Exploring the Birthday Week Effect on Hand, Foot, and Mouth Disease in Yunnan Province, China, From 2008 to 2022: Surveillance Data Analysis.

Background: Hand, foot, and mouth disease (HFMD) is a notable infectious disease predominantly affecting infants and children worldwide. Previous studies on HFMD have primarily focused on natural patterns, such as seasonality, but research on the influence of important social time points is lacking. Several studies have indicated correlations between birthdays and certain disease outcomes. Objective: This study aimed to explore the association between birthdays and HFMD. Methods: Surveillance data on HFMD from 2008 to 2022 in Yunnan Province, China, were collected. We defined the period from 6 days before the birthday to the exact birthday as the "birthday week." The effect of the birthday week was measured by the proportion of cases occurring during this period, termed the "birthday week proportion." We conducted subgroup analyses to present the birthday week proportions across sexes, age groups, months of birth, and reporting years. Additionally, we used a modified Poisson regression model to identify conditional subgroups more likely to contract HFMD during the birthday week. Results: Among the 973,410 cases in total, 116,976 (12.02%) occurred during the birthday week, which is 6.27 times the average weekly proportion (7/365, 1.92%). While the birthday week proportions were similar between male and female individuals (68,849/564,725, 12.19% vs 48,127/408,685, 11.78%; χ21=153.25, P<.001), significant differences were observed among different age groups (χ23=47,145, P<.001) and months of birth (χ211=16,942, P<.001). Compared to other age groups, infants aged 0-1 year had the highest birthday week proportion (30,539/90,709, 33.67%), which is 17.57 times the average weekly proportion. Compared to other months, patients born from April to July and from October to December, the peak months of the HFMD epidemic, had higher birthday week proportions. Additionally, a decreasing trend in birthday week proportions from 2008 to 2022 was observed, dropping from 33.74% (3914/11,600) to 2.77% (2254/81,372; Cochran-Armitage trend test: Z=-102.53, P<.001). The results of the modified Poisson regression model further supported the subgroup analyses findings. Compared with children aged >7 years, infants aged 0-1 year were more likely to contract HFMD during the birthday week (relative risk 1.182, 95% CI 1.177-1.185; P<.001). Those born during peak epidemic months exhibited a higher propensity for contracting HFMD during their birthday week. Compared with January, the highest relative risk was observed in May (1.087, 95% CI 1.084-1.090; P<.001). Conclusions: This study identified a novel "birthday week effect" of HFMD, particularly notable for infants approaching their first birthday and those born during peak epidemic months. Improvements in surveillance quality may explain the declining trend of the birthday week effect over the years. Higher exposure risk during the birthday period and potential biological mechanisms might also account for this phenomenon. Raising public awareness of the heightened risk during the birthday week could benefit HFMD prevention and control.

Dihydromyricetin suppresses endothelial NLRP3 inflammasome activation and attenuates atherogenesis by promoting mitophagy.

BACKGROUND: NOD-like receptor protein 3 (NLRP3) inflammasome activation is indispensable for atherogenesis. Mitophagy has emerged as a potential strategy to counteract NLRP3 inflammasome activation triggered by impaired mitochondria. Our previous research has indicated that dihydromyricetin, a natural flavonoid, can mitigate NLRP3-mediated endothelial inflammation, suggesting its potential to treat atherosclerosis. However, the precise underlying mechanisms remain elusive. This study sought to investigate whether dihydromyricetin modulates endothelial mitophagy and inhibits NLRP3 inflammasome activation to alleviate atherogenesis, along with the specific mechanisms involved. METHODS: Apolipoprotein E-deficient mice on a high-fat diet were administered daily oral gavages of dihydromyricetin for 14 weeks. Blood samples were procured to determine the serum lipid profiles and quantify proinflammatory cytokine concentrations. Aortas were harvested to evaluate atherosclerotic plaque formation and NLRP3 inflammasome activation. Concurrently, in human umbilical vein endothelial cells, Western blotting, flow cytometry, and quantitative real-time PCR were employed to elucidate the mechanistic role of mitophagy in the modulation of NLRP3 inflammasome activation by dihydromyricetin. RESULTS: Dihydromyricetin administration significantly attenuated NLRP3 inflammasome activation and vascular inflammation in mice on a high-fat diet, thereby exerting a pronounced inhibitory effect on atherogenesis. Both in vivo and in vitro, dihydromyricetin treatment markedly enhanced mitophagy. This enhancement in mitophagy ameliorated the mitochondrial damage instigated by saturated fatty acids, thereby inhibiting the activation and nuclear translocation of NF-κB. Consequently, concomitant reductions in the transcript levels of NLRP3 and interleukin-1ß (IL-1ß), alongside decreased activation of NLRP3 inflammasome and IL-1ß secretion, were discerned. Notably, the inhibitory effects of dihydromyricetin on the activation of NF-κB and subsequently the NLRP3 inflammasome were determined to be, at least in part, contingent upon its capacity to promote mitophagy. CONCLUSION: This study suggested that dihydromyricetin may function as a modulator to promote mitophagy, which in turn mitigates NF-κB activity and subsequent NLRP3 inflammasome activation, thereby conferring protection against atherosclerosis.

