Environmental Toxicant Exposure and Depressive Symptoms.

Importance: Recognizing associations between exposure to common environmental toxicants and mental disorders such as depression is crucial for guiding targeted mechanism research and the initiation of disease prevention efforts. Objectives: To comprehensively screen and assess the associations between potential environmental toxicants and depressive symptoms and to assess whether systemic inflammation serves as a mediator. Design, Setting, and Participants: A total of 3427 participants from the 2013-2014 and 2015-2016 waves of the National Health and Nutrition Examination and Survey who had information on blood or urine concentrations of environmental toxicants and depression scores assessed by the 9-item Patient Health Questionnaire (PHQ-9) were included. Statistical analysis was performed from July 1, 2023, to January 31, 2024. Exposures: Sixty-two toxicants in 10 categories included acrylamide, arsenic, ethylene oxide, formaldehyde, iodine, metals, nicotine metabolites, polycyclic aromatic hydrocarbons, volatile organic compound (VOC) metabolites; and perchlorate, nitrate, and thiocyanate. Main Outcomes and Measures: An exposome-wide association study and the deletion-substitution-addition algorithm were used to assess associations with depression scores (PHQ-9 ≥5) adjusted for other important covariates. A mediation analysis framework was used to evaluate the mediating role of systemic inflammation assessed by the peripheral white blood cell count. Results: Among the 3427 adults included, 1735 (50.6%) were women, 2683 (78.3%) were younger than 65 years, and 744 (21.7%) were 65 years or older, with 839 (24.5%) having depressive symptoms. In terms of race and ethnicity, 570 participants (16.6%) were Mexican American, 679 (19.8%) were non-Hispanic Black, and 1314 (38.3%) were non-Hispanic White. We identified associations between 27 chemical compounds or metals in 6 of 10 categories of environmental toxicants and the prevalence of depressive symptoms, including the VOC metabolites N-acetyl-S-(2-hydroxy-3-butenyl)-l-cysteine (odds ratio [OR], 1.74 [95% CI, 1.38, 2.18]) and total nicotine equivalent-2 (OR, 1.42 [95% CI, 1.26-1.59]). Men and younger individuals appear more vulnerable to environmental toxicants than women and older individuals. Peripheral white blood cell count mediated 5% to 19% of the associations. Conclusions and Relevance: In this representative cross-sectional study of adults with environmental toxicant exposures, 6 categories of environmental toxicants were associated with depressive symptoms with mediation by systemic inflammation. This research provides insight into selecting environmental targets for mechanistic research into the causes of depression and facilitating efforts to reduce environmental exposures.

Association between Volatile Organic Compound Exposure and Sex Hormones in Adolescents: The Mediating Role of Serum Albumin.

The associations between VOCs and sex hormones in adolescents remain unclear, and the role of serum albumin in these associations deserves to be explored. We conducted cross-sectional analyses using generalized linear models (GLMs), weighted quantile sum (WQS) regression, and mediation analysis, based on data from 584 adolescents from the National Health and Nutrition Examination Survey (NHANES). The GLM analyses revealed that seven kinds of mVOCs potentially affected sex hormone levels. According to the WQS regression results, 2-aminothiazoline-4-carboxylic acid (ATCA) was the major contributor to the significant associations of mixed mVOC exposure with testosterone, estradiol, and free androgen index in males; N-acetyl-S-(N-methylcarbamoyl)-L-cysteine (AMCC) was the major contributor to the significant associations of mixed mVOC exposure with sex hormone-binding globulin in males; and N-acetyl-S-(benzyl)-L-cysteine (BMA) was the major contributor to the significant associations of mixed mVOC exposure with the ratio of testosterone to estradiol in females. Moreover, serum albumin could mediate up to 9.2% of the associations between mixed exposure to mVOCs and sex hormones. Our findings could provide a reference for studies on the mechanisms underlying the effects of VOCs on sex hormones in adolescents and emphasize the necessity of reducing exposure to ATCA, AMCC, BMA, and their parent compounds.

The short-term effects of individual and mixed ambient air pollutants on suicide mortality: A case-crossover study.

