Systemic immune response of rainbow trout exposed to Flavobacterium psychrophilum infection.

Bacterial cold-water disease (BCWD) caused by Flavobacterium psychrophilum is one of the most serious bacterial diseases leading to significant economic loss for rainbow trout (Oncorhynchus mykiss) aquaculture. However, little is known about the systemic immune response of rainbow trout against F. psychrophilum infection. This study investigated the immune response of rainbow trout to F. psychrophilum infection using multiple experiments, including bacterial load detection, phagocyte activity assessment, enzyme activity evaluation, and gene expression profiling. Results showed that the spleen index and intestinal pathogen load reached a peak at 3 days post-infection, with strong pro-inflammatory gene expression observed in rainbow trout. Leukocytes RBA and PKA were significantly elevated in the spleen, blood and intestine at 7 days post-infection. Heat map analysis demonstrated that the spleen had a more substantial pro-inflammatory response compared to the intestine post-infection and exhibited higher expression levels of immune-related genes, including IgM, il1ß, il6, cd4, cd8a, cd8b, c1q, chathelicidin, inos, and lysozyme. Both Th1 and Th2 polarized responses in the spleen were activated, with Th2 (il4/13a, gata3) (FC > 4) being more intense than Th1 (tnfα, t-bet) (FC > 2). Tight junction proteins exhibited down-regulation followed by up-regulation post-infection. Collectively, the results of this study expand our current understanding of the immune response of rainbow trout post F. psychrophilum infection but also provide new avenues for investigation in salmonid aquaculture.

Ozone pollution and hospital admissions for cardiovascular events.

AIMS: The available literature on morbidity risk of cardiovascular diseases associated with ambient ozone pollution is still limited. This study examined the potential acute effects of exposure to ambient ozone pollution on hospital admissions of cardiovascular events in China. METHODS AND RESULTS: A two-stage multi-city time-series study approach was used to explore the associations of exposure to ambient ozone with daily hospital admissions (n = 6 444 441) for cardiovascular events in 70 Chinese cities of prefecture-level or above during 2015-17. A 10 µg/m3 increment in 2-day average daily 8 h maximum ozone concentrations was associated with admission risk increases of 0.46% [95% confidence interval (CI): 0.28%, 0.64%] in coronary heart disease, 0.45% (95% CI: 0.13%, 0.77%) in angina pectoris, 0.75% (95% CI: 0.38%, 1.13%) in acute myocardial infarction (AMI), 0.70% (95% CI: 0.41%, 1.00%) in acute coronary syndrome, 0.50% (95% CI: 0.24%, 0.77%) in heart failure, 0.40% (95% CI: 0.23%, 0.58%) in stroke and 0.41% (95% CI: 0.22%, 0.60%) in ischemic stroke, respectively. The excess admission risks for these cardiovascular events associated with high ozone pollution days (with 2-day average 8-h maximum concentrations ≥100 µg/m3 vs. < 70 µg/m3) ranged from 3.38% (95% CI: 1.73%, 5.06%) for stroke to 6.52% (95% CI: 2.92%, 10.24%) for AMI. CONCLUSION: Ambient ozone was associated with increased hospital admission risk for cardiovascular events. Greater admission risks for cardiovascular events were observed under high ozone pollution days. These results provide evidence for the harmful cardiovascular effects of ambient ozone and call for special attention on the control of high ozone pollution.

Long-term exposures to ambient particulate matter and ozone pollution with lower extremity deep vein thrombosis after surgical operations: a retrospective case-control study in Beijing, China.

