Respiratory Toxicology of Graphene-Based Nanomaterials: A Review.

Graphene-based nanomaterials (GBNs) consist of a single or few layers of graphene sheets or modified graphene including pristine graphene, graphene nanosheets (GNS), graphene oxide (GO), reduced graphene oxide (rGO), as well as graphene modified with various functional groups or chemicals (e.g., hydroxyl, carboxyl, and polyethylene glycol), which are frequently used in industrial and biomedical applications owing to their exceptional physicochemical properties. Given the widespread production and extensive application of GBNs, they can be disseminated in a wide range of environmental mediums, such as air, water, food, and soil. GBNs can enter the human body through various routes such as inhalation, ingestion, dermal penetration, injection, and implantation in biomedical applications, and the majority of GBNs tend to accumulate in the respiratory system. GBNs inhaled and substantially deposited in the human respiratory tract may impair lung defenses and clearance, resulting in the formation of granulomas and pulmonary fibrosis. However, the specific toxicity of the respiratory system caused by different GBNs, their influencing factors, and the underlying mechanisms remain relatively scarce. This review summarizes recent advances in the exposure, metabolism, toxicity and potential mechanisms, current limitations, and future perspectives of various GBNs in the respiratory system.

Differential expression profile of microRNAs in the lung tissues of coal workers with pneumoconiosis and patients with silicosis.

The purpose of this study was to characterize the microRNA (miRNA) profile of the lung tissues from coal workers' pneumoconiosis (CWP) and silicosis and to analyze the changes in downstream genes, biological processes, and signaling pathways based on the differently expressed miRNAs. Lung tissues from three CWP patients, eight silicosis patients, and four healthy controls were collected and analyzed for their miRNA profiles using Affymetrix® GeneChip® miRNA Arrays. Differentially expressed miRNAs (DEMs) were identified between the different groups. The miRanda and TargetScan databases were used to predict the putative target genes, and volcano and heat maps were drawn. Gene ontology (GO) and Kyoto encyclopedia of genes and genomes (KEGG) pathway enrichment analyses were then performed to screen the DEMs-associated biological process and signaling pathways, respectively. Further identification with a comprehensive literature research involving particle exposure, fibrosis, inflammation and lung cancer were used to further screen DEMs of CWP and silicosis. Microarray data showed that 375 and 88 miRNAs were differentially expressed in CWP and silicosis lung tissues compared with healthy lung tissues, while 34 miRNAs were differentially expressed in CWP compared with silicosis lung tissues. The GO and KEGG pathway analyses showed that, the target genes were mainly enriched in the TGF-ß, MAPK, p53 and other signal pathways. These results provided insight into the miRNA-related underlying mechanisms of CWP and silicosis, and they provided new clues for miRNAs as biomarkers for the diagnosis and differential diagnosis of these two diseases.

Characteristics of Diagnosed and Death Cases of Pneumoconiosis in Hubei Province, China, 1949-2019.

OBJECTIVE: This study aims to summarize the characteristics of diagnosed pneumoconiosis and pneumoconiosis death in the Hubei Province of China, between the years 1949 and 2019, and provide clues for the scientific prevention of pneumoconiosis. METHODS: We recruited 23,069 pneumoconiosis cases in Hubei Province, China, from 1949 to 2019. Basic information and occupational surveillance information were obtained from the Hubei Occupational Diseases and Health Risk Factors Information Surveillance System. RESULTS: The annually diagnosed pneumoconiosis cases showed an overall increasing trend from 1949 to 2019 in Hubei Province. The major types of pneumoconiosis were coal workers' pneumoconiosis (CWP, 49.91%) and silicosis (43.39%). Pneumoconiosis cases were mainly engaged in mining (75.32%) and manufacturing (12.72%), and were distributed in Huangshi (35.48%), Yichang (16.16%), and Jingzhou (7.97%). CWP (47.50%) and silicosis (44.65%) accounted for most of the deaths. CONCLUSIONS: The number of pneumoconiosis cases and deaths in Hubei increased in the period of 1949 to 2019. Silicosis and CWP contributed to the predominant types of pneumoconiosis. Prevention and control measures should continue to be taken to reduce the morbidity and mortality of pneumoconiosis.