The role of BTG2/PI3K/AKT pathway-mediated microglial activation in T-2 toxin-induced neurotoxicity.

T-2 toxin is one of the mycotoxins widely distributed in human food and animal feed. Our recent work has shown that microglial activation may contribute to T-2 toxin-induced neurotoxicity. However, the molecular mechanisms involved need to be further clarified. To address this, we employed high-throughput transcriptome sequencing and found altered B cell translocation gene 2 (BTG2) expression levels in microglia following T-2 toxin treatment. It has been shown that altered BTG2 expression is involved in a range of neurological pathologies, but whether it's involved in the regulation of microglial activation is unclear. The aim of this study was to investigate the role of BTG2 in T-2 toxin-induced microglial activation. The results of animal experiments showed that T-2 toxin caused neurobehavioral disorders and promoted the expression of microglial BTG2 and pro-inflammatory activation of microglia in hippocampus and cortical, while microglial inhibitor minocycline inhibited these changes. The results of in vitro experiments showed that T-2 toxin enhanced BTG2 expression and pro-inflammatory microglial activation, and inhibited BTG2 expression weakened T-2 toxin-induced microglial activation. Moreover, T-2 toxin activated PI3K/AKT and its downstream NF-κB signaling pathway, which could be reversed after knock-down of BTG2 expression. Meanwhile, the PI3K inhibitor LY294002 also blocked this process. Therefore, BTG2 may be involved in T-2 toxin's ability to cause microglial activation through PI3K/AKT/NF-κB pathway.

Rural-urban difference in the association between particulate matters and stroke incidence: The evidence from a multi-city perspective cohort study.

Available evidence suggests that air pollutants can cause stroke, but little research has investigated the confounding effects of urban-rural differences. Here, we investigated the urban-rural difference in the correlation between particulate matter (PM2.5 and PM10) exposure and stroke. This cohort study was based on a prospective multi-city community-based cohort (Guizhou Population Health Cohort Study (GPHCS)) in Guizhou Province, China. A total of 7988 eligible individuals (≥18 years) were enrolled with baseline assessments from November 2010 to December 2012, and follow-up was completed by June 2020. Two major particulate matters (PMs, including PM2.5 and PM10) were assessed monthly from 2000 by using satellite-based spatiotemporal models. The risk of stroke was estimated using a Cox proportional hazard regression model. The association between particulate matters' exposure and stroke in different areas (total, urban, and rural) and the potential modification effect of comorbidities (hypertension, diabetes, and dyslipidemia) and age (≤65/>65 years) were examined using stratified analyses. The risk of stroke increased for every 10 µg/m3 increase in mean PMs' concentrations during the previous 1 year at the residential address (HR: 1.26, 95%CI: 1.24, 1.29 (PM2.5); HR: 1.13, 95%CI: 1.11, 1.15 (PM10)). The presence of diabetes and dyslipidemia increased the risk of PM10-induced stroke in whole, urban, and rural areas. Specifically, people living in rural areas were more likely to experience the effects of PMs in causing a stroke. The risk of stroke due to PMs was statistically increased in the young and older populations living in rural areas. In conclusion, long-term exposure to PMs increased the risk of stroke and such association was more pronounced in people living in rural areas with lower income levels. Diabetes and dyslipidemia seemed to strengthen the association between PMs and stroke.