BACKGROUND: Lower extremity deep vein thrombosis (LEDVT) after surgical operations is a common and fatal disease leading to unfavorable outcomes including death. Nevertheless, there has been insufficient evidence on the associations between ambient air pollution and LEDVT, particularly studies from developing regions. METHODS: Based on 302 LEDVT cases and 302 controls in a general hospital in Beijing, China, this unmatched retrospective case-control study investigated the associations of fine particulate matter (PM2.5), inhalable particulate matter (PM10), and ozone (O3) with odds of LEDVT. RESULTS: Per 10 µg/m3 increase in PM2.5, PM10, and O3 at 3-month, 6-month, and 2-year average was associated with increased LEDVT odds [odds ratios (ORs) for PM2.5: 1.10 (95%CI: 1.05, 1.14), 1.14 (95%CI: 1.09, 1.18), and 1.30 (95%CI: 1.06, 1.61); ORs for PM10: 1.06 (95%CI: 1.02, 1.10), 1.12 (95%CI: 1.08, 1.16), and 1.29 (95%CI: 1.03, 1.61); ORs for O3: 1.00 (95%CI: 0.96, 1.04), 1.16 (95%CI: 1.02, 1.31), and 2.08 (95%CI: 1.03, 4.18), respectively]. The stratified analyses, exposure-responses curves, and sensitivity analyses further highlighted the robustness of our findings. CONCLUSIONS: Long-term exposures to ambient PM2.5, PM10, and O3 may increase the risk of LEDVT in patients after surgical operations. The results may be implicated in the prevention and control of adverse clinical outcomes of surgical patients associated with ambient air pollution.

The efficacy and safety of roxadustat for anemia in patients with dialysis-dependent chronic kidney disease: a systematic review and meta-analysis.

BACKGROUND: This meta-analysis aims to assess the efficacy and safety of roxadustat in treating anemia patients with dialysis-dependent (DD) chronic kidney disease (CKD). METHODS: We comprehensively searched 5 databases for randomized controlled trials (RCTs) investigating roxadustat for anemia in DD-CKD patients. RevMan 5.0 was used to extract and synthesize data for meta-analysis. RESULTS: Ten different RCTs (9 studies) and 5698 DD-CKD patients with anemia were included. Our findings revealed that when compared to the erythropoiesis-stimulating agents (ESAs) group, the roxadustat group showed increased hemoglobin levels [MD (Mean Difference) 0.25 g/dL (95%CI 0.14 g/dL to 0.36 g/dL), p < 0.00001] and improved iron-utilization by increasing serum iron [MD 1.85 µmol/L], total iron binding capacity [MD 35.73 µg/dL], transferrin saturation [MD 1.19%], and transferrin level [MD 0.40 g/L]. In addition, we found that roxadustat significantly decreased the low-density lipoprotein-cholesterol [MD -0.39 mmol/L] and total cholesterol [MD -0.6 mmol/L]. In patients with a C-reactive protein level that exceeds the upper limit of the normal range, hemoglobin levels were higher for roxadustat than for ESAs [MD 0.39 g/dL]. Treatment-emergent adverse events, treatment-emergent serious adverse events, and major adverse cardiovascular events were not significantly different between the two groups. CONCLUSIONS: The hemoglobin levels of DD-CKD patients were significantly increased and not affected by the inflammatory state after roxadustat treatment. Roxadustat also improved iron utilization, and it was not associated with higher treatment-emergent adverse events, treatment-emergent serious adverse events, and major adverse cardiovascular events when compared to ESAs.

Molecular characterization and expression analysis of claudin-4-like in rainbow trout involved in Flavobacterium psychrophilum infection.

The claudin family of proteins are pivotal components of tight junction (TJ) participating in the epithelial barrier function in fish. Our previous studies indicated that one of the claudins, claudin-4-like (OmCLDN4L) was differentially expressed in rainbow trout (Oncorhynchus mykiss) spleen post infection of Flavobacterium psychrophilum, which is the causative pathogen of bacterial coldwater disease (BCWD). However, little is known about the function of OmCLDN4L in rainbow trout against bacterial infection. In the present study, the OmCLDN4L was identified and functionally characterized from rainbow trout. The OmCLDN4L has an open reading frame (ORF) of 668 bp, encoding a 22.86 kDa four-transmembrane protein with function of bicellular tight junction and apical tight junction. OmCLDN4L has the highest similarity with CLDN28a, CLDN28b and CLDN30 in amino acid sequence. Phylogenetic analysis showed that all of CLDN4 and CLDN4-like from fish clustered together but diverged from their counterparts in mammals, with main differences lying in their N-terminus. RT-qPCR results indicated that OmCLDN4L was constitutively expressed in all tissues investigated under healthy conditions, primarily in mucus, liver, skin and intestine. The expression of OmCLDN4L in rainbow trout intestine was slightly down-regulated at day 1 while up-regulated at day 3 and day 7 post F. psychrophilum infection, with the similar profiling of CLDN30 and CLDN10e. The expression level of inflammatory cytokines TNF-α, IL4/13A, IL-6 and pattern recognition receptor TLR-2 showed the same trend with OmCLDN4L in the intestine at day 3 and day 7 post F. psychrophilum infection. Collectively, these findings demonstrate that OmCLDN4L participates in the immune response to bacterial infection, offering new insights into the molecular mechanism of intestinal barrier in rainbow trout against F. psychrophilum infection.

