Chimeric antigen receptor T (CAR-T) cell therapy is a novel cellular immunotherapy that is widely used to treat hematological malignancies, including acute leukemia, lymphoma, and multiple myeloma. Despite its remarka...Chimeric antigen receptor T (CAR-T) cell therapy is a novel cellular immunotherapy that is widely used to treat hematological malignancies, including acute leukemia, lymphoma, and multiple myeloma. Despite its remarkable clinical effects, this therapy has side effects that cannot be underestimated. Cytokine release syndrome (CRS) is one of the most clinically important and potentially life-threatening toxicities. This syndrome is a systemic immune storm that involves the mass cytokines releasing by activated immune cells. This phenomenon causes multisystem damages and sometimes even death. In this study, we reported the management of a patient with recurrent and refractory multiple myeloma and three patients with acute lymphocytic leukemia who suffered CRS during CAR-T treatment. The early application of tocilizumab, an anti-IL-6 receptor antibody, according to toxicity grading and clinical manifestation is recommended especially for patients who suffer continuous hyperpyrexia, hypotensive shock, acute respiratory failure, and whose CRS toxicities deteriorated rapidly. Moreover, low doses of dexamethasone (5-10 mg/day) were used for refractory CRS not responding to tocilizumab. The effective management of the toxicities associated with CRS will bring additional survival opportunities and improve the quality of life for patients with cancer.展开更多
CD19-targeted chimeric antigen receptor T-cell(CAR-T)therapy is effective in refractory/relapsed(R/R)B-cell acute lymphoblastic leukemia(B-ALL).This review focuses on achievements,current obstacles,and future directio...CD19-targeted chimeric antigen receptor T-cell(CAR-T)therapy is effective in refractory/relapsed(R/R)B-cell acute lymphoblastic leukemia(B-ALL).This review focuses on achievements,current obstacles,and future directions in CAR-T research.A high complete remission rate of 68%to 93%could be achieved after anti-CD19 CAR-T treatment for B-ALL.Cytokine release syndrome and CAR-T-related neurotoxicity could be managed.In view of difficulties collecting autologous lymphocytes,universal CAR-T is a direction to explore.Regarding the high relapse rate after anti-CD19 CAR-T therapy,the main solutions have been developing new targets including CD22 CAR-T,or CD19/CD22 dual CAR-T.Additionally,some studies showed that bridging into transplant post-CAR-T could improve leukemia-free survival.Some patients who did not respond to CAR-T therapy were found to have an abnormal conformation of the CD19 exon or trogocytosis.Anti-CD19 CAR-T therapy for R/R B-ALL is effective.From individual to universal CAR-T,from one target to multi-targets,CAR-T-cell has a chance to be off the shelf in the future.展开更多
Adoptive cellular immunotherapy with chimeric antigen receptor(CAR)T cells has emerged as a novel modality for treating relapsed and/or refractory B-cell non-Hodgkin lymphoma(B-NHL).With increasing approval of CAR T-c...Adoptive cellular immunotherapy with chimeric antigen receptor(CAR)T cells has emerged as a novel modality for treating relapsed and/or refractory B-cell non-Hodgkin lymphoma(B-NHL).With increasing approval of CAR T-cell products and advances in CAR T cell therapy,CAR T cells are expected to be used in a growing number of cases.However,CAR T-cell-associated toxicities can be severe or even fatal,thus compromising the survival benefit from this therapy.Standardizing and studying the clinical management of these toxicities are imperative.In contrast to other hematological malignancies,such as acute lymphoblastic leukemia and multiple myeloma,anti-CD19 CAR T-cell-associated toxicities in B-NHL have several distinctive features,most notably local cytokine-release syndrome(CRS).However,previously published guidelines have provided few specific recommendations for the grading and management of toxicities associated with CAR T-cell treatment for B-NHL.Consequently,we developed this consensus for the prevention,recognition,and management of these toxicities,on the basis of published literature regarding the management of anti-CD19 CAR T-cell-associated toxicities and the clinical experience of multiple Chinese institutions.This consensus refines a grading system and classification of CRS in B-NHL and corresponding measures for CRS management,and delineates comprehensive principles and exploratory recommendations for managing anti-CD19 CAR T-cell-associated toxicities in addition to CRS.展开更多
