AIM:To investigate the possible involvement of Sirtuin1(SIRT1)in rat orthotopic liver transplantation(OLT),when Institute Georges Lopez 1(IGL-1)preservation solution is enriched with trimetazidine(TMZ).METHODS:Male Sp...AIM:To investigate the possible involvement of Sirtuin1(SIRT1)in rat orthotopic liver transplantation(OLT),when Institute Georges Lopez 1(IGL-1)preservation solution is enriched with trimetazidine(TMZ).METHODS:Male Sprague-Dawley rats were used as donors and recipients.Livers were stored in IGL-1 preservation solution for 8h at 4℃,and then underwent OLT according to Kamada’s cuff technique without arterialization.In another group,livers were stored in IGL-1 preservation solution supplemented with TMZ,at10-6 mol/L,for 8 h at 4℃and then underwent OLT.Rats were sacrificed 24 h after reperfusion,and liver and plasma samples were collected.Liver injury(transaminase levels),mitochondrial damage(glutamate dehydrogenase activity)oxidative stress(malondialdehyde levels),and nicotinamide adenine dinucleotide(NAD+),the cofactor necessary for SIRT1 activity,were determined by biochemical methods.SIRT1 and its substrates(acFox O1,ac-p53),the precursor of NAD+,nicotinamide phosphoribosyltransferase(NAMPT),as well as the phosphorylation of adenosine monophosphate activated protein kinase(AMPK),p-m TOR,p-p70S6K(direct substrate of m TOR),autophagy parameters(beclin-1,LC3B)and MAP kinases(p-p38 and p-ERK)were determined by Western blot.RESULTS:Liver grafts preserved in IGL-1 solution enriched with TMZ presented reduced liver injury and mitochondrial damage compared with those preservedin IGL-1 solution alone.In addition,livers preserved in IGL-1+TMZ presented reduced levels of oxidative stress.This was consistent with enhanced SIRT1 protein expression and elevated SIRT1 activity,as indicated by decreased acetylation of p53 and Fox O1.The elevated SIRT1 activity in presence of TMZ can be attributed to the enhanced NAMPT protein and NAD+/NADH levels.Up-regulation of SIRT1 was consistent with activation of AMPK and inhibition of phosphorylation of m TOR and its direct substrate(p-p70S6K).As a consequence,autophagy mediators(beclin-1 and LC3B)were overexpressed.Furthermore,MAP kinases were regulated in livers preserved with IGL-1+TMZ,as they were characterized by enhanced p-ERK and decreased p-p38protein expression.CONCLUSION:Our study shows that IGL-1 preservation solution enriched with TMZ protects liver grafts from the IRI associated with OLT,through SIRT1 up-regulation.展开更多
AIM:To evaluate the prognostic value of pretreatment F D G p o s i t r o n e m i s s i o n t o m o g ra p h y c o m p u t e d tomography(PET-CT) in patients with hepatocarcinoma treated by liver transplantation(LT).ME...AIM:To evaluate the prognostic value of pretreatment F D G p o s i t r o n e m i s s i o n t o m o g ra p h y c o m p u t e d tomography(PET-CT) in patients with hepatocarcinoma treated by liver transplantation(LT).METHODS:The authors retrospectively analyzed the data of 27 patients(mean age 58 ± 9 years) who underwent FDG PET-CT before LT for hepatocarcinoma.Mean follow-up was 26 ± 18 mo.The FDG PET/CT was performed according to a standard clinical protocol:4 MBq FDG/kg body weight,uptake 60 min,low-dose non-enhanced CT.The authors measured the SUVmax and SUVmean of the tumor and the normal liver.The tumor/liver activity ratios(RSUVmax and RSUVmean) were tested as prognostic factors and compared to the following conventional prognostic factors:MILAN,CLIP,OKUDA,TNM stage,alphafoetoprotein level,portal thrombosis,size of the largest nodule,tumor differentiation,microvascular invasion,underlying cirrhosis and liver function.RESULTS:Overall and recurrence free survivals were80.7%and 67.4%at 3 years,and 70.6%and 67.4%at 5 years,respectively.According to a multivariate Cox model,only FDG PET/CT RSUVmax predicted recurrence free survival.Even though the MILAN criteria alone were not predictive,it is worth noting that none of the patients outside the MILAN criteria and with RSUVmax<1.15 relapsed.CONCLUSION:FDG PET/CT with an RSUVmax cutoff value of 1.15 is a strong prognostic factor for recurrence and death in patients with HCC treated by LT in this retrospective series.Further prospectivestudies should test whether this metabolic index should be systematically included in the preoperative assessment.展开更多
