Eliciting national and subnational sets of disability weights in mainland China: Findings from the Chinese disability weight measurement study.

Background: The disability weight (DW) quantifies the severity of health states from disease sequela and is a pivotal parameter for disease burden calculation. We conducted a national and subnational DW measurement in China. Methods: In 2020-2021, we conducted a web-based survey to assess DWs for 206 health states in 31 Chinese provinces targeting health workers via professional networks. We fielded questions of paired comparison (PC) and population health equivalence (PHE). The PC data were analysed by probit regression analysis, and the regression results were anchored by results from the PHE responses on the DW scale between 0 (no loss of health) and 1 (health loss equivalent to death). Findings: We used PC responses from 468,541 respondents to estimate DWs of health states. Eight of 11 domains of health had significantly negative coefficients in the regression of the difference between Chinese and Global Burden of Disease (GBD) DWs, suggesting lower DW values for health states with mention of these domains in their lay description. We noted considerable heterogeneity within domains, however. After applying these Chinese DWs to the 2019 GBD estimates for China, total years lived with disability (YLDs) increased by 14·9% to 177 million despite lower estimates for musculoskeletal disorders, cardiovascular diseases, mental disorders, diabetes and chronic kidney disease. The lower estimates of YLDs for these conditions were more than offset by higher estimates of common, low-severity conditions. Interpretation: The differences between the GBD and Chinese DWs suggest that there might be some contextual factors influencing the valuation of health states. While the reduced estimates for mental disorders, alcohol use disorder, and dementia could hint at a culturally different valuation of these conditions in China, the much greater shifts in YLDs from low-severity conditions more likely reflects methodological difficulty to distinguish between health states that vary a little in absolute DW value but a lot in relative terms. Funding: This work was supported by the National Natural Science Foundation of China [grant number 82173626], the National Key Research and Development Program of China [grant numbers 2018YFC1315302], Wuhan Medical Research Program of Joint Fund of Hubei Health Committee [grant number WJ2019H304], and Ningxia Natural Science Foundation Project [grant number 2020AAC03436].

Asthma mortality attributable to ambient temperatures: A case-crossover study in China.

BACKGROUND: Whether ambient temperature exposure contributes to death from asthma remains unknown to date. We therefore conducted a case-crossover study in China to quantitatively evaluate the association and burden of ambient temperature exposure on asthma mortality. METHODS: Using data from the National Mortality Surveillance System in China, we conducted a time-stratified case-crossover study of 15 888 individuals who lived in Hubei and Jiangsu province, China and died from asthma as the underlying cause in 2015-2019. Individual-level exposures to air temperature and apparent temperature on the date of death and 21 days prior were assessed based on each subject's residential address. Distributed lag nonlinear models based on conditional logistic regression were used to quantify exposure-response associations and calculate fraction and number of deaths attributable to non-optimum ambient temperatures. RESULTS: We observed a reverse J-shaped association between air temperature and risk of asthma mortality, with a minimum mortality temperature of 21.3 °C. Non-optimum ambient temperature is responsible for substantial excess mortality from asthma. In total, 26.3% of asthma mortality were attributable to non-optimum temperatures, with moderate cold, moderate hot, extreme cold and extreme hot responsible for 21.7%, 2.4%, 2.1% and 0.9% of asthma mortality, respectively. The total attributable fraction and number was significantly higher among adults aged less than 80 years in hot temperature. CONCLUSIONS: Exposure to non-optimum ambient temperature, especially moderate cold temperature, was responsible for substantial excess mortality from asthma. These findings have important implications for planning of public-health interventions to minimize the adverse respiratory damage from non-optimum ambient temperature.

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

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

Excess mortality in Wuhan city and other parts of China during the three months of the covid-19 outbreak: findings from nationwide mortality registries.

