The miR166 targets CsHDZ3 genes to negatively regulate drought tolerance in tea plant (Camellia sinensis).

Drought is the stressor with a significant adverse impact on the yield stability of tea plants. HD-ZIP III transcription factors (TFs) play important regulatory roles in plant growth, development, and stress responses. However, whether and how HD-ZIP III TFs are involved in drought response and tolerance in tea plants remains unclear. Here, we identified seven HD-ZIP III genes (CsHDZ3-1 to CsHDZ3-7) in tea plant genome. The evolutionary analysis demonstrated that CsHDZ3 members were subjected to purify selection. Subcellular localization analysis revealed that all seven CsHDZ3s located in the nucleus. Yeast self-activation and dual-luciferase reporter assays demonstrated that CsHDZ3-1 to CsHDZ3-4 have trans-activation ability whereas CsHDZ3-5 to CsHDZ3-7 served as transcriptional inhibitors. The qRT-PCR assay showed that all seven CsHDZ3 genes could respond to simulated natural drought stress and polyethylene glycol treatment. Further assays verified that all CsHDZ3 genes can be cleaved by csn-miR166. Overexpression of csn-miR166 inhibited the expression of seven CsHDZ3 genes and weakened drought tolerance of tea leaves. In contrast, suppression of csn-miR166 promoted the expression of seven CsHDZ3 genes and enhanced drought tolerance of tea leaves. These findings established the foundation for further understanding the mechanism of CsHDZ3-miR166 modules' participation in drought responses and tolerance.

Identification and Validation of the miR156 Family Involved in Drought Responses and Tolerance in Tea Plants (Camellia sinensis (L.) O. Kuntze).

The microRNA156 (miR156) family, one of the first miRNA families discovered in plants, plays various important roles in plant growth and resistance to various abiotic stresses. Previously, miR156s were shown to respond to drought stress, but miR156s in tea plants (Camellia sinensis (L.) O. Kuntze) have not been comprehensively identified and analyzed. Herein, we identify 47 mature sequences and 28 precursor sequences in tea plants. Our evolutionary analysis and multiple sequence alignment revealed that csn-miR156s were highly conserved during evolution and that the rates of the csn-miR156 members' evolution were different. The precursor sequences formed typical and stable stem-loop structures. The prediction of cis-acting elements in the CsMIR156s promoter region showed that the CsMIR156s had diverse cis-acting elements; of these, 12 CsMIR156s were found to be drought-responsive elements. The results of reverse transcription quantitative PCR (RT-qPCR) testing showed that csn-miR156 family members respond to drought and demonstrate different expression patterns under the conditions of drought stress. This suggests that csn-miR156 family members may be significantly involved in the response of tea plants to drought stress. Csn-miR156f-2-5p knockdown significantly reduced the Fv/Fm value and chlorophyll content and led to the accumulation of more-reactive oxygen species and proline compared with the control. The results of target gene prediction showed that csn-miR156f-2-5p targeted SQUAMOSA promoter binding protein-like (SPL) genes. Further analyses showed that CsSPL14 was targeted by csn-miR156f-2-5p, as confirmed through RT-qPCR, 5' RLM-RACE, and antisense oligonucleotide validation. Our results demonstrate that csn-miR156f-2-5p and CsSPL14 are involved in drought response and represent a new strategy for increasing drought tolerance via the breeding of tea plants.

Multiomics Analysis Reveals the Involvement of JsLHY in Controlling Aroma Production in Jasmine Flowers.

The Jasminum sambac flower is famous for its rich fragrance. However, our knowledge of the regulatory network for its aroma formation remains largely unknown and therefore needs further study. To this end, an integrated analysis of the volatilomics and transcriptomics of jasmine flowers at different flowering stages was performed. The results revealed many candidate transcription factors (TFs) may be involved in regulating the aroma formation of jasmine, among which the MYB-related TF LATE ELONGATED HYPOCOTYL (JsLHY) was identified as a hub gene. Using the DNA affinity purification sequencing method, dual-luciferase reporter, and yeast one-hybrid assays, we demonstrate that JsLHY can bind the gene promoter regions of six aroma-related structural genes (JsBEAT1, JsTPS34, JsCNL6, JsBPBT, JsAAAT5, and Js4CL7) and directly promote their expression. In addition, suppressing JsLHY expression decreased both the expression of JsLHY-bound genes and the content of related VOCs. The present study reveals how JsLHY participates in jasmine aroma formation.

