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Summary Background In the context of climate change and deforestation, Brazil is facing more frequent and unprecedented wildfires. Wildfire-related PM2·5 is associated with multiple adverse health outcomes; however, the magnitude of these associations in the Brazilian context is unclear. We aimed to estimate the association between daily exposure to wildfire-related PM2·5 and cause-specific hospital admission and attributable health burden in the Brazilian population using a nationwide dataset from 2000 to 2015. Methods In this nationwide time-series analysis, data for daily all-cause, cardiovascular, and respiratory hospital admissions were collected through the Brazilian Unified Health System from 1814 municipalities in Brazil between Jan 1, 2000, and Dec 31, 2015. Daily concentrations of wildfire-related PM2·5 were estimated using the 3D chemical transport model GEOS-Chem at a 2·0° latitude by 2·5° longitude resolution. A time-series analysis was fitted using quasi-Poisson regression to quantify municipality-specific effect estimates, which were then pooled at the regional and national levels using random-effects meta-analyses. Analyses were stratified by sex and ten age groups. The attributable fraction and attributable cases of hospital admissions due to wildfire-related PM2·5 were also calculated. Findings At the national level, a 10 μg/m3 increase in wildfire-related PM2·5 was associated with a 1·65% (95% CI 1·51–1·80) increase in all-cause hospital admissions, a 5·09% (4·73–5·44) increase in respiratory hospital admissions, and a 1·10% (0·78–1·42) increase in cardiovascular hospital admissions, over 0–1 days after the exposure. The effect estimates for all-cause hospital admission did not vary by sex, but were particularly high in children aged 4 years or younger (4·88% [95% CI 4·47–5·28]), children aged 5–9 years (2·33% [1·77–2·90]), and people aged 80 years and older (3·70% [3·20–4·20]) compared with other age groups. We estimated that 0·53% (95% CI 0·48–0·58) of all-cause hospital admissions were attributable to wildfire-related PM2·5, corresponding to 35 cases (95% CI 32–38) per 100 000 residents annually. The attributable rate was greatest for municipalities in the north, south, and central-west regions, and lowest in the northeast region. Results were consistent for all-cause and respiratory diseases across regions, but remained inconsistent for cardiovascular diseases. Interpretation Short-term exposure to wildfire-related PM2·5 was associated with increased risks of all-cause, respiratory, and cardiovascular hospital admissions, particularly among children (0–9 years) and older people (≥80 years). Greater attention should be paid to reducing exposure to wildfire smoke, particularly for the most susceptible populations. Funding Australian Research Council and Australian National Health and Medical Research Council.

The variant design node configuration is an effective method to solve a trade-off that exist in mass customization production between the requirements of product diversification and the product’s cost and delivery time. However, configuration changes in a product development network may generate an avalanche effect of design change propagation, which can consume substantial design resources. In order to control design change propagations, an evaluation method based on network nodes importance for variant design node schemes is proposed for a product development network. Firstly, the evaluation indexes, including the betweenness, variant deign node set importance, and network clustering coefficient, are integrated to describe the network characteristics of the set of variant design nodes. Then, combining the time and resource constraints for the variant design, a discrete particle swarm algorithm is employed to optimize the configuration of the nodes. The configuration solution for the variant design nodes satisfies the need to control the variant design propagation. Compared with the established greedy algorithm, the discrete particle swarm optimization can achieve better optimization performance in terms of the algorithm’s convergence and computation time. It is meaningful to understand the mechanism of product configuration change propagation in depth in order to choose the variant design nodes rationally and efficiently in complex product development networks. Lastly, an example of variant design for a type of cleaning robot product verifies the effectiveness of the proposed method.

Previous experimental studies have identified specific foods or nutrients are capable of mitigating adverse effects induced by air pollution. However, whether the dietary pattern can modify the associations between long-term particulate matter (PM) and increasing blood pressure (BP) among adults has not yet been assessed. We assessed whether the dietary pattern and various foods modify the associations between long-term exposure to PM (PM 1 , PM 2.5 , and PM 10 ), hypertensive BP (BP≥140/90 mm Hg, HBP), and BP in Chinese adults. This study included 61 081 participants from China Multi-Ethnic Cohort. PM was assessed through satellite-based random forest approaches. Outcomes were analyzed with logistic regression models and linear regression models. The dietary approaches to stop hypertension (DASH) diet was calculated for each participant. This study founds long-term exposure to PM was associated with HBP, systolic BP, and pulse pressure. The DASH diet modified the associations between PM, HBP, and some BP components. For each 10 μg/m 3 increase in PM 1 , PM 2.5 , and PM 10 , the participants with the lowest quintile of DASH score had HBP risks with odds ratios (95% CI) of 1.196 (1.084–1.319), 1.145 (1.09–1.202), and 1.080 (1.045–1.117), whereas those with the highest quintile of DASH score had lower HBP risks with odds ratios (95% CI) of 1.063 (0.953–1.185), 1.074 (1.017–1.133), and 1.038 (1.000–1.077). Consuming more fresh fruits, vegetables, dairy, and whole grains would reduce the risk of raised BP caused by PM. In conclusion, the DASH diet rich in antioxidant compounds may be a wide-reaching intervention to reduce the deleterious impact of PM.

BackgroundFew studies have examined the effects of ambient particulate matter with an aerodynamic diameter less than or equal to 2.5 μm (PM2.5) on hospital cost and length of hospital stay for respiratory diseases in China.MethodsWe estimated ambient air pollution exposure for respiratory cases through inverse distance-weighted averages of air monitoring stations based on their residential address and averaged at the city level. We used generalised additive models to quantify city-specific associations in 11 cities in Shanxi and a meta-analysis to estimate the overall effects. We further estimated respiratory burden attributable to PM2.5using the standards of WHO (25 µg/m3) and China (75 µg/m3) as reference.ResultsEach 10 µg/m3increase in lag03PM2.5corresponded to 0.53% (95% CI: 0.33% to 0.73%) increase in respiratory hospitalisation, an increment of 3.75 thousand RMB (95% CI: 1.84 to 5.670) in hospital cost and 4.13 days (95% CI: 2.51 to 5.75) in length of hospital stay. About 9.7 thousand respiratory hospitalisations, 132 million RMB in hospital cost and 145 thousand days of hospital stay could be attributable to PM2.5exposures using WHO’s guideline as reference. We estimated that 193 RMB (95% CI: 95 to 292) in hospital cost and 0.21 days (95% CI: 0.13 to 0.30) in hospital stay could be potentially avoidable for an average respiratory case.ConclusionSignificant respiratory burden could be attributable to PM2.5exposures in Shanxi Province, China. The results need to be factored into impact assessment of air pollution policies to provide a more complete indication of the burden addressed by the policies.

Limited epidemiological literature identified the associations between residential greenness and hypertension in low-/middle-income countries. A random sampling strategy was adopted to recruit 39,259 residents, ≥ 18 years, and from 5 counties in central China. Blood pressure was measured based on the protocol of the American Heart Association. Hypertension was defined according to the 2010 Chinese guidelines for the management of hypertension. The satellite-derived normalized difference vegetation index (NDVI) and enhanced vegetation index (EVI) were applied to estimate the residential greenness. Mixed logit model and mixed linear model were utilized to explore the relationships of residential greenness with hypertension and blood pressure. Higher residential greenness was associated with lower odds of hypertension and blood pressure levels. For instance, an interquartile range (IQR) increase in NDVI500m was linked with lower odds of hypertension (OR = 0.92, 95%CI 0.88 to 0.95), a decrease of -0.88 mm Hg (95% CI -1.17 to -0.58) and -0.64 mm Hg (95% CI -0.82 to -0.46) in SBP and DBP, respectively. The effect of residential greenness was more pronounced in males, smokers, and drinkers. Long-term exposure to residential greenness was linked with lower odds of hypertension. More prospective studies are needed to verify the hypothesis.

Although obesity reflected by BMI can enhance the association of air pollution with increase blood pressures (BP) and prevalent hypertension in susceptible population, there remains lack evidence on interactive effects of different obesity indices and air pollutants on BP and prevalent hypertension in rural adults. 39,259 individuals were recruited from the Henan Rural Cohort. Concentrations of air pollutants (PM1, PM2.5, PM10 and NO2) were evaluated by a spatio-temporal model based on satellites data. Independent associations of air pollutants and obesity reflected by BMI, WC, WHR, WHtR, BFP and VFI on BP indicators (SBP, DBP, MAP and PP) and prevalent hypertension were analyzed by linear regression and logistic regression models, respectively. Furthermore, their additive effects were quantified by RERI, AP and S. Six obesity indices enhanced the associations of four air pollutants and BP indicators. Individuals with high PM1 concentrations plus obesity classified by BMI, WC, WHR, WHtR, BFP and VFI had a 4.18-fold (95% CI: 3.86, 4.53), 3.58-fold (95% CI: 3.34, 3.84), 3.53-fold (95% CI: 3.28, 3.81), 4.02-fold (95% CI: 3.72, 4.35), 3.89-fold (95% CI: 3.59, 4.23), 3.87-fold (95% CI: 3.62, 4.14) increase in prevalent hypertension, respectively, compared to non-obese individuals with low PM1 concentrations; similar results were observed for combined effect of PM2.5, PM10 or NO2 and obesity indices on prevalent hypertension. The significant values of RERI, AP and S indicated additive effects of air pollutants and obesity indices on hypertension. Obesity amplified the effects of exposure to high levels of air pollutants on increased BP values and prevalent hypertension, implying that obese individuals may be susceptible to elevate BP and prevalent hypertension in relation to air pollution exposure. CLINICAL TRIAL REGISTRATION: The Henan Rural Cohort study has been registered at Chinese Clinical Trial Register (Registration number: ChiCTR-OOC-15006699, http://www.chictr.org.cn/showproj.aspx?proj=11375).