The role of ZC3H12D-regulated TLR4-NF-κB pathway in LPS-induced pro-inflammatory microglial activation.

Lipopolysaccharide (LPS) is an important neurotoxin that can cause inflammatory activation of microglia. ZC3H12D is a novel immunomodulator, which plays a remarkable role in neurological pathologies. It has not been characterized whether ZC3H12D is involved in the regulation of microglial activation. The aim of this study was to investigate the role of ZC3H12D in LPS-induced pro-inflammatory microglial activation and its potential mechanism. To elucidate this, we established animal models of inflammatory injury by intraperitoneal injection of LPS (10 mg/kg). The results of the open-field test showed that LPS caused impaired motor function in mice. Meanwhile, LPS caused pro-inflammatory activation of microglia in the mice cerebral cortex and inhibited the expression of ZC3H12D. We also constructed in vitro inflammatory injury models by treating BV-2 microglia with LPS (0.5 µg/mL). The results showed that down-regulated ZC3H12D expression was associated with LPS-induced pro-inflammatory microglial activation, and further intervention of ZC3H12D expression could inhibited LPS-induced pro-inflammatory activation of microglia. In addition, LPS activated the TLR4-NF-κB signaling pathway, and this process can also be reversed by promoting ZC3H12D expression. At the same time, the addition of resveratrol, a nutrient previously proven to inhibit pro-inflammatory microglial activation, can also reverse this process by increasing the expression of ZC3H12D. Summarized, our data elucidated that ZC3H12D in LPS-induced pro-inflammatory activation of brain microglia via restraining the TLR4-NF-κB pathway. This study may provide a valuable clue for potential therapeutic targets for neuroinflammation-related injuries.

High ambient temperature may increase the risk of anemia in pregnancy: Identifying susceptible exposure windows.

Anemia in pregnancy (AIP) is associated with multiple severe maternal and perinatal adverse outcomes. However, there is a lack of evidence on the association between environmental factors and AIP. Aim to explore the association between ambient temperature and the risk of AIP, and identify susceptible exposure windows, we conducted a matched case-control study from 2013 to 2016 in Xi'an, China, which included 710 women with AIP and 1420 women without AIP. The conditional logistic regression model was used to evaluate the association between ambient temperature and AIP at different gestational weeks and gestational months. The association between extreme temperature and AIP was evaluated using the distributed lag nonlinear model (DLNM). We conducted stratified analyses of age, parity, and season of conception, and estimated the interaction between ambient temperature and air pollutants on AIP. Ambient temperature was significantly positively associated with the risk of AIP, and the susceptible exposure windows were 2-25 gestational weeks and 1-6 gestational months, respectively. The strongest effect was observed in the week 8 and month 2, for each 1 °C increase in weekly and monthly mean temperature, the odds ratio (OR) for AIP was 1.038 (95 % confidence interval (CI): 1.022, 1.055) and 1.040 (95 % CI: 1.020, 1.060), respectively. Extreme heat may increase the risk of AIP. Stratified analyses showed that there was no significant difference among different age, parity, and season of conception groups. No significant interaction effect of ambient temperature with air pollution on AIP was found. In summary, high ambient temperature may increase the risk of AIP, and the first and second trimesters may be susceptible exposure windows. Understanding the effect of temperature on pregnant women will be beneficial to reduce the occurrence of AIP.

Construction of an EMT-related lncRNA prognostic signature for lung adenocarcinoma and functional verification of its hub gene LINC01615.

