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Objective To investigate potential causal pathways and temporal relationships of glucose metabolism and diabetes with heart rate variability (HRV). Methods The cohort study was developed in 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]). Cross-lagged panel analysis was used to examine the temporal relationships of glucose metabolism and diabetes with HRV. Results FPG, FPI, HOMA-IR, and diabetes were cross-sectionally negatively associated with HRV indices at baseline and follow-up (P Conclusions The findings provide strong evidence that elevated FPG and diabetes may be the causes rather than the consequences of HRV reduction over time.

PM

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 (P

The effect of long-term PMTo investigate the effects of long-term personal PMPersonal PMThe medians of personal PMLong-term high PM

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.

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.

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 (FDR0.05) 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.

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-β1 (TGF-β1) 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-β1 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-β1 could aggravate above adverse effects in a dose-response manner. All kinds of PAHs were positively associated with plasma TGF-β1 elevation, which in turn, were negatively related to HRV indices. Increased TGF-β1 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-β1 may play an essential role in such association.

Short-term effects of fine particulate matter (PMTo evaluate the association between personal PMA total of 7685 lung function tests were completed among 4697 urban adults in Wuhan, China. Plasma C-reactive protein (CRP), urinary 8-iso-prostaglandin-FAfter adjusting for confounders, each 10 μg/mShort-term personal exposure to PM

Background Disease caused by SARS-CoV-2 broke out in Wuhan in December 2019. We utilized confirmed cases outside Hubei Province to analyze epidemiologic characteristics and evaluate the effect of traffic restrictions implemented in Hubei beginning on 23 January 2020. Methods Information on 7015 confirmed cases from 19 January to 8 February 2020 in all provinces outside Hubei was collected from the national and local health commissions in China. Incubation period and interval times were calculated using dates of the following events: contact with an infected person, onset, first visit, and diagnosis. We evaluated changes in incubation period and interval times. Results The average age of all cases was 44.24 years. The median incubation period was 5 days and extended from 2 days on 23 January to 15 days on 8 February. The proportion of imported cases decreased from 85.71% to 33.19% after 23 January. In addition, lengths of intervals between onset and diagnosis, onset and first visit, and first visit and diagnosis decreased over time. Conclusions Rapidly transmitting COVID-19 has a short incubation period. The onset mainly occurred among young to middle-aged adults. Traffic restrictions played an important role in the decreased number of imported cases outside Hubei.

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 trend0.05). 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.

Polycyclic aromatic hydrocarbon (PAH) exposure has been considered a risk factor for cardiovascular diseases (CVD), whereas possible mechanisms for this association have not been fully understood. This study focused on exploring the potential effect of oxidatively damaged DNA on the relationships between PAH exposure and the 10-year atherosclerotic CVD (ASCVD) risk. Urinary levels of monohydroxy PAH metabolites (OH-PAHs) and 8-oxo-7,8-dihydro-2'-deoxyguanosine (8-oxodG, the typical biomarker for oxidatively damaged DNA) were measured among 3052 subjects in the baseline of the Wuhan-Zhuhai cohort. The relationships between urinary OH-PAHs, 8-oxodG and 10-year risk of ASCVD were analyzed by linear mixed models and logistic regression models, respectively. The mediation analysis was further applied to explore the role of 8-oxodG in the relationship between urinary OH-PAHs and 10-year ASCVD risk. After controlling for potential confounders, the log-transformed level of total urinary low molecular weight OH-PAHs (∑LMW OH-PAHs) was significantly associated with an elevated risk of 10-year ASCVD [odds ratio (OR) = 1.222, 95% confidence interval (CI): 1.065-1.402]. More specifically, significantly positive dose-response relationships between total urinary hydroxynaphthalene (∑OHNa), hydroxyfluorene (∑OHFlu), hydroxyphenanthrene (∑OHPh) and 10-year ASCVD risk were observed (all P for trend0.05). We also found positive relationships between urinary OH-PAH levels and 8-oxodG, as well as between urinary 8-oxodG levels and 10-year risk of ASCVD. Moreover, mediation analyses indicated that urinary 8-oxodG mediated 14.49%, 12.62% and 10.55% of the associations between urinary ∑LMW OH-PAHs, ∑OHNa, ∑OHFlu and 10-year ASCVD risk, respectively. These findings suggest that the oxidatively damaged DNA pathway may be a possible mechanism underlying PAH-associated ASCVD risk elevation.

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.

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.

This study was designed to analyze the risk factors for postoperative pancreatic fistula (POPF) after pancreaticoduodenectomy (PD). Between September 2015 and August 2017, 170 successive patients underwent a radical PD in the Department of Pancreatic Surgery, Union Hospital, Wuhan. We carried out a retrospective study of these cases and the prospective conditions, which might be related to POPF, were examined with univariate and multivariate analysis. POPF was defined as a drain output of any measurable volume of fluid with an amylase level more than 3 times the upper limit of serum amylase activity on postoperative day 3, accompanied by a clinically relevant condition according to the 2016 update of the International Study Group for Pancreatic Surgery (ISGPS) definition. In our study, the POPF was just referred to as grade B and grade C pancreatic fistula in accordance with the ISGPS consensus, because the former grade A pancreatic fistula is now redefined as a biochemical leak, namely no-POPF, which has no clinical impact and needs no other special therapy. Pancreatic fistula occurred in 44 (25.9%) patients after PD, with a mean length of hospital stay of 24.98 ± 14.30 days. Thirty-six patients (21.2%) developed grade B pancreatic fistula, and 8 patients (4.7%) had grade C pancreatic fistula. Among patients with grade C pancreatic fistula, 4 patients died, 3 patients were operated on again, and 3 patients developed multiple organ failure. Univariate analysis showed a significantly important association between POPF and the following factors: pancreas texture (soft vs hard: 39.1% vs 10.3%, P