Exposure to parabens and dysglycemia: Insights from a Chinese population.

BACKGROUND: Parabens, a widely exposed environmental endocrine disruptor, were reported to disturb glucose metabolism through various pathways in animal models, but epidemiologic studies are limited. Therefore, this study aimed to investigate the plasma parabens level in rural populations and their effects of single and mixed paraben exposure on T2DM based on the Henan Rural Cohort. METHODS: A total of 1713 participants (880 T2DM and 833 controls) from the Henan Rural Cohort Study were included in this case-control study. Generalized linear regression models were performed to assess the single and joint effects of parabens on T2DM and glucose metabolism indicators. In addition, the dose-response relationship of plasma parabens with T2DM and glucose metabolism indicators were explored by the restricted cubic splines. Bayesian kernel machine regression (BKMR) and quantile g-computation models were utilized to assess overall associations of paraben mixtures with T2DM and glucose metabolism indicators. RESULTS: Σparabens and methylparaben (MeP) exposure significantly increased the risk of T2DM (P < 0.01). However, ethylparaben (EtP) and butylparaben (BuP) were negatively related to T2DM (P < 0.01). Notably, non-linear relationships of EtP and BuP with T2DM were observed. When the level of EtP or BuP was above the inflection point observed in dose-response curve, the ORs and 95% CIs were 1.453 (1.252, 1.686) and 1.982 (1.444, 2.721), respectively. Moreover, the result of quantile g-computation also showed that exposure to high concentration of parabens mixture was positively related to the risk of T2DM. BKMR model indicated that parabens mixture was associated with glycometabolism following a U-shape and parabens mixture increased the risk of dysglycemia when all parabens concentrations were at or above their 55th percentile compared with the median. CONCLUSION: MeP or paraben mixture exposure levels showed a linear positive association with risk of T2DM. EtP and BuP were nonlinearly associated with glucose metabolism and moderate-high exposure contributed to T2DM.

The association of cortisol/testosterone ratio and sleep quality with coronary heart disease: A case-control study in Chinese rural population.

PURPOSE: There were limited studies that have probed into the combined effect of the cortisol/testosterone (C/T) ratio as a biomarker of stress and Pittsburgh Sleep Quality Index (PSQI) on coronary heart disease (CHD). This research aimed to explore the association of C/T ratio and PSQI with the risk of CHD in a rural Chinese population, as well as the interaction and combined effect between C/T ratio and PSQI on CHD. METHODS: A case-control study was performed including 307 individuals without CHD and 307 patients drawn from Henan Rural Cohort. Logistic regression was utilized to survey the independent and joint effects of the C/T ratio and PSQI on CHD. To estimate the interaction impact of the C/T ratio and sleep quality (PSQI) on CHD, a cross-product term was introduced in the generalized linear model. RESULTS: Higher C/T ratio and PSQI index scores are related to increased odds ratio for CHD (Odds ratios (ORs) and 95 % confidence interval (CI) were 1.17 (1.07, 1.29), p-trend < 0.001; 1.16 (1.09, 1.22), respectively). The odds ratio of C/T ratio for CHD increased with increasing PSQI in women (pinteraction = 0.018) and total population (pinteraction = 0.033). The combined group of high C/T ratio and high PSQI had the highest risk of CHD (Total: OR = 7.53, 95 % CI: 4.12-13.76). CONCLUSIONS: The risk of CHD was associated with low testosterone levels, high C/T ratios, and high PSQI scores. Additionally, poor sleep quality aggravated the effect of high C/T ratio on coronary heart disease.

Differential Expression of lncRNA-miRNA-mRNA and Their Related Functional Networks in New-Onset Type 2 Diabetes Mellitus among Chinese Rural Adults.

Increasing evidence suggested that the expression and inter-regulation of long noncoding RNA (lncRNA), microRNA (miRNA), and messenger RNA (mRNA) were related to the development of diabetes. Based on bioinformatics analysis, this study aimed to comprehensively analyze the dysregulated RNA molecules related to new-onset type 2 diabetes mellitus (T2DM). Twenty-four patients with new-onset T2DM were included as cases, and sex- and age-matched participants were included as controls. The differentially expressed lncRNAs, miRNAs, and mRNAs between the two groups were screened by RNA sequencing. LncRNA-miRNA-mRNA network and enrichment analysis were used to reveal the RNA molecules that were potentially associated with T2DM and their early changes. A total of 123 lncRNAs, 49 miRNAs, and 312 mRNAs were differentially expressed in the new-onset T2DM (fold change ≥ 1.5 and p value < 0.05). Functional analysis revealed that differentially expressed RNAs were likely to play essential roles in diabetes-related pathways. In addition, the protein-protein interaction (PPI) network screened multiple hub mRNAs, and lncRNA-miRNA-mRNA networks showed that a single miRNA could be related to multiple lncRNAs, and then they coregulated more mRNAs. SLC25A4, PLCB1, AGTR2, PRKN, and SCD5 were shown to be important mRNAs in T2DM, and miR-199b-5p, miR-202-5p, miR-548o-3p as well as miR-1255b-5p could be involved in their regulation. In conclusion, several new and previously identified dysregulated lncRNAs, miRNAs, and mRNAs were found to be vital biomarkers in T2DM. Their alterations and interactions could modulate the pathophysiology of T2DM. Those findings may provide new insights into the molecular mechanisms underlying the development of T2DM.

