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Background and Aims: There is no evidence on the longitudinal and causal associations between multiple pesticides and the incidence of type 2 diabetes mellitus (T2DM) in the Chinese rural population, and whether physical activity (PA) modified these associations remains unclear. Here, we aimed to investigate the longitudinal and causal associations between pesticides mixture and T2DM, and determine whether PA modified these associations., Methods: A total of 925 subjects with normal glucose and 925 subjects with impaired fasting glucose (IFG) were enrolled in this case-cohort study. A total of 51 targeted pesticides were quantified at baseline. Logistic regression, quantile g-computation, and Bayesian kernel machine regression (BKMR) were used to assess the individual and combined effects of pesticides on IFG and T2DM. Mendelian randomization (MR) analysis was employed to obtain the causal association between pesticides and T2DM., Results: After 3-year follow-up, one-unit increment in ln-isofenphos, ln-malathion, and ln-deltamethrin were associated with an increase conversion of IFG to T2DM (FDR-P<0.05). One quartile increment in organochlorine pesticides (OCPs), organophosphorus pesticides (OPs), herbicides and pyrethroids mixtures were related to a higher incidence of T2DM among IFG patients (P<0.05). The BKMR results showed a positive trend between exposure to pesticides mixture and T2DM. The MR analysis indicated a positive association between exposure to pesticides and T2DM risk (P<0.05). No any significant association was found between pesticides and IFG. In addition, compared to subjects with high levels of PA, those with low levels of PA were related to increased risk of T2DM with the increased levels of pesticides among IFG patients., Conclusions: Individual and combined exposure to pesticides increased the incidence of T2DM among IFG patients. MR analysis further supported the causal association of pesticides exposure with T2DM risk. Our study furtherly indicated that high levels of PA attenuated the diabetogenic effect of pesticides exposure., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)

Purpose: This study aimed to evaluate the relationships of separate and mixed exposure of neonicotinoids on cardiometabolic risk at baseline and follow-up and its change over 3 years, and further explore whether inflammatory markers levels and platelet traits (PLT) mediate these relationships., Methods: In this prospective cohort study from the Henan Rural Cohort Study, 2315 participants were involved at baseline, and 1841 participants completed cardiometabolic risk predictors determinations during the 3-year follow-up. Each neonicotinoid pesticide was normalized to imidacloprid (IMI eq ) using the relative potency factor approach. Quantile-based g-computation (Qgcomp) regression was used to evaluate the effect of the mixtures of neonicotinoids mediation analysis was employed to explore whether inflammatory markers levels and platelet traits mediated these relationships. A two-sample mendelian randomization (MR) study was further used to causal association., Results: Qgcomp regression revealed a statistically positive relationship between neonicotinoids mixture exposure and cardiometabolic risk score at baseline and follow-up over 3 years. Both neutrophils/monocytes and PLT were mediators in the relationship between IMI eq and cardiometabolic risk score at baseline and follow-up over 3 years. The causal risk effect of pesticide exposure were 2.50 (0.05, 4.95) and 5.24 (1.28, 9.19) for cardiometabolic risk indicators including insulin resistance and triglyceride, respectively. Nevertheless, there was no correlation discovered between pesticide exposure and other markers of cardiometabolic risk., Conclusion: Neonicotinoid insecticides exposure was connected to an increased cardiometabolic risk, especially in individuals with T2DM. Furthermore, inflammatory markers and PLT seem to be two vital mediators of these associations. Additionally, genetic evidence on pesticide exposure and cardiometabolic risk still needs to be validated by multiregional and multiethnic GWAS studies., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Aims: We aimed to investigate the association between serum cortisol, testosterone, and cortisol/testosterone (C/T) ratio and stroke., Materials and Methods: A total of 6157 subjects were included in this study. The serum levels of cortisol and testosterone were determined by liquid chromatography-tandem mass spectrometry method. The relationships of serum cortisol, testosterone, and C/T ratio levels with the odds ratios (ORs) of stroke were calculated using logistic regression analysis. The dose-response associations between serum cortisol, testosterone, and C/T ratio levels with stroke estimated by restricted cubic splines., Results: After adjusting for multiple variables, serum testosterone levels were negactively associated with stroke in males (per 1 unit, odds ratio (OR) = 0.83, 95 % confidence interval (CI): 0.70, 0.97). The serum C/T ratio is positively associated with stroke in both males and females (OR = 1.16, 95 % CI:1.04,1.34 in males and OR = 1.15, 95 % CI:1.02,1.31 in females). Restricted cubic splines showed a significant linear dose-response relationship between testosterone and C/T ratio and stroke in males (P for overall association <0.05, P for nonlinearity >0.05)., Conclusion: Our study findings show that serum testosterone levels are negatively correlated with stroke in males; meanwhile, serum C/T ratio is positively correlated with stroke in both males and females., Competing Interests: Declaration of competing interest The authors declare that they have no conflict of interest., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Background: The relationship between glucocorticoids and hypertension has shown inconsistent findings in previous studies. To address this, our study employed a nested case-control design in rural areas to further investigate the association between serum glucocorticoid levels and hypertension, and blood pressure-related indicators., Methods: This study employed a nested case-control design, involving 560 pairs of hypertensive cases and matched controls. The concentrations of serum cortisol (F), cortisone (E) and 11-deoxycortisol (S) were determined using liquid chromatography-tandem mass spectrometry. We employed various methods, including generalized linear model (GLM), conditional logistic regression model, restricted cubic spline regression, subgroup analysis, interaction, and joint effects, with adjustments for multiple covariates to analyze the relationships between glucocorticoids, hypertension, and blood pressure-related indicators., Results: After multivariable adjustments, ln-F, ln-F/E, and ln-S were positively associated with SBP, DBP, pulse pressure (PP), and mean arterial pressure (MAP), while ln-E was negatively associated with DBP and MAP ( P  < 0.05). Interestingly, ln-S showed no statistically significant association with hypertension prevalence ( P  > 0.05), whereas ln-F and ln-F/E were positively associated with it ( P  < 0.05). The adjusted odds ratios (ORs) and 95% confidence intervals (CIs) were 1.153 (1.011-1.315) for ln-F and 2.072 (1.622-2.645) for ln-F/E, respectively. In contrast, ln-E exhibited a negative association with hypertension prevalence (adjusted OR = 0.837, 95% CI 0.714-0.982). Moreover, a significant association was observed between the combined use of high-dose F/E and high-dose S with hypertension prevalence (adjusted OR = 3.273, 95% CI 2.013-5.321). Blood pressure indicators and hypertension prevalence significantly increased with elevated serum F and F/E concentrations ( P  < 0.05). Interaction analysis further revealed that among women, the positive association between F/E and hypertension prevalence was more pronounced than in men ( P  < 0.05), and S exhibited a more significant positive association with hypertension prevalence in the overweight population ( P  < 0.05)., Conclusion: Serum F/E and S levels demonstrated positive associations with hypertension and blood pressure-related indicators, and their combined influence exhibited a synergistic effect on hypertension. Notably, F, F/E, and S were associated with heightened hypertension risk, warranting particular attention in women and overweight populations., (Copyright © 2024 Wolters Kluwer Health, Inc. All rights reserved.)

Background: Toxicological and epidemiological studies have shown that environmental endocrine disruptors interfere with hormonal homeostasis. However, there is limited research on the effects of mixed exposure to nonpersistent endocrine disruptors on thyroid hormones and the factors (e.g., presence status of thyroid autoantibodies or nutritional status of organismal iodine) that may influence this association., Methods: Data were collected from the National Health and Nutrition Examination Survey (NHANES) 2007-2008 and 2011-2012. Relationships between single pollutants and thyroid hormone and thyroid autoantibody levels were assessed using generalized linear (GLM) and restricted cubic spline (RCS) regression models. Weighted quantile sum regression (WQS), group-weighted quantile sum regression (GWQS), quantile-based g-computation (qgcomp), and adaptive elasticity network (AENET) were applied to assess the mixed exposure effect. Next, subgroup analyses were performed on the basis of the urinary iodine concentration or thyroid autoantibody status to assess the modifying role of urinary iodine and thyroid autoantibodies., Results: A total of 2385 study participants were included in this study. Both the single-pollutant model and the multipollutant mixed model revealed that parabens and bis(2-ethylhexyl) phthalate (DEHP) metabolites were significantly and negatively associated with serum thyroxine (T4) levels. However, no associations were found between the target pollutants and thyroid autoantibodies (thyroglobulin antibodies (TgAb) and thyroid peroxidase antibodies (TPOAb)). In addition, this study revealed that urinary iodine or thyroid autoantibody status altered the associations of some of the target pollutants with thyroid hormones. WQS and qgcomp analyses, revealed that the associations of mixed pollutants with hormones differed depending on the urinary iodine or antibody status, especially T4 and thyroid-stimulating hormone (TSH)., Conclusion: Significant associations were found between phenols, parabens, and phthalates and serum thyroid hormone levels, with parabens and DEHP metabolites playing major roles. Urinary iodine and thyroid autoantibody status act as modifiers between environmental endocrine-disrupting pollutants and thyroid hormones., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)

Previous studies exploring the relationship between dietary potassium and magnesium intake and the risk of type 2 diabetes mellitus (T2DM) have yielded inconsistent results and the lack evidence from rural China. Therefore, we aimed to investigate the association between dietary potassium and magnesium intake and the risk of T2DM in rural China. Data was collected from the Henan Rural Cohort Study in 2017. A validated semi-quantitative food frequency questionnaire assessed dietary potassium and magnesium intake. Logistic regression models were used to calculate odds ratio (ORs) and 95% confidence intervals (CIs) to evaluate the effect of dietary potassium, magnesium and the potassium-magnesium ratio on the risk of T2DM. A total of 38384 individuals were included in the study, and 3616 participants developed T2DM. Logistic regression analysis revealed that the OR (95% CI) of the highest versus dietary potassium and magnesium and potassium-magnesium ratio intakes were 0.67 (0.59, 0.75), 0.76 (0.67, 0.88), and 0.57 (0.50, 0.66), respectively, compared to the subjects with the lowest quartile of intakes. In addition, gender partially influences the relationship between dietary magnesium and T2DM prevalence (P- interaction = 0.042). The group with the highest dietary potassium and dietary magnesium intake had the lowest risk of T2DM, with an OR (95% CI) of 0.63 (0.51-0.77). Dietary potassium and magnesium intake are important modifiable risk factors for T2DM in rural China. Dietary potassium intake > 1.8g/day, dietary magnesium intake > 358.6mg/day and < 414.7mg/day and potassium-magnesium ratio >5.1 should be encouraged to prevent better and manage T2DM., (© 2023. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

