochloride Injection>Shenmai Injection>Xuesaitong Injection>Safflower Yellow Pigment Injection>Tanshinone Sodium Ⅱ_A Sulfonate Injection>Dazhu Hongjingtian Injection;(3)in terms of increasing high-density lipoprotein cholesterol(HDL-C), SUCRA followed the order of conventional western medicine combined with Danhong Injection>Shenmai Injection>Safflower Yellow Pigment Injection>Xuesaitong Injection>Tanshinone Sodium Ⅱ_A Sulfonate Injection>Dazhu Hongjingtian Injection;(4)in terms of lowering low-density lipoprotein cholesterol(LDL-C), SUCRA followed the order of conventional western medicine combined with Safflower Yellow Pigment Injection>Danhong Injection>Shenmai Injection>Tanshinone Sodium Ⅱ_A Sulfonate Injection>Dazhu Hongjingtian Injection>Xuesaitong Injection;(5)in terms of safety, the overall adverse reactions of Chinese medicine injection combined with conventional western medicine were less than those of the control group. Current evidence indicated that Chinese medicine injection combined with conventional western medicine could improve the curative effect of stable angina pectoris with higher safety. Limited by the number and quality of included studies, the above conclusion needed to be verified by more high-quality studies.

The association between pregnancy-related anxiety and behavioral development in 18-month-old children: The mediating effects of parenting styles and breastfeeding methods.

BACKGROUND: Pregnancy-related anxiety (PRA) is a distinct type of anxiety from general anxiety, affects many pregnant women, and is correlated with poor behavioral development in children. However, the mediation paths were unclear. METHODS: A total of 2032 mother-infant pairs from the Ma'anshan Birth Cohort were included in the current study. Maternal PRA was assessed in the second and third trimesters. Children's behavioral development was evaluated at the age of 18 months. In addition, information on parenting styles and breastfeeding methods was obtained at postpartum. Multivariate regression and structural equation modeling were used to examine the associations between maternal PRA and children's behavioral development. RESULTS: Significant intercorrelations were found between maternal PRA, the potential mediators (parenting styles and breastfeeding methods), and 18-month-old children's ASQ scores. Parenting styles played an intermediary role in the relationship between maternal PRA and children's behavioral development (ß = 0.030, 95 % confidence interval: 0.017-0.051), and the mediating effect accounted for 29.1 % of the total effect. However, breastfeeding methods did not mediate the link between PRA and children's behavior. LIMITATIONS: Depression and postpartum anxiety were not controlled for in our analysis, which left us unable to estimate the independent impact of PRA on children's behavior. CONCLUSIONS: Parenting rather than breastfeeding is the mediating factor of behavioral problems in children caused by PRA.

Combined effects of prenatal phthalate exposure on cardiometabolic risk score among 4- to 7-year-old children: MABC study.

There is currently no consensus about the impact of prenatal phthalate exposure on blood pressure and glycolipids in children. Few studies consider the health effects as an integrated indicator. The combined effect of multiple phthalate exposures is often ignored. Based on the Ma'anshan Birth Cohort, 2298 woman-child pairs were included in this study. Maternal urine was collected in each trimester to analyze 6 phthalate metabolites. The overall cardiometabolic risk (CMR) score was calculated based on serum glycolipids and blood pressure for children aged 4-7 years. A higher score represents a less favorable CMR profile. The restricted cubic spline model was used to explore the relationship between prenatal phthalate exposure and childhood CMR score. In addition, the quantile g-computation and the Bayesian kernel machine regression were used to evaluate the combined effect. The MBP exposure in the 1st trimester (MBP-1st) and the MEP-2nd were non-linearly associated with the CMR score (Fnonlinear = 3.28 and 5.60, Pnonlinear = 0.0378 and 0.0038, respectively). The MBP-3rd (Flinear = 5.31, Plinear = 0.0012) and the ∑LMWP-3rd (Flinear = 4.37, Plinear = 0.0045) were negatively associated with the score in a linear manner. The phthalate mixture in the 2nd trimester increased the score (psil = 0.1747, 95% CI = 0.0077-0.3416), with the MEP being the most common [weights = 0.5290; posterior inclusion probability (PIP) = 0.40]. The phthalate mixture in the 3rd trimester decreased the score (psil = -0.2024, 95% CI = -0.4097－0.0048), with the MEHP (weights = -0.5101; PIP = 0.14) and the MBP (weights = -0.3993, PIP = 1.00) being the greatest contributors. In conclusion, the MBP-1st and the MEP-2nd are non-linearly associated with the cardiometabolic risk in children. The MBP-3rd and the ∑LMWP-3rd decrease the childhood risk. The combined exposure to phthalate mixture in the second and third trimester elevates and decreases the risk of childhood cardiometabolism, respectively.