It is critical to explore intervenable environmental factors in suicide mortality. Based on 30,688 suicide cases obtained from the Mortality Surveillance System of the Jiangsu Provincial Centre for Disease Control and Prevention, we utilized a case-crossover design, and found that the OR of suicide deaths increased by a maximum of 0.71 % (95 % CI: 0.09 %, 1.32 %), 0.68 % (95 % CI: 0.12 %, 1.25 %), 0.77 % (95 % CI: 0.19 %, 1.37 %), 2.95 % (95 % CI: 1.62 %, 4.29 %), 4.18 % (95 % CI: 1.55 %, 6.88 %), and 0.93 % (95 % CI: 0.10 %, 1.77 %), respectively, for per 10 µg/m3 increase in the particulate matter (PM) with diameters ≤ 2.5 µm (PM2.5), PM with diameters ≤ 10 µm (PM10), ozone (O3), nitrogen dioxide (NO2), sulfur dioxide (SO2), and per 0.1 mg/m3 increase in carbon monoxide (CO) concentrations with the conditional logistic regression analysis. People living in county-level cities were more susceptible. Particularly, a significant positive association was found between air pollutant mixture exposure and suicide deaths (OR=1.04,95 % CI: 1.01, 1.06). The excess fraction of suicide deaths due to air pollution reached a maximum of 8.07 %. In conclusion, we found associations between individual and mixed ambient air pollutants and suicide deaths, informing the development of integrated air pollution management and targeted measures for suicide prevention and intervention. ENVIRONMENTAL IMPLICATION: As a major contributor to the global burden of disease, air pollution was confirmed by accumulating studies to have adverse impact on mental health, and potentially lead to suicide deaths. However, systematic studies on the association between air pollution and suicide mortality are lacking. We explored the associations of multiple air pollutants and pollution mixtures with suicide deaths and assessed excess suicide mortality due to air pollution, emphasizing the importance of air pollution control on suicide prevention. Our study provides evidence to support mechanistic studies on the association between air pollution and suicide, and informs comprehensive air pollution management.

Microglial exosomes in paraquat-induced Parkinson's disease: Neuroprotection and biomarker clues.

The exact mechanisms underlying the initiation and exacerbation of Parkinson's disease (PD) by paraquat remain unclear. We have revealed that exosomes mediate neurotoxicity induced by low dose paraquat exposure by transmitting intercellular signaling. Exposure to 40 µM paraquat promoted exosome release from mouse microglia cells (BV2) in vitro. Paraquat exposure at 100 µM caused degeneration of mouse dopaminergic MN9D cells and inhibited microglia exosome uptake by fluorescently labeling exosomes. We established an incubation model for exosomes and dopaminergic neuron cells under PQ treatment. The results indicated that microglial exosomes alleviated degeneration, increasing proliferation and PD-related protein expression of dopaminergic neurons; however, paraquat reversed this effect. Then, through exosome high-throughput sequencing and qRT-PCR experiments, miR-92a-3p and miR-24-3p were observed to transfer from exosomes to dopaminergic neurons, inhibited by paraquat. The specificity of miR-92a-3p and miR-24-3p was verified in PD patients exosomes, indicating the potential diagnostic value of the exosomal miRNAs in paraquat-induced PD. These results suggest glia-neuron communication in paraquat-induced neurodegeneration and may identify stable paraquat-mediated PD biomarkers, offering clues for early recognition and prevention of pesticide-induced degenerative diseases.

Chaperones Hsc70 and Hsp70 play distinct roles in the replication of bocaparvovirus minute virus of canines.