Relationship of miRNA­126 and miRNA­122 expression with type 2 diabetes mellitus and related glucose metabolism parameters: A systematic review and meta­analysis.

There are increasing numbers of studies investigating the potential link between microRNAs (miRNAs) and type 2 diabetes mellitus (T2DM) risk. Based on the prior evidence and the differentially expressed candidate plasma exosome miRNAs in our established discovery study, the current meta-analysis studied miR-126 and miR-122 specifically. The purpose of the present study was to systematically and quantitatively evaluate the relationship of miR-126 and miR-22 expression level with T2DM risk as well as related glucose metabolism parameters. Moreover, the present study was performed based on the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guideline (PRISMA 2020 statement). PubMed, Embase, Web of Science, Cochrane and Chinese National Knowledge Infrastructure electronic databases were used to identify eligible original studies prior to May 3, 2022. The random-effects models were employed to explore the overall effect estimates [odds ratio (OR) and 95% confidence interval (CI), or correlation coefficient (r, 95% CI)]. The subgroup analyses were conducted to examine the potential sources of heterogeneity. The potential publication bias was assessed by the Begg's funnel plot and Egger's tests. A total of 46 articles were included in the present meta-analysis. The results revealed that higher exposure level of miR-126 was related to lower T2DM risk in 5 analytical epidemiological studies [OR=0.73, 95% CI: (0.55, 0.96)], lower fasting blood glucose (FBG) [N=22, r=-0.26, 95% CI: (-0.42, -0.10)], and lower homeostasis model assessment of insulin resistance (HOMA-IR) index [N=9, r=-0.28, 95% CI: (-0.52, -0.05)]. Besides, positive correlations were observed between miR-122 expression and FBG [N=10, r=0.34, 95% CI: (0.20, 0.48)], as well as HOMA-IR index [N=9, r=0.40, 95% CI: (0.16, 0.64)]. The relationship of miR-126 and miR-122 expression with T2DM risk and these glucose metabolism parameters may be influenced by study types, sample size, different source and mean age of participants. In conclusion, in the general healthy population, higher miR-126 expression was related to lower T2DM risk, FBG level and HOMA-IR index; higher miR-122 expression was closely correlated with higher FBG level and HOMA-IR index. These findings have notable clinical and public health implications for screening and control glucose metabolic disorders, insulin resistance and T2DM development.

The correlation between testosterone and stroke and the mediating role of blood pressure: The Henan rural cohort study.

AIMS: We aimed to investigate the association of serum testosterone with stroke and calculate the proportion explained by blood pressure on this association. MATERIALS AND METHODS: A total of 6175 subjects were included in this study. Serum testosterone was quantified by liquid chromatography-tandem mass spectrometry. The logistic regression model was used to evaluate the association between serum testosterone and stroke. Linear regression analysis was used to assess the associations of serum testosterone with blood pressure. In addition, mediation analysis was performed to identify the mediation effects of blood pressure on the association of serum testosterone with stroke. Sex-stratified analysis was employed throughout the research. RESULTS: After adjusting for multiple variables, serum testosterone levels were negatively associated with stroke in males (per 1 unit natural log-transformed, odds ratio (OR) = 0.81, 95% confidence interval (CI): 0.69-0.94; Tertile 3 vs Tertile 1, OR = 0.65, 95% CI:0.44-0.96). Furthermore, blood pressure played a partial mediating role in the relationship between testosterone and stroke in males. The indirect effect/total effect of systolic blood pressure, diastolic blood pressure and mean arterial pressure were 7.37%, 9.54% and 9.22%, respectively. Notably, the relationship between testosterone and stroke and the role of blood pressure in regulating them was not observed in females. CONCLUSION: This study describes that in rural Chinese males, testosterone can reduce the risk of stroke by affecting blood pressure. To some extent, we provide a new epidemiological evidence for the relationship between testosterone and stroke.

Associations of residential greenness, ambient air pollution, biological sex, and glucocorticoids levels in rural China.

