Associations of short-term ambient temperature exposure with lung function in middle-aged and elderly people: A longitudinal study in China.

The short-term associations of ambient temperature exposure with lung function in middle-aged and elderly Chinese remain obscure. The study included 19,128 participants from the Dongfeng-Tongji cohort's first (2013) and second (2018) follow-ups. The lung function for each subject was determined between April and December 2013 and re-assessed in 2018, with three parameters (forced vital capacity [FVC], forced expiratory volume in 1 s [FEV1], and peak expiratory flow [PEF]) selected. The China Meteorological Data Sharing Service Center provided temperature data during the study period. In the two follow-ups, a total of 25,511 records (average age: first, 64.57; second, 65.80) were evaluated, including 10,604 males (41.57%). The inversely J-shaped associations between moving average temperatures (lag01-lag07) and FVC, FEV1, and PEF were observed, and the optimum temperatures at lag04 were 16.5 °C, 18.7 °C, and 16.2 °C, respectively. At lag04, every 1 °C increase in temperature was associated with 14.07 mL, 9.78 mL, and 62.72 mL/s increase in FVC, FEV1, and PEF in the low-temperature zone (

Role and mechanism of WNT5A in benzo(a)pyrene-induced acute lung injury and lung function decline.

Benzo(a)pyrene was sparsely studied for its early respiratory impairment. The non-canonical ligand WNT5A play a role in pneumonopathy, while its function during benzo(a)pyrene-induced adverse effects were largely unexplored. Individual benzo(a)pyrene, plasma WNT5A, and spirometry 24-hour change for 87 residents from Wuhan-Zhuhai cohort were determined to analyze potential role of WNT5A in benzo(a)pyrene-induced lung function alternation. Normal bronchial epithelial cell lines were employed to verify the role of WNT5A after benzo(a)pyrene treatment. RNA sequencing was adopted to screen for benzo(a)pyrene-related circulating microRNAs and differentially expressed microRNAs between benzo(a)pyrene-induced cells and controls. The most potent microRNA was selected for functional experiments and target gene validation, and their mechanistic link with WNT5A-mediated non-canonical Wnt signaling was characterized through rescue assays. We found significant associations between increased benzo(a)pyrene and reduced 24-hour changes of FEF50% and FEF75%, as well as increased WNT5A. The benzo(a)pyrene-induced inflammation and epithelial-mesenchymal transition in BEAS-2B and 16HBE cells were attenuated by WNT5A silencing. hsa-miR-122-5p was significantly and positively associated with benzo(a)pyrene and elevated after benzo(a)pyrene induction, and exerted its effect by downregulating target gene TP53. Functionally, WNT5A participates in benzo(a)pyrene-induced lung epithelial injury via non-canonical Wnt signaling modulated by hsa-miR-122-5p/TP53 axis, showing great potential as a preventive and therapeutic target.

Associations of glucose metabolism and diabetes with heart rate variability: a population-based cohort study.

The present study aimed to investigate the potential causal pathways and temporal relationships of glucose metabolism and diabetes with heart rate variability (HRV). This cohort study was conducted among a sample of 3858 Chinese adults. At baseline and 6 years follow-up, participants underwent HRV measurement (low frequency [LF], high frequency [HF], total power [TP], standard deviation of all normal-to-normal intervals [SDNN], and square root of the mean squared difference between adjacent normal-to-normal intervals [r-MSSD]) and determination of glucose homeostasis (fasting plasma glucose [FPG] and insulin [FPI], homeostatic model assessment for insulin resistance [HOMA-IR]). The temporal relationships of glucose metabolism and diabetes with HRV were evaluated using cross-lagged panel analysis. FPG, FPI, HOMA-IR, and diabetes were cross-sectionally negatively associated with HRV indices at baseline and follow-up (P < 0.05). Cross-lagged panel analyses demonstrated significant unidirectional paths from baseline FPG to follow-up SDNN (ß = -0.06), and baseline diabetes to follow-up low TP group (ß = 0.08), low SDNN group (ß = 0.05), and low r-MSSD group (ß = 0.10) (P < 0.05). No significant path coefficients were observed from baseline HRV to follow-up impaired glucose homeostasis or diabetes. These significant findings persisted even after excluding participants who were taking antidiabetic medication. The results support that elevated FPG and the presence of diabetes may be the causes rather than the consequences of HRV reduction over time.