To investigate the associations between isocarbophos and isofenphos with impaired fasting glucose (IFG) and type 2 diabetes mellitus (T2DM), and to assess the mediation roles of inflammation cells. There were 2701 participants in the case-control study, including 896 patients with T2DM, 900 patients with IFG, 905 subjects with NGT. Plasma isocarbophos and isofenphos concentrations were measured using gas chromatography and triple quadrupole tandem mass spectrometry. Generalized linear models were used to calculate the relationships between plasma isofenphos and isocarbophos levels with inflammatory factor levels and T2DM. Inflammatory cell was used as mediators to estimate the mediating effects on the above associations. Isocarbophos and isofenphos were positively related with T2DM after adjusting for other factors. The odds ratio (95% confidence interval) (OR (95%CI)) for T2DM was 1.041 (1.015, 1.068) and for IFG was 1.066 (1.009, 1.127) per unit rise in ln-isocarbophos. The prevalence of T2DM increased by 6.4% for every 1 unit more of ln-isofenphos (OR (95% CI): 1.064 (1.041, 1.087)). Additionally, a 100% rise in ln-isocarbophos was linked to 3.3% higher ln-HOMA2IR and a 0.029 mmol/L higher glycosylated hemoglobin (HbA1c) (95% CI: 0.007, 0.051). While a 100% rise in ln-isofenphos was linked to increase in ln-HOMA2 and ln-HOMA2IR of 5.8% and 3.4%, respectively. Furthermore, white blood cell (WBC) and neutrophilic (NE) were found to be mediators in the relationship between isocarbophos and T2DM, and the corresponding proportions were 17.12% and 17.67%, respectively. Isofenphos and isocarbophos are associated with IFG and T2DM in the rural Chinese population, WBC and NE have a significant role in this relationship., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023. Published by Elsevier B.V.)

There is no evidence on the associations between persistent organic pollutants (POPs) and the incidence of chronic kidney disease (CKD) in the Chinese rural population. We aimed to investigate the individual and mixed effects of 22 POPs on the prevalence and incidence of CKD, and the joint effects of POPs and abnormal glucose metabolism as well as the modification effects of healthy lifestyle on these associations. A total of 2775 subjects, including 925 subjects with normal plasma glucose (NPG) and 925 subjects with prediabetes (PDM) and type 2 diabetes mellitus (T2DM), were enrolled from the Henan Rural Cohort Study. Logistic regression and quantile g-computation were performed to assess the individual and mixed effects of POPs on the risk of CKD. Joint effects of POPs and abnormal glucose metabolism status, as well as the modification effects of lifestyle on CKD were assessed. After 3-year follow-up, an increment of ln-o,p'-DDT was related to an elevated risk of CKD prevalence. Positive associations of p,p'-DDE and β-BHC with CKD incidence were observed (P < 0.05). In addition, participants with high levels of ∑POPs were associated elevated incidence risk of CKD (OR: 1.217, 95%CI: 1.008-1.469). One quartile increase in POPs mixture was associated with the increased incidence of CKD among T2DM patients (P < 0.05). Further, a higher risk of CKD was observed among PDM and T2DM patients with high levels of o,p'-DDT, p,p'-DDE, β-BHC, and ∑POPs than NPG subjects with low levels of pollutants. In addition, interactive effects of ∑POPs and lifestyle score on CKD incidence were found. Individual and mixed exposure to POPs increased the prevalence and incidence of CKD, and glucose metabolic status exacerbated the risk of CKD resulting from such exposures. Further, the modifying effects of lifestyle were observed, highlighting the importance of precision prevention for high-risk CKD population and healthy lifestyle intervention measures., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024. Published by Elsevier B.V.)

Background and Aims: Human studies about short-chain fatty acids (SCFAs), the gut microbiome, and Type 2 diabetes (T2DM) are limited. Here we explored the association between SCFAs and T2DM and the effects of gut microbial diversity on glucose status in rural populations., Methods and Results: We performed a cross-sectional study from the Henan Rural Cohort and collected stool samples. Gut microbiota composition and faecal SCFA concentrations were measured by 16S rRNA and GC-MS. The population was divided based on the tertiles of SCFAs, and logistic regression models assessed the relationship between SCFAs and T2DM. Generalized linear models tested the interactions between SCFAs and gut microbial diversity on glucose indicators (glucose, HbAlc and insulin). Compared to the lowest tertile of total SCFA, acetate and butyrate, the highest tertile exhibited lower T2DM prevalence, with ORs and 95% CIs of 0.291 (0.085-0.991), 0.160 (0.044-0.574) and 0.171 (0.047-0.620), respectively. Restricted cubic spline demonstrated an approximately inverse S-shaped association. We also noted interactions of the ACE index with the highest tertile of valerate on glucose levels (P-interaction = 0.022) and the Shannon index with the middle tertile of butyrate on insulin levels (P-interaction = 0.034). Genus Prevotella&#95;9 and Odoribacter were inversely correlated with T2DM, and the genus Blautia was positively associated with T2DM. These bacteria are common SCFA-producing members., Conclusions: Inverse S-shaped associations between SCFAs (total SCFA, acetate, and butyrate) and T2DM were observed. Valerate and butyrate modify glucose status with increasing gut microbial diversity., Competing Interests: Conflict of interest The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 The Italian Diabetes Society, the Italian Society for the Study of Atherosclerosis, the Italian Society of Human Nutrition and the Department of Clinical Medicine and Surgery, Federico II University. Published by Elsevier B.V. All rights reserved.)

Background and Objective: Considering the widespread use of organophosphorus pesticides (OPs) and the global prevalence of hypertension (HTN), as well as studies indicating that different glycemic statuses may respond differently to the biological effects of OPs. Therefore, this study, based on the Henan rural cohort, aims to investigate the association between OPs exposure and HTN, and further explores whether lipids mediate these associations., Methods: We measured the plasma levels of OPs in 2730 participants under different glycemic statuses using gas chromatography-triple quadrupole mass spectrometry (GC-MS/MS). A generalized linear model, Quantile g-computation (QGC), adaptive elastic net (AENET), and Bayesian kernel machine regression (BKMR) models were used to assess the impact of OPs exposure on HTN, with least absolute shrinkage and selection operator (LASSO) penalty regression identifying main OPs. Mediation models were used to evaluate the intermediary role of blood lipids in the OPs-HTN relationship., Results: The detection rates for all OPs were high, ranging from 76.35 % to 99.17 %. In the normal glucose tolerance (NGT) population, single exposure models indicated that malathion and phenthoate were associated with an increased incidence of HTN (P-FDR < 0.05), with corresponding odds ratios (ORs) and 95 % confidence intervals (CIs) of 1.624 (1.167,2.260) and 1.290 (1.072,1.553), respectively. QGC demonstrated a positive association between OP mixtures and HTN, with malathion and phenthoate being the primary contributors. Additionally, the AENET model's Exposure Response Score (ERS) suggested that the risk of HTN increases with higher ERS (P < 0.001). Furthermore, BKMR revealed that co-exposure to OPs increases HTN risk, with phenthoate having a significant impact. Furthermore, triglycerides (TG) mediated 6.55 % of the association between phenthoate and HTN. However, no association was observed in the impaired fasting glucose (IFG) and type 2 diabetes mellitus (T2DM) populations., Conclusions: Our findings suggest that in the NGT population, OPs may significantly contribute to the development of HTN, proposing TG as a potential novel target for HTN prevention., Competing Interests: Declaration of competing interest None declared., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Evidence of the relationship between fecal short-chain fatty acids (SCFA) levels, dietary quality and type 2 diabetes mellitus (T2DM) in rural populations is limited. Here, we aimed to investigate the association between fecal SCFA levels and T2DM and the combined effects of dietar quality on T2DM in rural China. In total, 100 adults were included in the case-control study. Dietary quality was assessed by the Alternate Healthy Eating Index 2010 (AHEI-2010), and SCFA levels were analysed using the GC-MS system. Generalised linear regression was conducted to calculate the OR and 95 % CI to evaluate the effect of SCFA level and dietary quality on the risk of T2DM. Finally, an interaction was used to study the combined effect of SCFA levels and AHEI-2010 scores on T2DM. T2DM participants had lower levels of acetic and butyric acid. Generalised linear regression analysis revealed that the OR (95 % CI) of the highest acetic and butyric acid levels were 0·099 (0·022, 0·441) and 0·210 (0·057, 0·774), respectively, compared with the subjects with the lowest tertile of level. We also observed a significantly lower risk of T2DM with acetic acid levels > 1330·106 μg/g or butyric acid levels > 585·031 μg/g. Moreover, the risks of higher acetic and butyric acid levels of T2DM were 0·007 (95 % CI: 0·001, 0·148), 0·005 (95 % CI: 0·001, 0·120) compared with participants with lower AHEI-2010 scores (all P < 0·05). Acetate and butyrate levels may be important modifiable beneficial factors affecting T2DM in rural China. Improving dietary quality for body metabolism balance should be encouraged to promote good health.

