The Long-Term Effect of Maternal Iron Levels in the Second Trimester on Mild Thinness among Preschoolers: The Modifying Effect of Small for Gestational Age.

The supplementation of multiple micronutrients throughout pregnancy can reduce the risk of adverse birth outcomes and various diseases in children. However, the long-term effect of maternal multiple micronutrient levels in the second trimester on the overall development of preschoolers remains unknown. Therefore, 1017 singleton mother-infant pairs and 6-year-old preschoolers were recruited based on the China-Wuxi Birth Cohort Study. Meanwhile, information on the demographic characteristics of pregnant women and preschoolers, maternal copper, calcium, iron, magnesium, and zinc levels in whole blood during the second trimester, and neonatal outcomes, were collected. We aimed to investigate the long-term impact of maternal copper, calcium, iron, magnesium, and zinc levels in the second trimester on mild thinness among 6-year-old preschoolers, and the modifying effect of small for gestational age (SGA), within the Chinese population. Multiple logistic regression models revealed that high-level maternal iron in the second trimester reduced the risk of mild thinness [adjusted OR: 0.46 (95% CI: 0.26, 0.80)] among 6-year-old preschoolers. However, no significant association was found for the remaining four maternal essential metal elements. Additionally, the restricted cubic spline function showed that the risk of mild thinness decreased when maternal iron concentration exceeded 7.47 mmol/L in whole blood during the second trimester. Furthermore, subgroup analysis indicated that the long-term protective effect of high-level maternal iron on mild thinness was only observed in SGA infants. Summarily, high-level maternal iron in the second trimester distinctly lowers the risk of mild thinness among 6-year-old preschoolers, especially in preschoolers with birth outcomes of SGA. Our findings offer evidence for the implementation of iron supplementation in the second trimester as a preventive measure against mild thinness in children.

PM2.5 and its respiratory tract depositions on blood pressure, anxiety, depression and health risk assessment: A mechanistic study based on urinary metabolome.

Effects of fine particulate matter (PM2.5) and regional respiratory tract depositions on blood pressure (BP), anxiety, depression, health risk and the underlying mechanisms need further investigations. A repeated-measures panel investigation among 40 healthy young adults in Hefei, China was performed to explore the acute impacts of PM2.5 exposure and its deposition doses in 3 regions of respiratory tract over diverse lag times on BP, anxiety, depression, health risk, and the potential mechanisms. We collected PM2.5 concentrations, its deposition doses, BP, the Self-Rating Anxiety Scale (SAS) score and the Self-Rating Depression Scale (SDS) score. An untargeted metabolomics approach was used to detect significant urine metabolites, and the health risk assessment model was used to evaluate the non-carcinogenic risks associated with PM2.5. We applied linear mixed-effects models to assess the relationships of PM2.5 with the aforementioned health indicators We further evaluate the non-carcinogenic risks associated with PM2.5. We found deposited PM2.5 dose in the head accounted for a large proportion. PM2.5 and its three depositions exposures at a specific lag day was significantly related to increased BP levels and higher SAS and SDS scores. Metabolomics analysis showed significant alterations in urinary metabolites (i.e., glucoses, lipids and amino acids) after PM2.5 exposure, simultaneously accompanied by activation of the cAMP signaling pathway. Health risk assessment presented that the risk values for the residents in Hefei were greater than the lower limits of non-cancer risk guidelines. This real-world investigation suggested that acute PM2.5 and its depositions exposures may increase health risks by elevating BP, inducing anxiety and depression, and altering urinary metabolomic profile via activating the cAMP signaling pathway. And the further health risk assessment indicated that there are potential non-carcinogenic risks of PM2.5 via the inhalation route in this area.

Association between short-term exposure to ambient air pollution and number of outpatient Helicobacter pylori infection visits.