Association of exposure to fine particulate matter wave over the preconception and pregnancy periods with adverse birth outcomes: Results from the project ELEFANT.

BACKGROUND: No study has explored the effects of sustained maternal exposure to high-level ambient fine particulate matter (PM2.5) within a short period, i.e., PM2.5 wave, on adverse birth outcomes, though increasing epidemiological studies demonstrated that exposure to single days of high ambient PM2.5 could increase risks of adverse birth outcomes. In this study, we aim to evaluate associations of maternal PM2.5 wave exposure around pregnancy with preterm birth (PTB), small for gestational age (SGA), and large for gestational age (LGA). METHODS: Totally 10,916 singleton pregnant women from all 16 districts in Tianjin, China, and their followed-up birth outcomes were included in this study. We defined PM2.5 wave as at least 2 consecutive days with daily average PM2.5 concentration exceeding 75 µg/m3, and 90th, 92.5th, 95th, 97.5th, 99th percentiles of PM2.5 distribution during the study period in Tianjin, respectively. Cox proportional hazard model was applied to evaluate the durational effects of PM2.5 wave during each exposure window on PTB, SGA, and LGA after adjusting for potential confounders. RESULTS: Exposure to PM2.5 wave over the preconception and pregnancy periods was associated with increased risks of adverse birth outcomes. For PTB, the strongest association was found during the first trimester when PM2.5 wave was defined as at least 4 consecutive days with daily average PM2.5 concentration >90th (HR, 10.46; 95% CI, 6.23-17.54); and for SGA (HR, 6.23; 95% CI, 3.34-11.64) and LGA (HR, 4.70; 95% CI, 3.35-6.59), the strongest associations both were found when PM2.5 wave was defined as at least 2 consecutive days with daily average PM2.5 concentration >99th. Additionally, the risks of adverse birth outcomes generally increased at higher PM2.5 thresholds or longer durations of PM2.5 wave. CONCLUSION: Prolonged exposure to high-level PM2.5 over preconception and pregnancy periods was associated with increasing risks of PTB, SGA and LGA.

Co-exposure to multiple air pollutants and sleep disordered breathing in patients with or without obstructive sleep apnea: A cross-sectional study.

BACKGROUND: Air pollution may be a contributing risk factor for obstructive sleep apnea (OSA). However, the health effects of co-exposure to multiple air pollutants on OSA patients remain unclear. OBJECTIVES: To assess the joint effect of multi-pollutant on sleep disordered breathing (SDB) parameters in patients with or without OSA and identify the dominant pollutants. METHODS: A total of 2524 outpatients from April 2020 to May 2021 were recruited in this cross-sectional study. Ambient air pollutant data were obtained from the nearest central monitoring stations to participants' residential address. SDB parameters were measured by the ApneaLink devices, including apnea-hypopnea index (AHI), hypopnea index (HI), oxygen desaturation index (ODI), average oxygen saturation (SpO2), percentage sleep time with <90% saturation (T90), and desaturation. Bayesian kernel machine regression (BKMR) was applied to evaluate the effects of multiple pollutants. RESULTS: Significant associations were observed between air pollutants and SDB parameters (including increases in AHI, HI, ODI, and desaturation) among patients with OSA. Co-exposure to air pollutants was positively correlated with AHI, HI, and ODI. PM10 and O3 dominated the effects of pollutant mixtures on OSA, with the highest posterior inclusion probability (PIP) values of 0.592 and 0.640, respectively. Stratified analysis showed that, compared to male patients with OSA, stronger effects on the SDB parameters were observed in female patients. Stronger associations were also found in the warm season than those in the cold season. CONCLUSION: Co-exposure to air pollutants was associated with SDB parameters among patients with OSA, PM10 and O3 might play the dominant roles.

