Mathematical modeling course has been one of the fast development courses in China since 1992,which mainly trains students’innovation ability.However,the teaching of mathematical modeling course is quite difficult si...Mathematical modeling course has been one of the fast development courses in China since 1992,which mainly trains students’innovation ability.However,the teaching of mathematical modeling course is quite difficult since it requires students to have a strong mathematical foundation,good ability to design algorithms,and programming skills.Besides,limited class hours and lack of interest in learning are the other reasons.To address these problems,according to the outcome-based education,we adopt the problem-based learning combined with a seminar mode in teaching.We customize cases related to computer and software engineering,start from simple problems in daily life,step by step deepen the difficulty,and finally refer to the professional application in computer and software engineering.Also,we focus on ability training rather than mathematical theory or programming language learning.Initially,we prepare the problem,related mathematic theory,and core code for students.Furtherly,we train them how to find the problem,and how to search the related mathematic theory and software tools by references for modeling and analysis.Moreover,we solve the problem of limited class hours by constructing an online resource learning library.After a semester of practical teaching,it has been shown that the interest and learning effectiveness of students have been increased and our reform plan has achieved good results.展开更多
Objective:To investigate the effects and mechanisms of tumor suppressor gene PTEN on the induction of anoikis of human bladder transitional carcinoma cells BIU-87.Methods:BIU-87 cells were transfected with GFP plasmid...Objective:To investigate the effects and mechanisms of tumor suppressor gene PTEN on the induction of anoikis of human bladder transitional carcinoma cells BIU-87.Methods:BIU-87 cells were transfected with GFP plasmids containing wild-type PTEN or phosphatase inactivating mutant PTEN(C124A-PTEN)in vitro.The PTEN expression and the phosphorylation levels of focal adhesion kinase(FAK)and protein kinase B(PKB/Akt)were detected by Western blotting.Flow cytometry assay and laser scanning confocal microscopy were used to analyze apoptosis in adherent and non-adherent cells.Results: Compared with the control group,PTEN expression in the cells transfected with wild-type PTEN increased to 210%–260%, while the phosphorylation level of FAK and Akt decreased 59%(P<0.01)and 89%(P<0.01),respectively.And the anoikis percentage increased from 8.32±0.57%to 37.62±2.12%.In the cells transfected with C124A-PTEN,neither the phos- phorylation of FAK and Akt nor the anoikis percentage had obviously changed,although the PTEN expression enhanced remarkably in comparison with the control.Conclusion:Through its phosphatase activity,tumor suppressor gene PTEN can suppress the phosphorylation of FAK and Akt,and induce anoikis in human bladder transitional carcinoma cells BIU-87.展开更多
Objective:To determine whether NF-κB is constitutively activated in human bladder cancer cell and,if so,to deter-mine the invasiveness inhibition of bladder cancer cells by nuclear factor-κB decoy—circular dumbbell...Objective:To determine whether NF-κB is constitutively activated in human bladder cancer cell and,if so,to deter-mine the invasiveness inhibition of bladder cancer cells by nuclear factor-κB decoy—circular dumbbell oligodeoxynucleotides(CD-ODN).Methods:NF-κBp65 activation was determined by immunohistochemical analysis of formalin-fixed,paraffin-embed-ded specimens from 38 cases of bladder transitional cell carcinoma patients.We quantified nuclear staining of RelA as a marker of NF-κBp65 activation.CD-ODN were transfected into human bladder cancer cell line BIU87 by lipofectamine.Luciferase reporter were applied to detecting NF-κB DNA binding activity.The expression levels of uPA were detected by RT-PCR and the cells’ invasion ability by transwell cell culture chamber.Results:P65 excessive activation existed in tumor cell(P<0.01),the activation degree correlated significantly with the expression of uPA(r=0.89,P<0.01),as well as related to tumor invasion-related clinicopathological features such as lymphatic metastasis(P<0.01)and pathological ranking(P<0.05);After transfection with CD-ODN,the activation of NF-κB in BIU87 cell line was suppressed remarkably,the expression level of uPA was decreased and the cells’ invasiveness was weakened as well.Conclusion:Excessively activated NF-κB is related to tumor progression pos-sibly due to its transcriptional regulation of invasion-related factors such as uPA.CD-ODN can efficiently suppress DNA binding activity of NF-κB to reduce the invasive potency of tumor.展开更多
