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With the rapid development of organ transplantation in China,the donation after cardiac death (DCD) donor organs are widely used.However,the quality of these organs is relatively poor,so the way to preserve and maintain organ still remains a severe problem.Among them,ischemic reperfusion injury (IRI) impairs the organs severely.Acetaldehyde dehydrogenase 2 (ALDH2) protects organs from stress conditions,including ischemia-reperfusion injury,and the activation and autophagy inhibition also protects the organs from stress conditions as well.Recent studies showed that ALDH2 can regulate autophagy to inhibit the organ injury during ischemia-reperfusion.Our study aims to discuss the new findings in this mechanism.
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Hepatic ischemia-reperfusion injury is an inevitable clinical phenomenon during the liver transplantation. The mechanism of hepatic ischemia-reperfusion injury is complex, with reactive oxygen species, inflammatory factors, calcium overload, neutrophils and Kupffer cells involved. If injury continues to getting worsen, liver cells will undergo necrosis, apoptosis, and autophagy. Interventions for hepatic ischemia-reperfusion injury mainly include ischemic preconditioning, drug pretreatment, chemical pretreatment, mild hypothermia pretreatment, and machine perfusion and gene-targeted therapy in recent years. With the indepth research of injury mechanism, new intervention methods continue to emerge, which will bring new ideas for clinical prevention and treatment of liver ischemia-reperfusion injury.
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Objective To investigate the diagnosis and treatment of antibody-mediated rejection after liver transplantation.Methods The clinical data of 1 case of antibody-mediated rejection after liver transplantation were collected.The patient had autoimmune liver disease (de-compensated stage) and received a liver transplantation with ABO-compatible.Triple immunosuppressive regimen of tacrolimus + mycophenolate mofetil + prednisone was used after operation.The valley of tacrolimus concentration was maintained at 8-10 μg/L.One month after transplantation,the liver function recovered to normal.Alanine aminotransferase was 16 U/L,aspartate aminotransferase was 37 U/L and total bilirubin was 17.3 U/L.Results Three months after operation,the liver function index increased sharply (total bilirubin was 186.3 U/L).The first pathological examination of liver biopsy at 14th week after operation showed the histological findings of acute rejection.Combining the data of clinical features,steroid pulse therapy was given,but the effect was poor.The biopsy of the retransplanted liver at 18th week after operation showed necrosis of minority hepatic cells and obvious attachment of lymphocytes in the central venous branch wall.Panel reactive antibodies test revealed that the HLA_ Ⅱ antibodies were intensively positive,suggesting the diagnosis of AMR.After treatment with plasma exchange and adjusting the immunosuppressant dosage,the function of the transplanted liver recovered gradually.Conclusion For liver transplantation with compatible blood type and recipient with autoimmune liver disease,we should alert the occurrence of acute AMR.Timely liver biopsy and PRA detection should be performed for definite diagnosis.Plasmapheresis is effective in treating acute AMR after liver transplantation.
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Objective To investigate the protective effect of glycyrrhizin against renal ischemiareperfusion injury in mice and its mechanisms.Methods Male C57BL/6 mice were divided into three groups of six.Bilateral flank incisions were made,the right kidney was removed and the left kidney was subjected to ischemia using a microvascular clamp,which was removed after 30 min.In the shamoperated group,the mice underwent anesthesia,bilateral flank incisions and a right nephrectomy.In the glycyrrhizin-treated group,the mice were injected with 60 mg/ kg glycyrrhizin 1 h prior to ischemia.In the saline-treated group,the mice were administered with 60 mg/ kg saline.The mice were sacrificed 6 h after reperfusion and the blood and kidney samples were immediately collected for kidney function,inflammatory response and signal pathway test.Results As compared with those in the saline-treated group,the mice in glycyrrhizin0-treated group exhibited notably decreased serum levels of creatine and blood urea nitrogen at 6 h following reperfusion (P＜0.01),the SOA level was significantly reduced (P＜0.01) and the SOD activity was increased.The activity of MPO (P＜0.01)in the glycyrrhizin-treated group was significantly reduced as compared with the saline-treated group,also the serum level of pro-inflammatory TNF-α (P＜0.05),IFN-γ (P＜0.05),IL-1β (P＜0.01) and IL-6 (P＜0.01).Furthermore,the phosphorylated-p38 protein level in the glycyrrhizin-treated group was notably as reduced compared with that in the saline-treated group.Conclusion Pretreatment with glycyrrhizin attenuates renal ischemia-reperfusion injury via inhibition of tissue inflammation by downregulating p38 mitogen-activated protein kinase signaling.
