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Summary: Background: In non-high-risk individuals, risk-category-based atherosclerotic cardiovascular disease (ASCVD) screening strategies may be more cost-effective than one-size-fits-all approaches. However, current decisions are constrained by a lack of research evidence. We aimed to explore appropriate risk-category-based screening interval strategies for non-high-risk individuals in ASCVD primary prevention in the Chinese population. Methods: We used data from 28,624 participants in the China Kadoorie Biobank (CKB) who had completed at least two field surveys. The risk assessment tools were the 10-year ASCVD risk prediction models developed based on the CKB cohort. We constructed multistate Markov models to model disease progression and estimate transition probabilities between different risk categories. The total person-years spent unidentified in the high-risk state over a 10-year period were calculated for each screening interval protocol. We also estimated the number of ASCVD events prevented, quality-adjusted life years (QALYs) gained, and costs saved when compared to the 3-yearly screening protocol. Findings: When compared to the uniform 3-yearly protocol, most risk-category-based screening interval protocols would identify more high-risk individuals timely, thus preventing more ASCVD events and gaining QALYs. A few of them would reduce total health-care costs. The protocol, which used 6-year, 3-year, and 2-year screening intervals for low-risk, intermediate-low-risk, and intermediate-high risk individuals, was optimal, and would reduce the person-years spent unidentified in the high-risk category by 17.9% (95% CI: 13.1%–21.9%), thus preventing an estimated 113 thousand (95% CI: 83–138) hard ASCVD events for Chinese adults aged 30–79 over a 10-year period. When using a lower cost of statin therapy, more screening protocols would gain QALYs while saving costs. Interpretation: For the primary prevention of ASCVD, risk-category-based screening protocols outperformed the one-size-fits-all approach in the Chinese population. Funding: This work was supported by National Natural Science Foundation of China (82192904, 82388102, 82192900) and grants (2023YFC2509400) from the National Key R&D Program of China. The CKB baseline survey and the first re-survey were supported by a grant from the Kadoorie Charitable Foundation in Hong Kong. The long-term follow-up is supported by grants from the UK Wellcome Trust (212946/Z/18/Z, 202922/Z/16/Z, 104085/Z/14/Z, 088158/Z/09/Z), grants (2016YFC0900500) from the National Key R&D Program of China, National Natural Science Foundation of China (81390540, 91846303, 81941018), and Chinese Ministry of Science and Technology (2011BAI09B01).

Background: Neoadjuvant therapy improves survival benefits in patients with locally advanced non-small cell lung cancer but increases tissue density, presenting challenges for surgeons. Objectives: To compare the differences in surgical complexity and short-term prognostic outcomes between neoadjuvant targeted therapy (NTT) and neoadjuvant chemoimmunotherapy (NCI). Design/methods: This study enrolled 106 patients underwent curative surgery after neoadjuvant therapy between January 2020 and December 2023 at the National Cancer Center of China. Differences in surgical complexity and short-term prognostic outcomes between the two neoadjuvant therapy cohorts were evaluated. The pathological indicators such as pathological response rate and lymph node upstaging/downstaging were then analyzed. Results: In total, 33 patients underwent NTT and 73 underwent NCI preoperatively. Patients who received NTT showed a higher minimally invasive surgery rate (84.8% versus 53.4%, p < 0.01), shorter operative time (144 versus 184 min, p < 0.01), lower conversion rate (3.3% versus 17.8%, p = 0.03), less postoperative drainage (day 3: 140 versus 200 mL, p = 0.03), and lower incidence of postoperative complications including arrhythmias (6.1% versus 26%, p = 0.02). The pathological response rate in the NTT and NCI groups was 70% and 75%, respectively, with the latter group showing a higher complete pathological response rate. The two groups had no significant differences in major pathological response and lymph node pathological response rate. Conclusion: Patients who received NTT presented fewer surgical challenges for surgeons and had better surgical outcomes than those who received NCI therapy, with comparable pathological response rates between the two cohorts. Accordingly, NTT is the preferred induction regimen for patients harboring mutation status.

Summary: Background: Previous observational studies established a positive relationship between snoring and stroke. We aimed to investigate the causal effect of snoring on stroke. Methods: Based on 82,339 unrelated individuals with qualified genotyping data of Asian descent from the China Kadoorie Biobank (CKB), we conducted a Mendelian randomization (MR) analysis of snoring and stroke. Genetic variants identified in the genome-wide association analysis (GWAS) of snoring in CKB and UK Biobank (UKB) were selected for constructing genetic risk scores (GRS). A two-stage method was applied to estimate the associations of the genetically predicted snoring with stroke and its subtypes. Besides, MR analysis among the non-obese group (body mass index, BMI

Objectives To explore the association between non-high-density lipoprotein (non-HDL) and mortality risk, both short-term and long-term, in Chinese people.Design A prospective cohort study.Setting The National Basic Public Health Service (BPHS) in China.Participants Including 621 164 elderly individuals around Hunan Province who underwent healthcare management receiving check-ups in China BPHS from 2010 to 2020. Exclusion criteria: (1) missing information on gender; (2) missing records of lipid screening; (3) missing information on key covariates; and (4) missing records of comorbidities (cardiovascular disease, hypertension, diabetes, cancer.)Primary and secondary outcome measures The study’s primary endpoint was all-cause and cause-specific mortality, sourced from Hunan’s CDC(Center for Disease Control and Prevention)-operated National Mortality Surveillance System, tracking participants until 24 February 2021.Results 26 758 (4.3%) deaths were recorded, with a median follow-up of 0.83 years. Association between non-HDL and mortality was non-linear after multivariable adjustment, with the optimum concentration (OC) being 3.29 and 4.85 mmol/L. Compared with OC, the risk increased by 1.12-fold for non-HDL

