Introduction:Allergen-specific CD4+T cells play a central role in autoimmune disorders,allergies and asthma,with Th2-type immunity being the typical functional response of CD4+T cells.This study aimed to investigate t...Introduction:Allergen-specific CD4+T cells play a central role in autoimmune disorders,allergies and asthma,with Th2-type immunity being the typical functional response of CD4+T cells.This study aimed to investigate the role of MBD2 in regulating Th2 cell differentiation.Methods:Splenic mononuclear cells were extracted from C57BL/6 mice,and CD4+T cells were isolated using magnetic beads and confirmed through flow cytometry.Lentivirus was employed to construct MBD2-silenced CD4+T cells.In vitro experiments were performed to treat splenogenic mononuclear cells and CD4+T cells with Ovalbumin(OVA),and Th2 cell ratios and IL-4 levels were assessed using flow cytometry and ELISA.Results:The purity of the isolated CD4+T cells was 95.73%,confirming successful isolation of primary CD4+T cells.Compared to the control group,the Th2 cell ratio exhibited an increase in the Th2-induced group.Treatment with 5-Aza(concentrations,1-100μM)promoted Th2 cell differentiation and increased IL-4 levels.Notably,when combined with Th2 induction and 10μM 5-Aza treatment,silencing MBD2 further amplified Th2 cell ratios and elevated IL-4 levels in cell supernatants.Furthermore,OVA(concentration,200μg/mL)induced the differentiation of CD4+T cells into Th2 cells and increased IL-4 secretion.Interestingly,silencing MBD2 significantly increased the Th2 cell ratio and IL-4 levels in OVA-treated CD4+T cells.Conclusion:In summary,OVA promoted CD4+T cell differentiation into Th2 cells and enhanced IL-4 levels.MBD2 was identified as a mediator of Th2 cell differentiation in splenic-derived CD4+T cells,influenced by OVA or 5-Aza treatment.展开更多
Objective: The purpose of this study is to assess the awareness on cardiac rehabilitation (CR) in patients with coronary heart disease (CHD).Methods: Inpatients diagnosed with coronary heart disease were recruited fro...Objective: The purpose of this study is to assess the awareness on cardiac rehabilitation (CR) in patients with coronary heart disease (CHD).Methods: Inpatients diagnosed with coronary heart disease were recruited from 3 hospitals in this study.The study employed a cardiac structured questionnaire to assess respondents' level of awareness,and bivariate to analyze the sociodemographic factors that influence the awareness on CR.Results: Of all 500 participants,66.40% were male and the mean age was 62.51 ± 9.96 years.The mean score of knowledge was 44.00 ± 17.00 (score range: 0-93),and the mean level of awareness was 47.31%(awareness range: 0-100%).The highest mean level of awareness was in the reexamination subscale (98%) and the lower were in the basic information about CR program,SP optimized medication and heart rate subscale.Bivariate analysis showed that higher age was associated with less knowledge.Patients with higher education level and better income status had better knowledge.And patients who lived in rural and had no jobs had less knowledge.Conclusions: This study showed low levels of awareness on CR program in CHD patients in Baoding.Therefore,the need for health education is indicated in this study to improve the awareness on CR among CHD patients.展开更多
Objective:The aim of this study was to summarize the evidence of health literacy and health outcomes in hypertensive patients.Methods:Articles published in English were searched from six databases:MEDLINE,CINAHL,Embas...Objective:The aim of this study was to summarize the evidence of health literacy and health outcomes in hypertensive patients.Methods:Articles published in English were searched from six databases:MEDLINE,CINAHL,Embase,ERIC,psycINFO,and SCOPUS.The articles published up to September 2017 were included.Results:Nineteen publications were included in the review.There was quality and consistent evidence that hypertensive patients with lower literacy had poorer knowledge.There was inconsistent evidence to show the relationship between health literacy and clinical outcomes,of systolic and diastolic blood pressure,and blood pressure control;behavioral outcomes,of self-care,self-efficacy,adherence;patientphysician interactions outcomes,of patient-physician communication,patient trust,involvement in decision making and other outcomes.Conclusion:The person with low health literacy is likely to have poor knowledge of hypertension.However,there is insufficient evidence to suggest that health literacy is associated with outcomes of hypertension independently.展开更多