Associations between personal noise exposure and heart rate variability were modified by obesity and PM2.5: The study among obese and normal-weight adults (SONA).

Noise pollution has been documented to increase the risks of cardiovascular disorders, which can be predicted by heart rate variability (HRV), nevertheless, there has been limited evidence on the modifiers of noise pollution. Environmental fine particulate matter (PM2.5) and obesity status are both growing major concerns of cardiovascular disease burden. Our study aims to investigate whether these two factors may modify the associations between noise exposure and HRV indices. An investigation was performed on 97 (53 normal-weight and 44 obese) participants aged 18-26 years, with continuous 5-min personal exposure assessment and ambulatory electrocardiogram monitoring for 24 h. This study found that personal exposure to noise was associated with decreased HRV level and imbalanced cardiac autonomic function, as indicated by decreases in standard deviation of normal-to-normal intervals (SDNN), square root of the mean squared differences of successive intervals (rMSSD), the percentage of R-R intervals that differ from each other by more than 50 ms (pNN50), low-frequency (LF) power, high-frequency (HF) power, and increases in LF-HF-Ratio. Stronger associations between personal noise exposure and HRV indices were observed among obese participants and participants with higher PM2.5 exposure levels compared to their counterparts. For SDNN, a 1 dB(A) increment in personal noise exposure at 3h-average was associated with a 1.25% (95%CI: -1.64%, -0.86%) decrease among obese participants, and a 0.11% (95%CI: -0.38%, 0.16%) decrease among normal-weight participants (P for subgroup difference<0.001); and a 0.87% (95%CI: -1.20%, -0.54%) decrease among participants with higher PM2.5 exposure levels, and a 0.22% (95%CI: -0.58%, 0.14%) decrease among participants with lower PM2.5 exposure levels (P for subgroup difference = 0.008). Obesity and PM2.5 may aggravate the adverse effects of noise on HRV, which has implications for targeted prevention of cardiovascular disease burden associated with noise pollution.

Ambient particulate air pollution, blood cell parameters, and effect modification by psychosocial stress: Findings from two studies in three major Chinese cities.

The associations between particulate matter (PM) exposure, psychosocial stress and blood cell parameters are bringing novel insights to characterize the early damage of multiple diseases. Based on two studies conducted in three Chinses cities using cross-sectional (Beijing, 425 participants) and panel study (Tianjin and Shanghai, 92 participants with 361 repeated measurements) designs, this study explored the associations between short-term exposure to ambient PM and blood cell parameters, and the effect modification by psychosocial stress. Increasing PM2.5 exposure was significantly associated with decreases in red blood cell (RBC) count and mean corpuscular hemoglobin concentration (MCHC), and increases in mean corpuscular volume (MCV), platelets count (PLT) and platelet hematocrit (PCT) in both studies. For instance, a 10 µg/m3 increment in PM2.5 concentration was associated with a 1.04% (95%CI: 0.16%, 1.92%) increase in PLT (4-d) and a 1.09% (95%CI: 0.31%, 1.87%) increase in PCT (4-d) in the cross-sectional study, and a 0.64% (95%CI: 0.06%, 1.22%) increase in PLT (1-d) and a 0.72% (95%CI: 0.33%, 1.11%) increase in PCT (1-d) in the panel study, respectively. In addition, stronger increases in MCV, PLT, and PCT associated with PM2.5 exposure were found in higher psychosocial stress group compared to lower psychosocial stress group (p for interaction <0.10), indicating that blood cell parameters of individuals with higher psychosocial stress might be more susceptible to the early damages of PM2.5 exposure.

Indoor formaldehyde levels in residences, schools, and offices in China in the past 30 years: A systematic review.