Prenatal single and combined exposure to phthalates associated with girls' BMI trajectory in the first six years.

Evidence of the influence of prenatal phthalate exposure on childhood longitudinal obesity markers is limited. Nested on the Ma'anshan birth cohort study, 990 mother-daughter pairs were included. Seven phthalate metabolites were determined in urine collected in each trimester. Each child underwent a physical examination from birth to 6 years of age twelve times. Latent class growth models were used to identify three trajectories of girls' body mass index (BMI). Logistic regression, quantile g-computation and Bayesian kernel machine regression models analyzed the relationships of prenatal exposure to individual and mixed phthalates with girls' body mass index (BMI) trajectory. Compared to the "lowest trajectory" class, prenatal average concentrations of mono(2-ethyl-5-hydroxyhexyl) phthalate (MEHHP, ORcrude = 2.095, 95 % CI = 1.014-4.328) and di(2-ethylhexyl) phthalate (DEHP, ORcrude = 2.336, 95 % CI = 1.022-5.338) during pregnancy were associated with an increased probability of being in the "highest trajectory" class. The average concentration of DEHP (ORcrude = 1.879, 95 % CI = 1.002-3.522) was associated with an increased probability of being in the "moderate trajectory" class. Stratified analyses by trimester of pregnancy mainly showed that third-trimester exposure to monoethyl phthalate (MEP, ORadjusted = 1.584, 95 % CI = 1.094-2.292), mono(2-ethyl-5-oxohexyl) phthalate (MEOHP, ORadjusted = 2.885, 95 % CI = 1.367-6.088), MEHHP (ORadjusted = 2.425, 95 % CI = 1.335-4.407), DEHP (ORadjusted = 2.632, 95 % CI = 1.334-5.193) and high molecular weight phthalate (ORadjusted = 2.437, 95 % CI = 1.239-4.792) was associated with an increased probability of being in the "highest trajectory" class. However, the mixture of phthalates was not significantly related to the girl's BMI trajectory. In conclusion, in utero exposure to phthalates, including MEP and DEHP metabolites (MEHHP and MEOHP), was significantly associated with early childhood high BMI trajectories in girls. The third trimester of pregnancy seemed to be the window of vulnerability to phthalate exposure for girls' high BMI trajectory at periods of prenatal development. No evidence supported a significant relationship between combined exposure to phthalate metabolites and girls' high BMI trajectory.

[Network Meta-analysis of Chinese medicine injections in treatment of hypertensive intracerebral hemorrhage].

