Potential causal links between long-term ambient particulate matter exposure and cardiovascular mortality: New evidence from a large community-based cohort in South China.

BACKGROUND: Cardiovascular disease (CVD) mortality is associated with long-term particulate matter (PM) exposure. However, evidence from large, highly-exposed population cohort and observational-data-based causal inference approaches remains limited. AIMS: We examined the potential causal links between PM exposure and the CVD mortality in South China. METHODS: 580,757 participants were recruited during 2009-2015 and followed up through 2020. Satellite-based annual concentrations of PM2.5, PM10, and PMcoarse (i.e., PM10 - PM2.5) at 1 km2 spatial resolution were estimated and assigned to each participant. Marginal structural Cox models with time-varying covariates, adjusted using inverse probability weighting, were developed to evaluate the association between prolonged PM exposure and CVD mortality. RESULTS: For overall CVD mortality, the hazard ratios and 95% confidence interval for each 1 µg/m3 increase in the annual average concentration of PM2.5, PM10, and PMcoarse were 1.033 (1.028-1.037), 1.028 (1.024-1.032), and 1.022 (1.012-1.033), respectively. All three PMs were linked to a higher mortality risk for myocardial infarction and ischemic heart disease (IHD). The mortality risk of chronic IHD and hypertension was linked to PM2.5 and PM10. Significant association between PMcoarse and other heart disease mortality was also observed. The older, women, less-educated participants, or inactive participants exhibited particularly higher susceptibility. Participants who were generally exposed to PM10 concentrations below 70 µg/m3 were more vulnerable to PM2.5-, PM10- and PMcoarse-CVD mortality risks. CONCLUSION: This large cohort study provides evidence for the potential causal links between increased CVD mortality and ambient PM exposure, as well as socio-demographics linked to the highest vulnerability.

The causal links between long-term exposure to major PM2.5 components and the burden of tuberculosis in China.

BACKGROUND: We aimed to estimate the causal impacts of long-term exposure to major PM2.5 components - including black carbon, organic matter, sulfate, nitrate, and ammonium - on the incidence and mortality of tuberculosis in China. METHODS: We collected annual and provincial-level tuberculosis incidence and mortality, concentrations of PM2.5 components, and socioeconomic indicators from between 2004 and 2018 in mainland China. We used the difference-in-differences (DID) causal inference approach with a generalized weighted quantile sum (gWQS) regression model to estimate the long-term effects and relative contributions of PM2.5 components' exposure on tuberculosis incidence and mortality. RESULTS: We found that long-term multi-components exposure was significantly associated with tuberculosis incidence (WQS index IR%:8.34 %, 95 % CI:4.54 %-12.27 %) and mortality (WQS index IR%:19.49 %, 95 % CI: 9.72 %-30.13 %). Primary pollutants, black carbon and organic matter, contributed most of the overall mixture effect (over 85 %). Nitrate showed a critical role in tuberculosis burden in not-aging provinces and in regions at the Q3 stratum (i.e., the 3rd quartile) of GDP per capita and urbanization rate. Meanwhile the contribution of sulfate to tuberculosis burden in regions at the Q1 stratum of GDP per capita and urbanization rate was the largest among the effect of secondary pollutants (i.e., sulfate, nitrate, and ammonium). CONCLUSION: The mitigation of black carbon and organic matter pollution may significantly reduce the tuberculosis burden in China. Controlling nitrate emissions and increasing clean energy (i.e., energy sources with limited pollution emissions, such as natural gas and clean coal) may also be effective in certain regions.

The complex role of air pollution on the association between greenness and respiratory mortality: Insight from a large cohort, 2009-2020.