BackgroundAir pollution is a major public health concern. Air Quality Health Index (AQHI) is a very important air quality risk communication tool. However, AQHI is usually constructed by single-pollutant model, which has obvious disadvantages.ObjectiveTo construct an AQHI based on the joint effects of multiple air pollutants (J-AQHI), and to provide a scientific tool for health risk warning and risk communication of air pollution.MethodsData on non-accidental deaths in Yunnan, Guangdong, Hunan, Zhejiang, and Jilin provinces from January 1, 2013 to December 31, 2018 were obtained from the corresponding provincial disease surveillance points systems (DSPS), including date of death, age, gender, and cause of death. Daily meteorological (temperature and relative humidity) and air pollution data (SO2, NO2, CO, PM2.5, PM10, and maximum 8 h O3 concentrations) at the same period were respectively derived from China Meteorological Data Sharing Service System and National Urban Air Quality Real-time Publishing Platform. Lasso regression was first applied to select air pollutants, then a time-stratified case-crossover design was applied. Each case was matched to 3 or 4 control days which were selected on the same days of the week in the same calendar month. Then a distributed lag nonlinear model (DLNM) was used to estimate the exposure-response relationship between selected air pollutants and mortality, which was used to construct the AQHI. Finally, AQHI was classified into four levels according to the air pollutant guidance limit values from World Health Organization Global Air Quality Guidelines (AQG 2021), and the excess risks (ERs) were calculated to compare the AQHI based on single-pollutant model and the J-AQHI based on multi-pollutant model.ResultsPM2.5, NO2, SO2, and O3 were selected by Lasso regression to establish DLNM model. The ERs for an interquartile range (IQR) increase and 95% confidence intervals (CI) for PM2.5, NO2, SO2 and O3 were 0.71% (0.34%–1.09%), 2.46% (1.78%–3.15%), 1.25% (0.9%–1.6%), and 0.27% (−0.11%–0.65%) respectively. The distribution of J-AQHI was right-skewed, and it was divided into four levels, with ranges of 0-1 for low risk, 2-3 for moderate risk, 4-5 for high health risk, and ≥6 for severe risk, and the corresponding proportions were 11.25%, 64.61%, 19.33%, and 4.81%, respectively. The ER (95%CI) of mortality risk increased by 3.61% (2.93–4.29) for each IQR increase of the multi-pollutant based J-AQHI , while it was 3.39% (2.68–4.11) for the single-pollutant based AQHI .ConclusionThe J-AQHI generated by multi-pollutant model demonstrates the actual exposure health risk of air pollution in the population and provides new ideas for further improvement of AQHI calculation methods.

Injury poses heavy burden on public health, but little evidence on the potential role of climate change on injury exists. Here, the authors collect data during 2013-2019 in six provinces of China to estimate the associations between temperature and injury mortality, and to project future mortality burden attributable to temperature change driven by climate change.

Abstract Associations of circulating metabolic biomarkers with type 2 diabetes (T2D) and their added value for risk prediction are uncertain among Chinese adults. A case-cohort study included 882 T2D cases diagnosed during 8-years’ follow-up and a subcohort of 789 participants. NMR-metabolomic profiling quantified 225 plasma biomarkers in stored samples taken at recruitment into the study. Cox regression yielded adjusted hazard ratios (HRs) for T2D associated with individual biomarkers, with a set of biomarkers incorporated into an established T2D risk prediction model to assess improvement in discriminatory ability. Mean baseline BMI (SD) was higher in T2D cases than in the subcohort (25.7 [3.6] vs. 23.9 [3.6] kg/m2). Overall, 163 biomarkers were significantly and independently associated with T2D at false discovery rate (FDR) controlled p

BackgroundDrowning is a serious public health problem worldwide. Previous epidemiological studies on the association between meteorological factors and drowning mainly focused on individual weather factors, and the combined effect of mixed exposure to multiple meteorological factors on drowning is unclear. ObjectiveWe aimed to investigate the combined effects of multiple meteorological factors on unintentional drowning mortality in China and to identify the important meteorological factors contributing to drowning mortality. MethodsUnintentional drowning death data (based on International Classification of Diseases, 10th Edition, codes W65-74) from January 1, 2013, to December 31, 2018, were collected from the Disease Surveillance Points System for Guangdong, Hunan, Zhejiang, Yunnan, and Jilin Provinces, China. Daily meteorological data, including daily mean temperature, relative humidity, sunlight duration, and rainfall in the same period were obtained from the Chinese Academy of Meteorological Science Data Center. We constructed a time-stratified case-crossover design and applied a generalized additive model to examine the effect of individual weather factors on drowning mortality, and then used quantile g-computation to estimate the joint effect of the mixed exposure to meteorological factors. ResultsA total of 46,179 drowning deaths were reported in the 5 provinces in China from 2013 to 2018. In an effect analysis of individual exposure, we observed a positive effect for sunlight duration, a negative effect for relative humidity, and U-shaped associations for temperature and rainfall with drowning mortality. In a joint effect analysis of the above 4 meteorological factors, a 2.99% (95% CI 0.26%-5.80%) increase in drowning mortality was observed per quartile rise in exposure mixture. For the total population, sunlight duration was the most important weather factor for drowning mortality, with a 93.1% positive contribution to the overall effects, while rainfall was mainly a negative factor for drowning deaths (90.5%) and temperature and relative humidity contributed 6.9% and –9.5% to the overall effects, respectively. ConclusionsThis study found that mixed exposure to temperature, relative humidity, sunlight duration, and rainfall was positively associated with drowning mortality and that sunlight duration, rather than temperature, may be the most important meteorological factor for drowning mortality. These findings imply that it is necessary to incorporate sunshine hours and temperature into early warning systems for drowning prevention in the future.

Although studies have estimated the associations of PM2.5 with total mortality or cardiopulmonary mortality, few have comprehensively examined cause-specific mortality risk and burden caused by ambient PM2.5. Thus, this study investigated the association of short-term exposure to PM2.5 with cause-specific mortality using a death-spectrum wide association study (DWAS). Individual information of 5,450,764 deaths during 2013–2018 were collected from six provinces in China. Daily PM2.5 concentration in the case and control days were estimated by a random forest model. A time-stratified case-crossover study design was applied to estimate the associations (access risk, ER) of PM2.5 with cause-specific mortality, which was then used to calculate the population-attributable fraction (PAF) of mortality and the corresponding mortality burden caused by PM2.5. Each 10 μg/m3 increase in PM2.5 concentration (lag03) was associated with a 0.80 % [95 % confidence interval (CI): 0.73 %, 0.86 %] rise in total mortality. We found greater mortality effect at PM2.5 concentrations