Exposure to formaldehyde causes a variety of adverse health outcomes, while the distributions of indoor formaldehyde in different building types are still not clear in China. In this study, based on the systematic review of previously published data and Monte Carlo simulation, we assessed geographical and temporal distributions of indoor formaldehyde concentrations in residences, schools, and offices across China. A total of 397 studies covered 34 provincial-level regions since 1986 were collected. The results showed that indoor formaldehyde concentrations in residences, schools, and offices in nationwide were decreasing over years due to the publishment of indoor air quality standards since 2002. During 2011 to 2015, the median concentrations of indoor formaldehyde in newly renovated residences, schools, and offices were 153 µg/m3 , 163 µg/m3 , and 94 µg/m3 , with an exceeding rate of 82%, 46%, and 91% considering a standard threshold of 100 µg/m3 at that time, while the exceeding rate was less than 5% for buildings that were renovated beyond one year. Our findings release the temporal trends and geographic distributions of indoor formaldehyde concentrations in residences, schools, and offices in China in the past 30 years, and provide basic data for the comprehensive evaluation of disease burden attributable to indoor formaldehyde exposure.

Indoor exposure to phthalates and its burden of disease in China.

China's profoundly rapid modernization in the past two decades has resulted in dramatic changes in indoor environmental exposures. Among these changes, exposure to phthalates has attracted increasing attention. We aimed to characterize indoor phthalate exposure and to estimate the disease burden attributable to indoor phthalate pollution from 2000 to 2017 in China. We integrated the national exposure level of indoor phthalates from literature through systematic review and Monte Carlo simulation. Dose-response relationships between phthalate exposure and health outcomes were obtained by systematic review and meta-analysis. Based on existing models for assessing probabilities of causation and a comprehensive review of available data, we calculated the disability-adjusted life years (DALYs) among the general Chinese population resulting from exposure to indoor phthalate pollution. We found that DnBP, DiBP, and DEHP were the most abundant phthalates in indoor environments of residences, offices, and schools with medians of national dust phase concentration from 74.5 µg/g to 96.3 µg/g, 39.6 µg/g to 162.5 µg/g, 634.2 µg/g to 1,394.7 µg/g, respectively. The national equivalent exposure for children to phthalates in settled dust was higher than that of adults except for DiBP and DnOP. Dose-response relationships associated with DEP, DiBP, DnBP, BBzP, and DEHP exposures were established. Between 2000 and 2017, indoor phthalate exposure in China has led to 3.32 million DALYs per year, accounting for 0.90% of total DALYs across China. The annual DALY associated with indoor phthalate pollution in China was over 2000 people per million, which is about 2~3 times of the DALY loss due to secondhand smoke (SHS) in six European countries or the sum of the DALY loss caused by indoor radon and formaldehyde in American homes. Our study indicates a considerable socioeconomic impact of indoor phthalate exposure for a modernizing human society. This suggest the need for relevant national standard and actions to reduce indoor phthalate exposure.

Health effects of exposure to indoor volatile organic compounds from 1980 to 2017: A systematic review and meta-analysis.

Exposure to volatile organic compounds (VOCs) indoors is thought to be associated with several adverse health effects. However, we still lack concentration-response (C-R) relationships between VOC levels in civil buildings and various health outcomes. For this paper, we conducted a systematic review and meta-analysis of observational studies to summarize related associations and C-R relationships. Four databases were searched to collect all relevant studies published between January 1980 and December 2017. A total of 39 studies were identified in the systematic review, and 32 of these were included in the meta-analysis. We found that the pooled relative risk (RR) for leukemia was 1.03 (95% CI: 1.01-1.05) per 1 µg/m3 increase of benzene and 1.25 (95%CI: 1.14-1.37) per 0.1 µg/m3 increase of butadiene. The pooled RRs for asthma were 1.08 (95% CI: 1.02-1.14), 1.02 (95% CI: 1.00-1.04), and 1.04 (95% CI: 1.02-1.06) per 1 µg/m3 increase of benzene, toluene, and p-dichlorobenzene, respectively. The pooled RR for low birth weight was 1.12 (95% CI: 1.05-1.19) per 1 µg/m3 increase of benzene. Our findings provide robust evidence for associations between benzene and leukemia, asthma, and low birth weight, as well as for health effects of some other VOCs.