Minute virus of canines (MVC) belongs to the genus Bocaparvovirus (formerly Bocavirus) within the Parvoviridae family and causes serious respiratory and gastrointestinal symptoms in neonatal canines worldwide. A productive viral infection relies on the successful recruitment of host factors for various stages of the viral life cycle. However, little is known about the MVC-host cell interactions. In this study, we identified that two cellular proteins (Hsc70 and Hsp70) interacted with NS1 and VP2 proteins of MVC, and both two domains of Hsc70/Hsp70 were mediated for their interactions. Functional studies revealed that Hsp70 was induced by MVC infection, knockdown of Hsc70 considerably suppressed MVC replication, whereas the replication was dramatically promoted by Hsp70 knockdown. It is interesting that low amounts of overexpressed Hsp70 enhanced viral protein expression and virus production, but high amounts of Hsp70 overexpression weakened them. Upon Hsp70 overexpressing, we observed that the ubiquitination of viral proteins changed with Hsp70 overexpression, and proteasome inhibitor (MG132) restored an accumulation of viral proteins. In addition, we verified that Hsp70 family inhibitors remarkably decreased MVC replication. Overall, we identified Hsc70 and Hsp70 as interactors of MVC NS1 and VP2 proteins and were involved in MVC replication, which may provide novel targets for anti-MVC approach.

Maternal exposure to ambient ozone and fetal conotruncal heart defects in China: A multicenter cohort study.

BACKGROUND: The relationships between maternal genetic and environmental exposure and conotruncal heart defects (CTDs) have been extensively investigated. Nevertheless, there is limited knowledge regarding the impact of ozone (O3) on the risk of CTDs. OBJECTIVE: To explore the correlation between maternal exposure to O3 and CTDs in China. METHODS: Pregnant women who underwent fetal echocardiography at Beijing Anzhen Hospital between January 2013 and December 2021 were enrolled. Their sociodemographic characteristics and lifestyle information, along with fetal data, were systematically collected. Fetal echocardiography was used to detect CTDs. Maternal exposure to ambient O3 during the embryonic period, the first trimester, the three months preceding the last menstrual period, and the perinatal period was estimated using residential addresses or hospital addresses associated with prenatal visits. The concentration of O3 was divided by quartiles, with the first quartile serving as a reference. Adjusted logistic regression models were employed to examine the associations between every 10 µg/m3 increase or quartile increase in ambient O3 exposure and CTDs. RESULTS: Among 24,278 subjects, 1069 exhibited fetuses with CTDs. Maternal exposure to ambient O3 during three pregnancy periods was associated with increased CTD risk. The adjusted odds ratio (OR) and 95% confidence interval (CI) were 1.271 (1.189-1.360) per 10 µg/m3 increase in O3 during the perinatal period. For each quartile of O3, the risk increased with increasing exposure concentration, particularly during the perinatal period (OR = 2.206 for quartile 2, 2.367 for quartile 3, and 3.378 for quartile 4, all P<0.05). CONCLUSIONS: Elevated maternal exposure to O3 during pregnancy, particularly in the perinatal period, is linked to an increased risk of fetal CTDs. Further longitudinal analyses are needed to validate these results.

Maternal Exposure to Extreme Cold Events and Risk of Congenital Heart Defects: A Large Multicenter Study in China.

Over the past decade, extreme temperature events have become more frequent and longer in duration. Previous studies on the association between extreme cold events (ECEs) and congenital heart defects (CHDs) are few and inconsistent. We conducted a national multicenter study in 1313 hospitals in 26 provinces in China and collected a total of 14 808 high CHD-risk participants from 2013 to 2021. We evaluated the ECEs experienced by each pregnant women during the embryonic period (3-8 weeks). The results indicated that ECEs experienced by pregnant women during the embryonic period were associated with the development of fetal CHD and were more strongly associated with some specific fetal CHD subtypes, such as pulmonary stenosis, pulmonary atresia, and tetralogy of Fallot. Of the CHD burden, 2.21% (95% CI: 1.43, 2.99%)-2.40% (95% CI: 1.26, 3.55%) of fetal CHD cases were attributable to ECEs during the embryonic period. Our findings emphasize the need to pay more attention to pregnant women whose embryonic period falls during the cold season to reduce cold spell detriments to newborns.

NS1-mediated enhancement of MVC transcription and replication promoted by KAT5/H4K12ac.