BackgroundThe United Nations Sustainable Development Goals for 2030 include reducing premature mortality from noncommunicable diseases by one-third. Although previous modeling studies have predicted premature mortality from noncommunicable diseases, the predictions for cancer and its subcategories are less well understood in China. ObjectiveThe aim of this study was to project premature cancer mortality of 10 leading cancers in Hunan Province, China, based on various scenarios of risk factor control so as to establish the priority for future interventions. MethodsWe used data collected between 2009 and 2017 from the Hunan cancer registry annual report as empirical data for projections. The population-attributable fraction was used to disaggregate cancer deaths into parts attributable and unattributable to 10 risk factors: smoking, alcohol use, high BMI, diabetes, physical inactivity, low vegetable and fruit intake, high red meat intake, high salt intake, and high ambient fine particulate matter (PM2.5) levels. The unattributable deaths and the risk factors in the baseline scenario were projected using the proportional change model, assuming constant annual change rates through 2030. The comparative risk assessment theory was used in simulated scenarios to reflect how premature mortality would be affected if the targets for risk factor control were achieved by 2030. ResultsThe cancer burden in Hunan significantly increased during 2009-2017. If current trends for each risk factor continued to 2030, the total premature deaths from cancers in 2030 would increase to 97,787 in Hunan Province, and the premature mortality (9.74%) would be 44.47% higher than that in 2013 (6.74%). In the combined scenario where all risk factor control targets were achieved, 14.41% of premature cancer mortality among those aged 30-70 years would be avoided compared with the business-as-usual scenario in 2030. Reductions in the prevalence of diabetes, high BMI, ambient PM2.5 levels, and insufficient fruit intake played relatively important roles in decreasing cancer premature mortality. However, the one-third reduction goal would not be achieved for most cancers except gastric cancer. ConclusionsExisting targets on cancer-related risk factors may have important roles in cancer prevention and control. However, they are not sufficient to achieve the one-third reduction goal in premature cancer mortality in Hunan Province. More aggressive risk control targets should be adopted based on local conditions.

Abstract Background Immunotherapy using immune checkpoint inhibitors (ICIs), such as antibody of programmed death-1 (PD-1)/programmed death-ligand 1 (PD-L1) has showed as a promising treatment for esophageal squamous cell carcinoma (ESCC), but resistance is unavoidable. This study aimed to find more immune-related genes to promote the efficiency of immunotherapy. Materials and methods Three datasets were downloaded from Gene Expression Omnibus (GEO) database. Gene differential analysis was performed to identify differentially expressed genes (DEGs), then ceRNA network was constructed based on differentially expressed lncRNAs and mRNAs. Next, Functional enrichment analysis and protein–protein interaction (PPI) network were built to reveal the potential function of mRNAs in ceRNA network. Survival analysis and immune cell infiltration level analysis were utilized to identify prognostic immune-related genes. Finally, pan-cancer analysis was performed to show the role of immune-related genes in other cancers. Results The data of 215 samples in total were obtained from GEO database (98 normal tissues and 117 tumor tissues), and 1685 differentially expressed mRNAs (176 downregulated and 1509 upregulated) and 3 upregulated lncRNAs (MCM3AP-AS1, HCP5 and GUSBP11, all upregulated) were found. ceRNA network was constructed to reveal some special correlation. Function enrichment showed some potential functions of mRNAs in ceRNA network such as mitotic cell cycle process, negative regulation of DNA-binding transcription factor activity, ossification, VEGFA-VEGFR2 signaling pathway, epithelial to mesenchymal transition, embryonic morphogenesis and so on. PPI network showed the physical interactions between each mRNA in ceRNA network. Through survival analysis and immune cell infiltration level analysis, GINS4 was confirmed as an immune-related prognostic gene in ESCC. GSEA showed some potential functions such as negative regulation of monocyte chemotaxis, antigen processing and presentation of endogenous peptide antigen via MHC class I via ER pathway, positive regulation of antigen processing and presentation, dendritic cell antigen processing and presentation and so on. Finally, pan-cancer analysis revealed that GINS4 might be a novel immune-related prognostic gene in ESCC and other cancers. Conclusion Our study suggested that GINS4 was correlated with prognosis and immune cell infiltration level of ESCC and other cancers. It may deserve further investigation as a potential immune-related prognostic biomarker of ESCC and other cancers.

Background: In China, there are few studies that have reported future estimations for cancer mortality. Therefore, this study aimed to assess cancer mortality in China and identify priorities for future cancer control strategies. Methods: Based on the Global Burden of Disease 2019 study, we extracted data on cancer-related deaths from 1990 to 2019 in Hunan Province, China. Under the current trends evaluated using a joinpoint regression model, we fitted a linear regression model for cancer mortality projections by 2025. Results: The age-standardized mortality rate of total cancer in Hunan, China, declined slowly and is projected to be 140.80 (95% confidence interval [CI]: 140.12–141.48) by 2025, with the mortality rate in men approximately twice that in women. In 2025, the top five causes of cancer-related deaths in males are projected to be lung, liver, colorectal, stomach, and esophageal cancers, with the corresponding causes in females being lung, breast, colorectal, liver, and cervical cancers. Between 2019 and 2025, male mortality rates due to liver and pancreatic cancer are expected to increase, while those due to the six leading female cancers will increase. Excess male deaths were associated with liver and esophageal cancers, while all main cancers in females will have excess mortality, except for colorectal cancer. Conclusion: A comprehensive cancer spectrum characteristic of both developing and developed countries will remain in Hunan, China. Lung cancer remains the most common cause of cancer-related deaths, and tobacco control efforts are urgently required. Additional efforts should be made to promote universal screening, improve access to cancer healthcare services, optimize medical payment models, and enhance access to valuable anticancer drugs.

