Objective To explore the dynamic changes of the cellular immune function in severe infection after liver transplantation,and to guide the individualized immunology adjustment. Methods 378 cases of liver transplantatio...Objective To explore the dynamic changes of the cellular immune function in severe infection after liver transplantation,and to guide the individualized immunology adjustment. Methods 378 cases of liver transplantation were analyzed retrospectively. Seventy - four cases ( infection group) suffered serious infection,including 54 cases cured ( cure group) ,20 cases died (展开更多
The inflammatory bowel diseases (IBDs) are chronic incurable conditions that primarily present in young patients. Being incurable, the IBDs may be part of the patient’s life for many years and these condit...The inflammatory bowel diseases (IBDs) are chronic incurable conditions that primarily present in young patients. Being incurable, the IBDs may be part of the patient’s life for many years and these conditions require therapies that will be effective over the long-term. Surgery in Crohn’s disease does not cure the disease with endoscopic recurrent in up to 70% of patients 1 year post resection. This means that, the patient will require many years of medications and the goal of the treating physician is to induce and maintain long-term remission without side effects. The development of the anti-tumour necrosis factor alpha (TNFα) agents has been a magnificent clinical advance in IBD, but they are not always effective, with loss of response overtime and, at times, discontinuation is required secondary to side effects. So what options are available if of the anti-TNFα agents can no longer be used? This review aims to provide other options for the physician, to remind them of the older established medications like azathioprine/6-mercaptopurine and methotrexate, the less established medications like mycophenolate mofetil and tacrolimus as well as newer therapeutic options like the anti-integins, which block the trafficking of leukocytes into the intestinal mucosa. The location of the intestinal inflammation must also be considered, as topical therapeutic agents may also be worthwhile to consider in the long-term management of the more challenging IBD patient. The more options that are available the more likely the patient will be able to have tailored therapy to treat their disease and a better long-term outcome.展开更多
OBJECTIVE To investigate the effect of phosphotyrosine interaction domain containing 1(PID1,NYGGF4)on promotion of IR and HCC,and explore its underlying mechanisms.METHODS Lentivirus were used to mediate the knockdown...OBJECTIVE To investigate the effect of phosphotyrosine interaction domain containing 1(PID1,NYGGF4)on promotion of IR and HCC,and explore its underlying mechanisms.METHODS Lentivirus were used to mediate the knockdown of PID1 in HFD induced IR mouse model as well as ob/ob mice.Intraperitoneal glucose and insulin tolerance were performed 4 weeks after lentivirus injection.Hydrodynamics-based transfection was applied to inducethe liver specific overexpression of PID1.Flow cytometry was exerted to detect the proportion and function of immune cells.qR T-PCR and Western blot were used to detect the expression of downstream pathways of PID1.Immunoprecipitation was used to determine the receptor of PID1.Chromatin immunoprecipitation(ChI P)was operated to measure the modification of H3K4me3 of PID1 promoter.RESULTS PID1 restriction improved insulin resistance,hyperglycemia and fatty liver.Conversely,hepatic knockdown of PID1 attenuated liver xenografted tumor growth.Moreover,PID1 liver-specific protooncogenes via hydrodynamics-based transfection established a primary hepatocellular carcinoma mouse model,induced an immunosuppressive environment,with the reduction of CD3^+,CD4^+,CD8^+T cel s,retarded maturation of dendritic cel s(DCs),pronounced differentiation of regulatory T cells(Tregs),and recruitment of MDSC.In addition,PID1 overexpression activated proliferation related genes,promoted anti-inflammatory genes,suppressed pro-inflammatory genes,induced glycolysis and lipid metabolism genes to facilitate tumorigenesis in liver.Importantly,PID1 exerted its tumor-promoting function through binding to epidermal growth factor receptor(EGFR)and activation of downstream MAPK pathway.As such,PID1 exist trimethylation of histone H3 at lysine 4(H3K4me3)modification and IR up-regulated the expression of PID1 by activation the H3K4me3 modification.CONCLUSION PID1 is a new gene that exerts both liver cancer-promoting and insulin resistance inducing function.IR accelerates liver cancer development and progressionpartially dependent on the activation of PID1.展开更多
