Objective:To investigate the association between hyperuricemia and the risk for stroke occurrence, as well as the mediating effect of hypertension on this association.Methods:In this study, the China Chronic Diseases and Nutrition Surveillance system in 2015 was used as baseline data. We identified hospital admissions for stroke using the electronic homepage of inpatient medical records from 2013-2020, and death data were obtained from the 2015-2020 National Mortality Surveillance System. A retrospective cohort was established after matching and linking the database. The Cox proportional hazard regression model was used to analyze the relationship between hyperuricemia and the risk of stroke and its subtypes. Restricted cubic spline analysis was conducted to examine the dose-response relationship between serum uric acid levels and the risk for stroke. Mediation analysis was performed to investigate the mediating effect of hypertension on the association between hyperuricemia and the risk for stroke and its subtypes. Subgroup analyses were conducted based on gender and age groups.Results:A total of 124 352 study subjects were included, with an accumulative follow-up time of 612 911.36 person-years. During the follow-up period, 4 638 cases of stroke were found, including 3 919 cases of ischemic stroke and 689 cases of hemorrhagic stroke. The incidence density of stroke was 756.72 per 100 000 person-years, 641.37 per 100 000 person-years for ischemic stroke, and 114.60 per 100 000 person-years for hemorrhagic stroke. Multivariable Cox proportional hazards regression models showed that after adjusting for covariates, compared to those without hyperuricemia, individuals with hyperuricemia had a 16% higher risk for stroke [hazard ratio ( HR)=1.16, 95% CI: 1.06-1.27], a 12% higher risk of ischemic stroke ( HR=1.12, 95% CI: 1.01-1.24), and a 39% higher risk of hemorrhagic stroke ( HR=1.39, 95% CI: 1.11-1.75). Mediation analysis showed that hypertension partially mediated the associations between hyperuricemia and the risk for stroke, ischemic stroke, and hemorrhagic stroke, with mediation proportions of 36.07%, 39.98%, and 25.34%, respectively. The mediating effect is pronounced in the male population and individuals below 65. Conclusion:Hyperuricemia is a risk factor for stroke, and hypertension partially mediates the effect of hyperuricemia on stroke.

AIM:To explore the promotion of ferroptosis by artesunate(Art)and its underlying mechanism in osteosarcoma.METHODS:Human osteosarcoma U-2 OS cells were divided into 4 groups:control,ferrostatin-1(Fer-1),Art,and Art+Fer-1 groups.Cell viability was measured by CCK-8 assay,while reactive oxygen species(ROS),Fe2+,and glutathione(GSH)levels were measured using biochemical assays.Mitochondrial morphology was evaluated by trans-mission electron microscopy.The mRNA and protein levels of p53,solute carrier family 7 member 11(SLC7A11)and glutathione peroxidase 4(GPX4)were determined by RT-qPCR and Western blot,respectively.RESULTS:It was found that Art significantly reduced the growth of U-2 osteosarcoma cells,as well as inducing ferroptosis by promoting the accu-mulation of Fe2+and ROS and reducing GSH levels,while the ferroptosis inhibitor ferrostatin-1 inhibited ferroptosis.It was also observed that Art affected mitochondrial morphology,resulting in smaller mitochondria,higher mitochondrial mem-brane density,and reduced numbers of cristae.Treatment with Art also downregulated both the mRNA and protein expres-sion of the ferroptosis-associated genes SLC7A11 and GPX4,while upregulating expression of p53,an upstream regulator of ferroptosis,thus inducing ferroptosis.CONCLUSION:Artesunate induces ferroptosis in osteosarcoma cells through the p53/SLC7A11/GPX4 signaling pathway.