Background MAP2K1 mutations, otherwise known as MEK mutations, are rare oncogenic alterations that have been implicated in MAPK pathway activation. The impact of MAP2K1 mutations in colorectal cancer on EGFR antibody response has not been characterized. Patients and Methods Antitumor activity was assessed in mouse xenograft models with SW48 cell lines harboring MAP2K1 mutation, and protein expression of the RAS signaling pathway was studied by Western blot analysis. We retrospectively identified patients with MAP2K1-mutated metastatic colorectal cancer patients treated at City of Hope Comprehensive Cancer Center between 2015 and 2020 using next-generation sequencing. Patients’ tumor characteristics, treatment response, and outcome are described. Additional patients with the MAP2K1 mutation were identified from The Cancer Genome Atlas and Memorial Sloan Kettering Cancer Center oncogenomic databases. Results Antitumor activity in mouse xenograft models demonstrated efficacy with combination therapy with EGFR and MEK inhibition with either BRAF or ERK inhibitors. Five patients treated at City of Hope between 2015 and 2020 harbored a MAP2K1 mutation at a frequency of 1%. APC and TP53 were common coalterations. All disease was RAS and BRAF wild type, except 1 case that harbored a concurrent KRAS mutation. Four RAS/BRAF wild-type MAP2K1-mutated patients was treated with anti-EGFR, anti-EGFR + MEK and BRAF inhibitors, and anti-EGFR + ERK inhibitors. All 4 patients experienced disease progression. Conclusion MAP2K1 mutation in colorectal cancer is associated with poor response to EGFR inhibition. EGFR inhibition with or without MEK, BRAF, or ERK inhibitors did not result in any clinical benefit in our limited experience.

There is growing evidence on the effect of face mask use in controlling the spread of COVID-19. However, few studies have examined the effect of local face mask policies on the pandemic. In this study, we developed a dynamic compartmental model of COVID-19 transmission in New York City (NYC), which was the epicenter of the COVID-19 pandemic in the USA. We used data on daily and cumulative COVID-19 infections and deaths from the NYC Department of Health and Mental Hygiene to calibrate and validate our model. We then used the model to assess the effect of the executive order on face mask use on infections and deaths due to COVID-19 in NYC. Our results showed that the executive order on face mask use was estimated to avert 99,517 (95% CIs 72,723–126,312) COVID-19 infections and 7978 (5692–10,265) deaths in NYC. If the executive order was implemented 1 week earlier (on April 10), the averted infections and deaths would be 111,475 (81,593–141,356) and 9017 (6446–11,589), respectively. If the executive order was implemented 2 weeks earlier (on April 3 when the Centers for Disease Control and Prevention recommended face mask use), the averted infections and deaths would be 128,598 (94,373–162,824) and 10,515 (7540–13,489), respectively. Our study provides public health practitioners and policymakers with evidence on the importance of implementing face mask policies in local areas as early as possible to control the spread of COVID-19 and reduce mortality. Supplementary Information The online version contains supplementary material available at 10.1007/s11524-021-00517-2.

Summary Background Exposure to temperature variability has been associated with increased risk of mortality and morbidity. We aimed to evaluate whether the association between short-term temperature variability and hospitalisation was affected by local socioeconomic level in Brazil. Methods In this time-series study, we collected city-level socioeconomic data, and daily hospitalisation and weather data from 1814 Brazilian cities between Jan 1, 2000, and Dec 31, 2015. All-cause and cause-specific hospitalisation data was from the Hospital Information System of the Unified Health System in Brazil. City-specific daily minimum and maximum temperatures came from a 0·25° × 0·25° Brazilian meteorological dataset. We represented city-specific socioeconomic level using literacy rate, urbanisation rate, average monthly household income per capita (using the 2000 and 2010 Brazilian census), and GDP per capita (using statistics from the Brazilian Institute of Geography and Statistics for 2000–15), and cities were categorised according to the 2015 World Bank standard. We used quasi-Poisson regression to do time-series analyses and obtain city-specific associations between temperature variability and hospitalisation. We pooled city-specific estimates according to different socioeconomic quartiles or levels using random-effect meta-analyses. Meta-regressions adjusting for demographic and climatic characteristics were used to evaluate the modification effect of city-level socioeconomic indicators on the association between temperature variability and hospitalisation. Findings We included a total of 147 959 243 hospitalisations (59·0% female) during the study period. Overall, we estimated that the hospitalisation risk due to every 1°C increase in the temperature variability in the current and previous day (TV0–1) increased by 0·52% (95% CI 0·50−0·55). For lower-middle-income cities, this risk was 0·63% (95% CI 0·58–0·69), for upper-middle-income cities it was 0·50% (0·47–0·53), and for high-income cities it was 0·39% (0·33–0·46). The socioeconomic inequality in vulnerability to TV0–1 was especially evident for people aged 0–19 years (effect estimate 1·21% [1·11–1·31] for lower-middle income vs 0·52% [0·41–0·63] for high income) and people aged 60 years or older (0·60% [0·50–0·70] vs 0·43% [0·31–0·56]), and for hospitalisation due to infectious diseases (1·62% [1·46–1·78] vs 0·56% [0·30–0·82]), respiratory diseases (1·32% [1·20–1·44] vs 0·55% [0·37–0·74]), and endocrine diseases (1·21% [0·99–1·43] vs 0·32% [0·02–0·62]). Interpretation People living in less developed cities in Brazil were more vulnerable to hospitalisation related to temperature variability. This disparity could exacerbate existing health and socioeconomic inequalities in Brazil, and it suggests that more attention should be paid to less developed areas to mitigate the adverse health effects of short-term temperature fluctuations. Funding None.

Aimed at the problem that the mining roadway is seriously affected by the repeated mining under the up-down successive cooperative mining mode, this paper takes Qiuci Coal Mine as the research back...

Our study aims to explore changes in bladder contractility and the phosphodiesterase type 5 (PDE5) signalling pathway in response to partial bladder outlet obstruction (PBOO). A surgically induced male rat PBOO model and human obstructed bladder tissues were used. Histological changes were examined by H&E and Masson's trichrome staining. Bladder strip contractility was measured via organ bath. The expressions of nitric oxide synthase (NOS) isoforms, PDE5, muscarinic cholinergic receptor (CHRM) isoforms and PDE4 isoforms in bladder were detected by RT‐PCR and Western blotting. The immunolocalization of the PDE5 protein and its functional activity were also determined. PBOO bladder tissue exhibited significant SM hypertrophy and elevated responsiveness to KCl depolarization and the muscarinic receptor agonist carbachol. NOS isoforms, PDE5, CHRM2, CHRM3 and PDE4A were up‐regulated in obstructed bladder tissue, whereas no change in PDE4B and PDE4D isoform expression was observed. With regard to PDE5, it was expressed in the SM bundles of bladder. Interestingly, obstructed bladder exhibited less relaxation responsiveness to sodium nitroprusside (SNP), but an exaggerated PDE5 inhibition effect. The up‐regulation of PDE5 could contribute to the lack of effect on Qmax for benign prostatic hyperplasia/lower urinary tract symptom (BPH/LUTS) patients treated with PDE5 inhibitors. Moreover, PDE5 (with presence of NO) and PDE4 may serve as new therapeutic targets for bladder diseases such as BPH‐induced LUTS and overactive bladder (OAB).

Heavy metal pollution in soil has an increasingly serious impact on the ecological environment, quality of agricultural and livestock products, and healthy living. Researches on detection methods a...