Microcystin-LR (MC-LR) is a reproductive toxin produced by cyanobacteria in the aquatic environment and can be ingested by humans through drinking water and the food chain, posing a threat to human reproductive health. However, the toxic mechanisms and prospective interventions for MC-LR-induced ovarian dysfunction at environmental doses are unknown. The mulberry fruit is a traditional natural product of plant origin, with various pharmacological effects, such as antioxidant and anti-inflammatory effects. Here, mice were exposed to MC-LR (10, 100 μg/L) in drinking water for 90 days, during which mice were gavage 600 mg/kg/week of mulberry fruit extract (MFE). It was found that MC-LR can accumulate in mouse ovaries, causing sexual hormone disturbance, inflammatory infiltration, and ovarian pathological damage. Results from RNA-seq were shown that CCL2, a chemokine associated with inflammatory response, was significantly increased in mouse ovary after MC-LR exposure. Further investigation revealed that MC-LR exposure aggravates apoptosis of granulosa cells via the CCL2-CCR10 axis-mediated Jak/Stat pathway. Importantly, MFE can significantly ameliorate these ovarian dysfunction phenotypes by inhibiting the activation of the CCL2-CCR10 axis. This study broadened new insights into the ovarian toxicity of MC-LR and clarified the pharmacological effects of mulberry fruit on ovarian function protection., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Ltd. All rights reserved.)

Background: Few studies are available on the relationship of androstenedione with inflammation and obesity and the effect of androstenedione and inflammation on the association between testosterone and obesity. This study intended to examine the mediation effect of inflammatory markers on the association of testosterone with obesity and the moderation effect of androstenedione on the association of testosterone with inflammation and obesity in Chinese rural men., Materials and Methods: This cross-sectional research enrolled 2536 male rural inhabitants from the Henan Rural Cohort study. The serum concentrations of testosterone and androstenedione were determined by liquid chromatography-tandem mass spectrometry. Linear and logistic regression were used to examine the relationships between testosterone, inflammatory markers, and obesity. Mediation and moderation analyses were carried out to evaluate the potential effects of inflammatory markers on the relationship between testosterone and obesity, as well as androstenedione on the relationships of testosterone with inflammation and obesity., Results: After adjusting for confounding factors, the results showed that testosterone and androstenedione were negatively related to obesity, and inflammatory markers were positively associated with obesity. Besides, testosterone and androstenedione were negatively associated with inflammatory markers. Mediation analysis showed that white blood cell, neutrophil, monocyte, and high-sensitivity C-reactive protein had mediating effects on the association between testosterone and obesity. The most vital mediator was high-sensitivity C-reactive protein, and its proportion of the effect was 11.02% (defined by waist circumference), 11.15% (defined by waist-to-hip ratio), 12.92% (defined by waist-to-height ratio), and full mediating effect (defined by body mass index). Moreover, androstenedione played negative moderation effects on the associations of testosterone with inflammation and obesity., Conclusion: Inflammatory markers and androstenedione were first found to have modifying effects on the association of testosterone with obesity. Higher levels of testosterone and androstenedione could reduce the inflammation level and risk of obesity, indicating their potential roles in the prevention and treatment of chronic diseases., (© 2023 American Society of Andrology and European Academy of Andrology.)

Purpose: To investigate the association between low-carbohydrate diet scores (LCDs) and the risk of type 2 diabetes in rural China., Methods: A total of 38,100 adults were included in the Henan Rural Cohort Study. Macronutrient intake was assessed via a validated food-frequency questionnaire to create low-carbohydrate diet (LCD) scores. Multivariate logistic regression models and subgroup analysis were performed to estimate the odds ratio (OR) and 95% confidence interval (95% CI)., Results: After multivariable adjustment, participants with a high total low-carbohydrate diet score have a high risk of T2D (extreme-quartile OR = 1.23, 95% CI: 1.04-1.41; P = 0.007), whereas plant-based LCD score is not related to T2D risk. Among individuals with a BMI < 24 (extreme-quartile OR = 1.22, 95% CI: 1.01-1.47; P < 0.001) or high levels of physical activity (extreme-quartile OR = 1.42, 95% CI: 1.17-1.72; P < 0.001), the animal-based LCD score is positively correlated with the risk of T2D., Conclusion: Among Chinese rural populations, high-fat-low carbohydrate diet is associated with an increased risk of type 2 diabetes. High intake of animal protein and fat also increases T2D risk in those who are overweight or have high physical activity., (© 2024. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Purpose: The aim of this study was to investigate the effect of solid fuel use on serum sex hormone levels. Furthermore, the effects of improved kitchen ventilation and duration of cooking time on the relationship between solid fuel use and serum sex hormone levels will be further explored., Methods: In this cross-sectional study, 5386 individuals were recruited. Gender and menopausal status modified associations between solid fuel type and serum sex hormone levels was investigated through generalized linear models and further analyzed by improving kitchen ventilation and length of cooking time on the relationship between solid fuel use and serum sex hormone levels. To identify the causal association, mendelian randomization of two-sample was performed., Results: In observational analyses, for ln-17-hydroxyprogesterone, ln-testosterone, and ln-androstenedione among premenopausal women, the estimated β and 95 % CI of sex hormone levels for the effect of solid fuel users was -0.337 (-0.657, -0.017), -0.233 (-0.47, 0.005), and - 0.240 (-0.452, -0.028) respectively, and - 0.150 (-0.296, -0.004) in ln-progesterone among postmenopausal women. It was found that combining solid fuels with long cooking periods or no ventilation more effectively reduced testosterone and androstenedione in premenopausal women. We further found the adverse effects of using solid fuel on progesterone, testosterone, and androstenedione levels were enhanced with the increases of PM 1 , PM 2.5 , PM 10 , and NO 2 . Corresponding genetic, the causal risk effect of solid fuel were - 0.056 (-0.513, 0.4) and 0.026 (-3.495, 3.547) for testosterone levels and sex hormone binding globulin, respectively., Conclusion: Using gas or solid fuel was negatively related to sex hormone levels. A combination of using solid fuels, cooking for a long time, or cooking without ventilation had a stronger effect on sex hormone levels. However, genetic evidence did not support causality for the associations. WHAT IS ALREADY KNOWN ON THIS TOPIC?: The mechanisms underlying these associations household air pollution (HAP) from incomplete combustion of such fuels and occurrence of chronic diseases remained obscure. Recent years, extensive evidences from animal as well as human researches have suggested that progestogen and androgen hormones are involved in the development of diabetes, hypertension, and cardiovascular disease, which indicated that changes in serum progestogen and androgen hormones levels might play a role in these pathological mechanisms. However, limited evidence exists examining the effect of HAP from solid fuel use on serum sex hormone levels., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024. Published by Elsevier B.V.)

Association between organochlorine pesticides (OCPs) exposure and type 2 diabetes mellitus (T2DM) remains contradictory, and the evidence is mostly focused on a single exposure. Here, we assessed the associations between individual and combined OCPs exposure and T2DM, and explored the underlying mechanism of sex hormones and the methylation levels of sex hormone receptors in above associations. A case-control study with 1812 participants was performed. Gas chromatography mass spectrometry, liquid chromatography-tandem mass spectrometry, and pyrosequencing were used to measure plasma OCPs, serum sex hormones, and whole blood methylation levels of sex hormone receptors, respectively. Generalized linear models were used to analyze the relationships between OCPs, sex hormones, the methylation levels of sex hormone receptors, and T2DM. Quantile based g-computation (QGC) and Bayesian Kernel Machine Regression (BKMR) were employed to assess the combined OCPs exposure. The roles of sex hormones and the methylation levels of their receptors were evaluated by moderating mediation models. After adjusting for covariates, each unit (2.718 ng/ml) increase in p,p'-DDE was associated with a higher risk of T2DM in males (odds ratio (OR) and 95% confidence interval (CI): 1.066 (1.023, 1.112)). QGC and BKMR showed a positive combined effect in the associations of OCPs mixtures on T2DM among premenopausal females, and positive effects but not statistically significant among males and postmenopausal females. p,p'-DDE was the largest contributor for the positive associations. Furthermore, testosterone mediated 21.149% of the associations of p,p'-DDE with T2DM moderated by the androgen receptor methylation (ARm) located in CpG island 1. Individual and mixtures of OCPs exposure were positively linked to elevated risk of T2DM. Testosterone and ARm may participate in the related processes of OCPs with T2DM, providing new insights into the adverse endocrine effects caused by OCPs and specific pathways for the etiology and control of diabetes., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier Ltd. All rights reserved.)

Objective: Glucose metabolism is impacted by circadian disruption. Dinner-bedtime interval (DBI) was an accessible indicator to reflect the alignment between dinner time and circadian clock. We aimed to investigate the association of DBI with type 2 diabetes mellitus (T2DM)., Methods: 7676 adult subjects from the Henan Rural Cohort were included. Their demographic information including dinner time and bedtime was collected. Fasting venous blood samples were collected for biochemical determinations. Generalized linear regression model was used to analyze the factors influencing DBI. Furthermore, logistic regression incorporated with restricted cubic spline model was applied to evaluate the association between DBI and T2DM., Results: The results of multiple linear regression model showed that age ( β : -0.018, 95% CI : -0.021, -0.015) was negatively correlated with DBI. Female ( β : 0.311, 95% CI : 0.229, 0.393), junior high school education ( β : 0.246, 95% CI : 0.187, 0.306), high school education or above ( β : 0.346, 95% CI : 0.259, 0.433), average monthly income with 1000-1999 CNY(0.102, 95% CI: 0.032, 0.171), average monthly income ≥ 2000 CNY ( β : 0.164, 95% CI : 0.076, 0.251), moderate physical activity ( β : 0.134, 95% CI : 0.071, 0.197), current smokers ( β : 0.214, 95% CI : 0.118, 0.309), current drinkers ( β : 0.099, 95% CI : 0.008, 0.190) were positively correlated with DBI. Furthermore, DBI was significantly associated with T2DM (adjusted OR : 0.910, 95% CI : 0.845-0.979, P  = 0.012). DBI longer than 3 h was associated with decreased risk of T2DM (adjusted OR : 0.773, 95% CI : 0.648-0.921, P  = 0.004)., Conclusions: DBI larger than 3 h is beneficial to T2DM prevention. Further investigation is required to verify the association., Competing Interests: Conflict of interestThere is no conflict of interest., (© The Author(s), under exclusive licence to Tehran University of Medical Sciences 2024. Springer Nature or its licensor (e.g. a society or other partner) holds exclusive rights to this article under a publishing agreement with the author(s) or other rightsholder(s); author self-archiving of the accepted manuscript version of this article is solely governed by the terms of such publishing agreement and applicable law.)

