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The evidence is increasing that prenatal air pollutant exposure contributes to elevated oxidative stress in children, but the underlying mechanism is unclear. A pilot study was conducted in China to explore the associations between prenatal ambient air pollution exposure and superoxide dismutase 2 (SOD2) promoter methylation in maternal and cord blood. After detection and analyses, SOD2 promoter methylation levels in umbilical cord blood were elevated as maternal SOD2 promoter methylation levels increased. In addition, the SOD2 promoter methylation levels in umbilical cord blood were positively associated with the particulate matter 10 (PM10) exposure concentrations during the entire pregnancy and the second trimester. In maternal peripheral blood, the SOD2 promoter methylation levels were positively associated with the exposure concentrations of PM10 (during the entire pregnancy and the second trimester) and nitrogen dioxide (NO2) (during the first trimester of pregnancy), whereas the levels were negatively associated with the exposure concentrations of NO2 during the third trimester of pregnancy. Additionally, interaction analyses revealed that the maternal SOD2 promoter methylation level and sulfur dioxide (SO2) exposure (during the entire pregnancy and the third trimester), as well as NO2 exposure (during the third trimester of pregnancy), had an interaction effect on the SOD2 promoter methylation level in umbilical cord blood. Furthermore, mediation analysis revealed that the associations between SOD2 promoter methylation in umbilical cord blood and PM10 exposure during the entire pregnancy and the second trimester were partly mediated by maternal SOD2 promoter methylation. In conclusion, prenatal exposure to air pollutants was significantly associated with SOD2 promoter methylation levels in umbilical cord blood, and this association may be affected by SOD2 promoter methylation levels in maternal peripheral blood. These associations may be one of the mechanisms by which prenatal air pollutant exposure leads to oxidative stress in newborns.

Background Evidence shows that low serum vitamin D concentrations account for an increased risk of obesity by inducing vitamin D receptor (VDR) hypofunction. Although the correlation between single nucleotide polymorphisms (SNPs) of VDR gene and obesity-related anthropometric measures (such as body mass index [BMI] and waist circumference[WC]) has already been tested, there are only few studies on the association between direct measures of body fat percentage (BFP) and triceps skinfold thickness and the SNPs of VDR. The aim of the present study was to evaluate the effect of VDR gene polymorphism on multiple obesity indexes in Han Chinese, including BMI, WC, BFP and triceps skinfold thickness. Methods In this cross-sectional study, five hundred and seventeen healthy Chinese adults were enrolled in the trial. Four loci in VDR gene (rs2228570 [FokI], rs2189480, rs2239179 and rs7975232[ApaI]) were genotyped by TaqMan probe assays. Obesity indexes including BMI, WC, BFP and triceps skinfold thickness were used to evaluate the relationship to the VDR SNPs. Multiple logistic regression, linear regression and general multifactor dimensionality reduction (GMDR) were performed to analyze the correlation of VDR gene and obesity indexes. Results None of the VDR SNPs were associated with BMI and WC, the C allele of FokI and the T allele of ApaI were associated with an increase in BFP (β = 0.069,P = 0.007; β = 0.087, P = 0.022 respectively); the G allele of rs2239179 and the T allele of ApaI were associated with an increase in triceps skin fold thickness (β = 0.074, P = 0.001; β = 0.122, P

A total of 649 children aged 7–13 years of age were recruited in a cross-sectional study in Tongxu County, China (2017) to assess the effects of interaction between single nucleotide polymorphisms (SNPs) in SOD2 and SOD3 gene and fluoride exposure on dental fluorosis (DF) status. Associations between biomarkers and DF status were evaluated. Logistic regression suggested that the risk of DF in children with rs10370 GG genotype and rs5746136 TT genotype was 1.89-fold and 1.72-fold than that in children with TT/CC genotype, respectively. Increased T-SOD activity was associated with a lower risk of DF (OR = 0.99). The rs2855262*rs10370*UF model was regarded as the optimal interaction model in generalized multifactor dimensionality reduction analyses. Our findings suggested that rs4880 and rs10370 might be useful genetic markers for DF, and there might be interactions among rs10370 in SOD2, rs2855262 in SOD3, and fluoride exposure on DF status.

Prenatal air pollution, protein C (PROC) gene abnormal methylation, and genetic mutation can cause a series of neonatal diseases, but the complex relationship between them remains unclear. Here, we recruited 552 mothers and their own babies during January 2010-January 2012 in Zhengzhou to explore such association. The air pollutant data was obtained from the Environmental Monitoring Stations. The rs1799809 genotype and the methylation levels at the promoter region of PROC in genomic DNA samples were detected respectively by TaqMan probe and quantitative methylation specific PCR using real-time PCR system. The results show that the levels of neonatal PROC methylation were negatively associated with concentrations of NO2 during the entire pregnancy, particularly during the third trimester. Of particular significance, only in newborns carrying rs1799809 AA genotype, negatively significant associations between PROC methylation levels and exposure concentrations of air pollutants were observed. Further, we observed a significant interactive effect between neonatal rs1799809 genotype and SO2 exposure during the entire pregnancy on neonatal PROC methylation levels. Prenatal exposure to ambient air pollutants specifically was associated with the neonatal PROC promoter methylation level of newborns carrying the rs1799809 AA genotype. Taken together, these findings suggest that neonatal PROC methylation levels are associated with prenatal exposure to ambient air pollutants, and this association can be modified by rs1799809 genotype.