Mortality and Years of Life Lost Due to Brain and Other Central Nervous System Cancer in Wuhan, China, from 2010 to 2019.

BACKGROUND: Brain cancer is one of the worst types of cancer worldwide. Understanding the epidemiology of CNS cancer is critical for properly allocating healthcare resources. METHODS: We collected data on CNS cancer deaths in Wuhan, China, during 2010-2019. We constructed the cause-eliminated life tables to calculate life expectancy (LE), mortality, and years of life lost (YLLs) by age and sex. The BAPC model was used to forecast the future trends of age-standardized mortality rate (ASMR). Decomposition analysis was adopted to explore the contribution of population growth, population aging, and age-specific mortality to the change in total CNS cancer deaths. RESULTS: In 2019, the ASMR of CNS cancer was 3.75, and the ASYR was 135.70 in Wuhan, China. ASMR was expected to decrease to 3.43 in 2024. The age distribution of deaths due to CNS cancer was concentrated in the middle-aged and older population, with a peak in the 65-69 age group. Caidian, Jianghan, and Qingshan had the greatest ASMRs in 2019 in Wuhan, with ASMRs of 6.32, 4.78, and 4.75, respectively. Population aging is critical to the change in total CNS cancer deaths. CONCLUSION: We analyzed the current status, temporal trends, and gender and age distributions of the burden of CNS cancer in Wuhan, during 2010-2019, providing a valuable reference for better lessening the CNS cancer burden.

Secular Trends of Liver Cancer Mortality and Years of Life Lost in Wuhan, China 2010-2019.

BACKGROUND: Liver cancer has caused a heavy burden worldwide. This study aimed to estimate the trends in the mortality and years of life lost (YLL) due to liver cancer and decompose the total deaths into three contributors: population growth, population aging, and mortality change. METHODS: Our study used data from the cause-of-death surveillance system in Wuhan. The mortality and YLL rates were standardized according to the sixth national population census in China. This study calculated the estimated annual percentage change (EAPC) to estimate the trends in the age-standardized mortality rate (ASMR) and age-standardized YLL rate (ASYR). Meanwhile, a decomposition analysis was used to explore the effect of population growth, population aging, and age-specific mortality change on the change in liver cancer deaths. RESULTS: The ASMR of liver cancer declined at an annual rate of 4.6% from 30.87 per 100,000 people in 2010 to 20.29 per 100,000 people in 2019, while the ASYR was at an annual rate of 5.6% from 969.35 per 100,000 people in 2010 to 581.82 per 100,000 people in 2019. Similar downward trends were seen in men and women. The decomposition analysis found that total deaths number changed by -12.42% from 2010 to 2019, of which population growth and population aging caused the total death numbers to increase by 9.75% and 21.15%, while the age-specific mortality change caused the total death numbers to decrease by 43.32%. CONCLUSION: Although the ASMR of liver cancer has declined in recent years in Wuhan, it still causes a heavy burden with the increasing population and rapid population aging and remains an essential public health issue. The government should take measures to reduce the burden of liver cancer, especially among men.

Temporal trends in lung cancer mortality and years of life lost in Wuhan, China, 2010-2019.

Objective: Lung cancer is responsible for millions of deaths yearly, and its burden is severe worldwide. This study aimed to investigate the burden of lung cancer in the population of Wuhan based on the surveillance data from 2010 to 2019. Methods: Data of this study was obtained from the Mortality Register System established by the Wuhan Center for Disease Control and Prevention. The study systematically analyzed the burden of lung cancer deaths in the population of Wuhan and its 13 administrative regions from 2010 to 2019 via the Joinpoint regression models, Age-Period-Cohort (APC) models, and decomposition analysis. Results: This study found the upward and downward trends in the age-standardized mortality rates (ASMRs) and age-standardized years of life lost rates (ASYLLRs) of lung cancer from 2010 to 2019. In Joinpoint regression models, the corresponding estimated annual percentage change (EAPC) were 1.00% and -1.90%, 0.60%, and -3.00%, respectively. In APC models, lung cancer mortality tended to increase with age for both sexes in Wuhan, peaking at the 85-89 age group; The period effects for different populations have started to gradually decline in recent years. In addition, the cohort effects indicated that the risk of lung cancer death was highest among those born in the 1950s-1955s, at 1.08 (males) and 1.01 (females). Among all administrative districts in Wuhan, the ASMR of lung cancer in the Xinzhou District has remained the highest over the study period. In decomposition analysis, both population aging (P<0.01) and population growth (P<0.01) aggravated (Z>0) lung cancer deaths in the Wuhan population. Conclusions: The burden of lung cancer death in the Wuhan population has shown a gradual decline in recent years, but the impact of aging and population growth on lung cancer mortality should not be ignored. Therefore, lung cancer surveillance must be strengthened to reduce the burden of lung cancer in Wuhan.