AIM:To compare the surgical outcomes between living-donor and deceased-donor liver transplantation in patients with hepatic carcinoma.METHODS:From January 2007 to December 2010,257 patients with pathologically confirm...AIM:To compare the surgical outcomes between living-donor and deceased-donor liver transplantation in patients with hepatic carcinoma.METHODS:From January 2007 to December 2010,257 patients with pathologically confirmed hepatic carcinoma met the eligibility criteria of the study.Forty patients who underwent living-donor liver transplantation(LDLT)constituted the LDLT group,and deceaseddonor liver transplantation(DDLT)was performed in217 patients.Patients in the LDLT group were randomly matched(1:2)to patients who underwent DDLT using a multivariate case-matched method,so 40 patients in the LDLT group and 80 patients in the DDLT group were enrolled into the study.We compared the two groups in terms of clinicopathological characteristics,postoperative complications,long-term cumulative survival and relapse-free survival outcomes.The modified Clavien-Dindo classification system of surgical complications was used to evaluate the severity of perioperative complications.Furthermore,we determined the difference in the overall biliary complication rates in the perioperative and follow-up periods between the LDLT and DDLT groups.RESULTS:The clinicopathological characteristics of the enrolled patients were comparable between the two groups.The duration of operation was significantly longer(553 min vs 445 min,P<0.001)in the LDLT group than in the DDLT group.Estimated blood loss(1188 mL vs 1035 mL,P=0.055)and the proportion of patients with intraoperative transfusion(60.0%vs 43.8%,P=0.093)were slightly but not significantly greater in the LDLT group.In contrast to DDLT,LDLT was associated with a lower rate of perioperative gradeⅡcomplications(45.0%vs 65.0%,P=0.036)but a higher risk of overall biliary complications(27.5%vs 7.5%,P=0.003).Nonetheless,21 patients(52.5%)in the LDLT group and 46 patients(57.5%)in the DDLT group experienced perioperative complications,and overall perioperative complication rates were similar between the two groups(P=0.603).No significant difference was observed in 5-year overall survival(74.1%vs 66.6%,P=0.372)or relapse-free survival(72.9%vs 70.9%,P=0.749)between the LDLT and DDLT groups.CONCLUSION:Although biliary complications were more common in the LDLT group,this group did not show any inferiority in long-term overall survival or relapse-free survival compared with DDLT.展开更多
"Through the revision to regulations on dangerous goods,the Chinese government has made a clearer elassification of dangerous goods and issued a series of policies to ensure the safe transportation of dangerous g..."Through the revision to regulations on dangerous goods,the Chinese government has made a clearer elassification of dangerous goods and issued a series of policies to ensure the safe transportation of dangerous goods,"said high-kevek delegates from the State展开更多
Fecal microbiota transplantation(FMT)is considered to be a highly successful therapy for recurrent and refractory Clostridium difficile infection(CDI)based on recent clinical trials.The pathogenesis of inflammatory bo...Fecal microbiota transplantation(FMT)is considered to be a highly successful therapy for recurrent and refractory Clostridium difficile infection(CDI)based on recent clinical trials.The pathogenesis of inflammatory bowel diseases(IBD)is thought to be due in part to perturbations in the gut microflora that disrupt homeostasis.FMT restores essential components of the microflora which could reverse the inflammatory processes observed in IBD.Case reports and series for the treatment of IBD by FMT have shown promise with regards to treatment success and safety despite the limitations of the reporting.Future studies will determine the optimal delivery and preparation of stool as well as the conditions under which the recipient will derive maximal benefit.The long term consequences of FMT with regards to infection,cancer,auto-immune,and metabolic diseases are not known and will require continued regulation and study.Despite these limitations,FMT may be beneficial for the treatment of ulcerative colitis and Crohn’s disease,particularly those with concurrent CDI or with pouchitis.展开更多