Background: Detergent is a chemical product commonly used in people's daily life. Contact with detergent solutions can damage the human skin barrier and cause skin diseases. Skin surface lipids (SSLs) play a decisive role in skin barrier function. This study aimed to observe the changes of SSLs in young adults after exposure to detergent solutions to explore the underlying mechanism of skin barrier function damage., Methods: A self-controlled study on youth adults was conducted in Zhengzhou, China, in November 2020. The study lasted for a total of 1 week, and skin barrier function was assessed by trans-epidermal water loss (TEWL) values. The changes of SSLs before and after exposure to the detergent with subjects were measured using ultra-performance liquid chromatography quadrupole time of flight mass spectrometry., Results: The skin barrier function of subjects' hands was impaired after exposure to detergent (TEWL value increased, p &lt; 0.001). A total of 520 SSLs were detected, divided into 6 main categories. The average relative abundance of these 6 major lipids decreased after exposure. Sphingolipids (mainly ceramides), free fatty acids (mainly long-chain fatty acids), cholesterol lipids, and glycerophospholipids are the most severely damaged lipids., Conclusion: Detergent solutions can damage the skin barrier function and SSLs of young hands; interventions targeting SSLs to eliminate detergent damage to human skin may be of value., (© 2023 S. Karger AG, Basel.)

Evidence shows the relationships of individual environmental PAHs by their urinary metabolites with relative telomere length (RTL), which may be affected by biological gender differences. Since plasma parent PAHs are not metabolized, it may reflect human exposure to PAHs more realistically in daily life. Thus, exploring joint associations between plasma parent PAHs and RTL is urgent, which may identify the major contributor to its adverse effect. In this study, 2577 participants were obtained from the Henan Rural Cohort. The level of PAHs in blood samples was detected by gas chromatography coupled with tandem mass spectrometry. RTL in blood samples was detected by quantitative polymerase chain reaction. Generalized linear models or quantile g-computation were performed to evaluate the associations between the individual or a mixture of PAHs and RTL. Results from generalized linear models showed that each unit increment in BghiP value corresponded to a 0.098 (95%CI: 0.067, 0.129) increment in RTL for men; each unit increment in BaP, BghiP and Flu value corresponded to a 0.041 (95%CI: 0.014, 0.068), 0.081 (95%CI: 0.055, 0.107) and 0.016 (95%CI: 0.005, 0.027) increment in RTL for women. Results from quantile-g computation revealed that each one-quantile increment in the mixture of 10 PAHs corresponded to a 0.057 (95%CI: 0.021, 0.094) and 0.047 (95%CI: 0.003, 0.091) increment in RTL values of women and men, but these associations were mainly ascribed to three PAHs for women (BaP, Flu and BghiP) and men (BaP, BghiP and Pyr), respectively. Similar results were found in smoking men and cooking women without smoking. Our study found that exposure to 10 PAHs mixture was positively associated with RTL across gender, mainly attributed to Flu, BaP and BghiP, implicating that gender-specific associations may be ascribed to tobacco and cooking smoke pollution. The findings provided clues for effective measures to control PAHs pollutants-related aging disease.Clinical trial registration The Henan Rural Cohort Study has been registered at the Chinese Clinical Trial Register (Registration number: ChiCTR-OOC-15006699). Date of registration: 06 July 2015. http://www.chictr.org.cn/showproj.aspx?proj=11375 ., (© 2023. The Author(s), under exclusive licence to Springer Nature B.V.)

Parabens and alkylphenols pose serious hazards to human health, yet there are few studies on their exposure profiles and health risks in rural Chinese populations. In this study, 804 participants were selected from the Henan Rural Cohort in mid-eastern China. The plasma levels of parabens (methylparaben, ethylparaben, propylparaben, butylparaben (BuP)) and alkylphenols (4-tert-butylphenol (4-t-BP), 4-tert-octylphenol (4-t-OP)) were analyzed via liquid chromatography-tandem mass spectrometry. Linear regression models were used to investigate factors that may influence pollutant exposure levels. The correlation between contaminants was assessed using Spearman's correlation. The human contaminant intake was estimated using the estimated daily intake (EDI). The health risk was assessed using the hazard quotient (HQ). The detection frequency of four parabens and two alkylphenols exceeded 75%, with median concentrations of 0.444, 0.067, 0.078, 0.053, 8.810, and 6.401 ng/mL, respectively. Significant correlations were observed between parabens, as well as between 4-t-BP and 4-t-OP. Regarding gender, paraben concentrations were higher in women than in men, except for BuP. The EDI for pollutants except 4-t-OP was lower than their respective tolerable/acceptable daily intake. In total, 85.70% of participants had 4-t-OP HQ > 1. A widespread exposure to parabens and alkylphenols among the rural population was found. The high health risks of alkylphenol exposure indicate that alkylphenols should be used with caution.

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., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier Ltd. All rights reserved.)

Evidence on the effect of long-term exposure to fine particulate matter (PM 2.5 ) on erythrocytosis and thrombocytosis prevalence was limited. We aimed to investigate the association of PM 2.5 and its constituents with the risks of erythrocytosis and thrombocytosis. The present study included a total of 33,585 participants from the Henan Rural Cohort at baseline between 2015 and 2017. A hybrid satellite-based model was employed to estimate the concentrations of PM 2.5 mass and its constituents (including black carbon [BC], nitrate [NO 3 - ], ammonium [NH 4 + ], inorganic sulfate [SO 4 2- ], organic matter [OM], and soil particles [SOIL]). The logistic regression model was used to assess the associations of single exposure to PM 2.5 and its constituents with the risks of erythrocytosis and thrombocytosis, and the quantile G-computation method was applied to evaluate their joint exposure risk. For the independent association, the odds ratios for erythrocytosis/thrombocytosis with 1 μg/m 3 increase was 1.049/1.043 for PM 2.5 mass, 1.596/1.610 for BC, 1.410/1.231 for NH 4 + , 1.205/1.139 for NO 3 - , 1.221/1.359 for OM, 1.300/1.143 for SO 4 2- , and 1.197/1.313 for SOIL. Joint exposure to PM 2.5 and its components was also positively associated with erythrocytosis and thrombocytosis. The estimated weight of NH 4 + was found to be the largest for erythrocytosis, while OM had the largest weight for thrombocytosis. PM 2.5 mass and its constituents were positively linked to prevalent erythrocytosis and thrombocytosis, both in single-exposure and joint-exposure models. Additionally, NH 4 + /OM was identified as a potentially responsible component for the association between PM 2.5 and erythrocytosis/thrombocytosis.

Background: Plasma polybrominated diphenyl ethers (PBDE) were used as flame retardants widely, however, epidemiological evidence for the association between PBDEs and type 2 diabetes mellitus (T2DM) is inconsistent. Moreover, the combined effects of PBDEs and blood lipid indicators on impaired fasting glucose (IFG) and T2DM remains largely unknown in rural areas lacking good waste recycling infrastructure., Methods: In this study, a total of 2607 subjects aged 18-79 years were included from the Henan Rural Cohort. Generalized linear and logistic regression models were applied to evaluate the associations of various PBDE pollutants on IFG and T2DM. Quantile g-computation regression and PBDE pollution score created by the adaptive elastic net were applied to evaluate the impact of PBDEs mixtures on IFG and T2DM. Interaction effects of individual PBDE pollutants and blood lipid indicators on IFG and T2DM were assessed by using Interaction plots., Results: The geometric mean concentrations (detection rates) were 0.09 ng/mL (100.0%), 0.12 ng/mL (97.8%), 0.22 ng/mL (94.7%), 0.16 ng/mL (99.2%) and 0.28 ng/mL (100.0%) for PBDE-28, PBDE-47, PBDE-99, and PBDE-153 respectively. However, PBDE-28, PBDE-99, PBDE-100, and ΣPBDEs were positively associated with IFG (odds ratios (ORs) (95% confidence intervals (CIs)): 1.14 (1.06, 1.23), 1.16 (1.04, 1.29), 1.25 (1.14, 1.37), and 1.27 (1.08, 1.50)). Similarly, PBDE-28, PBDE-47, PBDE-99, PBDE-100, and ΣPBDEs were positively associated with T2DM (ORs (95% CIs): 1.30 (1.10, 1.54), 1.13 (1.06, 1.22), 1.27 (1.13, 1.43), 1.27 (1.15, 1.40), and 1.30 (1.10, 1.54)). Moreover, five PBDE mixtures or jointly as PBDE pollution score, were significantly associated with an increased risk of T2DM (P < 0.05 for all). In addition, the harmful effect of PBDE exposure on T2DM was decreased with accompanying high-density lipoprotein cholesterol (HDL-C) levels increased., Conclusions: Our findings highlight the importance of managing PBDEs contamination and suggest that HDL-C may be a novel way to prevent T2DM., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 The Authors. Published by Elsevier Inc. All rights reserved.)