Lung cancer as adverse health effect by indoor radon exposure in China from 2000 to 2020: A systematic review and meta-analysis.

Indoor radon exposure is thought to be associated with adverse health effect as lung cancer. Lung cancer incidences in China have been the highest worldwide during the past two decades. It is important to quantitively address indoor radon exposure and its health effect, especially in countries like China. In this paper, we have conducted a meta-analysis based on indoor radon and its health effect studies from a systematic review between 2000 and 2020. A total of 8 studies were included for lung cancer. We found that the relative risk (RR) was 1.01 (95% CI: 1.01-1.02) per 10 Bq/m3 increase of indoor radon for lung cancer in China. The subgroup analysis found no significant difference between the conclusions from the studies from China and other regions. The health effect of indoor radon exposure is relatively consistent for the low-exposure and high-exposure groups in the subgroup analysis. With a better understanding of exposure level of indoor radon, the outcomes and conclusions of this study will provide supports for next phase of researches on estimation of environmental burden of disease by indoor radon exposures in countries like China.

Health effects of exposure to sulfur dioxide, nitrogen dioxide, ozone, and carbon monoxide between 1980 and 2019: A systematic review and meta-analysis.

The burden of disease attributed to the indoor exposure to sulfur dioxide (SO2 ), nitrogen dioxide (NO2 ), ozone (O3 ), and carbon monoxide (CO) is not clear, and the quantitative concentration-response relationship is a prerequisite. This is a systematic review to summarize the quantitative concentration-response relationships by screening and analyzing the polled effects of population-based epidemiological studies. After collecting literature published between 1980 and 2019, a total of 19 health outcomes in 101 studies with 182 health risk estimates were recruited. By meta-analysis, the leave-one-out sensitivity analysis and Egger's test for publication bias, the robust and reliable effects were found for SO2 (per 10 µg/m3 ) with chronic obstructive pulmonary diseases (COPD) (pooled relative risks [RRs] 1.016, 95% CI: 1.012-1.021) and cardiovascular diseases (CVD) (RR 1.012, 95%CI: 007-1.018), respectively. NO2 (per 10 µg/m3 ) had the pooled RRs for childhood asthma, preterm birth, lung cancer, diabetes, and COPD by 1.134 (1.084-1.186), 1.079 (1.007-1.157), 1.055 (1.010-1.101), 1.019 (1.009-1.029), and 1.016 (1.012-1.120), respectively. CO (per 1 mg/m3 ) was significantly associated with Parkinson's disease (RR 1.574, 95% CI: 1.069-2.317) and CVD (RR 1.024, 95% CI: 1.011-1.038). No robust effects were observed for O3 . This study provided evidence and basis for further estimation of the health burden attributable to the four gaseous pollutants.

Indoor exposure levels of radon in dwellings, schools, and offices in China from 2000 to 2020: A systematic review.

After decades of development, the indoor environment in China has changed. A systematic review was conducted from peer-reviewed scientific papers with field test data of indoor radon in China from 2000 to 2020 for three types of buildings. The mean concentrations of indoor radon for dwellings, school buildings, and office buildings are 54.6, 56.1, and 54.9 Bq/m3 . The indoor radon concentration was related to seasons, climate regions, ventilation, decoration, and other factors such as soil and outdoor air. Colder seasons, especially in severe colder areas of China, newer decorated buildings, closed windows, and doors were all associated with higher indoor radon concentrations. Variables like climate region and ventilation showed statistical significance in the correlation analysis. Regarding the increasing trend of indoor radon concentration in China during the last two decades, further study of indoor radon is necessary especially for school buildings and office buildings, and will help access its environmental burden of disease in China more accurately.

Indoor exposure levels and risk assessment of volatile organic compounds in residences, schools, and offices in China from 2000 to 2021: A systematic review.