AIMS: To evaluate the associations between residential greenness and glucocorticoid levels and whether air pollutants and sex modify the relationship between greenness and glucocorticoid level in Chinese rural adults. METHODS: We collected cross-sectional survey data from 6055 participants from the Henan Rural cohort. The three-year average residential greenness for participants was assessed using normalized difference vegetation index (NDVI) values from a satellite platform. Liquid chromatography-tandem mass spectrometry was employed to quantify the concentrations of glucocorticoids, which were measured by morning blood draw after at least 8 hr of fasting. A random forest model was employed to obtain the average concentrations of PM1, PM2.5, and PM10. A general linear regression model was performed to estimate the associations of NDVI500-m values with cortisol, 11-deoxycortisol, and cortisone. Furthermore, interaction plots were used to present the interaction effects of particulate matter, sex, and green space on glucocorticoid levels. RESULTS: After adjusting for multiple variables, an elevated average NDVI500-m value in the total population was associated with a decrease in cortisol levels (ß = -0.063, 95 % confidence interval (CI): - 0.118, - 0.008), and 11-deoxycortisol levels (ß = -0.118, 95 % CI: -0.190, -0.047), as well as an increase in cortisone levels (ß = 0.130, 95 % CI: 0.079, 0.181). By adding the interaction terms of air pollutants and residential greenness into the regression model, interaction effects between air pollutants and residential greenness were found (cortisol, PM2.5: P interaction=:0.018; PM10: P interaction=0.016; 11-deoxycortisol, all pollutants: P interaction< 0.001), suggesting that the protective effect of residential greenness on serum glucocorticoids disappeared accompanying with increased concentrations of particulate matter. Moreover, trends towards modification in the association between green space and glucocorticoid levels were also evident by sex, but these did not reach statistical significance (for all glucocorticoids: P interaction> 0.05). CONCLUSION: Long-term exposure to green space was negatively correlated with cortisol and 11-deoxycortisol levels, and positively correlated with cortisone levels. There may be sex differences in these associations. Moreover, the protective effect of residential greenness on serum glucocorticoids was altered by high levels of particulate matter.

Pesticide Residues in Commonly Consumed Vegetables in Henan Province of China in 2020.

Background: Pesticides are widely used in agricultural production to control insect pests and regulate plant growth in China, which may result in the presence of some pesticide residues in the vegetables. However, few studies of monitoring pesticides have been conducted in Henan Province. The aim of this study was to evaluate the level of pesticide residues in commonly consumed vegetables in the regions of Henan Province. Methods: In this study, we collected 5,576 samples of 15 different vegetables in 17 areas from Henan Province during 2020. Eight kinds of pesticides were analyzed by gas chromatography-mass spectrometry (GC-MS), including procymidone, lambda-cyhalothrin, cypermethrin, pendimethalin, isocarbophos, isazophos, fenthion and deltamethrin. The chi-square test was used to compare the detection rates of pesticide residues in different regions. Results: Of all the pesticides above, procymidone, lambda-cyhalothrin, cypermethrin, pendimethalin and isocarbophos were detected in vegetables, the detection rates were 27.0%, 16.2%, 11.4%, 3.5%, and 1.9%, respectively. However, isazophos, fenthion, and deltamethrin were not detected. In addition, procymidone, lambda-cyhalothrin, and cypermethrin were detected in urban areas, while pendimethalin was detected in rural areas. The detection rates of cypermethrin and pendimethalin in rural were 19.8% and 5.4%, respectively, which in urban were at relatively lower levels (13.7% and 1.9%, respectively) (P < 0.05). Compared the differences of pesticide detection rates among five areas of Henan province, we found that there were statistical differences in the detection rates of procymidone, cypermethrin and lambda-cyhalothrin in different regions (all P < 0.05). Conclusion: The results have revealed that the pesticide residues are present. Higher detection rates and more types of pesticides were found in rural areas than urban areas. In addition, there were higher detection rates in Eastern Henan. The findings provided valuable information on the current pesticide residues status, which can be a reference of pesticide supervision and management.

Ambient ozone exposure combined with residential greenness in relation to serum sex hormone levels in Chinese rural adults.