Association of Sleep Duration With All-Cause and Cardiovascular Mortality: A Prospective Cohort Study.

To clarify the association of sleep duration with all-cause and cardiovascular mortality, and further estimate the population attributable fraction (PAF) for the 10-year risk of cardiovascular disease (CVD) due to inappropriate sleep duration among US adults, we included data of the National Health and Nutrition Examination Survey (NHANES) from 2005 to 2014 by linkage to the National Death Index until December 31, 2015 in a prospective design. Cox proportional hazards models were used for multivariate longitudinal analyses. The Pooled Cohort Equations methods was adopted to calculate the predicted 10-year CVD risk. In the current study, sleep <5 h or longer than 9 h per day were significantly associated with elevated risks of all-cause mortality, and the multivariable-adjusted HRs across categories were 1.40 (95% CI, 1.14-1.71), 1.12 (95% CI, 0.91-1.38), 1 (reference), 1.35 (95% CI, 1.12-1.63), and 1.74 (95% CI, 1.42-2.12). Similarly, the HRs of cardiovascular mortality across categories were 1.66 (95% CI, 1.02-2.72), 1.15 (95% CI, 0.77-1.73), 1 (reference), 1.55 (95% CI, 1.05-2.29), and 1.81 (95% CI, 1.09-3.02). Under a causal-effect assumption, we estimated that 187 000 CVD events (PAF 1.8%, 0.9% to 2.3%) were attributable to short sleep duration and 947 000 CVD events (PAF 9.2%, 6.4% to 11.6%) were attributable to long sleep duration from 2018 to 2028. This study informed the potential benefit of optimizing the sleep duration for the primary prevention of CVD in a contemporary population.

Short-term exposure to ambient air pollution and type 2 diabetes mortality: A population-based time series study.

Acute health effects of air pollution on diabetes risk have not been fully studied in developing countries and the results remain inconsistent. This study aimed to investigate the association between short-term exposure to ambient air pollution and Type 2 diabetes mellitus (T2DM) mortality in China. Data on T2DM mortality from 2013 to 2019 were obtained from the Cause of Death Reporting System (CDRS) of Wuhan Center for Disease Control and Prevention. Air pollution data for the same period were collected from 10 national air quality monitoring stations of Wuhan Ecology and Environment Institute, including daily average PM2.5, PM10, SO2, and NO2. Meteorological data including daily average temperature and relative humidity were collected from Wuhan Meteorological Bureau. Generalized additive models (GAM) based on quasi-Poisson distribution were applied to evaluate the association between short-term exposure to air pollution and daily T2DM deaths. A total of 9837 T2DM deaths were recorded during the study period in Wuhan. We found that short-term exposure to PM2.5, PM10, SO2, and NO2 were positively associated with T2DM mortality, and gaseous pollutants appeared to have greater effects than particulate matter (PM). For the largest effect, per 10 µg/m3 increment in PM2.5 (lag 02), PM10 (lag 02), SO2 (lag 03), and NO2 (lag 02) were significantly associated with 1.099% (95% CI: 0.451, 1.747), 1.016% (95% CI: 0.517, 1.514), 3.835% (95% CI: 1.480, 6.189), and 1.587% (95% CI: 0.646, 2.528) increase of daily T2DM deaths, respectively. Stratified analysis showed that females or elderly population aged 65 and above were more susceptible to air pollution exposure. In conclusion, short-term exposure to air pollution was significantly associated with a higher risk of T2DM mortality. Further research is required to verify our findings and elucidate the underlying mechanisms.