基金Supported by Fondo de Investigaciones Sanitarias,No.FIS PI12/00519Eirini Pantazi is the recipient of a fellowship from AGAUR,No.2012FI_B00382,Generalitat de Catalunya,Barcelona,Catalonia,Spain
文摘AIM:To investigate the possible involvement of Sirtuin1(SIRT1)in rat orthotopic liver transplantation(OLT),when Institute Georges Lopez 1(IGL-1)preservation solution is enriched with trimetazidine(TMZ).METHODS:Male Sprague-Dawley rats were used as donors and recipients.Livers were stored in IGL-1 preservation solution for 8h at 4℃,and then underwent OLT according to Kamada’s cuff technique without arterialization.In another group,livers were stored in IGL-1 preservation solution supplemented with TMZ,at10-6 mol/L,for 8 h at 4℃and then underwent OLT.Rats were sacrificed 24 h after reperfusion,and liver and plasma samples were collected.Liver injury(transaminase levels),mitochondrial damage(glutamate dehydrogenase activity)oxidative stress(malondialdehyde levels),and nicotinamide adenine dinucleotide(NAD+),the cofactor necessary for SIRT1 activity,were determined by biochemical methods.SIRT1 and its substrates(acFox O1,ac-p53),the precursor of NAD+,nicotinamide phosphoribosyltransferase(NAMPT),as well as the phosphorylation of adenosine monophosphate activated protein kinase(AMPK),p-m TOR,p-p70S6K(direct substrate of m TOR),autophagy parameters(beclin-1,LC3B)and MAP kinases(p-p38 and p-ERK)were determined by Western blot.RESULTS:Liver grafts preserved in IGL-1 solution enriched with TMZ presented reduced liver injury and mitochondrial damage compared with those preservedin IGL-1 solution alone.In addition,livers preserved in IGL-1+TMZ presented reduced levels of oxidative stress.This was consistent with enhanced SIRT1 protein expression and elevated SIRT1 activity,as indicated by decreased acetylation of p53 and Fox O1.The elevated SIRT1 activity in presence of TMZ can be attributed to the enhanced NAMPT protein and NAD+/NADH levels.Up-regulation of SIRT1 was consistent with activation of AMPK and inhibition of phosphorylation of m TOR and its direct substrate(p-p70S6K).As a consequence,autophagy mediators(beclin-1 and LC3B)were overexpressed.Furthermore,MAP kinases were regulated in livers preserved with IGL-1+TMZ,as they were characterized by enhanced p-ERK and decreased p-p38protein expression.CONCLUSION:Our study shows that IGL-1 preservation solution enriched with TMZ protects liver grafts from the IRI associated with OLT,through SIRT1 up-regulation.
基金Supported by An unrestricted research grant from Astellas BelgiumSM and CM are Ph D fellows with grants from the Académie de Recherche et d’Enseignement Supérieur(ARES)of the Wallonia-Brussels Federation
文摘AIM:To evaluate the prognostic value of pretreatment F D G p o s i t r o n e m i s s i o n t o m o g ra p h y c o m p u t e d tomography(PET-CT) in patients with hepatocarcinoma treated by liver transplantation(LT).METHODS:The authors retrospectively analyzed the data of 27 patients(mean age 58 ± 9 years) who underwent FDG PET-CT before LT for hepatocarcinoma.Mean follow-up was 26 ± 18 mo.The FDG PET/CT was performed according to a standard clinical protocol:4 MBq FDG/kg body weight,uptake 60 min,low-dose non-enhanced CT.The authors measured the SUVmax and SUVmean of the tumor and the normal liver.The tumor/liver activity ratios(RSUVmax and RSUVmean) were tested as prognostic factors and compared to the following conventional prognostic factors:MILAN,CLIP,OKUDA,TNM stage,alphafoetoprotein level,portal thrombosis,size of the largest nodule,tumor differentiation,microvascular invasion,underlying cirrhosis and liver function.RESULTS:Overall and recurrence free survivals were80.7%and 67.4%at 3 years,and 70.6%and 67.4%at 5 years,respectively.According to a multivariate Cox model,only FDG PET/CT RSUVmax predicted recurrence free survival.Even though the MILAN criteria alone were not predictive,it is worth noting that none of the patients outside the MILAN criteria and with RSUVmax<1.15 relapsed.CONCLUSION:FDG PET/CT with an RSUVmax cutoff value of 1.15 is a strong prognostic factor for recurrence and death in patients with HCC treated by LT in this retrospective series.Further prospectivestudies should test whether this metabolic index should be systematically included in the preoperative assessment.