BackgroundSolid predominant adenocarcinoma (SPA) has been reported to be a subtype with poor prognosis and unsatisfactory response to chemotherapy and targeted therapy in lung adenocarcinoma (LUAD). However, the underlying mechanisms remain largely unknown and the suitability of immunotherapy for SPA has not been investigated.MethodsWe conducted a multi-omics analysis of 1078 untreated LUAD patients with clinicopathologic, genomic, transcriptomic, and proteomic data from both public and internal cohorts to determine the underlying mechanisms of poor prognosis and differential therapeutic responses of SPA and to investigate the potential of immunotherapy for SPA. The suitability of immunotherapy for SPA was further confirmed in a cohort of LUAD patients who received neoadjuvant immunotherapy in our center.ResultsAlong with its aggressive clinicopathologic behaviors, SPA had significantly higher tumor mutation burden (TMB) and number of pathways altered, lower TTF-1 and Napsin-A expression, higher proliferation score and a more immunoresistant microenvironment than non-solid predominant adenocarcinoma (Non-SPA), accounting for its worse prognosis. Additionally, SPA had significantly lower frequency of therapeutically targetable driver mutations and higher frequency of EGFR/TP53 co-mutation which was related to resistance to EGFR tyrosine kinase inhibitors, indicating a lower potential for targeted therapy. Meanwhile, SPA was enriched for molecular features associated with poor response to chemotherapy (higher chemoresistence signature score, lower chemotherapy response signature score, hypoxic microenvironment, and higher frequency of TP53 mutation). Instead, muti-omics profiling revealed that SPA had stronger immunogenicity and was enriched for positive biomarkers for immunotherapy (higher TMB and T cell receptor diversity; higher PD-L1 expression and more immune cell infiltration; higher frequency of gene mutations predicting efficacious immunotherapy, and elevated expression of immunotherapy-related gene signatures). Furthermore, in the cohort of LUAD patients who received neoadjuvant immunotherapy, SPA had higher pathological regression rates than Non-SPA and patients with major pathological response were enriched in SPA, confirming that SPA was more prone to respond to immunotherapy.ConclusionsCompared with Non-SPA, SPA was enriched for molecular features associated with poor prognosis, unsatisfactory response to chemotherapy and targeted therapy, and good response to immunotherapy, indicating more suitability for immunotherapy while less suitability for chemotherapy and targeted therapy.

Background: Although many studies have reported the mortality effect of temperature, there were few studies on the mortality risk of humidity, let alone the joint effect of temperature and humidity. This study aimed to investigate the joint and interaction effect of high temperature and relative humidity on mortality in China, which will deepen understanding the health risk of mixture climate exposure. Methods: The mortality and meteorological data were collected from 353 locations in China (2013–2017 in Jilin, Hunan, Guangdong and Yunnan provinces, 2009–2017 in Zhejiang province, and 2006–2011 in other Provinces). We defined location-specific daily mean temperature ≥ 75th percentile of distribution as high temperature, while minimum mortality relative humidity as the threshold of high relative humidity. A time-series model with a distributed lag non-linear model was first employed to estimate the location-specific associations between humid-hot events and mortality, then we conducted meta-analysis to pool the mortality effect of humid-hot events. Finally, an additive interaction model was used to examine the interactive effect between high temperature and relative humidity. Results: The excess rate (ER) of non-accidental mortality attributed to dry-hot events was 10.18% (95% confidence interval (CI): 8.93%, 11.45%), which was higher than that of wet-hot events (ER = 3.21%, 95% CI: 0.59%, 5.89%). The attributable fraction (AF) of mortality attributed to dry-hot events was 10.00% (95% CI: 9.50%, 10.72%) with higher burden for females, older people, central China, cardiovascular diseases and urban city. While for wet-hot events, AF was much lower (3.31%, 95% CI: 2.60%, 4.30%). We also found that high temperature and low relative humidity had synergistic additive interaction on mortality risk. Conclusion: Dry-hot events may have a higher risk of mortality than wet-hot events, and the joint effect of high temperature and low relative humidity may be greater than the sum of their individual effects.

BackgroundLittle is known about the effect of histology on the efficacy of immune checkpoint inhibitors (ICI) in non-small-cell lung cancer (NSCLC). We conducted a systematic review and meta-analysis to assess the potential differences in the efficacy of ICIs between squamous NSCLC (SQ-NSCLC) and non-squamous NSCLC (non-SQ-NSCLC).MethodsSystematic searches of PubMed, Embase, Scopus, and Cochrane Library databases were conducted. All randomized clinical trials of ICIs with available hazard ratios (HR) for progression-free survival (PFS) or overall survival (OS) according to histology were included. The primary endpoint was to assess the difference in the efficacy of ICIs between SQ-NSCLC and non-SQ-NSCLC, measured by the ratio of the HR in SQ-NSCLC to the HR in non-SQ-NSCLC (RHR).ResultsA total of 40 trials were included in the meta-analysis. ICI monotherapy could improve OS in both SQ-NSCLC (OS-HR 0.71, 95% CI 0.65-0.77) and non-SQ-NSCLC (OS-HR 0.80, 95% CI 0.73-0.87) while OS benefit was larger in SQ-NSCLC (OS-RHR 0.89, 95% CI 0.80-0.99). In terms of PFS, ICI monotherapy could reduce the risk of progression by 35% (PFS-HR 0.65, 95% CI 0.56-0.77) in SQ-NSCLC while the PFS benefit was smaller (10%) and not statistically significant in non-SQ-NSCLC (PFS-HR 0.90, 95% CI 0.76-1.07). Similarly, ICI-based combination treatments could reduce the risk of both progression and death in SQ-NSCLC (OS-HR 0.70, 95% CI 0.61-0.80; PFS-HR 0.56, 95% CI 0.48-0.65) and non-SQ-NSCLC (OS-HR 0.78, 95% CI 0.74-0.83; PFS-HR 0.63, 95% CI 0.57-0.69) while the survival benefits were larger in SQ-NSCLC (OS-RHR 0.83, 95% CI 0.70-0.99; PFS-RHR 0.82, 95% CI 0.70-0.96).ConclusionsICIs could deliver survival benefits in both SQ-NSCLC and non-SQ-NSCLC while the magnitude of survival benefits was histology-dependent. Future researches should consider the effect of histology on the efficacy of ICIs.Systematic Review Registrationhttps://www.crd.york.ac.uk/prospero/, identifier [CRD42022299603].