AIM:To investigate the effects and underlying mechanism of Toona sinensis bark extract(TAE)on the colon mucosal barrier and gut microbiota in mice with ulcerative colitis(UC)induced by dextran sulfate sodium(DSS).METHODS:Sixty C57BL/6J mice were randomly assigned to control,model,and mesalazine(0.2 g/kg)groups,as well as TAE groups(low,medium,and high-doses equal to crude drug concentrations of 2.3,4.6 and 9.2 g/kg,respectively).The UC model was induced by drinking of 2.5％DSS,and mean while the drugs were administered for 10 days.The mice were then evaluated in terms of weight,disease activity index(DAI),colon length,spleen index,and pathological changes in the colon tissues.In addition,the level of apoptosis in colon tissues was assessed by terminal de-oxynucleotidyl transferase dUTP nick-end labeling(TUNEL)fluorescence staining,and the expression of related proteins was evaluated by Western blot,levels of inflammatory factors were determined by enzyme-linked immunosorbent assays(ELISA),and the activities of total superoxide dismutase(T-SOD)and catalase(CAT)and malondialdehyde(MDA)content were assessed by biochemical assays.Furthermore,the constitution and diversity of the gut microbiota were inves-tigated by 16S rRNA gene sequencing.RESULTS:Compared with the control group,mice in the model group showed significantly reduced body weights(P<0.01),and the colon length was shortened significantly(P<0.05).Marked in-creases in the DAI and spleen index were observed(P<0.01),along with severe damage to the colon mucosa(P<0.01).Mechanistically,the level of intestinal epithelial cell apoptosis was significantly raised(P<0.01).The model group showed markedly reduced expression of occludin and claudin-1(P<0.01),the level of IL-10,and activities of T-SOD and CAT in the colon tissues(P<0.01).While the levels of IL-6,IL-1β,TNF-α,and the MDA content were increased signif-icantly(P<0.05).The abundance and diversity of the gut microbiota were decreased in the model group(P<0.05).Com-pared with the model group,all these indicators were ameliorated by the administration of TAE(P<0.05).The abundance of pathogenic bacteria,including Proteobacteria and Escherichia-Shigella,was decreased remarkably(P<0.05),while that of probiotics,including Bacteroidota and Muribaculaceae,were increased significantly(P<0.05).The abundance and diversity of the gut microbiota were increased.CONCLUSION:Taken together,Toona sinensis bark alcohol extract can alleviate damage to the intestinal mucosa by suppressing the apoptosis of intestinal epithelial cell,reducing the inflam-matory response,and mitigating oxidative stress.Treatment with TAE could also maintain the homeostasis of the gut micro-biota by regulating the abundance,ultimately meliorate the function of intestinal mucosal barrier.

Objective:To improve the longevity genetic research study design by applying self-organizing maps to select a control group for longevity study.Methods:This study included the Han population aged 90 years and above or less than 80 years who have died (control group) from the natural population-based cohort formed by the fusion of the Chinese Chronic Diseases and Risk Factors Surveillance in 2013 and the China Death Surveillance System. The subjects who died of injury, infectious diseases, parasitic diseases, and malignant tumors were excluded. The self-organizing maps method, with multiple iterations and self-organizing clustering, was used to select similar factors among the population aged 90 years and above and the control group, including demographic characteristics, diseases, living habits, social behaviors, and mental and psychological factors. The study used PLINK 1.9 software to evaluate the quality of whole genome sequencing and to conduct logistic regression of single nucleotide polymorphisms (SNPs) and longevity on autosomes. Q-Q plots were used to visualize the P value associated with SNPs and longevity. Results:There were 1 019 samples selected from the baseline of 177 099 survey participants for genome sequencing, including 517 in the longevity group and 502 in the control group. The longevity and the control groups are generally similar in smoking, drinking, diet, sleep duration, blood lipid level, and self-assessment oral health status but differ significantly in socio-economic status, physical activity time, BMI, and self-assessment health status. The whole genome sequencing results were controlled, and 4 618 216 SNPs were involved in association analysis. The Q-Q plot of longevity-related SNPs analysis results showed that the enrichment of P value 1e-4 was significantly lower than the expected P value, and significant signals were also detected among P<1e-7 regions. Conclusions:The self-organizing maps can comprehensively consider the influence of socioeconomic and behavioral risk factors and select longevity control samples among samples with actual age and cause of death in a large-scale natural population cohort to improve the efficiency of longevity genome association analysis. This study provides a methodological reference for nested case-control study sample selection from the large-scale natural population cohort.