BACKGROUND: Although emerging studies have illuminated the protective association between greenness and respiratory mortality, efforts to quantify the potentially complex role of air pollution in the causal pathway are still limited. We aimed to examine the potential roles of air pollution in the causal pathway between greenness and respiratory mortality in China. METHODS: We used data from a community-based prospective cohort of 654,115 participants in southern China (Jan 2009-Dec 2020). We evaluated the greenness exposure as a three-year moving average Normalized Difference Vegetation Index (NDVI) within the 500 m buffer around the residence. Cox proportional hazards model was applied to estimate the association between greenness and respiratory mortality. Causal mediation analysis combined with a four-way dimensional decomposition method was utilized to simultaneously quantify the interaction and mediation role of air pollution including PM2.5, PM10, or NO2 on the greenness-respiratory mortality relationship. FINDINGS: We observed 6954 respiratory deaths during 12 years of follow-up. Increasing NDVI level from the lowest to the highest quartile is associated with a 19 % (95%CI: 13-25 %) reduction in the respiratory mortality risk. For the total protective effect, the proportion attributable to the overall negative interaction between greenness and air pollution (PM2.5, PM10, or NO2) was 2.2 % (1.7-3.2 %), 3.5 % (0.4-3.7 %), or 25.0 % (22.8-27.1 %), respectively. Simultaneously, we estimated 25.5 % (20.1-32.0 %), 49.5 % (32.5-71.9 %), or 1.0 % (0.8-1.2 %) of the total protective association was mediated through a reduction in PM2.5, PM10, or NO2, respectively. INTERPRETATION: Increased greenness exposure mitigated respiratory mortality through both the antagonistic interaction and mediation pathway of air pollution (PM2.5, PM10, or NO2).

Potential causal links between long-term ambient particulate matter exposure and cerebrovascular mortality: Insights from a large cohort in southern China.

Cohort studies conducted in North America and Europe have linked cerebrovascular mortality to long-term exposure to particulate matter (PM). However, limited evidence from large cohorts in high-exposure areas and the traditional approach of association assessment may cause residual confounding issues. In this study, we aimed to investigate the causal links between cerebrovascular mortality and long-term exposure to PM2.5, PM10, and PM2.5-10 in an ongoing cohort study with 580,757 participants in southern China. Using satellite-based estimates of PM concentration at a 1-km2 spatial resolution, we assigned exposure levels to each participant and used the marginal structural Cox model to assess the association between PM exposure and cerebrovascular mortality while accounting for time-varying covariates. We also explored the potential modification effects of sociodemographic and behavioral factors on the PM-health associations. Adjusted hazard ratios (HR) for overall cerebrovascular mortality were 1.041 (95% confidence interval (CI): 1.034-1.049) and 1.032 (95% CI: 1.026-1.038) for each 1 µg/m3 increase in PM2.5, and PM10, respectively. Similar trends were observed in the mortality risk from stroke and ischemic stroke, with HRs ranging from 1.040 to 1.069 and 1.025 to 1.052, respectively, across 2 p.m. exposures. The impact of PM exposure was generally more apparent among women, participants with primary school diplomas and below, and the subgroup under low-exposure. Multiple sensitivity analyses confirmed the robustness of the results. In conclusion, this sizable prospective cohort study hypothesizes causal links between long-term PM exposure and cerebrovascular mortality, particularly among vulnerable participants, supporting the rationale for reducing PM concentration in China to reduce cerebrovascular mortality.

The impact of monthly air pollution exposure and its interaction with individual factors: Insight from a large cohort study of comprehensive hospitalizations in Guangzhou area.

Background: Although the association between short-term air pollution exposure and certain hospitalizations has been well documented, evidence on the effect of longer-term (e. g., monthly) air pollution on a comprehensive set of outcomes is still limited. Method: A total of 68,416 people in South China were enrolled and followed up during 2019-2020. Monthly air pollution level was estimated using a validated ordinary Kriging method and assigned to individuals. Time-dependent Cox models were developed to estimate the relationship between monthly PM10 and O3 exposures and the all-cause and cause-specific hospitalizations after adjusting for confounders. The interaction between air pollution and individual factors was also investigated. Results: Overall, each 10 µg/m3 increase in PM10 concentration was associated with a 3.1% (95%CI: 1.3%-4.9%) increment in the risk of all-cause hospitalization. The estimate was even greater following O3 exposure (6.8%, 5.5%-8.2%). Furthermore, each 10 µg/m3 increase in PM10 was associated with a 2.3%-9.1% elevation in all the cause-specific hospitalizations except for those related to respiratory and digestive diseases. The same increment in O3 was relevant to a 4.7%-22.8% elevation in the risk except for respiratory diseases. Additionally, the older individuals tended to be more vulnerable to PM10 exposure (P interaction: 0.002), while the alcohol abused and those with an abnormal BMI were more vulnerable to the impact of O3 (P interaction: 0.052 and 0.011). However, the heavy smokers were less vulnerable to O3 exposure (P interaction: 0.032). Conclusion: We provide comprehensive evidence on the hospitalization hazard of monthly PM10 and O3 exposure and their interaction with individual factors.

