Joint effects of heat-humidity compound events on drowning mortality in Southern China.

BACKGROUND: Several previous studies have examined the association of ambient temperature with drowning. However, no study has investigated the effects of heat-humidity compound events on drowning mortality. METHODS: The drowning mortality data and meteorological data during the five hottest months (May to September) were collected from 46 cities in Southern China (2013-2018 in Guangdong, Hunan and Zhejiang provinces). Distributed lag non-linear model was first conducted to examine the association between heat-humidity compound events and drowning mortality at city level. Then, meta-analysis was employed to pool the city-specific exposure-response associations. Finally, we analysed the additive interaction of heat and humidity on drowning mortality. RESULTS: Compared with wet-non-hot days, dry-hot days had greater effects (excess rate (ER)=32.34%, 95% CI: 24.64 to 40.50) on drowning mortality than wet-hot days (ER=14.38%, 95%CI: 6.80 to 22.50). During dry-hot days, males (ER=42.40%, 95% CI: 31.92 to 53.72), adolescents aged 0-14 years (ER=45.00%, 95% CI: 21.98 to 72.35) and urban city (ER=36.91%, 95% CI: 23.87 to 51.32) showed higher drowning mortality risk than their counterparts. For wet-hot days, males, adolescents and urban city had higher ERs than their counterparts. Attributable fraction (AF) of drowning attributed to dry-hot days was 23.83% (95% CI: 21.67 to 26.99) which was significantly higher than that for wet-hot days (11.32%, 95% CI: 9.64 to 13.48%). We also observed that high temperature and low humidity had an additive interaction on drowning mortality. CONCLUSION: We found that dry-hot days had greater drowning mortality risk and burden than wet-hot days, and high temperature and low humidity might have synergy on drowning mortality.

Pathological response and tumor stroma immunogenic features predict long-term survival in non-small cell lung cancer after neoadjuvant chemotherapy.

PURPOSE: Major pathological response (MPR) has become a surrogate endpoint for overall survival (OS) in non-small cell lung cancer (NSCLC) after neoadjuvant therapy, however, the prognostic histologic features and optimal N descriptor after neoadjuvant therapy are poorly defined. METHODS: We retrospectively analyzed data from 368 NSCLC patients who underwent surgery after neoadjuvant chemotherapy (NAC) from January 2010 to December 2020. The percentage of residual viable tumors in the primary tumor, lymph nodes (LN), and inflammation components within the tumor stroma were comprehensively reviewed. The primary endpoint was OS. RESULTS: Of the 368 enrolled patients, 12.0% (44/368) achieved MPR in the primary tumor, which was associated with significantly better OS (HR, 0.36 0.17-0.77, p = 0.008) and DFS (HR = 0.59, 0.36-0.92, p = 0.038). In patients who did not have an MPR, we identified an immune-activated phenotype in primary tumors, characterized by intense tumor-infiltrating lymphocyte or multinucleated giant cell infiltration, that was associated with similar OS and DFS as patients who had MPR. Neoadjuvant pathologic grade (NPG), consisting of MPR and immune-activated phenotype, identified 30.7% (113/368) patients that derived significant OS (HR 0.28, 0.17-0.46, p < 0.001) and DFS (HR 0.44, 0.31-0.61, p < 0.001) benefit from NAC. Moreover, the combination of NPG and the number of positive LN stations (nS) in the multivariate analysis had a higher C-index (0.711 vs. 0.663, p < 0.001) than the ypTNM Stage when examining OS. CONCLUSION: NPG integrated with nS can provide a simple, practical, and robust approach that may allow for better stratification of patients when evaluating neoadjuvant chemotherapy in clinical practice.

Non-high-density lipoprotein cholesterol levels as a risk factor for short-term mortality in elderly Chinese: a large-scale, population-based cohort study.