Objective:To quantitatively analyze the death and disability-adjusted life years (DALY) attributed to high level serum LDL-C in Chinese population in 2017.Methods:Data were obtained from the '2017 Global Burden of Disease Study (GBD2017)’. Population attributable fraction (PAF), number and rate of deaths and DALY attributable to high LDL-C were used to describe the burden of disease by gender, age groups, diseases and provinces in China. Both rates on mortality and DALY were standardized by GBD world population.Results:In 2017, 862 759 deaths were caused by high level serum LDL-C in China, that accounting for 8.25 % of the total deaths. Of the attributable deaths, 705 355 (81.76 %) persons died from ischemic heart disease (IHD), while the remaining 18.24 % from ischemic stroke (IS). High LDL-C accounted for 40.30 % of the total deaths from ischemic heart disease and 18.49 % from ischemic stroke. The highest PAF of death (13.70 %) appeared in Jilin province and the lowest in Zhejiang province (4.65 %). PAF of death was seen higher in females than in males, while both age-standardized rates of mortality and DALY appeared higher in males than in females. High LDL-C attributed mortality rate appeared as 61.08/100 000 after standardization in Chinese population. High LDL-C attributed DALYs were 18.16 million person years, among which 76.76 % were caused by IHD (13.94 million person years), with DALY rate as 1285.83/100 000. Among provinces, Heilongjiang showed the highest standardized DALY rate, and Zhejiang the lowest. The PAF, number of deaths, rates on mortality and DALY caused by high LDL-C were high among residents above 70 years old, with the DALY number as 8.56 million person years, highest seen in the age group from 50 to 69 years old. Conclusion:The burden of disease attributed to high level LDL-C was quite high and with gender, age group and interprovincial differences, in China in 2017.

Objective To explore the effect of fime particulate matters with an aerodynamic diameter less than 2.5 μtm (PM2.5) on daily cardiovascular disease mortality in seven cities of China.Methods Daily average concentrations of PM2.5,cardiovascular disease mortality data and environmental data were collected from January 1,2013 to December 31,2015 in seven cities of China,including Shijiazhuang,Haerbin,Shanghai,Wuhan,Guangzhou,Chengdu and Xi'an.We linked generalized additive model with Quasi-Poisson distribution to evaluate the association between daily concentrations of PM2.5 and cardiovascular disease mortality at single-city level and multi-city level,after adjusting for the long-term and seasonal trend,as well as meteorological factors and the effect of "days of week".Results The single-pollutant model indicated that there were marked differences in association strength in these cities,among which the effect in Guangzhou was strongest.At multi-city level,a 10 μg/m3 increase of PM2.5 was associated with an increase of 0.315％ (95％CI:0.133％-0.497％) of daily cardiovascular disease mortality.From lag0 to lag2,the effect of PM2.5 on cardiovascular disease mortality decreased,while it was strongest on lag01.In the two-pollutant model,the estimated effect decreased in all the cities with the adjustments of SO2 or NO2.The insignificant combined results suggested that PM2.5 might have combined effect with other pollutants.Each 10 μg/m3 increase of PM2.5 was associated with increases of 0.371％ (95％CI:0.141％-0.600％) and 0.199％ (95％ CI:0.077％-0.321％) of cardiovascular disease mortality in males and females,respectively.The effect of PM2.5 on cardiovascular disease mortality increased with age and decreased with educational level,although the differences between different subgroups were insignificant.The dose-response relationship between PM2.5 and cardiovascular disease mortality was non-linear and non-threshold,with a steeper curve at lower concentrations.Conclusion The increases of PM2.5 concentration can result in the increase of daily cardiovascular mortality.