To systematically evaluate the efficacy and safety of Chinese medicine injections in the treatment of hypertensive intracerebral hemorrhage, we collected the relevant randomized controlled trials(RCTs) by computer retrieval from PubMed, EMbase, Cochrane Library, Web of Science, Wanfang, CNKI, VIP, and CBM within the timespan from inception to December 30, 2021. The obtained index data were analyzed by RevMan 5.3 and Stata 15.0. Finally, 63 RCTs were selected for analysis, involving 5 953 patients. The experimental groups involved 9 Chinese medicine injections, including Danshen Injection, Danhong Injection, Sodium Aescinate Injection, Qingkailing Injection, Compound Shexiang Injection, Shuxuening Injection, Yinxing Damo Injection, Ginkgolide Injection, and Xingnaojing Injection. The network Meta-analysis showcased the following trends.(1)The surface under the cumulative ranking curve(SUCRA) in improving neurological function ranked in the order of surgical operation+conventional treatment of western medicine combined with Danhong Injection>combined with Xingnaojing Injection>combined with Ginkgolide Injection>combined with Compound Shexiang Injection>combined with Danshen Injection>combined with Sodium Aescinate Injection>combined with Qingkailing Injection>combined with Shuxuening Injection>combined with Yinxing Damo Injection.(2)In terms of National Institutes of Health stroke scale(NIHSS) score, the SUCRA ranked in the order of surgical operation+conventional treatment of western medicine combined with Xingnaojing Injection>combined with Compound Shexiang Injection>combined with Yinxing Damo Injection>combined with Ginkgolide Injection>combined with Danhong Injection>combined with Sodium Aescinate Injection.(3)In terms of Glasgow coma scale(GCS) score, the ranking of SUCRA was surgical operation+conventional treatment of western medicine combined with Yinxing Damo Injection>combined with Qingkailing Injection>combined with Sodium Aescinate Injection>combined with Danhong Injection>combined with Ginkgolide Injection>combined with Xingnaojing Injection.(4)The SUCRA in volume of residual cerebral hematoma ranked in the order of surgical operation+conventional treatment of western medicine combined with Sodium Aescinate Injection>combined with Xingnaojing Injection>combined with Danhong Injection>combined with Ginkgolide Injection>combined with Shuxuening Injection>combined with Compound Shexiang Injection. The experimental group had lower incidence of adverse reactions than the control group. The results of network Meta-analysis suggest that on the basis of surgical operation+conventional treatment of western medicine, the application of Chinese medicine injections can improve the efficacy of treating hypertensive intracerebral hemorrhage. However, in view of the great differences in the quality and number of studies included for different therapies, the SUCRA of Chinese medicine injections need to be further verified with high-quality multi-center, large-sample, randomized double-blind trials.

Sex Discrepancy Observed for Gestational Metabolic Syndrome Parameters and Polygenic Risk Associated With Preschoolers' BMI Growth Trajectory: The Ma'anshan Birth Cohort Study.

Background: Few studies have investigated the associations of childhood growth trajectories with the prenatal metabolic risks of mothers and their interaction with children's genetic susceptibility. Objective: To investigate the effects of gestational metabolic syndrome (GMS) risks and children's polygenic risk scores (PRSs), and their interaction effect on the BMI trajectory and obesity risk of offspring from birth to 6 years of age. Methods: A total of 2,603 mother-child pairs were recruited from the Ma'anshan birth cohort (Anhui Province of China) study. Data on maternal prepregnancy obesity, gestational weight gain (GWG), gestational diabetes mellitus (GDM), and hypertensive disorders of pregnancy (HDP) were used to evaluate maternal GMS risk. In addition, 1,482 cord blood samples were used to genotype 11 candidate single-nucleotide polymorphisms (SNPs) to calculate children's PRSs. The latent class growth model using the longitudinal BMI-for-age z scores (BMIz) was applied to validly capture the BMIz growth trajectory. Results: Maternal GMS status was associated with higher BMIz scores and with an increased risk of overweight/obesity. Positive relationships were revealed between PRS and the risk of overweight/obesity among girls. Additionally, maternal GMS significantly interacted with the child's PRS on BMIz scores and the risk of overweight/obesity among girls. Hierarchical BMI trajectory graphs by different exposure groups showed consistent findings, and both boys' and girls' BMIz trajectories were divided into three groups. Among girls, the higher the GMS risk or PRS they had, the higher the probability of being in the high BMIz trajectory group. Conclusions: Maternal GMS status increased BMIz scores and the risk of obesity in both boys and girls and elevated the child's BMI trajectory from birth to 6 years of age among girls. PRSs were significantly associated with children's BMI trajectory and the risk of obesity and modified the associations between maternal GMS status and obesity biomarkers only among girls. Thus, regarding childhood obesity, steps should be taken to decrease maternal metabolic risks before and during pregnancy, and sex discrepancies should be noted to identify high-risk populations after birth to hierarchically manage them.