Association between short-term exposure to ambient air pollution and dementia mortality in Chinese adults.

BACKGROUND: Short-term exposure to ambient air pollution has been linked to an increased risk of mortality from a variety of causes, but its effects on mortality from dementia remain largely unknown. OBJECTIVES: To investigate the association between short-term exposure to ambient air pollution and dementia mortality, and quantitatively assess the excess mortality. METHODS: In this time-stratified case-crossover study, 47,108 dementia deaths were identified in Jiangsu province, China during 2015-2019. Exposure to particulate matter with an aerodynamic diameter ≤ 2.5 µm (PM2.5), PM10, sulfur dioxide (SO2), nitrogen dioxide (NO2), carbon monoxide (CO), and ozone (O3) was assessed by extracting daily concentrations from a validated grid dataset based on each subject's residential address. Conditional logistic regression models were applied for exposure-response analyses. RESULTS: There were 47,108 case days and 159,852 control days during the study period. Each 10 µg/m3 increase of lag 04-day exposure to PM2.5, PM10, and NO2 was significantly associated with a 1.43 % (95 % CI: 0.77, 2.09 %), 1.06 % (0.59, 1.54 %), and 2.80 % (1.51, 4.10 %) increase in odds of dementia mortality, corresponding to an excess mortality of 4.87 %, 5.50 %, and 6.43 %, respectively. We estimated that reducing ambient air pollutant exposures to the WHO air quality guidelines would avoid up to 4.17 % of the dementia deaths, while the ambient air quality standards in China would only help avoid up to 0.39 %. CONCLUSIONS: This study provides consistent evidence that short-term exposure to PM2.5, PM10, and NO2 is associated with increased odds of dementia mortality, which can be translated to a considerable excess mortality. Our findings highlight a potential approach to prevent deaths from dementia by reducing individual exposures to ambient air pollution, especially in areas with high levels of ambient air pollution.

Short-Term Effects of Low-Level Ambient Air NO2 on the Risk of Incident Stroke in Enshi City, China.

Previous studies found that exposure to ambient nitrogen dioxide (NO2) was associated with an increased risk of incident stroke, but few studies have been conducted for relatively low NO2 pollution areas. In this study, the short-term effects of NO2 on the risk of incident stroke in a relatively low-pollution area, Enshi city of Hubei Province, China, were investigated through time-series analysis. Daily air-pollution data, meteorological data, and stroke incidence data of residents in Enshi city from 1 January 2015 to 31 December 2018 were collected. A time-series analysis using a generalised additive model (GAM) based on Poisson distribution was applied to explore the short-term effects of low-level NO2 exposure on the risk of incident stroke and stroke subtypes, as well as possible age, sex, and seasonal differences behind the effects. In the GAM model, potential confounding factors, such as public holidays, day of the week, long-term trends, and meteorological factors (temperature and relative humidity), were controlled. A total of 9122 stroke incident cases were included during the study period. We found that NO2 had statistically significant effects on the incidence of stroke and ischemic stroke, estimated by excess risk (ER) of 0.37% (95% CI: 0.04-0.70%) and 0.58% (95% CI: 0.18-0.98%), respectively. For the cumulative lag effects, the NO2 still had a statistically significant effect on incident ischemic stroke, estimated by ER of 0.61% (95% CI: 0.01-1.21%). The two-pollutant model showed that the effects of NO2 on incident total stroke were still statistically significant after adjusting for other air pollutants (PM2.5, PM10, SO2, CO, and O3). In addition, the effects of NO2 exposure on incident stroke were statistically significant in elderly (ER = 0.75%; 95% CI: 0.11-1.40%), males (ER = 0.47%; 95% CI: 0.05-0.89%) and cold season (ER = 0.83%; 95% CI: 0.15-1.51%) subgroups. Our study showed that, as commonly observed in high-pollution areas, short-term exposure to low-level NO2 was associated with an increased risk of incident stroke, including ischemic stroke. Males and elderly people were more vulnerable to the effects of NO2, and the adverse effects might be promoted in the cold season.