Background:Evaluating the impact of digestive system diseases is vital for devising effective prevention strategies.However,comprehensive reports on the burden of digestive system diseases in China are lacking.Our stu...Background:Evaluating the impact of digestive system diseases is vital for devising effective prevention strategies.However,comprehensive reports on the burden of digestive system diseases in China are lacking.Our study aimed to provide an overview of the burden and trends of digestive system diseases from 1990 to 2019 in China and its provinces.Methods:This cross-sectional study utilized the Global Disease Burden Study 2019 to estimate the incidence,mortality rate,disability-adjusted life years(DALYs),years of life disability,years of life lost,and changes in the burden of digestive diseases across Chinese provinces from 1990 to 2019.The analysis of disease burden primarily examines the characteristics of sub-disease distribution,time trends,age distribution,and sex distribution.Additionally,we compared provincial age-standardized DALYs for digestive diseases with the expected rates based on the socio-demographic index(SDI).Results:In 2019,there were 499.2 million cases of digestive system diseases in China,resulting in 1,557,310 deaths.Stomach cancer,colon and rectal cancer,and esophageal cancer are the top three diseases associated with mortality and DALY related to digestive system diseases.Meanwhile,cirrhosis and other chronic liver diseases,gastroesophageal reflux disease,and gallbladder and biliary diseases are the top three kinds of diseases with the highest prevalence among digestive system diseases.The risk of gastric cancer sharply increases among men after the age of 40 years,leading to a significant disparity in burden between men and women.As the SDI increased,the DALYs associated with digestive system diseases in China and its provinces showed a downward trend.Conclusion:Our study highlights the inverse correlation between DALYs associated with digestive system diseases and the SDI.展开更多
Background:Early detection of esophageal squamous cell carcinoma(ESCC)can considerably improve the prognosis of patients.Aberrant cell-free DNA(cfDNA)methylation signatures are a promising tool for detecting ESCC.Howe...Background:Early detection of esophageal squamous cell carcinoma(ESCC)can considerably improve the prognosis of patients.Aberrant cell-free DNA(cfDNA)methylation signatures are a promising tool for detecting ESCC.However,available markers based on cell-free DNA methylation are still inadequate.This study aimed to identify ESCC-specific cfDNA methylation markers and evaluate the diagnostic performance in the early detection of ESCC.Methods:We performed whole-genome bisulfite sequencing(WGBS)for 24 ESCC tissues and their normal adjacent tissues.Based on the WGBS data,we identified 21,469,837 eligible CpG sites(CpGs).By integrating several methylation datasets,we identified several promising ESCC-specific cell-free DNA methylation markers.Finally,we developed a dual-marker panel based on methylated KCNA3 and OTOP2,and then,we evaluated its performance in our training and validation cohorts.Results:The ESCC diagnostic model constructed based on KCNA3 and OTOP2 had an AUC of 0.91[95%CI:0.85-0.95],and an optimal sensitivity and specificity of 84.91%and 94.32%,respectively,in the training cohort.In the independent validation cohort,the AUC was 0.88[95%CI:0.83-0.92],along with an optimal sensitivity of 81.5%and specificity of 92.9%.The model sensitivity for stage I-II ESCC was 78.4%,which was slightly lower than the sensitivity of the model(85.7%)for stage III-IV ESCC.Conclusion:The dual-target panel based on cfDNA showed excellent performance for detecting ESCC and might be an alternative strategy for screening ESCC.展开更多