Despite the tremendous progress of chimeric antigen receptor T(CAR-T)cell therapy in hematological malignancies,their application in solid tumors has been limited largely due to T-cell exhaustion in the tumor microenv...Despite the tremendous progress of chimeric antigen receptor T(CAR-T)cell therapy in hematological malignancies,their application in solid tumors has been limited largely due to T-cell exhaustion in the tumor microenvironment(TME)and systemic toxicity caused by excessive cytokine release.As a key regulator of the immunosuppressive TME,TGF-βpromotes cytokine synthesis via the NF-κB pathway.Here,we coexpressed SMAD7,a suppressor of TGF-βsignaling,with a HER2-targeted CAR in engineered T cells.These novel CAR-T cells displayed high cytolytic efficacy and were resistant to TGF-β-triggered exhaustion,which enabled sustained tumoricidal capacity after continuous antigen exposure.Moreover,SMAD7 substantially reduced the production of inflammatory cytokines by antigen-primed CAR-T cells.Mechanistically,SMAD7 downregulated TGF-βreceptor I and abrogated the interplay between the TGF-βand NF-κB pathways in CAR-T cells.As a result,these CAR-T cells persistently inhibited tumor growth and promoted the survival of tumor-challenged mice regardless of the hostile tumor microenvironment caused by a high concentration of TGF-β.SMAD7 coexpression also enhanced CAR-T-cell infiltration and persistent activation in patient-derived tumor organoids.Therefore,our study demonstrated the feasibility of SMAD7 coexpression as a novel approach to improve the efficacy and safety of CAR-T-cell therapy for solid tumors.展开更多
Owing to their high significance in fundamental study and diverse applications,stimuli-responsive and fluorescent polymers,particularly those with cluster-triggered emission(CTE)featured by non-conjugated chromophores...Owing to their high significance in fundamental study and diverse applications,stimuli-responsive and fluorescent polymers,particularly those with cluster-triggered emission(CTE)featured by non-conjugated chromophores,have drawn tremendous attention in recent years.In this work,fluorescent and multi-responsive polysiloxane(FRPS)was synthesized by hydrolytic condensation polymerization of 3-aminopropyl methyl diethoxysilane(APMS)with 3-(N-isopropyl propionamide)iminopropyl methyl diethoxysilane(APMS-NIP),which was formed in situ through aza-Michael addition between APMS and N-isopropyl acrylamide.FRPS was not only highly sensitive to temperature,pH and CO_(2) in water,but also showed an enhanced and stimuli-adjustable fluorescence emission.The effects of monomer feeding,pH and CO_(2) on its lower critical solution temperature and fluorescent property were investigated.FRPS fluorescence emission was ascribed to CTE mechanism.In addition,FRPS was shown to be highly potential as physiological indicator for cell imaging,and for controlled release and trace detection of doxorubicin.This study provides therefore a type of stimuli-responsive and fluorescent material for potential applications in biomedical fields,and it is also of great significance for understanding of the fluorescence mechanism of polysiloxane-based stimuli-responsive polymers.展开更多
Non-aromatic fluorescent and multi-responsive materials,exhibiting inherent fluorescence emission and controlled phase change,have garnered significant attention in recent years.However,the underlying interaction betw...Non-aromatic fluorescent and multi-responsive materials,exhibiting inherent fluorescence emission and controlled phase change,have garnered significant attention in recent years.However,the underlying interaction between their fluorescent properties and phase transition remains unclear.In this study,we synthesized a series of catalyst-free aza-Michael addition-based polyethyleneimine(RFPEI)materials by reacting polyethyleneimine(PEI)with N-isopropyl acrylamide(NIPAM).The resulting RFPEI was comprehensively characterized,and demonstrated dual-phase transition behavior(LCST and UCST)in water,which could be finely tuned by adjusting its composition or external factors such as pH.Notably,upon UV irradiation(365 nm),RFPEI exhibited strong fluorescence emission.We further investigated the effects of NIPAM grafting percentage to PEI,polymer concentration,and pH on the LCST/UCST and fluorescent properties of RFPEI aqueous solutions.Moreover,we showcased the great potential of RFPEI as a versatile tool for physiological cell imaging,trace detection,and controlled release of doxorubicin.Our study presents a novel class of stimuli-responsive fluorescent materials with promising applications in the field of biomedicine.展开更多