The last two decades have witnessed rapid urbanization and economic growth accompanied by severe indoor air pollution of volatile organic compounds (VOCs) in China. However, indoor VOC pollution across China has not been well characterized and documented. This study is a systematic review of field measurements of eight target VOCs (benzene, toluene, xylenes, acetaldehyde, p-dichlorobenzene, butadiene, trichloroethylene, and tetrachloroethylene) in residences, offices, and schools in China from 2000 to 2021. The results show that indoor pollution of benzene, toluene, and xylenes has been more serious in China than in other countries. Spatiotemporal distribution shows lower indoor VOC levels in east and south-east regions and a declining trend from 2000 to 2021. Moving into a dwelling more than 1 year after decoration and improving ventilation could significantly reduce exposure to indoor VOCs. Reducing benzene exposure is urgently needed because it is associated with greater health risks (4.5 × 10-4 for lifetime cancer risk and 8.3 for hazard quotient) than any other VOCs. The present study enriches the database of indoor VOC levels and provides scientific evidence for improving national indoor air quality standards as well as estimating the attributable disease burden caused by VOCs in China.

Association and interaction of O3 and NO2 with emergency room visits for respiratory diseases in Beijing, China: a time-series study.

BACKGROUND: Ozone (O3) and nitrogen dioxide (NO2) are the two main gaseous pollutants in the atmosphere that act as oxidants. Their short-term effects and interaction on emergency room visits (ERVs) for respiratory diseases remain unclear. METHODS: We conducted a time-series study based on 144,326 ERVs for respiratory diseases of Peking University Third Hospital from 2014 to 2019 in Beijing, China. Generalized additive models with quasi-Poisson regression were performed to analyze the association of O3, NO2 and their composite indicators (Ox and Oxwt) with ERVs for respiratory diseases. An interaction model was further performed to evaluate the interaction between O3 and NO2. RESULTS: Exposure to O3, NO2, Ox and Oxwt was positively associated with ERVs for total respiratory diseases and acute upper respiratory infection (AURI). For instance, a 10 µg/m3 increase in O3 and NO2 were associated with 0.93% (95%CI: 0.05%, 1.81%) and 5.87% (95%CI: 3.92%, 7.85%) increase in AURI at lag0-5 days, respectively. Significant linear exposure-response relationships were observed in Ox and Oxwt over the entire concentration range. In stratification analysis, stronger associations were observed in the group aged < 18 years for both O3 and NO2, in the warm season for O3, but in the cold season for NO2. In interaction analysis, the effect of O3 on total respiratory emergency room visits and AURI visits was the strongest at high levels (> 75% quantile) of NO2 in the < 18 years group. CONCLUSIONS: Short-term exposure to O3 and NO2 was positively associated with ERVs for respiratory diseases, particularly in younger people (< 18 years). This study for the first time demonstrated the synergistic effect of O3 and NO2 on respiratory ERVs, and Ox and Oxwt may be potential proxies.

Chemical element concentrations in cord whole blood and the risk of preterm birth for pregnant women in Guangdong, China.

Maternal exposure to chemical elements, including essential and non-essential elements, have been found to be associated with preterm births (PTB). However, few studies have measured element concentrations in cord whole blood, which reflects activity at the maternal-fetal interface and may be biologically associated with PTBs. In this study, we determined concentrations of 21 elements in cord whole blood and explored the associations between element concentrations and PTB in a nested case-control study within a birth cohort in Guangdong, China. Finally, 515 preterm infants and 595 full-term infants were included. We performed single-element and multi-element logistic regressions to evaluate linear relationships between element concentrations and PTB. According to the results of single-element models, most essential elements (including K, Ca, Si, Zn, Se, Sr and Fe) were negatively associated with PTB, while Cu, V, Co and Sn were positively associated with PTB. Of the non-essential elements, Sb, Tl, and U were positively associated with PTB, while Pb was negatively associated with PTB. The multi-element model results for most elements were similar, except that the association between Mg and PTB was shown to be significantly positive, and the association for Cu became much larger. A possible explanation is that the effects of Mg and Cu may be influenced by other elements. We performed restricted cubic spline (RCS) regressions and found significantly non-linear exposure-response relationships for Mg, Se, Sr, K and Sb, indicating that the effects of these elements on PTB are not simply detrimental or beneficial. We also examined the joint effect using a Bayesian kernel machine regression (BKMR) model and found the risk of PTB decreased significantly with element mixture concentration when lnC was larger than the median. Bivariate interaction analysis suggested antagonistic effects of Sb on Zn and Sr, which may be attributed to Sb negating the antioxidant capacity of Zn and Sr. This study provides additional evidence for the effect of element exposures on PTB, and will have implications for the prevention of excessive exposures or inappropriate element supplementation during pregnancy.