We herein disclose a modular synthesis of 1-bromomethylene-THIQs involving a Catellani reaction of aryl iodides,aziridines,and terminal alkynes followed by an N-bromosuccinimide(NBS)-mediated cyclization.This approach...We herein disclose a modular synthesis of 1-bromomethylene-THIQs involving a Catellani reaction of aryl iodides,aziridines,and terminal alkynes followed by an N-bromosuccinimide(NBS)-mediated cyclization.This approach features mild reaction conditions,wide substrate scope,good step-economy and good scalability.Based on this new method,we have accomplished the concise total synthesis of(±)-cularine,formal synthesis of 8-oxopseudopalmatine as well as the first total synthesis of dactyllactone A,demonstrating the wide synthetic potential of this method.展开更多
Objective:To investigate the clinical features and epidemiology of diarrhea patients and analyze the current distribution of enteropathogens causing diarrhea in a comprehensive hospital in Beijing,China,in 2023.Materi...Objective:To investigate the clinical features and epidemiology of diarrhea patients and analyze the current distribution of enteropathogens causing diarrhea in a comprehensive hospital in Beijing,China,in 2023.Materials and Methods:From April to October 2023,we enrolled patients with diarrheal diseases who visited the gastrointestinal Clinic in our hospital.The patients'demographic,epidemiological,and clinical features were obtained via a questionnaire.Stool samples were examined for 20 enteropathogens by multiplex polymerase chain reaction testing.Results:We enrolled 260 patients;men and adults accounted for 55.77%and 95.77%of the patients,respectively.The median age was 37 years.Eighty-four enteropathogens,72 bacteria and 12 viruses,were identified in 74 patients.Enteroaggregative Escherichia coli was the predominant agent.Patients with and without pathogens detected in stool samples showed no significant differences in age,sex,gastrointestinal symptoms,and stool characteristics.Possible food-related events were recorded in 57.31%of the patients.Leukocyte counts in patients with bacterial infections were higher than those of patients with viral infections and those with no detected pathogens(p<0.05).Seasonality of bacterial distribution was observed(p<0.05).Conclusion:Bacteria were predominant pathogens among the diarrhea patients.The incidence of diarrhea was related to hot weather and foodborne illness.Bacterial diarrhea may cause systemic infection.The clinical symptoms of infectious diarrhea were usually non-specific and unrelated to the type of infection.Timely and comprehensive multi-pathogen surveillance might be helpful to detect suspected pathogens and promote epidemic prevention and control.展开更多
基金supported in part by the 2023 Schoollevel Education and Teaching Reform Project of Guangdong Ocean University。
文摘Mathematical modeling course has been one of the fast development courses in China since 1992,which mainly trains students’innovation ability.However,the teaching of mathematical modeling course is quite difficult since it requires students to have a strong mathematical foundation,good ability to design algorithms,and programming skills.Besides,limited class hours and lack of interest in learning are the other reasons.To address these problems,according to the outcome-based education,we adopt the problem-based learning combined with a seminar mode in teaching.We customize cases related to computer and software engineering,start from simple problems in daily life,step by step deepen the difficulty,and finally refer to the professional application in computer and software engineering.Also,we focus on ability training rather than mathematical theory or programming language learning.Initially,we prepare the problem,related mathematic theory,and core code for students.Furtherly,we train them how to find the problem,and how to search the related mathematic theory and software tools by references for modeling and analysis.Moreover,we solve the problem of limited class hours by constructing an online resource learning library.After a semester of practical teaching,it has been shown that the interest and learning effectiveness of students have been increased and our reform plan has achieved good results.
基金a grant from the National Natural Science Foundation ofChina(No.30271300).
