Mediation effect of platelet indices on the association of daytime nap duration with 10-year ASCVD risk.

Daytime nap is associated with the risk of atherosclerotic cardiovascular disease (ASCVD). However, the contribution of platelet to the association of daytime nap with ASCVD remains unclear. We analyzed the mediation effect of abnormal platelet indices on the association between daytime nap and 10-year ASCVD risk. The participants of this study were 2445 adults aged 30 to 74 years without ASCVD from the baseline Wuhan residents (n = 3053) of the Wuhan-Zhuhai (WHZH) Cohort Study. Participants completed the questionnaire and physical examination (including blood pressure, height, weight, and blood biochemical indicators). We assessed the association of daytime nap or nocturnal sleep duration with 10-year ASCVD risk and mediation effects of platelet indices on the associations using generalized linear models (GLM). Individuals with daytime nap duration of 30 or 60 min had a 1.37- (95%CI: 1.05, 1.78) or 1.44- (95%CI: 1.17, 1.78) fold increased risk of 10-year ASCVD compared with non-nappers. As compared with non-nappers, MPV values or MPV/PLT ratio mediated 15.29% or 6.18% of the association of daytime nap duration of 30 min with 10-year ADCVD risk as well as 19.21% or 7.61% of the association of daytime nap duration of 60 min with 10-year ADCVD risk (all p < .05). Platelet might partially contribute to increased 10-year ASCVD risk in individuals with daytime nap duration of 30 or 60 min.

Non-linear dose-response relation between urinary levels of nicotine and its metabolites and cognitive impairment among an elderly population in China.

BACKGROUND: Active smoking and exposure to environmental tobacco smoke may be related to cognitive function decline. We assessed the associations of urinary levels of nicotine and its metabolites with cognitive function. METHODS: A total of 553 elder adults at high risk of cognitive impairment and 2212 gender- and age-matched individuals at low risk of cognitive impairment were selected at a ratio of 1: 4 from the remained individuals (n = 6771) who completed the baseline survey of the Shenzhen Ageing-Related Disorder Cohort, after excluding those with either Alzheimer's disease, Parkinson's syndrome or stroke as well as those with missing data on variables (including active and passive smoking status, Mini-Cog score). Urinary levels of nicotine and its metabolites and cognitive function for all individuals were measured by high-performance liquid chromatography-tandem mass spectrometry (LC-MS/MS) and assessed using the Mini-Cog test, respectively. Associations of urinary levels of nicotine and its metabolites with cognitive function were analyzed by conditional logistic regression models. RESULTS: Individuals in the highest tertile of urinary OHCotGluc (OR: 1.52, 95%CI: 1.19-1.93) or NNO (OR: 1.50, 95%CI: 1.16-1.93) levels as well as in the second tertile of urinary ∑Nic level (OR: 1.43, 95%CI: 1.13-1.82) were at higher risk of cognitive impairment compared with those in the corresponding lowest tertile. Restricted cubic spline models revealed the non-linear dose-response relationships between urinary levels of OHCotGluc, NNO or ∑Nic and the risk of cognitive impairment. CONCLUSIONS: Urinary levels of OHCotGluc, NNO or ∑Nic exhibited a non-linear dose-response relationship with cognitive function in the urban elderly.

Seasonal modification of the associations of exposure to polycyclic aromatic hydrocarbons or phthalates of cellular aging.

Exposure to polycyclic aromatic hydrocarbons (PAHs) and phthalates link to oxidative stress and inflammatory response, which exert cellular aging. However, modification effect of seasonal factor on the association of PAHs or phthalates exposure with relative telomere length (RTL) or mitochondrial DNA copy number (mtDNA-CN) has remained unclear. In this pilot study, 106 subjects were from an urban population (n = 1240) who lived in the two districts in Wuhan city, China. Participants completed physical examinations and provided 191 blood samples for RTL and mtDNA-CN analysis and 627 urine samples for monohydroxylated-PAHs (OH-PAHs) and phthalate metabolites measurements in the winter and summer seasons. We assessed the associations of urinary OH-PAHs or phthalates metabolites with RTL or mtDNA-CN by linear regression analysis and linear mixed-effect models. We found that urinary OH-PAHs were positively associated with mtDNA-CN at lag 2 day and 3-day moving average, but negatively related to RTL at lag 0, lag 1 and lag 2 day and 3-day moving average (p < 0.05). Urinary phthalate metabolites were negatively associated with mtDNA lag 0, lag 1 and lag 2 day and 3-day moving average, but positively related to RTL at lag 0 day (p < 0.05). Seasonal factor modified the association of urinary OH-PAHs with mtDNA-CN as well as urinary phthalate metabolites with RTL. In vitro experiment showed that under certain conditions, benzo[a]pyrene increased mtDNA-CN at 48 h and di (2-ethylhexyl) phthalate did RTL at 24 h in HepG2 cells. Seasonal variations in the metabolisms of PAHs or phthalates in human body may affect the relation of PAHs or phthalates exposure with cellular aging.