Background: Previous studies indicated the beneficial influence of residential greenness on cardiovascular disease (CVD), however, the association of residential greenness with cardiac conduction performance remains unclear. This study aims to examine the epidemiological associations between residential greenness and cardiac conduction abnormalities in rural residents, simultaneously exploring the role of residential greenness for cardiac health in an explainable machine learning modeling study., Methods: A total of 27,294 participants were derived from the Henan Rural Cohort. Two satellite-based indices, the normalized difference vegetation index (NDVI) and the enhanced vegetation index (EVI), were used to estimate residential greenness. Independent and combined associations of residential greenness indices and physical activities with electrocardiogram (ECG) parameter abnormalities were evaluated using the logistic regression model and generalized linear model. The Gradient Boosting Machine (GBM) and the SHapely Additive exPlanations (SHAP) were employed in the modeling study., Results: The odds ratios (OR) and 95% confidence interval (CI) for QRS interval, heart rate (HR), QTc interval, and PR interval abnormalities with per interquartile range in NDVI were 0.896 (0.873-0.920), 0.955 (0.926-0.986), 1.015 (0.984-1.047), and 0.986 (0.929-1.045), respectively. Furthermore, the participants with higher physical activities plus residential greenness (assessed by EVI) were related to a 1.049-fold (1.017-1.081) and 1.298-fold (1.245-1.354) decreased risk for abnormal QRS interval and HR. Similar results were also observed in the sensitivity analysis. The NDVI ranked fifth (SHAP mean value 0.116) in the analysis for QRS interval abnormality risk in the modeling study., Conclusion: A higher level of residential greenness was significantly associated with cardiac conduction abnormalities. This effect might be strengthened in residents with more physical activities. This study indicated the cruciality of environmental greenness to cardiac functions and also contributed to refining preventive medicine and greenness design strategies., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023. Published by Elsevier Ltd.)

Since neonicotinoids (NNIs) are widely used around the world, they are extensively distributed in the environment and frequently occurred in humans. This study was conducted to assess the risk of NNIs residues in vegetables and fruits in Henan province, and evaluate the associations of NNIs single and mixed exposure with glucose metabolism, and further explore whether testosterone mediated these relationships in Henan rural population. The data of vegetables and fruits were collected from Henan Province in 2020-2021, and participants were drawn from the Henan Rural Cohort study. Hazard quotient (HQ) and hazard index (HI) were used to assess the risk of exposure to the individual and combined NNIs through vegetables or fruits intake. Relative potency factor (RPF) method was utilized to normalize each NNIs to imidacloprid (IMI RPF ). Generalized linear models were used to explore the effects of each NNIs and IMI RPF on glucose metabolism. Weight quartile sum (WQS) regression and Bayesian kernel machine regression (BKMR) model were applied to estimate the effect of NNIs mixtures on glucose metabolism. Mediation analysis was employed to explore whether testosterone mediated these relationships. The HQs and HI in both vegetables and fruits were much lower than 1, which indicated that NNIs in vegetables and fruits were not expected to cause significant adverse effects. However, plasma natural logarithm nitenpyram (Ln&#95;NIT), Ln&#95;thiacloprid-amid (Ln&#95;THD-A), and Ln&#95;IMI eq were positively associated with type 2 diabetes mellitus (T2DM) (odds ratio (OR) (95% confidence interval (CI)): 1.12 (1.05, 1.19), 1.21 (1.10, 1.32), and 1.48 (1.22, 1.80)). Both WQS regression and BKMR models observed significantly positive associations between NNIs mixture exposure and T2DM. Testosterone partially mediated these associations among women (PE = 6.67%). These findings suggest that human NNIs exposure may impair glucose metabolism and could contribute to rising rates of T2DM, and it's necessary to regulate the use of pesticides in rural areas., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier Ltd. All rights reserved.)

In this study 3307 samples of 24 vegetables and fruits from 18 regions of Henan Province, China, were collected in 2021 with the aim of assessing the levels of pesticide residues and analysing the differences between different sources in Henan Province. Thirteen kinds of pesticides were analysed by gas chromatography-mass spectrometry (GC-MS) and detection rates were compared by the chi-square test. In all samples, except ginger, pimento, edible fungi and yam, pesticide residues were detected. The detection rates of difenoconazole, acetamiprid, carbendazim, procymidone, emamectin benzoate, lambda-cyhalothrin, cypermethrin and dimethomorph in supermarkets and traditional farmers' markets were different. The difenoconazole group and the dimethomorph group were both statistically different ( P  < 0.05). This study showed common vegetables and fruits to contain pesticide residues in Henan Province and provided a scientific basis for their evaluation. Different sources take different regulatory measures to control pesticide residues to ensure food safety.

Background: Although it has been reported that herbicides exposure is related to adverse outcomes, available evidence on the associations of quantitatively measured herbicides with type 2 diabetes mellitus (T2DM) and prediabetes is still scant. Furthermore, the effects of herbicides mixtures on T2DM and prediabetes remain unclear among the Chinese rural population., Aims: To assess the associations of plasma herbicides with T2DM and prediabetes among the Chinese rural population., Methods: A total of 2626 participants were enrolled from the Henan Rural Cohort Study. Plasma herbicides were measured with gas chromatography coupled to triple quadrupole tandem mass spectrometry. Generalized linear regression analysis was employed to assess the associations of a single herbicide with T2DM, prediabetes, as well as indicators of glucose metabolism. In addition, the quantile g-computation and environmental risk score (ERS) structured by adaptive elastic net (AENET), and Bayesian kernel machine regression (BKMR) were used to estimate the effects of herbicides mixtures on T2DM and prediabetes., Results: After adjusting for covariates, positive associations of atrazine, ametryn, and oxadiazon with the increased odds of T2DM were obtained. As for prediabetes, each 1-fold increase in ln-transformed oxadiazon was related to 8.4% (95% confidence interval (CI): 1.033, 1.138) higher odds of prediabetes. In addition, several herbicides were significantly related to fasting plasma glucose, fasting insulin, and HOMA2-IR (false discovery rates adjusted P value < 0.05). Furthermore, the quantile g-computation analysis showed that one quartile increase in multiple herbicides was associated with T2DM (OR (odds ratio): 1.099, 95%CI: 1.043, 1.158), and oxadiazon was assigned the largest positive weight, followed by atrazine. In addition, the ERS calculated by the selected herbicides from AENET were found to be associated with T2DM and prediabetes, and the corresponding ORs and 95%CIs were 1.133 (1.108, 1.159) and 1.065 (1.016, 1.116), respectively. The BKMR analysis indicated a positive association between mixtures of herbicides exposure and the risk of T2DM., Conclusions: Exposure to mixtures of herbicides was associated with an increased risk of T2DM among Chinese rural population, indicating that the impact of herbicides exposure on diabetes should be paid attention to and measures should be taken to avoid herbicides mixtures exposure., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 The Authors. Published by Elsevier Inc. All rights reserved.)

Objective: The epidemiological evidence of human exposure to organophosphorus pesticides (OPPs) with type 2 diabetes mellitus (T2DM) and prediabetes (PDM) is scarce. We aimed to examine the association of T2DM/PDM risk with single OPP exposure and multi-OPP co-exposure., Methods: Plasma levels of ten OPPs were measured using the gas chromatography-triple quadrupole mass spectrometry (GC-MS/MS) among 2734 subjects from the Henan Rural Cohort Study. We used generalized linear regression to estimate odds ratios (ORs) or β with 95% confidence intervals (CIs), and constructed quantile g-computation and Bayesian kernel machine regression (BKMR) models to investigate the association of OPPs mixture with the risk of T2DM and PDM., Results: High detection rates ranged from 76.35% (isazophos) to 99.17% (malathion and methidathion) for all OPPs. Several plasma OPPs concentrations were in positive correlation with T2DM and PDM. Additionally, positive associations of several OPPs with fasting plasma glucose (FPG) values and glycosylated hemoglobin (HbA1c) levels were observed. In the quantile g-computation, we identified significantly positive associations between OPPs mixtures and T2DM as well as PDM, and fenthion had the greatest contribution for T2DM, followed by fenitrothion and cadusafos. As for PDM, the increased risk was largely explained by cadusafos, fenthion, and malathion. Furthermore, BKMR models suggested that co-exposure to OPPs was linked to an increased risk of T2DM and PDM., Conclusion: Our findings suggested that the individual and mixture of OPPs exposure were associated with an increased risk of T2DM and PDM, implying that OPPs might act an important role in the development of T2DM., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023. Published by Elsevier Ltd.)