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Objective To compare three different types of donor livers (C-Ⅰ,C-Ⅱ,C-Ⅲ) in clinical efficacy,complications and survival rate of liver transplantation.Methods Using the retrospective descriptive study method,the clinical data of 422 patients undergoing liver transplantation,including 124 cases of C-Ⅰ,81 cases of C-Ⅱ and 81 cases of C-Ⅲ in recent 6 years (from June 2010 to June 2016) were analyzed.The same surgical method was performed with piggyback liver transplantation.Observation indicators contained (1) recipient postoperative liver function;(2) the postoperative complications;(3) the recipient survival rate.SPSS 19.0 statistical software was used for analysis.Results (1) The curative effect was evaluated by the changes of ALT and TBIL among three groups of recipients postoperatively.As compared with C-Ⅰ transplantation group and CⅢ transplantation group,the level of ALT in C-Ⅱ transplantation group was significantly increased (P ＜0.05),the clinical efficacy was poorer.(2) The incidence of PNF was 3.23％ in C-Ⅰ group,9.88％ in C-Ⅱ group and 9.88％ in C-Ⅲ group (P＜0.05).The incidence of acute rejection was respectively 9.68％ in C-Ⅰ group,38.27％ in C-Ⅱ group and 38.27％ in C-Ⅲ group (P＜0.001).The incidence of SIRS was respectively 5.65％ in C-Ⅰ group,39.50％ in C-Ⅱ group and 39.50％ in C-Ⅲ group (P＜ 0.001).There were significant differences in the incidence of other complications among the three groups.(3) There were 14 deaths within 3 months,accounting for 17.28％,and the survival rate was 82.72％ in C-Ⅱ group,the 1-,3-,and 5-year survival rate was 76.55％,74.18％ and 76.55％ respectively in C-Ⅰ group,and that was 88.02％,85.72％ and 81.11％ respectively in C-Ⅲ group.Conclusion Since June 2015,C-Ⅰ donors grow up more quickly on year-on-year basis than C-Ⅱ.Simultaneously,the sort-term and long-term clinical efficacy is better in C-Ⅰ transplantation group than in C-Ⅱ transplantation group.How to repair the three types of Chinese standard donor organs and optimize the quality is still a hot point to ensure the healthy development of organ transplantation in China,which needs further investigation.
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Chinese donation after citizen's death (CDCD) is an important way to solve the donor shortage problem,but if we can't effectively control warm ischemia time of CDCD donor,it's easy to cause grafts primary nonfunction,early grafts dysfunction and biliary complications.Nowadays,with the development of surgical techniques,the definition of warm ischemia continues has been continuously updated.The understanding on different definitions may lay the foundation for improving the survival rate of liver and kidney and effectively protect liver and kidney function after transplantation.This paper overviewed the significance of different definitions of warm ischemia and its effect on liver and renal function,which could provide a reference for further experimental study and clinical practice.
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Primary hepatocellular carcinoma (HCC) is one of the most common malignancies worldwide and has a relatively high mortality rate.Liver transplantation has become an effective treatment for HCCs,but tumor recurrences after liver transplantation and donor shortages are the major limitations.The Milan criterion was the first standard and has been widely applied to liver transplantation of HCCs.Then,there are new emerging standards,namely University of California,San Francisco criterion (UCSF),Hangzhou and Shanghai criteria.Meanwhile,the comparison among these criteria laid the foundation for early prediction and prevention of post-transplantation tumor recurrence.In this review,clinical effect prediction and tumor recurrence after liver transplantation are also heated issues.