BACKGROUND: Long-term exposure to ambient ozone (O3) and residential greenness independently relate to altered hormones levels in urban settings and developed countries. However, independent and their joint associations with progestogen and androgen were sparsely studied in rural regions. MATERIALS AND METHODS: A total of 6211 individuals were recruited in this study. Random forest model was applied to predict the daily average concentrations of O3 using the satellites data. Residential greenness was reflected by the normalized difference vegetation index (NDVI). Liquid chromatography-tandem mass spectrometry was used to measure serum progestogen and androgen concentrations. Gender and menopausal status modified associations of long-term exposure to O3 and residential greenness with hormones levels were analyzed by generalized linear models. RESULTS: Long-term exposure to O3 was negatively related to 17-hydroxyprogesterone, testosterone, and androstenedione in both men and women (premenopausal and postmenopausal); the estimated ß and 95% CI of ln-progesterone in response to per 10 µg/m3 increment in O3 concentration was -0.560 (-0.965, -0.155) in postmenopausal women. Association of long-term exposure to O3 with serum androgen levels in premenopausal and postmenopausal women were alleviated by residing in places with higher greenness. Additionally, a prominent effect of long-term exposure to O3 related to decreased serum progestogen and androgen levels was found in participants with middle- or high-level of physical activity or lower education level. CONCLUSIONS: The results suggested that long-term exposure to high levels of O3 related to decreased serum androgen levels was attenuated by living in high greenness places in women regardless of menopause status. Future studies are needed to confirm the positive health effects of residential greenness on the potential detrimental effects due to exposure to O3.

Combined effects of air pollution in adulthood and famine exposure in early life on type 2 diabetes.

Famine exposure or air pollution is linked to type 2 diabetes mellitus (T2DM). However, their combined effects on T2DM remain largely unknown. A total of 11,640 individuals were obtained from the Henan Rural Cohort Study. According to their birthdate, participants were divided into three famine exposure subgroups: fetal exposed, childhood exposed, and unexposed groups. The air pollutants (particles with aerodynamics diameters ≤ 1.0 µm (PM1), ≤ 2.5 µm, and ≤ 10 µm, and nitrogen dioxide) concentrations of each individual were estimated by a spatiotemporal model. Participants were divided into low or high air pollution exposure groups taking the 1st quartile value of air pollutants as the cut-off point. Logistic regression model was used to analyze independent and joint associations between air pollution exposure, famine exposure, and T2DM. Positive associations of air pollution and famine exposure with T2DM were found. Participants who experienced fetal or childhood famine and also were exposed to high concentrations of any kind of the air pollutants had a much higher risk for T2DM than those with no famine and low air pollutants exposure (taking PM1.0 for example, the odds ratio [OR]: 1.76, 95% confidence interval [CI]: 1.25, 2.47 for fetal famine, and OR: 1.64, 95%CI: 1.13, 2.40 for childhood famine). After stratified analysis, similar results were observed in women. The results indicated that both famine exposure in early life and air pollution exposure in adulthood are related to increased risk for prevalent T2DM, and they have combined effects on T2DM.

Serum cortisol-to-cortisone ratio and 11-deoxycortisol are associated with hypertension and blood pressure in Chinese rural population: a cross sectional study.

OBJECTIVE: The present study aimed to investigate the associations of cortisol-to-cortisone ratio (F/E) and 11-deoxycortisol (S) in hypertension and blood pressure among Chinese rural population. METHODS: A total of 6233 participants from the Henan Rural Cohort Study were included. Serum cortisol (F), cortisone (E), and S were assessed using liquid chromatography-tandem mass spectrometry. Generalized linear model (GLM) and logistic regression model were performed to assess the associations of F, E, F/E, and S with blood pressure and hypertension. Moreover, the sex specificity of the associations was assessed. RESULTS: Serum F, F/E, and S were positively associated with systolic blood pressure (SBP), diastolic blood pressure (DBP), and pulse pressure (PP), while E was negatively associated with SBP and PP. There were no statistically significant associations of F and E with the prevalence of hypertension, while F/E and S were positively associated with hypertension [odds ratios (ORs) and 95% confidence intervals (CIs)] of F/E and S were 1.28 (1.13, 1.44) and 1.10 (1.04, 1.17), respectively. Also, the combination of high F/E and S was significantly associated with hypertension. The blood pressure indicators and the prevalence of hypertension increased with an incremental in the serum concentration of F, F/E, and S (all Ptrend < 0.05). In addition, the positive association between F/E and SBP was stronger in women than that in men, and F/E was strongly positively associated with hypertension only in women (all Pinteraction < 0.05). CONCLUSION: Serum F/E and S were positively associated with hypertension and blood pressure. Additionally, their combination has a synergistic effect on hypertension. Moreover, the associations of F and F/E with hypertension and blood pressure were in a sex-specific manner.

Gender-Specific Independent and Combined Effects of the Progesterone and 17-Hydroxyprogesterone on Metabolic Syndrome: From the Henan Rural Cohort Study.