文摘Objective:To investigate the effects and mechanisms of tumor suppressor gene PTEN on the induction of anoikis of human bladder transitional carcinoma cells BIU-87.Methods:BIU-87 cells were transfected with GFP plasmids containing wild-type PTEN or phosphatase inactivating mutant PTEN(C124A-PTEN)in vitro.The PTEN expression and the phosphorylation levels of focal adhesion kinase(FAK)and protein kinase B(PKB/Akt)were detected by Western blotting.Flow cytometry assay and laser scanning confocal microscopy were used to analyze apoptosis in adherent and non-adherent cells.Results: Compared with the control group,PTEN expression in the cells transfected with wild-type PTEN increased to 210%–260%, while the phosphorylation level of FAK and Akt decreased 59%(P<0.01)and 89%(P<0.01),respectively.And the anoikis percentage increased from 8.32±0.57%to 37.62±2.12%.In the cells transfected with C124A-PTEN,neither the phos- phorylation of FAK and Akt nor the anoikis percentage had obviously changed,although the PTEN expression enhanced remarkably in comparison with the control.Conclusion:Through its phosphatase activity,tumor suppressor gene PTEN can suppress the phosphorylation of FAK and Akt,and induce anoikis in human bladder transitional carcinoma cells BIU-87.
基金Supported by agrant from the National Natural Science Foundation of China(No.30271300).
文摘Objective:To determine whether NF-κB is constitutively activated in human bladder cancer cell and,if so,to deter-mine the invasiveness inhibition of bladder cancer cells by nuclear factor-κB decoy—circular dumbbell oligodeoxynucleotides(CD-ODN).Methods:NF-κBp65 activation was determined by immunohistochemical analysis of formalin-fixed,paraffin-embed-ded specimens from 38 cases of bladder transitional cell carcinoma patients.We quantified nuclear staining of RelA as a marker of NF-κBp65 activation.CD-ODN were transfected into human bladder cancer cell line BIU87 by lipofectamine.Luciferase reporter were applied to detecting NF-κB DNA binding activity.The expression levels of uPA were detected by RT-PCR and the cells’ invasion ability by transwell cell culture chamber.Results:P65 excessive activation existed in tumor cell(P<0.01),the activation degree correlated significantly with the expression of uPA(r=0.89,P<0.01),as well as related to tumor invasion-related clinicopathological features such as lymphatic metastasis(P<0.01)and pathological ranking(P<0.05);After transfection with CD-ODN,the activation of NF-κB in BIU87 cell line was suppressed remarkably,the expression level of uPA was decreased and the cells’ invasiveness was weakened as well.Conclusion:Excessively activated NF-κB is related to tumor progression pos-sibly due to its transcriptional regulation of invasion-related factors such as uPA.CD-ODN can efficiently suppress DNA binding activity of NF-κB to reduce the invasive potency of tumor.
基金supported by the First Affiliated Hospital of Naval Medical University(2019YXK006)the Science and Technology Commission of Shanghai Municipality(21Y31900100)
文摘Background:Evaluating the impact of digestive system diseases is vital for devising effective prevention strategies.However,comprehensive reports on the burden of digestive system diseases in China are lacking.Our study aimed to provide an overview of the burden and trends of digestive system diseases from 1990 to 2019 in China and its provinces.Methods:This cross-sectional study utilized the Global Disease Burden Study 2019 to estimate the incidence,mortality rate,disability-adjusted life years(DALYs),years of life disability,years of life lost,and changes in the burden of digestive diseases across Chinese provinces from 1990 to 2019.The analysis of disease burden primarily examines the characteristics of sub-disease distribution,time trends,age distribution,and sex distribution.Additionally,we compared provincial age-standardized DALYs for digestive diseases with the expected rates based on the socio-demographic index(SDI).Results:In 2019,there were 499.2 million cases of digestive system diseases in China,resulting in 1,557,310 deaths.Stomach cancer,colon and rectal cancer,and esophageal cancer are the top three diseases associated with mortality and DALY related to digestive system diseases.Meanwhile,cirrhosis and other chronic liver diseases,gastroesophageal reflux disease,and gallbladder and biliary diseases are the top three kinds of diseases with the highest prevalence among digestive system diseases.The risk of gastric cancer sharply increases among men after the age of 40 years,leading to a significant disparity in burden between men and women.As the SDI increased,the DALYs associated with digestive system diseases in China and its provinces showed a downward trend.Conclusion:Our study highlights the inverse correlation between DALYs associated with digestive system diseases and the SDI.
基金supported by the Science and Technology Commission of Shanghai Municipality(No.21Y31900100).