T cell-redirecting bispecific antibodies are specifically designed to bind to tumor-associated antigens,thereby engaging with CD3 on the T cell receptor.This linkage between tumor cells and T cells actively triggers T...T cell-redirecting bispecific antibodies are specifically designed to bind to tumor-associated antigens,thereby engaging with CD3 on the T cell receptor.This linkage between tumor cells and T cells actively triggers T cell activation and initiates targeted killing of the identified tumor cells.These antibodies have emerged as one of the most promising avenues within tumor immunotherapy.However,despite success in treating hematological malignancies,significant advancements in solid tumors have yet to be explored.In this review,we aim to address the critical challenges associated with T cellredirecting bispecific antibodies and explore novel strategies to overcome these obstacles,with the ultimate goal of expanding the application of this therapy to include solid tumors.展开更多
Chimeric antigen receptor(CAR)-T-cell therapies have exhibited remarkable efficacy in the treatment of hematologic malignancies,with 9 CAR-T-cell products currently available.Furthermore,CAR-T cells have shown promisi...Chimeric antigen receptor(CAR)-T-cell therapies have exhibited remarkable efficacy in the treatment of hematologic malignancies,with 9 CAR-T-cell products currently available.Furthermore,CAR-T cells have shown promising potential for expanding their therapeutic applications to diverse areas,including solid tumors,myocardial fibrosis,and autoimmune and infectious diseases.Despite these advancements,significant challenges pertaining to treatment-related toxic reactions and relapses persist.Consequently,current research efforts are focused on addressing these issues to enhance the safety and efficacy of CAR-T cells and reduce the relapse rate.This article provides a comprehensive overview of the present state of CAR-T-cell therapies,including their achievements,existing challenges,and potential future developments.展开更多
A series of controllable amphiphilic block copolymers composed of poly(ethylene oxide)(PEO) as the hydrophilic block and poly(ε-caprolactone)(PCL) as the hydrophobic block with the amino terminal group at the end of ...A series of controllable amphiphilic block copolymers composed of poly(ethylene oxide)(PEO) as the hydrophilic block and poly(ε-caprolactone)(PCL) as the hydrophobic block with the amino terminal group at the end of the PEO chain(PCL-b-PEO-NH2) were synthesized.Based on the further reaction of reactive amino groups,diblock copolymers with functional carboxyl groups(PCL-b-PEO-COOH) and functional compounds RGD(PCL-b-PEO-RGD) as well as the triblock copolymers with thermosensitive PNIPAAm blocks(PCL-b-PEO-b-PNIPAAM) were synthesized.The well-controlled structures of these copolymers with functional groups and blocks were characterized by gel permeation chromatography(GPC) and 1H NMR spectroscopy.These copolymers with functionalized hydrophilic blocks were fabricated into microspheres for the examination of biofunctions via cell culture experiments and in vitro drug release.The results indicated the significance of introducing functional groups(e.g.,NH2,COOH and RGD) into the end of the hydrophilic block of amphiphilic block copolymers for biomedical potentials in tissue engineering and controlled drug release.展开更多