Ambient air pollution may be associated with diabetes mellitus. However, evidence from developing countries is limited although the concentrations of air pollution are disproportionably higher in these countries. We collected daily data on diabetes mortality, air pollution, and weather conditions from 16 Chinese provincial cities during 2007–2013. A quasi-Poisson regression combined with a distributed lag model was used to quantify the city-specific mortality risk of PM10 (particulate matter with aerodynamic diameter

Background Despite large reductions in under-5 lower respiratory infection (LRI) mortality in many locations, the pace of progress for LRIs has generally lagged behind that of other childhood infectious diseases. To better inform programmes and policies focused on preventing and treating LRIs, we assessed the contributions and patterns of risk factor attribution, intervention coverage, and sociodemographic development in 195 countries and territories by drawing from the Global Burden of Diseases, Injuries, and Risk Factors Study 2017 (GBD 2017) LRI estimates. Methods We used four strategies to model LRI burden: the mortality due to LRIs was modelled using vital registration data, demographic surveillance data, and verbal autopsy data in a predictive ensemble modelling tool; the incidence of LRIs was modelled using population representative surveys, health-care utilisation data, and scientific literature in a compartmental meta-regression tool; the attribution of risk factors for LRI mortality was modelled in a counterfactual framework; and trends in LRI mortality were analysed applying changes in exposure to risk factors over time. In GBD, infectious disease mortality, including that due to LRI, is among HIV-negative individuals. We categorised locations based on their burden in 1990 to make comparisons in the changing burden between 1990 and 2017 and evaluate the relative percent change in mortality rate, incidence, and risk factor exposure to explain differences in the health loss associated with LRIs among children younger than 5 years. Findings In 2017, LRIs caused 808 920 deaths (95% uncertainty interval 747 286–873 591) in children younger than 5 years. Since 1990, there has been a substantial decrease in the number of deaths (from 2 337 538 to 808 920 deaths; 65·4% decrease, 61·5–68·5) and in mortality rate (from 362·7 deaths [330·1–392·0] per 100 000 children to 118·9 deaths [109·8–128·3] per 100 000 children; 67·2% decrease, 63·5–70·1). LRI incidence declined globally (32·4% decrease, 27·2–37·5). The percent change in under-5 mortality rate and incidence has varied across locations. Among the risk factors assessed in this study, those responsible for the greatest decrease in under-5 LRI mortality between 1990 and 2017 were increased coverage of vaccination against Haemophilus influenza type b (11·4% decrease, 0·0–24·5), increased pneumococcal vaccine coverage (6·3% decrease, 6·1–6·3), and reductions in household air pollution (8·4%, 6·8–9·2). Interpretation Our findings show that there have been substantial but uneven declines in LRI mortality among countries between 1990 and 2017. Although improvements in indicators of sociodemographic development could explain some of these trends, changes in exposure to modifiable risk factors are related to the rates of decline in LRI mortality. No single intervention would universally accelerate reductions in health loss associated with LRIs in all settings, but emphasising the most dominant risk factors, particularly in countries with high case fatality, can contribute to the reduction of preventable deaths. Funding Bill & Melinda Gates Foundation.

Summary Background Climate change is increasing the risks of injuries, diseases, and deaths globally. However, the association between ambient temperature and renal diseases has not been fully characterized. This study aimed to quantify the risk and attributable burden for hospitalizations of renal diseases related to ambient temperature. Methods Daily hospital admission data from 1816 cities in Brazil were collected during 2000 and 2015. A time-stratified case-crossover design was applied to evaluate the association between temperature and renal diseases. Relative risks (RRs), attributable fractions (AFs), and their confidence intervals (CIs) were calculated to estimate the associations and attributable burden. Findings A total of 2,726,886 hospitalizations for renal diseases were recorded during the study period. For every 1°C increase in daily mean temperature, the estimated risk of hospitalization for renal diseases over lag 0–7 days increased by 0·9% (RR = 1·009, 95% CI: 1·008–1·010) at the national level. The associations between temperature and renal diseases were largest at lag 0 days but remained for lag 1–2 days. The risk was more prominent in females, children aged 0–4 years, and the elderly ≥ 80 years. 7·4% (95% CI: 5·2–9·6%) of hospitalizations for renal diseases could be attributable to the increase of temperature, equating to 202,093 (95% CI: 141,554–260,594) cases. Interpretation This nationwide study provides robust evidence that more policies should be developed to prevent heat-related hospitalizations and mitigate climate change. Funding China Scholarship Council, and the Australian National Health and Medical Research Council

Smoke exposure from landscape and coal mine fires can have severe impacts on human health. The ability of health studies to accurately identify potential associations between smoke exposure and health is dependent on the techniques utilised to quantify exposure concentrations for the population at risk. The evolution of spatial modelling techniques capable of better characterising this association has potential to provide more precise health effect estimates. We reviewed the literature to identify and assess the spatial modelling techniques available to estimate smoke PM2.5 or PM10 concentrations from open biomass or coal mine fires. Four electronic databases were searched: MEDLINE, EMBASE, Scopus and Web of Science. Studies were included if they utilised any method for modelling the spatial distribution of PM2.5 or PM10 concentrations from open biomass or coal mine fires and had applied the modelled PM to health data. Studies based on un-adjusted monitoring data, or which were not in English, were excluded. We identified 28 studies which utilised five spatial modelling techniques to assess exposure from open biomass fires: dispersion models, land use regression, satellite remote sensing, spatial interpolation and blended models. No studies of coal mine fires were identified. We found the most effective models combined multiple techniques to enhance the strengths and mitigate the weaknesses of the underlying individual techniques. “Blended” models have the potential to facilitate research in regions currently under represented in biomass or coal mine fire studies as well as enhancing the power of studies to identify associations with health outcomes.

Background Although exposure to ambient air pollution (AAP) increases the risk for arteriosclerotic cardiovascular disease (ASCVD), evidence on the association of solid fuel use with ASCVD and its association modified by ambient air pollution remains limited. Methods A total of 16,779 adults were derived from the Henan Rural Cohort Study. Concentrations of ambient air pollutants (PM1, PM2.5, PM10, and NO2) were estimated by a spatiotemporal model based on satellites data. Solid fuel use was assessed by a self-reported questionnaire. The associations of solid fuel use with high 10-year ASCVD risk and the modified association by exposure to air pollutants were explored using logistic regression models. Results There were positive associations of AAP exposure with high 10-year ASCVD risk among individuals with self-cooking. The joint associations between high AAP exposures and solid fuel use with high 10-year ASCVD risk were found. Compared to clean fuel user with low PM2.5 exposure, the odds ratios (ORs) and 95% confidence intervals (CIs) of high 10-year ASCVD risk was 1.25 (1.09, 1.42) for solid fuel user with low PM2.5 exposure, 1.93 (1.75, 2.12) for clean fuel user with high PM2.5 exposure, and 3.08 (2.67, 3.54) for solid fuel user with high PM2.5 exposure, respectively. Their additive effect on high 10-year ASCVD risk was observed (relative excess risk due to interaction (RERI): 0.90 (95 %CI: 0.50, 1.30), attributable proportion due to interaction (AP): 0.29 (95 %CI: 0.19, 0.40), and synergy index (SI): 1.77 (95 %CI: 1.38, 2.26)). Conclusion This study showed a synergistic effect of AAP and household air pollution reflected by solid fuel use on high 10-year ASCVD risk, suggesting that reducing solid cooking fuels and controlling air pollution may have a joint effect on public health improvement.

The efficacy of anti-PD-1 therapy is not as expected in patients with hepatocellular carcinoma (HCC). Yes-associated protein 1 (YAP1) was overexpressed and activated in HCC. This study aimed to investigate the potential mechanism and inhibitor of YAP1 on immune evasion, and promote anti-PD-1 therapy in HCC. Here, we showed that dihydroartemisinin (DHA), an FDA approved drug, directly suppressed YAP1 expression, leading to break immune evasion in liver tumor niche, characterized by decreased PD-L1 in liver tumor cells and increased CD8+ T cell infiltration. Mechanismly, YAP1 is not only directly related to PD-L1, but also involved in activating the JAK1/STAT1, 3 pathways. Moreover, Yap1 knockout elevated CD4+ and CD8+ T cells in liver tumor niche of Yap1LKO mice. Consistently, verteporfin, YAP1 inhibitor, decreased TGF-β in liver tumor niche and exhausted CD8+ T cells in spleen. Furthermore, DHA combined with anti-PD-1 treatment promoted CD4+ T cell infiltration in the spleen and CD8+ T cells in tumor tissues. Thus, we provide a new combined therapeutic strategy for anti-PD-1 with DHA, a potent YAP1 inhibitor, in HCC.