A number of studies have explored the association between ambient temperature and preterm birth (PTB), but rarely among adolescent mothers.To estimate the effects of ambient temperature on the risk of PTB and gestational age of newborns delivered by adolescent mothers in rural areas of Henan province.We obtained 5394 medical records of adolescent mothers with results of pre-pregnancy physical examination and pregnancy outcomes from the National Free Preconception Health Examination Project (NFPHEP) in Henan province. Meteorological information was obtained from the China Meteorological Data Sharing Service System. Individual exposure levels were evaluated with an inverse distance-weighted model. A multiple logistic regression model and multiple linear regression model were used to estimate the effects of ambient temperature on the risk of PTB and gestational age, respectively. Stratified and interaction analyses were also performed.Of newborns in this study, 3.45% (186/5394) were PTB. Mean, maximum and minimum temperature during the entire pregnancy, especially the last 1-4 weeks of pregnancy, were positively associated with the risk of PTB and negatively associated with gestational age (P 0.05). Nevertheless, a masking effect was observed that gestational age was positively associated with ambient temperature during the first trimester of pregnancy, due to the strongly inverse correlation between ambient temperature during the early and late stages of pregnancy. Stratified analyses showed that increasing temperature during the last 1-4 weeks of pregnancy increased the risk of PTB and decreased gestational age in newborns born in the cold season (P 0.05). Furthermore, interaction analyses showed that birth season modified the effects of temperature on the gestational age (PElevated ambient temperature can decrease gestational age and increase the risk of PTB in offspring of adolescent mothers in rural areas. The birth season may modify the effects of temperature on gestational age.

Excessive fluoride exposure has detrimental effects on the thyroid gland, which may be modified by iodine. However, the role of iodine in it remains unclear. This study aims to evaluate the role of iodine in thyroid abnormalities caused by fluoride exposure in school-age children. A total of 446 children aged 7-12 years were recruited from Tongxu County, Henan province, in 2017 (ZZUIRB 2017-018). We obtained demographic information through questionnaire surveys. The concentrations of urinary fluoride (UF) and urinary iodine (UI) were determined by the ion-selective electrode method and the catalytic spectrophotometric method, respectively. The radiation immunoassay was used to determine the serum concentrations of total triiodothyronine (TT3), total thyroxine (TT4), and thyroid-stimulating hormone (TSH). The B-mode ultrasound was performed to assess thyroid volumes (Tvols). The associations between fluoride exposure and thyroid-related indicators were tested by linear regression models. We found that Tvols increased by 0.22 (95% CI: 0.14, 0.31) cm3 with each standard deviation increment of UF. Moreover, Tvols in boys were more susceptible to fluoride exposure than those in girls, and the Tvols of children with high urinary iodine are less susceptible to fluoride exposure (P for interaction < 0.05). We also observed that TT3 levels were negatively related to UF concentrations at moderate urinary iodine levels (≤ 300 μg/l). Fluoride exposure can elevate the Tvols of school-age children, especially in boys, and high levels of iodine may alleviate this effect to some extent.

Changes in the preconception ambient temperature (PAT) can affect the gametogenesis, disturbing the development of the embryo, but the health risks of PAT on the developing fetus are still unclear. Here, based on the National Free Preconception Health Examination Project in the rural areas of Henan Province, we evaluate the effects of PAT on preterm birth (PTB). Data of 1,231,715 records from self-reported interviews, preconception physical examination, early gestation follow-up, and postpartum follow-up were collected from 1 January 2013 to 31 December 2016. Generalized additive models were used to assess the cumulative and lag effects of PAT upon PTB. The significant cumulative effects of mean temperature within 2 weeks and 3 weeks on the risk of PTB, especially upon late PTB (34-36 weeks) (P0.05), were observed. Exposure to extreme heat (90th percentile) within 2 weeks (RR = 1.470) and 3 weeks (RR = 1.375) before conception could increase the risk of PTB. After stratifying PTB, exposure to extreme heat within 2 weeks before conception can increase the risks of early (34 weeks) and late PTB (P0.05). Besides, exposure to extreme cold (10th percentile) within 3 weeks or longer before conception can elevate the risk of PTB, especially late PTB. The significant lag effects of temperature changes on the risk of early PTB (lag-8 days or earlier) were observed. In conclusion, the risk of PTB was susceptible to PAT changes within 2 weeks or longer before conception. Our findings provide (i) guidance for rural couples to make pregnancy plans and (ii) scientific evidence for the government to formulate policies to prevent PTB.

To assess heavy metal pollution and human health risk, a total of 28 topsoil samples were collected during four seasons from seven agricultural soil sites near a famous smelter in Jiyuan, China. The maximum concentrations of Cd, Pb, Hg, As, Zn, Cu, Ni, and Cr were 26.00, 2601.00, 3.29, 65.00, 410.00, 156.30, 54.80, and 73.60 mg kg−1, respectively. Compared with the sampling site nearest to the smelter, the concentrations of six metals at the farthest site were decreased significantly (P 3.0, and all sites had very high ecological risks related to Cd and Hg. The non-carcinogenic risk for children (based on combined exposure to the eight metals) was above the safety level. The carcinogenic risk of As for adults (8.98 × 10–6) and children (1.49 × 10–5) exceeded the acceptable level (1 × 10–6). Results suggest a serious health risk in the polluted areas, particularly for children. Abbreviation Cd: Cadmium; Pb: Lead; Hg: Mercury; As: Arsenic; Zn: Zinc; Cu: Copper; Ni: Nickel; Cr: Chromium; P: Nemerow index; RI: Potential ecological risk index; Ei: Monomial potential ecological risk of a specific heavy metal; HI: non-carcinogenic hazard index; CR: Carcinogenic risk; TN: Total nitrogen; TP: Total phosphorus; OM: Organic matter; MC: Moisture content; ADD: Average daily dose