Ambient air pollution and cerebrovascular disease mortality: an ecological time-series study based on 7-year death records in central China.

Most studies of short-term exposure to ambient air pollution and cerebrovascular diseases focused on specific stroke-related outcomes, and results were inconsistent due to data unavailability and limited sample size. It is unclear yet how ambient air pollution contributes to the total cardiovascular mortality in central China. Daily deaths from cerebrovascular diseases were obtained from the Disease Surveillance Point System (DSPs) of Wuhan Center for Disease Control and Prevention during the period from 2013 to 2019. Air pollution data were obtained from Wuhan Ecology and Environment Institute from 10 national air quality monitoring stations, including average daily PM2.5, PM10, SO2, NO2, and O3. Average daily temperature and relative humidity were obtained from Wuhan Meteorological Bureau. We performed a Poisson regression in generalized additive models (GAM) to examine the association between ambient air pollution and cerebrovascular disease mortality. We observed a total of 84,811 deaths from cerebrovascular diseases from 1 January 2013 to 31 December 2019 in Wuhan. Short-term exposure to PM2.5, PM10, SO2, and NO2 was positively associated with daily deaths from cerebrovascular diseases, and no significant association was found for O3. The largest effect on cerebrovascular disease mortality was found at lag0 for PM2.5 (ERR: 0.927, 95% CI: 0.749-1.105 per 10 µg/m3) and lag1 for PM10 (ERR: 0.627, 95% CI: 0.493-0.761 per 10 µg/m3), SO2 (ERR: 2.518, 95% CI: 1.914, 3.122 per 10 µg/m3), and NO2 (ERR: 1.090, 95% CI: 0.822-1.358 per 10 µg/m3). The trends across lags were statistically significant. The stratified analysis demonstrated that females were more susceptible to SO2 and NO2, while elder individuals aged above 65 years old, compared with younger people, suffered more from air pollution, especially from SO2. Short-term exposure to PM2.5, PM10, SO2, and NO2 were significantly associated with a higher risk of cerebrovascular disease mortality, and elder females seemed to suffer more from air pollution. Further research is required to reveal the underlying mechanisms.

miR­155­5p downregulation inhibits epithelial­to­mesenchymal transition by targeting SIRT1 in human nasal epithelial cells.

Epithelial-to-mesenchymal transition (EMT) in nasal epithelial cells is involved with tissue remodeling of nasal polyps. The present study investigated the molecular mechanisms through which miR­155­5p regulated EMT in chronic rhinosinusitis (CRS). Patients were divided into the following groups: CRSsNP, CRS without nasal polyposis group, CRSwNP, CRS with nasal polyposis and controls. The expression of transforming growth factor (TGF)­ß1, EMT markers, sirtuin 1 (SIRT1) and miR­155­5p were determined by western blotting and reverse transcription­quantitative PCR. Cell morphology following TGF­ß1 treatment in the presence of miR­155­5p inhibitors or controls was observed under a microscope. Target genes and potential binding sites between miR­155­5p and SIRT1 were predicted by TargetScan and confirmed using dual­luciferase reporter assay. In patients with CRS, the expression levels of E­cadherin were downregulated and the expression levels of TGF­ß1, mesenchymal markers and miR­155­5p were upregulated. Additionally, these changes in expression levels were reduced or increased to a greater extent in the CRSwNP group compared with the CRSsNP group. Furthermore, TGF­ß1 expression promoted EMT in human nasal epithelial cells (HNEpCs) and upregulated miR­155­5p expression. These effects were reversed by miR­155­5p inhibitors. Additionally, SIRT1 was predicted as a target gene of miR­155­5p. Downregulation of miR­155­5p upregulated epithelial marker expression and downregulated mesenchymal marker expression by regulating SIRT1. Therefore, the downregulation of miR­155­5p inhibited EMT in HNEpCs by targeting SIRT1.

Trends in incidence and mortality of female breast cancer during transition in Central China.