Background Regularly updated data on stroke and its pathological types, including data on their incidence, prevalence, mortality, disability, risk factors, and epidemiological trends, are important for evidence-based stroke care planning and resource allocation. The Global Burden of Diseases, Injuries, and Risk Factors Study (GBD) aims to provide a standardised and comprehensive measurement of these metrics at global, regional, and national levels. Methods We applied GBD 2019 analytical tools to calculate stroke incidence, prevalence, mortality, disability-adjusted life-years (DALYs), and the population attributable fraction (PAF) of DALYs (with corresponding 95% uncertainty intervals [UIs]) associated with 19 risk factors, for 204 countries and territories from 1990 to 2019. These estimates were provided for ischaemic stroke, intracerebral haemorrhage, subarachnoid haemorrhage, and all strokes combined, and stratified by sex, age group, and World Bank country income level. Findings In 2019, there were 12·2 million (95% UI 11·0–13·6) incident cases of stroke, 101 million (93·2–111) prevalent cases of stroke, 143 million (133–153) DALYs due to stroke, and 6·55 million (6·00–7·02) deaths from stroke. Globally, stroke remained the second-leading cause of death (11·6% [10·8–12·2] of total deaths) and the third-leading cause of death and disability combined (5·7% [5·1–6·2] of total DALYs) in 2019. From 1990 to 2019, the absolute number of incident strokes increased by 70·0% (67·0–73·0), prevalent strokes increased by 85·0% (83·0–88·0), deaths from stroke increased by 43·0% (31·0–55·0), and DALYs due to stroke increased by 32·0% (22·0–42·0). During the same period, age-standardised rates of stroke incidence decreased by 17·0% (15·0–18·0), mortality decreased by 36·0% (31·0–42·0), prevalence decreased by 6·0% (5·0–7·0), and DALYs decreased by 36·0% (31·0–42·0). However, among people younger than 70 years, prevalence rates increased by 22·0% (21·0–24·0) and incidence rates increased by 15·0% (12·0–18·0). In 2019, the age-standardised stroke-related mortality rate was 3·6 (3·5–3·8) times higher in the World Bank low-income group than in the World Bank high-income group, and the age-standardised stroke-related DALY rate was 3·7 (3·5–3·9) times higher in the low-income group than the high-income group. Ischaemic stroke constituted 62·4% of all incident strokes in 2019 (7·63 million [6·57–8·96]), while intracerebral haemorrhage constituted 27·9% (3·41 million [2·97–3·91]) and subarachnoid haemorrhage constituted 9·7% (1·18 million [1·01–1·39]). In 2019, the five leading risk factors for stroke were high systolic blood pressure (contributing to 79·6 million [67·7–90·8] DALYs or 55·5% [48·2–62·0] of total stroke DALYs), high body-mass index (34·9 million [22·3–48·6] DALYs or 24·3% [15·7–33·2]), high fasting plasma glucose (28·9 million [19·8–41·5] DALYs or 20·2% [13·8–29·1]), ambient particulate matter pollution (28·7 million [23·4–33·4] DALYs or 20·1% [16·6–23·0]), and smoking (25·3 million [22·6–28·2] DALYs or 17·6% [16·4–19·0]). Interpretation The annual number of strokes and deaths due to stroke increased substantially from 1990 to 2019, despite substantial reductions in age-standardised rates, particularly among people older than 70 years. The highest age-standardised stroke-related mortality and DALY rates were in the World Bank low-income group. The fastest-growing risk factor for stroke between 1990 and 2019 was high body-mass index. Without urgent implementation of effective primary prevention strategies, the stroke burden will probably continue to grow across the world, particularly in low-income countries. Funding Bill & Melinda Gates Foundation.

Residential greenness may be beneficial for cardiovascular health, but the evidence is still scarce, especially in developing countries. This study aimed to assess the associations between exposure to residential greenness and 10-year atherosclerotic cardiovascular disease (ASCVD) risk in a large rural Chinese adult population. This was a cross-sectional study based on 31,162 participants aged 35–74 years with complete data on predictors of the 10-year ASCVD risk from the Henan Rural Cohort Study. The satellite-derived Normalized Difference Vegetation Index (NDVI) and Enhanced Vegetation Index (EVI) were used to quantify residential greenness in a buffer radius of 500 m, 1000 m, and 3000 m. The high 10-years ASCVD risk was defined as the estimated risk ≥10% based on prediction equations from the China-PAR Project for Chinese populations. Multivariable-adjusted logistic regression models were performed to estimate the associations of greenness exposures with high 10-year ASCVD risk, and mediation analyses were employed to the potential mediators. For per interquartile range (IQR) increase in NDVI500−m, NDVI1000−m, NDVI3000−m, EVI500−m, EVI1000−m, and EVI3000−m, the adjusted OR (95% CI) of high 10-years ASCVD risk was 0.828 (0.793–0.866), 0.850 (0.817–0.885), 0.823 (0.792–0.855), 0.848 (0.809–0.889), 0.863 (0.826–0.901), 0.843 (0.805–0.883), respectively. Strong associations of NDVI500−m and EVI500−m with high 10-years ASCVD risk were found among participants with lower education level and lower averaged monthly income. The associations of greenness exposures with high 10-year ASCVD risk were partially explained by particulate matter with an aerodynamic diameter ≤1 µm, BMI, and physical activity. Enhancing residential greenness exposure may be beneficial for reducing the high 10-year ASCVD risk in rural Chinese adults.

Background Although many cohort studies have documented the long-term effects of ambient air pollution on mortality, but they suffer from residual confounding, being unable to control unmeasured confounders, and are often not population representative. A recently developed variant of difference-in-difference (DID) approach is promising to address these limitations. Methods We collected annual all-cause death data from 2,193 statistical areas level-2 (SA2) in Australia during 2001-2015. Area-level annual mean concentrations of PM2.5 and NO2 were derived from widely used grid (0.01°×0.01° and 0.1°×0.1°, respectively) datasets. The variant of DID method was used to evaluate the causal relationship between annual PM2.5 and NO2 and all-cause mortality. We further developed this method by considering non-linear associations and lag impacts using distributed lag non-linear model. Results The impacts of low PM2.5 (1.94-12.00 µg/m3) and NO2 (0-7.41 µg/m3) on all-cause mortality were non-linear and lasted for 0-3 year and 0-6 year, respectively. The moving average PM2.5 (0-3 year) and NO2 (0-6 year) showed non-significant impacts below the thresholds (4.44 µg/m3 and 1.10 µg/m3) observed, while every 1 µg/m3 increase above the thresholds were associated with 2.4% (95%CI: 1.6-3.3%) and 9.4% (95%CI: 7.9-10.8%) increase in all-cause mortality, respectively. We estimated that 3.0% (95%CI: 2.0-3.9%) and 9.9% (8.3-11.3%) deaths were attributable to PM2.5 and NO2, respectively. Conclusions We further developed the causal DID model and documented the deadly impacts of long-term exposure to low PM2.5 and NO2 with thresholds and lag periods. Key messages Long-term exposure to low PM2.5 and NO2 are still deadly but have thresholds.

Summary Background Exposure to temperature variability has been associated with increased risk of mortality and morbidity. We aimed to evaluate whether the association between short-term temperature variability and hospitalisation was affected by local socioeconomic level in Brazil. Methods In this time-series study, we collected city-level socioeconomic data, and daily hospitalisation and weather data from 1814 Brazilian cities between Jan 1, 2000, and Dec 31, 2015. All-cause and cause-specific hospitalisation data was from the Hospital Information System of the Unified Health System in Brazil. City-specific daily minimum and maximum temperatures came from a 0·25° × 0·25° Brazilian meteorological dataset. We represented city-specific socioeconomic level using literacy rate, urbanisation rate, average monthly household income per capita (using the 2000 and 2010 Brazilian census), and GDP per capita (using statistics from the Brazilian Institute of Geography and Statistics for 2000–15), and cities were categorised according to the 2015 World Bank standard. We used quasi-Poisson regression to do time-series analyses and obtain city-specific associations between temperature variability and hospitalisation. We pooled city-specific estimates according to different socioeconomic quartiles or levels using random-effect meta-analyses. Meta-regressions adjusting for demographic and climatic characteristics were used to evaluate the modification effect of city-level socioeconomic indicators on the association between temperature variability and hospitalisation. Findings We included a total of 147 959 243 hospitalisations (59·0% female) during the study period. Overall, we estimated that the hospitalisation risk due to every 1°C increase in the temperature variability in the current and previous day (TV0–1) increased by 0·52% (95% CI 0·50−0·55). For lower-middle-income cities, this risk was 0·63% (95% CI 0·58–0·69), for upper-middle-income cities it was 0·50% (0·47–0·53), and for high-income cities it was 0·39% (0·33–0·46). The socioeconomic inequality in vulnerability to TV0–1 was especially evident for people aged 0–19 years (effect estimate 1·21% [1·11–1·31] for lower-middle income vs 0·52% [0·41–0·63] for high income) and people aged 60 years or older (0·60% [0·50–0·70] vs 0·43% [0·31–0·56]), and for hospitalisation due to infectious diseases (1·62% [1·46–1·78] vs 0·56% [0·30–0·82]), respiratory diseases (1·32% [1·20–1·44] vs 0·55% [0·37–0·74]), and endocrine diseases (1·21% [0·99–1·43] vs 0·32% [0·02–0·62]). Interpretation People living in less developed cities in Brazil were more vulnerable to hospitalisation related to temperature variability. This disparity could exacerbate existing health and socioeconomic inequalities in Brazil, and it suggests that more attention should be paid to less developed areas to mitigate the adverse health effects of short-term temperature fluctuations. Funding None.