Bone mineral density (BMD) changes were reported to be associated with excessive fluoride exposure and abnormal expression of RUNX2. However, whether the alteration of methylation status, a most commonly used marker for the alteration of gene expression in epidemiological investigation, of RUNX2 is associated with low-to-moderate fluoride exposure and BMD changes has not been reported. Our study aims to explore the role of RUNX2 promoter methylation in BMD changes induced by low-to-moderate fluoride exposure. A total of 1124 adults (413 men and 711 women) were recruited from Kaifeng City in 2017. We measured BMD using ultrasound bone densitometer. Concentrations of urinary fluoride (UF) were measured using ion-selective electrode, and the participants were grouped into control group (CG) and excessive fluoride group (EFG) according to the concentration of UF. We extracted DNA from fasting peripheral blood samples and then detected the promoter methylation levels of RUNX2 using quantitative methylation-specific PCR. Relationships between UF concentration, RUNX2 promoter methylation and BMD changes were analyzed using generalized linear model and logistic regression. Results showed in EFG (UF concentration > 1.6 mg/L), BMD was negatively correlated with UF concentration (β: −0.14; 95%CI: −0.26, −0.01) and RUNX2 promoter methylation (β: −0.13; 95%CI: −0.22, −0.03) in women. The methylation rate of RUNX2 promoter increased by 2.16% for each 1 mg/L increment in UF concentration of women in EFG (95%CI: 0.37, 3.96). No any significant associations between UF concentration, RUNX2 promoter methylation, and BMD were observed in the individuals in CG. Mediation analysis showed that RUNX2 promoter methylation mediated 18.2% (95% CI: 4.2%, 53.2%) of the association between UF concentration and BMD of women in EFG. In conclusion, excessive fluoride exposure (>1.6 mg/L) is associated with changes of BMD in women, and this association is mediated by RUNX2 promoter methylation.

Prenatal exposure to air pollutants is believed to be associated with adverse birth outcomes. However, the potential mechanisms, especially the epigenetic modified effects, still remain unclear. This study was designed to explore the association of air pollution, H19/DMR methylation levels, and birth weight and length. A total of 527 mother-infant pairs were recruited from Houzhai Center Hospital, Zhengzhou. Air pollution data during the study period was collected. The methylation at H19 promoter region and H19 DMR in maternal and cord bloods were determined using real-time PCR analysis. Ridge regression was used to analyze the association of air pollutants exposure during gestation with H19/DMR methylation and birth weight and length respectively. Results showed that prenatal exposure to NO2 was associated with higher H19 methylation in cord blood. Whereas SO2 and PM10 exposure were associated with lower H19 and H19 DMR methylation respectively. After stratification by pregnancy trimesters, the association of H19 methylation in cord blood with PM10 exposure also was found. Furthermore, prenatal exposures to air pollutants also were associated with birth weight and length. Specifically, with the increase of maternal SO2 exposure during the entire pregnancy, birth weight and length significantly decreased. While birth weight and birth length were significantly increased with NO2 exposure. The stratified analysis also found the associations between PM10 exposure and birth sizes in different trimesters. In conclusion, the gene methylation level in cord blood might be associated with prenatal environmental exposures. Birth weight and length were associated with both prenatal environmental exposures and genetic factors.

Due to the poor living and healthcare conditions, preterm birth (PTB) in rural population is a pressing health issue. However, PTB studies in rural population are rare. To explore the effects of air pollutants on PTB in rural population, we collected 697,316 medical records during 2014–2016 based on the National Free Preconception Health Examination Project. Logistic regression models were used to estimate the association between air pollutants and PTB and the modifying effects of demographic characteristics. Relative contribution and principal component analysis-generalized linear model (PCA-GLM) analysis were used to explore the most significant air pollutant and gestational period. Our results demonstrated that PTB risk is positively associated with exposure to air pollutants including PM10, PM2.5, SO2, NO2, and CO, while negatively associated with O3 exposure (P

Soil contamination with heavy metals is a worldwide problem especially in China. The interrelation of soil bacterial community structure, antibiotic resistance genes, and heavy metal contamination in soil is still unclear. Here, seven agricultural areas (G1-G7) with heavy metal contamination were sampled with different distances (741 to 2556 m) to the factory. Denaturing gradient gel electrophoresis (DGGE) and Shannon index were used to analyze bacterial community diversity. Real-time fluorescence quantitative PCR was used to detect the relative abundance of ARGs sul1, sul2, tetA, tetM, tetW, one mobile genetic elements (MGE) inti1. Results showed that all samples were polluted by Cadmium (Cd), and some of them were polluted by lead (Pb), mercury (Hg), arsenic (As), copper (Cu), and zinc (Zn). DGGE showed that the most abundant bacterial species were found in G7 with the lightest heavy metal contamination. The results of the principal component analysis and clustering analysis both showed that G7 could not be classified with other samples. The relative abundance of sul1 was correlated with Cu, Zn concentration. Gene sul2 are positively related with total phosphorus, and tetM was associated with organic matter. Total gene abundances and relative abundance of inti1 both correlated with organic matter. Redundancy analysis showed that Zn and sul2 were significantly related with bacterial community structure. Together, our results indicate a complex linkage between soil heavy metal concentration, bacterial community composition, and some global disseminated ARG abundance.