BackgroundThe Spring Festival is one of the most important traditional festivals in China. This study aimed to estimate the mortality risk attributable to the Spring Festival.MethodsBetween 2013 and 2017, daily meteorological, air pollution, and mortality data were collected from 285 locations in China. The Spring Festival was divided into three periods: pre-Spring Festival (16 days before Lunar New Year's Eve), mid-Spring Festival (16 days from Lunar New Year's Eve to Lantern Festival), and post-Spring Festival (16 days after Lantern Festival). The mortality risk attributed to the Spring Festival in each location was first evaluated using a distributed lag nonlinear model (DLNM), and then it was pooled using a meta-analysis model.ResultsWe observed a dip/rise mortality pattern during the Spring Festival. Pre-Spring Festival was significantly associated with decreased mortality risk (ER: −1.58%, 95%CI: −3.09% to −0.05%), and mid-Spring Festival was unrelated to mortality risks, while post-Spring Festival was significantly associated with increased mortality risk (ER: 3.63%, 95%CI: 2.15–5.12%). Overall, a 48-day Spring Festival period was associated with a 2.11% (95%CI: 0.91–3.33%) increased mortality. We also found that the elderly aged over 64 years old, women, people with cardiovascular disease (CVD), and people living in urban areas were more vulnerable to the Spring Festival.ConclusionOur study found that the Spring Festival significantly increased the mortality risk in China. These findings suggest that it is necessary to develop clinical and public health policies to alleviate the mortality burden associated with the Spring Festival.

Abstract Background Several studies have investigated the associations between ambient temperature and years of life lost (YLLs), but few focused on the difference of life loss attributable to temperature among different socioeconomic development levels. Objectives We investigated the disparity in temperature-YLL rate relationships and life loss per death attributable to nonoptimal temperature in regions with various development levels. Methods Three hundred sixty-four Chinese counties or districts were classified into 92 high-development regions (HDRs) and 272 low-development regions (LDRs) according to socioeconomic factors of each location using K-means clustering approach. We used distributed lag non-linear models (DLNM) and multivariate meta-analysis to estimate the temperature-YLL rate relationships. We calculated attributable fraction (AF) of YLL and temperature-related average life loss per death to compare mortality burden of temperature between HDRs and LDRs. Stratified analyses were conducted by region, age, sex and cause of death. Results We found that non-optimal temperatures increased YLL rates in both HDRs and LDRs, but all subgroups in LDRs were more vulnerable. The disparity of cold effects between HDRs and LDRs was significant, while the difference in heat effect was insignificant. The overall AF of non-optimal temperature in LDRs [AF = 12.2, 95% empirical confidence interval (eCI):11.0–13.5%] was higher than that in HDRs (AF = 8.9, 95% eCI: 8.3–9.5%). Subgroups analyses found that most groups in LDRs had greater AFs than that in HDRs. The average life loss per death due to non-optimal temperature in LDRs (1.91 years, 95% eCI: 1.72–2.10) was also higher than that in HDRs (1.32 years, 95% eCI: 1.23–1.41). Most of AFs and life loss per death were caused by moderate cold in both HDRs and LDRs. Conclusions Mortality burden caused by temperature was more significant in LDRs than that in HDRs, which means that more attention should be paid to vulnerable populations in LDRs in planning adaptive strategies.

We determined whether a town-level comprehensive intervention program could lower the salt intake of a population. The parallel, cluster randomized controlled trial was carried out between October 2018 and January 2020 in 48 towns from 12 counties across 6 provinces in China. All participants were asked to complete the 24 h urine collections, anthropometric measurements and questionnaires at the baseline and one-year post-intervention survey. A total of 2693 participants aged 18 to 75 years were recruited at the baseline. A total of 1347 individuals in 24 towns were allocated to the intervention group and the others were allocated to the control group. Valid information from 2335 respondents was collected in the follow-up survey. The 24-h urinary sodium excretion was 189.7 mmol/24 h for the intervention group and 196.1 mmol/24 h for the control group at baseline. At a one-year follow-up, the mean effect of salt intake did not show a significant change (p = 0.31) in the intervention group compared to the control group. However, the mean result of potassium excretion in the intervention group increased by 2.18 mmol/24 h (85.03 mg/24 h) (p = 0.004) and systolic blood pressure decreased by 2.95 mmHg (p < 0.001). The salt-related knowledge and attitude toward salt reduction improved significantly in the intervention group (p < 0.05). A longer period of intervention and follow-up assessment might be needed to evaluate the long-term effectiveness of the program on salt reduction.

Summary: Although numerous studies have investigated premature deaths attributable to temperature, effects of temperature on years of life lost (YLL) remain unclear. We estimated the relationship between temperatures and YLL, and quantified the YLL per death caused by temperature in China. We collected daily meteorological and mortality data, and calculated the daily YLL values for 364 locations (2013–2017 in Yunnan, Guangdong, Hunan, Zhejiang, and Jilin provinces, and 2006–2011 in other locations) in China. A time-series design with a distributed lag nonlinear model was first employed to estimate the location-specific associations between temperature and YLL rates (YLL/100,000 population), and a multivariate meta-analysis model was used to pool location-specific associations. Then, YLL per death caused by temperatures was calculated. The temperature and YLL rates consistently showed U-shaped associations. A mean of 1.02 (95% confidence interval: 0.67, 1.37) YLL per death was attributable to temperature. Cold temperature caused 0.98 YLL per death with most from moderate cold (0.84). The mean YLL per death was higher in those with cardiovascular diseases (1.14), males (1.15), younger age categories (1.31 in people aged 65–74 years), and in central China (1.34) than in those with respiratory diseases (0.47), females (0.87), older people (0.85 in people ≥75 years old), and northern China (0.64) or southern China (1.19). The mortality burden was modified by annual temperature and temperature variability, relative humidity, latitude, longitude, altitude, education attainment, and central heating use. Temperatures caused substantial YLL per death in China, which was modified by demographic and regional characteristics.

BackgroundTo investigate the effects of short-term exposure to sulfur dioxide (SO2) and carbon monoxide (CO) in the central and southern China areas on ischemic heart disease (IHD) and non-accidental deaths.MethodWe investigated the associations between short-term exposure to SO2 and CO in a city in south-central China and IHD and non-accidental death using a time-series design and generalized additive models with up to a 5-day lag adjusting for day of the week, temperature, air pressure, wind speed, and relative humidity. The relative risks of IHD and non-accidental death per 10-unit increase in SO2 and CO were derived from zero to five days in single-pollutant models.ResultsBetween 2016 and 2018, a total of 10,507 IHD and 44,070 non-accidental deaths were identified. The largest significant relative risk for IHD death was lag 02 for both SO2 (1.080; 95% confidence interval: 1.075-1.084) and CO (5.297; 95% confidence interval: 5.177-5.418) in single-pollutants models. A significant association was shown at all lag multiple-day moving averages. Two-pollutant models identified an association between SO2 and mortality when adjusting for CO. In stratified analyses, SO2 exhibited a stronger association with death during the cold season, while CO exhibited a stronger association with mortality from IHD during the warm season. The risk of death was more robust in the elderly for both pollutants, but was greater in men for CO and in women for SO2.ConclusionsOverall, we found an association between short-term exposure to low-level SO2 and CO and the risk of IHD and non-accidental death.