基金Supported by Key Discipline and Specialty Foundation of Shanghai Municipal Commission of Health and Family PlanningTraining Program for Superb Academic Leaders in Shanghai Health System,No.XBR2011029Special Fund for Building of Leading Talent Teams in Shanghai
文摘AIM:To compare the surgical outcomes between living-donor and deceased-donor liver transplantation in patients with hepatic carcinoma.METHODS:From January 2007 to December 2010,257 patients with pathologically confirmed hepatic carcinoma met the eligibility criteria of the study.Forty patients who underwent living-donor liver transplantation(LDLT)constituted the LDLT group,and deceaseddonor liver transplantation(DDLT)was performed in217 patients.Patients in the LDLT group were randomly matched(1:2)to patients who underwent DDLT using a multivariate case-matched method,so 40 patients in the LDLT group and 80 patients in the DDLT group were enrolled into the study.We compared the two groups in terms of clinicopathological characteristics,postoperative complications,long-term cumulative survival and relapse-free survival outcomes.The modified Clavien-Dindo classification system of surgical complications was used to evaluate the severity of perioperative complications.Furthermore,we determined the difference in the overall biliary complication rates in the perioperative and follow-up periods between the LDLT and DDLT groups.RESULTS:The clinicopathological characteristics of the enrolled patients were comparable between the two groups.The duration of operation was significantly longer(553 min vs 445 min,P<0.001)in the LDLT group than in the DDLT group.Estimated blood loss(1188 mL vs 1035 mL,P=0.055)and the proportion of patients with intraoperative transfusion(60.0%vs 43.8%,P=0.093)were slightly but not significantly greater in the LDLT group.In contrast to DDLT,LDLT was associated with a lower rate of perioperative gradeⅡcomplications(45.0%vs 65.0%,P=0.036)but a higher risk of overall biliary complications(27.5%vs 7.5%,P=0.003).Nonetheless,21 patients(52.5%)in the LDLT group and 46 patients(57.5%)in the DDLT group experienced perioperative complications,and overall perioperative complication rates were similar between the two groups(P=0.603).No significant difference was observed in 5-year overall survival(74.1%vs 66.6%,P=0.372)or relapse-free survival(72.9%vs 70.9%,P=0.749)between the LDLT and DDLT groups.CONCLUSION:Although biliary complications were more common in the LDLT group,this group did not show any inferiority in long-term overall survival or relapse-free survival compared with DDLT.
文摘"Through the revision to regulations on dangerous goods,the Chinese government has made a clearer elassification of dangerous goods and issued a series of policies to ensure the safe transportation of dangerous goods,"said high-kevek delegates from the State
文摘Fecal microbiota transplantation(FMT)is considered to be a highly successful therapy for recurrent and refractory Clostridium difficile infection(CDI)based on recent clinical trials.The pathogenesis of inflammatory bowel diseases(IBD)is thought to be due in part to perturbations in the gut microflora that disrupt homeostasis.FMT restores essential components of the microflora which could reverse the inflammatory processes observed in IBD.Case reports and series for the treatment of IBD by FMT have shown promise with regards to treatment success and safety despite the limitations of the reporting.Future studies will determine the optimal delivery and preparation of stool as well as the conditions under which the recipient will derive maximal benefit.The long term consequences of FMT with regards to infection,cancer,auto-immune,and metabolic diseases are not known and will require continued regulation and study.Despite these limitations,FMT may be beneficial for the treatment of ulcerative colitis and Crohn’s disease,particularly those with concurrent CDI or with pouchitis.
