OBJECTIVE Nowadays,with the living habits and diet structure changes,the morbidity and mortality of hypertension has been rising yearly,which induced by adverse lifestyles,excessive alcohol and poor diet.However,the a...OBJECTIVE Nowadays,with the living habits and diet structure changes,the morbidity and mortality of hypertension has been rising yearly,which induced by adverse lifestyles,excessive alcohol and poor diet.However,the animal models of hypertension resulted from adverse lifestyles have rarely been reported.It is essential to set up some more systematic models to study the characters of hypertension and evaluate the efficacy of traditional Chinese medicine(TCM).METHODS To build the rat model of human lifehabitual hypertension,SD rats had free access to alcohol with high-sucrose-fat diet(AHSFD),alcohol with high-fat diet(AHFD),high-sucrose-fat diet(HSFD),high-fat diet(HFD)and alcohol etc.Various of indicators were detected systematically to explore the features of hypertension models which included blood pressure(BP),liver and kidney functions,the lipid profiles and indexes quantifying TCM symptoms.Then we choose one of the stable and sustained animal models,studying the effects of RPA.E(which extracted from a TCM)on modulating the level of hypertension and the preliminary mechanism in this abstract.RESULTS ①The BP level,serum TC,TG,LDL-C of AHSFD-induced and AHFD-induced rats increased significantly,while the HDL-C reduced in the 4th week.② The BP level HSFD-induced rats increased significantly in the 6th week,serum TC,TG increased in 10 th week.③ The BP level of alcohol-induced rats increased significantly in the 9th week,serum TC,TG increased in 24 th week.④ The level of serum ALT,AST,UA and Cr of all model rats increased significantly after 12 weeks.Meanwhile the microcirculation increased significantly after8 weeks.⑤ After 4-week administration,RPA.E could significantly reduce BP of AHFD-induced hypertensive rats,and could reduce the serum TC,LDL-C,HDL-C,ALT,AST level after 8-week.CONCLUSION The rats induced by AHSFD,AHFD,HSFD and alcohol can raise BP obviously with underlying hepatic and kidney damage,the lipid profiles disorder and TCM symptoms change,while the AH(S)FD-induced hypertension models are earlier and more stable.RPA.E could mildly reduce BP level,and improve the lipid profiles disorders,hepatic damage,which reflects the characteristics of TCM on antihypertensive effects.The above models have their own characteristics,can be used to study the causes and pathogenesis of hypertension complicating metabolic disorder and the related treatment drug screening.展开更多
Objective Despite dramatic advances in surgical technique and perioperative care,some children still suffered serious adverse event in early postoperative period which were associated with increased morbidity and mort...Objective Despite dramatic advances in surgical technique and perioperative care,some children still suffered serious adverse event in early postoperative period which were associated with increased morbidity and mortality.There was little information regarding the impact of adverse events on the postoperative recovery,especially the serious adverse events occurring immediately after surgery.We sought to evaluate the early postoperative serious adverse events and examine the impact of them on postoperative recovery.展开更多
Trade credit,as an effective tool for integrating and coordinating material,information,and financial flows in supply chain management,is becoming increasingly widespread.We explore how a manufacturer can design optim...Trade credit,as an effective tool for integrating and coordinating material,information,and financial flows in supply chain management,is becoming increasingly widespread.We explore how a manufacturer can design optimal trade credit contracts when a risk-averse retailer hides its sales cost information(adverse selection)and selling effort level(moral hazard).We develop incentive models for a risk-averse supply chain when adverse selection and moral hazard coexist,which are then compared with the results under single information asymmetry(moral hazard).Moreover,we analyze the effects of private information and risk-aversion coefficient on contract parameters,selling effort level and the profit or utility of the supply chain.The study shows that when the degree of retailer’s risk aversion is within a certain range,reasonable trade credit contracts designed by the manufacturer can effectively induce the retailer to report its real sales cost and encourage it to exert appropriate effort.Furthermore,we find that the optimal trade credit period,optimal transfer payment,and retailer’s optimal sales effort level under dual information asymmetry are less than those under single information asymmetry.Numerical analysis are conducted to demonstrate the effects of the parameters on decisions and profits.展开更多