Objective: To investigate the current status, temporal trend and achieving Health China 2030 reduction target of probability of premature mortality caused by four main non-communicable diseases (NCDs) including cardiovascular and cerebrovascular diseases, tumour, diabetes, and chronic respiratory disease in China both at national and provincial level during 1990 to 2015. Methods: Using the results of Global Burden of Disease study 2015 (GBD 2015), according to the method of calculating premature mortality probability recommended by WHO, the current status and temporal trend by different gender from 1990 to 2015 were calculated, analyzed, and compared. Referring to " Health China 2030" target of reduction 30% of probability of premature mortality caused by major NCDs, we evaluated the difficulty of achieving the reduction target among provinces (not including Taiwan). Results: From 1990 to 2015, the probabilities of premature mortality in cardiovascular and cerebrovascular diseases, tumour, and chronic respiratory disease were all declined consistently for both men and women in China, the total of four main NCDs decreased from 30.69% to 18.54% with higher decreasing in women (from 25.97% to 12.40%) than that in men (from 34.94% to 24.19%). In 2015, the top five provinces in terms of probability of premature mortality caused by four main NCDs were Qinghai (28.81%), Tibet (25.88%), Guizhou (24.67%), Guangxi (23.56%), and Xinjiang (23.21%) in turn, while the top five provinces with the lowest probability were Shanghai (8.40%), Beijing (9.39%), Hong Kong (10.10%), Macao (10.31%), and Zhejiang (11.70%). If achieving the " Health China 2030" target, the probabilities of premature mortality in Qinghai and Tibet with the highest probability should decline to about 20.17%, and 18.12%, respectively in 2030, while 5.88%, and 6.57% in Shanghai and Beijing, respectively. From 1990 to 2015, the probability of premature mortality of four main NCDs declined by 2.00% a year on average, the top five provinces with the fastest decline were Beijing (3.48%), Shanghai (3.24%), Zhejiang (2.81%), Fujian (2.75%), and Guangdong (2.67%), and 11 provinces including these five provinces could achieve the " Health China 2030" target by the usual rate of decline, while other 22 provinces could not achieve the target, they need greater rate of decline in order to achieve the target. Conclusion From 1990 to 2015, the probabilities of premature mortality of four main NCDs were declined consistently in China both at national and provincial level, compared with women, the men had higher probabilities and declined slower, there were significant different in probabilities of premature mortality and their change speed among provinces. Based on the results from 1990 to 2015, there were about two thirds of the provinces, which the task of achieving the Health China 2030 target will be daunting.

Objective: To estimate the impact of risk factors control on non-communicable diseases (NCDs) mortality, life expectancy and the numbers of labor force lost in China in 2030. Methods: We used the results of China from Global Burden of Disease Study 2013, according to the correlation between death of NCDs and exposure of risk factors and the comparative risk assessment theory, to calculate population attributable fraction (PAF) and disaggregate deaths of NCDs into parts attributable and un-attributable. We used proportional change model to project risk factors exposure and un-attributable deaths of NCDs in 2030, then to get deaths of NCDs in 2030. Simulated scenarios according to the goals of global main NCDs risk factors control proposed by WHO were constructed to calculate the impact of risk factors control on NCDs death, life expectancy and the numbers of labor force lost. Results: If the risk factors exposure changed according to the trend of 1990 to 2013, compared to the numbers (8.499 million) and mortality rate (613.5/100 000) of NCDs in 2013, the death number (12.161 million) and mortality rate (859.2/100 000) would increase by 43.1% and 40.0% respectively in 2030, among which, ischemic stroke (increasing by 103.3% for death number and 98.8% for mortality rate) and ischemic heart disease (increasing by 85.0% for death number and 81.0% for mortality rate) would increase most quickly. If the risk factors get the goals in 2030, the NCDs deaths would reduce 2 631 thousands. If only one risk factor gets the goal, blood pressure (1 484 thousands NCDs deaths reduction), smoking (717 thousands reduction) and BMI (274 thousands reduction) would be the most important factors affecting NCDs death. Blood pressure control would have greater impact on ischemic heart disease (662 thousands reduction) and hemorrhagic stroke (449 thousands reduction). Smoking control would have the greatest effect on lung cancer (251 thousands reduction) and chronic obstructive pulmonary disease (201 thousands reduction). BMI control would have the greatest impact on ischemic heart disease (86 thousands reduction) and hypertensive heart disease (45 thousands reduction). If the risk factors exposure changed according to the trend of 1990 to 2013, in 2030, the life expectancy of Chinese population would reach to 79.0 years old, compared to 2013, increasing by 3.3 years old, the labor force at the age of 15-64 years old would loss 1.932 million. If the risk factors get the goals in 2030, life expectancy would increase to 81.7 years old and the number of labor force lost would decrease to 1.467 million. Blood pressure, smoking and BMI control would have much greater impact on life expectancy (4.9, 4.0 and 3.8 years old respectively) and labor force lost (630 thousands, 496 thousands and 440 thousands respectively). Conclusion Risk factors control would play an important role in reducing NCD death, improving life expectancy of residents and reducing loss of labor force. Among them, the control of blood pressure raising, smoking and BMI raising would have a greater contribution to the improvement of population health status.