Helicobacter pylori infection (HPI) is an important risk factor of gastrointestinal diseases, but factors leading to it are still not fully understood. To investigate the association between short-term exposure to air pollution and HPI during outpatient visits, we collected daily data for HPI outpatient visits and air pollutant concentrations during 2014-2021 in Hefei, Anhui Province, China. A time-stratified case-crossover design was performed to analyze the acute impacts of air pollution on HPI outpatient visits. We also explored potential effect modifiers. A total of 9072 outpatient visits were recorded. We found positive and statistically significant associations of acute exposure to nitrogen dioxide (NO2), sulfur dioxide (SO2), and carbon monoxide (CO) with HPI outpatient visits. Threshold concentrations of the three pollutants with same-day exposure (lag 0 day) for outpatient visits were 37 µg/m3 for NO2, 8 µg/m3 for SO2, and 0.8 mg/m3 for CO. The odds ratios for HPI outpatient visits at the 95th percentile of NO2, SO2, and CO against the thresholds were 1.207 (1.120-1.302), 1.175 (1.052-1.312), and 1.110 (1.019-1.209), respectively. The associations were more evident in patients older than 45 years, females, with health insurance, and in cold seasons. Null associations of exposure to either ozone (O3) or particulate matter (PM) were observed. In summary, short-term exposure to NO2, SO2, and CO above certain concentrations, but not PM or O3, may trigger the increased risk of outpatient visits due to HP infection in Chinese population.

The long non-coding RNA PANDAR regulates cell proliferation and epithelial-to-mesenchymal transition in glioma.

Glioma is one of the most aggressive intracranial tumors in the central nervous system. The long non-coding RNA P21 associated ncRNA DNA damage activated (PANDAR) has been reported to be an oncogene or tumor suppressor in several cancers. However, the prognostic value and biological function of PANDAR in glioma have not been described. Here, we report that expression of PANDAR is significantly up-regulated in glioma tissues and cell lines. PANDAR expression was correlated with tumor size (p=0.044) and World Health Organization (WHO) grades (p=0.005), as shown by chi-squared test. Moreover, significant upregulation of PANDAR was found to correlate with poor prognosis in glioma, as shown using Kaplan-Meier method and Cox multivariate survival analysis. Furthermore, PANDAR knockdown suppressed cell proliferation, G1/S transition, migration and invasion, and promoted apoptosis in glioma cell lines (U251 and U87). PANDAR knockdown decreased expression of CDK4, Bcl-2, N-cadherin and Vimentin, but increased E-cadherin expression in glioma cells. In conclusion, our data suggest PANDAR as a potential prognostic biomarker and therapeutic candidate for glioma.

Mechanistic insights into the health benefits of fish-oil supplementation against fine particulate matter air pollution: a randomized controlled trial.

BACKGROUND: Dietary fish-oil supplementation might attenuate the associations between fine particulate matter (PM2.5) and subclinical biomarkers. However, the molecular mechanisms remain to be elucidated. This study aimed to explore the molecular mechanisms of fish-oil supplementation against the PM2.5-induced health effects. METHODS: We conducted a randomized, double-blinded, and placebo-controlled trial among healthy college students in Shanghai, China, from September 2017 to January 2018. A total of 70 participants from the Fenglin campus of Fudan University were included. We randomly assigned participants to either supplementation of 2.5-gram fish oil (n = 35) or sunflower-seed oil (placebo) (n = 35) per day and conducted four rounds of health measurements in the last two months of the trial. As a post hoc exploratory study, the present untargeted metabolomics analysis used remaining blood samples collected in the previous trial and applied a Metabolome-Wide Association Study framework to compare the effects of PM2.5 on the metabolic profile between the sunflower-seed oil and fish oil groups. RESULTS: A total of 65 participants completed the trial (34 of the fish oil group and 31 of the sunflower-seed oil group). On average, ambient PM2.5 concentration on the day of health measurements was 34.9 µg/m3 in the sunflower-seed oil group and 34.5 µg/m3 in the fish oil group, respectively. A total of 3833 metabolites were significantly associated with PM2.5 in the sunflower-seed oil group and 1757 in the fish oil group. Of these, 1752 metabolites showed significant between-group differences. The identified differential metabolites included arachidonic acid derivatives, omega-3 fatty acids, omega-6 fatty acids, and omega-9 fatty acids that were related to unsaturated fatty acid metabolism, which plays a role in the inflammatory responses. CONCLUSION: This trial suggests fish-oil supplementation could mitigate the PM2.5-induced inflammatory responses via modulating fatty acid metabolism, providing biological plausibility for the health benefits of fish-oil supplementation against PM2.5 exposure. TRIAL REGISTRATION: This study is registered at ClinicalTrails.gov (NCT03255187).

Acute cardiorespiratory response to air quality index in healthy young adults.