Triazine herbicides exposure, natural immunoglobulin M antibodies, and fasting plasma glucose changes: Association and mediation analyses in general Chinese urban adults.

The effects of triazine herbicides on glucose metabolism remain unclear. In this study, we aimed to assess the associations between serum triazine herbicides and glycemia-related risk indicators in general adults, and to evaluate the mediating role of natural immunoglobulin M antibodies (IgM) in the above associations among uninfected participants. We measured the concentrations of atrazine, cyanazine, and IgM in serum, as well as fasting plasma glucose (FPG), and fasting plasma insulin in 4423 adult participants from the Wuhan-Zhuhai cohort baseline population, enrolled in 2011-2012. Generalized linear models were used to evaluate the associations of serum triazine herbicides with glycemia-related risk indicators, and mediation analyses were performed to evaluate the mediating role of serum IgM in the above associations. The median levels of serum atrazine and cyanazine were 0.0237 µg/L and 0.0786 µg/L, respectively. Our study found significant positive associations of serum atrazine, cyanazine, and Σtriazine with FPG levels, risk of impaired fasting glucose (IFG), abnormal glucose regulation (AGR), and type 2 diabetes (T2D). Additionally, serum cyanazine and Σtriazine were found to be significant positive associated with the homeostatic model assessment of insulin resistance (HOMA-IR) levels. Significant negative linear relationships were observed in associations of serum IgM with serum triazine herbicides, FPG, HOMA-IR levels, the prevalence of T2D, and AGR (P < 0.05). Furthermore, we observed a significant mediating role by IgM in the associations of serum triazine herbicides with FPG, HOMA-IR, and AGR, with the proportions ranging from 2.96% to 7.71%. To ensure the stability of our findings, we conducted sensitivity analyses in normoglycemic participants and found that the association of serum IgM with FPG and the mediating role by IgM remained stable. Our results suggest that triazine herbicides exposure is positively associated with abnormal glucose metabolism, and decreasing serum IgM may partly mediate these associations.

Cross-sectional and longitudinal relationships between ozone exposure and glucose homeostasis: Exploring the role of systemic inflammation and oxidative stress in a general Chinese urban population.

The adverse health effects of ozone pollution have been a globally concerned public health issue. Herein we aim to investigate the association between ozone exposure and glucose homeostasis, and to explore the potential role of systemic inflammation and oxidative stress in this association. A total of 6578 observations from the Wuhan-Zhuhai cohort (baseline and two follow-ups) were included in this study. Fasting plasma glucose (FPG) and insulin (FPI), plasma C-reactive protein (CRP, biomarker for systemic inflammation), urinary 8-hydroxy-2'-deoxyguanosine (8-OHdG, biomarker for oxidative DNA damage), and urinary 8-isoprostane (biomarker for lipid peroxidation) were repeatedly measured. After adjusting for potential confounders, ozone exposure was positively associated with FPG, FPI, and homeostasis model assessment of insulin resistance (HOMA-IR), and negatively associated with HOMA of beta cell function (HOMA-ß) in cross-sectional analyses. Each 10 ppb increase in cumulative 7-days moving average ozone was associated with a 13.19%, 8.31%, and 12.77% increase in FPG, FPI, and HOMA-IR, respectively, whereas a 6.63% decrease in HOMA-ß (all P < 0.05). BMI modified the associations of 7-days ozone exposure with FPI and HOMA-IR, and the effects were stronger in subgroup whose BMI ≥24 kg/m2. Consistently high exposure to annual average ozone was associated with increased FPG and FPI in longitudinal analyses. Furthermore, ozone exposure was positively related to CRP, 8-OHdG, and 8-isoprostane in dose-response manner. Increased CRP, 8-OHdG, and 8-isoprostane could dose-dependently aggravate glucose homeostasis indices elevations related to ozone exposure. Increased CRP and 8-isoprostane mediated 2.11-14.96% of ozone-associated glucose homeostasis indices increment. Our findings suggested that ozone exposure could cause glucose homeostasis damage and obese people were more susceptible. Systemic inflammation and oxidative stress might be potential pathways in glucose homeostasis damage induced by ozone exposure.

Lipid peroxidation mediates the association between iron overload and liver injury: cross-sectional and longitudinal analyses in general Chinese urban adults.

