Unveiling causal connections: Long-term particulate matter exposure and type 2 diabetes mellitus mortality in Southern China.

Evidence of the potential causal links between long-term exposure to particulate matters (PM, i.e., PM1, PM2.5, and PM1-2.5) and T2DM mortality based on large cohorts is limited. In contrast, the existing evidence usually suffers from inherent bias with the traditional association assessment. A prospective cohort of 580,757 participants in the southern region of China were recruited during 2009 and 2015 and followed up through December 2020. PM exposure at each residential address was estimated by linking to the well-established high-resolution simulation dataset. Hazard ratios (HRs) were calculated using time-varying marginal structural Cox models, an established causal inference approach, after adjusting for potential confounders. During follow-up, a total of 717 subjects died from T2DM. For every 1 µg/m3 increase in PM2.5, the adjusted HRs and 95% confidence interval (CI) for T2DM mortality was 1.036 (1.019-1.053). Similarly, for every 1 µg/m3 increase in PM1 and PM1-2.5, the adjusted HRs and 95% CIs were 1.032 (1.003-1.062) and 1.085 (1.054-1.116), respectively. Additionally, we observed a generally more pronounced impact among individuals with lower levels of education or lower residential greenness which as measured by the Normalized Difference Vegetation Index (NDVI). We identified substantial interactions between NDVI and PM1 (P-interaction = 0.003), NDVI and PM2.5 (P-interaction = 0.019), as well as education levels and PM1 (P-interaction = 0.049). The study emphasizes the need to consider environmental and socio-economic factors in strategies to reduce T2DM mortality. We found that PM1, PM2.5, and PM1-2.5 heighten the peril of T2DM mortality, with education and green space exposure roles in modifying it.

Residential greenness and chronic obstructive pulmonary disease in a large cohort in southern China: Potential causal links, risk trajectories, and mediation pathways.

INTRODUCTION: Residential greenness may influence COPD mortality, but the causal links, risk trajectories, and mediation pathways between them remain poorly understood. OBJECTIVES: We aim to comprehensively identify the potential causal links, characterize the dynamic progression of hospitalization or posthospital risk, and quantify mediation effects between greenness and COPD. METHODS: This study was conducted using a community-based cohort enrolling individuals aged ≥ 18 years in southern China from January 1, 2009 to December 31, 2015. Greenness was characterized by normalized difference vegetation index (NDVI) around participants' residential addresses. We applied doubly robust Cox proportional hazards model, multi-state model, and multiple mediation method, to investigate the potential causal links, risk trajectories among baseline, COPD hospitalization, first readmission due to COPD or COPD-related complications, and all-cause death, as well as the multiple mediation pathways (particulate matter [PM], temperature, body mass index [BMI] and physical activity) connecting greenness exposure to COPD mortality. RESULTS: Our final analysis included 581,785 participants (52.52% female; average age: 48.36 [Standard Deviation (SD): 17.56]). Each interquartile range (IQR: 0.06) increase in NDVI was associated with a reduced COPD mortality risk, yielding a hazard ratio (HR) of 0.88 (95 % CI: 0.81, 0.96). Furthermore, we observed per IQR (0.04) increase in NDVI was inversely associated with the risk of multiple transitions (baseline - COPD hospitalization, baseline - death, and readmission - death risks), especially a declined risk of all-cause death after readmission (HR = 0.66 [95 %CI: 0.44, 0.99]). Within the observed association between greenness and COPD mortality, three mediators were identified, namely PM, temperature, and BMI (HR for the total indirect effect: 0.773 [95 % CI: 0.703, 0.851]), with PM showing the highest mediating effect. CONCLUSIONS: Our findings revealed greenness may be a beneficial factor for COPD morbidity, prognosis, and mortality. This protective effect is primarily attributed to the reduction in PM concentration.

Long-term exposure to particulate matter and COPD mortality: Insights from causal inference methods based on a large population cohort in southern China.