PURPOSE: Following the implementation of breast cancer (BC) control strategies for years in Central China, the outcome needs to be evaluated and further strategies based on long-term surveillance should be formulated. Therefore, we examined the trends of BC incidence and mortality during 1990-2014 and projected them to 2024 in Wuhan, Central China. PATIENTS AND METHODS: The incidence and mortality data of BC were extracted from the Wuhan Cancer Registry. The average annual percentage changes (AAPCs) of the age-standardized incidence rate (ASIR) and age-standardized mortality rate (ASMR) were analyzed using Joinpoint regression. The Nordpred R-package was used to project BC incidence and mortality between 2015 and 2024. The age-period-cohort analysis was applied to evaluate the age, period, and cohort effects on the trends of BC incidence and mortality. RESULTS: Overall, the ASIR increased markedly from 20.01 to 44.26 per 100,000 (AAPC=3.3%, 95% CI: 1.7%, 5.0%) during 1990-2014, and it was projected to keep increasing in the next decade (AAPC=3.0%, 95% CI: 2.0%, 4.1%). The ASMR of BC leveled off during the study period (AAPC=0.4%, 95% CI: -0.2%, 0.9%). The BC mortality of the older group (aged 50-79 years) showed significant upward trends in both observed and projected periods. Strong age, period, and cohort effects were observed in BC incidence, and BC mortality was significantly driven by age and cohort effects. CONCLUSION: The ASIR in Wuhan was approaching those areas with the highest BC risk in China, and the evident increase in BC incidence suggested that prior strategies for BC control should be adopted. In particular, further strategies for reducing BC mortality in older age groups should be reinforced in Wuhan, Central China.

Relationships between functional fitness and cognitive impairment in Chinese community-dwelling older adults: a cross-sectional study.

OBJECTIVE: The aim of this study was to investigate the associations between each functional fitness (FF) domain and cognitive impairment (CI) in Chinese community-dwelling older adults. DESIGN: A community-based, cross-sectional study was conducted. SETTING: Participants were selected by multistage stratified random sampling in Wuhan City, Hubei Province, Central China, during December 2015-May 2016. PARTICIPANTS: A total of 2096 (1031 male and 1065 female) adults older than 65 years were included in our study. Exclusion criteria were age <65 years, losing self-living ability, previously diagnosed with dementia by a neurological physician, severe physical pain, congestive heart failure, dizziness and uncontrolled hypertension (exceeding 160/100 mm Hg). PRIMARY AND SECONDARY OUTCOME MEASURES: The Senior Fitness Test and the Mini-Mental State Examination were used to measure FF (including 30 s chair stand, 30 s arm curl, 2 min step, 8 foot up-and-go, chair sit-and-reach and back scratch) and screen CI, respectively. Activities of daily living and instrumental activities of daily living questionnaires were administered to evaluate functional status (FS). RESULTS: 32.16% were classified as the CI group. The results showed that the CI group had significantly lower frequency of 30 s chair stand, 30 s arm curl and 2 min step, and longer time to complete the 8 foot up-and-go, shorter chair sit-and-reach and back scratch distance than the non-CI adults (p<0.05). Except for back scratch, older adults with moderate and high levels of FF were less likely to have CI than those with low levels, adjusted by sociodemographics, chronic disease, health condition, health behaviour and FS (p<0.05). CONCLUSIONS: The relationship between FF and CI was independent of FS decline in Chinese community-dwelling older people.

Persistent effect at 30-month post intervention of a community-based randomized trial of KM2H2 in reducing stroke and heart attack among senior hypertensive patients.

BACKGROUND: The effect of the Keep Moving toward Healthy Heart and Healthy Brain (KM2H2) program at 6-month post intervention has been assessed.  The purpose of this study is to evaluate the KM2H2 program at 30-month post intervention. METHODS: A total of 450 senior hypertensive patients from 12 community health centers were randomized by center to either receive KM2H2 plus standard care (6 centers, n = 232) or standard care only (6 centers, n = 218). Data for outcome measures at 30-month post intervention were analyzed. New cases of stroke and heart attack were verified with medical records; levels of physical activity were assessed using self-reported questionnaire. In addition to comparative analysis, adjusted incidence rate and program effects were determined using mixed effects modeling method. RESULTS: At the 30-month follow-up, the adjusted incidence rate [95% CI] of stroke was 11.81% [5.90, 17.72] for patients in the intervention group and 19.78% [14.07, 25.50] (p = 0.03) for the control group. The adjusted incidence rate of heart attack was 3.34% [1.91, 8.58] and 6.68% [1.64, 11.73] for the intervention and control groups (p = 0.16), respectively; the proportion and the duration of engaging in regular physical activity were significantly greater for the intervention group than the control group. The reductions in blood pressure between the intervention and the control was not statistically significant. CONCLUSIONS: The KM2H2 program showed a persistent effect up to 30 months post intervention in enhancing physical activity and reducing the risk of cardio-cerebrovascular events, particularly stroke. These findings demonstrate the persistent effect of the KM2H2 and suggest the need for a full-scale evaluation of the intervention program for practical use. TRIAL REGISTRATION: ISRCTN Register ISRCTN12608966 . Registered 03 March 2015. Retrospectively registered.