OBJECTIVE: To assess excess all cause and cause specific mortality during the three months (1 January to 31 March 2020) of the coronavirus disease 2019 (covid-19) outbreak in Wuhan city and other parts of China. DESIGN: Nationwide mortality registries. SETTING: 605 urban districts and rural counties in China's nationally representative Disease Surveillance Point (DSP) system. PARTICIPANTS: More than 300 million people of all ages. MAIN OUTCOME MEASURES: Observed overall and weekly mortality rates from all cause and cause specific diseases for three months (1 January to 31 March 2020) of the covid-19 outbreak compared with the predicted (or mean rates for 2015-19) in different areas to yield rate ratio. RESULTS: The DSP system recorded 580 819 deaths from January to March 2020. In Wuhan DSP districts (n=3), the observed total mortality rate was 56% (rate ratio 1.56, 95% confidence interval 1.33 to 1.87) higher than the predicted rate (1147 v 735 per 100 000), chiefly as a result of an eightfold increase in deaths from pneumonia (n=1682; 275 v 33 per 100 000; 8.32, 5.19 to 17.02), mainly covid-19 related, but a more modest increase in deaths from certain other diseases, including cardiovascular disease (n=2347; 408 v 316 per 100 000; 1.29, 1.05 to 1.65) and diabetes (n=262; 46 v 25 per 100 000; 1.83, 1.08 to 4.37). In Wuhan city (n=13 districts), 5954 additional (4573 pneumonia) deaths occurred in 2020 compared with 2019, with excess risks greater in central than in suburban districts (50% v 15%). In other parts of Hubei province (n=19 DSP areas), the observed mortality rates from pneumonia and chronic respiratory diseases were non-significantly 28% and 23% lower than the predicted rates, despite excess deaths from covid-19 related pneumonia. Outside Hubei (n=583 DSP areas), the observed total mortality rate was non-significantly lower than the predicted rate (675 v 715 per 100 000), with significantly lower death rates from pneumonia (0.53, 0.46 to 0.63), chronic respiratory diseases (0.82, 0.71 to 0.96), and road traffic incidents (0.77, 0.68 to 0.88). CONCLUSIONS: Except in Wuhan, no increase in overall mortality was found during the three months of the covid-19 outbreak in other parts of China. The lower death rates from certain non-covid-19 related diseases might be attributable to the associated behaviour changes during lockdown.

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

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

Short-Term Exposure to Ambient Air Pollution and Asthma Mortality.

Rationale: Short-term exposure to air pollution has been associated with asthma exacerbation and increased healthcare use caused by asthma, but its effect on asthma mortality remains largely unknown. Objectives: To quantitatively assess the association between short-term exposure to air pollution and asthma mortality. Methods: We investigated 4,454 individuals who lived in Hubei province, China, and died from asthma between 2013 and 2018. A case-crossover design and conditional logistic regression models were applied for data analyses. Exposures to particulate matter ≤2.5 µm in aerodynamic diameter (PM2.5), particulate matter ≤10 µm in aerodynamic diameter (PM10), sulfur dioxide (SO2), nitrogen dioxide (NO2), carbon monoxide (CO), and ozone (O3) were estimated by inverse distance weighted averages of all monitoring stations within 50 km from each case's home address. Measurements and Main Results: Each interquartile range (IQR) increase of PM2.5 (lag 3; IQR, 47.1 µg/m3), NO2 (lag 03; IQR, 26.3 µg/m3), and O3 (lag 3; IQR, 52.9 µg/m3) were positively associated with asthma mortality, with odds ratios of 1.07 (95% confidence interval, 1.01-1.12), 1.11 (95% confidence interval, 1.01-1.22), and 1.09 (95% confidence interval, 1.01-1.18), respectively. There was no evidence of departure from linearity for these associations. Further adjustment for other pollutants did not change the associations materially. We did not observe significant associations between PM10, SO2, and CO exposures and asthma mortality. Overall, the estimates remained consistent in various sensitivity analyses. Conclusions: Our results provide new evidence that short-term exposures to PM2.5, NO2, and O3 may increase asthma mortality risk. Further studies are needed to confirm our findings in other populations.

Sharply Reduced but Still Heavy Self-Harm Burdens in Hubei Province, China, 1990-2015.