Although increasing evidence suggests that estrogen receptor α (ESRα) genetic variation could modify bone damage caused by environmental fluoride exposure, little is known about epigenetic mechanisms in relation to bone changes. A case-control study was conducted among farmers aged 18-55 years in Henan Province, China. X-ray was used to detect bone changes. Methylation status was determined by methylation-specific PCR. Genotypes were identified by Taqman probe and real-time PCR. In this study, we found that methylation status in the promoter region of the ESRα gene was lower in bone change cases than that in controls, which was only observed in male farmers after stratification by gender. Furthermore, methylation level was negatively associated with the urinary fluoride concentration in male farmers. No significant association was found between the distribution of ESRα rs2941740 genotypes and the risk of bone changes. Multivariate logistic regression analysis showed that after adjusting for age and gender, increased serum calcium and methylation status were protective factors for bone changes. No interaction effect was observed between fluoride exposure and ESRα rs2941740 polymorphism on bone changes. In conclusion, the current work suggests that bone changes are associated with methylation status, which might be modulated by fluoride exposure in male farmers. Methylation status and bone changes were not modified by ESRα gene rs2941740 polymorphism in the promoter region.

To assess the association between fluoride exposure and children���s behavioural outcomes, we recruited 325 resident school-age children (7���13 years old) lived in Tongxu County of Henan Province in China. We measured urinary fluoride (UF) concentrations using the ion-selective electrode method. Children���s behavioural outcomes were assessed by Conners��� Parent Rating Scale-Revised, including conduct problems, learning problems, psychosomatic problems, impulsive-hyperactive, anxiety, and ADHD index. It turned out that each 1.0 mg/L increment in UF concentration corresponded with an elevation in the psychosomatic problem score of 4.01 (95% CI: 2.74, 5.28) and a 97% (OR = 1.97, 95% CI: 1.19, 3.27) increase in the prevalence of psychosomatic problems after adjusting for potential influencing factors. The sensitivity analysis results were consistent with those observed in our preliminary analysis. Our study suggests that fluoride exposure is positively related to the behavioural problem in school-age children, psychosomatic problem in particular.

Excessive exposure to fluoride has been reported to affect bone mineral density (BMD). CALCA expression plays a critical part in bone formation. However, the role of CALCA in the association between fluoride and BMD is not known. We conducted a cross-sectional study and recruited 722 women in rural areas of Henan Province, China, to assess the relationship between fluoride exposure, CALCA methylation, and BMD. Urinary levels of fluoride, CALCA methylation, and BMD were measured by a fluoride ion-selective electrode, standalone ultrasound bone densitometer, and quantitative methylation-specific polymerases chain reaction, respectively. The association among fluoride exposure, CALCA methylation, and BMD was age-specific. Specifically, BMD was negatively correlated with methylation (β: -0.008; 95% CI: -0.016, 0.000) and fluoride exposure (β: -0.063; 95% CI: -0.129, -0.002) in women over 45 years and 50-54 years of age, respectively, whereas methylation was positively correlated with fluoride exposure (β: 4.953; 95% CI: 1.162, 8.743) in women aged 40-44 years. Besides, increased BMD in women aged 45-49 years induced by the interactive effect of the highest methylation of CALCA exon 1 (tertile 3) and fluoride exposure was observed (P for interaction 0.05). Our findings suggest an age-specific association between exposure to excessive fluoride, CALCA methylation, and BMD in a rural population of women in China. Notably, the susceptibility of BMD to fluoride exposure may be modified by CALCA methylation.

Meteorological conditions during pregnancy can affect birth outcome, which has been linked to the H19/H19-differentially methylated region (DMR). However, the detailed mechanisms underlying this association are unclear. This was investigated in the present study to provide epidemiological evidence for elucidating the pathogenesis of adverse birth outcomes. A total of 550 mother-newborn pairs were recruited in Zhengzhou, China from January 2010 to January 2012. Meteorological data including temperature (T), relative humidity (RH), and sunshine duration (SSD) were obtained from the China Meteorological Data Sharing Service System. Bisulfite sequencing PCR was performed to determine the methylation levels of H19/H19-DMR using genomic DNA extracted from maternal peripheral and umbilical cord blood. The results showed that H19-DMR methylation status in cord blood was positively associated with that in maternal blood. Neonatal H19-DMR methylation was negatively associated with T and RH during the first trimester and positively associated with these variables during the third trimester. There was a positive correlation between neonatal H19-DMR methylation and SSD during the second trimester and a negative correlation during the third trimester. Similar associations were observed between maternal H19-DMR methylation and prenatal meteorological conditions. We also observed significant interaction effects of maternal H19/H19-DMR methylation and most prenatal meteorological factors on neonatal methylation, and found that changes in the methylation status of maternal H19-DMR were responsible for the effects of prenatal meteorological conditions on neonatal methylation. In summary, neonatal H19-DMR methylation was significantly associated with prenatal meteorological conditions, which was modified and mediated by maternal H19-DMR methylation changes. These findings provide insights into the relationship between meteorological factors during pregnancy and adverse birth outcomes or disease susceptibility in offspring, and can serve as a reference for environmental policy-making.

