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Objective:To explore the feasibility of a stable pig-to-monkey orthotopic liver transplantation (LT) model and provide a favorable experimental tool for preclinical studies of xenotransplantation.Methods:In this retrospective analysis, the authors reviewed the perioperative conditions and outcomes of 7 pig-to-monkey orthotopic liver transplants performed by a xenotransplantation research team of Second Xiangya Hospital.Gene-edited Banna miniature pigs were selected as donors and rhesus monkeys with similar anatomical characteristics, physiology, biochemistry and immune mechanism to humans were selected as recipients for pig-monkey xenogeneic orthotopic LT.Based upon classic transplantation procedures, whole liver xenogeneic orthotopic transplantation was performed.Surgical processes were modified for minimizing intraoperative hemorrhage and shortening anhepatic period.A bile duct drainage tube was implanted for observing bile secretion.ATG + anti-CD20 + snake venom factor and FK-506 were utilized for immunoinduction pre-operation while tacrolimus, mycophenolate mofetil (MMF) and methyl prednisolone for postoperative immunomaintenance therapy.Antibiotics and antiviral agents were also applied and thrombin complex for improving coagulation functions.Results:All procedures were successfully completed.After the stability and maturity of our model, in case No.7, donor's acquisition operative duration was 42 min without heat ischemic time, donor's trimming time 87 min, donor cold retention time 128 min, recipient's operative duration 123 min and anhepatic phase 27 min.Subhepatic inferior vena cava was occluded for 38 min.Blood loss was around 10 ml.And 4/7 models survived post-operation and the longest survival time was 27 h. Among 3 non-survival cases, the causes were anesthesia accident (n=1) and immaturity of early operation (n=2). Model No.7 had a biliary secretion volume of 86 ml post-operation.Conclusions:Qualified donor acquisition, high-quality vascular anastomosis, intraoperative reduction of blood loss, shortening of anhepatic period, strict fluid replenishing and careful monitoring are essential for boosting the success rate of pig-monkey liver xenotransplantation model.Optimization of donor gene combination and advanced immunosuppression protocol help to further achieve the long-term survival of pig-monkey liver xenotransplantation model.
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Objective To investigate the efficacy and safety of programmed cell death protein-1 (PD-1) monoclonal antibody on the treatment of malignant tumor after solid organ transplantation (SOT). Methods The relevant literatures in 7 databases were searched. The data on 54 cases of recipients with malignant tumors treated with PD-1 monoclonal antibody after SOT were collected, and the clinical effects and rejection of SOT recipients treated with PD-1 monoclonal antibody were analyzed. Results Total 32 acceptable articles including 54 SOT recipients were incorporated, including 43 males and 11 females aged 14-79 years old. There are 29 renal transplant recipients, 19 liver transplant recipients and 6 heart transplant recipients. The types of PD-1 monoclonal antibody agent used by SOT recipients included pembrolizumab for 28 patients and nivolumab for 26 patients. The overall remission rate, disease progression rate and fatality rate of PD-1 monoclonal antibody for postoperative malignant tumors of SOT recipients were 32% (17/54), 44% (24/54) and 36% (19/54), respectively. After treatment with PD-1 monoclonal antibody for postoperative malignant tumors of SOT recipients, the incidence of rejection was 39% (21/54), indicating no significant correlation between rejection and type of PD-1 monoclonal antibody (P > 0.05). Conclusions PD-1 monoclonal antibody can effectively treat postoperative malignant tumors of SOT recipients, and may induce rejection during the treatment. But rejection is not the most common cause for death of recipients.
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Objective To evaluate the outcome of 1iver transplantation for acute-on-chronic liver failure (ACLF) patients .Methods We included 453 consecutive patients with previously cirrhosis who underwent liver transplantation between January 2013 and December 2017 .Patients were categorized as no ACLF (n=294) and ACLF(n=159) according to EASL-CLIF consortium criteria .Furthermore ,we used ACLF grades to categorize the ACLF patients .Their clinical data were reviewed and their 90-days survival outcomes were compared .Results Compared with the no ACLF group ,the length of stay in the ICU was significantly prolonged for all patients with ACLF ,and the 90-days survival rate after transplantation was significantly reduced in ACLF group .The length of stay in the ICU was shorter in Grade 1 and Grade 2 group when compared to Grade 3 group .The 90-days survival rate of no ACLF ,Grade 1 ,Grade 2 and Grade 3 group were 93 .20％ ,92 .59％ ,93 .33％ and 73 .68％ ,respectively .There were no statistically significant differences in 90-days survival rate among the no ACLF ,Grade 1 and Grade 2 group .However , the 90-days survive rate of Grade 3 group was lower than that of other groups .Conclusions Liver transplantation has been shown to be safe and effective with good outcome in patients with ACLF and should be offered in early course of ACLF before onset of multi-organ failure .