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 <3.29 mmol/L (HR: 1.12 (1.09 to 1.15)) and 1.08-fold for non-HDL ≥4.85 mmol/L (HR: 1.08 (1.02 to 1.13)) for all-cause mortality. Furthermore, there is also an increased risk of cardiovascular mortality (HR for non-HDL <3.29: 1.10 (1.06 to 1.32) and HR for non-HDL ≥4.85: 1.07 (1.01 to 1.14)). However, cancer mortality risk was significantly increased only for non-HDL <3.29 mmol/L (HR: 1.11 (1.04 to 1.18)). Non-optimum concentration of non-HDL had significant effects on both the long-term and the short-term risk of mortality, especially for risks of mortality for all-cause (log HR:0 .086 (0.038 to 0.134)), cardiovascular (log HR:0 .082 (0.021 to 0.144)), and cancer (log HR:0 .187 (0.058 to 0.315)) within 3 months. A two-sided value of p <0.05 was considered to be statistically significant. CONCLUSIONS: Non-HDL was non-linearly associated with the risk of mortality, and non-optimal concentrations of non-HDL significantly increased short-term mortality in elderly Chinese, which needs more attention for cardiovascular disease prevention.

The comparison of mortality burden between exposure to dry-cold events and wet-cold events: A nationwide study in China.

BACKGROUND: Most previous studies have focused on the health effect of temperature or humidity, and few studies have explored the combined health effects of exposure to temperature and humidity. This study aims to estimate the relationship between humidity-cold events and mortality, and then to compare the mortality burden between exposure to dry-cold events and wet-cold events, and finally to explore whether there was an additive interaction of temperature and humidity on mortality. METHODS: In the study, Daily mortality data during 2006-2017 were collected from Centers for Disease Control and Prevention in China, and daily mean temperature and daily mean relative humidity data from 698 weather stations in China were obtained from the China Meteorological Data Sharing Service system. We first employed time-series design with a distributed lag nonlinear model and a multivariate meta-analysis model to examine the association between humidity-cold events with mortality. RESULTS: We found that humidity-cold events significantly increased mortality risk, and the effect of wet-cold events (RR:1.24, 95%CI:1.20,1.29) was higher than that of dry-cold events (RR:1.14, 95%CI:1.10,1.18). Dry-cold events and wet-cold events accounted for 2.41 % and 2.99 % excess deaths, respectively with higher burden for the elderly ≥85 years old, Central China and CVD. In addition, there is a synergistic additive interaction between low temperature and high humidity in winter. CONCLUSION: This study showed that humidity-cold events significantly increased mortality risk, and the effect of wet-cold events was higher than that of dry-cold events.

Effect of home cook interventions for salt reduction in China: cluster randomised controlled trial.

OBJECTIVE: To determine the effects of salt reduction interventions designed for home cooks and family members. DESIGN: Cluster randomised controlled trial. SETTING: Six provinces in northern, central, and southern China from 15 October 2018 to 30 December 2019. PARTICIPANTS: 60 communities from six provinces (10 communities from each province) were randomised; each community comprised 26 people (two people from each of 13 families). INTERVENTIONS: Participants in the intervention group received 12 month interventions, including supportive environment building for salt reduction, six education sessions on salt reduction, and salt intake monitoring by seven day weighed record of salt and salty condiments. The control group did not receive any of the interventions. MAIN OUTCOME MEASURE: Difference between the two groups in change in salt intake measured by 24 hour urinary sodium during the 12 month follow-up. RESULTS: 1576 participants (775 (49.2%) men; mean age 55.8 (standard deviation 10.8) years) from 788 families (one home cook and one other adult in each family) completed the baseline assessment. After baseline assessment, 30 communities with 786 participants were allocated to the intervention group and 30 communities with 790 participants to the control group. During the trial, 157 (10%) participants were lost to follow-up, and the remaining 706 participants in the intervention group and 713 participants in the control group completed the follow-up assessment. During the 12 month follow-up, the urinary sodium excretion decreased from 4368.7 (standard deviation 1880.3) mg per 24 hours to 3977.0 (1688.8) mg per 24 hours in the intervention group and from 4418.7 (1973.7) mg per 24 hours to 4330.9 (1859.8) mg per 24 hours in the control group. Compared with the control group, adjusted mixed linear model analysis showed that the 24 hour urinary sodium excretion in the intervention group was reduced by 336.8 (95% confidence interval 127.9 to 545.7) mg per 24 hours (P=0.002); the systolic and diastolic blood pressures were reduced by 2.0 (0.4 to 3.5) (P=0.01) and 1.1 (0.1 to 2.0) mm Hg (P=0.03), respectively; and the knowledge, attitude, and behaviours in the intervention group improved significantly. CONCLUSIONS: The community based salt reduction package targeting home cooks and family members was effective in lowering salt intake and blood pressure. This intervention has the potential to be widely applied in China and other countries where home cooking remains a major source of salt intake. TRIAL REGISTRATION: Chinese Clinical Trial Registry ChiCTR1800016804.