Histone modifications function in both cellular and viral gene expression. However, the roles of acetyltransferases and histone acetylation in parvoviral infection remain poorly understood. In the current study, we found the histone deacetylase (HDAC) inhibitor, trichostatin A (TSA), promoted the replication and transcription of parvovirus minute virus of canines (MVC). Notably, the expression of host acetyltransferases KAT5, GTF3C4, and KAT2A was increased in MVC infection, as well as H4 acetylation (H4K12ac). KAT5 is not only responsible for H4K12ac but also crucial for viral replication and transcription. The viral nonstructural protein NS1 interacted with KAT5 and enhanced its expression. Further study showed that Y44 in KAT5, which may be tyrosine-phosphorylated, is indispensable for NS1-mediated enhancement of KAT5 and efficient MVC replication. The data demonstrated that NS1 interacted with KAT5, which resulted in an enhanced H4K12ac level to promote viral replication and transcription, implying the epigenetic addition of H4K12ac in viral chromatin-like structure by KAT5 is vital for MVC replication.IMPORTANCEParvoviral genomes are chromatinized with host histones. Therefore, histone acetylation and related acetyltransferases are required for the virus to modify histones and open densely packed chromatin structures. This study illustrated that histone acetylation status is important for MVC replication and transcription and revealed a novel mechanism that the viral nonstructural protein NS1 hijacks the host acetyltransferase KAT5 to enhance histone acetylation of H4K12ac, which relies on a potential tyrosine phosphorylation site, Y44 in KAT5. Other parvoviruses share a similar genome organization and coding potential and may adapt a similar strategy for efficient viral replication and transcription.

The impact of short-term exposures to ambient NO2, O3, and their combined oxidative potential on daily mortality.

It is widely recognized that air pollution exerts substantial detrimental effects in human health and the economy. The potential for harm is closely linked to the concentrations of pollutants like nitrogen dioxide (NO2) and ozone (O3), as well as their collective oxidative potential (OX). Yet, due to the challenges of directly monitoring OX as an independent factor and the influences of different substances' varying ability to contain or convey OX, uncertainties persist regarding its actual impact. To provide further evidence to the association between short-term exposures to NO2, O3, and OX and mortality, this study conducted multi-county time-series analyses with over-dispersed generalized additive models and random-effects meta-analyses to estimate the mortality data from 2014 to 2020 in Jiangsu, China. The findings reveal that short-term exposures to these pollutants are linked to increased risks of all-cause, cardiovascular, and respiratory mortality, where NO2 demonstrates 2.11% (95% confidence interval: 1.79%, 2.42%), 2.28% (1.91%, 2.66%), and 2.91% (2.13%, 3.69%) respectively per every 10 ppb increase in concentration, and the effect of O3 is 1.11% (0.98%, 1.24%), 1.39% (1.19%, 1.59%), and 1.82% (1.39%, 2.26%), and OX is 1.77% (1.58%, 1.97%), 2.19% (1.90%, 2.48%), and 2.90% (2.29%, 3.52%). Notably, women and individuals aged over 75 years exhibit higher susceptibility to these pollutants, with NO2 showing a greater impact, especially during the warm seasons. The elevated mortality rates associated with NO2, O3, and OX underscore the significance of addressing air pollution as a pressing public health issue, especially in controlling NO2 and O3 together. Further research is needed to explore the underlying mechanisms and possible influential factors of these effects.

ASC/inflammasome-independent pyroptosis in ovarian cancer cells through translational augmentation of caspase-1.

Canonical pyroptosis is type of programmed cell death depending on active caspase-1, and the inflammasome carries out caspase-1 activation. Here, we showed that docosahexaenoic acid (DHA) induced ovarian cancer cell deaths in caspase-1-dependent manner. DHA increased caspase-1 activity and led to interleukin-1ß secretion and gasdermin D cleavage while disulfiram inhibited DHA-induced cell death, suggesting that DHA triggered pyroptosis. Intriguingly, ASC, the molecule recruiting caspase-1 to inflammasome for activation, was dispensable for DHA-induced pyroptosis. Instead, we observed remarkable elevation in caspase-1 abundance concurrent with the activation of caspase-1 in DHA-treated cells. As ectopically overexpressing caspase-1 resulted in robust amount of active caspase-1, we reason that DHA activates caspase-1 and pyroptosis through the generation of excessive amount of caspase-1 protein. Mechanistically, DHA increased caspase-1 by specifically accelerating caspase-1 protein synthesis via the p38MAPK/Mnk1 signaling pathway. We have uncovered an unknown pyroptosis mechanism in which caspase-1-dependent pyroptosis can occur without the participation of ASC/inflammasome.