Carbohydrates are fundamental molecules involved in nearly all aspects of lives,such as being involved in formating the genetic and energy materials,supporting the structure of organisms,constituting invasion and host...Carbohydrates are fundamental molecules involved in nearly all aspects of lives,such as being involved in formating the genetic and energy materials,supporting the structure of organisms,constituting invasion and host defense systems,and forming antibiotics secondary metabolites.The naturally occurring carbohydrates and their derivatives have been extensively studied as therapeutic agents for the treatment of various diseases.During 2000 to 2021,totally 54 carbohydrate-based drugs which contain carbohydrate moities as the major structural units have been approved as drugs or diagnostic agents.Here we provide a comprehensive review on the chemical structures,activities,and clinical trial results of these carbohydrate-based drugs,which are categorized by their indications into antiviral drugs,antibacterial/antiparasitic drugs,anticancer drugs,antidiabetics drugs,cardiovascular drugs,nervous system drugs,and other agents.展开更多
The discovery that mutations in the EGFR gene are detected in up to 50%of lung adenocarcinoma patients,along with the development of highly efficacious epidermal growth factor receptor(EGFR)tyrosine kinase inhibitors(...The discovery that mutations in the EGFR gene are detected in up to 50%of lung adenocarcinoma patients,along with the development of highly efficacious epidermal growth factor receptor(EGFR)tyrosine kinase inhibitors(TKIs),has revolutionized the treatment of this frequently occurring lung malignancy.Indeed,the clinical success of these TKIs constitutes a critical milestone in targeted cancer therapy.Three generations of EGFR-TKIs are currently approved for the treatment of EGFR mutation-positive non-small cell lung cancer(NSCLC).The first-generation TKIs include erlotinib,gefitinib,lapatinib,and icotinib;the second-generation ErbB family blockers include afatinib,neratinib,and dacomitinib;whereas osimertinib,approved by the FDA on 2015,is a third-generation TKI targeting EGFR harboring specific mutations.Compared with the first-and second-generation TKIs,third-generation EGFR inhibitors display a significant advantage in terms of patient survival.For example,the median overall survival in NSCLC patients receiving osimertinib reached 38.6 months.Unfortunately,however,like other targeted therapies,new EGFR mutations,as well as additional drug-resistance mechanisms emerge rapidly after treatment,posing formidable obstacles to cancer therapeutics aimed at surmounting this chemoresistance.In this review,we summarize the molecular mechanisms underlying resistance to third-generation EGFR inhibitors and the ongoing efforts to address and overcome this chemoresistance.We also discuss the current status of fourthgeneration EGFR inhibitors,which are of great value in overcoming resistance to EGFR inhibitors that appear to have greater therapeutic benefits in the clinic.展开更多
Mutated and activated RAS is a key oncogene that drives various human cancers.RAS-targeted therapy has been an extensive research focus but has made little progress given its long history.Several novel binding sites,e...Mutated and activated RAS is a key oncogene that drives various human cancers.RAS-targeted therapy has been an extensive research focus but has made little progress given its long history.Several novel binding sites,especially the Cys12 mutation in KRAS G12C,have been identified,paving the way for irreversible inhibitor development.A series of clinical trials have proven their efficacies,and the first RAS G12C-targeting drug sotorasib(AMG-510)received approval for non-small cell lung cancer treatment in May,2021.In another approach,the development of indirect RAS inhibitors that target components of the RAS signaling pathway,including the upstream enzyme farnesyl transferase and the downstream effector molecules SOS1,MEK,AKT,and SHP2,has also made significant progress.This review systematically summarizes the latest progress in RAS signaling pathway-targeted drugs,discusses clinical challenges,and proposes beneficial strategies for RAStargeted therapy.展开更多
基金supported by grants from the National Natural Science Foundation of China(Nos.81760009 and 81560007).