Summary Ambient air pollution has been shown to be associated with the pathogenesis of dementia and mild cognitive impairment (MCI). However, few studies have examined these associations in well-characterized populations with low residential mobility, similar living habits, and a standardized assessment of both air pollution exposure and clinical outcome. This study examined the associations of long-term exposure to particulate matter (PM) air pollution with dementia and MCI, using data from the Chinese Veteran Clinical Research Platform. The cognitive function of elderly veterans from 277 communities in 18 Chinese cities was examined. Participants' daily exposures to aerodynamic diameters ≤2.5 μm (PM2.5) and ≤10 μm (PM10) during the 3 years prior to the survey were estimated using a satellite-based prediction. The adjusted odds ratios (ORs) and 95% confidence intervals of MCI associated with each 10 μg/m3 increase in PM2.5 and PM10 were 1.52 (1.39, 1.67) and 1.04 (1.00, 1.08), and those of dementia associated with PM2.5 and PM10 were 1.27 (1.11, 1.46) and 1.13 (1.05, 1.21), respectively. This demonstrates that long-term exposure to PM2.5 and PM10 can increase the prevalence of dementia/MCI among veterans in China. Higher ORs were observed for those with ≤9 years of educational attainment, those who actively attended physical activities, those who never smoked, former drinkers, and those who did not suffer from cerebral infarction. Improvement of ambient air quality, especially decreasing levels of PM2.5, may help to decrease the risk of dementia/MCI. Given the statistically significant association between PM and cognitive impairment demonstrated here, future studies should focus on examining the causal effect of PM pollution on dementia and MCI., Graphical abstract, Public summary • Dementia and MCI are emerging as major public health problems, and PM2.5 is hypothesized to be associated with dementia and MCI • We examined the cognitive function of elderly veterans from 277 communities (a well-characterized population with low residential mobility, similar living habits, standardized assessment of both exposure and outcome), in 18 Chinese cities from December 2009 to December 2011 • Long-term exposure to PM, especially PM2.5 showed associations with dementia and MCI • The effect was more pronounced for people with no more than nine years of education • Besides, people with fewer other risk factors (lack of physical activities, smoking, drinking, cerebral infarction) are more susceptible to PM2.5 • Improvement of ambient air quality, especially PM2.5, might be helpful to decrease the risk of dementia and MCI

Background Population-based studies on the associations of long-term exposure to particulate matter (PM) with androgen and progesterone are still scant. Residential greenness is benefits health by promoting physical activity, reducing air pollution, and improving mental health, but it remains unclear whether it is related to androgen and progesterone levels among humans. Aims This study aimed to explore the individual and interactive effects of PM and residential greenness on serum testosterone and progesterone levels among rural Chinese adults. Methods A total of 6017 subjects were recruited from the baseline of the Henan Rural Cohort Study in 2016. Serum testosterone and progesterone were measured with liquid chromatography-tandem mass spectrometry. Particulate matters (PM) (PM1, PM2.5, and PM10) were assessed by machine learning algorithms. Residential greenness was assessed using the normalized difference vegetation index (NDVI) within 500-m, 1000-m, and 3000-m buffers around participants’ residences. The effects of air pollutants and residential greenness and their interaction on serum testosterone and progesterone levels were assessed using linear mixed-effects models with township as a random intercept. Results After adjusting for potential confounding factors, a 1 μg/m3 increase in PM2.5 or PM10 was associated with a 0.037 or 0.030 ng/ml increase in serum testosterone, respectively, in females and with a 0.111 or 0.182 ng/ml decrease in serum progesterone, respectively, in males. A 1 μg/m3 increase in PM1, PM2.5 or PM10 was associated with a 0.222, 0.306, or 0.295 ng/ml decrease in serum progesterone, respectively, among females. Moreover, a 0.1-unit increase in NDVI was associated with a 0.310 ng/ml increase in serum testosterone and a 0.170 ng/ml increased in serum progesterone in males, as well as with a 0.143 ng/ml increase in serum progesterone in females. Interaction effects of PM and residential greenness on serum testosterone and progesterone levels were observed, indicating that the effects of residential greenness on serum testosterone and progesterone were modified by high levels of PM. In addition, physical activity significantly mediated 2.92% of the estimated association between greenness and testosterone levels. Conclusions Our study suggested that long-term exposure to PM was positively associated with serum testosterone in males but negatively associated with progesterone levels in both genderssin. In addition, positive associations of residential greenness with serum testosterone and progesterone levels were observed, but they were modified by high levels of PM. Furthermore, the estimated effects of residential greenness on testosterone levels were partly mediated by physical activity.

Robust evidence is needed for the hazardous effects of outdoor particulate matter (PM) on mortality and morbidity from all types of cancers. To summarize and meta-analyze the association between PM and cancer, published articles reporting associations between outdoor PM exposure and any type of cancer with individual outcome assessment that provided a risk estimate in cohort studies were identified via systematic searches. Of 3,256 records, 47 studies covering 13 cancer sites (30 for lung cancer, 12 for breast cancer, 11 for other cancers) were included in the quantitative evaluation. The pooled relative risks (RRs) for lung cancer incidence or mortality associated with every 10-μg/m3 PM2.5 or PM10 were 1.16 (95% confidence interval [CI], 1.10–1.23; I2 = 81%) or 1.22 (95% CI, 1.02–1.45; I2 = 96%), respectively. Increased but non-significant risks were found for breast cancer. Other cancers were shown to be associated with PM exposure in some studies but not consistently and thus warrant further investigation., Graphical abstract, Public summary • Updated evidence for the association between PM and lung cancer risk has been provided • Associations between PM and cancer risks from 13 sites were summarized • Further studies should be conducted to fill the research gaps

Background Ambient temperature may contribute to seasonality of mortality; in particular, a warming climate is likely to influence the seasonality of mortality. However, few studies have investigated seasonality of mortality under a warming climate. Methods Daily mean temperature, daily counts for all-cause, circulatory, and respiratory mortality, and annual data on prefecture-specific characteristics were collected for 47 prefectures in Japan between 1972 and 2015. A quasi-Poisson regression model was used to assess the seasonal variation of mortality with a focus on its amplitude, which was quantified as the ratio of mortality estimates between the peak and trough days (peak-to-trough ratio (PTR)). We quantified the contribution of temperature to seasonality by comparing PTR before and after temperature adjustment. Associations between annual mean temperature and annual estimates of the temperature-unadjusted PTR were examined using multilevel multivariate meta-regression models controlling for prefecture-specific characteristics. Results The temperature-unadjusted PTRs for all-cause, circulatory, and respiratory mortality were 1.28 (95% confidence interval (CI): 1.27–1.30), 1.53 (95% CI: 1.50–1.55), and 1.46 (95% CI: 1.44–1.48), respectively; adjusting for temperature reduced these PTRs to 1.08 (95% CI: 1.08–1.10), 1.10 (95% CI: 1.08–1.11), and 1.35 (95% CI: 1.32–1.39), respectively. During the period of rising temperature (1.3 °C on average), decreases in the temperature-unadjusted PTRs were observed for all mortality causes except circulatory mortality. For each 1 °C increase in annual mean temperature, the temperature-unadjusted PTR for all-cause, circulatory, and respiratory mortality decreased by 0.98% (95% CI: 0.54–1.42), 1.39% (95% CI: 0.82–1.97), and 0.13% (95% CI: − 1.24 to 1.48), respectively. Conclusion Seasonality of mortality is driven partly by temperature, and its amplitude may be decreasing under a warming climate., YC was supported by a Senior Research grant (2019R1A2C1086194) from the National Research Foundation of Korea (NRF), funded by the Ministry of Science, ICT (Information and Communication Technologies). YK was supported by JSPS KAKENHI Grant Number JP19K17104. AT was supported by the JSPS Invitational Fellowships for Research in Japan (Grant S18149). YG was supported by the Career Development Fellowship of the Australian National Health and Medical Research Council (Grants APP1107107 and APP1163693). AG was supported by the Medical Research Council UK (Grants MR/M022625/1 and MR/R013349/1), by the Natural Environment Research Council UK (Grant NE/R009384/1), and by the European Union’s Horizon 2020 Project Exhaustion (Grant ID: 820655). YH was supported by the Environment Research and Technology Development Fund (S-14) of the Environmental Restoration and Conservation Agency, Japan.

It is unclear how to develop a model based on the combined satellite data and ground monitoring data to accurately estimate daily NO2 levels. Furthermore, the conventional cross-validation (CV) results represent average levels but the model performance may vary greatly from grid to grid. It is an essential issue to evaluate model's prediction ability in different grids and determine the factors affecting model extrapolating ability, which have never been well examined to date. The aim of this study was to compare the ability of three different methods to estimate the daily NO2 across mainland China during 2014–2016; and to develop a novel two-stage meta-analysis method for exploring the influence of the number and the distribution of nearby sites on grid-level prediction accuracy. For better estimating the daily NO2 level, we developed and compared three methods, including universal kriging model, satellite-based method (Non-linear exposure-lag-response model & Extreme gradient boosting combined technique) and the kriging-calibrated satellite method. For exploring influencing factors, the two-stage meta-analysis method was purposed. The kriging-calibrated satellite method had an overall CV R-square and root mean square error (RMSE) of 0.85 and 7.87μg/m3, better than the Universal Kriging model and the satellite-based method (CV R2 = 0.57 and 0.81). The two-stage meta-analysis method revealed that the model performance did decrease with the sparser distribution of nearby sites. And adding 5 sites within 50 km in the random mode can bring 17.51% improvement in model extrapolating ability. The kriging-calibration can help satellite-based machine learning to provide more accurate NO2 prediction. Our novel evaluation method can provide the suggestion of adding new sites effectively within a limit budget.

BackgroundHeat exposure has been related to increased morbidity and mortality for several health outcomes. There is little evidence whether this is also true for COPD. This study quantified the relationship between ambient heat and hospitalisation for COPD in the Brazilian population.MethodsData on hospitalisations for COPD and weather conditions were collected from 1642 cities during the 2000–2015 hot seasons. A time-stratified, case-crossover design was used for city-specific analyses, which were then pooled at the regional and national levels using random-effect meta-analyses. Stratified analyses were performed by sex, age group and early/late hot season. Annual change in the association was examined using a random-effect meta-regression model.ResultsThe OR of hospitalisation was 1.05 (95% CI 1.04 to 1.06) for every 5℃ increase in daily mean temperature at the national level, with the effect estimate stronger in the late hot season compared with the early hot season. The effect was similar in women and in men but was greatest for those aged ≥75 years. The association was stronger in the central west and southeast regions and minimal in the northeast. Assuming a causal relationship, 7.2% of admissions were attributable to heat exposure. There was no significant temporal decline in the impact of ambient heat over the 16-year study period.ConclusionIn Brazil, exposure to ambient heat was positively associated with hospitalisation for COPD, particularly during the late hot season. These data add to the growing evidence base implicating global warming as being an important contributor to the future healthcare burden.