Background:The literature recommends that reduced dosage of CPT-11 should be applied in patients with UGT1 A1 homozygous mutations,but the impact of UGT1 A1 heterozygous mutations on the adverse reactions of CPT-11 is...Background:The literature recommends that reduced dosage of CPT-11 should be applied in patients with UGT1 A1 homozygous mutations,but the impact of UGT1 A1 heterozygous mutations on the adverse reactions of CPT-11 is still not fully clear.Methods:A total of 107 patients with UGT1 A1 heterozygous mutation or wild-type,who were treated with CPT-11 from January 2018 to September 2021 in Peking University Third Hospital,were retrospectively enrolled.The adverse reaction spectra of patients with UGT1 A1*6 and UGT1 A1*28 mutations were analyzed.Adverse reactions were evaluated according to National Cancer Institute Common Terminology Criteria for Adverse Events(NCI-CTCAE) 5.0.The efficacy was evaluated according to Response Evaluation Criteria in Solid Tumors(RECIST) 1.1.The genotypes of UGT1 A1*6 and UGT1 A1*28 were detected by digital fluorescence molecular hybridization.Results:There were 43 patients with UGT1 A1*6 heterozygous mutation,26 patients with UGT1 A1*28 heterozygous mutation,8 patients with UGT1 A1*6 and UGT1 A1*28 double heterozygous mutations,61 patients with heterozygous mutation at any gene locus of UGT1 A1*6 and UGT1 A1*28.Logistic regression analysis showed that the presence or absence of vomiting(P=0.013) and mucositis(P=0.005) was significantly correlated with heterozygous mutation of UGT1 A1*28,and the severity of vomiting(P<0.001) and neutropenia(P=0.021) were significantly correlated with heterozygous mutation of UGT1 A1*6.In colorectal cancer,UGT1 A1*6 was significantly correlated to diarrhea(P=0.005),and the other adverse reactions spectrum was similar to that of the whole patient cohort,and efficacy and prognosis were similar between patients with different genotypes and patients treated with reduced CPT-11 dosage or not.Conclusion:In clinical use,heterozygous mutations of UGT1 A1*6 and UGT1 A1*28 are related to the risk and severity of vomiting,diarrhea,neutropenia and mucositis in patients with Pan-tumor and colorectal cancer post CPT-11 therpy.In colorectal cancer,UGT1 A1*6 is significantly related to diarrhea post CPT-11 use,efficacy and prognosis is not affected by various genotypes or CPT-11 dosage reduction.展开更多
基金The project supported by National Natural Science Foundation of China(81274123,81374003)National Major Scientific and Technological Specialized Project for the Significant Formulation of New Drugs,China(2011ZX09101-002-07,2009ZX09502-016)
文摘OBJECTIVE Nowadays,with the living habits and diet structure changes,the morbidity and mortality of hypertension has been rising yearly,which induced by adverse lifestyles,excessive alcohol and poor diet.However,the animal models of hypertension resulted from adverse lifestyles have rarely been reported.It is essential to set up some more systematic models to study the characters of hypertension and evaluate the efficacy of traditional Chinese medicine(TCM).METHODS To build the rat model of human lifehabitual hypertension,SD rats had free access to alcohol with high-sucrose-fat diet(AHSFD),alcohol with high-fat diet(AHFD),high-sucrose-fat diet(HSFD),high-fat diet(HFD)and alcohol etc.Various of indicators were detected systematically to explore the features of hypertension models which included blood pressure(BP),liver and kidney functions,the lipid profiles and indexes quantifying TCM symptoms.Then we choose one of the stable and sustained animal models,studying the effects of RPA.E(which extracted from a TCM)on modulating the level of hypertension and the preliminary mechanism in this abstract.RESULTS ①The BP level,serum TC,TG,LDL-C of AHSFD-induced and AHFD-induced rats increased significantly,while the HDL-C reduced in the 4th week.② The BP level HSFD-induced rats increased significantly in the 6th week,serum TC,TG increased in 10 th week.③ The BP level of alcohol-induced rats increased significantly in the 9th week,serum TC,TG increased in 24 th week.④ The level of serum ALT,AST,UA and Cr of all model rats increased significantly after 12 weeks.Meanwhile the microcirculation increased significantly after8 weeks.⑤ After 4-week administration,RPA.E could significantly reduce BP of AHFD-induced hypertensive rats,and could reduce the serum TC,LDL-C,HDL-C,ALT,AST level after 8-week.CONCLUSION The rats induced by AHSFD,AHFD,HSFD and alcohol can raise BP obviously with underlying hepatic and kidney damage,the lipid profiles disorder and TCM symptoms change,while the AH(S)FD-induced hypertension models are earlier and more stable.RPA.E could mildly reduce BP level,and improve the lipid profiles disorders,hepatic damage,which reflects the characteristics of TCM on antihypertensive effects.The above models have their own characteristics,can be used to study the causes and pathogenesis of hypertension complicating metabolic disorder and the related treatment drug screening.