BACKGROUND: Little is known about the acute health impacts of air quality index (AQI) on cardiorespiratory risk factors. OBJECTIVES: To assess the short-term links of AQI with cardiorespiratory risk factors in young healthy adults. METHODS: We performed a longitudinal panel study with 4 repeated visits in 40 healthy young adults in Hefei, Anhui Province, China from August to October 2021. Cardiorespiratory factors included systolic blood pressure (BP), diastolic BP (DBP), mean arterial pressure (MAP) and fractional exhaled nitric oxide (FeNO). We collected hourly AQI data from a nearby air quality monitoring site. Linear mixed-effects model was applied to assess the effects of AQI on BP and FeNO. RESULTS: The study participants (75.0% females) provided 160 pairs of valid health measurements with average age of 24 years. The mean AQI level was 44.43 during the study period. There were significant positive associations of AQI with three BP parameters and FeNO at different lag periods. For example, an interquartile range increase in AQI (26.54 unit) over lag 0-24 h was associated with increments of 6.69 mmHg (95%CI: 2.95-10.44), 5.71 mmHg (95%CI: 3.30-8.13), 6.04 mmHg (95%CI: 3.46-8.62) and 5.67% (95%CI: 1.05%-16.05%) in SBP, DBP, MAP and FeNO, respectively. The results were robust after controlling for PM1. We did not find effect modifications by gender, BMI, physical activity, or AQI category level on the associations. CONCLUSIONS: The current findings on associations of AQI with cardiorespiratory factors might add evidence of the acute adverse cardiorespiratory consequences following air pollution.

Short-term effects of personal exposure to temperature variability on cardiorespiratory health based on subclinical non-invasive biomarkers.

Growing literatures have explored the cardiorespiratory health effects of the daily temperature, but such effects of temperature variability remain unclear. We investigated the acute associations of personal levels of temperature variability with cardiorespiratory biomarkers. This is a panel study with four repeated measurements among forty eligible college students in Hefei, Anhui Province, China. We collected personal-level temperature data using temperature/humidity data loggers. Temperature variability parameters included diurnal temperature range (DTR), the standard-deviation of temperature (SDT) and temperature variability (TV). Cardiorespiratory health indicators included three BP parameters [systolic BP (SBP), diastolic BP (DBP) and mean article pressure (MAP)], fractional exhaled nitric oxide (FeNO), and four saliva biomarkers [C-reactive protein (CRP), cortisol, alpha-amylase and lysozyme]. Linear mixed-effect models were then used to assess the associations of temperature variability with these cardiorespiratory biomarkers. We found that short-term exposure to the three temperature variability parameters was associated with these cardiorespiratory biomarkers. The magnitude, direction and significance of these associations varied by temperature variability parameters, by biomarkers and by lags of exposure. Specifically, temperature variability parameters were inversely associated with BP and saliva lysozyme; positively associated with airway inflammation biomarkers (FeNO and saliva CRP) and stress response biomarkers (saliva cortisol and alpha-amylase). The results were robust to further control for air pollutants, and these associations were more prominent in females and in subjects with abnormal body mass index. Our findings suggested that acute exposure to temperature variability could significantly alter cardiorespiratory biomarker profiles among healthy young adults in China.

Fine particulate matter, airway inflammation, stress response, non-specific immune function and buccal microbial diversity in young adults.

Fine particulate matter (PM2.5) has been associated with risk of oral and respiratory diseases. However, the biological mechanisms of adverse oral and respiratory health response to PM2.5 fluctuation have not been well characterized. This study aims to explore the relationships of PM2.5 with airway inflammation, salivary biomarkers and buccal mucosa microbiota. We performed a panel study among 40 college students involving 4 follow-ups from August to October 2021 in Hefei, Anhui Province, China. Health outcomes included fractional exhaled nitric oxide (FeNO), salivary biomarkers [C-reactive protein (CRP), cortisol, lysozyme and alpha-amylase] and buccal mucosa microbial diversity. Linear mixed-effect models were applied to explore the cumulative impacts of PM2.5 on health indicators. PM2.5 was positively correlated with FeNO, CRP, cortisol and alpha-amylase, while negatively with lysozyme. Per 10-µg/m3 increase in PM2.5 was linked to maximum increments in FeNO of 10.71% (95%CI: 2.01%, 19.41%) at lag 0-24 h, in CRP of 7.10% (95%CI: 5.39%, 8.81%) at lag 0-24 h, in cortisol of 1.25% (95%CI: 0.44%, 2.07%) at lag 0-48 h, and in alpha-amylase of 2.12% (95%CI: 0.53%, 3.71%) at lag 0-24 h, while associated with maximum decrement in lysozyme of 0.53% (95%CI: 0.12%, 0.95%) at lag 0-72 h. Increased PM2.5 was linked to reduction in the richness and evenness of buccal microbe and o_Bacillales and o_Bacteroidales were identified as differential microbes after PM2.5 inhalation. Bio-information analysis indicated that immunity system pathway was the most important enriched abundant process altered by PM2.5 exposure. In summary, short-term PM2.5 exposure may impair oral and respiratory health by inducing inflammatory and stress responses, weakening immune function and altering buccal mucosa microbial diversity.