Relationship of individual and mixed prenatal phthalate exposure with placental structure and efficiency in the prospective Ma'anshan Birth Cohort Study.

BACKGROUND: Few studies have investigated the associations between prenatal phthalate exposure and placental structure and function with inconsistent conclusions. METHODS: Nested on the Ma'anshan Birth Cohort study, 2723 women provided spot urine samples during the first, second and third trimesters of pregnancy to analyze six phthalate metabolites. The outcomes of interest were placental weight, efficiency (birth weight/placental weight), chorionic disc area and disc eccentricity. The relationships of prenatal exposure to a single phthalate with placental measures were analyzed. The associations between prenatal phthalate mixture exposure and placental measures were also evaluated. RESULTS: Most phthalate metabolites were significantly associated with placental weight, efficiency and chorionic disc area during the whole gestation and in each trimester of pregnancy, with different directions of relationships. Sensitivity analyses revealed similar findings, indicating the robustness of the statistical results. Furthermore, inverted U-shaped nonlinear relationships of prenatal exposure to some phthalate metabolites with placental weight, efficiency and chorionic plate area were observed. However, quantile g-computation mixture models did not reveal any association between maternal combined exposure to the total phthalate metabolites and placental measures. CONCLUSIONS: Maternal exposure to most phthalates and their metabolites was associated with placental weight, efficiency and chorionic plate area in both a linear manner and an inverted U-shaped nonlinear manner. However, the mixture of multiple phthalate metabolites was not observed to be associated with any placental measure.

Lag associations of gestational phthalate exposure with maternal serum vitamin D levels: Repeated measure analysis.

Few studies have investigated the relationships between gestational phthalate exposure and maternal circulating vitamin D. In the Ma'anshan birth cohort, 3265 pregnant women were included. Each woman provided up to three urine and serum samples for measurement of phthalates and 25(OH)D and calcium, respectively. Linear mixed models were performed to analyse the association between phthalate metabolites and 25(OH)D and calcium. Stratified analyses of the relationship between phthalates and 25(OH)D by urine collection season were conducted. Finally, the post hoc lag effect of phthalate exposure on 25(OH)D was determined if longitudinal associations were significant. Some phthalate metabolites were associated with increased 25(OH)D but with decreased calcium. Furthermore, the relationship of phthalate exposure with 25(OH)D varied with urine collection season. Phthalate metabolites collected in summer and autumn were associated with an increase in 25(OH)D, while monobenzyl phthalate collected in winter and spring was inversely associated with 25(OH)D. Finally, high-molecular-weight phthalates had lag associations with 25(OH)D with a 1-trimester lag period. Low-molecular-weight phthalates exhibited lag associations with 25(OH)D with a 2-trimester lag period. In conclusion, the positive cross-sectional correlation between phthalate metabolites and 25(OH)D was partly affected by urine collection season. This study suggested that gestational phthalate exposure would have a lag association with maternal 25(OH)D levels.

Sex-specific mediation of placental inflammatory biomarkers in the effects of prenatal phthalate coexposure on preschooler cognitive development.