文摘Objective To explore the dynamic changes of the cellular immune function in severe infection after liver transplantation,and to guide the individualized immunology adjustment. Methods 378 cases of liver transplantation were analyzed retrospectively. Seventy - four cases ( infection group) suffered serious infection,including 54 cases cured ( cure group) ,20 cases died (
文摘The inflammatory bowel diseases (IBDs) are chronic incurable conditions that primarily present in young patients. Being incurable, the IBDs may be part of the patient’s life for many years and these conditions require therapies that will be effective over the long-term. Surgery in Crohn’s disease does not cure the disease with endoscopic recurrent in up to 70% of patients 1 year post resection. This means that, the patient will require many years of medications and the goal of the treating physician is to induce and maintain long-term remission without side effects. The development of the anti-tumour necrosis factor alpha (TNFα) agents has been a magnificent clinical advance in IBD, but they are not always effective, with loss of response overtime and, at times, discontinuation is required secondary to side effects. So what options are available if of the anti-TNFα agents can no longer be used? This review aims to provide other options for the physician, to remind them of the older established medications like azathioprine/6-mercaptopurine and methotrexate, the less established medications like mycophenolate mofetil and tacrolimus as well as newer therapeutic options like the anti-integins, which block the trafficking of leukocytes into the intestinal mucosa. The location of the intestinal inflammation must also be considered, as topical therapeutic agents may also be worthwhile to consider in the long-term management of the more challenging IBD patient. The more options that are available the more likely the patient will be able to have tailored therapy to treat their disease and a better long-term outcome.
基金supported by National Natural Science Foundation of China(81673440,81273521,and 91229114)
文摘OBJECTIVE To investigate the effect of phosphotyrosine interaction domain containing 1(PID1,NYGGF4)on promotion of IR and HCC,and explore its underlying mechanisms.METHODS Lentivirus were used to mediate the knockdown of PID1 in HFD induced IR mouse model as well as ob/ob mice.Intraperitoneal glucose and insulin tolerance were performed 4 weeks after lentivirus injection.Hydrodynamics-based transfection was applied to inducethe liver specific overexpression of PID1.Flow cytometry was exerted to detect the proportion and function of immune cells.qR T-PCR and Western blot were used to detect the expression of downstream pathways of PID1.Immunoprecipitation was used to determine the receptor of PID1.Chromatin immunoprecipitation(ChI P)was operated to measure the modification of H3K4me3 of PID1 promoter.RESULTS PID1 restriction improved insulin resistance,hyperglycemia and fatty liver.Conversely,hepatic knockdown of PID1 attenuated liver xenografted tumor growth.Moreover,PID1 liver-specific protooncogenes via hydrodynamics-based transfection established a primary hepatocellular carcinoma mouse model,induced an immunosuppressive environment,with the reduction of CD3^+,CD4^+,CD8^+T cel s,retarded maturation of dendritic cel s(DCs),pronounced differentiation of regulatory T cells(Tregs),and recruitment of MDSC.In addition,PID1 overexpression activated proliferation related genes,promoted anti-inflammatory genes,suppressed pro-inflammatory genes,induced glycolysis and lipid metabolism genes to facilitate tumorigenesis in liver.Importantly,PID1 exerted its tumor-promoting function through binding to epidermal growth factor receptor(EGFR)and activation of downstream MAPK pathway.As such,PID1 exist trimethylation of histone H3 at lysine 4(H3K4me3)modification and IR up-regulated the expression of PID1 by activation the H3K4me3 modification.CONCLUSION PID1 is a new gene that exerts both liver cancer-promoting and insulin resistance inducing function.IR accelerates liver cancer development and progressionpartially dependent on the activation of PID1.