Association between longitudinal dietary patterns and changes in obesity: a population-based cohort study.

Introduction: Research on the trajectory of dietary patterns and changes in obesity has been inconclusive. Methods: This study described the dietary intake and adiposity trajectories of Chinese adults and assessed the association between dietary trajectories and changes in body mass index (BMI) and waist-to-hip ratio (WHR). We used data from 3, 643 adults who participated in the China Health and Nutrition Survey from 1997 to 2015. Detailed dietary data were collected by conducting three consecutive 24-h recalls. Multitrajectories of diet scores were identified by a group-based multitrajectory method. We described the change in BMI and WHR using group-based trajectory modeling. We assessed the associations between dietary trajectories and changes in people with obesity using a logistic regression model. Results: Our study revealed four trajectories of low-carbohydrate (LCD) and low-fat diet (LFD) scores. Three adiposity trajectories were identified according to the baseline level and developmental trend of BMI and WHR. Compared with the reference group, which was characterized by sustained healthy dietary habits with healthy diet scores at baseline and sustained maintenance of healthy diet scores, the other three diet trajectories had a higher risk of falling into the adverse adiposity trajectory. Discussion: Maintaining a healthy LCD and LFD can markedly decrease the risk of adiposity.

Exploring the association between circRNA expression and pediatric obesity based on a case-control study and related bioinformatics analysis.

OBJECTIVE: Our present study utilized case-control research to explore the relationship between specific circRNAs and pediatric obesity through a literature review and bioinformatics and to predict their possible biological functions, providing ideas for epigenetic mechanism studies of pediatric obesity. METHODS: CircRNAs related to pediatric obesity were preliminarily screened by a literature review and qRT-PCR. CircRNA expression in children with obesity (n = 75) and control individuals (n = 75) was confirmed with qRT-PCR in a case-control study. This was followed by bioinformatics analyses, such as GO analysis, KEGG pathway analysis, and ceRNA network construction. Multivariate logistic regression was utilized to analyze the effects of circRNAs on obesity. A receiver operating characteristic (ROC) curve was also drawn to explore the clinical application value of circRNAs in pediatric obesity. RESULTS: Has_circ_0046367 and hsa_circ_0000284 were separately validated to be statistically downregulated and upregulated, respectively, in the peripheral blood mononuclear cells of children with obesity and revealed as independent indicators of increased CHD risk [hsa_circ_0046367 (OR = 0.681, 95% CI: 0.480 ~ 0.967) and hsa_circ_0000284 (OR = 1.218, 95% CI: 1.041 ~ 1.424)]. The area under the ROC curve in the combined analysis of hsa_circ_0046367 and hsa_circ_0000284 was 0.706 (95% CI: 0.623 ~ 0.789). Enrichment analyses revealed that these circRNAs were actively involved in neural plasticity mechanisms, cell secretion and signal regulation. CONCLUSION: The present research revealed that low expression of hsa_circ_0046367 and high expression of hsa_circ_0000284 are risk factors for pediatric obesity and that neural plasticity mechanisms are closely related to obesity.

A novel TRIM22 gene polymorphism promotes the response to PegIFNα therapy through cytokine-cytokine receptor interaction signaling pathway in chronic hepatitis B.

IMPORTANCE: Pegylated interferon alfa (PegIFNα) has limited efficacy in the treatment of chronic hepatitis B (CHB). Although many biomarkers related to hepatitis B virus (HBV) have been proposed to stratify patients, the response rate to PegIFNα is still unsatisfactory. Herein, our data suggest that the single-nucleotide polymorphism (SNP) rs10838543 in TRIM22 potentiates a positive clinical response to PegIFNα treatment in patients with hepatitis B e antigen-positive CHB by increasing the levels of IFNL1, CCL3, and CCL5. These observations can help guide treatment decisions for patients with CHB to improve the response rate to PegIFNα.