Association of body mass index with serum anti-Müllerian hormone and inhibin B levels among 8323 women attending a reproductive medical center: a cross-sectional study.

PURPOSE: To assess the association of body mass index (BMI) with serum anti-Müllerian hormone (AMH) and inhibin B (InB) levels among women attending a reproductive medical center. METHODS: We conducted a cross-sectional study of 8323 women (96.4% were Han race) without polycystic ovary syndrome (PCOS) from the reproductive medical center of Tongji Hospital in Wuhan, China for assisted reproductive technology treatment between January 2016 and May 2018. For each participant, BMI and levels of serum AMH and InB were measured at entry by trained clinical technicians. Multivariate linear regression models were used to quantitatively estimate the associations of continuous and categorical BMI with serum AMH and InB levels. RESULTS: Each 1 kg/m2 increase in BMI was significantly associated with a 1.02% (95% CI: 0.40, 1.65%) and 3.59% (3.11, 4.06%) reduction in AMH and InB levels, respectively. No departure from linearity was observed for either AMH or InB (both P for nonlinear trend >0.05). Overweight and obesity were significantly associated with a 6.01% (0.70, 11.04%) and 18.64% (2.29, 32.26%) reduction in AMH level, and were significantly associated with a 18.80% (15.23, 22.23%) and a 35.44% (25.47, 44.08%) reduction in InB level, respectively. In addition, the association between BMI and AMH level was significantly stronger among women ≥32 years. CONCLUSIONS: BMI was linearly and inversely associated with AMH and InB levels among women without PCOS. Both overweight and obesity were significantly associated with lower AMH and InB levels.

Blood volatile organic aromatic compounds concentrations across adulthood in relation to total and cause specific mortality: A prospective cohort study.

OBJECTIVE: We aimed to evaluate the relationship between blood volatile organic aromatic compounds (VOACs) across adulthood and mortality. METHODS: A total of 16,968 participants from the National health and Nutrition Examination Surveys (NHANES 1988-1994 and 1999-2014) were included in the present study. Cox proportional hazards models were used to explore the associations between VOACs and total or cause-specific mortality. RESULTS: A total of 1,282 deaths occurred among 16,968 participants with a median follow-up of 8.06 years. We observed significant positive dose-response relationship between VOACs including benzene, ethylbenzene, o-xylene, m-/p-xylene and BEX (the sum of benzene, ethylbenzene, m-/p-and o-xylene concentrations) and total mortality, the multiple adjusted hazard ratios (HRs) and 95% confidence intervals (CIs) were 1.24 (1.13, 1.36), 1.15 (1.04, 1.27), 1.10 (1.00, 1.23), 1.09 (1.01, 1.19) and 1.21 (1.08, 1.35), respectively. In addition, all VOACs significantly elevated risk of the mortality from cancer, and benzene was associated with risk of the mortality from heart disease and the HRs and 95% CIs was 1.39 (1.09-1.77). For non-smokers, benzene, ethylbenzene and BEX were associated with elevated risk of total mortality and the mortality from cancer, and benzene was associated with risk of the mortality from heart disease. CONCLUSIONS: Blood VOACs are associated with increased risks of total and specific-cause mortality, which are also observed among non-smokers.

The clinical study of CBCT imaging technology in the restoration of upper anterior teeth of the elderly.