This study aims to explore the association of combined exposure to cooking fuel type and ambient ozone (O 3 ) levels with hepatic fibrosis indices among rural adults. A total of 21,010 participants were derived from the Henan Rural Cohort. Information regarding cooking fuel type was collected through a questionnaire, and the concentration of ground-level O 3 for each subject was obtained from the Tracking Air Pollution in China (TAP) dataset. A generalized linear model was used to examine the independent association of cooking fuel type or O 3 exposure with hepatic fibrosis indices (FIB-4, APRI, and AST/ALT), and their possible interactions with advanced fibrosis were conducted. Compared to clean fuel users, solid fuel users had increased the risk of advanced fibrosis, the adjusted odds ratio (OR) of its assessment by FIB-4 1.240 (1.151, 1.336), by APRI 1.298 (1.185, 1.422), and by AST/ALT 1.135 (1.049, 1.227), respectively. Compared to low O 3 exposure, the adjusted ORs of advanced fibrosis assessed by FIB-4, APRI, and AST/ALT in women with high O 3 exposure were correspondingly 1.219 (1.138, 1.305), 1.110 (1.017, 1.212), and 0.883 (0.822, 0.949). The adjusted ORs of advanced fibrosis assessed by FIB-4, APRI, and AST/ALT for solid fuel users with high O 3 exposure relative to clean fuel users with low O 3 exposure in women were 1.557 (1.381, 1.755), 1.427 (1.237, 1.644), and 0.979 (0.863, 1.108), respectively. Significant additive effect of O 3 exposure and solid fuel use on FIB-4-defined advanced fibrosis was observed in women, which was quantified by RERI (0.265, 95%CI: 0.052, 0.477), AP (0.170 95%CI: 0.045, 0.295), and SI (1.906, 95%CI: 1.058, 3.432). Solid fuel users with high O 3 exposure were significantly associated with elevated hepatic fibrosis indices among rural women, suggesting that poor air quality may induce hepatocellular injury, and women might be more vulnerable to air pollution. The findings indicate that using cleaner fuels in cooking is an effective measure to maintain sustainable development of the environment and gain beneficial effect on human health. Clinical trial registration: The Henan Rural Cohort Study has been registered at the Chinese Clinical Trial Register (registration number: ChiCTR-OOC-15006699). Date of registration: 06 July 2015. http://www.chictr.org.cn/showproj.aspx?proj=11375., (© 2023. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Objective: This study aimed to evaluate the recent prevalence and the distributions of morphological subtypes of anaemia in the rural population., Design: Anaemia was defined according to the WHO and the Chinese criteria, and the morphological subtypes of anaemia were classified based on the erythrocyte parameters. The age-standardised prevalence was calculated according to the data of the Population Census 2010 in China., Setting: A cross-sectional study in Henan Province., Participants: 33 585 subjects aged 18-79 years old., Results: The standardised prevalence of anaemia across the WHO and the Chinese definitions was 13·63 % and 5·45 %, respectively. Regardless of which criteria was used, the standardised prevalence of anaemia was higher among women than among men and that increased with age in men, while markedly decreased after menopause in women. There were shifts in morphological patterns of anaemia using the WHO and the Chinese criteria that the standardised prevalence of microcytic anaemia was 3·74 % and 2·97 %, normocytic anaemia was 9·20 % and 2·34 %, and macrocytic anaemia was 0·75 % and 0·14 %, respectively. Besides, there were differences in the influencing factors of anaemia according to different criteria or gender. However, age, education level and renal damage were consistently significantly associated with anaemia in all participants., Conclusions: Anaemia may still be a serious health problem in rural China. It is necessary to reformulate prevention and management strategies to reduce the disease burden of anaemia.

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 (p interaction  = 0.018) and total population (p interaction  = 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., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier Inc. All rights reserved.)

Background: Limited studies have focused on the risk assessment of stroke in rural regions. Moreover, the application of artificial intelligence in stroke risk scoring system is still insufficient. This study aims to develop a simplified and visualized risk score with good performance and convenience for rural stroke risk assessment, which is combined with a machine learning (ML) algorithm., Methods: Participants of the Henan Rural Cohort were enrolled in this study. The total participants (n = 38,322) were randomly split into a train set and a test set in the ratio of 7:3. An ML algorithm was used to select variables and the logistic regression was then applied to construct the scoring system. The C-statistic and the Brier score (BS) were used to evaluate the discrimination and calibration. The Framingham stroke risk profile (FSRP) and the self-reported stroke risk function (SRSRF) were chosen to be compared., Results: The Rural Stroke Risk Score (RSRS) was produced in this study, including age, drinking status, triglyceride, type 2 diabetes mellitus, hypertension, waist circumference, and family history of stroke. On validation, the C-statistic was 0.757 (95% CI 0.749-0.765) and the BS was 0.058 in the test set. In addition, the discrimination of RSRS was 6.02% and 7.34% higher than that of the FSRP and SRSRF, respectively., Conclusions: A well-performed scoring system for assessing stroke risk in rural residents was developed in this study. This risk score would facilitate stroke screening and the prevention of cardiovascular disease in economically underdeveloped areas., (© 2023. Fondazione Società Italiana di Neurologia.)

This cross-sectional study aimed to investigate differences in skin surface lipids (SSL) and explore related metabolic pathways among females of different ages in Henan Province. Ultra-performance liquid chromatography quadrupole time-of-flight mass spectrometry (UPLC-QTOF-MS) was used to determine the lipid composition of the skin surface of 58 female volunteers who were divided into three age groups. Statistical analysis was performed using Progenesis QI, Ezinfo, and MetaboAnalyst. Multivariate and enrichment analysis were used to identify the different SSL among the groups. A total of 530 lipid entities were identified and classified into eight classes. Among these, 63 lipids were significantly different between the groups. Lower levels of glycerolipids (GLs) and sphingolipids (SPs) were observed in the middle-aged group, while higher levels of GLs were found in the elder group. GLs belonged to the largest and statistically significant enrichment of lipid metabolic pathways, and the lipid individuals enriched to the sphingoid bases metabolism were the most and statistically significant. These findings suggest that there are differences in hand SSL among females of different ages, which may be related to GLs and sphingoid bases metabolism.

Aims: To explore the dose-response relationship of fruit and vegetable (F&V) intake and type 2 diabetes (T2D) risk in rural China., Methods: A total of 38798 adults were recruited from the Henan Rural Cohort Study. F&V intake was assessed by a validated food-frequency questionnaire. Logistic regression and restricted cubic splines analysis were conducted to calculate the odds ratio (OR) for T2D relative to F&V intake and investigate the dose-response relationship., Results: Higher intake of fruit or combined F&V was in connection with a lower risk of T2D, after adjusting for multiple confounders. After analyzing the dose-response relationship, we found that the odds of T2D decreased significantly with fruit consumption ≥ 260 g/day or F&V intake between 600 and 1000 g/day. And in subgroup analysis, we found that the negative correlation between fruit consumption and T2D was more pronounced in non-current smokers and non-current drinkers., Conclusions: High intake of fruit alone or combined F&V is related to a reduced risk of T2D in rural China. Fruit intake ≥ 260 g/day and total F&V consumption of 600-1000 g/day should be encouraged to promote good health., Competing Interests: Conflict of interest None., (Copyright © 2023. Published by Elsevier Ltd.)

Sex hormones have been shown to be negatively associated with hypertension, but the relationship between serum progesterone levels and hypertension has not been adequately studied. Therefore, we aimed to evaluate the association between progesterone and hypertension among Chinese rural adults. A total of 6222 participants were recruited, which included 2577 men and 3645 women. The concentration of serum progesterone was detected by liquid chromatography-mass spectrometer system (LC-MS/MS). Logistic regression and linear regression were used to assess the associations between progesterone levels and hypertension and blood pressure related indicators, respectively. Constrained splines were used to fit the dose-response relationships of progesterone with hypertension and blood pressure related indicators. Moreover, the interactive effects of several lifestyle factors and progesterone were identified by a generalized linear model. After fully adjusting the variables, progesterone levels were inversely associated with hypertension in men [odds ratio (OR): 0.851, 95% confidence interval (CI): 0.752, 0.964]. Among men, a 2.738 ng/ml increase in progesterone was associated with a 0.557 mmHg decrease in diastolic blood pressure (DBP) (95% CI: -1.007, -0.107) and a 0.541 mmHg decrease in mean arterial pressure (MAP) (95% CI: -1.049, -0.034), respectively. Similar results were observed in postmenopausal women. Interactive effect analysis showed that only a significant interaction was observed between progesterone and educational attainment on hypertension in premenopausal women (p=0.024). Elevated levels of serum progesterone were associated with hypertension in men. Except for premenopausal women, a negative association of progesterone with blood pressure related indicators was observed., Competing Interests: The authors declare that they have no conflict of interest., (Thieme. All rights reserved.)

Background and Aims: The relationship between reproductive factors and type 2 diabetes (T2D) is controversial; therefore, we explored the causal relationship of age at menarche (AAM), age at natural menopause (ANM), with the risk of T2D and glycemic traits using two-sample Mendelian randomization., Methods and Results: We used publicly available data at the summary level of genome-wide association studies, where AAM (N = 329,345), ANM (N = 69,360), T2D (N = 464,389). The inverse variance weighting (IVW) method was employed as the primary method. To demonstrate the robustness of the results, we also conducted various sensitivity analysis methods including the MR-Egger regression, the weighted median (WM) and the MR Pleiotropy RESidual Sum and Outlier (MR-PRESSO) test. After excluding IVs associated with confounders, we found a causal association between later AAM and reduced risk of T2D (OR 0.81 [95% CI 0.75, 0.87]; P = 2.20 × 10 -8 ), lower levels of FI (β -0.04 [95% CI -0.06, -0.01]; P = 2.19 × 10 -3 ), FPG (β -0.03 [95% CI -0.05, -0.007]; P = 9.67 × 10 -5 ) and HOMA-IR (β -0.04 [95% CI -0.06, -0.01]; P = 4,95 × 10 -3 ). As for ANM, we only found a causal effect with HOMA-IR (β -0.01 [95% CI -0.02, -0.005]; P = 1.77 × 10 -3 ), but not with T2D., Conclusions: Our MR study showed a causal relationship between later AAM and lower risk of developing T2D, lower FI, FPG and HOMA-IR levels. This may provide new insights into the prevention of T2D in women., Competing Interests: Disclosure The authors have nothing to disclose., (Copyright © 2023 The Italian Diabetes Society, the Italian Society for the Study of Atherosclerosis, the Italian Society of Human Nutrition and the Department of Clinical Medicine and Surgery, Federico II University. Published by Elsevier B.V. All rights reserved.)

To explore the independent and combined effects of ESRα methylation and progesterone on impaired fasting glucose (IFG) and type 2 diabetes mellitus (T2DM), a case-control study including 901 subjects was conducted. Generalized linear models were performed to assess the independent and combined effects of ESRα methylation and progesterone on IFG or T2DM. Methylation level of cytosine-phosphoguanine (CpG) 1 in the estrogen receptor α ( ESRα ) gene was positively related to IFG in both men (odds ratio ( OR ) (95% confidence interval ( CI )): 1.77 (1.05, 3.00)) and postmenopausal women ( OR (95% CI ): 1.82 (1.09, 3.04)), whereas the association between CpG 1 and T2DM was not significant. Positive associations of progesterone with IFG and T2DM were observed in both men ( OR (95% CI ): 2.03 (1.18, 3.49) and 3.00 (1.63, 5.52)) and postmenopausal women ( OR (95% CI ): 2.13 (1.27, 3.56) and 3.30 (1.85, 5.90)). Participants with high CpG 1 methylation plus high progesterone had an increased risk of IFG and T2DM, both in men and postmenopausal women. ESRα methylation and progesterone were positively associated with IFG, and the positive association between progesterone and T2DM was also found. Importantly, we firstly found the combined effects of ESRα methylation and progesterone on IFG and T2DM.