Application of the protection motivation theory in predicting cigarette smoking among adolescents in China.

Reducing tobacco use among adolescents in China represents a significant challenge for global tobacco control. Existing behavioral theories developed in the West - such as the Protection Motivation Theory (PMT) - may be useful tools to help tackle this challenge. We examined the relationships between PMT factors and self-reported cigarette smoking behavior and intention among a random sample of vocational high school students (N=553) in Wuhan, China. Tobacco-related perceptions were assessed using the PMT Scale for Adolescent Smoking. Among the total sample, 45% had initiated cigarette smoking, and 25% smoked in the past month. Among those who never smoked, 15% indicated being likely or very likely to smoke in a year. Multiple regression modeling analysis indicated the significance of the seven PMT constructs, the four PMT perceptions and the two PMT pathways in predicting intention to smoke and actual smoking behavior. Overall, perceived rewards of smoking, especially intrinsic rewards, were consistently positively related to smoking intentions and behavior, and self-efficacy to avoid smoking was negatively related to smoking. The current study suggests the utility of PMT for further research examining adolescent smoking. PMT-based smoking prevention and clinical smoking cessation intervention programs should focus more on adolescents' perceived rewards from smoking and perceived efficacy of not smoking to reduce their intention to and actual use of tobacco.

[Psychological factors of adopting and maintaining physical activity for individuals with hypertension in a community].

OBJECTIVE: To examine the impact of psychosocial factors on physical activity, so as to provide guidance for the development of an effective physical activity intervention program for individuals with hypertension. METHODS: This study used a baseline data from an intervention study on regular physical activity among hypertensive individuals. A multi-stage, stratified random sampling was utilized and finally 12 communities from 6 urban districts were chosen. Questionnaires were administrated through face-to-face interviews. A total of 586 participants were recruited and finally 559 completed the interviews with the response rate as 95.4%. Descriptive statistics and Cronbach's α coefficients were used to test the reliability. General Linear Model analysis was used to analyze the relationship between stages of physical activity and psychological factors. RESULTS: Psychosocial measures on physical activity demonstrated good reliability with Cronbach α coefficient from 0.7 to 0.9. The scores for each psychological measures increased by increasing the scores of stages of physical activity. General Linear Model analysis revealed self-efficacy (ß = 0.379) while enjoyment of physical activity (ß = 0.234) was significantly correlated with physical activity (P < 0.05). The behavioral processes and family support marginally increased the physically activity (ß = 0.069 for behavioral processes and ß = 0.163 for family support, P < 0.10). CONCLUSION: Our findings were informative for the development of community-based intervention programs on physical activity among hypertensive individuals. It indicated that physical activity intervention programs should be psychosocial theory-based, especially increasing their self-confidence and enjoyment, as well as with family support, in order to adopt and maintain the physical activities.

Time trends and age-period-cohort analyses on incidence rates of nasopharyngeal carcinoma during 1993-2007 in Wuhan, China.