OBJECTIVE: To evaluate and analyze the clinical effect of CBCT imaging technology on the restoration of upper anterior teeth of the elderly. METHODS: 36 elderly patients with upper anterior teeth loss in our hospital from January 2018 to January 2020 were selected for implant restoration. Patients were equally randomized into a curved tomographic restoration group (TR group) and a CBCT restoration group (CR group). Patients in the two groups underwent traditional implant restoration. Then we compared and analyzed the implant migration, the adjustment time of first wearing, and the success rate of axial gingival recession and restoration satisfaction of patients in the two groups. RESULTS: The neck offset and the root offset of the implants in the CR group was (0.77±0.15) mm and (0.83±0.17) mm, respectively, which were significantly lower than (1.25±0.27) mm and (1.73±0.29) mm in the TR group (t=6.593, t=11.359, all P<0.01). The initial wearing adjustment time of patients in the CR group [(8.73±1.94) min] was significantly less than (18.79±4.85) min in the TR group (t=8.171, P<0.01); the CR group had a significantly higher success rate of axial gingival recession as compared to the CR group (94.44% vs 61.11%, χ2=6.0857, P<0.05); The restoration satisfaction rate of patients in the CR group was 100%, which was significantly higher than 77.78% of the TR group (χ2=8.7429, P<0.05). CONCLUSION: The CBCT imaging technology has a significant clinical effect on the restoration of the upper anterior teeth of the elderly, which effectively reduces the deviation of implant placement, shorten the adjustment time of their initial wearing, and greatly improves the success rate of axial gingival recession, effectively guarantees the long-term stability and aesthetics of dental implant restoration, and significantly enhances the satisfaction of patients.

Short-Term Exposure to Ambient Air Pollution and Mortality From Myocardial Infarction.

BACKGROUND: Short-term exposure to ambient air pollution has been linked to occurrence of myocardial infarction (MI); however, only a limited number of studies investigated its association with death from MI, and the results remain inconsistent. OBJECTIVES: This study sought to investigate the association of short-term exposure to air pollution across a wide range of concentrations with MI mortality. METHODS: A time-stratified case-crossover study was conducted to investigate 151,608 MI death cases in Hubei province (China) from 2013 to 2018. Based on each case's home address, exposure to particulate matter with an aerodynamic diameter ≤2.5 µm (PM2.5), particulate matter with an aerodynamic diameter ≤10 µm (PM10), sulfur dioxide, nitrogen dioxide (NO2), carbon monoxide, and ozone on each of the case and control days was assessed as the inverse distance-weighted average concentration at neighboring air quality monitoring stations. Conditional logistic regression models were implemented to quantify exposure-response associations. RESULTS: Exposure to PM2.5, PM10, and NO2 (mean exposure on the same day of death and 1 day prior) was significantly associated with increased odds of MI mortality. The odds associated with PM2.5 and PM10 exposures increased steeply before a breakpoint (PM2.5, 33.3 µg/m3; PM10, 57.3 µg/m3) and flattened out at higher exposure levels, while the association for NO2 exposure was almost linear. Each 10-µg/m3 increase in exposure to PM2.5 (<33.3 µg/m3), PM10 (<57.3 µg/m3), and NO2 was significantly associated with a 4.14% (95% confidence interval [CI]: 1.25% to 7.12%), 2.67% (95% CI: 0.80% to 4.57%), and 1.46% (95% CI: 0.76% to 2.17%) increase in odds of MI mortality, respectively. The association between NO2 exposure and MI mortality was significantly stronger in older adults. CONCLUSIONS: Short-term exposure to PM2.5, PM10, and NO2 was associated with increased risk of MI mortality.

Sources of 24-h personal exposure to PM2.5-bound metals: results from a panel study in Wuhan, China.