The association of heatwave with drowning mortality in five provinces of China.

Drowning is a serious public health problem in the world. Several studies have found that ambient temperature is associated with drowning, but few have investigated the effect of heatwave on drowning. This study aimed to explore the associations between heatwave and drowning mortality, and further estimate the mortality burden of drowning attributed to heatwave in China. Drowning mortality data were collected in 71 prefectures in China during 2013-2018 from provincial vital register system. Meteorological data at the same period were collected from European Centre for Medium-Range Weather Forecasts (ECMWF). A distributed lag non-linear model (DLNM) was first to explore the association between heatwave and drowning mortality in each prefecture. Secondly, the prefecture-specific associations were pooled using meta-analysis. Finally, attributable fractions (AFs) of drowning deaths caused by heatwave were estimated. Compared to normal day, the mortality risk of drowning significantly increased during heatwave (RR = 1.20, 95%CI: 1.18-1.23). Higher risks were observed in males (RR = 1.23, 95%CI: 1.20-1.27) than females (RR = 1.18, 95%CI: 1.13-1.23), in children aged 5-14 years old (RR = 1.24, 95%CI: 1.15-1.33) than other age groups, in urban city (RR = 1.32, 95%CI: 1.28-1.36) than rural area (RR = 1.09, 95%CI: 1.07-1.12) and in Jilin province (RR = 2.85, 95%CI: 1.61-5.06) than other provinces. The AF of drowning deaths due to heatwave was 11.4 % (95%CI: 10.0 %-12.9 %) during heatwave and 1.0 % (95%CI: 0.9 %-1.1 %) during study period, respectively. Moreover, the AFs during study period were higher for male (1.2 %, 95%CI: 1.0 %-1.3 %), children 5-14 years (1.1 %, 95%CI: 0.7 %-1.6 %), urban city (1.6 %, 95%CI: 1.4 %-1.8 %) than their correspondents. These differences were also observed in AFs during heatwave. We found that heatwave may significantly increase the mortality risk of drowning mortality, and its mortality burden attributable to heatwave was noteworthy. Targeted intervention should be carried out to decrease drowning mortality during heatwave.

The Combined Effects of Short-Term Exposure to Multiple Meteorological Factors on Unintentional Drowning Mortality: Large Case-Crossover Study.

BACKGROUND: Drowning 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. OBJECTIVE: We 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. METHODS: Unintentional 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. RESULTS: A 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. CONCLUSIONS: This 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.

Mortality burden based on the associations of ambient PM2.5 with cause-specific mortality in China: Evidence from a death-spectrum wide association study (DWAS).

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 < 50 µg/m3. Stratified analyses showed greater ERs in females (1.01 %, 95 %CI: 0.91 %, 1.11 %), children ≤ 5 years (2.17 %, 95 %CI: 0.85 %, 3.51 %), and old people ≥ 70 years. We identified 33 specific causes (level 2) of death which had significant associations with PM2.5, including 16 circulatory diseases, 9 respiratory diseases, and 8 other causes. The PAF estimated based on the overall association between PM2.5 and total mortality was 3.16 % (95 %CI: 2.89 %, 3.40 %). However, the PAF was reduced to 2.88 % (95 %CI: 1.88 %, 3.81 %) using the associations of PM2.5 with 33 level 2 causes of death, based on which 250.15 (95 %CI: 163.29, 330.93) thousand deaths were attributable to short-term PM2.5 exposure across China in 2019. Overall, this study provided a comprehensive picture on the death-spectrum wide association between PM2.5 and morality in China. We observed robust positive cause-specific associations of PM2.5 with mortality risk, which may provide more precise basis in assessing the mortality burden of air pollution.