Background Atopic dermatitis (AD) is the most common skin disorder in infancy. However, the diagnosis and definite significance of infantile AD remains a debated issue. Objective To analyse the phenotypes of AD in infancy, to establish diagnostic criteria and to estimate the prevalence of this condition in China. Methods This is a multicentric study, in which 12 locations were chosen from different metropolitan areas of China. Following careful and complete history-taking and skin examination, the definite diagnosis of AD was made and the severity based on the SCORAD index was determined by local experienced dermatologists. Based on the detailed phenotyping, the major and representative clinical features of infantile AD were selected to establish the diagnostic criteria and evaluate their diagnostic efficacy. Results A total of 5967 infants were included in this study. The overall point prevalence of AD was 30.48%. The infantile AD developed as early as at the second month of life, and its incidence peaked in the third month of life at 40.81%. The proportion of mild, moderate and severe AD was 67.40%, 30.57% and 2.03%, respectively. The most commonly seen manifestations in the infantile AD were facial dermatitis (72.07%), xerosis (42.72%) and scalp dermatitis (27.93%). We established the novel diagnostic criteria of infants, which included: (i) onset after 2 weeks of birth; (ii) pruritus and/or irritability and sleeplessness comparable with lesions; and (iii) all two items above with one of the following items can reach a diagnosis of AD: (i) eczematous lesions distributed on cheeks and/or scalp and/or extensor limbs, and (ii) eczematous lesions on any other parts of body accompanied by xerosis. Conclusions In China, the prevalence of AD in infancy is 30.48% according to clinical diagnosis of dermatologists. The novel Chinese diagnostic criteria for AD in infants show a higher sensitivity and comparable specificity.

Evidence of the short-term effect of SO2 on hospital admissions for cause-specific cardiovascular diseases (CVD) is still limited. This study aimed to examine the short-term associations between SO2 and cause-specific CVD hospital admission in Beijing. A total of 460,938 hospitalizations for total CVD were obtained from electronic hospitalization summary reports from 2013 to 2017. A time series analysis was conducted to investigate the association between SO2 exposure and hospitalizations for total and cause-specific CVD, including coronary heart disease (CHD), atrial fibrillation (AF), and heart failure (HF). Stratified analysis was also conducted by age group (18–64 years and ≥65 years), sex and season. A generalized additive quasi-Poisson model was used to examine the associations between SO2 and cause-specific CVD after controlling for seasonality, day of the week, public holidays, and weather conditions. We found an almost linear relationship between the exposure to SO2 and cause-specific CVD admissions. A 10 μg/m3 increase in the two-day average concentration (lag0-1) of SO2 was associated with an increase of 1.38% (95% CI:0.99%; 1.77%) in hospital admission for total CVD, 1.58% (95% CI: 1.16%; 2%) for CHD and 1.69% (95% CI:0.41%; 2.99%) for AF. Nevertheless, a statistically significant association was not observed for admissions for HF. The observed associations in the single-pollutant models were robust to the inclusion of pollutants in the two-pollutant model, but the estimate was attenuated when adjusting for fine particulate matter (PM2.5). No difference in the association was observed for the effect modifiers of sex, season and age. A statistically significant association between hospitalizations and SO2 was observed. The observed association between SO2 and hospitalization might not be independent of fine particulate matter ( PM 2.5 ), and further studies should be conducted to demonstrate the independent effect of SO2.

Purpose We summarized the evidence on the effects of heat and cold exposures on mortality in China. We included studies published on this topic in both Chinese and English, thereby filling a gap in knowledge using data from a country that consists of one-fifth of the world's population. Methods We conducted a systematic search of peer-reviewed studies on the association between daily mean temperature and mortality published from 2001 up to July 2018. We searched one Chinese database (China National Knowledge infrastructure, http://www.cnki.net ) and three English databases (PubMed, Scopus, Web of Science). We converted the effect estimates of heat/cold to rate ratios (RRs) associated with 1° increase/decrease beyond the heat/cold reference temperatures. For studies that provided lag-specific estimates, we used both the maximum and minimum of RR estimates. We calculated summary effect estimates for all-cause and cause-specific mortalities, as well as RRs stratified by sex, age, and socioeconomic status. We also investigated patterns of heat and cold adaptation at different latitudes, and at different reference temperatures. Results In total, 45 articles were included in this systematic review. For every 1° temperature increase/decrease beyond reference points, the rate of non-accidental mortality increased by 2% (RR, 1.02; 95% confidence interval (95% CI [1.01–1.02]) for heat and 4% (RR, 1.04; 95% CI [1.03–1.04]) for cold, respectively; the rate of cardiovascular mortality increased 3% (RR, 1.03; 95% CI [1.03–1.04]) for heat and 6% (RR, 1.06; 95% CI [1.04–1.07]) for cold; the rate of respiratory mortality increased 2% (RR, 1.02; 95% CI [1.01–1.03]) for heat and 2% (RR, 1.02; 95% CI [1.00–1.04]) for cold; the rate of cerebrovascular mortality increased 2% (RR, 1.02; 95% CI [1.02–1.03]) for heat and 3% (RR, 1.03; 95% CI [1.02–1.04]) for cold. We identified a variation in optimal temperature range related to latitude of the residential area, and differences in people's capability to adapt to heat versus cold. Conclusion We found consistent evidence of the association between temperature and mortality, as well as evidence of patterns in human adaptation, and we discussed the implications of our findings.

Studies worldwide have estimated the number of deaths attributable to long-term exposure to fine airborne particles (PM2.5), but limited information is available on short-term exposure, particularly in China. In addition, most existing studies have assumed that short-term PM2.5-mortality associations were linear. For this reason, the use of linear exposure-response functions for calculating disease burden of short-term exposure to PM2.5 in China may not be appropriate. There is an urgent need for a comprehensive, evidence-based assessment of the disease burden related to short-term PM2.5 exposure in China. Here, we explored the non-linear association between short-term PM2.5 exposure and all-cause mortality in 104 counties in China; estimated county-specific mortality burdens attributable to short-term PM2.5 exposure for all counties in the country and analyzed spatial characteristics of the mortality burden due to short-term PM2.5 exposure in China. The pooled PM2.5-mortality association was non-linear, with a reversed J-shape. We found an approximately linear increased risk of mortality from 0 to 62 μg/m3 and decreased risk from 62 to 250 μg/m3. We estimated a total of 169,862 additional deaths from short-term PM2.5 exposure throughout China in 2015. Models using linear exposure-response functions for the PM2.5-mortality association estimated 32,186 deaths attributable to PM2.5 exposure, which is 5.3 times lower than estimates from the non-linear effect model. Short-term PM2.5 exposure contributed greatly to the death burden in China, approximately one seventh of the estimates from the chronic effect. It is essential and crucial to incorporate short-term PM2.5-related mortality estimations when considering the disease burden attributable to PM2.5 in developing countries such as China. Traditional linear effect models likely underestimated the mortality burden due to short-term exposure to PM2.5. Keywords: PM2.5, Short-term, Mortality burden, Non-linear

No evidence exists concerning the association between blood pressure and ambient particles with aerodynamic diameter

Background The epidemiological evidence on relationships between long-term exposure to particulate matter and hypertension and blood pressure has been inconclusive. Limited evidence was available for particulate matter with an aerodynamic diameter ≤ 1 μm (PM1) in rural areas of developing countries. Objective This study aimed to investigate the associations between long-term exposure to PM1 and hypertension and blood pressure among rural Chinese population. Methods This study included 39,259 participants who had completed the baseline survey from Henan Rural Cohort. Participants' exposure to PM1 was assessed by a satellite-based spatiotemporal model. The binary logistic regression model was used to examine the association between long-term PM1 exposure and hypertension, and multivariable linear regression model was used to investigate the associations between long-term PM1 exposure and systolic blood pressure (SBP), diastolic blood pressure (DBP), mean arterial pressure (MAP) and pulse pressure (PP). Moreover, we examined potential effect modifications by demographic, lifestyle and diet factors. Results The mean concentration of PM1 for all participants during the 3-year before baseline survey was 59.98 μg/m3. Each 1 μg/m3 increase in PM1 concentration was significantly associated with an increase of 4.3% [Odds ratio(OR) = 1.043, 95% confidence interval(CI): 1.033, 1.053] in odds for hypertension, an increase of 0.401 mm Hg (95% CI, 0.335, 0.467), 0.328 mm Hg (95% CI, 0.288, 0.369), 0.353 mm Hg (95% CI, 0.307, 0.399) and 0.073 mm Hg (95% CI, 0.030, 0.116) in SBP, DBP, MAP and PP, respectively. Further stratified analyses showed that the effect of PM1 on hypertension and blood pressure could be modified by sex, lifestyle and diet. Conclusions This study suggests that long-term exposure to ambient PM1 increases the risk of hypertension and is associated with elevations in blood pressure in rural Chinese adults, especially in male and those with unhealthy habits., Highlights • Rural cohort participants were exposed to high level of PM1 during the study period. • PM1 was related to increased risk of hypertension and elevated blood pressure. • Males and those with unhealthy habits were more susceptible to the adverse effect.