文摘Introduction:Allergen-specific CD4+T cells play a central role in autoimmune disorders,allergies and asthma,with Th2-type immunity being the typical functional response of CD4+T cells.This study aimed to investigate the role of MBD2 in regulating Th2 cell differentiation.Methods:Splenic mononuclear cells were extracted from C57BL/6 mice,and CD4+T cells were isolated using magnetic beads and confirmed through flow cytometry.Lentivirus was employed to construct MBD2-silenced CD4+T cells.In vitro experiments were performed to treat splenogenic mononuclear cells and CD4+T cells with Ovalbumin(OVA),and Th2 cell ratios and IL-4 levels were assessed using flow cytometry and ELISA.Results:The purity of the isolated CD4+T cells was 95.73%,confirming successful isolation of primary CD4+T cells.Compared to the control group,the Th2 cell ratio exhibited an increase in the Th2-induced group.Treatment with 5-Aza(concentrations,1-100μM)promoted Th2 cell differentiation and increased IL-4 levels.Notably,when combined with Th2 induction and 10μM 5-Aza treatment,silencing MBD2 further amplified Th2 cell ratios and elevated IL-4 levels in cell supernatants.Furthermore,OVA(concentration,200μg/mL)induced the differentiation of CD4+T cells into Th2 cells and increased IL-4 secretion.Interestingly,silencing MBD2 significantly increased the Th2 cell ratio and IL-4 levels in OVA-treated CD4+T cells.Conclusion:In summary,OVA promoted CD4+T cell differentiation into Th2 cells and enhanced IL-4 levels.MBD2 was identified as a mediator of Th2 cell differentiation in splenic-derived CD4+T cells,influenced by OVA or 5-Aza treatment.
基金This work was supported by the Health and Family Planning Commission of Hebei(No.20140085)
文摘Objective: The purpose of this study is to assess the awareness on cardiac rehabilitation (CR) in patients with coronary heart disease (CHD).Methods: Inpatients diagnosed with coronary heart disease were recruited from 3 hospitals in this study.The study employed a cardiac structured questionnaire to assess respondents' level of awareness,and bivariate to analyze the sociodemographic factors that influence the awareness on CR.Results: Of all 500 participants,66.40% were male and the mean age was 62.51 ± 9.96 years.The mean score of knowledge was 44.00 ± 17.00 (score range: 0-93),and the mean level of awareness was 47.31%(awareness range: 0-100%).The highest mean level of awareness was in the reexamination subscale (98%) and the lower were in the basic information about CR program,SP optimized medication and heart rate subscale.Bivariate analysis showed that higher age was associated with less knowledge.Patients with higher education level and better income status had better knowledge.And patients who lived in rural and had no jobs had less knowledge.Conclusions: This study showed low levels of awareness on CR program in CHD patients in Baoding.Therefore,the need for health education is indicated in this study to improve the awareness on CR among CHD patients.
基金The work was supported by the Health and Family Planning Commission of Hebei(No.20150485)in China.
文摘Objective:The aim of this study was to summarize the evidence of health literacy and health outcomes in hypertensive patients.Methods:Articles published in English were searched from six databases:MEDLINE,CINAHL,Embase,ERIC,psycINFO,and SCOPUS.The articles published up to September 2017 were included.Results:Nineteen publications were included in the review.There was quality and consistent evidence that hypertensive patients with lower literacy had poorer knowledge.There was inconsistent evidence to show the relationship between health literacy and clinical outcomes,of systolic and diastolic blood pressure,and blood pressure control;behavioral outcomes,of self-care,self-efficacy,adherence;patientphysician interactions outcomes,of patient-physician communication,patient trust,involvement in decision making and other outcomes.Conclusion:The person with low health literacy is likely to have poor knowledge of hypertension.However,there is insufficient evidence to suggest that health literacy is associated with outcomes of hypertension independently.
基金supported by the National Natural Science Foundation of China(82173662,22031011,and 21621002)Natural Science Foundation of Shanghai(20ZR1410400,China)+2 种基金the Shanghai Municipal Science and Technology Major Project,the State Key Basic Research Program of the China(2018YFC0310905)the Extraordinary 2025 Elite Project of Fudan University,the Open Funding of Key Laboratory of Diagnosis and Treatment of Severe Hepato-pancreatic Diseases of Zhejiang Province(2018E10008,China)the Open Funding of State Key Laboratory of Bio-organic and Natural Products Chemistry.