BACKGROUND: The epithelial-mesenchymal transition (EMT) plays a vital role in the progression of lung adenocarcinoma (LUAD). Long non-coding RNAs (lncRNAs) participate in the EMT process as an important regulatory factor and have the potential to serve as prognostic biomarkers. We aimed to construct a novel lncRNA prognostic signature for LUAD based on EMT-related lncRNAs, identify EMT-related hub lncRNA, and investigate its biological functions. METHODS: RNA-seq data, clinical and survival information were obtained from The Cancer Genome Atlas database. The EMT-related lncRNA prognostic signature (EMTscore) was constructed using the Least Absolute Shrinkage and Selection Operator Cox regression analysis. The efficiency of EMTscore in predicting the prognosis of LUAD was evaluated through the area under the time-dependent receiver operating characteristic (ROC) curves. The hub lncRNA of the prognostic signature was selected using a co-expression network map, and its effects on cell proliferation and metastasis were explored by in vitro experiments. RESULTS: We constructed a prognostic signature (EMTscore) containing 8 tumor-high expressed lncRNAs. The EMTscore performed well in predicting overall survival rates with AUC values of 0.708 at 5 years in the training set. EMTscore could independently predict the survival of LUAD, with HR = 4.011 (95% CI 2.430-6.622) in the multivariate Cox regression. Importantly, we identified LINC01615 as the hub lncRNA in the EMTscore and revealed that LINC01615 enhanced the proliferation, migration, and EMT of lung cancer cells. CONCLUSIONS: A new EMT-related lncRNA prognostic signature named EMTscore was developed, and LINC01615 was identified as the hub lncRNA of EMTscore. The hub lncRNA LINC01615 had an oncogenic biological function in LUAD.

The association between intermediate-term sulfur dioxide exposure and outpatient visits for Parkinson's disease: a time-series study in southwestern China.

Parkinson's disease (PD) is the second most common human neurodegenerative disorder, and the pathogenesis of it remains poorly understood. Limited studies have shown that both long- and short-term exposure to air pollutants may be associated with increased risk of PD while lacking evidence on the effects of intermediate-term exposure. In this study, over-dispersed Poisson generalized additive models (GAMs) were applied to explore the association between intermediate-term sulfur dioxide (SO2) exposure and outpatient visits for PD in Chongqing, China, and further stratified analyses were performed by age and gender. A total of 39,984 PD cases from January 1, 2014, to December 31, 2019 (2191 days) were included. The association of intermediate-term SO2 exposure with outpatient visits for PD was statistically significant: per 1 µg/m3 increase of SO2 corresponded to 2.34% (95% CI: 0.88%, 3.80%) elevation in monthly PD outpatient visits at lag 0 (the concurrent month). Stratified analyses showed that the associations between SO2 and PD outpatient visits were stronger in younger (≤ 60 years) and female patients. In conclusion, intermediate-term SO2 exposure can be associated with an increased risk of PD outpatient visits. Our results highlight the importance of recognizing the role of intermediate-term SO2 exposure in the development of PD. In addition to focusing on the effects of long-term or short-term air pollutants, it is necessary to pay more attention to the health effects of intermediate-term exposure time windows of air pollutants, which will facilitate policy formulation and public health interventions for health risks.

Unexpected association between ambient ozone and adult insomnia outpatient visits: A large-scale hospital-based study.

Growing evidence indicates that short-term ozone (O3) exposure has substantial health consequences, but the relationship between short-term ambient O3 and insomnia, a common sleep disorder, is not clear. This study aimed to investigate the short-term effects of ambient O3 exposure on outpatient visits for adult insomnia and to explore the potential modifiers. A large-scale multihospital-based study was carried out in Chongqing, the largest city in Southwest China. Daily data on outpatient visits for adult insomnia, average concentrations of ambient air pollutants and meteorological factors were collected. We conducted quasi-Poisson regression with generalized additive model to assess the association between ambient O3 and outpatient visits for adult insomnia in varied windows of exposure. Subgroup analyses were applied to identify its modifiers. Totally, 140,159 adult insomnia outpatient visits were identified. The daily maximum 8-h average concentration of O3 was 69 µg/m3 during the study period, which greatly below the updated Chinese and WHO recommended limits (daily maximum 8-h average, O3: 100 µg/m3). Short-term O3 exposure was significantly negatively associated with outpatient visits for adult insomnia in different lag periods and the greatest decrease of outpatient visits for adult insomnia was found at lag 02 [0.93% (95% CI: 0.48%, 1.38%)]. Additionally, stronger links between O3 and adult insomnia outpatient visits were presented in cool seasons, and we did not observe any significant modified effects of gender and age. Moreover, the negative O3-insomnia association remained robust after controlling for other common air pollutants and comorbidities. In summary, short-term exposure to lower level of ambient O3, was associated with reduced daily outpatient visits for adult insomnia and such association showed to be more obvious in cool seasons.