Atmospheric PM2.5-bound metals have been widely addressed, but research on the exposure levels and sources of personal PM2.5-bound metals among urban community residents is limited. The aim of this study is to explore the exposure levels and sources of 24-h personal PM2.5-bound metals among community inhabitants in Wuhan, China. We conducted a penal study of 216 observations with measurements of 16 metals bounded to 24-h personal PM2.5 samples in April-May, 2014, 2017. Analyses of covariance were used to compare PM2.5-bound metal levels across different living habits and ambient conditions. Principal component analysis (PCA) with varimax rotation was performed to explore PM2.5-bound metal sources. Personal PM2.5-bound aluminum (Al) (113.41 ng/m3) showed the highest geometric mean (GM) concentration, followed by lead (Pb) (90.89 ng/m3), zinc (Zn) (67.71 ng/m3), and iron (Fe) (51.85 ng/m3). The elevated levels of PM2.5-bound Al, vanadium (V), manganese (Mn), arsenic (As), rubidium (Rb), cadmium (Cd), and thallium (Tl) were found in participants with cigarette smoke exposure, compared with those without. The concentrations of Rb and strontium (Sr) were positively associated with the time spent outdoors. The increased concentration of nickel (Ni) was found in individuals who spent > 30 min/day in traffic. The elevated levels of V, Mn, and cobalt (Co) were associated with a short distance from dwellings to the main road. The results of PCA showed that PM2.5-bound metals might come from five sources: As, selenium (Se), Rb, Cd, Tl, and Pb from cigarette smoke exposure; Al, V, Mn, Fe, and Sr from crustal dust; copper (Cu) and antimony (Sb) from industrial activities; Ni and Co from traffic emission; and Zn from coal combustion. The concentrations of PM2.5-bound metals in this study were at moderate levels. Cigarette smoke exposure, industrial activities, traffic emission, and coal combustion might be major anthropogenic sources of personal PM2.5-bound metal exposures in Wuhan, China.

Exogenous Clara cell protein 16 attenuates silica particles-induced inflammation in THP-1 macrophages by down-regulating NF-κB and caspase-1 activation.

Inhalation of silica particles leads to pulmonary inflammatory responses. Clara cell protein 16 (CC16) has been reported to played a protective role in inflammatory lung diseases. However, its role on silica particles-induced inflammation has not been fully clarified. In this study, THP-1 macrophages were exposed to 75 µg/cm2 silica particles with or without 2 µg/mL exogenous CC16 (recombinant CC16, rCC16) for 24 hr. The production of inflammatory cytokines, including interleukin (IL)-1ß, tumor necrosis factor (TNF)-α and IL-6, in the cell supernatants of different groups was detected through ELISA kits and real-time RT-PCR, respectively. The nuclear translocation of nuclear factor (NF)-κB, protein levels of pro-IL-1ß, the nucleotide-binding domain-like receptor protein 3 (NLRP3) and caspase-1 were evaluated via immunofluorescence or western blot. Results showed that, at 75 µg/cm2 silica particle concentration, the treatment of rCC16 significantly decreased IL-1ß, TNF-α and IL-6 protein release and mRNA levels in THP-1 macrophages. Compared to those only exposed to silica particles, THP-1 macrophages exposed to both silica particles and rCC16 showed significantly lower nuclear levels and higher cytosol levels of NF-κB p65, as well as lower co-localization coefficients through immunofluorescence. Additionally, the administration of rCC16 significantly attenuated the increase of pro-IL-1ß, NLRP3 and caspase-1 levels induced by silica particle exposure. Our results suggested that exogenous CC16 could inhibit silica particles-induced inflammation in THP-1 macrophages, mainly through suppressing NF-κB pathway and caspase-1 activation.

Different biological effects of PM2.5 from coal combustion, gasoline exhaust and urban ambient air relate to the PAH/metal compositions.

Few studies have compared the biological effects of PM2.5 from coal combustion, gasoline exhaust and urban ambient air, and the roles of polycyclic aromatic hydrocarbons (PAHs) and metals playing in the process remain unclear. In this study, PM2.5 samples from coal combustion, gasoline exhaust and urban ambient air were analyzed for 16 PAHs and 23 metals. Cytotoxic and inflammatory effects of different PM2.5 were evaluated on differentiated THP-1 and A549 cells, respectively. We found that the coal combustion PM2.5 samples induced stronger cytotoxic and inflammatory effects (p < 0.05). Pearson's correlation and principal component analysis showed that the PAHs containing four or more benzenoid rings and specific metals of cadmium, thallium, zinc and lead were positively related to the biological effects. Our results suggested that coal combustion PM2.5 might be a more serious health hazard. Specific PAHs and metals might be account for the PM2.5 induced biological effects.