BACKGROUND: Evidence of the association between long-term exposure to particulate matter (PM) and chronic obstructive pulmonary disease (COPD) mortality from large population-based cohort study is limited and often suffers from residual confounding issues with traditional statistical methods. We hereby assessed the casual relationship between long-term PM (PM2.5, PM10 and PM10-2.5) exposure and COPD mortality in a large cohort of Chinese adults using state-of-the-art causal inference approaches. METHODS: A total of 580,757 participants in southern China were enrolled in a prospective cohort study from 2009 to 2015 and followed up until December 2020. Exposures to PM at each residential address were obtained from the Long-term Gap-free High-resolution Air Pollutant Concentration dataset. Marginal structural Cox models were used to investigate the association between COPD mortality and annual average exposure levels of PM exposure. RESULTS: During an average follow-up of 8.0 years, 2250 COPD-related deaths occurred. Under a set of causal inference assumptions, the hazard ratio (HR) for COPD mortality was estimated to be 1.046 (95 % confidence interval: 1.034-1057), 1.037 (1.028-1.047), and 1.032 (1.006-1.058) for each 1-µg/m3 increase in annual average concentrations of PM2.5, PM10, and PM10-2.5 respectively. Additionally, the detrimental effects appeared to be more pronounced among the elderly (age ≥ 65) and inactive participants. The effect estimates of PM2.5, PM10, and PM10-2.5 tend to be greater among participants who were generally exposed to PM10 concentrations below 70 µg/m3 than that among the general population. CONCLUSION: Our results support causal links between long-term PM exposure and COPD mortality, highlighting the urgency for more effective strategies to reduce PM exposure, with particular attention on protecting potentially vulnerable groups.

Epidemiology of hepatitis B virus infection: results from a community-based study of 0.15 million residents in South China.

Limited information is available about the current epidemic status of hepatitis B virus (HBV) in Guangdong province in South China, where hepatitis B is endemic. We sought to provide an up-to-date assessment of hepatitis B prevalence in a large population through a community-based study. A total of 169,211 local residents were recruited using the stratified cluster random sampling method from 2014 to 2015, and each participant's information was collected using an interviewer-administered questionnaire. Accordingly, the prevalence of hepatitis B surface antigen (HBsAg) in the total population was 8.76%. HBsAg prevalence was lowest (0.29%) among children aged 0-12 years and highest (12.71%) among those aged 23-59 years. Moreover, the prevalence (8.82%) in males approximately equalled that (8.65%) in females (P > 0.05). Overall, vaccination was effective in preventing HBV infection, regardless of age. Among adults aged 23-59 years, male sex tended to keep the HBsAg persistence. However, reduced persistence for participants with occasional physical exercise and drinking was observed. For participants older than 59 years, a history of prior surgery placed people at high risk for infection. Although Guangdong has successfully decreased the HBsAg prevalence among children, it is urgent to expand vaccination to adults, and employ interventions to reduce the infection risk.

[Voltage-activated potassium channel blockers inhibit anisodamine-induced relaxation of rabbit aortic smooth muscles precontracted with noradrenaline].

Anisodamine, which is originally extracted from scopolia tangutica and is currently produced in China, is a tropane alkaloid and a muscarinic cholinoceptor blocker. Our previous study found that anisodamine did not alter high K(+)-evoked contraction of rabbit aortic rings using isometric tension recording methods, but could attenuate noradrenaline (NA)-, histamine- or 5-hydroxytryptamine-induced contraction in an endothelium-independent manner. Since the high K(+)-elicited depolarization non-selectively inhibits potassium channels in vascular smooth muscle cell (VSMC) membrane, the vasodilation effect of some potassium channel activators may be inhibited or abolished in high K(+) solution. We hypothesized that some potassium channels in VSMC membrane might play a role in the anisodamine-induced relaxation of blood vessels. The present experiment was designed to investigate whether potassium channel blockers inhibit anisodamine-induced relaxation of the rabbit isolated aortic rings. In a 8-min period, 1, 3 and 10 micromol/L of anisodamine, significantly relaxed the 0.01 micromol/L NA precontracted aortic ring by (19.1+/-3.1)%, (30.1+/-3.8)% and (38.3+/-4.2)%, respectively, compared with the controls [by (4.8+/-2.4)%, (5.1+/-1.8)% and (5.6+/-2.5)%, respectively] (P<0.01). 10 mmol/L of CsCl (a non-selective potassium channel blocker), 1 mmol/L of 4-aminopyridine [a selective voltage-activated potassium channel (K(V)) blocker], 10 mumol/L BaCl2 (a selective inwardly-rectifying potassium channel blocker), 10 micromol/L of glibenclamide (a selective ATP-sensitive potassium channel blocker), 3 micromol/L of charybdotoxin (a large- and intermediate-conductance Ca(2+)-activated potassium channels blocker) and 3 micromol/L of apamin (a selective small conductance Ca(2+)-activated potassium channel blocker) significantly increased the NA-induced contraction by (14.4+/-3.2)%, (16.3+/-5.8)%, (12.7+/-4.2)%, (13.6+/-2.0)%, (11.1+/-5.5)% and (13.4+/-4.3)%, respectively, compared with the control [by (5.6 +/-1.2)%] (P<0.01). In the presence of 10 and 30 mmol/L CsCl or 1 and 3 mmol/L 4-aminopyridine, anisodamine-induced relaxation of the 0.01 micromol/L NA contracted rabbit aortic rings [(28.8+/-3.0)% and (15.9+/-3.7)% or (29.7+/-3.9)% and (19.0+/-5.0)%] significantly deceased, compared with that in the absence of any potassium channel blocker [(38.3+/-4.2)% (P<0.01)] in a 8-min period. However, in the presence of 10, 30 micromol/L of BaCl2, 10, 30 micromol/L of glibenclamide, 3 micromol/L of charybdotoxin, or 3 micromol/L apamin, 10 micromol/L anisodamine-induced relaxation [(37.1+/-3.8)%, (36.2+/-4.7)%, (36.1+/-2.7)%, (35.6+/-3.3)%, (37.8+/-2.0)% and (39.3 +/-4.7) %, respectively] did not decrease, compared with the control [(38.3+/-4.2)%] (P>0.05). This study suggests that K(V) blockers inhibit anisodamine-induced relaxation of the rabbit aortic smooth muscle precontracted with NA and implies that the K(V) in VSMC membrane plays a role in anisodamine-induced relaxation of blood vessels.