The relative and interactive effects of urinary multiple metals exposure on hyperuricemia among urban elderly in China.

Objective: Independent and interactive effects of multiple metals levels in urine on the risk of hyperuricemia (HUA) in the elderly were investigated. Methods: A total of 6,508 individuals from the baseline population of the Shenzhen aging-related disorder cohort were included in this study. We detected urinary concentrations of 24 metals using inductively coupled plasma mass spectrometry, fitted unconditional logistic regression models, and the least absolute shrinkage and selection operator regression models for the selection of metals as well as unconditional stepwise logistic regression models and restricted cubic spline logistic regression models for assessing the associations of urinary metals and HUA risk, and finally applied generalized linear models to determine the interaction with urinary metals on the risk of HUA. Results: Unconditional stepwise logistic regression models showed the association between urinary vanadium, iron, nickel, zinc, or arsenic and HUA risk (all P < 0.05). We revealed a negative linear dose-response relationship between urinary iron levels and HUA risk (P overall < 0.001, P nonliner = 0.682), a positive linear dose-response relationship between urinary zinc levels and HUA risk (P overall < 0.001, P nonliner = 0.513), and an additive interaction relationship between urinary low-iron and high-zinc levels and HUA risk (RERI = 0.31, 95% CI: 0.03-0.59; AP = 0.18, 95%CI: 0.02-0.34; S = 1.76, 95%CI: 1.69-3.49). Conclusion: Urinary vanadium, iron, nickel, zinc, or arsenic levels were associated with HUA risk, and the additive interaction of low-iron (<78.56 µg/L) and high-zinc (≥385.39 µg/L) levels may lead to a higher risk of HUA.

Correlating metal exposures and dietary habits with hyperuricemia in a large urban elderly cohort by artificial intelligence.

Epidemiological studies using conventional statistical methods have reported an association between individual metal exposure and hyperuricemia (HUA). There is also evidence that diet may influence HUA development, although the available data are inconsistent. We therefore used an elastic net regression (ENR) model to screen the usefulness of various environmental and dietary factors as predictors of HUA in a large sample cohort. This study included 6217 subjects drawn from the Shenzhen Aging Related Disorder Cohort. We obtained information on the subjects' dietary habits via face-to-face interviews and used inductively coupled plasma mass spectrometry (ICP-MS) to measure the urinary concentrations of 24 metals to which elderly persons in large urban areas may be exposed. An elastic net regression (ENR) model was generated to screen the utility of the metals and dietary factors as predictors of HUA, and we demonstrated the superiority of the ENR model by comparing it to a traditional logistic regression model. The identified predictors were used to create a clinically usable nomogram for identifying patients at risk of developing HUA. The area under curve (AUC) value of the final model was 0.692 for the training set and 0.706 for the test set. Important predictors of HUA were Zn, As, V, and Fe as well as consumption of wheat, beans, and rice; the corresponding estimated odds ratios and 95% confidence intervals were 1.091 (0.932,1.251), 1.190 (1.093,1.286), 0.924 (0.793,1.055), 0.704 (0.626,0.781), 0.998 (0.996,1.001), 0.993 (0.989,0.998), and 1.001 (0.998,1.002), respectively. In contrast to previous studies, we found that both urinary metal concentrations and dietary habits are important for predicting HUA risk. Exposure to specific metals and consumption of specific foods were identified as important predictors of HUA, indicating that the incidence of this disease could be reduced by reducing exposure to these metals and promoting improved dietary habits.

Effect modification by aging on the associations of nicotine exposure with cognitive impairment among Chinese elderly.