Background and purpose Several clinical trials have demonstrated that dual antiplatelet therapy (DAPT) benefited patients with transient ischaemic attack (TIA) with an ABCD2 score ≥4. The present study aimed to investigate whether the ABCD3-I score could be a more appropriate tool for selection of patients with TIA to receive DAPT in real-world settings. Methods We derived data from the TIA database of The First Affiliated Hospital of Zhengzhou University. The predictive outcome was ischaemic stroke at 90 days. The additive interaction effect was presented by the attributable proportion due to interaction. Kaplan-Meier curves were plotted to present cumulative stroke rates in different risk categories with monotherapy and DAPT. Cox proportional hazards regression was used to determine risk factors associated with stroke. Results Among 785 patients, the mean (SD) age was 56.95 (12.73) years and 77 patients (9.8%) had an ischaemic stroke at 90 days. A total of 55.8% of patients (attributable proportion due to interaction; 95% confidence interval, 20.8%-90.9%) were attributed to additive interaction of ABCD3-I score and antiplatelet therapy. Kaplan-Meier curves showed a significant difference between patients receiving monotherapy and DAPT in high-risk patients with TIA (P = 0.021). DAPT reduced 90-day stroke risk in high-risk patients with TIA as assessed independently by ABCD3-I score (adjusted hazard ratio, 0.43; 95% confidence interval, 0.20-0.92, P = 0.031). The benefit did not exist in low- and medium-risk patients by ABCD3-I score (patients with ABCD2 score ≥ 4 or Conclusions High-risk patients with TIA assessed by ABCD3-I score received the most pronounced clinical benefit from early use of DAPT in real-world clinical experience.

Background: Most evidences regarding ambient PM2.5 or PM10 (particulate matter of median aerodynamic diameter ≤2.5 μm or ≤10 μm) and preterm birth (PTB) come from western countries which has relatively low PM pollution exposure, and the results are still inconsistent. This study aims to examine whether exposure to high concentrations of PM2.5 or PM10 was associated with PTB (

Background: The evidence for adverse effects of ambient particulate matter (PM) pollution on mental health is limited. Studies in Western countries suggested higher risk of autism spectrum disorder (ASD) associated with PM air pollution, but no such study has been done in developing countries. Methods: A case-control study was performed in Shanghai with a multi-stage random sampling design. Children's exposures to PM1, PM2.5 and PM10 (particulate matter with aerodynamic diameter

Background: Limited evidence is available on the health effects of particulate matter with an aerodynamic diameter of

Background In 2014, the Morwell brown coal mine, located in the Latrobe Valley of South eastern Australia, caught fire covering nearby areas in plumes of smoke over a 6-week period. Aims To investigate the association between exposure to mine fire related air pollution and the risk of mortality. Methods Time series models were used to evaluate the risk of mortality during the first 30 days of the mine fire, when the smoke was most intense, and in the following six months. Associations were also investigated between mine fire related PM2.5 and mortality. Results During the 30-day mine fire period, there was an increased risk of death from injury in the most exposed town of Morwell, however no increased risk was observed for all-cause, cardiovascular or respiratory mortality. In the broader Latrobe Valley, males and residents aged 80 and above were at greatest risk of death from injury during the mine fire. In Morwell, during the six months after the mine fire there was an increased risk of all-cause mortality and death from Ischaemic Heart Disease (IHD). Males and residents aged 80 and above in the broader Latrobe Valley, were at increased risk of death from IHD six months after the fire. Conclusions Coal mine fire exposure was associated with an increase in injury deaths during the mine fire and cardiovascular deaths in the six months after the fire. These findings assist in identifying at risk groups, and improving targeted health advice for future air pollution exposures in the community.

Long-term exposure to air pollutants and residential greenness related to advanced fibrosis have been sparsely studied in low- and middle-income countries. A total of 29883 participants were selected from a cross-sectional survey of the Henan Rural Cohort. Concentrations of air pollutants (particulate matter with an aerodynamic diameter ≤ 1.0 μm (PM1), ≤ 2.5 μm (PM2.5), ≤ 10 μm (PM10) and nitrogen dioxide (NO2)) for participants were predicted by using a spatiotemporal model. Residential greenness of each participant was indicated by Enhanced Vegetation Index (EVI) and Normalized Difference Vegetation Index (NDVI). Independent and joint associations of air pollutants and residential greenness indices with prevalent advanced fibrosis reflected by fibrosis-4 score (FIB4), aspartate-to-platelet-ratio index (APRI) and ALT/AST ratio were analyzed by generalized linear mixed models and their interactive effect on prevalent advanced fibrosis were visualized by using the interplot method. Long-term exposure to PM1, PM2.5, PM10 and NO2 were positively related to FIB4 or APRI as well as prevalent intermediate-high advanced fibrosis; EVI was negatively related to FIB4 or APRI as well as prevalent intermediate-high advanced fibrosis. Negative associations of residential greenness indices (EVI or NDVI) with prevalent advanced fibrosis were decreased as increased air pollutants (PM1, PM2.5, PM10 or NO2) (P < 0.05 for all). This study indicated that residential greenness may partially attenuate negative effect of long-term exposure to air pollutants related to increased prevalent intermediate-high advanced fibrosis, implying that residential greenness may be an effective strategy to reduce the burden of prevalent hepatic fibrosis and its related disease in association with exposure high levels of air pollutants. The Henan Rural Cohort study has been registered at Chinese Clinical Trial Register (Registration number: ChiCTR-OOC-15006699, http://www.chictr.org.cn/showproj.aspx?proj=11375 )

Background Low socio-economic status (SES) and exposure to single-air pollutant relate to increased prevalent atherosclerotic cardiovascular diseases (ASCVD), however, interactive effect between SES and exposure to single- or multiple-air pollutants on high 10-year ASCVD risk remains unclear. Methods A total of 31,162 individuals were derived from the Henan Rural Cohort Study. Concentrations of air pollutants (particulate matter with an aerodynamic diameter ≤ 1.0 μm (PM1), ≤2.5 μm (PM2.5) or ≤10 μm (PM10), nitrogen dioxide (NO2)) were assessed using a spatiotemporal model based on satellites data. Independent and joint associations of SES, single- and multiple- air pollutants with high 10-year ASCVD risk were evaluated using logistic regression models, quantile g-computation and structural equation models. The interactive effects of SES and exposure to single- or multiple air pollutants on high 10-year ASCVD risk were visualized by using Interaction plots. Results Exposure to single air pollutant (PM1, PM2.5, PM10 or NO2) related to increased high 10-year ASCVD risk among individuals with low education level or personal average monthly income, compared to the ones with high education level or personal average monthly income. Furthermore, similar results of exposure to mixture of air pollutants with high 10-year ASCVD risk were observed. Positive interactive effects between low SES and exposure to high single air pollutant or the mixture of air pollutants on high 10-year ASCVD risk were observed. Conclusion Positive association of low SES with high 10-year ASCVD risk was amplified by exposure to high levels of single air pollutant or a mixture of air pollutants, implying that individuals with low SES may more susceptible to air pollution-related adverse health effect.

There is an established association between air pollution and cardiovascular disease (CVD), which is likely to be mediated by systemic inflammation. The present study evaluated links between long-term exposure to ambient air pollution and high-sensitivity C reactive protein (hs-CRP) in an older Chinese adult cohort (n = 7915) enrolled in the World Health Organization (WHO) study on global aging and adult health (SAGE) China Wave 1 in 2008–2010. Multilevel linear and logistic regression models were used to assess the associations of particulate matter (PM) and nitrogen dioxide (NO2) on log-transformed hs-CRP levels and odds ratios of CVD risk derived from CRP levels adjusted for confounders. A satellite-based spatial statistical model was applied to estimate the average community exposure to outdoor air pollutants (PM with an aerodynamic diameter of 10 μm or less (PM10), 2.5 μm or less (PM2.5), and 1 μm or less (PM1) and NO2) for each participant of the study. hs-CRP levels were drawn from dried blood spots of each participant. Each 10 μg/m3 increment in PM10, PM2.5, PM1, and NO2 was associated with 12.8% (95% confidence interval, (CI): 9.1, 16.6), 15.7% (95% CI: 10.9, 20.8), 10.2% (95% CI: 7.3, 13.2), and 11.8% (95% CI: 7.9, 15.8) higher serum levels of hs-CRP, respectively. Our findings suggest that air pollution may be an important factor in increasing systemic inflammation in older Chinese adults.