BACKGROUND: Declines in incidence rates of nasopharyngeal carcinoma (NPC) were observed in Hong Kong and Taiwan but not other high-risk regions in China, while evidences from low-risk regions in China are still lacking. This study aimed to examine the time trends (1993-2007) of NPC in Wuhan (a low-risk region) and assess the birth cohort and calendar period effects on the observed temporal trends. METHOD: Using data from Wuhan Cancer Registry, age-standardized annual incidence rates of NPC were calculated by the direct method using the WHO World Standard Population (2000) as the reference. Trend in incidence rates of NPC during 1993-2007 was evaluated. Age-period-cohort models were also applied to assess the effects of age, calendar time and birth cohort on the observed temporal trends. RESULTS: A total of 1685 new NPC cases (1210 males and 475 females) were diagnosed during 1993-2007 in Wuhan. The annual percentage change in incidence rates of NPC were 0.15% (95% confidence interval: -3.88% to 4.34%) for males and -1.17% (95% confidence interval: -4.85% to 2.66%) for females. No obvious cohort or period effect on the incidence rates of NPC was observed. CONCLUSION: The incidence rates of NPC remained stable during 1993-2007 in Wuhan, a low-risk region in China.

Part 2. Association of daily mortality with ambient air pollution, and effect modification by extremely high temperature in Wuhan, China.

Fewer studies have been published on the association between daily mortality and ambient air pollution in Asia than in the United States and Europe. This study was undertaken in Wuhan, China, to investigate the acute effects of air pollution on mortality with an emphasis on particulate matter (PM*). There were three primary aims: (1) to examine the associations of daily mortality due to all natural causes and daily cause-specific mortality (cardiovascular [CVD], stroke, cardiac [CARD], respiratory [RD], cardiopulmonary [CP], and non-cardiopulmonary [non-CP] causes) with daily mean concentrations (microg/m3) of PM with an aerodynamic diameter--10 pm (PM10), sulfur dioxide (SO2), nitrogen dioxide (NO2), or ozone (O3); (2) to investigate the effect modification of extremely high temperature on the association between air pollution and daily mortality due to all natural causes and daily cause-specific mortality; and (3) to assess the uncertainty of effect estimates caused by the change in International Classification of Disease (ICD) coding of mortality data from Revision 9 (ICD-9) to Revision 10 (ICD-10) code. Wuhan is called an "oven city" in China because of its extremely hot summers (the average daily temperature in July is 37.2 degrees C and maximum daily temperature often exceeds 40 degrees C). Approximately 4.5 million residents live in the core city area of 201 km2, where air pollution levels are higher and ranges are wider than the levels in most cities studied in the published literature. We obtained daily mean levels of PM10, SO2, and NO2 concentrations from five fixed-site air monitoring stations operated by the Wuhan Environmental Monitoring Center (WEMC). O3 data were obtained from two stations, and 8-hour averages, from 10:00 to 18:00, were used. Daily mortality data were obtained from the Wuhan Centres for Disease Prevention and Control (WCDC) during the study period of July 1, 2000, to June 30, 2004. To achieve the first aim, we used a regression of the logarithm of daily counts of mortality due to all natural causes and cause-specific mortality on the daily mean concentrations of the four pollutants while controlling for weather, temporal factors, and other important covariates with generalized additive models (GAMs). We derived pollutant effect estimations for 0-day, 1-day, 2-day, 3-day, and 4-day lagged exposure levels, and the averages of 0-day and 1-day lags (lag 0-1 day) and of 0-day, 1-day, 2-day, and 3-day lags (lag 0-3 days) before the event of death. In addition, we used individual-level data (e.g., age and sex) to classify subgroups in stratified analyses. Furthermore, we explored the nonlinear shapes ("thresholds") of the exposure-response relations. To achieve the second aim, we tested the hypothesis that extremely high temperature modifies the associations between air pollution and daily mortality. We developed three corresponding weather indicators: "extremely hot," "extremely cold," and "normal temperatures." The estimates were obtained from the models for the main effects and for the pollutant-temperature interaction for each pollutant and each cause of mortality. To achieve the third aim, we conducted an additional analysis. We examined the concordance rates and kappa statistics between the ICD-9-coded mortality data and the ICD-10-coded mortality data for the year 2002. We also compared the magnitudes of the estimated effects resulting from the use of the two types of ICD-coded mortality data. In general, the largest pollutant effects were observed at lag 0-1 day. Therefore, for this report, we focused on the results obtained from the lag 0-1 models. We observed consistent associations between PM10 and mortality: every 10-microg/m3 increase in PM10 daily concentration at lag 0-1 day produced a statistically significant association with an increase in mortality due to all natural causes (0.43%; 95% confidence interval [CI], 0.24 to 0.62), CVD (0.57%; 95% CI, 0.31 to 0.84), stroke (0.57%; 95% CI, 0.25 to 0.88), CARD (0.49%; 95% CI, 0.04 to 0.94), RD (0.87%; 95% CI, 0.34 to 1.41), CP (0.52%; 95% CI, 0.27 to 0.77), and non-CP (0.30%; 95% CI, 0.05 to 0.54). In general, these effects were stronger in females than in males and were also stronger among the elderly (> or = 65 years) than among the young. The results of sensitivity testing over the range of exposures from 24.8 to 477.8 microg/m3 also suggest the appropriateness of assuming a linear relation between daily mortality and PM10. Among the gaseous pollutants, we also observed statistically significant associations of mortality with NO, and SO2, and that the estimated effects of these two pollutants were stronger than the PM10 effects. The patterns of NO2 and SO2 associations were similar to those of PM10 in terms of sex, age, and linearity. O3 was not associated with mortality. In the analysis of the effect modification of extremely high temperature on the association between air pollution and daily mortality, only the interaction of PM10 with temperature was statistically significant. Specifically, the interaction terms were statistically significant for mortality due to all natural (P = 0.014), CVD (P = 0.007), and CP (P = 0.014) causes. Across the three temperature groups, the strongest PM10 effects occurred mainly on days with extremely high temperatures for mortality due to all natural (2.20%; 95% CI, 0.74 to 3.68), CVD (3.28%; 95% CI, 1.24 to 5.37), and CP (3.02%; 95% CI, 1.03 to 5.04) causes. The weakest effects occurred at normal temperature days, with the effects on days with low temperatures in the middle. To assess the uncertainty of the effect estimates caused by the change from ICD-9-coded mortality data to ICD-10-coded mortality data, we compared the two sets of data and found high concordance rates (> 99.3%) and kappa statistics close to 1.0 (> 0.98). All effect estimates showed very little change. All statistically significant levels of the estimated effects remained unchanged. In conclusion, the findings for the aims from the current study are consistent with those in most previous studies of air pollution and mortality. The small differences between mortality effects for deaths coded using ICD-9 and ICD-10 show that the change in coding had a minimal impact on our study. Few published papers have reported synergistic effects of extremely high temperatures and air pollution on mortality, and further studies are needed. Establishing causal links between heat, PM10, and mortality will require further toxicologic and cohort studies.