Background In 2011, the United Nations set a target to reduce premature mortality from non-communicable diseases (NCDs) by 25% by 2025. While studies have reported the target in some countries, no studies have been done in China. This study aims to project the ability to reach the target in Hunan Province, China, and establish the priority for future interventions. Methods We conducted the study during 2019–2020. From the Global Burden of Disease Study 2016, we extracted death data for Hunan during 1990–2016 for four main NCDs, namely cancer, cardiovascular disease (CVD), chronic respiratory diseases, and diabetes. We generated estimates for 2025 by fitting a linear regression to the premature mortality over the most recent trend identified by a joinpoint regression model. We also estimated excess premature mortality attributable to unfavorable changes over time. Results The rate of premature mortality from all NCDs in Hunan will be 19.5% (95% CI [19.0%–20.1%]) by 2025, with the main contributions being from CVD (8.2%, 95% CI [7.9%–8.5%]) and cancer (7.9%, 95% CI [7.8%–8.1%]). Overall, it will be impossible to achieve the target, with a relative reduction of 16.4%. Women may be able to meet the target except with respect to cancer, and men will not except with respect to chronic respiratory diseases. Most of the unfavorable changes have occurred since 2008–2009. Discussion More urgent efforts, especially for men, should be exerted in Hunan by integrating population-wide interventions into a stronger health-care system. In the post lock-down COVID-19 era in China, reducing the NCD risk factors can also lower the risk of death from COVID-19.

Bladder urothelial carcinoma (BC) has been identified as one of the most common malignant neoplasm worldwide. High-grade bladder urothelial carcinoma (HGBC) is aggressive with a high risk of recurrence, progression, metastasis, and poor prognosis. Therefore, HGBC clinical management is still a challenge. We performed the present study to seek new urine biomarkers for HGBC and investigate how they promote HGBC progression and thus affect the prognosis based on large-scale sequencing data. We identified the overlapped differentially expressed genes (DEGs) by combining GSE68020 and The Cancer Genome Atlas (TCGA) datasets. Subsequent receiver operating characteristic (ROC) curves, Kaplan-Meier (KM) curves, and Cox regression were conducted to test the diagnostic and prognostic role of the hub genes. Chi-square test and logistic regression were carried out to analyze the associations between clinicopathologic characteristics and the hub genes. Ultimately, we performed gene set enrichment analysis (GSEA), protein-protein interaction (PPI) networks, and Bayesian networks (BNs) to explore the underlying mechanisms by which ECM1, CRYAB, CGNL1, and GPX3 are involved in tumor progression. Immunohistochemistry based on The Human Protein Atlas and quantitative real-time polymerase chain reaction based on urine samples confirmed the downregulation and diagnostic values of the hub genes in HGBC. In conclusion, our study indicated that CRYAB, CGNL1, ECM1, and GPX3 are potential urine biomarkers of HGBC. These four novel urine biomarkers will have attractive applications to provide new diagnostic methods, prognostic predictors and treatment targets for HGBC, which could improve the prognosis of HGBC patients, if validated by further experiments and larger prospective clinical trials.

Abstract Background Urbanization is associated with an increased risk for a number of diseases, including obesity, diabetes, and cancer, which all also show associations with the microbiome. While microbial community composition has been shown to vary across continents and in traditional versus Westernized societies, few studies have examined urban-rural differences in neighboring communities within a single country undergoing rapid urbanization. In this study, we compared the gut microbiome, plasma metabolome, dietary habits, and health biomarkers of rural and urban people from a single Chinese province. Results We identified significant differences in the microbiota and microbiota-related plasma metabolites in rural versus recently urban subjects from the Hunan province of China. Microbes with higher relative abundance in Chinese urban samples have been associated with disease in other studies and were substantially more prevalent in the Human Microbiome Project cohort of American subjects. Furthermore, using whole metagenome sequencing, we found that urbanization was associated with a loss of microbial diversity and changes in the relative abundances of Viruses, Archaea, and Bacteria. Gene diversity, however, increased with urbanization, along with the proportion of reads associated with antibiotic resistance and virulence, which were strongly correlated with the presence of Escherichia and Shigella. Conclusions Our data suggest that urbanization has produced convergent evolution of the gut microbial composition in American and urban Chinese populations, resulting in similar compositional patterns of abundant microbes through similar lifestyles on different continents, including a loss of potentially beneficial bacteria and an increase in potentially harmful genes via increased relative abundance of Escherichia and Shigella.

Background Cost-effective strategies of chronic disease control, integrated health education and health promotion play important roles in the programs of chronic disease demonstration districts in China. The performance of these districts can be directly assessed by their health education and promotion work. However, there have been only a few performance assessments done on these programs, most of which made without the inclusion of proper quality indicators. This study was designed to establish a framework of indicators for outcome evaluation of health education and promotion efforts in Chinese districts, and explore the factors involved in promoting these efforts. Methods A modified two-round Delphi survey was first used to construct quality indicators on a nine-point Likert scale. With those indicators, the rank sum ratio (RSR) method was then conducted through rank conversion and parametric statistics, to assess and classify the performance of ten districts or counties randomly chosen both from demonstration and non-demonstration districts in the Hunan province. Results The Delphi process produced seven themes and 25 sub-themes as quality indicators. The seven themes included organizational management, financial support, professional personnel, health education and promotion, residents’ health awareness and behaviors, residents’ satisfaction, and residents’ health literacy. The districts were classified into four levels by RSR as follows: One demonstration district at the first-ranked level, five other demonstration districts at the second-ranked level, all non-demonstration districts at the third-ranked level. None were at the fourth-qualified level. Discussion Chronic disease demonstration districts performed better on the work of health education and health promotion than the non-demonstration districts. The work should be focused on the following measures of chronic diseases: organizational management, financial support, media-related broadcasting, technical support, community-based promotion and supportive environment, and people’s enhanced awareness and health literacy.