A number of epidemiological studies have reported that chronic exposure to high concentrations of fluoride not only causes dental and skeletal fluorosis but additionally affects serum levels of reproductive hormones. However, possible interaction between fluoride exposure and estrogen receptor alpha (ESRα) gene polymorphisms on sex hormone-binding globulin (SHBG) and androgen binding protein (ABP) of male farmers has not been detailed. Here, we conducted a cross-sectional study including 348 male farmers with different fluoride exposure levels from drinking water in Henan province of China to explore effects of fluoride exposure and ESRα genetic variation on serum SHBG and ABP levels. We found serum SHBG levels in male farmers from the high exposure group to be lower than those of the low exposure group. We also found that concentrations of SHBG affected ABP levels. Furthermore, fluoride exposure and single nucleotide polymorphisms at the XbaI and rs3798577 loci of the ESRα gene affected serum ABP levels. Our findings suggest that chronic fluoride exposure from drinking water is associated with alterations of serum SHBG and ABP concentrations in local male farmers and that the effect of fluoride exposure on ABP levels vary depending on ESRα gene polymorphisms.

The aim of this study was to explore the influence of fluoride exposure and ERα gene polymorphisms on reproductive hormone concentrations of women in accordance with endemic fluorosis residence.A cross sectional study was conducted in Tongxu county, Henan Province, China. A total of 679 women were recruited using cluster sampling and each subject provided fasting blood and an associated urine sample. We measured the concentrations of serum gonadotropin releasing hormone (GnRH), follicle-stimulating hormone, luteinizing hormone, and estradiol and urinary fluoride.In the defluoridation project group (DFPG), serum GnRH was lower in women carrying C/C genotype compared to in those carrying C/T and T/T genotypes of ERα gene rs3798577 (p0.05). In the endemic fluorosis group (EFG), serum GnRH was lower in women carrying Pp genotype compared to in those carrying PP and pp genotypes of ERα PvuII (p0.05). Serum GnRH in women from EFG who carried Pp, pp, Xx and xx genotypes in ERα gene PvuII and XbaI was lower than in those in the control group (CG) who carried same genotypes (p0.05). Furthermore, serum GnRH in women from EFG was significantly lower than in those in CG, regardless of whether the women were carrying C/C, C/T or T/T genotypes of ERα rs3798577 (p0.05). Serum estradiol concentrations in EFG were significantly lower than in CG when the women were carrying the Pp, Xx and T/T genotypes in ERα gene (p0.05).Interaction of ERα gene and fluoride exposure may influence women's serum reproductive hormone concentrations.背景与目的：探讨氟暴露及ERα 基因多态性对氟病区女性生殖激素浓度的影 响。方法与研究设计：按照饮用水中氟浓度分为氟病区组、改水组和对照组。 采用整群抽样的方法选择中国通许县居住的679 名成年女性为研究对象，采集 研究对象空腹静脉血及晨尿样本， 并测量血清促性腺激素释放激素 （gonadotropin releasing hormone, GnRH）、卵泡刺激素、促黄体生成素、雌二 醇和尿氟浓度。结果：改水组携带ERα rs3798577 C/C 基因型女性血清GnRH 浓 度低于携带C/T 和T/T 基因型女性（p0.05）。氟病区组携带ERα PvuII Pp 基 因型女性血清GnRH 浓度低于携带PP 和pp 基因型女性（p0.05）。携带ERα PvuII Pp、pp 和ERα XbaI Xx、xx 基因型的女性血清GnRH 浓度低于对照区携 带相同基因型的女性（p0.05）。此外，无论其携带的ERα rs3798577 基因型是 C/C 、C/T 或T/T ， 氟病区组女性血清GnRH 浓素均低于对照区女性 （p0.05）。携带ERα PvuII Pp, ERα XbaI Xx 和ERα rs3798577 T/T 基因型的氟 病区女性血清雌二醇浓度低于携带相同基因型的对照区女性（p0.05）。结 论：ERα 基因和氟暴露的交互作用可能影响女性血清生殖激素的浓度。.

Vitamin D receptor (VDR) genetic polymorphisms are considered to be associated with type 2 diabetes mellitus (T2DM), but this is inconclusive. The aim of this study is to quantify the association between polymorphisms of BsmI and FokI in the VDR gene and T2DM risk through literature review.Original articles published from 1999 to June 2014 were discovered through PubMed, ISI Web of Science, China National Knowledge Infrastructure, Chinese Wanfang Database, and the Chinese Biomedical Literature Database. The pooled odds ratios (ORs) with 95% confidence intervals (CIs) were calculated with software STATA version 12.0.Twenty-three articles containing 30 case-control studies were included. The association between the BsmI polymorphism and T2DM was weak in two genetic models (Bb vs bb and BB+Bb vs bb). The subgroup analysis showed that this association was only found in the studies with a small sample size (200). A strong association between FokI polymorphism and T2DM indicated that this gene polymorphism was possibly a risk factor for T2DM (ff vs FF: OR=1.57, 95% CI: 1.28-1.93, p0.001; Ff vs FF: OR=1.54, 95% CI: 1.31-1.81, p0.001; ff+Ff vs FF: OR=1.57, 95% CI: 1.35-1.83, p0.001), especially in Chinese populations.More reliable conclusions about associations between VDR genetic polymorphisms and T2DM will depend on studies with larger sample size and by ethnicity.背景与目的： 研究发现维生素D受体（VDR）基因多态性与2 型糖尿病 （T2DM）的发病关系密切，但相关文献报道结论并不一致。本研究的目的是 通过文献系统综述对VDR受体基因BsmI和FokI位点单核苷酸多态性与T2DM的 关联性进行评价。方法与研究设计：于PubMed 、ISI Web of Science、中国期 刊全文数据库（CNKI） 、中国万方数据库和中国生物医学文献数据库 （CBM）中检索1999年至2014年期间发表的所有相关文献。运用Stata 12.0软 件，通过计算OR值和95% CI来评价位点BsmI和FokI变异与T2DM的关联性。 结果：共23篇文献30个病例对照研究纳入本次meta分析中。分析结果显示 BsmI位点单核苷酸多态性与T2DM易患性在两种基因模型中（Bb vs bb 和 BB+Bb vs bb）存在弱的相关性。亚组分析显示这种弱的相关性主要出现在样 本量较小的研究中（200）。FokI位点单核苷酸多态性与T2DM易患性（ff vs FF：OR=1.57，95% CI：1.28-1.93，p0.001; Ff vs FF：OR=1.54，95% CI： 1.31-1.81，p0.001; ff+Ff vs FF：OR=1.57，95% CI：1.35-1.83，p0.001）存 在强的相关性，提示该位点基因突变是T2DM的危险因素，尤其是在中国汉族 人群中。结论：有关VDR基因与T2DM的关联分析还需要大样本量和不同种族 研究的支持。.