The aims of this study were to describe fatal and non-fatal self-harm burdens, as well as burdens from the main preventable risk factors, and to investigate the different suicide methods in Hubei province in central China utilizing data from both Global Burden of Disease Study 2015 and Hubei Disease Surveillance Points system. All self-harm burdens including mortality, years of life lost (YLLs), prevalence, years lived with disability (YLDs), and disability adjusted life-years (DALYs) consistently demonstrated downward trends in Hubei from 1990 to 2015, with a bigger decline gap observed among females and narrower decreasing amplitudes among the elderly. Hubei experienced much higher age-standardized rates for self-harm mortality (22.0 per 100,000), YLLs (560.1 per 100,000) and DALYs (563.9 per 100,000) than the national (9.0, 292.3 and 295.0 per 100,000 respectively) and global levels (11.5, 453.3 and 457.9 per 100,000 respectively) in 2015. Self-harm burdens have begun shifting from females to males and the elderly suffered more self-harm burdens than other age groups. Alcohol use accounted for 20.9% of all self-harm DALYs for males, whereas intimate partner violence accounted for 24.4% of all self-harm DALYs for females. Poisoning, mainly pesticide self-poisoning, was still the most common method of suicide. Effective interventions by multi-sectoral collaboration are urgently needed to reduce the alarmingly heavy self-harm burdens in Hubei.

Unintentional Poisoning in China, 1990 to 2015: The Global Burden of Disease Study 2015.

OBJECTIVES: To estimate the unintentional poisoning burden and risk factors in China from 1990 to 2015. METHODS: We extracted data from the Global Burden of Disease Study 2015 to compare mortality, prevalence, disability-adjusted life years (DALYs), years of life lost, years lived with a disability, and risk factors of unintentional poisoning in China. We determined the median of the percent change and 95% uncertainty interval for the period between 1990 and 2015. RESULTS: The age-standardized unintentional poisoning death rate decreased by 61.8% from 1990 (4.1 per 100 000) to 2015 (1.6 per 100 000). The age-standardized prevalence decreased from 1990 (87.9 per 100 000) to 2010 (39.0 per 100 000), but rebounded in 2015 (42.6 per 100 000). All risk factors combined accounted for 14.9% of unintentional poisoning DALYs in 2015. The leading risk factors for unintentional poisoning DALYs were alcohol and drug use and occupational risks. CONCLUSIONS: China has made substantial progress in reducing the mortality attributable to unintentional poisoning, but the prevalence and absolute number of patients has been increasing again since 2010. The growing contribution from alcohol and drug use requires increased attention.

Activation of Akt/GSK3ß and Akt/Bcl-2 signaling pathways in nickel-transformed BEAS-2B cells.

The Akt signaling pathway has been implicated in a wide range of cellular functions involving cell survival and proliferation, angiogenesis, metabolism and cell migration. Accumulating evidence suggests that Akt perturbations play an important role in human malignancy. Here, we investigated Akt perturbation in nickel-transformed cells. Chronic treatment of human bronchial epithelial BEAS-2B cells with low doses of nickel chloride resulted in cell transformation demonstrated by anchorage-independent (AI) growth, increased cell growth and alterations of cell growth pattern. Western blot assays show that phosphorylation of Akt at Ser473, but not that of p38, JNK and ERK, was increased in nickel-transformed cells compared with controls. Inhibition of Akt or PI3K by pharmacological or biochemical interference suppressed nickel AI growth and cell growth of transformed cells. Activation of Akt led to inhibition of GSK3ß by phosphorylation at Ser9 in nickel-transformed cells. In addition, two major anti-apoptotic proteins of the Bcl family, Bcl-2 and Bcl-XL, were increased in nickel-transformed cells. By employing the small interfering RNA technique (siRNA), our results showed that siRNA Akt attenuated the expression of Bcl-2 and Bcl-XL in nickel-transformed cells, indicating that induction of Bcl-2 and Bcl-XL was likely mediated through Akt. ROS generation was decreased in nickel-transformed cells compared with controls. Moreover, down-regulation of retinoblastoma protein (Rb) was observed in nickel-transformed cells. Taken together, these findings demonstrate that activation of Akt, followed by GSK3ß inhibition and Bcl-2, Bcl-XL up-regulation and decrease of ROS generation, along with a synergistic effect of Rb down-regulation may cause apoptosis resistance, contributing to the overall mechanism of nickel carcinogenesis.