Many studies have linked temperature with respiratory deaths, but epidemiological evidence of temperature-attributable years of life lost (YLL) from respiratory diseases is limited. Daily respiratory YLL rates were calculated using mortality data from 364 locations of China during 2006–2017, and meteorological data were collected for the same period. First, the distributed lag non-linear model (DLNM) was applied to estimate specific temperature-respiratory YLL rate associations in each location. Then multivariable meta-analysis was conducted to pool the location-specific estimates. Finally, we calculated the average life loss per death (LLD) to quantify the respiratory mortality burden of non-optimal temperature. Subgroup analyses were conducted by gender, age, region and cause of death. Inversely J-shaped association was observed between non-optimal temperature and respiratory YLL rate in China. The minimum YLL-rate temperature was 26.9 °C nationwide. An average of 1.37 years (95% CI: 1.06–1.65) LLD was attributable to non-optimal temperatures with 2.06 years (95% CI: 1.57–2.60) for pneumonia, 2.03 years (95% CI: 1.76–2.31) for chronic lower respiratory infections (LRTI), 0.88 years (95% CI: 0.65–1.09) for chronic obstructive pulmonary disease (COPD), most of which was attributed to moderate cold (0.73 years, 95% CI: 0.65–0.80). LLD caused by non-optimal temperature was higher in males, the young, and north China. Exposure to non-optimal temperature increases respiratory YLL rate in China, most of which were attributed to moderate cold. People with respiratory diseases including pneumonia, chronic LRTI and COPD are vulnerable to non-optimal temperature exposure. The result of this study provides useful information to reduce temperature-related respiratory disease burden.

The evidence is limited for the mortality burden of temperature variability between neighboring days. This study developed a novel indicator to measure temperature variability between neighboring days and quantify its mortality burden. Daily mortality and meteorological data during 2006–2017 from 364 locations across China were collected. We first employed a distributed lag non-linear model and multivariable meta-analysis to investigate the association between the diurnal temperature range (DTR) with the years of life lost (YLL) rate and the association between the nocturnal temperature range (NTR) with the YLL rate. Then, we calculated the weight temperature variability between neighboring days (weight-TVN) based on the attributable YLL rate of the DTR and NTR. The relationship between the weight-TVN and YLL rate was analyzed, and the attributable fraction (AF) of the YLL and weight-TVN related life loss per death was calculated to quantify the mortality burden. Stratified analyses were conducted by region, season, gender, age group and cause of death. The DTR-YLL rate curve and NTR-YLL rate curve were both J-shaped and a higher YLL rate attributable to DTR was observed than NTR. There was a significant association between the weight-TVN and YLL rate. An estimated AF of the weight-TVN was 6.02% (95%CI: 3.71%–8.33%). The average life loss per death due to weight-TVN was 0.93 year (95%CI: 0.57–1.29). Stratification analyses showed that the AFs of weight-TVN were relatively larger in southern China, in the cold season, in the elderly, females and patients with respiratory illnesses. Although the AF of weight-TVN among the young group (AF = 4.74%, 95%CI: 1.79%–7.69%) was lower than for the elderly (AF = 6.06%, 95%CI: 3.72%–8.41%), weight-TVN related life loss per death among the young population (1.51, 95%CI: 0.57–2.45) was much higher than in the elderly (0.59, 95%CI: 0.36–0.82). A novel indicator to measure temperature variability between neighboring days was developed, and temperature fluctuation between adjacent days significantly increased the mortality burden. Our results indicate that more attention should be paid to short-term temperature fluctuation.

Previous studies have shown that Hunan Province has a high incidence of stroke and a high proportion of intracerebral hemorrhage (ICH). Considering the changes over the past three decades, little is known about the current epidemiological characteristics of stroke in Hunan Province. In 2013, a cross-sectional study was conducted at seven national disease surveillance points (DSPs) in Hunan Province. A multistage cluster sampling method was used to select a representative sample. A total of 21,156 participants aged 20 years and older were examined. Among the 21,156 participants, the number of prevalent strokes, incident strokes and deaths was 307, 87, and 36, respectively. The 2010 China census-standardized prevalence, incidence and mortality were 1191.0 per 100,000 people [95% confidence interval (CI) 1044.8–1337.2], 333.6 per 100,000 person-years (95% CI 255.7–411.5) and 129.7 per 100,000 person-years (95% CI 81.1–178.3), respectively. Ischemic stroke (IS), ICH, subarachnoid hemorrhage (SAH), and stroke of undetermined type (UND) constituted 50.6, 41.4, 5.7, and 2.3% of all incident stroke cases, respectively. Tianxin, Liuyang, Wuling, and Hongjiang have high proportions of ICH (61.5, 58.3, 60, and 50%, respectively). Hypertension is the most common risk factor for prevalent stroke (71.34%), followed by smoking (30.62%) and alcohol use (25.73%). In conclusion, Hunan Province has an extremely heavy stroke burden. The high proportion of ICH is not limited to the Changsha community; it represents an important issue for all of Hunan Province.

Summary: Background: China has high stroke rates despite the population being relatively lean. Uncertainty persists about the relevance of adiposity to risk of stroke types. We aimed to assess the associations of adiposity with incidence of stroke types and effect mediation by blood pressure in Chinese men and women. Methods: The China Kadoorie Biobank enrolled 512 891 adults aged 30–79 years from ten areas (five urban and five rural) during 2004–08. During a median 9 years (IQR 8–10) of follow-up, 32 448 strokes (about 90% confirmed by neuroimaging) were recorded among 489 301 participants without previous cardiovascular disease. Cox regression analysis was used to produce adjusted hazard ratios (HRs) for ischaemic stroke (n=25 210) and intracerebral haemorrhage (n=5380) associated with adiposity. Findings: Mean baseline body-mass index (BMI) was 23·6 kg/m2 (SD 3·2), and 331 723 (67·8%) participants had a BMI of less than 25 kg/m2. Throughout the range examined (mean 17·1 kg/m2 [SD 0·9] to 31·7 kg/m2 [2·0]), each 5 kg/m2 higher BMI was associated with 8·3 mm Hg (SE 0·04) higher systolic blood pressure. BMI was positively associated with ischaemic stroke, with an HR of 1·30 (95% CI 1·28–1·33 per 5 kg/m2 higher BMI), which was generally consistent with that predicted by equivalent differences in systolic blood pressure (1·25 [1·24–1·26]). The HR for intracerebral haemorrhage (1·11 [1·07–1·16] per 5 kg/m2 higher BMI) was less extreme, and much weaker than that predicted by the corresponding difference in systolic blood pressure (1·48 [1·46–1·50]). Other adiposity measures showed similar associations with stroke types. After adjustment for usual systolic blood pressure, the positive associations with ischaemic stroke were attenuated (1·05 [1·03–1·07] per 5 kg/m2 higher BMI); for intracerebral haemorrhage, they were reversed (0·73 [0·70–0·77]). High adiposity (BMI >23 kg/m2) accounted for 14·7% of total stroke (16·5% of ischaemic stroke and 6·7% of intracerebral haemorrhage). Interpretation: In Chinese adults, adiposity was strongly positively associated with ischaemic stroke, chiefly through its effect on blood pressure. For intracerebral haemorrhage, leanness, either per se or through some other factor (or factors), might increase risk, offsetting the protective effects of lower blood pressure. Funding: UK Wellcome Trust, UK Medical Research Council, British Heart Foundation, Cancer Research UK, Kadoorie Charitable Foundation, Chinese Ministry of Science and Technology, Chinese National Natural Science Foundation.