The role of extreme high humidex in depression in chongqing, China: A time series-analysis.

As global climate change intensifies, people are paying increasing attention to the impact of temperature changes on adverse mental health outcomes, especially depression. While increasing attention has been paid to the effect of temperature, there is little research on the effect of humidity. We aimed to investigate the association between humidex, an index combining temperature and humidity to reflect perceived temperature, and outpatient visits for depression from 2014 to 2019 in Chongqing, the largest and one of the most hot and humid cities of China. We also aimed to further identify susceptible subgroups. A distributed lag non-linear model (DLNM) was used to explore the concentration-response relationship between humidex and depression outpatient visits. Hierarchical analysis was carried out by age and gender. A total of 155,436 visits for depression were collected from 2014 to 2019 (2191 days). We found that depression outpatient visits were significantly associated with extremely high humidex (≥40). The significant positive single-lag day effect existed at lag 0 (RR = 1.029, 95%CI: 1.000-1.059) to lag 2 (RR = 1.01, 95%CI: 1.004-1.028), and lag 12 (RR = 1.013, 95%CI: 1.002-1.024). The significant cumulative adverse effects lasted from lag 01 to lag 014. Hierarchical analyses showed that females and the elderly (≥60 years) appeared to be more susceptible to extremely high humidex. The attributable numbers (AN) and fraction (AF) of extremely high humidex on depression outpatients were 1709 and 1.10%, respectively. Extremely high humidex can potentially increase the risk of depression, especially in females and the elderly. More protective measures should be taken in vulnerable populations.

The role of MAPK/NF-κB-associated microglial activation in T-2 toxin-induced mouse learning and memory impairment.

T-2 toxin is a mycotoxin with multiple toxic effects and has emerged as an important food pollutant. Microglia play a significant role in the toxicity of various neurotoxins. However, whether they participate in the neurotoxicity of T-2 toxin has not been reported. To clarify this point, an in vivo mouse model of T-2 toxin (4 mg/kg) poisoning was established. The results of Morris water maze and open-field showed that T-2 toxin induced learning and memory impairment and locomotor inhibition. Meanwhile, T-2 toxin induced microglial activation, while inhibiting microglia activation by minocycline (50 mg/kg) suppressed the toxic effect of the T-2 toxin. To further unveil the potential mechanisms involved in T-2 toxin-induced microglial activation, an in vitro model of T-2 toxin (0, 2.5, 5, 10 ng/mL) poisoning was established using BV-2 cells. Transcriptomic sequencing revealed lots of differentially expressed genes related to MAPK/NF-κB pathway. Western blotting results further confirmed that T-2 toxin (5 ng/mL) induced the activation of MAPKs and their downstream NF-κB. Moreover, the addition of inhibitors of NF-κB and MAPKs reversed the microglial activation induced by T-2 toxin. Overall, microglial activation may contribute a considerable role in T-2 toxin-induced behavioral abnormalities, which could be MAPK/NF-κB pathway dependent.

Association between ambient carbon monoxide levels and hospitalization costs of patients with myocardial infarction: Potential effect modification by ABO blood group.