The objective of this study is to investigate the mediating effect of placental inflammatory biomarkers on the relationship between prenatal phthalate coexposure and cognitive development in preschoolers. A subgroup of 1660 mother-child pairs from the Ma'anshan Birth Cohort study were included. We measured the levels of phthalate metabolites of dibutyl phthalate (DBP), butyl benzyl phthalate (BBzP), and di (2-ethylhexyl) phthalate (DEHP) in all the women included in the study from three urine samples collected in each of the trimesters. A potency-weighted sum of coexposure to DBP, BBzP, and DEHP (indicator: ∑PAE) was calculated. The mRNA of the proinflammatory cytokine IL-6 and the classically activated macrophage (M1) biomarker CD68 was analyzed using placental tissues. The Wechsler Preschool and Primary Scale of Intelligence-Fourth Edition-Chinese was used to evaluate the full-scale intelligence quotient (FSIQ) of children aged 2.5-6 years. Average ∑PAEs and ∑PAEs in each trimester were associated with IL-6 and CD68. ∑PAE in the first trimester was positively associated with IL-6 (ß = 0.11, 95% CIs = 0.03-0.19) and CD68 (ß = 0.16, 95% CIs = 0.04-0.28), and negatively associated with FSIQ (ß =-0.06, 95% CIs = -0.11 to -0.02), verbal comprehension (ß =-0.06, 95% CIs = -0.11 to -0.01), and processing speed (ß =-0.07, 95% CIs = -0.12 to -0.01). Additionally, sex discrepancies were observed for the mediating effects of placental inflammation on the relationships between ∑PAE and children's cognitive development. For instance, the association between ∑PAE in early pregnancy and FSIQ was partially mediated by IL-6 (estimated proportion mediated: 21.85%) and CD68 (estimated proportion mediated: 16.2%). Gender-specific associations and trimester-specific relationships of prenatal multiple phthalate coexposure were revealed. ∑PAE in the first trimester of pregnancy was associated with increased of placental inflammation, and a decrease in preschoolers' cognitive development. In boys, placental IL-6 and CD68 elevation resulting from phthalates might be potential mechanisms of poor cognitive development.

Effects of single and combined gestational phthalate exposure on blood pressure, blood glucose and gestational weight gain: A longitudinal analysis.

Few studies have investigated the association of gestational exposure to phthalate with metabolic risk and have reached inconsistent conclusions. Based on the Ma'anshan Birth Cohort, 3273 women were included in the present study. All participants provided up to three urine samples for 7 phthalate metabolite measurements. The hazard index (HI) was used to evaluate the cumulative risk of multiple phthalate coexposures. The outcomes of interest included hypertensive disorders of pregnancy (HDOP), gestational diabetes mellitus (GDM), and gestational weight gain (GWG). The incidences of HDOP, GDM, and excessive GWG were 5.93%, 13.09%, and 28.95%, respectively. Exposure to a single phthalate metabolite or a specific diester during the first trimester of pregnancy elevated blood pressure (BP) and fasting plasma glucose (FPG) in the third trimester and body weight gain throughout pregnancy. However, inverse relationships were revealed for some phthalate metabolites, which were inconsistent with the results of their diesters. The HI value during the first trimester was positively associated with subsequent BP, FPG, and GWG. In addition, HI during the first trimester increased the risks of GDM [odds ratio (OR) = 1.34, 95% confidence intervals (CIs) = 1.02-1.75)] and excessive GWG (OR = 1.76, 95% CIs = 1.41-2.19) in a linear manner thereafter. Notably, phthalates might directly increase maternal blood glucose and pressure, and these changes were secondary effects of the obesiogenic effects of certain phthalates. In conclusion, exposure to single and multiple phthalates during the first trimester of pregnancy increased the risks of maternal metabolic syndrome components. However, the conflicting findings between phthalates and their metabolites need to be interpreted carefully.

Repeated measures of prenatal phthalate exposure and maternal hemoglobin concentration trends: The Ma'anshan birth cohort (MABC) study.