Association of Exposure to Ambient Fine Particulate Matter Constituents With Semen Quality Among Men Attending a Fertility Center in China.

Ambient fine particulate matter (PM2.5) exposure has been linked to decreased semen quality, but the associations between PM2.5 constituent exposures and semen quality remain unknown. We enrolled 1081 men whose partners underwent assisted reproductive technology procedures in Wuhan, China in 2014-2015, and examined their semen quality. Daily average concentrations of PM2.5 constituents including 10 metals/metalloid elements and 4 water-soluble ions were continuously determined for 1 week per month at 2 fixed monitoring stations. Linear mixed models were used to examine the associations of exposures to PM2.5 and its constituents with semen quality. Each interquartile range (36.5 µg/m3) increase in PM2.5 exposure was significantly associated with 8.5% (95% CI: 2.3%, 14.4%) and 8.1% (95% CI: 0.7%, 15.0%) decrease in sperm concentration and total sperm number, respectively. Antimony, cadmium, lead, manganese, and nickel exposures were significantly associated with decreased sperm concentration, whereas manganese exposure was also significantly associated with decreased total motility. Nonsmokers were more susceptible to PM2.5 constituent exposures, especially for antimony and cadmium (all P for effect modification <0.05). These findings suggest that PM2.5 and certain constituents may adversely affect semen quality, especially sperm concentration, and provide new evidence to formulate pollution abatement strategies for male reproductive health.

Urinary polycyclic aromatic hydrocarbon metabolites and adult asthma: a case-control study.

Polycyclic aromatic hydrocarbons (PAHs) exposure was reported to be associated with childhood asthma. However, the quantitative relationship between PAHs exposure and adult asthma and possible inflammatory pathways are less clear. We aimed to investigate potential associations between urinary PAHs metabolites and adult asthma. We enrolled 507 adult asthma cases and 536 matched controls. The concentrations of 12 urinary PAHs metabolites and plasma cytokines of interleukin (IL)-9 and eotaxin were measured. Potential associations between urinary PAHs metabolites and adult asthma were analyzed by logistic regression. The relationships between urinary PAHs metabolites and plasma cytokines were determined by generalized linear regression. After adjusted for covariates, each 1-unit-increase in natural log-transformed concentrations of 2-hydroxyfluorene (2-OHFLU), 4- hydroxyphenanthrene (4-OHPHE), 1-OHPHE, 2-OHPHE, 1-Hydroxypyrene (1-OHPYR) and ∑OH-PAHs were significantly associated with elevated risk of adult asthma with odds ratios of 2.04, 2.38, 2.04, 1.26, 2.35 and 1.34, respectively. And the associations were more pronounced in the subjects who were female, younger than 45 years, smoker and had history of occupational dust exposure. No associations were observed between urinary PAHs metabolites levels and expressions of IL-9 and eotaxin. Our results demonstrated that elevated urinary PAHs metabolites levels were associated with increased risk of asthma in adults.

MiRNA-Regulated Changes in Extracellular Matrix Protein Levels Associated With a Severe Decline in Lung Function Induced by Silica Dust.