BACKGROUND: Although the concentrations of progesterone (P4) and 17-hydroxyprogesterone (17-OHP) have been correlated with some characteristics of metabolic syndrome (MetS), the relationships with MetS are inconclusive. Therefore, we investigated the relationship between P4 and 17-OHP with MetS. METHODS: In all, the present study includes 4807 participants. Serum P4 and 17-OHP were measured through liquid chromatography-tandem mass spectrometry. Logistic regression and restricted cubic splines were used to assess the independent and combined effects of P4 and 17-OHP on MetS. RESULTS: After adjusting for multiple variables, the positive association of P4 with MetS was observed in postmenopausal women (Third tertiles vs First tertiles: OR = 1.49, 95% CI: 1.20-1.86) and the negative association of 17-OHP with MetS was observed in men (Third tertiles vs First tertiles: OR = 0.43, 95% CI: 0.32-0.58). Compared with the combination of low P4 and low 17-OHP, the combination of high P4 and high 17-OHP were significantly related to MetS in postmenopausal women (OR = 1.71, 95% CI: 1.18-2.48). Moreover, the combination of low P4 and high 17-OHP was negatively associated with MetS in men (OR = 0.41, 95% CI: 0.24-0.69). CONCLUSION: The association between P4 and MetS in postmenopausal women was positive, whereas 17-OHP was negatively associated with MetS in men. Additionally, their combination has a synergistic effect on MetS in postmenopausal women and an antagonistic effect on MetS in men.

Associations of serum androgens with coronary heart disease and interaction with age: The Henan Rural Cohort Study.

BACKGROUND AND AIMS: We aimed to investigate the associations of testosterone and androstenedione with coronary heart disease, and the interaction effect of testosterone or androstenedione and age on coronary heart disease. METHODS AND RESULTS: A total of 6178 participants were included in this study. Serum testosterone and androstenedione were detected by liquid chromatography-tandem mass spectrometry. Logistic regression and restricted cubic splines were used to assess the independent effects of testosterone and androstenedione on coronary heart disease. Interactive plots were employed to examine the interaction effects of testosterone or androstenedione with age on coronary heart disease. After adjusting for multiple variables, serum testosterone and androstenedione levels were negatively associated with coronary heart disease in males (tertile 3 vs tertile 1, odd ratio (OR) = 0.56, 95% confidence interval (CI) (0.33, 0.96), and OR = 0.40, 95% CI (0.22, 0.74)). Per 1 unit increase in ln-testosterone and ln-androstenedione was associated with a 24% (OR = 0.76, 95% CI (0.63, 0.91)) and 30% (OR = 0.69, 95% CI (0.55, 0.86)) lower risk of coronary heart disease, respectively. Additionally, the positive association of age with coronary heart disease was attenuated by increasing concentrations of ln-testosterone and ln-androstenedione concentration in males. CONCLUSIONS: The results indicated that serum testosterone and androstenedione were negatively associated with coronary heart disease risk in Chinese rural males. To some extent, this study supports the application of hormone therapy in males with coronary heart disease, which can contribute to reducing the burden of coronary heart disease and related cardiovascular disease.

Combined effects of progesterone and SOCS3 DNA methylation on T2DM: a case-control study.

BACKGROUND: This study aims to investigate the independent and combined effects of progesterone and suppressor of cytokine signaling (SOCS)-3 DNA methylation on type 2 diabetes mellitus (T2DM) among men and postmenopausal women in rural China. METHODS: A case-control study with 914 participants (329 T2DM, 585 controls) was conducted. Serum progesterone was detected with liquid chromatography-tandem mass spectrometry. DNA methylation of SOCS3 was determined by MethylTarget™. Linear regression was applied to evaluate the associations of progesterone and SOCS3 methylation with marks of glucose metabolism. Logistic regression was employed to investigate the independent and combined effects of progesterone and SOCS3 methylation with T2DM in men and postmenopausal women. RESULTS: After multiple adjustment, progesterone was positively associated with T2DM in both men (odds ratio (OR) (95% confidence interval (CI)): 2.77 (1.79, 4.29)) and postmenopausal women (OR (95% CI): 1.85 (1.26, 2.72)). Methylation level of Chr17:76,356,190 or Chr17:76,356,199 (SOCS3) was negatively associated with T2DM in both men (OR (95% CI): 0.58 (0.39, 0.86) or 0.27 (0.14, 0.51)) and postmenopausal women (OR (95% CI): 0.43 (0.29, 0.65) or 0.53 (0.28, 0.99)). Subjects with high progesterone and low Chr17:76,356,190 or Chr17:76,356,199 methylation were more susceptible to have a higher prevalence of T2DM (men: OR (95% CI): 5.20 (2.49, 10.85) or 5.62 (2.74, 11.54); postmenopausal women: OR (95% CI): 3.66 (1.85, 7.26) or 3.27 (1.66, 6.45)). CONCLUSIONS: The independent and combined effects of progesterone and SOCS3 methylation on T2DM were found among men and postmenopausal women, suggesting that ensuring low levels of progesterone and high methylation of SOCS3 could reduce the prevalence of T2DM. Trial registration The Chinese Clinical Trial registration: The Henan Rural Cohort Study, ChiCTR-OOC-15006699. Registered 06 July 2015, http://www.chictr.org.cn/showproj.aspx?proj=11375.