A prospective cohort study of a Chinese population was conducted to investigate the relationship between prenatal phthalates exposure and maternal hemoglobin or anemia. Based on the Ma'anshan Birth Cohort study, 7 phthalate metabolites were quantified in spot pregnancy urine samples (n = 9263) from 3269 pregnant women during each trimester. The maternal hemoglobin concentrations were obtained from electronic medical records at the same three time points for each participant during pregnancy. Anemia was defined as a hemoglobin concentration below 110 g/L in pregnant women. Repeated measures and trimester-specific analyses were used to estimate the effects of phthalates exposure on maternal hemoglobin and anemia. The prevalence of anemia was 3.6%, 27.0%, and 26.5% during the first, second and third trimester, respectively. Repeated measures analysis showed that hemoglobin concentrations decreased by 0.55, 0.19, 0.57, 0.49, and 0.54 g/L with each 1 ln-transformed concentration increase of MBP, MBzP, MEHP, MEOHP, and MEHHP, respectively. Exposure to MMP, MBP, MEHP, MEOHP, and MEHHP increased the risk of anemia by 1.11-fold, 1.21-fold, 1.20-fold, 1.13-fold, and 1.16-fold, respectively. Trimester-specific regression models stratified by the sample collection time during pregnancy generated consistent results. This is the first study focusing on the effect of prenatal phthalate exposures on hemoglobin or anemia in pregnant Chinese women. We found that prenatal phthalates exposure not only decreased the concentrations of hemoglobin but also showed associations with the prevalence of anemia. Associations appeared stronger for the subsample representing women pregnant with a male fetus than those pregnant with a female fetus. Anemia remains a moderate public health problem in China, and effective measures should be implemented.

Temporal Variability of Cumulative Risk Assessment on Phthalates in Chinese Pregnant Women: Repeated Measurement Analysis.

The assessment of the combined effects of multiple phthalate exposures at low levels is a newly developed concept to avoid underestimating their actual cumulative health risk. A previous study included 3455 Chinese pregnant women. Each woman provided up to three urine samples (in total 9529). This previous study characterized the concentrations of phthalate metabolites. In the present study, the data from 9529 samples was reanalyzed to examine the cumulative risk assessment (CRA) with two models: (1) the creatinine-based and (2) the volume-based. Hazard index (HI) values for three phthalates, dibutyl phthalate, butyl benzyl phthalate, and di(2-ethylhexyl) phthalate, in the first, second, and third trimesters of pregnancy, were calculated, respectively. In creatinine-based model, 3.43%, 14.63%, and 17.28% of women showed HI based on the European Food Safety Authority tolerable daily intake exceeding 1 in the first, second, and third trimester of pregnancy, respectively. The intraclass correlation coefficient of HI was 0.49 (95% confidence interval: 0.46-0.53). Spearman correlations between HI of the creatinine model and ∑androgen disruptor (a developed potency weighted approach) ranged from 0.824 to 0.984. In summary, this study suggested a considerable risk of cumulative exposure to phthalates during the whole gestation in Chinese pregnant women. In addition, moderate temporal reproducibility indicated that single HI, estimated by the phthalate concentration in single spot of urine, seemed representative to describe the throughout pregnancy CRA. Finally, strong correlation between HI of the creatinine model and ∑androgen disruptor revealed that the creatinine-based model was more appropriate to evaluate the CRA.

[Effects of alcohol on benign prostate hyperplasia induced by testosterone propionate in mice].

OBJECTIVE: To study the effects of alcohol administration on benign prostate hyperplasia(BPH) and the reproductive toxicity during development of benign prostate hyperplasia. METHODS: Seventy adult male Kunming mice were randomly divided into seven groups:control (group CON), negative control (group NC, injected subcutaneously with soybean oil, 25 mg/(kg·d), intragastric administration of distilled water, 7.5 ml/(kg·d)), alcohol for 7 and 21 days (group AL7 and AL21, intragastric administration with wine of 50% alcohol, 7.5 ml/(kg·d)), testosterone propionate for 7 and 21 days (group TP7 and TP21, injected subcutaneously with testosterone propionate, 25 mg/(kg·d)), testosterone propionate+alcohol for 7 days (group TP+AL7, injected subcutaneously with testosterone propionate, 25 mg/(kg·d), and intragastric administration with wine of 50% alcohol, 7.5 ml/(kg·d)),10 mice in each groups. Twenty-four hours after the last administration, mice were sacrificed. The indexes of prostate and testis and the parameters of sperm were determined in mice. The levels of free radicals, antioxidation and histopathological changes in testis and prostate were determined. RESULTS: Compared with the control, TP7d group, AL7 and AL21d groups, the prostate coefficient of TP + AL7d group was increased significantly and the quantity and quality of sperm were decreased significantly (P<0.05), the content of MDA in prostate and testis was increased significantly, meanwhile the activities of SOD and GPx were decreased significantly (P< 0.05). Compared with TP21d group, the prostate coefficient of TP + AL7d group had no significant difference (P>0.05). CONCLUSIONS: The typical BPH state could be induced after 7-day treatment of testosterone propionate and alcohol. The testicular and sperm were damaged which enhanced the oxidative stress in reproductive system. The results indicated that alcohol could significantly promote the prostate hyperplasia induced by testosterone propionate in mice.