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Objective To evaluate the effect of donor risk index (DRI) on the early prognosis of liver transplantation for acute-on-chronic liver failure (ACLF). Methods Clinical data of 159 ACLF recipients undergoing liver transplantation were retrospectively analyzed. According to the calculation formula of DRI, all recipients were divided into DRI < 1.65 group (n=96) and DRI≥1.65 group (n=63). Based on the Chronic Liver Failure Consortium acute-on-chronic liver failure score (CLIF-C ACLFs), all recipients were divided into CLIF-C ACLFs < 48 group (n=78) and CLIF-C ACLFs≥48 group (n=81). The early prognosis indexes including the length of intensive care unit (ICU) stay and the length of postoperative hospital stay of the recipients in each group were observed after liver transplantation. The 90 dsurvival rate of the recipients after liver transplantation was analyzed by Kaplan-Meier survival curve. The risk factors affecting the early prognosis of ACLF recipients after liver transplantation were analyzed by Cox's hazards regression model. Results The length of ICU stay and the length of postoperative hospital stay did not significantly differ between the DRI < 1.65 group and DRI≥1.65 group (both P > 0.05). The length of postoperative hospital stay did not significantly differ between the CLIF-C ACLFs < 48 group and CLIF-C ACLFs≥48 group (P > 0.05). The length of ICU stay in the CLIF-C ACLFs < 48 group was 4 (3-14) d, significantly shorter than 7 (1-33) d in the CLIF-C ACLFs≥48 group (P < 0.05). The CLIF-C ACLFs was a risk factor of the early prognosis of ACLF recipients after liver transplantation (P < 0.05). The postoperative 90 d survival rate did not significantly differ between the DRI < 1.65 group and DRI≥1.65 group (P > 0.05). The postoperative 90 d survival rate in the CLIF-C ACLFs < 48 group was 94%, significantly higher than 79% in the CLIF-C ACLFs≥48 group (P < 0.05). Conclusions The early prognosis of ACLF recipients after liver transplantation is correlated with the severity of the disease rather than the DRI. Liver transplantation should be performed early and promptly.
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Objective To construct the orthotopic mouse liver transplantation model and cover troubleshooting,in order to provide experimental techniques support for organ transplantation pathology and immunology studies.Methods Male C57BL/6 mice,10-12 weeks,were selected as the allograft donors.Male C3H mice with same age were selected as the allograft recipients.The orthotopic mouse liver transplantation model consisted of 3 stages,including harvesting the donor liver,back-table preparation of the liver graft and transplantation of the donor liver into the recipient.The average time for harvesting the donor livers was (40 ± 8.8) min,(23 ± 4.7) min for preparing the donor livers and (75 ± 9.6) min for transplanting the donor livers into the recipient.Results Seventy pairs of mice were used for the preliminary experiments.For the formal experiments,the allograft transplantation was established on 220 pairs with 90.4％ successful rate.Conclusion It is the skillful and high quality microsurgical technique that is the guarantee of establishing the orthotopic mouse liver transplantation model successfully.
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ObjectiveTo investigate the expression of T helper (Th) 17 cells and the related interleukin 17 (IL-17) in acute renal allograft rejection in mice and its significance.Methods We established a mouse renal allograft model,in which mice were randomly divided into a renal isograft group and an acute renal allograft rejection group.Three and 7 d after the transplantation,the serum interferon (IFN)-γand IL-17 levels in the mice were determined by enzyme-linked immunosorbent assay,the percentage of Th1 and Th17 cells in the total kidney-infiltrating lymphocytes was investigated by flow cytometry,and the transplanted kidney species were given routine pathological examination after fixation with 10％ formalin.ResultsCompared with the isograft group,the allograft mice showed a significantly higher content of IL-17 (P ＜0.05 ) but not IFN-γ in the serum 3 d after transplantation,and showed significantly higher serum IL-17 and IFN-γcontents 7 d after transplantation (P ＜ 0.05 ).Also,compared with the isograft group,the allograft mice exhibited significantly higher percentage of Th1 and Th17 cells on both day 3 and day 7 ( P ＜ 0.05 ).In the allograft group,the contents of serum IFN-γand IL-17 and the percentage of Th1 and Th17 cells were significantly higher on day 7 than on day 3 (P ＜ 0.05 ).Routine pathological examination indicated that,as time passed,the allograft mice showed gradually stronger rejection responses.ConclusionTh17 cells might play an important role in the development of acute renal allograft rejection,and IL-17 can be used as an early indicator of acute rejection.