Diet frequency may potentially influence metabolic health. However, general population-based evidence on the association between meal frequency and type 2 diabetes mellitus (T2DM) remains limited and inconclusive. Thus, this study aimed to investigate the association between meal frequency and T2DM in resource limited area. A total of 29,405 qualified participants were enrolled from the Henan rural cohort study. Data on meal frequency were collected through a validated face-to-face questionnaire survey. Logistic regression models were utilized to explore the association between meal frequency and T2DM. Compared with 21 times per week meal frequency group, the adjusted odds ratios ( ORs ) and 95% confidence intervals ( 95%CIs ) were 0.75 (0.58, 0.95) and 0.70 (0.54, 0.90) for 16-20 times/week group and 14-15 times/week group, respectively. For the analysis of the three meals, significant associations were only found between dinner frequency and T2DM. Compared with seven times per week dinner group, the ORs ( 95%CIs ) were 0.66 (0.42, 0.99) and 0.51 (0.29, 0.82) for the group with three to six times/week and zero to two times/week. Reduced meal frequency, especially dinner frequency, was associated with lower prevalence of T2DM, which suggests that an appropriate reduction in meal frequency per week may have a role in decreasing the risk of T2DM.

Evidence on the potential risk factors of normocytic anemia, the most prevalent morphology subtype of anemia, was scarce to date. The purpose of this study is to investigate the association of cooking fuel use or daily cooking duration with normocytic anemia and further explore the modification effect of mechanical ventilation. Participants totaling 29,448 from the Henan Rural Cohort were included in this study. Normocytic anemia was defined by hemoglobin (based on the World Health Organization criteria) and mean corpuscular volume. Cooking-related data was collected by questionnaire, and the average daily cooking duration was calculated by the weekly cooking frequency and the cooking duration of each meal. Logistic regression models were employed to derive the combined and independent associations of cooking fuel type and daily cooking duration with normocytic anemia and the modification effect of ventilation. Compared with people who never cooked, both clean fuel and solid fuel users were significantly associated with increased prevalent normocytic anemia [OR (95% CI) = 1.196 (1.014, 1.411) and 1.335 (1.105, 1.614), respectively], and the effect estimates on normocytic anemia risk were 1.260 (1.043, 1.523), 1.320 (1.104, 1.578), and 1.310 (1.081, 1.587) in participants who daily cooked < 1 h/day, 1-2 h/day, and ≥ 2 h/day, respectively. These relationships were attenuated in subjects with mechanical ventilation (All P < 0.05). Cooking with solid fuel or for a long duration are independently associated with prevalent normocytic anemia in rural population, and mechanical ventilation could attenuate these associations. Future efforts to reduce the burden of anemia could target the universal use of ventilation and solid fuel use or cooking duration reduction.Clinical trial registration: The Henan Rural Cohort Study has been registered at Chinese Clinical Trial Register (Registration number: ChiCTR-OOC-15006699). Date of registration: 06 July, 2015. http://www.chictr.org.cn/showproj.aspx?proj=11375., (© 2023. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Background: Evidence on the associations of fine particulate matter (PM 2.5 ) constituents and glucose metabolism is limited in resource-limited areas. This study aimed to explore the associations of PM 2.5 constituents with glucose metabolism in rural areas, and to further specify the most responsible constituent., Methods: A total of 38,442 adults were recruited from the Henan Rural Cohort Study during 2015-2017. Three-year averaged concentrations of PM 2.5 mass and its constituents (black carbon (BC), ammonium (NH 4 + ), nitrate (NO 3 - ), organic matter (OM), inorganic sulfate (SO 4 2- ), soil particles (SOIL) and sea salt (SS)) were estimated by a hybrid satellite-based model. Generalized linear model was applied to explore the associations of PM 2.5 mass and its constituents with type 2 diabetes mellitus (T2DM), fasting blood glucose (FBG), insulin, and HOMA-β. Proportion and residual analyses were employed to specify the most responsible constituent., Results: The adjusted odds ratio (OR) for T2DM associated with 1 μg/m 3 increase was 1.02 for PM 2.5 mass, 1.28 for BC, 1.15 for NH 4 + , 1.08 for NO 3 - , 1.10 for OM, 1.11 for SO 4 2- , and 1.12 for SOIL. Significant associations of PM 2.5 mass and its constituents with elevated FBG, decreased insulin and HOMA-β were also observed. Proportion and residual analyses indicated that BC was the most responsible constituent, in which 1 percentage increment in the proportion of BC in PM 2.5 corresponded with 1.51-fold risk for T2DM, 0.17 mmol/L increase in FBG, 2.18 μU/mL decrease in insulin, and 38.26 % decrease in HOMA-β; and 1 μg/m 3 increment in the PM 2.5 -adjusted BC corresponded with 1.59-fold risk for T2DM, 0.53 mmol/L increase in FBG, 4.79 μU/mL decrease in insulin, and 91.32 % decrease in HOMA-β., Conclusions: PM 2.5 mass and its constituents (BC, NH 4 + , NO 3 - , OM, SO 4 2- , SOIL) were associated with T2DM, increased FBG, decreased insulin and HOMA-β, of which BC was most responsible for these associations., Trial Registration: The Henan Rural Cohort Study has been registered at Chinese Clinical Trial Register (Registration number: ChiCTR-OOC-15006699). Date of registration: 06 July 2015. http://www.chictr.org.cn/showproj.aspx?proj=11375., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2022 Elsevier B.V. All rights reserved.)

Smoking contributes to the formation of skin wrinkles and reduces skin function, but the mechanism is not yet fully proven. This study aims to compare and analyze the effects of smoking on skin lipids and to further investigate the harmful effects of smoking on the skin. A total of 40 subjects (20 male smokers and 20 healthy control males) were recruited for this study. Measurement of hand skin-surface lipids (SSLs) in smoking and healthy control groups was undertaken using ultra-performance liquid chromatography quadrupole time-of-flight mass spectrometry (UPLC-Q-TOF-MS). Multivariate data analysis was used to investigate the differences in SSLs between the two groups. There were 1230 lipids detected in the two groups and significant differences in SSLs' composition were observed between them. Under selected conditions, 26 types of lipid with significant differences were observed between the two groups ( p < 0.05). Sphingolipids (SP) and glycerolipids (GL) were significantly increased, and sterol lipids (ST) were significantly reduced. Smoking causes changes in skin lipids that disrupt skin homeostasis, making the skin more fragile and more susceptible to skin aging and diseases.

Background: With the launch of the COVID-19 vaccines, the vaccination rate has become a hot issue of concern. However, the evidence for the relationship between college students' attitudes toward vaccines and anxiety and depressive symptoms has been limited., Methods: In total, 140,259 college students were recruited using a cluster sampling method in Zhengzhou, Xinxiang, Xinyang city of Henan Province, China, May 21-27, 2021. Anxiety symptoms were determined by the Generalized Anxiety Disorder tool (GAD-7) and depressive symptoms were determined by the Patient Health Questionnaire (PHQ-9). Multiple logistic regression was performed to estimate the association between students' attitudes toward the vaccines and anxiety and depressive symptoms., Results: The results indicate that 22.45% of students are unclear whether the vaccine can protect them from infection and 45.57% are unclear whether the vaccine is safe and has no side effects. In addition, after adjusting, the model showed that students who think vaccines can protect them and are safe had 0.128 (95%CI 0.110-0.150; P trend < 0.001) times lower risk of anxiety compared to their counterparts who think vaccines can neither protect them nor are safe. Similar ORs were found in depression (aOR = 0.157; 95%CI 0.137-0.180)., Conclusion: This large-scale study has shown an association between symptoms of anxiety and depression and reluctance to obtain vaccination., Supplementary Information: The online version contains supplementary material available at 10.1007/s10389-023-01830-7., Competing Interests: Conflict of interestThe authors declare that they have no conflict of interest., (© The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature 2023, Springer Nature or its licensor (e.g. a society or other partner) holds exclusive rights to this article under a publishing agreement with the author(s) or other rightsholder(s); author self-archiving of the accepted manuscript version of this article is solely governed by the terms of such publishing agreement and applicable law.)

Background: Associations of combined different cooking fuel types and cooking duration with sleep quality were scarcely reported. This study aimed to explore the associations of exposure to household air pollution (HAP) from different cooking fuel types and cooking duration with sleep quality and examine the effect modification of kitchen ventilation on these associations., Methods: A total of 28,135 eligible participants were obtained from the Henan rural cohort study. Sleep quality was assessed by the Pittsburgh sleep quality index (PSQI), and participants with a PSQI score > 5 were identified as having poor sleep quality. A questionnaire was used to collect the cooking fuel types, cooking frequency, cooking duration, and kitchen ventilation. The average daily cooking duration was calculated as the cooking frequency per week multiplied by the cooking duration for each meal divided by 7., Results: Both domestic fuel use and cooking duration were positively related to poor sleep quality. The solid fuel users with a cooking duration ≥1.5 h/day had a higher prevalence of poor sleep quality (OR: 1.390, 95% CI: 1.233, 1.567), relative to those who never cooked. Notably, the estimated OR and 95% CI for poor sleep quality of clean fuel users with a cooking duration <1.5 h/day plus mechanical or natural ventilation versus those who never cooked was 1.05 (0.933, 1.187) or 1.306 (1.163, 1.466) and these associations were modified by kitchen ventilation., Conclusion: Positive associations of combined different cooking fuel types and cooking duration with the prevalence of poor sleep quality were attenuated by kitchen ventilation, implying that installing mechanical ventilation may be an effective measure to improve sleep quality in low- and middle-income countries. These results need to be confirmed by future studies, which measure HAP more accurately using personal monitoring devices or behavior diaries., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2022 Elsevier B.V. All rights reserved.)