Combined oxidant capacity, redox-weighted oxidant capacity and elevated blood pressure: A panel study.

BACKGROUND: Evidence is limited on the potential health effects of Ox (sum value) and Oxwt(weighted value), the two surrogates for ozone (O3) and nitrogen dioxides (NO2). OBJECTIVES: To investigate the impacts of Ox and redox-weighted oxidant capacity (Oxwt) on blood pressure (BP). METHODS: A panel study was conducted with four repeated follow-up visits among 40 healthy college students in Hefei, Anhui Province, China from August to October, 2021. We measured BP by using an automated sphygmomanometer and obtained hourly data of air pollutants at a nearby site. The sum of O3 and NO2 (Ox) and their weighted average (Oxwt) were obtained as exposure variables. We applied linear mixed-effect models to evaluate the effects of Ox and Oxwton systolic BP (SBP), diastolic BP (DBP), mean arterial pressure (MAP) and pulse pressure (PP). RESULTS: Totally, 160 pairs of valid BP values were obtained. The 24-h mean levels of Ox and Oxwt were 64.38 µg/m3 and 110.28 µg/m3, respectively. Overall, both Ox and Oxwt were significantly linked with SBP, DBP and MAP at most lag periods, whereas non-significant with PP. A 10-µg/m3 increase in Oxwt at lag 0-24 h was linked to increases of 2.43 mmHg (95% CI: 0.96, 3.91) in SBP, 2.31 mmHg (95% CI: 1.37, 3.26) in DBP and 2.35 mmHg (95% CI: 1.35, 3.36) in MAP, while the corresponding effect estimates for Ox were 1.51 mmHg (95%CI: 0.60, 2.43), 1.43 mmHg (95% CI: 0.85, 2.02) and 1.46 mmHg (95%CI: 0.83, 2.09). In two-pollutant models, our results were almost unchanged after controlling for simultaneous exposure to other pollutants. The effects were more pronounced among males and those with physical activity. CONCLUSIONS: The findings provide first-hand evidence that short-term exposure to Ox and Oxwt was associated with BP increases in young adults.

Short-term ambient air pollution exposure and adult primary insomnia outpatient visits in Chongqing, China: A time-series analysis.

Growing evidence suggest that air pollutants can be associated with sleep disorders. However, no study has explored the association of short-term air pollution exposure with primary insomnia, a specific type of sleep disorders. To evaluate the correlation of short-term air pollution exposure with adult primary insomnia outpatient visits in Chongqing, China, we collected data of adult primary insomnia outpatient visits and air pollutants' concentrations between 2013 and 2019 and the associations were estimated with single-day lags as well as moving average lags using a generalized additive model. Totally, 23,919 outpatient visits for adult primary insomnia were identified. The daily data of adult insomnia outpatient visits, air pollutants (NO2, CO, SO2, O3, PM10 and PM2.5) and meteorological conditions (daily mean temperature and relative humidity) were gathered. Short-term exposure to multiple air pollutants, especially NO2 and SO2, was associated with adult primary insomnia visits. A 10 µg/m3 increase in NO2 and SO2 at lag 05 corresponded to increased primary insomnia outpatient visits 3.87% (95% CI: 1.50%-6.24%) and 7.22% (95% CI: 2.10%-12.35%), respectively. Moreover, stronger links were presented in females and cool seasons for NO2 while in the elderly for SO2. Collectively, this time-series study suggested that short-term exposure to air pollutants, especially to NO2 and SO2, was associated with higher risk of adult primary insomnia outpatient visits, and such association could to be sex-, age-, and season-modified.

Paternal exposure to microcystin-LR induces fetal growth restriction partially through inhibiting cell proliferation and vascular development in placental labyrinth.