Psychological resilience mediates the association between sleep quality and anxiety symptoms: A repeated measures study in college students.

OBJECTIVE: To explore the association between sleep quality and anxiety symptoms, and the mediation effect of psychological resilience on this association by a repeated measures study. METHODS: In this study, 127 college students were randomly recruited and their sleep quality and psychological status were repeatedly collected using the Pittsburgh Sleep Quality Index (PSQI) scale, Connor-Davidson resilience scale (CD-RISC), and 7-items generalized anxiety disorder scale (GAD-7). Linear mixed-effects models were used to explore the association between sleep quality and anxiety symptoms, and a mediated effects analysis was used to explore the role played by psychological resilience in this association. RESULTS: This study found a positive association between sleep quality and anxiety symptoms (ß = 0.40, 95% confidence interval: 0.27, 0.52). Psychological resilience scores and its various dimensions play a significant mediating role in this association. CONCLUSIONS: Although the role of sleep quality in anxiety disorders is not fully understood, this study highlights the importance of improving sleep quality while enhancing psychological resilience to prevent the onset of anxiety symptoms in college students.

Association of Short-Term Co-Exposure to Particulate Matter and Ozone with Mortality Risk.

A complex regional air pollution problem dominated by particulate matter (PM) and ozone (O3) needs drastic attention since the levels of O3 and PM are not decreasing in many parts of the world. Limited evidence is currently available regarding the association between co-exposure to PM and O3 and mortality. A multicounty time-series study was used to investigate the associations of short-term exposure to PM1, PM2.5, PM10, and O3 with daily mortality from different causes, which was based on data obtained from the Mortality Surveillance System managed by the Jiangsu Province Center for Disease Control and Prevention of China and analyzed via overdispersed generalized additive models with random-effects meta-analysis. We investigated the interactions of PM and O3 on daily mortality and calculated the mortality fractions attributable to PM and O3. Our results showed that PM1 is more strongly associated with daily mortality than PM2.5, PM10, and O3, and percent increases in daily all-cause nonaccidental, cardiovascular, and respiratory mortality were 1.37% (95% confidence interval (CI), 1.22-1.52%), 1.44% (95% CI, 1.25-1.63%), and 1.63% (95% CI, 1.25-2.01%), respectively, for a 10 µg/m3 increase in the 2 day average PM1 concentration. We found multiplicative and additive interactions of short-term co-exposure to PM and O3 on daily mortality. The risk of mortality was greatest among those with higher levels of exposure to both PM (especially PM1) and O3. Moreover, excess total and cardiovascular mortality due to PM1 exposure is highest in populations with higher O3 exposure levels. Our results highlight the importance of the collaborative governance of PM and O3, providing a scientific foundation for pertinent standards and regulatory interventions.

Butylphthalide regulation of nerve cells in rats with cerebral infarction through jnk/p38mapk signaling pathway15.

To investigate the regulatory effect of butylphthalide (NBP) on the nerve cells of rats with cerebral infarction (CI) through the JNK/p38MAPK signaling pathway, 135 SPF SD male rats were and randomly assigned into the control group (n=45, sham surgery + peanut oil gavage), model group (n=45, CI model + peanut oil gavage), and NBP group (n= 45, CI model + NBP gavage). The comparison of the neurological function score between the model group and the NBP group, as well as the integrated locomotor ability score, Slit2 expression level, blood-brain barrier permeability, micro vessel density (MVD), CI volume, neuronal apoptosis rate of the brain tissue and expression levels of brain tissue p-JNK and p-p38MAPK protein among three groups was conducted. NBP inhibits the expression of JNK/p38MAPK signaling pathway, promotes the expression of Slit2 in CI rats, improves the neurological function and locomotor ability of CI rats, while promoting micro vascularization of the brain tissue, protecting the blood-brain barrier, reducing the volume of CI and the apoptosis of nerve cells.

Butylphthalide regulation of nerve cells in rats with cerebral infarction through jnk/p38mapk signaling pathway.