文摘Carbohydrates are fundamental molecules involved in nearly all aspects of lives,such as being involved in formating the genetic and energy materials,supporting the structure of organisms,constituting invasion and host defense systems,and forming antibiotics secondary metabolites.The naturally occurring carbohydrates and their derivatives have been extensively studied as therapeutic agents for the treatment of various diseases.During 2000 to 2021,totally 54 carbohydrate-based drugs which contain carbohydrate moities as the major structural units have been approved as drugs or diagnostic agents.Here we provide a comprehensive review on the chemical structures,activities,and clinical trial results of these carbohydrate-based drugs,which are categorized by their indications into antiviral drugs,antibacterial/antiparasitic drugs,anticancer drugs,antidiabetics drugs,cardiovascular drugs,nervous system drugs,and other agents.
基金The study was supported by the Natural Science Foundation of Shanghai(No.20ZR1410400)the Extraordinary 2025 Elite Project of Fudan University,the National Natural Science Foundation of China(No.81772590 and 81572395)+1 种基金the Open Funding of Key Laboratory of Diagnosis and Treatment of Severe Hepato-pancreatic Diseases of Zhejiang Province(No.2018E10008)the CAS Interdisciplinary Innovation Team JCTD-2019-07.All figures showing EGFR kinase structure and binding modes were generated using PyMol 2.4.1(www.pymol.org).
文摘The discovery that mutations in the EGFR gene are detected in up to 50%of lung adenocarcinoma patients,along with the development of highly efficacious epidermal growth factor receptor(EGFR)tyrosine kinase inhibitors(TKIs),has revolutionized the treatment of this frequently occurring lung malignancy.Indeed,the clinical success of these TKIs constitutes a critical milestone in targeted cancer therapy.Three generations of EGFR-TKIs are currently approved for the treatment of EGFR mutation-positive non-small cell lung cancer(NSCLC).The first-generation TKIs include erlotinib,gefitinib,lapatinib,and icotinib;the second-generation ErbB family blockers include afatinib,neratinib,and dacomitinib;whereas osimertinib,approved by the FDA on 2015,is a third-generation TKI targeting EGFR harboring specific mutations.Compared with the first-and second-generation TKIs,third-generation EGFR inhibitors display a significant advantage in terms of patient survival.For example,the median overall survival in NSCLC patients receiving osimertinib reached 38.6 months.Unfortunately,however,like other targeted therapies,new EGFR mutations,as well as additional drug-resistance mechanisms emerge rapidly after treatment,posing formidable obstacles to cancer therapeutics aimed at surmounting this chemoresistance.In this review,we summarize the molecular mechanisms underlying resistance to third-generation EGFR inhibitors and the ongoing efforts to address and overcome this chemoresistance.We also discuss the current status of fourthgeneration EGFR inhibitors,which are of great value in overcoming resistance to EGFR inhibitors that appear to have greater therapeutic benefits in the clinic.
基金the National Natural Science Foundation of China(No.82173662,81772590 and 81572395)the Natural Science Foundation of Shanghai(No.20ZR1410400)the Extraordinary 2025 Elite Project of Fudan University,the Open Funding of Key Laboratory of Diagnosis and Treatment of Severe Hepato-pancreatic Diseases of Zhejiang Province,and the CAS Interdisciplinary Innovation Team JCTD-2019-07.
文摘Mutated and activated RAS is a key oncogene that drives various human cancers.RAS-targeted therapy has been an extensive research focus but has made little progress given its long history.Several novel binding sites,especially the Cys12 mutation in KRAS G12C,have been identified,paving the way for irreversible inhibitor development.A series of clinical trials have proven their efficacies,and the first RAS G12C-targeting drug sotorasib(AMG-510)received approval for non-small cell lung cancer treatment in May,2021.In another approach,the development of indirect RAS inhibitors that target components of the RAS signaling pathway,including the upstream enzyme farnesyl transferase and the downstream effector molecules SOS1,MEK,AKT,and SHP2,has also made significant progress.This review systematically summarizes the latest progress in RAS signaling pathway-targeted drugs,discusses clinical challenges,and proposes beneficial strategies for RAStargeted therapy.