Vitamin D and risk of preterm birth: Up-to-date meta-analysis of randomized controlled trials and observational studies.

AIM: We performed a meta-analysis of randomized controlled trials (RCT) and observational studies to answer the two following questions: (i) whether low maternal circulating 25 hydroxyvitamin D (25-OHD) is associated with an increased risk of preterm birth (PTB) or spontaneous PTB (sPTB); and (ii) whether vitamin D supplementation alone during pregnancy can reduce the risk of PTB. METHODS: Literature search was carried out using Pubmed, Web of Science and Embase databases up to June 2016. Pooled OR or relative risk (RR) with 95%CI were computed using fixed or random effects models depending on the size of heterogeneity. Subgroup analysis was used to explore potential sources of between-study heterogeneity. Publication bias was evaluated using Egger's test and Begg's test. RESULTS: Twenty-four articles (six RCT and 18 observational studies) were identified. Maternal circulating 25-OHD deficiency (pooled OR, 1.25; 95%CI: 1.13-1.38) rather than insufficiency (pooled OR, 1.09; 95%CI: 0.89-1.35) was associated with an increased risk of PTB, and vitamin D supplementation alone during pregnancy could reduce the risk of PTB (pooled RR, 0.57; 95%CI: 0.36-0.91). This was also the case for the sPTB subgroup (circulating 25-OHD <50 vs >50 nmol/L; pooled OR, 1.45; 95%CI: 1.20-1.75). CONCLUSIONS: Maternal circulating 25-OHD deficiency could increase PTB risk and vitamin D supplementation alone during pregnancy could reduce PTB risk. Extrapolation of the results, however, must be done with caution, and there is urgent need for larger, better-designed RCT to confirm this effect.

Current evidence on the association between rs3757318 of C6orf97 and breast cancer risk: a meta-analysis.

BACKGROUND: A common genetic variant rs3757318, located in intron of C6orf97, was firstly identified to be associated with breast cancer (BC) risk by a genome-wide association (GWA) study. However, subsequent validation studies with different ethnicities have yielded conflicting results. MATERIALS AND METHODS: We performed a meta-analysis to synthesize all available data for evaluating the precise effect of this variant on BC susceptibility. RESULTS: A total of 8 articles containing 11 studies with 62,891 cases and 65,635 controls were included in this meta-analysis. When compared to the G allele, the rs3757318-A allele was significantly associated with BC risk with the pooled OR of 1.21 (95% CI=1.15 - 1.29, P<0.001) but with obvious between-study heterogeneity (P=0.040). Stratified analysis suggested that diversity of ethnicity along with control source may explain part of the heterogeneity. Similarly, significant associations were also identified in heterozygote, homozygote, dominant and recessive genetic models. Sensitivity and publication bias analyses indicated robust stability of our results. CONCLUSIONS: Our present meta-analysis demonstrated that the variant rs3757318 is associated with increased BC risk. Nevertheless, further studies are needed to clarify the underlying biological mechanisms.

Genetic variant in SWI/SNF complexes influences hepatocellular carcinoma risk: a new clue for the contribution of chromatin remodeling in carcinogenesis.