Interaction between testosterone and obesity on hypertension: A population-based cross-sectional study.

BACKGROUND AND AIMS: We aimed to evaluate the effects of serum testosterone, obesity and their interaction on blood pressure (BP) parameters and hypertension among Chinese rural adults. METHODS: A total of 6199 adults were recruited from the Henan Rural Cohort Study. Serum testosterone was measured by liquid chromatography-tandem mass spectrometry. Logistic regression and linear regression were used to evaluate the association between testosterone, hypertension and BP parameters (including systolic blood pressure (SBP), diastolic blood pressure (DBP), pulse pressure (PP), and mean arterial pressure (MAP)). A generalized linear model was performed to identify the interactive effects of testosterone and obesity on hypertension. RESULTS: High levels of serum testosterone were associated with a lower prevalence of hypertension in males (odds ratio (OR): 0.69, 95% confidence interval (CI): 0.53, 0.89). After stratification by obesity, observed associations were only found in non-obese males. Each one-unit increase in ln-testosterone was associated with a 1.23 mmHg decrease in SBP, 0.97 mmHg decrease in DBP, and 1.05 mmHg decrease in MAP among males. Moreover, interactive effects between testosterone and obesity on hypertension and BP parameters were found, indicating that protective effects of serum testosterone on hypertension and BP parameters were counteracted and accompanied by increased values of obesity-related indicators in males, and additional testosterone increased BP parameters and prevalence of hypertension at high levels of waist-to-hip ratio and waist-to-height ratio in females. CONCLUSIONS: Elevated levels of serum testosterone were associated with decreased BP parameters and prevalent hypertension in males, and obesity modifying effects of serum testosterone on BP parameters and hypertension.

Long-term exposure to particulate matter and residential greenness in relation to androgen and progesterone levels among rural Chinese adults.

BACKGROUND: Population-based studies on the associations of long-term exposure to particulate matter (PM) with androgen and progesterone are still scant. Residential greenness is benefits health by promoting physical activity, reducing air pollution, and improving mental health, but it remains unclear whether it is related to androgen and progesterone levels among humans. AIMS: This study aimed to explore the individual and interactive effects of PM and residential greenness on serum testosterone and progesterone levels among rural Chinese adults. METHODS: A total of 6017 subjects were recruited from the baseline of the Henan Rural Cohort Study in 2016. Serum testosterone and progesterone were measured with liquid chromatography-tandem mass spectrometry. Particulate matters (PM) (PM1, PM2.5, and PM10) were assessed by machine learning algorithms. Residential greenness was assessed using the normalized difference vegetation index (NDVI) within 500-m, 1000-m, and 3000-m buffers around participants' residences. The effects of air pollutants and residential greenness and their interaction on serum testosterone and progesterone levels were assessed using linear mixed-effects models with township as a random intercept. RESULTS: After adjusting for potential confounding factors, a 1 µg/m3 increase in PM2.5 or PM10 was associated with a 0.037 or 0.030 ng/ml increase in serum testosterone, respectively, in females and with a 0.111 or 0.182 ng/ml decrease in serum progesterone, respectively, in males. A 1 µg/m3 increase in PM1, PM2.5 or PM10 was associated with a 0.222, 0.306, or 0.295 ng/ml decrease in serum progesterone, respectively, among females. Moreover, a 0.1-unit increase in NDVI was associated with a 0.310 ng/ml increase in serum testosterone and a 0.170 ng/ml increased in serum progesterone in males, as well as with a 0.143 ng/ml increase in serum progesterone in females. Interaction effects of PM and residential greenness on serum testosterone and progesterone levels were observed, indicating that the effects of residential greenness on serum testosterone and progesterone were modified by high levels of PM. In addition, physical activity significantly mediated 2.92% of the estimated association between greenness and testosterone levels. CONCLUSIONS: Our study suggested that long-term exposure to PM was positively associated with serum testosterone in males but negatively associated with progesterone levels in both genderssin. In addition, positive associations of residential greenness with serum testosterone and progesterone levels were observed, but they were modified by high levels of PM. Furthermore, the estimated effects of residential greenness on testosterone levels were partly mediated by physical activity.

Long-term exposure to PM1 and PM2.5 is associated with serum cortisone level and meat intake plays a moderation role.