Iron overload has been associated with acute/chronic organ failure, but whether iron overload induces liver injury remains unclear. The objectives of this study were to assess the relationship between urinary iron and serum alanine aminotransferase (ALT, a biomarker for liver injury), and investigate the potential mediating roles of lipid peroxidation and oxidative DNA damage in such association. Levels of urinary iron, serum ALT, and urinary biomarkers of lipid peroxidation (8-iso-prostaglandin-F2α [8-iso-PGF2α]) and oxidative DNA damage (8-hydroxy-deoxyguano-sine [8-OHdG]) were measured among 5386 observations of 4220 participants from the Wuhan-Zhuhai cohort. The relationships of urinary iron with serum ALT and risk of hyperALT were evaluated by linear mixed model and logistic regression model, respectively. The mediating roles of 8-iso-PGF2α and 8-OHdG were assessed by mediation analyses. This cross-sectional analysis found that urinary iron was positively associated with ALT (ß = 0.032; 95% CI: 0.020, 0.044) and hyperALT prevalence (OR = 1.127; 95% CI: 1.065, 1.192). After 3 years of follow-up, participants with persistent high iron levels had increased risk of developing hyperALT (RR = 3.800; 95% CI: 1.464, 9.972) when compared with those with persistent low iron levels. In addition, each 1% increase in urinary iron was associated with a 0.146% (95% CI: 0.128%, 0.164%) increase and a 0.192% (95% CI: 0.154%, 0.229%) increase in 8-iso-PGF2α and 8-OHdG, respectively. Urinary 8-iso-PGF2α (ß = 0.056; 95% CI: 0.039, 0.074) was positively associated with ALT, while the association between 8-OHdG and ALT was insignificant. Furthermore, increased 8-iso-PGF2α significantly mediated 22.48% of the urinary iron-associated ALT increment. Our study demonstrated that iron overload was significantly associated with liver injury, which was partly mediated by lipid peroxidation. Controlling iron intake and regulating lipid peroxidation may help in preventing liver injury.

Associations of selenium exposure with blood lipids: Exploring mediating DNA methylation sites in general Chinese urban non-smokers.

Selenium (Se) is widely distributed in the total environment and people are commonly exposed to Se, while the potential effects and mechanisms of Se exposure on blood lipids have not been well established. This study aimed to assess the associations of urinary Se (SeU) with blood lipids and explore the potential mediating DNA methylation sites. We included 2844 non-smoke participants from the second follow-up (2017-2018) of the Wuhan-Zhuhai cohort (WHZH) in this study. SeU and blood lipids [i.e., total cholesterol (TC), triglycerides (TG), low-density lipoprotein cholesterol (LDL), and high-density lipoprotein cholesterol (HDL)] for all participants were determined. The associations of SeU with blood lipids were analyzed by generalized linear models. Then, we conducted the blood lipids related epigenome-wide association studies (EWAS) among 221 never smokers, and the mediation analysis was conducted to explore the potential mediating cytosine-phosphoguanine (CpG) sites in the above associations. In this study, the SeU concentration of the participants in this study was 1.40 (0.94, 2.08) µg/mmol Cr. The SeU was positively associated with TC and LDL, and not associated with TG and HDL. We found 131, 3, and 1 new CpG sites related to TC, HDL, and LDL, respectively. Mediation analyses found that the methylation of cg06964030 (within MIR1306) and cg15824094 (within PLCH2) significantly mediated the positive association between SeU and TC. In conclusion, high levels of Se exposure were associated with increased TC and LDL among non-smokers, and the methylation of MIR1306 and PLCH2 partly mediated Se-associated TC increase. These findings provide new insights into the effects and mechanisms of Se exposure on lipids metabolism and highlight the importance of controlling Se exposure and intake for preventing high blood lipids.

PM2.5-related DNA methylation and the association with lung function in non-smokers.