To investigate the regulatory effect of n-butylphthalide (NBP) on the nerve cells of rats with cerebral infarction (CI) through the JNK/p38MAPK signaling pathway, 135 SPF SD male rats were and randomly assigned into the control group (n=45, sham surgery + peanut oil gavage), model group (n=45, CI model + peanut oil gavage), and NBP group (n= 45, CI model + NBP gavage). The comparison of the neurological function score between the model group and the NBP group, as well as the integrated locomotor ability score, Slit2 expression level, blood-brain barrier permeability, micro vessel density (MVD), CI volume, neuronal apoptosis rate of the brain tissue and expression levels of brain tissue p-JNK and p-p38MAPK protein among three groups was conducted. NBP inhibits the expression of JNK/p38MAPK signaling pathway, promotes the expression of Slit2 in CI rats, improves the neurological function and locomotor ability of CI rats, while promoting micro vascularization of the brain tissue, protecting the blood-brain barrier, reducing the volume of CI and the apoptosis of nerve cells.

Hyperuricemia and coronary heart disease: The mediating role of blood pressure and thrombospondin 3.

BACKGROUND & AIMS: Although hyperuricemia is a known risk factor for coronary heart disease (CHD), little is known about the role of blood pressure in mediating this association. The purpose of this study is to investigate the role of blood pressure-related indicators and Thrombospondin 3 (THBS3) in the association between hyperuricemia and CHD. METHODS AND RESULTS: Our observational epidemiology study included 593 CHD cases and 760 controls from a residential stable sample. We also chose 43 new CHD patients and 43 controls to test the expression levels of THBS3 using ELISA kits. We used logistic regression models and mediating effect analysis to investigate the relationships between hyperuricemia and CHD, as well as the mediating role of blood pressure-related indicators and THBS3. In the general population (OR: 2.001 [95% CI: 1.528-2.622]), male population (OR: 1.591 [95% CI: 1.119-2.262]), and female population (OR: 2.813 [95% CI: 1.836-4.310]), hyperuricemia is an independent risk factor for CHD. In general, average systolic blood pressure (SBP) and average pulse pressure difference (PPD) mediated 3.35% and 4.59%, respectively, of the association between hyperuricemia and CHD, and 6.60% and 6.60% in women. However, in the male population, we have not yet found that blood pressure-related indicators had a significant mediating effect. Meanwhile, we found that THBS3 mediated 19.23% of the association between hyperuricemia and CHD. CONCLUSIONS: Average SBP, PPD, and THBS3 all play a role in the association of hyperuricemia and CHD. In the female population, similar mediating results in blood pressure-related indicators were observed.

Association of longitudinal patterns of nighttime sleep duration and daytime napping duration with risk of multimorbidity.

OBJECTIVES: To determine whether longitudinal trajectories of nighttime sleep duration and daytime napping duration are related to subsequent multimorbidity risk. To explore whether daytime napping can compensate for negative effects of short nighttime sleep. METHODS: The current study included 5262 participants from China Health and Retirement Longitudinal Study. Self-reported nighttime sleep duration and daytime napping duration were collected from 2011 to 2015. The 4-year sleep duration trajectories were conducted by group-based trajectory modeling. The 14 medical conditions were defined by self-reported physician diagnoses. Multimorbidity was diagnosed as participants with 2 or more of the 14 chronic diseases after 2015. Associations between sleep trajectories and multimorbidity were assessed by Cox regression models. RESULTS: During 6.69 years of follow-up, we observed multimorbidity in 785 participants. Three nighttime sleep duration trajectories and three daytime napping duration trajectories were identified. Participants with persistent short nighttime sleep duration trajectory had the higher risk of multimorbidity (hazard ratio = 1.37, 95% confidence interval: 1.06-1.77), compared with those with persistent recommended nighttime sleep duration trajectory. Participants with persistent short nighttime sleep duration and persistent seldom daytime napping duration had the highest risk of multimorbidity (hazard ratio = 1.69, 95% confidence interval: 1.16-2.46). CONCLUSIONS: In this study, persistent short nighttime sleep duration trajectory was associated with subsequent multimorbidity risk. Daytime napping could compensate for the risk of insufficient night sleep.