Excessive fluoride intake has been shown to affect dentin and cementum mineralization throughout life. Some studies indicated that a HindIII polymorphism, of osteocalcin (OC) gene, was associated with bone metabolism-related diseases. Therefore, it is possible that the variation in OC genotypes will be associated with dental fluorosis (DF) status and/or serum caciotropic hormone level. A case-control study was conducted among children aged 8-12 years in Henan Province, PR China to investigate the association between dental fluorosis, serum calciotropic hormone level, and polymorphisms in the OC gene. HindIII polymorphism in OC gene was genotyped using the PCR-RFLP procedure. OC and calcitonin (CT) level in serum was detected using radioimmunoassay. No significant difference was observed for OC HindIII genotypes among the cases with dental fluorosis, the controls from endemic fluorosis area (EFA) and the controls from non-endemic fluorosis area (NEFA). A significant negative correlation was observed between serum calcium and OC level. No significant relationship was found between OC HindIII polymorphisms and the level of OC and CT. In conclusion, OC HindIII polymorphisms may not be a useful genetic marker for differential risk of dental fluorosis among children in PR China.

Many studies have demonstrated that exposure to excess fluoride was associated with a variety of diseases. Little is known about the variation of testosterone (T) levels caused by fluoride exposure. The aim of this study is to explore the association of fluoride exposure and age with serum T and androgen-binding protein (ABP) levels in male farmers. A cross-sectional study was conducted in a county of Henan Province, China, including high fluoride exposure from drinking water villages and control villages. Male farmers aged 18-55 years old who lived in these villages were recruited by cluster sampling and divided into a higher fluoride exposure group (HFG) and a lower fluoride exposure group (LFG) according to the level of urinary fluoride. Levels of T and ABP in serum were measured using chemiluminescence immunoassay (CLIA) and enzyme-linked immunosorbent assay (ELISA) respectively. Markedly lower T levels were observed in male farmers from the HFG than in those from the LFG (t = 2.496, P

Vitamin D and the vitamin D receptor (VDR) are associated with susceptibility to type 2 diabetes mellitus (T2DM). The purpose of the present study was to screen more single nucleotide polymorphisms (SNPs) of VDR and assess their effects on the risk of T2DM in Han Chinese.Four SNPs were genotyped in 1191 individuals (397 cases, 794 controls). Allele frequencies and genotype distributions were analyzed. Effects were investigated by evaluating genotype distribution with regard to phenotypes, insulin resistance, and β-cell function. Haplotype analysis and gene risk score (GRS) were used to evaluate the combined and additive roles of VDR SNPs on T2DM pathogenesis.There was a significant association between rs739837 and T2DM in two models and allele frequency distribution. The novel locus rs2239179 differed significantly between cases and controls, especially in males and those aged55 years, in three models and allele frequency distribution. The TT genotype of rs739837 was associated with higher triglyceride than GG and TG genotypes, and higher total cholesterol levels than the GG genotype. Compared with the GTGA haplotype, the GCGG haplotype reduced the risk of T2DM. Trend Chi-squared tests showed that there was significant association between the weighted GRS and the risk of T2DM (PThis study provides novel evidence that rs739837 is associated with lipid metabolism in T2DM patients. The rs739837 and rs2239179 SNPs were associated with the risk of T2DM in Han Chinese. The VDR SNPs had combined and additive effects on the risk of T2DM.

The effects of fluoride exposure on the functions of reproductive and endocrine systems have attracted widespread attention in academic circle nowadays. However, it is unclear whether the gene-environment interaction may modify the secretion and activity of hypothalamus-pituitary- ovarian (HPO) axis hormones. Thus, the aim of this study was to explore the influence of fluoride exposure and follicle stimulating hormone receptor (FSHR) gene polymorphism on reproductive hormones in Chinese women. A cross sectional study was conducted in seven villages of Henan Province, China during 2010-2011. A total of 679 women aged 18-48 years were recruited through cluster sampling and divided into three groups, i.e. endemic fluorosis group (EFG), defluoridation project group (DFPG), and control group (CG) based on the local fluoride concentration in drinking water. The serum levels of gonadotropin releasing hormone (GnRH), follicle stimulating hormone (FSH), luteinizing hormone (LH), and estradiol (E2) were determined respectively and the FSHR polymorphism was detected by real time PCR assay. The results provided the preliminary evidence indicating the gene-environment interaction on HPO axis hormones in women.