BACKGROUND: Although short-term exposure to particulate matter (PM) was associated with increased glucocorticoids (GCs) levels, available evidence on associations of long-term exposure to PM and GCs levels is still scant. Previous studies has showed that meat intake is associated with sex hormones levels, but it is unknown whether meat intake is associated with GCs levels. Furthermore, the role of meat intake in the associations between PM and GCs levels remains unclear. AIMS: The aims of this study were to explore the associations of long-term exposure to PM and GCs levels among Chinese rural adults, and the role of meat intake in these associations. MATERIALS AND METHODS: A total of 6223 subjects were recruited from the Henan Rural Cohort Study. Serum GCs levels were measured with liquid chromatography-tandem mass spectrometry. The concentrations of PM (PM1 and PM2.5) for each subject were assessed with machine learning algorithms. The food frequency questionnaire (FFQ) was used to obtain each participant' information on meat intake. The effects of PM and meat intake on GCs levels were assessed using generalized linear models. In addition, modification analyses were performed to identify the role of meat intake played in the associations of PM with serum GCs levels. RESULTS: Per 1 µg/m3 increment in PM1 or PM2.5 concentration was associated with a 0.364 ng/ml (95% confidence interval (CI): 0.234, 0.494) or 0.227 ng/ml (95%CI: 0.110, 0.343) increase in serum cortisone, respectively. In addition, the moderation effects of total meat intake and red meat intake on the associations of long-term exposure to PM1 or PM2.5 with serum cortisone were observed (P < 0.05), indicating that individuals who had high levels of PM1 or PM2.5 and meat intake were more susceptible to have a higher state of serum cortisone. CONCLUSIONS: Our findings suggested that long-term exposure to PM1 or PM2.5 was associated with serum cortisone. Moreover, meat intake was found to be a significant moderator in the association of PM1 or PM2.5 with serum cortisone levels.

C-Reactive Protein Mediates the Effect of Serum Progesterone on Obesity for Men and Postmenopausal Women in Henan Rural Cohort Study.

PURPOSE: Studies of progesterone with obesity have been lacking, and no prior studies have investigated progesterone and C-reactive protein in rural natural populations. This study aimed to investigate the association of serum progesterone with obesity based on anthropometric parameters in Henan Rural Cohort, then further to explore the potential role of C-reactive protein in this association. PATIENTS AND METHODS: A total of 4687 participants (2474 men and 2213 postmenopausal women) from the Henan Rural Cohort study were included. Logistic regression analysis, linear regression analysis, and restricted cubic splines were performed to estimate the relationships between progesterone, C-reactive protein, obesity, and obesity-related parameters. Mediation analysis was carried out to assess the intermediary role of C-reactive protein played in the association between progesterone and obesity. RESULTS: After controlling for confounders, the odds ratios of obesity no matter how obesity was defined was associated with progesterone (P trend <0.05). Moreover, progesterone was related to obesity-related parameters. Also, C-reactive protein increased with the elevation of progesterone, and C-reactive protein was associated with obesity no matter how obesity was defined (P trend <0.001). Mediation analysis indicated that hsCRP had the mediating effects on the obesity, and the proportion of the effects were 15.35% and full mediating effect (defined by body mass index), 15.46% and 12.24% (defined by waist circumference), 19.14% and 12.12% (defined by waist-to-hip ratio), 23.81% and 15.09% (defined by waist-to-height ratio) for men and postmenopausal women, relatively. CONCLUSION: In the Chinese rural men and postmenopausal women population, progesterone and C-reactive protein are related to obesity. We firstly found C-reactive protein partly mediates the effect of progesterone on obesity, indicating that systemic inflammation played a critical role in the association.

The mediation role of SOCS3 methylation in the effect of serum testosterone on type 2 diabetes.

BACKGROUND: Previous studies reported that testosterone and DNA methylation of suppressor of cytokine signaling-3 (SOCS3) were associated with type 2 diabetes (T2D). Testosterone affects SOCS3 gene expression. Therefore, we aimed to investigate how the SOCS3 methylation mediates the relationship between testosterone and T2D among Chinese rural adults. METHODS: A case-control study comprised 365 T2D patients and 651 controls was conducted. Liquid chromatography-tandem mass spectrometry and MethylTarget were used to determine the levels of serum testosterone and DNA methylation of SOCS3 gene, respectively. The odds ratio (OR) of testosterone or SOCS3 methylation for T2D was calculated using logistic regression models, and ß value of testosterone for SOCS3 methylation was evaluated by linear regression models. Furthermore, through mediation analysis the mediating effect of SOCS3 methylation on the association of testosterone with T2D was estimated. RESULTS: After adjusting for multiple variables, the protective effect of testosterone on T2D was found in men (OR = 0.61, 95% confidence interval [CI]: 0.47-0.80), and the methylation of Chr17:76356190 or Chr17:76356199 was negatively related to T2D in both men and women. Moreover, testosterone was positively associated with Chr17:76356190 methylation in men and Chr17:76356199 methylation in women (both P < .05). The mediation analysis showed that the Chr17:76356190 methylation partly mediated effect of testosterone on T2D in men was approximately 8.2%. CONCLUSIONS: High levels of serum testosterone in men and Chr17:76356190 and Chr17:76356199 (SOCS3) methylation were related to a lower prevalent T2D. In addition, Chr17:76356190 methylation partially mediated the effect of testosterone on T2D in Chinese rural men.