Microcystin-leucine arginine (MC-LR) has reproductive and developmental toxicities. Previous studies indicated that gestational exposure to MC-LR induced fetal growth restriction in mice. The aim of this study was to further evaluate the effect of paternal MC-LR exposure before mating on fetal development. Male mice were intraperitoneally injected with either normal saline or MC-LR (10 µg/kg) daily for 35 days. Male mouse was then mated with female mice with 1:1 ratio. There was no significant difference on the rates of mating and pregnancy between MC-LR-exposed male mice and controls. Body weight and crown-rump length were reduced in fetuses whose fathers were exposed to MC-LR. Despite no difference on relative thickness of labyrinthine layer, cell proliferation, as measured by Ki67 immunostaining, was reduced in labyrinth layer of MC-LR-exposed mice. Moreover, blood sinusoid area in labyrinth layer was decreased in the fetus whose father was exposed to MC-LR before mating. Correspondingly, cross-sectional area of CD34-positive blood vessel in labyrinth layer was lower in fetuses whose fathers were exposed to MC-LR than in controls. These results provide evidence that paternal MC-LR exposure before mating induces fetal growth restriction partially through inhibiting cell proliferation and vascular development in labyrinth layer.

Long-term 1-nitropyrene exposure induces endoplasmic reticulum stress and inhibits steroidogenesis in mice testes.

1-Nitropyrene (1-NP) is a representative nitro-polycyclic aromatic hydrocarbon from diesel exhaust. Recently, we found that maternal 1-NP exposure caused fetal growth retardation and disturbed cognitive development in adolescent female offspring. To investigate long-term 1-NP exposure on spermatogenesis and steroidogenesis, male mice were exposed to 1-NP (1.0 mg/kg/day) by gavage for 70 days. There was no significant difference on relative testicular weight, number of testicular apoptotic cells and epididymal sperm count between 1-NP-exposed mice and controls. Although long-term 1-NP exposure did not influence number of Leydig cells, steroidogenic genes and enzymes, including STAR, P450scc, P45017α and 17ß-HD, were downregulated in 1-NP-expoed mouse testes. Correspondingly, serum and testicular testosterone (T) levels were reduced in 1-NP-exposed mice. Additional experiment showed that testicular GRP78 mRNA and protein were upregulated by 1-NP. Testicular phospho-IRE1α and sliced xbp-1 mRNA, a downstream molecule of IRE1α, were elevated in 1-NP-exposed mice. Testicular phospho-PERK and phospho-eIF2α, a downstream molecule of PERK pathway, were increased in 1-NP-exposed mice. Testicular NOX4, a subunit of NAPDH oxidase, and HO-1, MDA, two oxidative stress markers, were increased in 1-NP-exposed mice. Testicular GSH and GSH/GSSG were decreased in 1-NP-exposed mice. These results suggest that long-term 1-NP exposure induces reactive oxygen species-evoked ER stress and disrupts steroidogenesis in mouse testes.

Alleviated systemic oxidative stress effects of combined atmospheric oxidant capacity by fish oil supplementation: A randomized, double-blinded, placebo-controlled trial.

BACKGROUND: Combined atmospheric oxidant capacity (Ox), represented by the sum of nitrogen dioxide (NO2) and ozone (O3), is an important hazardous property of outdoor air pollution mixture. It remains unknown whether its adverse effects can be ameliorated by dietary fish-oil supplementation. OBJECTIVE: To assess the effects of fish-oil supplementation against oxidative stress induced by acute Ox exposure. METHODS: We conducted a randomized, double-blinded and placebo-controlled study among 65 young adults in Shanghai, China between September 2017 and January 2018. We randomly assigned participants to receive either 2.5 g/day of fish oil or placebo, and conducted four repeated physical examinations during the last two months of treatments. Ox concentrations were calculated as the sum of hourly measurements of NO2 and O3. We measured six biomarkers on systemic oxidative stress and antioxidant activity. Linear mixed-effect models were used to assess the short-term effects of Ox on biomarkers in each group. RESULTS: During our study period, the 72-h average Ox concentration was 93.6 µg/m3. Short-term exposure to Ox led to weaker changes in all biomarkers in the fish oil group than in the placebo group. Compared with the placebo group, for a 10-µg/m3 increase in Ox, there were smaller decrements in myeloperoxidase (MPO, difference = 5.92%, lag = 0-2 d, p = 0.03) and malondialdehyde (MDA, difference = 5.00%, lag = 1 d, p = 0.04) in the fish-oil group; there were also larger increments in total antioxidant capacity (TAC, difference = 16.33%, lag = 2 d, p = 0.02) and in glutathione peroxidase (GSH-Px, difference = 8.89%, lag = 0-2 d, p = 0.03) in the fish-oil group. The estimated differences for MPO were robust to adjustment for all co-pollutants and the differences for other biomarkers remained for some co-pollutants. CONCLUSIONS: This trial provides first-hand evidence that dietary fish-oil supplementation may alleviate the systemic oxidative stress induced by Ox.