Objective_To study the effect of Y-27632 on invasion and motility of SGC-7901 gastric carcinoma cells, and to find whether Y-27632 excerts the effect by attenuating SRF expression.Methods_SGC-7901 gastric carcinoma cells were divided into 3 groups:1)blank control group;2)Y-27632 group;3)siRNA-SRF-1107 group. Transfected siRNA-SRF or incubated by Y-27632 48 h.The effect of Y-27632 on proliferation suppressions of SGC-7901 gastric carcinoma cells was detected by CCK-8 assay.Cell invasion was examined by Transwell and wound healing test.The expression of SRF, ROCK1, E-cadherin, β-catenin, F-actin, MRTF-A and Cyclin D1 were detected by Western blot.Results_Y-27632 inhibited invasion (P<0.05)but had no effect on proliferation of SGC-7901 gastric carcinoma cells.Y-27632 reduced ROCK1, MRTF-A, F-actin, SRF protein expressions by 37.0%, 44.3%, 62.7%and 62.7%respectively, and E-cadherin protein expression was up-regulated by 2.64 folds(P<0.05).Conclusions_The inhibition of ROCK and up-regulation of E-cadherin by Y-27632 can inhibit the invasion and migration of SGC-7901 gastric carcinoma cells that is explained at least, in part, by attenuating SRF expression.

OBJECTIVETo assess the burden of disease attributable to ambient particulate matter pollution in 1990 and 2010 in China.

METHODSOn the basis of the results of the Global Burden of Diseases Study 2010 (GBD 2010) for China's estimates, we used population attributable fractions (PAF) to examine the burden of disease (mortality and disability-adjusted life years (DALY)) attributable to ambient particulate matter pollution in 1990 and 2010 in China, with 95% uncertainty interval (95% UI) estimate, and increasing rate to explore the trends of attributed burden of disease across the study period of 20 years.

RESULTSIn 2010, 38.9% (95% UI: 27.0%-49.4%) of lower respiratory infections for < 5 years children, 27.2% (95% UI: 10.2%-37.5%) of lung cancer, 29.9% (95% UI: 25.8%-34.2%) of ischemic heart disease, 35.0% (95% UI: 27.4%-41.1%) of stroke, and 21.0% (95% UI: 10.7%-30.3%) of chronic obstructive pulmonary disease (COPD) for ≥ 25 years adults were attributable to ambient particulate matter pollution, which accounted for 1.235 (95% UI: 1.038-1.410) million deaths and 25.230 (95% UI: 21.770-28.600) million person years DALY in total, and increased by 33.4% and 4.0%, respectively by comparison with that in 1990 (0.926 million and 24.260 million person years). Lung cancer accounted for the largest increasing rate of 154.5% (from 0.055 million to 0.140 million) and 130.1% (from 1.330 million person years to 3.060 million person years), followed by ischemic heart disease (118.5%, from 0.130 million to 0.284 million, and 86.6%, from 3.280 million person years to 6.120 million person years) and stroke (41.0%, from 0.429 million to 0.605 million, and 33.8%, from 8.970 million person years to 12.000 million person years). The attributed mortality for both gender mostly occurred in age group of 60-79 years (male: 0.260 million and 0.404 million accounting for 53.7% and 54.8%; female: 0.214 million and 0.236 million accounting for 48.5% and 47.5%) both in 1990 and 2010. The age group of 40-79 years accounted for the most portion of attributed DALY for both gender (male: 8.458 million person years and 13.460 million person years accounting for 62.9% and 83.8%; female: 6.360 million person years and 7.152 million person years accounting for 58.9% and 78.0%). The increasing rates were higher for male than for female.

CONCLUSIONThe burden of disease attributable to ambient particulate matter pollution was very high in China with significant increase in mortality and disability, which indicates the highly necessity for government to take actions to reduce ambient particulate matter pollution and its health hazards.

Adult ; Air Pollution ; Child ; China ; Cost of Illness ; Environmental Pollution ; Female ; Humans ; Lung Neoplasms ; Male ; Mortality ; Particulate Matter ; Quality-Adjusted Life Years ; Respiratory Tract Infections ; Stroke