Previous researches have reported the association between air pollution and various diseases. However, few researches have investigated whether air pollutants are associated with the economic loss resulting from patients' hospitalization, especially the economic loss of hospitalization due to acute cardiovascular events. The purpose of our research was to explore the association between the levels of carbon monoxide (CO), taken as an index of pollution, and the hospitalization costs of myocardial infarction (MI), and the potential effect modification by the ABO blood group. A total of 3237 MI inpatients were included in this study. A multiple linear regression model was used to evaluate the association between ambient CO levels and hospitalization costs of MI patients. Moreover, we performed stratified analyses by age, gender, body mass index (BMI), season, hypertension, and ABO blood types. There was a positive association between the levels of CO in the air and the costs of hospitalization caused by MI. Furthermore, such association was stronger in males, BMI ≥25, <65 years, with hypertension, and non-O blood group. Interestingly, we found the association was particularly significant in patients with blood group B. Overall, our study first found that ambient CO levels could have an impact on the hospitalization costs for MI patients, and those with blood group B can be more sensitive.

Association between maternal short-term exposure to ambient air pollution and the risk of fetal distress: A matched case-control study.

BACKGROUND: Ambient air pollution has been linked to gestational complications. However, the evidence on the relationship between air pollution and fetal distress is limited. OBJECTIVES: To investigate the relationship between maternal short-term air pollution exposure and fetal distress, and to identify a potential susceptible population. METHODS: This matched case-control study, involving 313 pregnancy women with fetal distress was conducted in Xi'an, the largest city in Northwest China from 2013 to 2016. Each woman with fetal distress was randomly matched with four women without fetal distress of the same age, same gestational week, and registration in the same period (n = 1252). Inverse distance-weighted (IDW) interpolation was applied to estimate maternal air pollution exposure based on the residential addresses. We employed conditional logistic regression model to evaluate the relationship between air pollutants and fetal distress. Distributed lag nonlinear model (DLNM) was performed to examine the exposure-response relationship between air pollutants and fetal distress. RESULTS: Maternal short-term exposure to PM10, PM2.5-10 (PMc), SO2, NO2, and CO was associated with increased risk of fetal distress. Each 10 µg/m3 increment in PM10, PMc, SO2 at lag 014, and NO2 at lag 010, the odds ratio (ORs) of fetal distress were 1.027 (95 % confidence interval (CI): 1.004, 1.050), 1.058 (95 % CI: 1.014, 1.105), 1.140 (95 % CI: 1.029, 1.264), and 1.158 (95 % CI: 1.046, 1.283), respectively. Similarly, with a 0.1 mg/m3 increment in CO at lag 014, the OR of fetal distress was 1.029 (95 % CI: 1.002, 1.058). Stratified analyses showed that the estimate associations of PM10, PM2.5 and CO appeared to be stronger, although not statistically significantly, among women with gestational complications. CONCLUSION: Maternal short-term exposure to ambient air pollution may increase the risk of fetal distress. Understanding the detrimental role of air pollution in fetal distress can help us better develop preventative methods in reducing its' impact on maternal and fetal health.

The association between short-term ambient sulfur dioxide exposure and hospitalization costs of ischemic stroke: a hospital-based study in Chongqing, China.

Evidence of the short-term effects of ambient sulfur dioxide (SO2) exposure on the economic burden of ischemic stroke is limited. This study aimed to explore the association between short-term ambient SO2 exposure and hospitalization costs for ischemic stroke in Chongqing, the most populous city in China. The hospital-based study included 7271 ischemic stroke inpatients. Multiple linear regression models were used to estimate the association between SO2 concentration and hospitalization costs. Propensity score matching was used to compare the patients' characteristics when exposed to SO2 concentrations above and below 20 µg/m3. It is found that short-term SO2 exposure was positively correlated with the hospitalization costs of ischemic stroke. The association was more evident in males, people younger than 65, and people hospitalized in the cool seasons. Besides, among the components of hospitalization costs, medicine costs were most significantly associated with SO2. More interesting, the lower concentration of SO2, the higher costs associated with 1 µg/m3 SO2 change. Above all, SO2 was positively associated with hospitalization costs of ischemic stroke, even at its low levels. The measures to reduce the level of SO2 can help reduce the burden of ischemic stroke.

Lipopolysaccharide induces inflammatory microglial activation through CD147-mediated matrix metalloproteinase expression.