Chromatin remodeling has been newly established as an important cancer genome characterization and recent exome and whole-genome sequencing studies of hepatocellular carcinoma (HCC) showed that recurrent inactivating mutations in SWI/SNF subunits involved in the molecular basis of hepatocarcinogenesis. To test the hypothesis that genetic variants in the key subunits of SWI/SNF complexes may contribute to HCC susceptibility, we systematically assessed associations of genetic variants in SWI/SNF complexes with HCC risk using a two-staged case-control study in Chinese population. A set of 24 single nucleotide polymorphisms (SNPs) in SWI/SNF complexes were examined in stage 1 with 502 HCC patients and 487 controls and three promising SNPs (SMARCA4 rs11879293, rs2072382 and SMARCB1 rs2267032) were further genotyped in stage 2 comprising 501 cases and 545 controls for validation. SMARCA4 rs11879293 presented consistently significant associations with the risk of HCC at both stages, with an OR of 0.73 (95% CI: 0.62-0.87) using additive model in combined analysis. Moreover, the decreased risk of HCC associated with SMARCA4 rs11879293 AG/AA was more evident among HBsAg positive individuals (OR = 0.47, 95% CI: 0.27-0.80) in combined analysis. The study highlighted the potential role of the SWI/SNF complexes in conferring susceptibility to HCC, especially modified HCC risk by HBV infection.

Ethyl (Z)-4-ferrocenyl-2-(4-hy-droxy-anilino)-4-oxobutenoate.

In the title compound, [Fe(C(5)H(5))(C(17)H(16)NO(4))], the O=C-C=C-N mean plane is twisted with respect to the mean planes of the benzene and substituted cyclo-penta-dienyl rings by 44.2 (2) and 13.8 (3)°, respectively. Furthermore, the O=C-C=C-N mean plane and the O=C-O(ester) plane make a dihedral angle of 55.5 (6)°. Consistent with this large dihedral angle, the linking C-C bond [1.507 (6) Å] does not show any (delocalized) double-bond character.

Interactions between genetic variants in the adiponectin, adiponectin receptor 1 and environmental factors on the risk of colorectal cancer.

BACKGROUND: Metabolic syndrome traits play an important role in the development of colorectal cancer. Adipokines, key metabolic syndrome cellular mediators, when abnormal, may induce carcinogenesis. METHODOLOGY/PRINCIPAL FINDINGS: To investigate whether polymorphisms of important adipokines, adiponectin (ADIPOQ) and its receptors, either alone or in combination with environmental factors, are implicated in colorectal cancer, a two-stage case-control study was conducted. In the first stage, we evaluated 24 tag single nucleotide polymorphisms (tag SNPs) across ADIPOQ ligand and two ADIPOQ receptors (ADIPOR1 and ADIPOR2) among 470 cases and 458 controls. One SNP with promising association was then analyzed in stage 2 among 314 cases and 355 controls. In our study, ADIPOQ rs1063538 was consistently associated with increased colorectal cancer risk, with an odds ratio (OR) of 1.94 (95%CI: 1.48-2.54) for CC genotype compared with TT genotype. In two-factor gene-environment interaction analyses, rs1063538 presented significant interactions with smoking status, family history of cancer and alcohol use, with ORs of 4.52 (95%CI: 2.78-7.34), 3.18 (95%CI: 1.73-5.82) and 1.97 (95%CI: 1.27-3.04) for smokers, individuals with family history of cancer or drinkers with CC genotype compared with non-smokers, individuals without family history of cancer or non-drinkers with TT genotype, respectively. Multifactor gene-environment interactions analysis revealed significant interactions between ADIPOQ rs1063538, ADIPOR1 rs1539355, smoking status and BMI. Individuals carrying one, two and at least three risk factors presented 1.18-fold (95%CI:0.89-fold to 1.58-fold), 1.87-fold (95%CI: 1.38-fold to 2.54-fold) and 4.39-fold (95%CI: 2.75-fold to 7.01-fold) increased colorectal cancer risk compared with those who without risk factor, respectively (P(trend) <0.0001). CONCLUSIONS/SIGNIFICANCE: Our results suggest that variants in ADIPOQ may contribute to increased colorectal cancer risk in Chinese and this contribution may be modified by environmental factors, such as smoking status, family history of cancer and BMI.