Active and passive exposure to tobacco smoke may increase risk of cognitive decline. However, effects of enhanced the aging process on the association of urinary nicotine metabolites with cognitive impairment remain unclear. In this study, 6657 Chinese older adults completed the physical examinations and cognitive tests. We measured urinary nicotine metabolite levels, mitochondrial DNA copy number (mtDNA-CN), and relative telomere length (RTL) and analyzed effects of urinary nicotine metabolites and their interaction with mtDNA-CN or RTL on cognitive impairment by generalized linear models and qg-computation, respectively. Each 1-unit increase in urinary 3-OHCot, 3-OHCotGluc, CotGluc, or NicGluc levels corresponded to a 1.05-, 1.09-, 1.04-, and 0.90-fold increased risk of cognitive impairment. Each 1-quantile increment in the mixture level of 8 nicotine metabolites corresponded to an increment of 1.40- and 1.34-fold risk of cognitive impairment in individuals with longer RTL or low mtDNA-CN. Urinary 3-OHCotGluc and RTL or mtDNA-CN exhibited an additive effect on cognitive impairment in addition to the mixture of 8 nicotine metabolites and mtDNA-CN. The findings suggested that aging process may increase the risk of tobacco-related cognitive impairment.

Study design and baseline characteristics of Shenzhen ageing-related disorder cohort in China.

PURPOSE: The Shenzhen ageing-related disorder cohort was designed to detect the associations of lifestyle, environmental and genetic factors with major ageing-related disorders, especially neurological and mental disorders. PARTICIPANTS: The cohort was a community-dwelling prospective study of 9411 elderly adults aged 60 to 92 years from 51 community health service centres in Luohu district of Shenzhen, China. The baseline data were collected between 2017 and 2018, including demographics and socioeconomics, lifestyles, medical history, family history of major non-communicable chronic disease, environmental exposures, clinical analysis of blood and urine, clinical imaging measurements, anthropometric measures and neurological function and mental health assessments. Blood and urinary samples were collected at baseline. All participants will be followed for physiological and psychological disorders and updated lifestyle and environmental exposures every 5 years. FINDINGS TO DATE: The mean age of the participants was 67.73 years at baseline, and 42.74% were males. The prevalences of individuals with unhealthy conditions were as follows: overweight/obesity (54.38%), hypertension (58.24%), diabetes mellitus (22.30%), dyslipidaemia (75.69%), chronic bronchitis (1.45%), myocardial infarction (0.55%), coronary heart disease (5.69%), stroke (1.10%), cancer (2.18%), arthritis (5.04%), Alzheimer's disease (0.18%), Parkinson's disease (0.23%), brain injury (5.75%), cognitive impairment (5.39%) and depression status (3.28%). The mean scores for the Lawton-Brody Activities of Daily Living Scale and the Social Support Rate Scale were 14.15 and 39.54, respectively. FUTURE PLANS: 2000 new entrants from Luohu district will be recruited every year until 2028. The data collection is expected to be ended at the end of 2030. The data will be used to assess the causality of ageing-related disorders, especially neurological and mental disorders through integrating environmental, genetic and lifestyle factors. The data sets generated and/or analysed during the current study are not publicly available at this stage, but are available from the corresponding author on reasonable request.

Interaction between diet- and exercise-lifestyle and phthalates exposure on sex hormone levels.

Phthalate can affect sex hormones secretion. Exercise and diet habits affect sex hormones levels. However, interaction of phthalates exposure and diet or exercise habits with sex hormones is unclear. We enrolled 106 residents aged 11-88 years (48 males and 58 females) from two communities, Wuhan city, China during the winter of 2014 and summer of 2015. Data were collected on socio-demographic characteristics and lifestyle by a questionnaire in two seasons. Participants provided the blood and urine samples over 3 consecutive days for measuring sex hormones and urinary phthalate metabolites. We assessed the associations of urinary phthalate metabolites levels, lifestyle with hormones levels, the interaction of phthalate exposure and lifestyle with hormones levels using multivariate binary logistic regression models. High urinary mono-(2-ethyl-5-oxyhexyl) phthalate (MEOHP) levels and no exercise had an additive interaction on abnormal serum progesterone (PROG) levels in winter as well as on abnormal serum follicle-stimulating hormone (FSH) or luteinizing hormone (LH) levels in summer. High urinary MEOHP levels and red meat intake (>1 time/day) had an additive interaction with abnormal levels of serum FSH only in the winter. Phthalates exposure may confer differential susceptibility to abnormal hormones levels in individuals with no exercise or eating meat >1 time/day.