文摘Background:Early detection of esophageal squamous cell carcinoma(ESCC)can considerably improve the prognosis of patients.Aberrant cell-free DNA(cfDNA)methylation signatures are a promising tool for detecting ESCC.However,available markers based on cell-free DNA methylation are still inadequate.This study aimed to identify ESCC-specific cfDNA methylation markers and evaluate the diagnostic performance in the early detection of ESCC.Methods:We performed whole-genome bisulfite sequencing(WGBS)for 24 ESCC tissues and their normal adjacent tissues.Based on the WGBS data,we identified 21,469,837 eligible CpG sites(CpGs).By integrating several methylation datasets,we identified several promising ESCC-specific cell-free DNA methylation markers.Finally,we developed a dual-marker panel based on methylated KCNA3 and OTOP2,and then,we evaluated its performance in our training and validation cohorts.Results:The ESCC diagnostic model constructed based on KCNA3 and OTOP2 had an AUC of 0.91[95%CI:0.85-0.95],and an optimal sensitivity and specificity of 84.91%and 94.32%,respectively,in the training cohort.In the independent validation cohort,the AUC was 0.88[95%CI:0.83-0.92],along with an optimal sensitivity of 81.5%and specificity of 92.9%.The model sensitivity for stage I-II ESCC was 78.4%,which was slightly lower than the sensitivity of the model(85.7%)for stage III-IV ESCC.Conclusion:The dual-target panel based on cfDNA showed excellent performance for detecting ESCC and might be an alternative strategy for screening ESCC.
基金supported by the National Natural Science Foundation of China(21801193,21871213 and 22071189)the Natural Science Foundation of Jiangsu Province(BK20210119,Hong-Gang Cheng)+1 种基金the Fundamental Research Funds for the Central Universities(2042021kf0214 and 2042020kf0039)the Start-up Funding from Wuhan University。
文摘We herein disclose a modular synthesis of 1-bromomethylene-THIQs involving a Catellani reaction of aryl iodides,aziridines,and terminal alkynes followed by an N-bromosuccinimide(NBS)-mediated cyclization.This approach features mild reaction conditions,wide substrate scope,good step-economy and good scalability.Based on this new method,we have accomplished the concise total synthesis of(±)-cularine,formal synthesis of 8-oxopseudopalmatine as well as the first total synthesis of dactyllactone A,demonstrating the wide synthetic potential of this method.
基金National Natural Science Foundation of China,Grant/Award Number:81902112。
文摘Objective:To investigate the clinical features and epidemiology of diarrhea patients and analyze the current distribution of enteropathogens causing diarrhea in a comprehensive hospital in Beijing,China,in 2023.Materials and Methods:From April to October 2023,we enrolled patients with diarrheal diseases who visited the gastrointestinal Clinic in our hospital.The patients'demographic,epidemiological,and clinical features were obtained via a questionnaire.Stool samples were examined for 20 enteropathogens by multiplex polymerase chain reaction testing.Results:We enrolled 260 patients;men and adults accounted for 55.77%and 95.77%of the patients,respectively.The median age was 37 years.Eighty-four enteropathogens,72 bacteria and 12 viruses,were identified in 74 patients.Enteroaggregative Escherichia coli was the predominant agent.Patients with and without pathogens detected in stool samples showed no significant differences in age,sex,gastrointestinal symptoms,and stool characteristics.Possible food-related events were recorded in 57.31%of the patients.Leukocyte counts in patients with bacterial infections were higher than those of patients with viral infections and those with no detected pathogens(p<0.05).Seasonality of bacterial distribution was observed(p<0.05).Conclusion:Bacteria were predominant pathogens among the diarrhea patients.The incidence of diarrhea was related to hot weather and foodborne illness.Bacterial diarrhea may cause systemic infection.The clinical symptoms of infectious diarrhea were usually non-specific and unrelated to the type of infection.Timely and comprehensive multi-pathogen surveillance might be helpful to detect suspected pathogens and promote epidemic prevention and control.