The aim of this study was to explore the association of parathyroid hormone (PTH) gene Bst BI polymorphism, calciotropic hormone levels, and dental fluorosis of children. A case-control study was conducted in two counties (Kaifeng and Tongxu) in Henan Province, China in 2005-2006. Two hundred and twenty-five children were recruited and divided into three groups including dental fluorosis group (DFG), non-dental fluorosis group (NDFG) from high fluoride areas, and control group (CG). Urine fluoride content was determined using fluoride ion selective electrode; PTH Bst BI were genotyped using PCR-RFLP; osteocalcin (OC) and calcitonin (CT) levels in serum were detected using radioimmunoassay. Genotype distributions were BB 85.3% (58/68), Bb 14.7% (10/68) for DFG; BB 77.6% (52/67), Bb 22.4% (15/67) for NDFG; and BB 73.3% (66/90), Bb 27.7% (24/90) for CG. No significant difference of Bst BI genotypes was observed among three groups (P0.05). Serum OC and urine fluoride of children were both significantly higher in DFG and NDFG than in CG (P0.05, respectively), while a similar situation was not observed between DFG and NDFG in high fluoride areas (P0.05). Serum OC level of children with BB genotype was significantly higher compared to those with Bb genotype in high fluoride areas (P0.05). However, no significant difference of serum CT or calcium (Ca) was observed. In conclusion, there is no correlation between dental fluorosis and PTH Bst BI polymorphism. Serum OC might be a more sensitive biomarker for detecting early stages of dental fluorosis, and further studies are needed.

To explore removal effect of riverside pumping project on microcystins in the Yellow River.In the summer and autumn of 2008, water samples of the Yellow River and five selected tube-wells in "9 x 5" beach of riverside pumping project were collected and microcystin contents in water were determined using ELISA.Microcystin contents in water in the Yellow River were less than microcystin-LR reference value in Drinking Water Standards. The average contents of the autumn of microcystins were more higher than those of the summer (P0.01). Microcystins contents of five tube-wells were more lower than those of the Yellow River. Removal effect of riverside pumping project on microcystins has nothing to do with the distance from the trunk of the Yellow River.Riverside pumping project has a good removal efficiency on microcystins.

To study of endocrine disturbing effect of fluoride on human hypothalamus-hypophysis-testis axis hormones.Sunying County, Kaifeng City was selected as polluted district which the fluoride in drinking water was 3.89 mg/L, and Shenlilou county was selected as control district which the fluoride was less than 1.0 mg/L. 150 individual lived there more than 5 years were srlected randomly. And investigated by medical examination, then blood and urine sample were collected, and the serum level of gonadotropin-releasing hormone (GnRH), luteinizing hormone (LH), testosterone (T) and estradiol (E2) were measured by RIA method, and the urine level of fluoride were measured. Other than that, the concentration of fluoride in the water, food, soil and air were detected by the standard methods.The concentrations of fluoride in the water, food and soil of the fluoride polluted district were significantly higher than those of control district (P0.05), and the concentration fluoride in the air of two district were not found. There was no significant difference of serum level of GnRH between fluoride polluted district and control district (P0.05). The serum level of LH in men of fluoride polluted district was significantly higher than that of control group (P0.05), and the serum level of T in men of fluoride polluted district was significantly less than that of control group (P0.05). There was no significant difference of serum level of LH between fluoride polluted district and control district (P0.05), and the serum level of T in women of fluoride polluted district was significantly higher than that of control group (P0.05). There was no significant difference of serum level of E2 between fluoride polluted district and control district (P0.05).Fluoride could effect hormone levels of each layer of the hypothalamus-hypophysis-testis axis, and show the reproductive endocrine disturbing effects. The reproductive endocrine disturbing effects of male maybe more severe than those of female.

To explore the distribution of ER Rsa I genotype in children who lived in the areas with or without high fluoride, and evaluate the relationship between ER Rsa I gene polymorphism and children's dental fluorosis.Children aged 8 to 12 years, born and raised in high fluoride areas and control areas in two counties of Henan Province were recruited. The Rsa I marker of ER gene was genotyped in 237 children composed of both dental fluorosis cases and controls by PCR-RFLP procedure. Urine fluoride was detected with fluoride ion selective electrode method.The frequency distribution of ER Rsa I genotype was rr 60.81% (45/74), Rr 27.02% (20/74), RR 12.16% (9/74) in children with fluorosis; rr 73.91% (51/69), Rr 20.29% (14/69), RR 5.80% (4/69) in children without fluorosis from high fluoride areas, and rr 63.83% (60/94), Rr 34.04% (32/94), RR 2.13% (2/94) in the children without fluorosis from control areas respectively. There were no significant differences in the three groups (P0.05), but children carrying allele R of ER Rsa I had a significantly increased risk of dental fluorosis (OR=1.821, 95% CI: 1.013-3.274) compared to children carrying the allele r in endemic fluorosis areas.Although no significant difference was found in ER Rsa I genotype between cases and non-dental fluorosis in endemic fluorosis areas, children carrying R allele of ER Rsa I had a higher risk compared to children carrying r allele, and the further study is needed.