Short-term effects of gaseous pollutants on cause-specific mortality in Wuhan, China.

In Asia, limited studies have been published on the association between daily mortality and gaseous pollutants of nitrogen dioxide (NO2), ozone (O3), and sulfur dioxide (SO2). Our previous studies in Wuhan, China, demonstrated long-term air pollution effects. However, no study has been conducted to determine mortality effects of air pollution in this region. This study was to determine the acute mortality effects of the gaseous pollutants in Wuhan, a city with 7.5 million permanent residents during the period from 2000 to 2004. There are approximately 4.5 million residents in Wuhan who live in the city's core area of 201 km2, where air pollution levels are highest, and pollution ranges are wider than the majority of the cities in the published literature. We used the generalized additive model to analyze pollution, mortality, and covariate data. We found consistent NO2 effects on mortality with the strongest effects on the same day. Every 10-microg/m3 increase in NO2 daily concentration on the same day was associated with an increase in nonaccidental (1.43%; 95% confidence interval [CI]: 0.87-1.99%), cardiovascular (1.65%; 95% CI: 0.87-2.45%), stroke (1.49%; 95% CI: 0.56-2.43%), cardiac (1.77%; 95% CI: 0.44-3.12%), respiratory (2.23%; 95% CI: 0.52-3.96%), and cardiopulmonary mortality (1.60%; 95% CI: 0.85-2.35%). These effects were stronger among the elderly than among the young. Formal examination of exposure-response curves suggests no-threshold linear relationships between daily mortality and NO2, where the NO2 concentrations ranged from 19.2 to 127.4 microg/m3. SO2 and O3 were not associated with daily mortality. The exposure-response relationships demonstrated heterogeneity, with some curves showing nonlinear relationships for SO2 and O3. We conclude that there is consistent evidence of acute effects of NO2 on mortality and suggest that a no-threshold linear relationship exists between NO2 and mortality.