Interactions between long-term ambient particle exposures and lifestyle on the prevalence of hypertension and diabetes: insight from a large community-based survey.

INTRODUCTION: Evidence on the interaction of lifestyle and long-term ambient particle (PM) exposure on the prevalence of hypertension, diabetes, particularly their combined condition is limited. We investigate the associations between PM and these outcomes and whether the associations were modified by various lifestyles. METHODS: This was a large population-based survey during 2019-2021 in Southern China. The concentrations of PM were interpolated and assigned to participants by the residential address. Hypertension and diabetes status were from questionnaires and confirmed with the community health centres. Logistic regression was applied to examine the associations, followed by a comprehensive set of stratified analyses by the lifestyles including diet, smoking, drinking, sleeping and exercise. RESULTS: A total of 82 345 residents were included in the final analyses. For each 1 µg/m3 increase in PM2.5, the adjusted OR for the prevalence of hypertension, diabetes and their combined condition were 1.05 (95% CI 1.05 to 1.06), 1.07 (95% CI 1.06 to 1.08) and 1.05 (95% CI 1.04 to 1.06), respectively. We observed that the association between PM2.5 and the combined condition was greatest in the group with 4-8 unhealthy lifestyles (OR=1.09, 95% CI 1.06 to 1.13) followed by the group with 2-3 and those with 0-1 unhealthy lifestyle (P interaction=0.026). Similar results and trends were observed in PM10 and/or in those with hypertension or diabetes. Individuals who consumed alcohol, had inadequate sleep duration or had poor quality sleep were more vulnerable. CONCLUSION: Long-term PM exposure was associated with increased prevalence of hypertension, diabetes and their combined condition, and those with unhealthy lifestyles suffered greater risks of these conditions.

A mouse model of swine influenza virus H9N2 infection with acute lung injury.

UNLABELLED: BALB/c mice inoculated intranasally with A/swine/HeBei/012/2008/ (H9N2) virus (SIV), showing acute lung injury (ALI)/acute respiratory distress syndrome (ARDS), were observed for morbidity (lung histopathology, lung coefficient, lung wet/dry weight (W/D) ratio, arterial blood gas characteristics and inflammatory cells in bronchial alveolar lavage fluid (BALF)) and mortality. The results showed that, (1) on days 1-4 post infection (p.i.), mice appeared depressed and showed ruffled fur, reduced food intake, weight loss and hypoxemia with a decreased arterial partial oxygen pressure and an increased partial carbon dioxide pressure. (2) From day 4 p.i., mice began to die and showed pulmonary edema, hemorrhage and inflammatory cells in the alveolar exudate. The lung coefficient and lung W/D ratio significantly increased. (3) On days 3-8 p.i., inflammatory cells, especially alveolar macrophages and polymorphonuclears (PMNs) in BALF significantly increased. (4) The mortality rate reached 62.5%. This study established a successful animal model of ALI induced by infection with H9N2 SIV which may help in further investigations of the pathogenesis of human ALI/ARDS induced by H9N2 SIV infection. KEYWORDS: wine influenza virus; H9N2 subtype; acute lung injury; mouse.

A review on COVID-19 transmission, epidemiological features, prevention and vaccination.