[Objectives]To determine the optimal preparation technology of Clerodendrum bungei Steud.extract gel by orthogonal test and gel quality test method in General Rule 0114 of Chinese Pharmacopoeia(Volume IV,2020 Edition)...[Objectives]To determine the optimal preparation technology of Clerodendrum bungei Steud.extract gel by orthogonal test and gel quality test method in General Rule 0114 of Chinese Pharmacopoeia(Volume IV,2020 Edition),and to study its anorectal pharmacodynamics and drug release in vitro.[Methods]Carbomer 940,propylene glycol and absolute ethyl alcohol were selected as the main factors,and the preparation technology of C.bungei Steud.extract gel was optimized by orthogonal test.The mouse model of ulcerative hemorrhoids was established with glacial acetic acid(HAC)and compared with Ma Yinglong musk hemorrhoids ointment.The recovery of trauma was compared between the two groups.At the same time,porcine small intestine was used as semi-permeable membrane to make diffusion cell to simulate anal environment,and the drug release in vitro was studied.[Results]The C.bungei Steud.extract gel was smooth in appearance and good in stability.It could effectively treat anal ulcer in mice and release quickly in vitro.[Conclusions]The formula is reasonable,and the effect of animal experiment is remarkable,which can provide a new treatment plan for ulcerative hemorrhoids.展开更多
Orderly execution of two critical events during the cell cycle––DNA replication and chromosome segregation––ensures the stable transmission of genetic materials. The cohesin complex physically connects sister chro...Orderly execution of two critical events during the cell cycle––DNA replication and chromosome segregation––ensures the stable transmission of genetic materials. The cohesin complex physically connects sister chromatids during DNA replication in a process termed sister chromatid cohesion. Timely establishment and dissolution of sister chromatid cohesion is a prerequisite for accurate chromosome segregation, and is tight regulated by the cell cycle machinery and cohesin-associated proteins. In this review, we discuss recent progress in the molecular understanding of sister chromatid cohesion during the mitotic cell cycle.展开更多
文摘Chimeric antigen receptor T (CAR-T) cell therapy is a novel cellular immunotherapy that is widely used to treat hematological malignancies, including acute leukemia, lymphoma, and multiple myeloma. Despite its remarkable clinical effects, this therapy has side effects that cannot be underestimated. Cytokine release syndrome (CRS) is one of the most clinically important and potentially life-threatening toxicities. This syndrome is a systemic immune storm that involves the mass cytokines releasing by activated immune cells. This phenomenon causes multisystem damages and sometimes even death. In this study, we reported the management of a patient with recurrent and refractory multiple myeloma and three patients with acute lymphocytic leukemia who suffered CRS during CAR-T treatment. The early application of tocilizumab, an anti-IL-6 receptor antibody, according to toxicity grading and clinical manifestation is recommended especially for patients who suffer continuous hyperpyrexia, hypotensive shock, acute respiratory failure, and whose CRS toxicities deteriorated rapidly. Moreover, low doses of dexamethasone (5-10 mg/day) were used for refractory CRS not responding to tocilizumab. The effective management of the toxicities associated with CRS will bring additional survival opportunities and improve the quality of life for patients with cancer.
文摘CD19-targeted chimeric antigen receptor T-cell(CAR-T)therapy is effective in refractory/relapsed(R/R)B-cell acute lymphoblastic leukemia(B-ALL).This review focuses on achievements,current obstacles,and future directions in CAR-T research.A high complete remission rate of 68%to 93%could be achieved after anti-CD19 CAR-T treatment for B-ALL.Cytokine release syndrome and CAR-T-related neurotoxicity could be managed.In view of difficulties collecting autologous lymphocytes,universal CAR-T is a direction to explore.Regarding the high relapse rate after anti-CD19 CAR-T therapy,the main solutions have been developing new targets including CD22 CAR-T,or CD19/CD22 dual CAR-T.Additionally,some studies showed that bridging into transplant post-CAR-T could improve leukemia-free survival.Some patients who did not respond to CAR-T therapy were found to have an abnormal conformation of the CD19 exon or trogocytosis.Anti-CD19 CAR-T therapy for R/R B-ALL is effective.From individual to universal CAR-T,from one target to multi-targets,CAR-T-cell has a chance to be off the shelf in the future.