Effects of filtered fresh air ventilation on classroom indoor air and biomarkers in saliva and nasal samples: A randomized crossover intervention study in preschool children.

To evaluate the short-term effects of filtered fresh air ventilation system on classroom indoor air and biomarkers in saliva and nasal samples in preschool children, a randomized crossover study was conducted in a kindergarten in Shanghai, China in 2016. Two classrooms at the same grade (n = 43) were selected and fresh air ventilation systems (FAVS) with high efficiency particulate air filter (HEPA) were installed. In the first week, FAVS-HEPA was run in one classroom for 2 continuous school days and the other classroom was remained as usual with no use of FAVS-HEPA. After one week of wash-out, the ventilation modes exchanged between two classrooms and another 2 days of intervention were repeated. Real-time indoor and outdoor air pollution and climate factors (PM2.5, Temp and relative humidity (R.H.)) were measured. Saliva and nasal internal mucosa samples were collected immediately at the end of each intervention scenario. Linear mixed-effect regression model was applied to evaluate the effects of intervention on children's health indicators controlling for age, gender, height, BMI and temperature. The results showed, with FAVS-HEPA, the classroom indoor fine particulate matter (PM2.5)(29.1 ±â€¯17.9 µg/m3) was on average significantly lower than that without FAVS-HEPA (85.7 ±â€¯43.2 µg/m3). By regression analysis, each 10 µg/m3 decrease of indoor PM2.5 during the 8 school hours in the first intervention day was associated with an average of 1.76% (95% confidence interval (CI) 0.43-3.08%) increase in saliva lysozyme. This percentage increased to 2.41% (95%CI 0.52-4.26%) if related to the PM2.5 level in 16 school hours over 2 days of intervention. A total of 19 nasal bacterial taxa were lower in subjects exposed to FAVS-HEPA, compared to that with no use of FAVS-HEPA, despite the general bacteria diversity levels in nasal samples were not statistically different. Among others, Providencia species showed significant effects in mediating the associations between higher PM2.5 and lower lysozyme. In conclusion, using FAVS-HEPA was effective in decreasing the classroom indoor PM2.5. Saliva lysozyme, as a non-specific immune biomarker, was significantly inversely associated with indoor PM2.5. Certain nasal bacteria might play key roles in mediating PM2.5 exposure and children's lysozyme levels.

Effects of personal nitrogen dioxide exposure on airway inflammation and lung function.

BACKGROUND: Few epidemiological studies have evaluated the respiratory effects of personal exposure to nitrogen dioxide (NO2), a major traffic-related air pollutant. The biological pathway for these effects remains unknown. OBJECTIVES: To evaluate the short-term effects of personal NO2 exposure on lung function, fractional exhaled nitric oxide (FeNO) and DNA methylation of genes involved. METHODS: We conducted a longitudinal panel study among 40 college students with four repeated measurements in Shanghai from May to October in 2016. We measured DNA methylation of the key encoding genes of inducible nitric oxide synthase (NOS2A) and arginase (ARG2). We applied linear mixed-effect models to assess the effects of NO2 on respiratory outcomes. RESULTS: Personal exposure to NO2 was 27.39 ±â€¯23.20 ppb on average. In response to a 10-ppb increase in NO2 exposure, NOS2A methylation (%5 mC) decreased 0.19 at lag 0 d, ARG2 methylation (%5 mC) increased 0.21 and FeNO levels increased 2.82% at lag 1 d; and at lag 2 d the percentage of forced vital capacity, forced expiratory volume in 1 s and peak expiratory flow in predicted values decreased 0.12, 0.37 and 0.67, respectively. The model performance was better compared with those estimated using fixed-site measurements. These effects were robust to the adjustment for co-pollutants and weather conditions. CONCLUSIONS: Our study suggests that short-term personal exposure to NO2 is associated with NOS2A hypomethylation, ARG2 hypermethylation, respiratory inflammation and lung function impairment. The use of personal measurements may better predict the respiratory effects of NO2.