Short-term exposure to ambient nitrogen dioxide and increased hospitalization burden for depression in China: a multicity analysis.

Evidence for the increased hospitalization burden, including admissions, expenditures and length of hospital stay (LOS) for depression attributable to ambient nitrogen dioxide (NO2) is lacking. We investigated the associations between short-term exposure to ambient NO2 and attributable admissions, hospitalization expenditures and LOS for depression in 57 Chinese cities during 2013-2017 using a well-established two-stage time-series study approach. Short-term exposure to ambient NO2 was associated with significantly increased admissions, hospitalization expenditures and LOS for depression, and the attributable fractions were 6.87% (95% CI: 2.90%, 10.65%), 7.12% (3.01%, 11.04%) and 6.12% (2.59%, 9.50%) at lag02, respectively. The projected total attributable admissions, hospitalization expenditures and LOS for depression related to ambient NO2 at the national level were 23,335 (9,863, 36,181) admissions, 318.70 (134.43, 492.21) million CNY and 539.55 (227.99, 836.99) thousand days during the study period, respectively. Short-term exposure to ambient NO2 is associated with increased hospitalization burden for depression.

Changes in arachidonic acid (AA)- and linoleic acid (LA)-derived hydroxy metabolites and their interplay with inflammatory biomarkers in response to drastic changes in air pollution exposure.

BACKGROUND: Untargeted metabolomics analyses have indicated that fatty acids and their hydroxy derivatives may be important metabolites in the mechanism through which air pollution potentiates diseases. This study aimed to use targeted analysis to investigate how metabolites in arachidonic acid (AA) and linoleic acid (LA) pathways respond to short-term changes in air pollution exposure. We further explored how they might interact with markers of antioxidant enzymes and systemic inflammation. METHODS: This study included a subset of participants (n = 53) from the Beijing Olympics Air Pollution (BoaP) study in which blood samples were collected before, during, and after the Beijing Olympics. Hydroxy fatty acids were measured by liquid chromatography/mass spectrometry (LC/MS). Native total fatty acids were measured as fatty acid methyl esters (FAMEs) using gas chromatography. A set of chemokines were measured by ELISA-based chemiluminescent assay and antioxidant enzyme activities were analyzed by kinetic enzyme assays. Changes in levels of metabolites over the three time points were examined using linear mixed-effects models, adjusting for age, sex, body mass index (BMI), and smoking status. Pearson correlation and repeated measures correlation coefficients were calculated to explore the relationships of metabolites with levels of serum chemokines and antioxidant enzymes. RESULTS: 12-hydroxyeicosatetraenoic acid (12-HETE) decreased by 50.5% (95% CI: -66.5, -34.5; p < 0.0001) when air pollution dropped during the Olympics and increased by 119.4% (95% CI: 36.4, 202.3; p < 0.0001) when air pollution returned to high levels after the Olympics. In contrast, 13-hydroxyoctadecadienoic acid (13-HODE) elevated significantly (p = 0.023) during the Olympics and decreased nonsignificantly after the games (p = 0.104). Interleukin 8 (IL-8) correlated with 12-HETE (r = 0.399, BH-adjusted p = 0.004) and 13-HODE (r = 0.342, BH-adjusted p = 0.014) over the three points; it presented a positive and moderate correlation with 12-HETE during the Olympics (r = 0.583, BH-adjusted p = 0.002) and with 13-HODE before the Olympics (r = 0.543, BH-adjusted p = 0.008). CONCLUSION: AA- and LA-derived hydroxy metabolites are associated with air pollution and might interact with systemic inflammation in response to air pollution exposure.