PM2.5 exposure leads to lung function alteration. The potential pathway underlying above association, especially the role of DNA methylation is unclear. The objectives of this study are to evaluate the associations of personal PM2.5 concentrations with DNA methylation at the epigenome-wide level, and investigate how PM2.5-related DNA methylation affects lung function. A total of 402 observations of non-smokers were selected from the Wuhan-Zhuhai cohort. PM2.5 exposure was estimated through a model established in the same population. Blood DNA methylation levels were determined through Illumina Infinium MethylationEPIC BeadChips. Lung function was tested through spirometry on the day of blood sampling. The associations of PM2.5 exposure with DNA methylation and DNA methylation with lung function were determined through linear mixed models. Ten PM2.5-related CpG sites (mapped to 7 different genes) were observed with false discovery rate <0.05. Methylation levels of cg24821877, cg24862131, cg23530876, cg11149743 and cg10781276 were positively associated with PM2.5 concentrations. While methylation levels of cg10314909, cg08968107, cg18362281, cg24663971 and cg17834632 were negatively associated with PM2.5 concentrations. The top CpG was cg24663971 (P = 1.51✕10-9). Among the above 10 sites, significantly positive associations of methylation levels of cg24663971 with FVC%pred and FEV1%pred, and cg10314909 with FVC, FVC%pred, and FEV1%pred were observed. Age had modification effect on the associations between cg24663971 methylation and FVC%pred, and the associations were more obvious among participants with age ≥58 years. In conclusion, PM2.5 exposure was associated with DNA methylation, and PM2.5-related DNA methylation was associated with lung function among Wuhan urban non-smokers.

Assessment for the associations of twenty-three metal(loid)s exposures with early cardiovascular damage among Chinese urban adults with five statistical methods: Insight into assessing health effect of multipollutant exposure.

The topic of cardiovascular hazards from multiple metal (loid)s exposures has attracted widespread attention. Here, we measured concentrations of twenty-three urinary metal (loid)s and mean platelet volume (MPV), an early cardiovascular damage biomarker, for 3396 Chinese adults. We aimed to comprehensively assess the associations of single metal (loid) and multiple metal (loid)s (as a mixture) with MPV by combined use of five statistical methods, including general linear models, Bayesian kernel machine regression (BKMR), weight quartile sum (WQS) regression, quantile g-computation (QGC), and adaptive elastic network regression (AENR). And based on that, we hope to provide insight into assessing the health effect of multipollutant exposure. After adjustment for potential covariates, at least three methods jointly suggested that of twenty-three metal (loid)s, iron, arsenic, and antimony were positively while aluminum, tungsten, and thallium were inversely associated with MPV. The environmental risk score of metal (loid)s construed by AENR was significantly positively associated with MPV, while the association between overall twenty-three metal (loid)s mixture and MPV was neutralized to be insignificant in QGC and BKMR. Conclusively, single metal (loid) may be inversely (iron, arsenic, and antimony) and positively (aluminum, tungsten, and thallium) associated with early cardiovascular damage, while the association of overall twenty-three metal (loid)s mixture with MPV was insignificant when concurrent exposures exist. It is crucial to select appropriate statistical methods based on study purpose and principles/characteristics of statistical methods, and combined employment of multimethod is insightfully suggested when assessing health effects of multipollutant exposure.

AMER3 variants modify the U-shaped association of urinary total hydroxyphenanthrene with fasting plasma glucose: A newfound gene-environment interaction.

As a polycyclic aromatic hydrocarbon, environmental exposure to phenanthrene is widespread worldwide. The potential effects and mechanism of phenanthrene exposure on fasting plasma glucose (FPG) have not been well determined. In this study, we aim to explore the effects of phenanthrene exposure and AMER3 variants on fasting plasma glucose (FPG) through a longitudinal epidemiological study. Repeated measurements of five urinary hydroxyphenanthrene (OHPh) for 5739 participants with 7083 observations from the Wuhan-Zhuhai cohort were performed to analyze the relationships between total OHPh (ΣOHPh) and FPG using linear mixed models and restricted cubic spline functions. Then, we genotyped 2777 participants (4104 observations) using the Infinium OmniZhongHua-8 BeadChip and included all 14 single nucleotide polymorphisms (SNPs) within the AMER3 gene to analyze the interaction of the AMER3 on the relationship between ΣOHPh and FPG. We observed a U-shaped relationship between ΣOHPh and FPG, and the turning point of ΣOHPh was 2.512 µg/mmol Cr. When lower than the turning point, ΣOHPh was negatively associated with FPG, while higher than the turning point, ΣOHPh was positively associated with FPG. Furthermore, we observed interactions (Pint <0.05) between two common variants (rs72854995 and rs72854999) of the AMER3 and ΣOHPh on FPG change: the U-shaped relationship was still observed in the GG genotype groups but not in the allele A carriers. Our results suggested that the AMER3 gene can modify the U-shaped relationship between phenanthrenes exposure and FPG, which showed a new gene-environment interaction and will provide a new perspective on the relationship between phenanthrene exposure and FPG.