Reduced reactive oxygen species-generating capacity contributes to the enhanced cell growth of arsenic-transformed epithelial cells.

Reactive oxygen species (ROS) have been implicated in the activation of protein kinases, DNA damage responses, and cell apoptosis. The details of how ROS regulate these intracellular biochemical and genetic processes remain to be fully understood. By establishing transformed bronchial epithelial cells through chronic low-dose arsenic treatment, we showed that the capacity of ROS generation induced by arsenic is substantially reduced in the transformed cells relative to the nontransformed cells. Such a reduction in ROS generation endows cells with premalignant features, including rapid growth, resistance to arsenic toxicity, and increased colony formation of the transformed cells. To validate these observations, the capability of ROS generation was restored in the transformed cells by treatment with inhibitors or siRNAs to silence the function of superoxide dismutase (SOD) or catalase and cell growth was determined following these treatments. Enhancement in ROS generation suppressed cell growth and colony formation of the transformed cells significantly. Despite the fact that the transformed cells showed a decreased expression of NF-kappaB signaling proteins IKKbeta and IKKgamma, the proteolytic processing p105 and p100 and NF-kappaB DNA binding activity were elevated in these cells. Increasing ROS generation by silencing SOD and catalase reduced the DNA binding activity of NF-kappaB in the transformed cells. Taken together, the transformed cells induced by arsenic exhibited a decrease in ROS generation, which is responsible for the enhanced cell growth and colony formation of the transformed cells, most likely through a sustained alternative activation of the NF-kappaB transcription factor.

Arsenic inhibits neurite outgrowth by inhibiting the LKB1-AMPK signaling pathway.

BACKGROUND: Arsenic (As) is an environmental pollutant that induces numerous pathological effects, including neurodevelopmental disorders. OBJECTIVES AND METHODS: We evaluated the role of the LKB1-AMPK pathway in As-induced developmental neurotoxicity using Neuro-2a (N2a) neuroblastoma cells as a model of developing neurons. RESULTS: The addition of low concentrations of As (

Cr(VI) induces mitochondrial-mediated and caspase-dependent apoptosis through reactive oxygen species-mediated p53 activation in JB6 Cl41 cells.

Cr(VI) compounds are known to cause serious toxic and carcinogenic effects. Cr(VI) exposure can lead to a severe damage to the skin, but the mechanisms involved in the Cr(VI)-mediated toxicity in the skin are unclear. The present study examined whether Cr(VI) induces cell death by apoptosis or necrosis using mouse skin epidermal cell line, JB6 Cl41 cells. We also investigated the cellular mechanisms of Cr(VI)-induced cell death. This study showed that Cr(VI) induced apoptotic cell death in a dose-dependent manner, as demonstrated by the appearance of cell shrinkage, the migration of cells into the sub-G1 phase, the increase of Annexin V positively stained cells, and the formation of nuclear DNA ladders. Cr(VI) treatment resulted in the increases of mitochondrial membrane depolarization and caspases activation. Electron spin resonance (ESR) and fluorescence analysis revealed that Cr(VI) increased intracellular levels of reactive oxygen species (ROS) such as hydrogen peroxide and superoxide anion radical in dose-dependent manner. Blockage of p53 by si-RNA transfection suppressed mitochondrial changes of Bcl-2 family composition, mitochondrial membrane depolarization, caspase activation and PARP cleavage, leading to the inhibition of Cr(VI)-induced apoptosis. Further, catalase treatment prevented p53 phosphorylation stimulated by Cr(VI) with the concomitant inhibition of caspase activation. These results suggest that Cr(VI) induced a mitochondrial-mediated and caspase-dependent apoptosis in skin epidermal cells through activation of p53, which are mainly mediated by reactive oxidants generated by the chemical.

Reactive oxygen species-activated Akt/ASK1/p38 signaling pathway in nickel compound-induced apoptosis in BEAS 2B cells.