Erratum to "Projections of cancer mortality by 2025 in central China: A modeling study of global burden of disease 2019" [Heliyon 9(2), February 2, 2023, Article e13432].

[This corrects the article DOI: 10.1016/j.heliyon.2023.e13432.].

Projection of Premature Cancer Mortality in Hunan, China, Through 2030: Modeling Study.

BACKGROUND: The 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. OBJECTIVE: The 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. METHODS: We 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. RESULTS: The 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. CONCLUSIONS: Existing 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.

Projections of cancer mortality by 2025 in central China: A modeling study of global burden of disease 2019.

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.

Multi-omics analysis unravels the underlying mechanisms of poor prognosis and differential therapeutic responses of solid predominant lung adenocarcinoma.

Background: Solid 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. Methods: We 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. Results: Along 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. Conclusions: Compared 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.

Risk and prognosis of secondary thoracic cancers after radiation therapy for esophageal cancer.

BACKGROUND AND AIM: Radiation therapy (RT) is a crucial modality for the local control of esophageal cancer (EC), but the effect of RT on the development of secondary thoracic malignancies is still unclear. This study aims to identify the association between RT for the treatment of primary EC and subsequent secondary thoracic cancer (STC). METHODS: The primary EC patients were retrieved from the Surveillance, Epidemiology, and End Results (SEER) database. Fine-Gray competing risk regression and standardized incidence ratio (SIR) were used to evaluate the radiotherapy-associated cancer risk. Overall survival (OS) was compared by Kaplan-Meier analysis. RESULTS: A total of 40 255 EC patients from the SEER database were identified, of which 17 055 patients (42.37%) did not receive radiotherapy (NRT) and 23 200 patients (57.63%) had been treated with RT. After 12 months of latency, 162 patients (0.95%) in the NRT group and 272 patients (1.17%) in the RT group developed STC. The incidences of the RT group were significantly higher than the NRT group. Patients who have primary EC were at an increased risk of developing STC (SIR = 1.79, 95% CI: 1.63-1.96). The SIR of STC was 1.37 (95% CI: 1.16-1.60) in the NRT group and 2.10 (95% CI: 1.87-2.34) in the RT group. The OS of STC patients in the RT group was significantly lower than the NRT group (P = 0.006). CONCLUSION: The RT for primary EC was associated with higher risks of developing STC than patients unexposed to radiotherapy. The EC patients treated with RT, especially young patients, require long-term monitoring of the risk of STC.

Temperature-related mortality in China from specific injury.

Injury poses heavy burden on public health, accounting for nearly 8% of all deaths globally, but little evidence on the role of climate change on injury exists. We collect data during 2013-2019 in six provinces of China to examine the effects of temperature on injury mortality, and to project future mortality burden attributable to temperature change driven by climate change based on the assumption of constant injury mortality and population scenario. The results show that a 0.50% (95% confident interval (CI): 0.13%-0.88%) increase of injury mortality risk for each 1 °C rise in daily temperature, with higher risk for intentional injury (1.13%, 0.55%-1.71%) than that for unintentional injury (0.40%, 0.04%-0.77%). Compared to the 2010s, total injury deaths attributable to temperature change in China would increase 156,586 (37,654-272,316) in the 2090 s under representative concentration pathways 8.5 scenario with the highest for transport injury (64,764, 8,517-115,743). Populations living in Western China, people aged 15-69 years, and male may suffer more injury mortality burden from increased temperature caused by climate change. Our findings may be informative for public health policy development to effectively adapt to climate change.

The joint and interaction effect of high temperature and humidity on mortality in China.

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.