Improved Variable Selection Algorithm Using a LASSO-Type Penalty, with an Application to Assessing Hepatitis B Infection Relevant Factors in Community Residents.

OBJECTIVES: In epidemiological studies, it is important to identify independent associations between collective exposures and a health outcome. The current stepwise selection technique ignores stochastic errors and suffers from a lack of stability. The alternative LASSO-penalized regression model can be applied to detect significant predictors from a pool of candidate variables. However, this technique is prone to false positives and tends to create excessive biases. It remains challenging to develop robust variable selection methods and enhance predictability. MATERIAL AND METHODS: Two improved algorithms denoted the two-stage hybrid and bootstrap ranking procedures, both using a LASSO-type penalty, were developed for epidemiological association analysis. The performance of the proposed procedures and other methods including conventional LASSO, Bolasso, stepwise and stability selection models were evaluated using intensive simulation. In addition, methods were compared by using an empirical analysis based on large-scale survey data of hepatitis B infection-relevant factors among Guangdong residents. RESULTS: The proposed procedures produced comparable or less biased selection results when compared to conventional variable selection models. In total, the two newly proposed procedures were stable with respect to various scenarios of simulation, demonstrating a higher power and a lower false positive rate during variable selection than the compared methods. In empirical analysis, the proposed procedures yielding a sparse set of hepatitis B infection-relevant factors gave the best predictive performance and showed that the procedures were able to select a more stringent set of factors. The individual history of hepatitis B vaccination, family and individual history of hepatitis B infection were associated with hepatitis B infection in the studied residents according to the proposed procedures. CONCLUSIONS: The newly proposed procedures improve the identification of significant variables and enable us to derive a new insight into epidemiological association analysis.

Protective mechanism of adenosine to the rat arterial endothelial dysfunction induced by hydrogen peroxide.

This study was designed to examine the in vitro effects of adenosine (Ado) on hydrogen peroxide-induced endothelial dysfunction in rats. Endothelial dysfunction was induced by exposing isolated rat mesenteric arteries to hydrogen peroxide (0.5 mM) for 12 h using an organ culture system. The protective effects of adenosine were tested by exposing isolated mesenteric arteries to adenosine (3 x 10(-7) mol/l, 10(-6) mol/l, 3 x 10(-6) mol/l)+hydrogen peroxide (0.5 mM) for 12 h. This exposure to hydrogen peroxide induced a significant concentration-dependent inhibition of endothelium-dependent relaxation (EDR). Coculture of segments of mesenteric artery with adenosine (3 x 10(-7), 10(-6), and 3 x 10(-6) mol/l) attenuated the hydrogen peroxide-induced impairment of vasorelaxation. This impairment was accompanied by a reduction in nitrite/nitrate, nitric oxide (NO) synthase (NOS), superoxide dismutase (SOD) and glutathione peroxidase (GSH-Px) activities and an increasing in malondislehyde (MDA) and lactate dehydrogenase (LDH) activities in the aorta. These results indicate that adenosine can be used to attenuate hydrogen peroxide-induced endothelial dysfunction, an effect that may be related to antioxidation, thus enhancing NO production by preventing the decrease in NOS.