Long-term personal PM2.5 exposure and lung function alternation: A longitudinal study in Wuhan urban adults.

BACKGROUND: The effect of long-term PM2.5 exposure on lung function has not been well established. OBJECTIVES: To investigate the effects of long-term personal PM2.5 exposure on lung function decline, obstructive, and restrictive ventilatory disorders. METHOD: Personal PM2.5 concentrations were evaluated using an estimation model. Lung function parameters including forced vital capacity (FVC), forced expiratory volume in 1 s (FEV1) and peak expiratory flow (PEF) were measured in 3053 Wuhan participants from the Wuhan-Zhuhai cohort and were repeated every 3 years. Participants were classified into persistently high exposure group, persistently low exposure group and inconsistent exposure group according to the median of PM2.5 concentration of each visit. Mixed linear models with subject-specific random intercept were used to assess the association of 3-year change of lung function with personal PM2.5 exposure, and generalized linear models were used to assess the association of 6-year change of lung function with personal PM2.5 exposure. Cox regression models were applied to assess the associations of PM2.5 with obstructive and restrictive ventilatory disorders. RESULTS: The medians of personal PM2.5 concentrations at baseline and two follow-ups were 153.18, 209.57 and 83.78 µg/m3, respectively. Compared with participants in the persistently low exposure group, participants in the persistently high exposure group showed a 2.99 % (95 % CI: 0.91, 5.08), a 380.15 mL/s (95 % CI: 32.82, 727.48) and a 5.98 % (95 % CI: 0.84, 11.11) additional decline in FEV1/FVC, PEF and PEFpred after 6 years, respectively. Stratified analyses showed that age, gender, body mass index, smoking status and drinking status had no significant modification effect on the associations. The associations of PM2.5 exposure with obstructive and restrictive ventilatory disorders were not significant, except for a positive association between persistently high PM2.5 exposure and restrictive ventilatory disorder among ever drinkers. CONCLUSION: Long-term high PM2.5 exposure was associated with FEV1/FVC, PEF and PEFpred declines.

Longitudinal relationships of polycyclic aromatic hydrocarbons exposure and genetic susceptibility with blood lipid profiles.

OBJECTIVE: We aim to analyze the effects of polycyclic aromatic hydrocarbons (PAHs) exposure and genetic predisposition on blood lipid through a longitudinal epidemiological study. METHODS: We enrolled 4,356 observations who participated at baseline (n = 2,435) and 6-year follow-up (n = 1,921) from Wuhan-Zhuhai cohort. Ten urinary PAHs metabolites and blood lipid (i.e., total cholesterol [TC], triglycerides [TG], low-density lipoprotein cholesterol [LDL-C], and high-density lipoprotein cholesterol [HDL-C]) were measured at both baseline and follow-up. The polygenic risk scores (PRS) of blood lipid were constructed by the corresponding genome-wide association studies. Linear mixed models were fit to identify associations between urinary PAHs metabolites, blood lipid, and lipid-PRSs in the repeated-measure analysis. Besides, longitudinal relationships of blood lipid with urinary PAHs metabolites and respective lipid-PRSs were examined by using linear regression models. RESULTS: Compared with subjects who had persistently low urinary total hydroxyphenanthrene (ΣOHPh), those with persistently high levels had an average increase of 0.137 mmol/l for TC and 0.129 mmol/l for LDL-C over 6 years. Each 1-unit increase of TC-, TG-, LDL-C-, and HDL-C-specific PRS were associated with an average increase of 0.438 mmol/l for TC, 0.264 mmol/l for TG, 0.198 mmol/l for LDL-C, and 0.043 mmol/l for HDL-C over 6 years, respectively. Compared with subjects who had low genetic risk and persistently low ΣOHPh, subjects with high LDL-specific PRS and persistently high ΣOHPh had an average increase of 0.652 mmol/l for LDL-C. CONCLUSIONS: Our results suggest that high-level ΣOHPh exposure is associated with an average increase of LDL-C over 6 years, and those relationships can be aggravated by a higher LDL-C-genetic risk. No significant relationships were observed between other PAHs metabolites (including hydroxynaphthalene, hydroxyfluorene, and hydroxypyrene) and blood lipid changes over 6 years. Our findings emphasize the importance of preventing PAHs exposure, particularly among those with a higher genetic predisposition of hyperlipidemia.