Injuryrelated mortality among children aged 0-14 years in Hunan Province during 2014-2021 / 中国学校卫生

Objective@#To explore injury related mortality among children aged 0-14 years in Hunan, to provide reliable data support for injury prevention among children aged 0-14 years in the region.@*Methods@#A descriptive analysis on child mortality data from 2014 to 2021 of injuries collected from 28 death surveillance spots in Hunan was conducted.@*Results@#The mortality rate of injures among children aged 0-14 years in Hunan decreased from 20.19/100 000 (adjusted mortality: 25.32/100 000) in 2014 to 11.05/100 000 (adjusted mortality: 13.71/100 000) in 2021 (APC=-9.4%, P <0.05), and the annual average mortality rate was 14.86/100 000, there were 17.29/100 000 boys and 11.96/100 000 girls, with statistically significant gender differences ( χ 2= 27 835.54 , P <0.05). The average mortality rate of drowning among different causes of injury and death was 5.98/100 000, followed by the average mortality rate of road traffic accidents of 3.38/100 000.@*Conclusion@#There is a downward trend of deaths due to injures for children aged 0-14 years in Hunan during 2014-2021, with an obvious gender difference. Drowning and traffic accidents are the main cause of injury related deaths for children aged 0-14 years. Steady monitoring of children injury is vital for children injury prevention. Children safety and health education, and related effective policies and legal provisions should be developed and enhanced.

Effect of histology on the efficacy of immune checkpoint inhibitors in advanced non-small cell lung cancer: A systematic review and meta-analysis.

Background: Little 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). Methods: Systematic 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). Results: A 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). Conclusions: ICIs 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 Registration: https://www.crd.york.ac.uk/prospero/, identifier [CRD42022299603].

A Town-Level Comprehensive Intervention Study to Reduce Salt Intake in China: Cluster Randomized Controlled Trial.

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.

The role of NMR-based circulating metabolic biomarkers in development and risk prediction of new onset type 2 diabetes.

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 < 0.05, and 138 at FDR-controlled p < 0.01. Branched chain amino acids (BCAA), apolipoprotein B/apolipoprotein A1, triglycerides in VLDL and medium and small HDL particles, and VLDL particle size were strongly positively associated with T2D (HRs 1.74-2.36 per 1 SD, p < 0.001). HDL particle size, cholesterol concentration in larger HDL particles and docosahexaenoic acid levels were strongly inversely associated with T2D (HRs 0.43-0.48, p < 0.001). With additional adjustment for plasma glucose, most associations (n = 147 and n = 129 at p < 0.05 and p < 0.01, respectively) remained significant. HRs appeared more extreme among more centrally adipose participants for apolipoprotein B/apolipoprotein A1, BCAA, HDL particle size and docosahexaenoic acid (p for heterogeneity ≤ 0.05). Addition of 31 selected biomarkers to an established T2D risk prediction model modestly, but significantly, improved risk discrimination (c-statistic 0.86 to 0.91, p < 0.001). In relatively lean Chinese adults, diverse metabolic biomarkers are associated with future risk of T2D and can help improve established risk prediction models.

Future injury mortality burden attributable to compound hot extremes will significantly increase in China.

BACKGROUND: As climate change, compound hot extremes (CHEs), daytime and nighttime persistent hot extremes, are projected to become much more frequent and intense, which may pose a serious threat to human health. However, evidence on the impact of CHEs on injury is rare. METHODS: We collected injury death data and daily meteorological data from six Chinese provinces during 2013-2018. A time-stratified case-crossover design with two-stage analytic approach was applied to assess the associations of CHEs with injury mortality by intention, mechanism, age and gender. Using the projected daily temperatures of five General Circulation Models (GCMs), we projected the frequency of CHEs and CHEs-attributable mortality burden of injury under three Representative Concentration Pathway (RCP) scenarios. RESULTS: CHEs were significantly associated with increased injury mortality risk (RR = 1.14, 95%CI: 1.09-1.19), with strong effects on unintentional injuries (RR = 1.16, 95%CI:1.11,1.22) and intentional injuries (RR = 1.11, 95%CI:0.99,1.25). Female (RR = 1.21,95%CI: 1.13-1.29) and the elderly (RR = 1.30, 95%CI: 1.22-1.39) were more susceptible to CHEs. Both the frequency and injury mortality burden of CHEs showed a steep rising trend under RCP8.5 scenario, with a 7.37-fold and 8.22-fold increase respectively, by the end of the century, especially in southern, eastern, central and northwestern China. CONCLUSION: CHEs were associated with increased injury mortality risk, and the CHEs-attributable injury mortality burden was projected to aggravate substantially in the future as global warming. It is urgent to develop targeted adaptation policies to alleviate the health burden of CHEs.