Impact of short-term exposure to fine particulate matter air pollution on urinary metabolome: A randomized, double-blind, crossover trial.

BACKGROUND: Metabolomics is a novel tool to explore the biological mechanisms of the health effects of fine particulate matter (PM2.5) air pollution. Very few studies have examined the urinary metabolomic changes associated with PM2.5 exposure. OBJECTIVE: To assess the alternation in urine metabolomics in response to short-term PM2.5 exposure. METHODS: We conducted a randomized, double-blind, crossover trial of 9-day real or sham indoor air purification among 45 healthy college students in Shanghai, China. Urine samples were collected immediately at the end of each intervention stage and were analyzed for metabolomics using ultrahigh performance liquid chromatography-mass spectrometry. Orthogonal partial least square-discriminant analysis and linear mixed effect models were used to examine metabolomic changes between interventional scenarios and their associations with continuous PM2.5 exposure. RESULTS: The time-weighted average personal PM2.5 exposure in the real-purified scenario was 50% lower than in the sham-purified air scenario (28.3 µg/m3 VS 56.9 µg/m3). A total of 40 differentiated urinary metabolites at a false discovery rate <0.05 were identified for the effects of both intervention and continuous PM2.5 exposure, including 16 lipids, 5 purine metabolites, 2 neurotransmitters, and 3 coenzymes. CONCLUSIONS: This real-world randomized crossover trial demonstrated that short-term PM2.5 exposure could result in significant changes in urinary metabolomic profile, which may further lead to perturbation in energy metabolism, oxidative stress and inflammation.

Cardiovascular Benefits of Fish-Oil Supplementation Against Fine Particulate Air Pollution in China.

BACKGROUND: Few studies have evaluated the health benefits of omega-3 fatty acid supplementation against fine particulate matter (aerodynamic diameter <2.5 µm [PM2.5]) exposure in highly polluted areas. OBJECTIVES: The authors sought to evaluate whether dietary fish-oil supplementation protects cardiovascular health against PM2.5 exposure in China. METHODS: This is a randomized, double-blinded, and placebo-controlled trial among 65 healthy college students in Shanghai, China. Participants were randomly assigned to either the placebo group or the intervention group with dietary fish-oil supplementation of 2.5 g/day from September 2017 to January 2018, and received 4 rounds of health examinations in the last 2 months of treatments. Fixed-site PM2.5 concentrations on campus were measured in real time. The authors measured blood pressure and 18 biomarkers of systematic inflammation, coagulation, endothelial function, oxidative stress, antioxidant activity, cardiometabolism, and neuroendocrine stress response. Acute effects of PM2.5 on these outcomes were evaluated within each group using linear mixed-effect models. RESULTS: The average PM2.5 level was 38 µg/m3 during the study period. Compared with the placebo group, the fish-oil group showed relatively stable levels of most biomarkers in response to changes in PM2.5 exposure. Between-group differences associated with PM2.5 exposure varied by biomarkers and by lags of exposure. The authors observed beneficial effects of fish-oil supplementation on 5 biomarkers of blood inflammation, coagulation, endothelial function, oxidative stress, and neuroendocrine stress response in the fish-oil group at a false discovery rate of <0.05. CONCLUSIONS: This trial shows that omega-3 fatty acid supplementation is associated with short-term subclinical cardiovascular benefits against PM2.5 exposure among healthy young adults in China. (Effect of Dietary Supplemental Fish Oil in Alleviating Health Hazards Associated With Air Pollution; NCT03255187).

Household renovation before and during pregnancy in relation to preterm birth and low birthweight in China.

From October 2010 to April 2012, we conducted a cross-sectional study of associations between household environments and childhood health among preschool children in eight Chinese cities. Here, we analyze associations of early household renovation with preterm birth (PTB), low birthweight (LBW), term low birthweight (Term-LBW), and small for gestational age (SGA). Parents responded to questions about household renovation and their children's gestational age and birthweight. In the multivariate logistic regression analyses, household renovation in the year before pregnancy was significantly associated with LBW (sample size: N = 25 813; adjusted odds ratio (OR) with 95% confidence intervals (CIs): 1.23, 1.01-1.50) and Term-LBW (N = 24 823; 1.29, 1.01-1.67). Household renovation during pregnancy was significantly associated with PTB (N = 25 202; 1.28, 1.01-1.69). These significant associations were also found in the two-level (city-child) logistic regression analyses and in the sensitivity analyses among 21 009 children with complete data in all studied variates. Stronger associations were found in certain subgroups. Our findings indicate that household renovation within one year before pregnancy might be a risk factor for LBW and Term-LBW, while household renovation during pregnancy could be a risk factor for PTB.