A review of practical statistical methods used in epidemiological studies to estimate the health effects of multi-pollutant mixture.

Environmental risk factors have been implicated in adverse health effects. Previous epidemiological studies on environmental risk factors mainly analyzed the impact of single pollutant exposure on health, while in fact, humans are constantly exposed to a complex mixture consisted of multiple pollutants/chemicals. In recent years, environmental epidemiologists have sought to assess adverse health effects of exposure to multi-pollutant mixtures based on the diversity of real-world environmental pollutants. However, the statistical challenges are considerable, for instance, multicollinearity and interaction among components of the mixture complicate the statistical analysis. There is currently no consensus on appropriate statistical methods. Here we summarized the practical statistical methods used in environmental epidemiology to estimate health effects of exposure to multi-pollutant mixture, such as Bayesian kernel machine regression (BKMR), weighted quantile sum (WQS) regressions, shrinkage methods (least absolute shrinkage and selection operator, elastic network model, adaptive elastic-net model, and principal component analysis), environment-wide association study (EWAS), etc. We sought to review these statistical methods and determine the application conditions, strengths, weaknesses, and result interpretability of each method, providing crucial insight and assistance for addressing epidemiological statistical issues regarding health effects from multi-pollutant mixture.

Longitudinal relationships between polycyclic aromatic hydrocarbons exposure and heart rate variability: Exploring the role of transforming growth factor-ß in a general Chinese population.

We aim to investigate the long-term adverse effects of polycyclic aromatic hydrocarbons (PAHs) exposure on heart rate variability (HRV) reduction, and to assess the potential role of transforming growth factor-ß1 (TGF-ß1) in such relationship. We enrolled 2985 adult residents with 4100 observations who participated at baseline and 6-years follow-up from Wuhan-Zhuhai cohort. Ten detectable urinary PAHs metabolites and two HRV indices were repeatedly measured at baseline and follow-up; and plasma TGF-ß1 levels were also determined for all subjects. We observed that both total urinary low molecular weight PAHs (ΣLWM OH-PAH) and total urinary high molecular weight PAHs (ΣHWM OH-PAH) were negatively associated with HRV reductions (P < 0.05). Subjects with persistent high levels of ΣHWM OH-PAH had a significant reduction in HRV over 6 years, and the incensement of TGF-ß1 could aggravate above adverse effects in a dose-response manner. All kinds of PAHs were positively associated with plasma TGF-ß1 elevation, which in turn, were negatively related to HRV indices. Increased TGF-ß1 significant mediated 1.34-3.62% of PAHs-associated HRV reduction. Our findings demonstrated that long-term high levels of PAHs exposure could cause HRV reductions, and TGF-ß1 may play an essential role in such association.

The methylation of the AMER3 gene mediates the negative association between urinary polycyclic aromatic hydrocarbon metabolites and fasting plasma glucose in non-smokers: A new clue for the development of hypoglycemic agents.

Polycyclic aromatic hydrocarbons (PAHs) have been reported to cause various health damages. However, some PAH derivatives are still used as agents, and some of them have hypoglycemic effects. Till now, few studies explored the relationship between urinary PAH metabolites and fasting plasma glucose (FPG). In this study, A total of 2682 non-smokers in the second follow-up of the Wuhan-Zhuhai cohort were included to explore the relationship between urinary PAH metabolites and FPG. FPG related epigenome-wide association study (EWAS) was conducted among 212 never smokers, and the mediation analysis was performed to find potential mediator cytosine-phosphoguanine (CpG) sites in the above relationship. The concentration of total urinary PAH metabolites was 3.60 (2.37, 5.85) µg/mmol Cr. The urinary PAH metabolites were negatively associated with FPG. Each 1-U increase in ln-transformed levels of 1-hydroxynaphthalene, 4-hydroxyphenanthrene, 9-hydroxyphenanthrene, or 2- hydroxyphenanthrene was associated with 0.008-, 0.007-, 0.010-, or 0.010- unit decreased in ln-transformed levels of FPG, respectively (all p < 0.05). We found 28 new CpG sites related to FPG (FDR <0.05) through EWAS. Mediation analysis found that cg11350141 on AMER3 mediated 41.91% of the negative association of total urinary PAH metabolites with FPG. These results provide a new clue for the development of hypoglycemic agents.

Systemic inflammation mediates the association of heavy metal exposures with liver injury: A study in general Chinese urban adults.