Benign prostatic hyperplasia (BPH) is a common disease in aging males. It has been proven that the Hedgehog (HH) is implied as an effective and fundamental regulatory growth factor signal for organogenesis, homeostasis, and regeneration. Smoothened (SMO), as the major control point of HH signals, activates aberrantly in most human solid tumors. However, the specific function of SMO and its downstream glioma-associated oncogene (GLI) family in BPH has not been well understood. Here, we first revealed that the SMO cascade was upregulated in BPH tissues and was localized in both the stromal and the epithelium compartments of human prostate tissues. Cyclopamine, as a specific SMO inhibitor, was incubated with BPH-1 and WPMY-1, and intraperitoneally injected into a BPH rat model established by castration with testosterone supplementation. SMO inhibition could induce cell apoptosis, cell cycle arrest at the G0/G1 phase, and a reduction of tissue fibrosis markers, both in vitro and in vivo. Finally, a tissue microarray, containing 104 BPH specimens, was constructed to analyze the correlations between the expression of SMO cascade and clinical parameters. The GLI2 was correlated positively with nocturia and negatively with fPSA. The GLI3 was in a positive relationship with International Prostate Symptom Score and nocturia. In conclusion, our study suggested that SMO cascade could play important roles in the development of BPH and it might be rediscovered as a promising therapeutic target for BPH.

Context Evidence regarding the association of long-term exposure to air pollution on bone strength or osteoporosis is rare, especially in highly polluted low- and middle-income countries. Little is known about whether the association between air pollution and bone strength changes at different bone strength distributions. Objective Using the baseline data from the China Multi-Ethnic Cohort, we investigated the association between long-term air pollution exposure and bone strength. Methods We used multiple linear models to estimate the association between air pollution and bone strength, and we conducted quantile regression models to investigate the variation of this association in the distribution of bone strength. The 3-year concentrations of PM1, PM2.5, PM10, and NO2 for each participant were assessed using spatial statistical models. Bone strength was expressed by the calcaneus quantitative ultrasound index (QUI) measured by quantitative ultrasound, with higher QUI values indicating greater bone strength. Results A total of 66 598 participants were included. Our analysis shows that every 10 μg/m3 increase in 3-year average PM1, PM2.5, PM10, and NO2 was associated with −5.38 units (95% CI: −6.17, −4.60), −1.89 units (95% CI: −2.33, −1.44), −0.77 units (95% CI: −1.08, −0.47), and −2.02 units (95% CI: −2.32, −1.71) changes in the QUI, respectively. In addition, populations with higher bone strength may be more susceptible to air pollution. Conclusion Long-term exposure to PM1, PM2.5, PM10, and NO2 was significantly associated with decreased bone strength in southwestern China adults. Air pollution exposure has a more substantial adverse effect on bones among populations with higher bone strength.

Background The prevalence of metabolic syndrome (MetS) rapidly increased over the past decades. However, little evidence exists about the effects of long-term exposure to ambient air pollution on MetS in children and adolescents. Objective This study aims to assess the association between long-term ambient air pollution and the prevalence of MetS in a large population of Chinese children and adolescents. Methods In 2013, a total of 9,897 children and adolescents aged 10 to 18 years were recruited from seven provinces/municipalities in China. MetS was defined based on the recommendation by the International Diabetes Federation (IDF). Satellite based spatio-temporal models were used to estimate exposure to ambient air pollution (including particles with diameters ≤1.0 µm (PM1), ≤2.5 µm (PM2.5), and ≤10 µm (PM10), and nitrogen dioxide (NO2)). Individual exposure was calculated according to 94 schools addresses. After adjustment for a range of covariates, generalized linear mixed-effects models were utilized to evaluate the associations between air pollutants and the prevalence of MetS and its components. In addition, several stratified analyses were examined according to sex, weight status, outdoor physical activity time, and sugar-sweetened beverages (SSBs) intake. Results The prevalence of MetS was 2.8%. The odds ratio of MetS associated with a 10 μg/m3 increase in PM1, PM2.5, PM10 and NO2 was 1.20 (95%CI: 0.99, 1.46), 1.31 (95%CI: 1.05, 1.64), 1.32 (95%CI: 1.08, 1.62), and 1.33 (95%CI: 1.03, 1.72), respectively. Regarding the MetS components, we observed associations between all pollutants and abdominal obesity. In addition, long-term PM1 and NO2 exposures were associated with the prevalence of elevated fasting blood glucose. Stratified analyses detected that the associations between air pollutants and the prevalence of MetS were stronger in boys (Pinteraction Conclusions We found that long-term exposure to PM2.5, PM10, and NO2 were positively associated with the prevalence of MetS in children and adolescents. Our findings may have certain public health implications for some comprehensive strategy of environment improvement and lifestyles changes in order to reduce the burden of non-communicable disease.

Background Air pollution is a potential environmental risk for sleep disturbance. However, the evidence is very limited in China. On the other hand, physical activity (PA) is a preventive behavior that can improve insomnia, but whether PA mitigates the negative impact of air pollution on insomnia is unknown. Methods We obtained data from the baseline of China Multi-Ethnic Cohort (CMEC) survey, and examined the association between air pollution and insomnia, as well as PA's modification effect of on this association. We included 70,668 respondents and assessed insomnia by self-reported symptoms collected using electronic questionnaires. Using satellite data, we estimated the residence-specified, three-year average PM1, PM2.5, PM10 (particulate matter with aerodynamic diameters of ≤1 μm, ≤2.5 μm and 10 μm, respectively), O3 (ozone), and NO2 (nitrogen dioxide) concentrations. We established the associations between air pollutants and insomnia through logistic regression. We evaluated the modification impact of total and domain-specific PA (leisure, occupation, housework, transportation) by introducing an interaction term. Results Positive associations were observed between long-term exposure to PM1, PM2.5, PM10, and O3 and insomnia symptoms, with ORs (95% CI) of 1.09 (1.03–1.16), 1.11 (1.07–1.15), 1.07 (1.05–1.10) and 1.15 (1.11–1.20), respectively. As total PA increased, the ORs of air pollution for insomnia tended to decrease and then rise. We observed varying modification effects of domain-specific PA. With an increase in leisure PA, the ORs for PM2.5 and PM10 significantly declined. However, increased ORs of air pollutants were related to insomnia among participants with higher levels of occupational and housework PA. Conclusion Long-term exposure to higher concentrations of PM1, PM2.5, PM10, and O3 increases the risk of insomnia symptoms. Moderate to high levels of leisure PA alleviate the harmful effects of air pollution on insomnia, while high levels of occupation and housework PA intensify such effects.

BACKGROUND: Recent studies suggest that household endotoxin and allergens can modify the impact of air pollutants on development of asthma; however, epidemiological evidence is limited and conflicting. OBJECTIVES: To investigate whether pet ownership modified the association between ambient air pollution and asthma in children. METHODS: We conducted a population-based cross-sectional study, the Seven Northeast Cities Study in China and recruited a total of 59,754 children from 94 schools during 2012-2013. Long-term air pollutant concentrations, including airborne particulate matter with a diameter of 1 μm or less (PM1 ), PM2.5 , PM10 , and nitrogen dioxide (NO2 ) from 2009 to 2012 were estimated using a random forest model. We collected information of respiratory health in children using the Epidemiologic Standardization Project Questionnaire of the American Thoracic Society (ATS-DLD-78-A). Regression models were used to evaluate associations between pet ownership and air pollution on asthma after adjusting for potential covariates. RESULTS: Exposure to increasing levels of air pollutants was associated with higher prevalence of asthma, but associations were significantly attenuated in children who owned pets. For example, compared to children without pets, those who owned pets did not have an increased risk of symptoms of asthma (odds ratio, 1.01, 95% confidence interval: 0.78, 1.30), wheeze (0.96, 95% confidence interval [CI]: 0.76, 1.21), and cough (1.01, 95% CI: 0.87, 1.18) for each 10 µg/m3 increase in PM1 (P-int

Evidence on the health benefits of green space in residential environments is still limited, and few studies have investigated the potential association between blue space and type 2 diabetes mellitus (T2DM) prevalence. This study included 39,019 participants who had completed the baseline survey from the Henan Rural Cohort Study, 2015&ndash, 2017. The Normalized Difference Vegetation Index (NDVI) and Enhanced Vegetation Index (EVI) were employed to characterize the residential green space, and the distance from the participant&rsquo, s residential address to the nearest water body was considered to represent the residential blue space. Mixed effect models were applied to evaluate the associations of the residential environment with T2DM and fasting blood glucose (FBG) levels. An interquartile range (IQR) increase in NDVI and EVI was significantly associated with a 13.4% (odds ratio (OR): 0.866, 95% Confidence interval (CI): 0.830,0.903) and 14.2% (OR: 0.858, 95% CI: 0.817,0.901) decreased risk of T2DM, respectively. The residential green space was associated with lower fasting blood glucose levels in men (%change, &minus, 2.060 in men vs. &minus, 0.972 in women) and the elderly (%change, &minus, 1.696 in elderly vs. &minus, 1.268 in young people). Additionally, people who lived more than 5 km from the water body had a 15.7% lower risk of T2DM (OR: 0.843, 95% CI: 0.770,0.923) and 1.829% lower fasting blood glucose levels (95% CI: &minus, 2.335%,&minus, 1.320%) than those who lived closer to the blue space. Our findings suggest that residential green space was beneficially associated with T2DM and fasting blood glucose levels. However, further research is needed to explore more comprehensively the relationship between residential blue space and public health.