Background: Socioeconomic status (SES) was a crucial influencing factor of household air pollution (HAP). However, few studies have explored the potential effect modification of SES on the associations of HAP with type 2 diabetes mellitus (T2DM) and glucose homeostasis., Methods: A total of 20900 participants were obtained from the Henan Rural Cohort. HAP reflected by cooking fuel type and cooking duration was assessed via questionnaire. SES was evaluated by two dimensions: educational level and average monthly income. Associations of cooking fuel type, cooking duration with T2DM and glucose homeostasis indices (insulin, fasting plasma glucose (FPG), and HOMA-β) were assessed by the generalized linear model. Analyses were also conducted in different SES groups to explore the potential effect modification., Results: Significant negative association of cooking fuel type and cooking duration with T2DM, FPG, and HOMA-β was not observed. However, cooking with solid fuel and long-duration cooking were associated with decreased insulin level in women, and the adjusted coefficients were - 0.35 (95% confidence interval (95% CI): - 0.53, - 0.17) and - 0.36 (95% CI: -0.50, -0.21), respectively. Results from stratified analyses showed that these associations were more prominent in women with low average monthly income, with corresponding coefficient of - 0.57 (95% CI: -0.77, -0.37) for cooking with solid fuel and - 0.34 (95% CI: -0.52, -0.16) for long-duration cooking. Among women with low average monthly income, the largest decreased insulin level was observed in those who cooked with solid fuel, long-duration and poor kitchen ventilation, while the negative association of cooking fuel type and cooking duration with insulin level was slightly alleviated in the good kitchen ventilation group., Conclusions: Low average monthly income aggravated the negative association of HAP and insulin level among rural women, while improving kitchen ventilation may be a practical intervention., Trail Registration: The Henan Rural Cohort Study has been registered at Chinese Clinical Trial Register (Registration number: ChiCTR-OOC-15006699). Date of registration: 06 July, 2015. http://www.chictr.org.cn/showproj.aspx?proj=11375., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2022 The Authors. Published by Elsevier Inc. All rights reserved.)

Background: This study aimed to estimate healthy life expectancy (HLE) regarding anxiety, depression and their comorbidity among rural older adults., Methods: A total of 12,851 subjects (5790 men and 7061 women) enrolled from the Henan Rural Cohort Study were used to evaluate healthy status expectancy (HSE), and 10,096 (4475 men and 5621 women) of them were used to estimate health-adjusted life expectancy (HALE). The life expectancy was calculated using period life table, and HSE and HALE indicators were calculated via the Sullivan method., Results: For participants aged 60, the depression-free life expectancy (DFLE), anxiety-free life expectancy (AFLE), and depression- and anxiety-free life expectancy (DAFLE) were 23.0993, 23.3314, and 22.7206 years, respectively. The quality-adjusted life expectancy (QALE) of those with neither anxiety nor depression, with anxiety, with depression, and with comorbidity was 22.0727, 20.8751, 18.1484, and 17.0823 years, respectively. The ratio of DFLE (AFLE) to LE increased with age among both genders, while the DAFLE/LE showed a decreasing trend. Regardless of HSE or HALE indicators, women tended to have higher HLE, while HLE/LE was lower than men. Furthermore, all HLE indicators associated with anxiety were the largest in both genders compared to indicators regarding depression., Limitations: The HLE may be overestimated ignoring institutional population in the study., Conclusion: Anxiety and depression played essential roles in the quality of life among rural older adults, especially depression. Comorbidity would intensify the adverse effect in rural areas, especially for older men. More attention should be paid to the psychological problems among rural older population., Competing Interests: Conflict of interest The authors declared no conflict of interest., (Copyright © 2022 Elsevier B.V. All rights reserved.)

The association of ozone with type 2 diabetes mellitus (T2DM) is uncertain. Moreover, the moderating effect of physical activity on this association is largely unknown. This study aims to evaluate the independent and combined effects of ozone and physical activity on T2DM and fasting blood glucose (FBG) in a Chinese rural adult population. A total of 39,192 participants were enrolled in the Henan Rural Cohort Study. Individual ozone exposure was assessed by using a satellite-based random forest model. The logistic regression and generalized linear models were used to evaluate the associations of ozone and physical activity with T2DM and FBG, respectively. Interaction plots were used to visualize the interaction effects of ozone and physical activity on T2DM or FBG. An interquartile range (IQR) increase in ozone exposure concentration was related to a 53.3% (odds ratio (OR),1.533; 95% confidence interval (CI), 1.426, 1.648) increase in odds of T2DM and a 0.292 mmol/L (95%CI, 0.263, 0.321) higher FBG level, respectively. The effects of ozone on T2DM and FBG generally decreased as physical activity levels increased. Negative additive interactions between ozone and physical activity on T2DM risk were observed (relative excess risk due to interaction (RERI), -0.261; 95%CI, -0.473, -0.048; attributable proportion due to interaction (AP), -0.203; 95%CI, -0.380, -0.027; synergy index (S), 0.520; 95%CI, 0.299, 0.904). The larger effects of ozone were observed among elderly and men on T2DM and FBG than young and women. Long-term exposure to ozone was associated with higher odds of T2DM and higher FBG levels, and these associations might be attenuated by increasing physical activity levels. In addition, there was a negative additive interaction (antagonistic effect) between ozone exposure and physical activity level on T2DM risk, suggesting that physical activity might be an effective method to reduce the burden of T2DM attributed to ozone exposure. Trail registration: The Henan Rural Cohort Study has been registered at Chinese Clinical Trial Register (registration number: ChiCTR-OOC-15006699). Date of registration: 06 July 2015, http://www.chictr.org.cn/showproj.aspx?proj=11375., (© 2022. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Purpose: Dinner-bedtime interval was reported to be associated with general obesity. However, the association between dinner-bedtime interval and abdominal obesity is still unclear. This study was conducted to investigate the association of dinner-bedtime interval and abdominal obesity., Methods: A total of 7600 participants from Henan rural cohort study were included in this study. A standard questionnaire was used to obtain the time of dinner and sleep by the way of face-to-face interview. Sleep quality of each participant was evaluated by Pittsburgh Sleep Quality Index. Logistic regression and restricted cubic spline were used to assess the association between dinner-bedtime interval and abdominal obesity. Line regression was used to estimate the association between dinner-bedtime interval and lipid metabolism indexes. The mediation effect of sleep quality on the relationship between dinner-bedtime interval and abdominal obesity was evaluated., Results: In male, increased dinner-bedtime interval was associated with abdominal obesity risk (Adjusted OR: 1.084, 95% CI 1.009-1.164). Compared with participants with dinner-bedtime interval ≤ 2 h, those dinner-bedtime interval > 2 h had an elevated risk of abdominal obesity (Adjusted OR: 1.199, 95% CI 1.009-1.425). In addition, a positive linear dose-response relationship was detected between dinner-bedtime interval and abdominal obesity. Moreover, total cholesterol concentration increased by 0.047 mmol/L for each 1-h increase in dinner-bedtime interval (P = 0.019). In addition, sleep quality mediated 11.45% of the relationship between dinner-bedtime interval and abdominal obesity (adjusted mediation effect: - 0.010, 95% CI - 0.019 to - 0.003). But in female, these associations were not significant., Conclusion: It is suggested that increased dinner-bedtime interval was related to a higher risk of abdominal obesity in rural China and this association was differed by sex., Level of Evidence: Level V: cross-sectional descriptive study., (© 2022. The Author(s), under exclusive licence to Springer Nature Switzerland AG.)

Although household air pollution (HAP) is associated with an increased risk of mental disorders, evidence remains scarce for the relationship between HAP and suicidal ideation. A total of 21,381 qualified participants were enrolled on the Henan Rural Cohort Study. HAP information including cooking fuel type, cooking duration and kitchen ventilation was collected by questionnaires. Suicidal ideation was evaluated by item nine of the Patient Health Questionnaire-9 (PHQ-9). Independent and combined associations of cooking fuel type and cooking duration with suicidal ideation were explored by logistic regression models. Analyses were conducted in different kitchen ventilation groups to detect the potential effect modification. The adjusted odds ratio (OR) and 95% confidence interval (95% CI) of solid fuel users versus clean fuel users for suicidal ideation was 1.37 (1.16, 1.62), and the risk of suicidal ideation increased by 15% (95% CI: 5%, 26%) for each additional hour of the cooking duration. Participants cooking with solid fuel for long durations were related to the highest risk of suicidal ideation (OR (95% CI): 1.51 (1.22, 1.87)). However, all these associations were not observed in those cooking with mechanical ventilation. Mechanical ventilation ameliorated relationships between solid fuel use and long-duration cooking with suicidal ideation.

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.

It is worth paying attention to the level of worry and fear of students during the normalization of the epidemic. We conducted the cross-sectional study that included 182,991 high school students using an online survey to assess worry and fear levels and its influencing factors in three cities in Henan Province, China, from May 21 to May 27, 2021. Worry and fear levels were measured using a five-item Likert-type scale. Multinomial logistic regression was used to analyze the risk factors. Approximately 65.42% of students reported being high worry about the coronavirus disease 2019 (COVID-19) epidemic, and about 41.44% of students reported being high fear about the COVID-19 epidemic. In addition, compared with female, male had lower odds of suffering from a high worry, and compared with senior high school students, junior high school students were more likely to suffer from a high worry. Students lived in rural had highest odds increased likelihood of high worry. Similar results in fear levels. During the normalization period of the COVID-19 epidemic, many students have high levels of worry and fear. This study has implications for potential influencers of worry and fear levels in follow-up work., Competing Interests: The authors declare no conflict of interest., (© 2022 Wiley Periodicals LLC.)