文摘Objective Despite dramatic advances in surgical technique and perioperative care,some children still suffered serious adverse event in early postoperative period which were associated with increased morbidity and mortality.There was little information regarding the impact of adverse events on the postoperative recovery,especially the serious adverse events occurring immediately after surgery.We sought to evaluate the early postoperative serious adverse events and examine the impact of them on postoperative recovery.
基金supported by the Plan Project of Shanghai Philosophy and Social Science(2017BGL014)the National Natural Science Foundation of China(71832001)the Fundamental Research Funds for the Central Universities(2232020B-04,2232018H-07).
文摘Trade credit,as an effective tool for integrating and coordinating material,information,and financial flows in supply chain management,is becoming increasingly widespread.We explore how a manufacturer can design optimal trade credit contracts when a risk-averse retailer hides its sales cost information(adverse selection)and selling effort level(moral hazard).We develop incentive models for a risk-averse supply chain when adverse selection and moral hazard coexist,which are then compared with the results under single information asymmetry(moral hazard).Moreover,we analyze the effects of private information and risk-aversion coefficient on contract parameters,selling effort level and the profit or utility of the supply chain.The study shows that when the degree of retailer’s risk aversion is within a certain range,reasonable trade credit contracts designed by the manufacturer can effectively induce the retailer to report its real sales cost and encourage it to exert appropriate effort.Furthermore,we find that the optimal trade credit period,optimal transfer payment,and retailer’s optimal sales effort level under dual information asymmetry are less than those under single information asymmetry.Numerical analysis are conducted to demonstrate the effects of the parameters on decisions and profits.
文摘Background:The literature recommends that reduced dosage of CPT-11 should be applied in patients with UGT1 A1 homozygous mutations,but the impact of UGT1 A1 heterozygous mutations on the adverse reactions of CPT-11 is still not fully clear.Methods:A total of 107 patients with UGT1 A1 heterozygous mutation or wild-type,who were treated with CPT-11 from January 2018 to September 2021 in Peking University Third Hospital,were retrospectively enrolled.The adverse reaction spectra of patients with UGT1 A1*6 and UGT1 A1*28 mutations were analyzed.Adverse reactions were evaluated according to National Cancer Institute Common Terminology Criteria for Adverse Events(NCI-CTCAE) 5.0.The efficacy was evaluated according to Response Evaluation Criteria in Solid Tumors(RECIST) 1.1.The genotypes of UGT1 A1*6 and UGT1 A1*28 were detected by digital fluorescence molecular hybridization.Results:There were 43 patients with UGT1 A1*6 heterozygous mutation,26 patients with UGT1 A1*28 heterozygous mutation,8 patients with UGT1 A1*6 and UGT1 A1*28 double heterozygous mutations,61 patients with heterozygous mutation at any gene locus of UGT1 A1*6 and UGT1 A1*28.Logistic regression analysis showed that the presence or absence of vomiting(P=0.013) and mucositis(P=0.005) was significantly correlated with heterozygous mutation of UGT1 A1*28,and the severity of vomiting(P<0.001) and neutropenia(P=0.021) were significantly correlated with heterozygous mutation of UGT1 A1*6.In colorectal cancer,UGT1 A1*6 was significantly correlated to diarrhea(P=0.005),and the other adverse reactions spectrum was similar to that of the whole patient cohort,and efficacy and prognosis were similar between patients with different genotypes and patients treated with reduced CPT-11 dosage or not.Conclusion:In clinical use,heterozygous mutations of UGT1 A1*6 and UGT1 A1*28 are related to the risk and severity of vomiting,diarrhea,neutropenia and mucositis in patients with Pan-tumor and colorectal cancer post CPT-11 therpy.In colorectal cancer,UGT1 A1*6 is significantly related to diarrhea post CPT-11 use,efficacy and prognosis is not affected by various genotypes or CPT-11 dosage reduction.