Heavy metal exposures have been reported to be associated with increased risk for liver injury. However, the potential mechanisms of the association remain unclear. A repeated-measure study of 9367 observations was conducted to quantify the associations of urinary heavy metals with serum alanine aminotransferase (ALT), a biomarker for liver injury, and assess the mediating role of systemic inflammation in such associations among general Chinese adults. In single-metal models, positive dose-response relationships between urinary vanadium (V), chromium (Cr), copper (Cu), arsenic (As), cadmium (Cd), tungsten (W), and lead (Pb) and serum ALT were observed. In the multiple-metal model containing the seven metals mentioned above, V and Cu remained positively associated with ALT. In longitudinal analyses of 3-6 years, each 1-unit increase in log-transformed levels of V and Cu was associated with an additional rate of annual ALT increase (95% CI) for 1.3% (0.7-1.8%) and 1.3% (0.7-2.0%), respectively. Plasma CRP concentrations were not only positively associated with urinary Cu and Cd, but also positively related with ALT. Furthermore, mediation analyses showed that CRP mediated 4.70% and 7.03% of urinary Cu- and Cd-associated ALT elevations. Our study provides clues for the prevention of heavy metal-induced liver injury.

IL-22: A potential mediator of associations between urinary polycyclic aromatic hydrocarbon metabolites with fasting plasma glucose and type 2 diabetes.

Previous studies found that exposure to polycyclic aromatic hydrocarbons (PAHs) was associated with type 2 diabetes (T2D) prevalence. However, the potential mechanism is still unclear. In this study, we investigated 3031 Chinese urban adults to discover the relationship between PAH exposure and plasma Interleukin-22 (IL-22) and potential role of IL-22 in the association between PAH and fasting plasma glucose (FPG) or risk of T2D. After adjustment for potential confounders, significant dose-response relationships were observed between several urinary PAH metabolites with FPG and the prevalence of T2D. Each 1-U increase in ln-transformed value of 2-hydroxynaphthalene (2-OHNa), 2-hydroxyphenanthrene (2-OHPh), 3-hydroxyphenanthrene (3-OHPh), 4-hydroxyphenanthrene (4-OHPh), 9-hydroxyphenanthrene (9-OHPh), 1-hydroxypyrene (1-OHP) or total PAH metabolites was significantly associated with a 0.053, 0.026, 0.037, 0.045, 0.051, 0.041 or 0.047 unit decrease in IL-22 level, respectively. In addition, plasma IL-22 level was negatively associated with FPG and prevalence of T2D in a dose-dependent manner. Mediation analysis showed that IL-22 mediated 8.48 %, 3.87 %, 6.64 %, 6.47 %, and 8.67 % of the associations between urinary 2-OHNa, 1-OHPh, 3-OHPh, 4-OHPh, and 9-OHPh with the prevalence of T2D, respectively. These results indicated that urinary PAHs metabolites were inversely associated with plasma levels of IL-22, but positively related to FPG and the T2D prevalence. Downregulation of IL-22 might play a significant role in mediating PAHs exposure-associated risk increasement of T2D.

Personal PM2.5 exposure and lung function: Potential mediating role of systematic inflammation and oxidative damage in urban adults from the general population.

BACKGROUND: Short-term effects of fine particulate matter (PM2.5) exposure on lung function have been reported. However, few studies have assessed PM2.5 exposure on the personal level, and the mechanism underlying the effects of PM2.5 exposure on lung function remains less clear. OBJECTIVES: To evaluate the association between personal PM2.5 exposure and lung function alteration in general population and to explore the roles of systematic inflammation and oxidative damage in this association. METHODS: A total of 7685 lung function tests were completed among 4697 urban adults in Wuhan, China. Plasma C-reactive protein (CRP), urinary 8-iso-prostaglandin-F2α (8-iso-PGF2α) and 8-hydroxy-2'-deoxyguanosine (8-OHdG) levels were measured. Personal PM2.5 exposure levels were estimated using an estimation model from the actual measurements of individual PM2.5 levels in 191 participants. Mixed linear models were used to evaluate the association between personal PM2.5 exposure and lung function. Mediation analyses were conducted to investigate the roles of CRP, 8-iso-PGF2α and 8-OHdG in above associations. RESULTS: After adjusting for confounders, each 10 µg/m3 increase in the previous-day personal PM2.5 exposure was associated with 2.94 mL, 2.02 mL and 16.14 mL/s decreases in forced vital capacity (FVC), forced expiration volume in 1 s (FEV1) and peak expiratory flow, respectively. The associations were more obvious among never smokers compared with current smokers. Cumulative 7-day exposure to PM2.5 led to the strongest adverse effects on lung function. Among never smokers with high PM2.5 exposure levels, a positive relationship was observed between personal PM2.5 level and urinary 8-iso-PGF2α, and 8-iso-PGF2α meditated 4.69% and 12.30% of the association between the 7-day moving PM2.5 concentration and FVC and FEV1, respectively. We did not observe a significant positive association between PM2.5 exposure and plasma CRP or urinary 8-OHdG. CONCLUSION: Short-term personal exposure to PM2.5 is associated with reduced pulmonary ventilation function. Urinary 8-iso-PGF2α partly mediates these associations.