基金supported by funds from the National Natural Science Foundation of China(Grant Nos.81830002,81830004,82070168,and 32070951)the Translational Research grant of NCRCH(Grant No.2020ZKZC04)National Key R&D Program of China(Grant No.2021YFA1100800)。
文摘Adoptive cellular immunotherapy with chimeric antigen receptor(CAR)T cells has emerged as a novel modality for treating relapsed and/or refractory B-cell non-Hodgkin lymphoma(B-NHL).With increasing approval of CAR T-cell products and advances in CAR T cell therapy,CAR T cells are expected to be used in a growing number of cases.However,CAR T-cell-associated toxicities can be severe or even fatal,thus compromising the survival benefit from this therapy.Standardizing and studying the clinical management of these toxicities are imperative.In contrast to other hematological malignancies,such as acute lymphoblastic leukemia and multiple myeloma,anti-CD19 CAR T-cell-associated toxicities in B-NHL have several distinctive features,most notably local cytokine-release syndrome(CRS).However,previously published guidelines have provided few specific recommendations for the grading and management of toxicities associated with CAR T-cell treatment for B-NHL.Consequently,we developed this consensus for the prevention,recognition,and management of these toxicities,on the basis of published literature regarding the management of anti-CD19 CAR T-cell-associated toxicities and the clinical experience of multiple Chinese institutions.This consensus refines a grading system and classification of CRS in B-NHL and corresponding measures for CRS management,and delineates comprehensive principles and exploratory recommendations for managing anti-CD19 CAR T-cell-associated toxicities in addition to CRS.
基金supported by a grant from the National Natural Science Foundation of China(No.81972870)the Independent Research Topic of State Key Laboratory of Cancer Biology of Fourth Military Medical University(CBSKL2022ZZ20)+2 种基金Shaanxi Innovative Research Team for Key Science and Technology(S2022-ZC-TD-0065)the Natural Science Foundation of Henan Province(No.222300420264)Tangdu Hospital-key research project(2022TDGS007).
文摘Despite the tremendous progress of chimeric antigen receptor T(CAR-T)cell therapy in hematological malignancies,their application in solid tumors has been limited largely due to T-cell exhaustion in the tumor microenvironment(TME)and systemic toxicity caused by excessive cytokine release.As a key regulator of the immunosuppressive TME,TGF-βpromotes cytokine synthesis via the NF-κB pathway.Here,we coexpressed SMAD7,a suppressor of TGF-βsignaling,with a HER2-targeted CAR in engineered T cells.These novel CAR-T cells displayed high cytolytic efficacy and were resistant to TGF-β-triggered exhaustion,which enabled sustained tumoricidal capacity after continuous antigen exposure.Moreover,SMAD7 substantially reduced the production of inflammatory cytokines by antigen-primed CAR-T cells.Mechanistically,SMAD7 downregulated TGF-βreceptor I and abrogated the interplay between the TGF-βand NF-κB pathways in CAR-T cells.As a result,these CAR-T cells persistently inhibited tumor growth and promoted the survival of tumor-challenged mice regardless of the hostile tumor microenvironment caused by a high concentration of TGF-β.SMAD7 coexpression also enhanced CAR-T-cell infiltration and persistent activation in patient-derived tumor organoids.Therefore,our study demonstrated the feasibility of SMAD7 coexpression as a novel approach to improve the efficacy and safety of CAR-T-cell therapy for solid tumors.