Associations between ambient temperature and daily hospital admissions for rheumatic heart disease in Shanghai, China.

Rheumatic heart disease (RHD) remains a serious public health burden in developing countries. We conducted a time-series study to explore the association between ambient temperature and daily hospital admissions for RHD in Shanghai, China. We collected data on daily hospital admissions for RHD from 2013 to 2015 from the database of Shanghai Health Insurance System. We applied the generalized additive models together with the distributed lag nonlinear model to estimate the association between temperature and RHD hospital admissions after controlling for relative humidity, time trend, day of the week, and holidays. Stratification analyses by age and gender were performed to evaluate their potential effect modification. A total of 4178 cases of RHD hospitalizations were identified over the study period. There were almost linear, positive, and significant associations between daily mean temperature and RHD hospital admissions with higher risks at hotter days. Compared to reference temperature (0 °C), the cumulative risks of moderate heat (the 90th percentile of temperature, 28.0 °C) and extreme heat (the 99th percentile of temperature, 33.5 °C) over lags 0-5 days were 2.55 (95% confidence interval 1.14, 5.73) and 3.22 (95% confidence interval 1.36, 7.61), respectively. These associations were significantly stronger in older people than in younger people. This study indicated larger risks of RHD hospital admissions associated with higher temperature, especially in older people. Our findings provided first-hand epidemiological evidence regarding the effects of ambient temperature on RHD incidence.

Urinary phthalate metabolites in relation to childhood asthmatic and allergic symptoms in Shanghai.

BACKGROUND: Few studies can be found on phthalate exposure in relation to childhood asthma and allergic symptoms from Mainland China, where a persistent increase in prevalence of childhood asthma and allergic disease has been observed. OBJECTIVES: This study aimed to assess the exposure levels to phthalates and its relationship with asthmatic and allergic symptoms among children in Shanghai, which has the highest prevalence of childhood asthma in Mainland China. METHODS: A follow-up study (2013-2014) of 434 children aged 5-10 years was conducted, based on the China, Children, Homes, Health (CCHH) study (2011-2012) in Shanghai, China. Information on asthmatic and allergic symptoms (wheeze, rhinitis, and eczema) were collected using validated questionnaires. Ten phthalate metabolites in morning urine samples were analyzed by high-performance liquid chromatography with triple quadrupole tandem mass spectrometry (HPLC-MS/MS). Multivariable logistic regression was used to estimate the associations between symptoms and urinary phthalate metabolites controlling for demographics, family history of allergic diseases and other covariates. RESULTS: Nine out of 10 phthalate metabolites were detected in all subjects (average detection rate of 93.2%). By multivariable logistic regression analyses, the 4th quartile of Mono­n­butyl phthalate (MnBP) (reference: 1st quartile) had adjusted prevalence odds ratios (aPORS) and 95% confidence intervals (95%CIs) of 2.27(1.06-4.88), 2.14(1.02-4.46) and 2.98(1.19-7.50) for wheeze, rhinitis and eczema, respectively, while those of Mono­isobutyl phthalate (MiBP) were 2.23(1.08-4.62) and 2.96(1.02-8.60) for rhinitis and eczema, respectively. The highest quartile of mono­2­ethyl­5­hydroxyhexyl phthalate(MEHHP) and mono­2­ethyl­5­oxohexyl phthalate(MEOHP) had aPORS and 95%CIs of 3.10(1.10-8.74) and 2.63(1.02-6.80) for eczema, respectively. By summing up the 4 low molecular weight metabolites (∑4LMWP) and all 9 metabolites (∑9Total), the highest quartiles of ∑4LMWP and∑9Total were significantly associated with all symptoms. In most of the above associations, a significantly increasing trend from the 1st to the 4th quartile was observed. Subjects with 2 or 3 concomitant symptoms (reference: no symptoms) had significant positive associations with a higher level (the 4th quartile) of phthalate metabolites. CONCLUSIONS: Low MW metabolites such as MnBP and MiBP, high MW DEHP and the total amount of phthalate metabolites might have adverse health effects on asthma and allergic symptoms in Chinese children.