Microglia-mediated neuroinflammation plays a vital role in the pathophysiological processes of multiple neurodegenerative diseases. Lipopolysaccharide (LPS) is an environmental poison that can induce inflammatory microglial activation. Matrix metalloproteinases (MMPs) are vital factors regulating microglial activation, and CD147 is a key MMP inducer, which can induce inflammation by inducing MMPs. However, whether it is involved in the regulation of microglial activation has not been reported. In this study, the role of CD147 in LPS-induced microglial inflammatory activation was investigated by establishing in vivo and in vitro models. The results suggested that LPS-induced microglial activation was accompanied by the induction of CD147 expression while the inhibition of CD147 expression could inhibit LPS-induced microglial inflammatory activation. In addition, the results also indicated that the role of CD147 in LPS-induced pro-inflammatory activation of microglia was related to its downstream MMP-3, MMP-8, and autophagy. Furthermore, the inhibition of MMP-3, MMP-8, and autophagy attenuated LPS-induced inflammatory activation of microglia. At the same time, there was a certain interaction between MMPs and autophagy, which is shown that inhibiting the expression of MMPs could inhibit autophagy, whereas inhibiting autophagy could inhibit the expression of MMPs. Taken together, we provided the first evidence that CD147/MMPs can be involved in LPS-induced inflammatory activation of microglia through an autophagy-dependent manner.

Role of p53 methylation in manganese-induced cyclooxygenase-2 expression in BV2 microglial cells.

Manganese (Mn) is an essential cofactor for many enzymes and plays an important role in normal growth and development. However, excess exposure to manganese (Mn) may be an important environmental factor leading to neurodegeneration. The overexpression of microglial cyclooxygenase-2 (COX-2) plays a key role in neuroinflammation in neurodegenerative diseases. The existing data suggest that Mn can induce neuroinflammation by up-regulating COX-2 expression. However, the mechanisms involved in Mn-induced microglial COX-2 up-regulation remain to be determined. The aim of this study was to investigate the role of p53 in Mn-induced COX-2 expression in microglial cells. The results showed that Mn exposure induced the up-regulation of COX-2 and inhibited the expression of p53 in BV2 microglial cells. The addition of p53 activator and the over-expression of p53 blocked the expression of COX-2 and prostaglandin E2 (PGE2), a COX-2 downstream effector, induced by Mn. Further, Mn increased the methylation of p53 DNA in microglia, while the addition of demethylation reagent 5-Aza-dC enhanced the expression of p53 but decreased the expression of COX-2. These results suggested that Mn may inhibit p53 expression through induction of DNA methylation, which can further induce the expression of COX-2 in microglial cells.

Association between short-term ambient nitrogen dioxide and type 2 diabetes outpatient visits: A large hospital-based study.

Type 2 diabetes (T2DM) as a non-communicable disease imposes heavy disease burdens on society. Limited studies have been conducted to assess the effects of short-term air pollution exposure on T2DM, especially in Asian regions. Our research aimed to determine the association between short-term exposure to ambient nitrogen dioxide (NO2) and outpatient visits for T2DM in Chongqing, the largest city in western China, based on the data collected from November 28, 2013 to December 31, 2019. A generalized additive model (GAM) was applied, and stratified analyses were performed to investigate the potential modifying effects by age, gender, and season. Meanwhile, the disease burden was revealed from attributable risk. Positive associations between short-term NO2 and daily T2DM outpatient visits were observed. The strongest association was observed at lag 04, with per 10 µg/m3 increase of NO2 corresponded to increased T2DM outpatient visits at 1.57% [95% confidence interval (CI): 0.48%, 2.65%]. Stronger associations were presented in middle-aged group (35-64 years old), male group, and cool seasons (October to March). Moreover, there were 1.553% (8664.535 cases) of T2DM outpatient visits attributable to NO2. Middle-aged adults, males, and patients who visited in cool seasons suffered heavier burdens. Conclusively, short-term exposure to NO2 was associated with increased outpatient visits for T2DM. Attention should be paid to the impact of NO2 on the burden of T2DM, especially for those vulnerable groups.

Elder people can be more susceptible to the association between short-term ambient air pollution and sleep disorder outpatient visits: a time-series study.