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Objective To sum up the experiences in liver transplantations from donation after brain death (DBD),and compare the clinical effect,complications and influential factors with international situation.Methods The retrospective descriptive study was adopted.All the data of 66 DBD liver donors and the matched recipients from authors' affiliations during June 2010 and June 2013 were collected.Original articles,meta-analysis and data reports with high academic influence were read and data were analyzed with SPSS 22.0.Results The incidence of serious complications,vascular complications and biliary complications during the first year among 66 recipients was 21.2％,10.6％,and 6.1％,respectively.Compared to international situation,graft 1-,3-,and 5-year survival rate was similar (P＞0.05) (83％,80％ and 73％ respectively),similar to that of recipients.There was no statistically significant difference in primary nonfunction and vascular complications between our center and other centers.As for biliary complications,morbidity was lower in our center (P＜0.05).The 3-and 5-year survival rate of recipients was also similar (P＞0.05),though the 1-year survival rate was slightly lower (P＜ 0.05).Conclusion These findings provide evidence that patient's prognosis under DBD liver transplantation in our center is acceptable,and long-term survival rate has reached international level.Still,1-year survival rate of recipients is unsatisfactory.In order to achieve a good clinical efficacy,we need to find out disadvantages during donor maintenance,recipient selection,surgical procedure and postoperative management.
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Liver transplantation is the most effective treatment for end-stage liver diseases.To expand the donor source,the Ministry of Health (MOH) initiated a new national program called Donation of Citizen's Deceased (DCD) to address the need for organ transplantation in 2010.However,it has been proven that DCD liver transplantation has the poorer graft function in short-and long-term outcome compared to live donor liver transplantation.In order to improve the effect of DCD liver transplantation,the preconditioning of DCD liver,as an effective measure,is gaining more and more attention.This review summarizes the recent research progress on the application of preconditioning in DCD liver transplantation during perioperative period.
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Objective To establish the rabbit brain death model,and observe the change of kidney function and morphology in the brain death rabbits,fully evaluate the possibility of transplantation surgery carried out with brain death donor kidney.Method 40 male healthy New Zealand rabbits were randomly divided into sham group (n =20) and brain death group (n =20),and each group further was divided into four groups according to 2,4,6 and 8 h after brain death groups.At the end of the experiment,the blood samples and kidney tissues were collected.The level of blood urea nitrogen(BUN),serum creatinine (Cr) and the apoptosis of kidney cells were determined by automatic biochemistry analyzer and TUNEL method,respectively.The morphology changes of liver were detected by HE staining.Result Although BUN values were with no obviously alteration (P＞0.05) within 8 h after brain death,the renal Cr levels in the states of 2,4 and 8 h (P＜0.05) brain death were found significantly increased compared with shamed groups.The denaturalization in the epithelial cells of renal tubule,glomerulus atrophygradually,swelling and vacuolation of epithelial cells,edema in the interstitium and inflammatory cell infiltration and partly occlusion in proximal convoluted tubule gradually emerged in the brain dead groups.The inflammatory factor intercellular adhesion molecule (ICMA) and the apoptosis index in brain dead groups increased in a time dependent manner but the expressions of protective factor HSP70 conducted a contrary tendency.Conclusin Brain death could lead to the damage of kidney function and morphology and this injury aggravated in a time dependent manner.The alterations might be relevant to the production of inflammatory factors.Within 8 h after brain death there were obvious changes in the kidney function and morphology,which provide experimental basis for the rational use of brain death donor kidney transplantation.
