Objective To observe the effects of Qingzhi soft capsule(QSC) on improving experimental memory in mice.Methods The model of vascular dementia was made by means of bilateral carotid artery ligation and reperfusion after 8 minutes in mice.Another model of learn and memory disorder was induced by subcutaneous injection of sodium nitrite.The effects of Qingzhi soft capsule on memory disorder were evaluated by step-down test,Y-maze test in mice.Results Compared with sham-operated group,for the mice model of vascular dementia suffered cerebral ischemia and neural cell injury,the step down latency of animal model was shorter(P

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.

Our previous studies indicate that phosphatidylinositol 4-kinase IIα can promote the growth of multi-malignant tumors via HER-2/PI3K and MAPK pathways. However, the molecular mechanisms of this pathway and its potential for clinical application remain unknown. In this study, we found that PI4KIIα could be an ideal combinatorial target for EGFR treatment via regulating EGFR degradation. Results showed that PI4KIIα knockdown reduced EGFR protein level, and the expression of PI4KIIα shows a strong correlation with EGFR in human breast cancer tissues (r = 0.77, P < 0.01). PI4KIIα knockdown greatly prolonged the effects and decreased the effective dosage of AG-1478, a specific inhibitor of EGFR. In addition, it significantly enhanced AG1478-induced inhibition of tumor cell survival and strengthened the effect of the EGFR-targeting anti-cancer drug Iressa in xenograft tumor models. Mechanistically, we found that PI4KIIα suppression increased EGFR ligand-independent degradation. Quantitative proteomic analysis by stable isotope labeling with amino acids in cell culture (SILAC) and LC-MS/MS suggested that HSP90 mediated the effect of PI4KIIα on EGFR. Furthermore, we found that combined inhibition of PI4KIIα and EGFR suppressed both PI3K/AKT and MAPK/ERK pathways, and resulted in downregulation of multiple oncogenes like PRDX2, FASN, MTA2, ultimately leading to suppression of tumor growth. Therefore, we conclude that combined inhibition of PI4KIIα and EGFR exerts a multiple anti-tumor effect. Dual inhibition of EGFR at protein and activity level via combinatorial blocking of PI4KIIα presents a novel strategy to combat EGFR-dependent tumors.
Animals ; Antineoplastic Agents ; pharmacology ; Breast Neoplasms ; metabolism ; pathology ; Cell Line, Tumor ; Cell Survival ; drug effects ; ErbB Receptors ; antagonists & inhibitors ; metabolism ; Female ; HSP90 Heat-Shock Proteins ; metabolism ; Humans ; MCF-7 Cells ; Male ; Mice ; Mice, Inbred BALB C ; Mice, Nude ; Minor Histocompatibility Antigens ; Mitogen-Activated Protein Kinases ; metabolism ; Phosphatidylinositol 3-Kinases ; metabolism ; Phosphotransferases (Alcohol Group Acceptor) ; antagonists & inhibitors ; genetics ; metabolism ; Proto-Oncogene Proteins c-akt ; metabolism ; Quinazolines ; pharmacology ; Transplantation, Heterologous ; Tyrphostins ; pharmacology

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 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.

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