OBJECTIVE: The aim of this study was to explore the potential role of extracellular matrix (ECM) regulated by miRNAs in lung function decline. METHODS: We convened 270 silica dust exposed subjects and divided them into three groups according to lung function data. MiRNAs were measured by real-time quantitative polymerase chain reaction detecting system and ECM-related proteins were detected by enzyme linked immunosorbent assay. Data were analyzed by t test, Chi-squared tests, nonparametric Mann-Whitney U test, and Spearman rank correlation coefficient. RESULTS: Lower miR-200c and miR-29c were observed in subjects with severe lung function decline and higher ECM proteins were observed in subjects with mild or severe lung function decline. MiRNA and ECM were significantly correlated with FVC%, FEV1%, MMF%, and PEF% (r: 0.204 to 0.458, P < 0.01) and that miRNA were significantly correlated with ECM (r: 0.309 to 0.687, P < 0.01). CONCLUSION: The abnormal ECM regulated by miRNAs may play an important role in lung function decline associated with silica dust exposure.

Inverse Association between Ambient Sulfur Dioxide Exposure and Semen Quality in Wuhan, China.

Evidence concerning the association between ambient gaseous air pollutant exposures and semen quality is sparse, and findings in previous studies remain largely inconsistent. We enrolled 1759 men and performed 2184 semen examinations at a large reproductive medical center in Wuhan, China, between 2013 and 2015. Inverse distance weighting interpolation was performed to estimate individual exposures to SO2, NO2, CO, and O3 during the entire period (lag 0-90 days) and key periods (lag 0-9, 10-14, 70-90 days) of sperm development. Linear mixed models were used to analyze exposure-response relationships. SO2 exposure with 0-90 days lag was significantly associated with monotonically decreased sperm concentration (ß for each interquartile range increase of exposure: -0.14; 95% CI: -0.23, -0.05), sperm count (-0.21; -0.30, -0.12) and total motile sperm count (-0.16; -0.25, -0.08). Significant associations were observed for total and progressive motility only when SO2 exposure was at the highest quintile (all Ptrend < 0.05). Similar trends were observed for SO2 exposure with 70-90 days lag. NO2, CO, or O3 exposure was not significantly associated with semen quality. Our results suggest that ambient SO2 exposure adversely affects semen quality and highlight the potential to improve semen quality by reducing ambient SO2 exposure during early stages of sperm development.

Short-term effects of ambient air pollution on pediatric outpatient visits for respiratory diseases in Yichang city, China.

Previous studies have suggested that short-term exposure to ambient air pollution was associated with pediatric hospital admissions and emergency room visits for certain respiratory diseases; however, there is limited evidence on the association between short-term air pollution exposure and pediatric outpatient visits. Our aim was to quantitatively assess the short-term effects of ambient air pollution on pediatric outpatient visits for respiratory diseases. We conducted a time-series study in Yichang city, China between Jan 1, 2014 and Dec 31, 2015. Daily counts of pediatric respiratory outpatient visits were collected from 3 large hospitals, and then linked with air pollution data from 5 air quality monitoring stations by date. We used generalized additive Poisson models to conduct linear and nonlinear exposure-response analyses between air pollutant exposures and pediatric respiratory outpatient visits, adjusting for seasonality, day of week, public holiday, temperature, and relative humidity. Each interquartile range (IQR) increase in PM2.5 (lag 0), PM10 (lag 0), NO2 (lag 0), CO (lag 0), and O3 (lag 4) concentrations was significantly associated with a 1.91% (95% CI: 0.60%, 3.23%), 2.46% (1.09%, 3.85%), 1.88% (0.49%, 3.29%), 2.00% (0.43%, 3.59%), and 1.91% (0.45%, 3.39%) increase of pediatric respiratory outpatient visits, respectively. Similarly, the nonlinear exposure-response analyses showed monotonic increases of pediatric respiratory outpatient visits by increasing air pollutant exposures, though the associations for NO2 and CO attenuated at higher concentrations. These associations were unlikely modified by season. We did not observe significant association for SO2 exposure. Our results suggest that short-term exposures to PM2.5, PM10, NO2, CO, and O3 may account for increased risk of pediatric outpatient visits for respiratory diseases, and emphasize the needs for reduction of air pollutant exposures for children.

Short-term Effects of Outdoor Air Pollution on Lung Function among Female Non-smokers in China.