To establish the predictive model of eutrophication in the main water source in Zhengzhou City.Water temperature (WT), secchi-depth (SD), total phosphorus (TP), total nitrogen (TN), light illuminance (LI), chemical oxygen demand (CODMn), chlorophyll-a (Chla) were monitored in Xiliu lake and Huayuankou pool. Grading points method and comprehensive trophic state index method were used to evaluate the trophic state. Backpropagation artificial neural network with Levenberg-Marquardt algorithm was used to establish the forcasting model of eutrophication after the raw data normalized treated using standardization function.The results of evaluation of grade method revealed that the two waters source were in nutritional state and the tendencies of year grade indexes were from the lower critical value to eutrophic state to higher critical value of eutrophication of xiliu lake. The scope of hidden nodes was determined from 2 to 15 according to the calculated results using function of J = (mean square root of n + M) + a and the hidden nodes was 10 according to the training result. All of the physical chemistry factors were brought into the model. The training error was 1e-11 and the coefficient correlation of the network fitness result was 0.871. The fitting result was close to the aim and the predictive model of eutrophication in the main resource water in Zhengzhou City was established successfully.Eutrophication forcasting model could be established using artificial neural network, and the method of artificial neural network should be better to meet the actual demand.

Objectives: To investigate the relationship between dental fluorosis, polymorphisms in the COL1A2 gene, and serum calciotropic hormone levels. Methods: We conducted a case-control study among children between 8 and 12 years of age with (n = 75) and without (n = 165) dental fluorosis in two counties in Henan Province, China. The PvuII and RsaI polymorphisms in the COL1A2 gene were genotyped using the PCR-RFLP procedure. Calcitonin and osteocalcin levels in the serum were measured using radioimmunassays. Results: Children carrying the homozygous genotype PP of COL1A2 PvuII had a significantly increased risk of dental fluorosis (OR =4.85, 95% CI: 1.22–19.32) compared to children carrying the homozygous genotype pp in an endemic fluorosis village (EFV). However, the risk (OR = 1.07, 95% CI: 0.45–2.52) was not elevated when the control population was recruited from a non-endemic fluorosis village. Additionally, fluoride levels in urine and osteocalcin levels in serum were found to be significantly lower in controls from non-endemic villages compared to cases. However, the differences in fluoride and osteocalcin levels were not observed when cases were compared to a control population from endemic fluorosis villages. Conclusions: This study provides the first evidence of an association between polymorphisms in the COL1A2 gene with dental fluorosis in high fluoride exposed populations. Future studies are needed to confirm the association.

To investigate the contaminative, condition of planktonic algae, cyanobacteria, toxigenic microcystis and microcystin in Huayuankou Conservation Pool of Yellow River.From March 2005 to January 2006, water samples were taken 15 times by 2. 5L plastic sampler from Huayuankou Conservation Pool. The density of algae were counted by using blood cell counter. Phycocyanin intergenic spacer region (PC-IGS) and microcystin synthetase gene B (mcyB) of toxigenic microcystis was identified by the whole cell PCR. The concentration of microcystin was determined by ELISA kit. The positive results of PCR and ELISA were compared.Bacillariophyta, chlorophyta, cyanophyta (cyanobacteria) and euglenophyta were main algaes in Huayuankou conservation pool, and the dominant algae and cell density changed seasonally. Algae cell density and cyanobacteria cell density were higher in summer and autumn than in spring and winter. From July to November, 2005, PC-IGS and mcyB were detected positively by whole cell PCR. Microcystin was positively detected from July, the concentration of microcystin changed from 0 to 0.25microg/L, it was more higher in summer than other seasons.Toxigenic microcystis and microcystin could be detected in Huayuankou Conservation Pool of Yellow River. Whole cell PCR could be used to identify toxigenic microcystis.

To analyze the toxic characteristic of microcystis in a life water source.Microcystis in Huayuankou conservation pool and Xiliu lake were isolated by 96-microbiological assay and supreme dilution methods. Phycocyanin intergenic spacer region (PC-IGS) and microcystin synthetase gene B (McyB) were detected by whole-cell PCR method, And toxicities of microcystis were identified by solid pole of extraction (SPE) and high performance liquid chromatography (HPLC) method.The microcystis of the water source were cyanobacteria which could contain PC-IGS and McyB expressing positively, Comparition with reported meyB of Microcystis aeruginosa in Genbank, the homology of gene sequence was 99%. The main toxic isomers of the three microcystis were MC-LR, whose proportions of the whole toxin were 97.9%, 98.6% and 99.3%, respectively.The microcystis of the main life water source maybe poisonous and the main isomer maybe MC-LR.

To investigate the contaminative condition of the floating algae (especially toxic cyanobacteria) in Xiliu Lake, and establish a whole-cell PCR method for identifying the toxic cyanobacteria.The surface water of Xiliu Lake was sampled by plastic sampler from March, 2004, and the number of algae was counted by using blood cell counter. The phycocyanin intergenic spacer region (PC-IGS) and microcystin synthetase gene B (mcyB) were identified by whole-cell PCR in water samples, and the amplified product of mcyB was inserted into T vector and sequenced.Cyanobacteria, Chlorophyta, Bacillariophyta and Euglenophyta were main algae, and cyanobacteria was the dominant algae in summer and autumn. From July 7 to September 27,2 004, PC-IGS was detected positively in 11 samples, and from July 29 to September 27, mcyB was-detieted positively in 9 samples. Compared with the reported mcyB of Microcystis aeruginosa in Genbank, the homology of gene sequence was more than 97 t he homology of amino acid sequence was more than 94%.In summer and autumn toxic cyanobacteria could be detected in Xiliu Lake. Toxic cyanobacteria could be identified successfully by whole-cell PCR.