Summary: Background: The age-specific association between blood pressure and vascular disease has been studied mostly in high-income countries, and before the widespread use of brain imaging for diagnosis of the main stroke types (ischaemic stroke and intracerebral haemorrhage). We aimed to investigate this relationship among adults in China. Methods: 512 891 adults (59% women) aged 30–79 years were recruited into a prospective study from ten areas of China between June 25, 2004, and July 15, 2008. Participants attended assessment centres where they were interviewed about demographic and lifestyle characteristics, and their blood pressure, height, and weight were measured. Incident disease was identified through linkage to local mortality records, chronic disease registries, and claims to the national health insurance system. We used Cox regression analysis to produce adjusted hazard ratios (HRs) relating systolic blood pressure to disease incidence. HRs were corrected for regression dilution to estimate associations with long-term average (usual) systolic blood pressure. Findings: During a median follow-up of 9 years (IQR 8–10), there were 88 105 incident vascular and non-vascular chronic disease events (about 90% of strokes events were diagnosed using brain imaging). At ages 40–79 years (mean age at event 64 years [SD 9]), usual systolic blood pressure was continuously and positively associated with incident major vascular disease throughout the range 120–180 mm Hg: each 10 mm Hg higher usual systolic blood pressure was associated with an approximately 30% higher risk of ischaemic heart disease (HR 1·31 [95% CI 1·28–1·34]) and ischaemic stroke (1·30 [1·29–1·31]), but the association with intracerebral haemorrhage was about twice as steep (1·68 [1·65–1·71]). HRs for vascular disease were twice as steep at ages 40–49 years than at ages 70–79 years. Usual systolic blood pressure was also positively associated with incident chronic kidney disease (1·40 [1·35–1·44]) and diabetes (1·14 [1·12–1·15]). About half of all vascular deaths in China were attributable to elevated blood pressure (ie, systolic blood pressure >120 mm Hg), accounting for approximately 1 million deaths (

Summary: Background: In developed countries, smoking is associated with increased risk of diabetes. Little is known about the association in China, where cigarette consumption has increased (first in urban, then in rural areas) relatively recently. Moreover, uncertainty remains about the effect of smoking cessation on diabetes in China and elsewhere. We aimed to assess the associations of smoking and smoking cessation with risk of incident diabetes among Chinese adults. Methods: The prospective China Kadoorie Biobank enrolled 512 891 adults (59% women) aged 30–79 years during 2004–08 from ten diverse areas (five urban and five rural) across China. Participants were interviewed at study assessment clinics, underwent physical measurements, and had a non-fasting blood sample taken. Participants were separated into four categories according to smoking history: never-smokers, ever-regular smokers, ex-smokers, and occasional smokers. Incident diabetes cases were identified through linkage with diabetes surveillance systems, the national health insurance system, and death registries. All analyses were done separately in men and women and Cox regression was used to yield adjusted hazards ratios (HRs) for diabetes associated with smoking. Findings: 68% (n=134 975) of men ever smoked regularly compared with 3% (n=7811) of women. During 9 years' follow-up, 13 652 new-onset diabetes cases were recorded among 482 589 participants without previous diabetes. Among urban men, smokers had an adjusted HR of 1·18 (95% CI 1·12–1·25) for diabetes. HRs increased with younger age at first smoking regularly (1·12, 1·20, and 1·27 at ≥25 years, 20–24 years, and

BackgroundBreastfeeding confers substantial benefits to child health and has also been associated with lower risk of maternal cardiovascular diseases (CVDs) in later life. However, the evidence on the effects of CVD is still inconsistent, especially in East Asians, in whom the frequency and duration of breastfeeding significantly differ from those in the West. Methods and ResultsIn 2004–2008, the nationwide China Kadoorie Biobank recruited 0.5 million individuals aged 30 to 79 years from 10 diverse regions across China. During 8 years of follow‐up, 16 671 incident cases of coronary heart disease and 23 983 cases of stroke were recorded among 289 573 women without prior CVD at baseline. Cox regression yielded adjusted hazard ratios (HRs) and 95% CIs for incident CVD by breastfeeding. Overall, ≈99% of women had given birth, among whom 97% reported a history of breastfeeding, with a median duration of 12 months per child. Compared with parous women who had never breastfed, ever breastfeeding was associated with a significantly lower risk of CVD, with adjusted HRs of 0.91 (95% CI, 0.84–0.99) for coronary heart disease and 0.92 (95% CI, 0.85–0.99) for stroke. Women who had breastfed for ≥24 months had an 18% (HR, 0.82; 0.77–0.87) lower risk of coronary heart disease and a 17% (HR, 0.83; 0.79–0.87) lower risk of stroke compared with women who had never breastfed. Among women who ever breastfed, each additional 6 months of breastfeeding per child was associated with an adjusted HR of 0.96 (95% CI, 0.94–0.98) for coronary heart disease and 0.97 (95% CI, 0.96–0.98) for stroke. ConclusionsAmong Chinese women, a history of breastfeeding was associated with an ≈10% lower risk of CVD in later life and the magnitude of the inverse association was stronger among those with a longer duration of breastfeeding.