基金This work was financially supported by Nature Science Foundation of Shandong Province,China(Nos.ZR2021MB112 and ZR2022MB051)Science and Technology Bureau of Jinan City(No.2021GXRC105)+1 种基金Postdoctoral Science Foundation of China(No.2022M712343)as well as by Basic and Applied Basic Research Foundation(No.2020A1515110374)of Guangdong Province,China.
文摘Owing to their high significance in fundamental study and diverse applications,stimuli-responsive and fluorescent polymers,particularly those with cluster-triggered emission(CTE)featured by non-conjugated chromophores,have drawn tremendous attention in recent years.In this work,fluorescent and multi-responsive polysiloxane(FRPS)was synthesized by hydrolytic condensation polymerization of 3-aminopropyl methyl diethoxysilane(APMS)with 3-(N-isopropyl propionamide)iminopropyl methyl diethoxysilane(APMS-NIP),which was formed in situ through aza-Michael addition between APMS and N-isopropyl acrylamide.FRPS was not only highly sensitive to temperature,pH and CO_(2) in water,but also showed an enhanced and stimuli-adjustable fluorescence emission.The effects of monomer feeding,pH and CO_(2) on its lower critical solution temperature and fluorescent property were investigated.FRPS fluorescence emission was ascribed to CTE mechanism.In addition,FRPS was shown to be highly potential as physiological indicator for cell imaging,and for controlled release and trace detection of doxorubicin.This study provides therefore a type of stimuli-responsive and fluorescent material for potential applications in biomedical fields,and it is also of great significance for understanding of the fluorescence mechanism of polysiloxane-based stimuli-responsive polymers.
基金supported by Nature Science Foundation of Shandong Province,China(Nos.ZR2021MB112 and ZR2022MB051)Science and Technology Bureau of Jinan City(2021GXRC105)+1 种基金Postdoctoral Science Foundation of China(2022M712343)as well as by Basic and Applied Basic Research Foundation(2020A1515110374)of Guangdong Province,China.
文摘Non-aromatic fluorescent and multi-responsive materials,exhibiting inherent fluorescence emission and controlled phase change,have garnered significant attention in recent years.However,the underlying interaction between their fluorescent properties and phase transition remains unclear.In this study,we synthesized a series of catalyst-free aza-Michael addition-based polyethyleneimine(RFPEI)materials by reacting polyethyleneimine(PEI)with N-isopropyl acrylamide(NIPAM).The resulting RFPEI was comprehensively characterized,and demonstrated dual-phase transition behavior(LCST and UCST)in water,which could be finely tuned by adjusting its composition or external factors such as pH.Notably,upon UV irradiation(365 nm),RFPEI exhibited strong fluorescence emission.We further investigated the effects of NIPAM grafting percentage to PEI,polymer concentration,and pH on the LCST/UCST and fluorescent properties of RFPEI aqueous solutions.Moreover,we showcased the great potential of RFPEI as a versatile tool for physiological cell imaging,trace detection,and controlled release of doxorubicin.Our study presents a novel class of stimuli-responsive fluorescent materials with promising applications in the field of biomedicine.
基金supported by the National Natural Science Foundation of China(Nos.32070940 and 81991491)the China Postdoctoral Science Foundation(No.2021M700115)+2 种基金the Postdoctoral Innovation Talents Support Program(No.BX20220189,China)the Science and Technology Planning Project of Fujian Province(No.2022L3080,China)the CAMS Innovation Fund for Medical Sciences(No.2019RU022,China).
文摘T cell-redirecting bispecific antibodies are specifically designed to bind to tumor-associated antigens,thereby engaging with CD3 on the T cell receptor.This linkage between tumor cells and T cells actively triggers T cell activation and initiates targeted killing of the identified tumor cells.These antibodies have emerged as one of the most promising avenues within tumor immunotherapy.However,despite success in treating hematological malignancies,significant advancements in solid tumors have yet to be explored.In this review,we aim to address the critical challenges associated with T cellredirecting bispecific antibodies and explore novel strategies to overcome these obstacles,with the ultimate goal of expanding the application of this therapy to include solid tumors.