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OBJECTIVE@#To investigate the role of T helper cell 17(Th17) cells and their cytokines IL-17 in heart allograft rejection in mice.@*METHODS@#The heart transplantation models were randomly divided into 2 groups: a allograft group (n=12) and an isograft group (n=12).On the post-operative day (POD) 3 and 7, serum IL-17 level was tested by enzyme-linked immunosorbent assay, and Th17 cells in heart grafts were measured by flow cytometry. The heart grafts were harvested and saved in 10% formalin, and then embedded in paraffin.@*RESULTS@#Compared with the iso-graft group, the allograft group had a higher serum level of IL-17 on POD3 and POD7 (P<0.05), and the level of IL-17 was higher on POD7 than that on POD3 (P<0.05). The allograft group had more Th17 cells infiltrating in grafts on POD3 and POD7 (P<0.05) and there were more Th17 cells infiltrating on POD7 than that on POD3 (P<0.05). Histological examination showed that the prolongation of post transplantation time resulted in more rejection pathological changes.@*CONCLUSION@#Th17 cells may play an important role in the development of heart transplant rejection. IL-17 may serve as a predictive parameter for allograft rejection in the future.
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Animals , Male , Mice , Graft Rejection , Blood , Diagnosis , Allergy and Immunology , Heart Transplantation , Allergy and Immunology , Interleukin-17 , Blood , Mice, Inbred BALB C , Mice, Inbred C57BL , Random Allocation , Th17 Cells , Allergy and ImmunologyABSTRACT
Objective To study the efficacy of emergency orthotopic liver transplantation(EOLT) for acute(hepatic) failure(ALT).Methods A retrospective review was undertaken on the clinical data of 8 patients undergoing emergency liver transplantation for ALT.Results The 8 patients completely regained consciousness in 12 to 72 hours after operation.No case developed central nervous complications.One case of severe(hepatitis) complicated by acute renal failure died of respiratory infection and ARDS on postoperative day 7.One case who refused to take medication died from chronic rejection 12 months after operation.One case was(complicated) by bile duct stricture and biliary sludge at 14 months postoperatively and survived for 18 months.Four of the other 5 cases were followed up for 17 months and 1 cases for 14 months,and thir quality of life was excellent.3 of them have returned to work.Conclusions Emergency orthotopic liver thansplantation is an effective means to treat ALF.Intensive care and effective treatment preoperatively are pre-requisite(conditions) to ensure the success of EOLT.
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0.05).Anastomotic inflammatory reaction occurred in 2 patients(3.2%) in BAR group and 13 patients(20.0%) in manual group.The difference was statistically significant(P
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Objective To investigate the arterial blood supply of the pancreas head and provide a theoretical basis for the gastroduodenal artery reconstruction in pancreatic transplantation(PT).Methods Photograms of digital subtraction artery(DSA)which performing on 300 patients were analyzed to recognize the aberrations of arterial blood supply of pancreatic head.Results In 300 DSA photograms,the gastroduodenal artery(GD.a)was identified in 131 cases,and the anterior superior pancreaicduodenal artery(ASPD.a)and posterior superior pancreaicduodenal artery(PSPD.a)in 79 cases.The rate of aberrant origin of pancreatic transverse artery(PT.a)from GD.a was 12.98℅.There are some minor sources of blood supply to the pancreas head from GD.a.The rate of absence of an ASPD.a-AIPD.a anastomosis and PSPD.a-PIPD.a anastomosis was 15.19℅and 24.05℅,respectively.Conclusions The reconstruction of gastroduodenal artery can ensure a complete blood supply to the pancreatic head and duodenum in PT.