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has caused hundreds of millions of infections and millions of deaths over past two years. Currently, many countries have still not been able to take the pandemic under control. In this review, we systematically summarized what we have done to mitigate the COVID-19 pandemic, from the perspectives of virus transmission, public health control measures, to the development and vaccination of COVID-19 vaccines. As a virus most likely coming from bats, the SARS-CoV-2 may transmit among people via airborne, faecal-oral, vertical or foodborne routes. Our meta-analysis suggested that the R0 of COVID-19 was 2.9 (95% CI: 2.7-3.1), and the estimates in Africa and Europe could be higher. The median Rt could decrease by 23-96% following the nonpharmacological interventions, including lockdown, isolation, social distance, and face mask, etc. Comprehensive intervention and lockdown were the most effective measures to control the pandemic. According to the pooled R0 in our meta-analysis, there should be at least 93.3% (95% CI: 89.9-96.2%) people being vaccinated around the world. Limited amount of vaccines and the inequity issues in vaccine allocation call for more international cooperation to achieve the anti-epidemic goals and vaccination fairness.

Solasonine Causes Redox Imbalance and Mitochondrial Oxidative Stress of Ferroptosis in Lung Adenocarcinoma.

Ferroptosis, a type of iron-dependent oxidative cell death caused by excessive lipid peroxidation, is emerging as a promising cancer therapeutic strategy. Solasonine has been reported as a potential compound in tumor suppression, which is closely linked to ferroptosis. However, ferroptosis caused by solasonine is insufficiently identified and elaborated in lung adenocarcinoma, a fatal disease with high morbidity and mortality rates. First, the biochemical and morphological changes in Calu-1 and A549 cells exposed to solasonine are observed using a cell death assay and a microscope. The cell viability assay is performed after determining the executive concentration of solasonine to assess the effects of solasonine on tumor growth in Calu-1 and A549 cells. The ferroptosis is then identified by using ferroptosis-related reagents on CCK-8, lipid peroxidation assessment, Fe2+, and ROS detection. Furthermore, the antioxidant system, which includes GSH, Cys, GPx4, SLC7A11, and mitochondrial function, is measured to identify the potential pathways. According to the results, solasonine precisely exerts antitumor ability in lung adenocarcinoma cells. Ferroptosis is involved in the solasonine-induced cell death, as well as the accumulation of lipid peroxide, Fe2+, and ROS. Moreover, the failures of antioxidant defense and mitochondrial damage are considered to make a significant contribution to the occurrence of ferroptosis caused by solasonine. The study describes the potential process of ferroptosis caused by solasonine when dealing with lung adenocarcinoma. This encouraging evidence suggests that solasonine may be useful in the treatment of lung cancer.

Molecular characterization and pathogenicity of swine influenza H9N2 subtype virus A/swine/HeBei/012/2008/(H9N2).

The H9N2 subtype influenza virus (IV) is a remarkable member of the influenza A viruses because it can infect not only chickens, ducks and pigs, but also humans. Pigs are susceptible to both human and avian influenza viruses and have been proposed to be intermediate hosts for the generation of pandemic influenza viruses through reassortment or adaptation to the mammalian host. To further understand the genetic characteristics and evolution, we investigated the source and molecular characteristics of the H9N2 subtype swine influenza virus (SIV), and observed its pathogenicity in BALB/c mice. The BALB/c mice were inoculated intranasally with 100 median mouse infectious dose of A/swine/HeBei/012/2008/(H9N2) viruses to observe the pathogenicity. The HA, NP, NA and M gene were cloned, sequenced and phylogenetically analyzed with related sequences available in GenBank. The infected mice presented with inactivity, weight loss and laboured respiration, while the pathological changes were characterized by diffuse alveolar damage in the lung. The nucleotide and deduced amino acid sequence of HA, NP, NA and M gene was similar with that of A/chicken/Hebei/4/2008(H9N2). The HA protein contained 6 glycosylation sites and the motif of HA cleavage site was PARSSR GLF, which is characteristic of low pathogenic IV. In the HA, NP, M and NA gene phylogenetic trees, the isolate clustered with A/chicken/Hebei/4/2008(H9N2). The isolate possibly came from A/chicken/Hebei/4/2008(H9N2) and was partially varied during its cross-species spread.