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Objective To explore the differential proteins in livers with the help of proteomics,which provide experimental basis for the study of influence factors of liver injury in the state of brain-death.Methods Slow intracranial pressure method was used to establish the rabbit brain death model.Each liver tissue from 6 h after brain death of rabbit was collected.Total proteins were extracted and separated by two-dimensional gel electrophoresis.The image was analyzed by PDQuest software.The differentially expressed proteins between the two groups in more than two-fold were identified by matrix-assisted laser desorption ionization time of flight mass spectrometry and retrieved in the NCBI database to identify the corresponding protein.And the different proteins were re-identified by western blot.Results Two-dimensional gel electrophoresis showed that there were about 973 ± 34 and 987 ± 38 protein spots in sham and brain death groups.A total of 52 differentially expressed protein spots between the two groups,29 were up-regulated,and 23 were down-regulated.10 different proteins were:DPYL4,ALDH2,PRDX6,PDK1,THTM,RUNX1,PPA1,ADH,GCLR,CYB5.RUNX1 is a protein of interest,so the expression of RUNX1 was detected by western blot and it showed that the expression of RUNX1 in liver decreased gradually in a time-dependent manner.Conclusions Two-dimensional gel electrophoresis and mass spectrometry identification is a reliable platform and powerful tool for differential proteomics studies.Identified protein RUNX1 may be related with liver injury after brain death,which is beneficial for the understanding of the mechanism of liver damage after brain death.
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Objective To compare the outcome of donation after cardiac death (DCD) versus donation after brain death (DBD) for liver transplantation.Method Such databases as PubMed,Cochrane Central Register of Controlled Trials (CENTRAL),EMbase,the ISI Web of Knowledge databases and CBMdisk were searched from Month 1990 to March 2011 for collecting the randomized controlled trials (RCTs),case control studies and cohort analysis about DCD versus DBD for liver transplantation,and the references of those trials were also searched by hand.After study selection,assessment and data extraction conducted by two reviewers independently,meta-analyses were performed by using the RevManS.1 software.The quality of evidence was assessed by using the GRADEpro software.Result DCD group had similar MELD of recipients with DBD group before operation [Z =1.37,95％ CI(-2.25,0.26),P =0.17],and DCD group got shorter cold ischemia time than DBD group [Z=2.26,95％CI(-1.76,-0.12),P =0.02].DCD group had higher hiliary complication incidence [Z =6.37,95％ CI(1.89,3.31),P＜0.000 01],higher vascular complication incidence [Z =2.14,95％ CI(1.03,2.17),P =0.03],higher liver primary non-function (PNF) incidence [Z =4.43,95％ CI (2.02,6.17),P＜0.000 01],lower 1-year graft survival rate [Z =3.78,95％ CI(0.84,0.94),P =0.0002] and lower 3 year graft survival rate[Z=2.54,95％ CI(0.73,0.96),P =0.01] than DBD group.The quality of the result was verified from low to moderate.Conclusion Liver transplantation using DCD had higher incidence of complications and lower 1-year and 3-year graft survival rate than DBD.For the poor quality of the original studies,a prudent choice is suggested.More randomized controlled trials are needed.
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Objective To establish the rabbit brain death model,observe the change of liver function and morphology in the brain death rabbits,and evaluate the possibility of transplantation surgery carried out with brain death donor liver.Methods 40 healthy New Zealand rabbits were randomly divided into sham group (n=20) and brain death group (n=20),and each group was further divided into four subgroups according to 2,4,6 and 8 h after brain death.At the end of the experiment,the blood samples and liver tissues were collected.The level of alanine transaminase (ALT),aspartate transaminase (AST) and the apoptosis of liver cells were determined by automatic biochemistry analyzer and TUNEL method respectively.The morphology changes of liver were detected by HE staining,and the levels of interleukin (IL)-1β,IL-6,IL-8,tumor necrosis factor (TNF)-α were detected by competitive inhibition ELISA.Results In 2,4,6 and 8 h group,the level of ALT and AST increased,especially in 8 h group,which were significantly different from 6 h group's.Under light microscope,there was no significant change in liver 2 and 4 h after brain death.However,in 8 h after brain death,liver cells degenerated significantly,liver cord structure disappeared,some liver cells necrosis,which was consistent with the results of apoptosis index.The levels of IL-1β,IL-6,IL-8,TNF-α were obviously increased in a time dependent manner compared with sham group.Conclusions Brain death could lead to the damage of liver function and morphology and this injury aggravated with time,which might be relevant with the production of inflammatory mediators.8 h after brain death,there were obvious change in the liver function and morphology.