Epidemiological characteristics and transmission dynamics of paediatric cases with coronavirus disease 2019 in Hubei province, China.

AIM: This study aimed to identify the epidemiological characteristics and transmission dynamics of paediatric cases. METHODS: Information on 1369 paediatric cases with COVID-19 from 8 December 2019 to 7 March 2020 in Hubei province was extracted from the National Infectious Disease Surveillance System. The analysis included epidemic curves, temporal-spatial distribution, clinical classification and interval times between onset and diagnosis. RESULTS: Among 1369 paediatric cases, the median age was 9 years and 58.2% of them were males. The proportion of severe and critical cases in children was lower than that in adults and the proportion of asymptomatic cases in children was five times greater than for adult cases. The first paediatric case was reported on 2 January 2020, and the daily number of new paediatric cases remained high from 1 February through to 22 February. The epidemiological curve of paediatric cases lagged behind that of adults by 19 days, and the first spike of the epidemic curve in senior high school students occurred 1 week earlier than in other paediatric groups. The proportion of clustered cases among children was about twice that for adults. The median of the interval in paediatric cases between onset and diagnosis, isolation and notification were 3, 0 and 3 days, respectively, and all of those were significantly shorter than in adults. CONCLUSIONS: The epidemic curve of child cases lagged behind that of adult cases by 19 days, and the major form of transmission observed was in clusters.

Heavy metals exposure, lipid peroxidation and heart rate variability alteration: Association and mediation analyses in urban adults.

Exposure to heavy metals was reported to be associated with heart rate variability (HRV) alteration. However, possible pathway of such association remains unclear. In this research, we investigated the possible role of lipid peroxidation in the associations between urinary heavy metals and HRV. We performed a cross-sectional study using baseline data of Wuhan-Zhuhai cohort. Urinary heavy metals (including lead, barium, antimony, cadmium, zinc, copper, iron and manganese), urinary 8-iso-prostaglandin-F2α levels (common biomarker for lipid peroxidation) and HRV indices (SDNN, r-MSSD, low frequency, high frequency and total power) were measured among 3022 participants. We conducted multivariable linear regression models to quantify associations between urinary 8-iso-prostaglandin-F2α (8-iso-PGF2α) and heavy metals or HRV indices. The potential role of 8-iso-PGF2α in the association of urinary heavy metals with HRV was evaluated through mediation analyses. After adjusting for potential confounders, urinary manganese, iron, copper, zinc, cadmium, antimony and barium were identified to be negatively associated with one or more HRV parameters. Each one-unit growth of log-transformed levels of urinary manganese, iron, copper, zinc, antimony and barium was associated with a 1.9%, 1.5%, 4.7%, 4.0%, 2.7% and 1.3% decrease in SDNN, respectively. We observed positive dose-response relationships between all eight urinary heavy metals and 8-iso-PGF2α, as well as negative association of urinary 8-iso-PGF2α with SDNN and total power (all P trend<0.05). The proportions mediated by 8-iso-PGF2α on SDNN were 4.6% for manganese, 9.3% for iron, 19.8% for antimony and 11.0% for barium. The proportions mediated by 8-iso-PGF2α on total power were 6.9% for manganese and 10.1% for cadmium (all P value < 0.05). This study suggested that urinary manganese, iron, copper, zinc, cadmium, antimony and barium were negatively associated with HRV indices. Lipid peroxidation may partly mediate the associations of urinary manganese, iron, cadmium, antimony and barium with specific HRV indices.