Mediating factors explaining the associations between polycyclic aromatic hydrocarbons exposure, low socioeconomic status and diabetes: A structural equation modeling approach.

Exposure to polycyclic aromatic hydrocarbons (PAHs) is linked with increased risk of diabetes, whereas socioeconomic status (SES) may contribute to the development of diabetes. However, the mechanisms underlying the relationships between them are unclear. We used structural equation modeling (SEM) to identify mediating factors in the associations of PAHs exposure, low SES with diabetes risk. Data were collected from 2751 Wuhan participants at baseline from the Wuhan-Zhuhai Cohort Study (n = 3053). They answered the questionnaires regarding socio-demographic, participated physical examinations and provided urine samples for measurements of urinary monohydroxy-polycyclic aromatic hydrocarbons (OH-PAHs) levels. SEM was used to identify the mediating factors (such as hypertension, body mass index (BMI), triglycerides (TG) and total cholesterol (TCHO)) in the associations of low SES or PAHs exposure with diabetes risk. We observed that partial effect of PAHs exposure (ß = 0.281, p = 0.034), BMI (ß = 0.182, p = 0.000), TG (ß = 0.358, p = 0.000), TCHO (ß = 0.203, p = 0.009) or hypertension (ß = 0.385, p = 0.000) on diabetes was directive. Moreover, low SES also exhibited a directive effect on PAHs exposure (ß = -0.084, p = 0.000), BMI (ß = 0.301, p = 0.000), hypertension (ß = 0.134, p = 0.003) and TG (ß = 0.087, p = 0.001). PAHs exposure directly affected TCHO levels (ß = 0.080, p = 0.002) and TG (ß = 0.076, p = 0.017). The proportion of the effect of PAHs exposure on diabetes mediated by TG and TCHO was 15.6%. The proportion of the effect of low SES on diabetes mediated by BMI, hypertension and TG was 89.1%. The results suggested that low SES increased diabetes risk, which may be partially explained by BMI, hypertension and triglycerides, and exposure to high levels of PAHs may have indirect contribution to increased risk for diabetes with dyslipidemia.

Transcription factor USF2 is developmentally regulated in fetal lung and acts together with USF1 to induce SP-A gene expression.

Expression of the pulmonary surfactant protein A (SP-A) gene is lung specific, developmentally regulated, and enhanced by hormones and factors that increase cAMP. We previously identified two E-box-like enhancers termed distal binding element (DBE) and proximal binding element (PBE) in the 5'-flanking region of the rabbit (r) SP-A gene that are essential for cAMP induction of rSP-A promoter activity (Gao E, Alcorn JL, and Mendelson CR. J Biol Chem 268: 19697-19709, 1993). We also found that DBE and PBE serve as binding sites for the basic helix-loop-helix-leucine zipper transcription factor, upstream stimulatory factor-1 (USF1) (Gao E, Wang Y, Alcorn JL, and Mendelson CR. J Biol Chem 272: 23398-23406, 1997). In the present study, PBE was used to screen a rabbit fetal lung cDNA expression library; a cDNA insert encoding the structurally related rabbit upstream stimulatory factor-2 (rUSF2) was isolated. The levels of rUSF2 mRNA reach peak levels in fetal rabbit lung at 28 days of gestation, in concert with the time of maximal induction of SP-A gene transcription. In yeast two-hybrid analysis, rUSF2 was found to preferentially form heterodimers, compared with homodimers, with rUSF1. Binding complexes of nuclear proteins isolated from fetal rabbit lung type II cells with the DBE and PBE were supershifted by anti-rUSF2 antibodies. Binding activity was enriched in nuclear proteins from type II cells compared with fibroblasts. Overexpression of rUSF2 in transfected lung A549 cells increased rSP-A promoter activity and acted synergistically with rUSF1. We suggest that heterodimers of USF2 and USF1 bound to two E-box elements in the SP-A gene 5'-flanking region serve a key role in developmental and hormonal regulation of SP-A gene expression in pulmonary type II cells.