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Objective To explore the way to establish the brain death model for rabbits and pathophysiological changes before and after brain death.Methods 80 healthy male New Zealand rabbits were divided into brain death group (n =60) and sham operation group (n =20),The 60 brain death rabbits were established by increasing intracranial pressure in a modified,slow,and intermittent way.The sham operation rabbits were only maintained with anesthesia.Results The 56 brain death rabbits were established successfully and maintained for 10 h with the respiration and circulation supports.2 rabbits died due to anesthetic accident,the other 2 died because of improper pressure.The surgical success rate is 93.3％ (56/60).The changes of mean artery pressure (MAP) and heart rate (HR) in brain death group were more significant than in sham operation group:MAP and HR fluctuated and showed the increased tendency.The mean MAP and HR during increasing intracranial pressure were (400.24±18.36) mm Hg (1 mm Hg=0.133 kPa) and (258.00 ± 25.70) beats/min respectively,which was significantly higher than before and after increasing intracranial pressure (P＜0.05).Conclusions The brain death model for rabbits could be established by increasing intracranial pressure in a modified,slow,and intermittent way successfully and maintained 10 h.the MAP and HR before and after brain death showed characteristic changes.The model is helpful to the further observation of organ changes in brain dead state.
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Objective To explore the differential proteins between livers of control and brain dead grups,and to provide an experimental basis for the assessment of liver quality in brain dead rabbits.Methods 60 healthy male New Zealand rabbits were divided into two groups.The brain dead group (n=30) contained rabbits 2 hours (B1),6 hours (B2),and 8 hours(B3) after brain death.The sham group (n=30) contained groups of 2 hours (C1),6 hours (C2),and 8 hours (C3).At the end of the relevant experiments,blood samples and liver tissues were collected.The level of ALT and AST were determined by an automatic biochemistry analyzer and the morphologic changes of the livers were detected by HE staining.The differentially expressed proteins were screened and identified by two-dimensional gel electrophoresis,PDQuest software,matrix-assisted laser desorption ionization time of flight mass spectrometry,and the NCBI database.Results In 8 hour brain dead group,the level of ALT increased comparing with 6 h (P＜0.05),but there was no significant statistical difference in the other groups.Under real time observation with the light microscope,the livers of the brain dead groups had increased edema and infiltration of lymphocytes in the portal area,especially in the 8 hour group.However,infiltration of neutrophils also appeared in the 8 hour control group and all groups had no damage in the liver cell.There were 10 kinds of differentially expressed proteins through the two-dimensional gel electrophoresis,mass spectrometry analysis,and database query.One protein of interest was ALDH2,which showed a gradually decreasing expression in the liver when the braid dead time increased.Conclusion Brain death could lead to no damage of liver function and little damage to liver morphology.The identified protein ALDH2 may be related with liver injury after brain death and could be a new indicator in the assessment of liver quality in brain dead rabbits.
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Biliary complication (BC) after liver transplantation has attracted increased attention from a clinical and research perspective.BC,which affects the long-term outcome of the liver transplant,includes diseases of biliary stricture,biliary obstruction,biliary fistula,and many more that need an operation or interventional therapy.The occurrence of these diseases is related to the surgical operation,biliary tract variation,vessel injury,and quality of the donor graft.This article reviews BC and its etiology,diagnosis,and therapy in order to help future clinical and experimental studies.