文摘Chimeric antigen receptor(CAR)-T-cell therapies have exhibited remarkable efficacy in the treatment of hematologic malignancies,with 9 CAR-T-cell products currently available.Furthermore,CAR-T cells have shown promising potential for expanding their therapeutic applications to diverse areas,including solid tumors,myocardial fibrosis,and autoimmune and infectious diseases.Despite these advancements,significant challenges pertaining to treatment-related toxic reactions and relapses persist.Consequently,current research efforts are focused on addressing these issues to enhance the safety and efficacy of CAR-T cells and reduce the relapse rate.This article provides a comprehensive overview of the present state of CAR-T-cell therapies,including their achievements,existing challenges,and potential future developments.
基金supported by the National Natural Science Foundation of China (Grant Nos 50873109 and 50830103)Chinese Academy of Sciences
文摘A series of controllable amphiphilic block copolymers composed of poly(ethylene oxide)(PEO) as the hydrophilic block and poly(ε-caprolactone)(PCL) as the hydrophobic block with the amino terminal group at the end of the PEO chain(PCL-b-PEO-NH2) were synthesized.Based on the further reaction of reactive amino groups,diblock copolymers with functional carboxyl groups(PCL-b-PEO-COOH) and functional compounds RGD(PCL-b-PEO-RGD) as well as the triblock copolymers with thermosensitive PNIPAAm blocks(PCL-b-PEO-b-PNIPAAM) were synthesized.The well-controlled structures of these copolymers with functional groups and blocks were characterized by gel permeation chromatography(GPC) and 1H NMR spectroscopy.These copolymers with functionalized hydrophilic blocks were fabricated into microspheres for the examination of biofunctions via cell culture experiments and in vitro drug release.The results indicated the significance of introducing functional groups(e.g.,NH2,COOH and RGD) into the end of the hydrophilic block of amphiphilic block copolymers for biomedical potentials in tissue engineering and controlled drug release.
基金Supported by National Natural Science Foundation of China(31671954)。
文摘[Objectives]To determine the optimal preparation technology of Clerodendrum bungei Steud.extract gel by orthogonal test and gel quality test method in General Rule 0114 of Chinese Pharmacopoeia(Volume IV,2020 Edition),and to study its anorectal pharmacodynamics and drug release in vitro.[Methods]Carbomer 940,propylene glycol and absolute ethyl alcohol were selected as the main factors,and the preparation technology of C.bungei Steud.extract gel was optimized by orthogonal test.The mouse model of ulcerative hemorrhoids was established with glacial acetic acid(HAC)and compared with Ma Yinglong musk hemorrhoids ointment.The recovery of trauma was compared between the two groups.At the same time,porcine small intestine was used as semi-permeable membrane to make diffusion cell to simulate anal environment,and the drug release in vitro was studied.[Results]The C.bungei Steud.extract gel was smooth in appearance and good in stability.It could effectively treat anal ulcer in mice and release quickly in vitro.[Conclusions]The formula is reasonable,and the effect of animal experiment is remarkable,which can provide a new treatment plan for ulcerative hemorrhoids.
基金supported by the Welch Foundation(I-1441 to H.Y.)the Clayton Foundation,and Cancer Prevention and Research Institute of Texas(RP110465-P3 and RP120717-P2 to H.Y.)
文摘Orderly execution of two critical events during the cell cycle––DNA replication and chromosome segregation––ensures the stable transmission of genetic materials. The cohesin complex physically connects sister chromatids during DNA replication in a process termed sister chromatid cohesion. Timely establishment and dissolution of sister chromatid cohesion is a prerequisite for accurate chromosome segregation, and is tight regulated by the cell cycle machinery and cohesin-associated proteins. In this review, we discuss recent progress in the molecular understanding of sister chromatid cohesion during the mitotic cell cycle.