Short-term exposures to outdoor air pollutants have been associated with lower lung function, but the results are inconsistence. The effects of different pollutant levels on lung function changes are still unclear. We quantified the effects of outdoor air pollution exposure (NO2, PM10, O3, and PM2.5) on lung function among 1,694 female non-smokers from the Wuhan-Zhuhai Cohort in China by using linear mixed model. We further investigated the associations in the two cities with different air quality levels separately to quantify the effects of different pollutant level exposure on lung function. We found the moving averages of NO2, PM10, and PM2.5 concentrations were significantly associated with reduced FVC. In city at high pollutant level, the moving average of NO2, PM10, O3, and PM2.5 exposures were significantly associated with both FVC and FEV1 reductions. In the low-level air pollution city, PM10 (Lag03-Lag05) and O3 concentrations (Lag01-Lag03) were significantly associated with reduced FVC, while PM10 (Lag03-Lag05), O3 (Lag0-Lag03), and PM2.5 (Lag04-Lag06) exposure were significantly associated with reduced FEV1. Our results suggest that outdoor air pollution is associated with short-term adverse effects on lung function among female non-smokers. The adverse effects may persist for longer durations within 7 days at higher air pollutant levels.

Plasma LncRNA-ATB, a Potential Biomarker for Diagnosis of Patients with Coal Workers' Pneumoconiosis: A Case-Control Study.

LncRNA-ATB (lncRNA was activated by transforming growth factor-ß) has been reported to be involved in specific physiological and pathological processes in human diseases, and could serve as biomarkers for cancers. However, the role of lncRNA-ATB in coal workers' pneumoconiosis (CWP) is still unknown. This study aimed to investigate the association between lncRNA-ATB and CWP. Quantitative real-time polymerase chain reaction was performed to detect plasma lncRNA-ATB expression in 137 CWP patients, 72 healthy coal miners and 168 healthy controls. LncRNA-ATB was significantly upregulated in CWP (p < 0.05). Compared with the healthy controls and healthy coal miners, the odds ratios (ORs) (95% confidence interval (CI)) for CWP were 2.57 (1.52-4.33) and 2.17 (1.04-4.53), respectively. LncRNA-ATB was positively associated with transforming growth factor-ß1 (TGF-ß1) (r = 0.30, p = 0.003) and negative correlated with vital capacity (VC) (r = -0.18, p = 0.033) and forced vital capacity (FVC) (r = -0.18, p = 0.046) in CWP patients. Compared with healthy controls, the area under the curve (AUC) was 0.84, resulting in a 71.17% sensitivity and 88.14% specificity. When compared with healthy coal miners, the AUC was 0.83, the sensitivity and specificity were 70.07% and 86.36%, respectively. LncRNA-ATB expression is commonly increased in CWP and significantly correlates with the TGF-ß1 in CWP patients. Furthermore, elevated lncRNA-ATB was associated with CWP risk and may serve as a potential biomarker for CWP.

Exogenous Gas6 attenuates silica-induced inflammation on differentiated THP-1 macrophages.

Growth arrest specific 6 (Gas6) has been reported to be related to the modulation of innate immunity. To investigate the potential effect of Gas6 on the regulation of inflammations induced by silica, differentiated THP-1 macrophages were exposed to different concentrations of silica for 6h and 24h. Additionally, silica-activated macrophages were treated with Gas6 antibody and Gas6 respectively. Expression levels of Gas6 and inflammatory cytokines (TNF-α, IL-1ß and IL-6) were measured. Our results showed that both cell viability and Gas6 expression were suppressed by silica in dose-dependent manners. After pretreatment with Gas6 antibody, silica induced a significant decrease in cell viability and a significant increase in inflammatory cytokines at two time points. Moreover, addition of Gas6 significantly suppressed silica induced TNF-α, IL-1ß and IL-6 levels in negative dose-dependent manners, not only in mRNA levels but also in protein levels. Our results suggested that exogenous Gas6 might attenuate inflammations induced by silica on macrophages.