Androgen receptor DNA methylation is an independent determinant of glucose metabolic disorders in women; testosterone plays a moderating effect.

BACKGROUND: We have previously shown that serum testosterone was associated with impaired fasting glucose (IFG) and type 2 diabetes (T2D). Testosterone can be acting through binding the androgen receptor (AR). Therefore, we aimed to explore the independent associations of AR DNA methylation (ARm) with IFG and T2D and the moderation effects of serum testosterone on the associations. METHODS: A case-control study with 1065 participants including 461 men and 604 women was performed. ARm in peripheral blood sample and serum testosterone were measured using pyrosequeuncing and liquid chromatography-tandem mass, respectively. Multivariable logistic regression was performed to estimate the associations of ARm (including 2 cytosine-phosphoguanine [CpG] islands and average methylation levels) with different glucose status. Serum testosterone was used as a moderator to estimate the moderation effect. RESULTS: After multivariate adjustment, CpG 1, 2 and CpG average methylation were all significantly associated with IFG (CpG 1: Odds ratio (OR) = 4.80, 95% confidence interval (CI): 2.24-10.27; CpG 2: OR = 4.35, 95% CI: 2.50-7.58; CpG average: OR = 11.73, 95% CI: 5.36-25.67) in women. In addition, testosterone played negative moderation effects in above associations. Moreover, no significant independent associations of methylation levels with T2D was observed both in men and women. CONCLUSION: Our findings demonstrate that ARm was positively associated with IFG in women and the associations would be weakened by testosterone. The individuals experiencing low testosterone and ARm levels reported a lower state of IFG than those who experienced high levels of testosterone and ARm in women.

Serum Vitamin D Affected Type 2 Diabetes though Altering Lipid Profile and Modified the Effects of Testosterone on Diabetes Status.

Numerous studies have investigated the associations between serum vitamin D or testosterone and diabetes; however, inconsistencies are observed. Whether there is an interaction between vitamin D and testosterone and whether the lipid profile (total cholesterol (TC), triglyceride (TG), high-density lipoprotein cholesterol (HDL-C), and low-density lipoprotein cholesterol (LDL-C)) mediates the association between vitamin D and diabetes is unclear. To investigate the effect of vitamin D and testosterone on impaired fasting glucose (IFG) or type 2 diabetes mellitus (T2DM), 2659 participants from the Henan Rural Cohort were included in the case-control study. Generalized linear models were utilized to estimate associations of vitamin D with IFG or T2DM and interactive effects of vitamin D and testosterone on IFG or T2DM. Principal component analysis (PCA) and mediation analysis were used to estimate whether the lipid profile mediated the association of vitamin D with IFG or T2DM. Serum 25(OH)D3, 25(OH)D2, and total 25(OH)D levels were negatively correlated with IFG (odds ratios (ORs) (95% confidence intervals (CIs)): 0.99 (0.97, 1.00), 0.85 (0.82, 0.88), and 0.97 (0.96, 0.98), respectively). Similarity results for associations between serum 25(OH)D2 and total 25(OH)D with T2DM (ORs (95%CIs): 0.84 (0.81, 0.88) and 0.97 (0.96, 0.99)) were observed, whereas serum 25(OH)D3 was negatively correlated to T2DM only in the quartile 2 (Q2) and Q3 groups (both p < 0.05). The lipid profile, mainly TC and TG, partly mediated the relationship between 25(OH)D2 or total 25(OH)D and IFG or T2DM and the proportion explained was from 2.74 to 17.46%. Furthermore, interactive effects of serum 25(OH)D2, total 25(OH)D, and testosterone on T2DM were observed in females (both p for interactive <0.05), implying that the positive association between serum testosterone and T2DM was vanished when 25(OH)D2 was higher than 10.04 ng/mL or total 25(OH)D was higher than 40.04 ng/mL. Therefore, ensuring adequate vitamin D levels could reduce the prevalence of IFG and T2DM, especially in females with high levels of testosterone.