Nickel compounds are carcinogenic to humans, possibly through induction of reactive oxygen species (ROS) that damage macromolecules including DNA and proteins. The aim of the present study is to elucidate the role of the ROS-mediated Akt/apoptosis-regulating signal kinase (ASK) 1/p38 pathway in nickel-induced apoptosis. Exposure of human bronchial epithelial cells (BEAS-2B) to nickel compounds induced the generation of ROS and activation of Akt that is associated with the activation of ASK1 and p38 mitogen-activated protein kinase. Immunoblotting suggested a down-regulation of several antiapoptotic proteins, including Bcl-2 and Bcl-xL in the nickel compound-treated cells. Indeed, a notable cell apoptosis following nickel compound treatment is evident as revealed by flow cytometry analysis. N-Acetyl-L-cysteine (NAC, a general antioxidant) and vitamin E or catalase (a specific H(2)O(2) inhibitor) all decreased nickel-induced ROS generation. Scavenging of nickel-induced ROS by NAC or catalase attenuated Akt, ASK1, and p38 MAPK activation and apoptosis, which implies involvement of ROS in the Akt/ASK1/p38 pathway. In addition, nickel-induced activation of p38 MAPK was attenuated by a small interference of RNA specific to ASK1 (siRNA ASK1), implying that p38 MAPK was downstream of ASK1, while ASK1 activation was not reversely regulated by the inhibition of p38 MAPK by SB203580, a widely used p38 MAPK inhibitor. Silencing Akt by siRNA reduced the activation of ASK1 and p38 MAPK and cell apoptosis, whereas without nickel stimulation, siRNA Akt had no effect on the activation of ASK1 and p38 MAPK. Thus, these results suggest that the ROS-dependent Akt-ASK1-p38 axis is important for nickel-induced apoptosis.

Cadmium induces intracellular Ca2+- and H2O2-dependent apoptosis through JNK- and p53-mediated pathways in skin epidermal cell line.

Cadmium is a toxic heavy metal and has been widely used in industry. The skin is an important target for this metal. The mechanisms by which cadmium leads to damage to the skin are unclear at present. The aims of this study were to examine whether cadmium induces apoptosis in mouse skin epidermal cell line, JB6 Cl41 cells, and to investigate the cellular mechanisms by which cadmium causes cytotoxicity in the cells. The present study showed that cadmium induced cell death by apoptosis in a dose-dependent manner, as proven by the appearance of cell shrinkage, the increase of Annexin V positively stained cells, and the formation of nuclear DNA ladders. Cadmium-induced apoptosis involved a mitochondria-mediated mechanism but not caspase-dependent pathway in that the critical apoptotic events induced by cadmium, such as the decrease of Bcl-2/Bcl-xL, the increase of GADD45alpha, and the nuclear translocation of apoptosis inducing factor, were not affected by the inhibition of executive caspases. In contrast, blockage of p53 and JNK by pharmacological inhibitors or small interference RNA transfection suppressed the cadmium-induced apoptosis with the concomitant inhibition of antiapoptotic Bcl-2 family proteins and GADD45alpha, respectively. Furthermore, the activation of p53 and JNK and their downstream proteins in cadmium-exposed cells were inhibited by individual treatment with catalase and Bapta-acetoxymethyl. These results suggest that cadmium induces apoptosis via the activation of JNK- and p53-mediated signaling, where calcium ion and hydrogen peroxide act as the pivotal mediators of the apoptotic signaling.

HIV/AIDS knowledge, attitudes and behaviors assessment of Chinese students: a questionnaire study.

The objective of this study was to assess students' knowledge, attitudes and practices on HIV and AIDS. A questionnaire was administered to a cross section of 259 Chinese undergraduates. Respondents were asked to provide information about knowledge and attitudes about HIV/AIDS. Study results indicated that the majority of undergraduates had a moderate level of HIV and AIDS knowledge, acceptance and attitudes towards people with HIV and AIDS. Boys had more acceptance and positive attitudes towards people with HIV and AIDS than girls. Students majoring in medicine performed better (more knowledgeable and accepting) than non-medical students. Differences between students with various monthly expenditures were found-- 6.2% of students had 3-5 sexual partners which has rarely been found in Chinese students; most students did not know HIV VCT centers and most students did not show their confidence for controlling of HIV and AIDS in China. In conclusion, students' knowledge about HIV/AIDS was uneven. A peer educational program to talk about self esteem, healthy sexual attitudes, being human-accepting and loving should be developed in the near future.