Sleep disorders attract increasing concerns. However, the evidence of the association between ambient air pollution and sleep disorders is limited. Therefore, our aim was to determine the association between short-term air pollution exposure and outpatient visits for sleep disorders in Xi'an, the largest city in Northwest China. Baseline outpatient data of daily sleep disorders between 2011 and 2013 were collected. Quasi-Poisson distribution was applied by adjusting the day of the week and weather conditions. A total of 49,282 sleep disorder outpatient visits were recorded. The most significant association between air pollutants and outpatient visits was observed on concurrent day: per 10 µg/m3 increase of NO2, SO2, and PM10 at lag 0 corresponded to increased outpatient sleep disorder visits at 0.22% (95% CI: 0.03%, 0.42%), 1.53% (95% CI: 0.53, 2.53%), and 2.57% (95% CI: 1.33%, 3.82%), respectively. As for gender-specific analysis, there was no statistically significant difference between males and females. The result of season-specific analysis showed no statistically significant difference between warm seasons and cool seasons, either. As for age-specific analysis, obvious associations were observed in 20-40 age group (NO2) and > 40 age group (PM10 and SO2), while no evident association was found for the young age group (< 20 years old). Conclusively, short-term exposure to air pollutants, especially gaseous air pollutants, might increase the risk of sleep disorders, and such association appears to be more obvious in elder people. We provide novel data that there may be age differences in the relationship between short-term air pollution exposure and sleep disorders.

The relationship between short-term PM2.5 exposure and outpatient visits for acne vulgaris in Chongqing, China: a time-series study.

Many researches have reported the air pollution impacts, either long term or short term, on inflammatory skin diseases, but there are few studies on the relation between PM2.5 and acne vulgaris. To determine the correlation between short-term PM2.5 exposure and acne outpatient visits, data for 120,842 acne vulgaris outpatient visits between December 2013 and December 2019 were obtained from three large hospitals in Chongqing, China. Both single-pollutant models and two-pollutant models were established to explore the relationship between PM2.5 exposure and acne outpatient visits. The stratified analyses were conducted through two-sample z-tests to investigate the possible gender (male or female) and age (< 25 years or ≥ 25 years) differences in PM2.5 effects. The results demonstrated positive correlations between PM2.5 concentrations and acne outpatient visits. A 10 µg/m3 increase in PM2.5 concentration was associated with a 1.71% (95% CI: 1.06-2.36%) increase in acne outpatient visits at lag 0-7 day. Stratified analyses showed that PM2.5 effects were greater in individuals aged ≥ 25 years than those aged < 25 years, but no gender difference was found. In conclusion, short-term PM2.5 exposure was positively associated with the risk of acne outpatient visits, especially for people ≥ 25 years old.

More obvious association between short-term ambient nitrogen dioxide and atrial fibrillation outpatient visits in cool seasons: A hospital-based study in northwestern China.

Atrial fibrillation (AF) is the most common sustained heart rhythm disorder associated with high mortality and morbidity. Limited studies have been conducted to assess the relationship between short-term exposure to ambient air pollution and AF attacks. This study aimed to explore the association between short-term ambient nitrogen dioxide (NO2) exposure and outpatient visits for AF in Xi'an, China. Data on daily AF outpatient visits and air pollutants from 2013 to 2019 (2555 days) were obtained. A time-series approach using over-dispersed Poisson generalized additive model (GAM) was employed, and stratified analyses were performed to investigate the potential modifying effects by season, age, and gender. A total of 8307 outpatient visits for AF were recorded. Increased levels of NO2 were associated with increased AF outpatient visits, and the most significant effect estimates were observed at lag 03: A 10 µg/m3 increase of NO2 at lag 03 was related to an elevation of 5.59% (95% CI: 2.67%, 8.51%) in daily outpatient visits for AF. Stratified analyses showed that there were no gender and age difference in the effect of NO2, while more obvious association was observed in cool seasons (October to March) than in warm seasons (April to September). In summary, short-term ambient NO2 exposure can be positively associated with daily outpatient visits for AF, especially in cool seasons. This work provided novel data that the association between air pollutants and AF can vary by seasons, further supporting that the prevention of cardiovascular health effects should be strengthened in winter.