| 1.Prognostic impact of high sodium donor liver transplantation on the recipient and analysis of factors of transplantation liver lossBackgroundSince Professor Starzl performed the first liver transplant in 1963,liver transplantation has remained the only treatment for end-stage liver disease for 60 years.The shortage of donor livers has severely limited the development of liver transplantation,and the severe reality has forced the transplant communities to look to marginal donor livers to alleviate the severe mismatch between supply and demand.Marginal donor livers are generally considered to include high sodium donor livers,elderly donor livers,steatosis donor livers,donor livers after circulatory death,and split liver transplantation.Among them,the predonor high sodium state as a common state in the intensive care unit and how its donor liver affects the recipient’s prognosis has always been subject to different conclusions.ObjectivesTo investigate the effect of high-sodium donor liver transplantation from DCD on the prognosis of the recipient and the risk factors for transplantation liver loss.MethodsA retrospective cohort study was used.Clinicopathological data of 125 DCD liver transplantation donor livers and recipients,Of the 125 donors,there were 93 males and 32 females;92 males and 33 females,aged 48(41-55)years,admitted to Xijing Hospital of Air Force Military Medical University from January 2015 to June 2021 were collected.According to the last serum sodium level of the donor liver,9 cases with donor liver sodium level≥170 mmol/L were set as group 1(very high sodium),33 cases with donor liver sodium level≥150 mmol/L but<170 mmol/L were set as group 2(moderately high sodium);83 cases with donor liver sodium level<150 mmol/L were set as group 3(normal sodium),and the risk factors for liver loss in 125 transplantation cases were also discussed.Observation indexes:(1)Postoperative recovery.(2)Follow-up status and survival analysis.Normally distributed measures were expressed as X±S,and repeated measures were analyzed by repeated measures ANOVA;skewed measures were expressed as M[Q1,Q3],and the Kruskal-Wallis test was used for comparison between groups.Count data were expressed as absolute numbers,and the Pearson chi-square test or Fisher test was used.Survival curves were plotted using the Kaplan-Meier method,Log-rank test was used for survival analysis,and independent risk factors affecting the prognosis of transplanted liver were identified using a multifactorial Cox risk regression model.p<0.05 was considered a statistically significant difference.Results(1)Postoperative recovery.The changes of alanine aminotransferase(ALT),aspartate aminotransferase(AST),total bilirubin(TBil),alkaline phosphatase(ALP),prothrombin time(PT),international normalized ratio(IRI),albumin(Alb),and creatinine(Cr)in group 1 from postoperative day 1 to day 14 were 736±972 IU/L～75±46 IU/L,1290± 1651 IU/L～38±20 IU/L,102±98 μmol/L～33±11 μmol/L,66±34 IU/L～104±54 IU/L,19.9±3.3s～11.3±1.0s,1.76±0.31～1.00±0.08,34±5g/L～38±3 g/L,91 ±41 μmol/L～76± 19μmol/L,and the changes of the above indicators in group 2 were 505±377IU/L～48 ± 46IU/L,855±727 IU/L～24±17 IU/L,64±42 μmol/L～32±22 μmol/L,68±51 IU/L～91±46 IU/L,16.8±3.5 s～11.9± 1.2 s,and 1.47±0.30～1.04±0.09,33±4 g/L～40±5 g/L,106±32μmol/L～97±27 μmol/L,and the changes of the above indicators in group 3 were 637±525 IU/L～65±60 IU/L,929± 1193 IU/L～33±27 IU/L,66±48 μmol/L～33±36 μmol/L,64±28 IU/L～125±64IU/L,17.2±4.7s～13.3± 12.8s,1.51 ±0.42～1.05±0.13,35±6 g/L～39±4 g/L,and 105±44 μmol/L～94±40 μmol/L.The overall effect results showed that in the three groups of recipients after liver transplantation.The differences were statistically significant when comparing the trends of TBil changes(time effect,between-group effect,and interaction effect)in the 3 groups of recipients after liver transplantation(F between-group=5.42,F time=22.78,F interaction=3.85,P<0.05),and the differences were statistically significant when comparing the time effects of ALT,AST,ALP,PT,IRI,Alb,and Cr in the three groups of recipients after liver transplantation(F time=50.17,36.24,19.24,10.55,59.61,41.94,10.82,P<0.05).(2)Follow-up and survival analysis.125 recipients were followed up.9 recipients in group 1 had 2,0,0,0,0 cases of early allograft dysfunction(EAD),1-year postoperative biliary complications,1-year postoperative vascular complications,and 1-year postoperative rejection,respectively;33 recipients in group 2 had 2,3,0,1 cases of the above indexes,respectively;The above indexes were 10,20,1,6 cases in group 3 with 83 recipients,and the differences were not statistically significant when comparing the above indexes in the three groups χ2=1.58,0.60,5.19,1.62,0.97,P>0.05).The cumulative survival rates of transplanted liver at 1 and 3 years were 100.00%and 100.00%in group 1,94.74%and 77.16%in group 2,and 91.57%and 89.30%in group 3;the differences were not statistically significant when comparing the cumulative survival rates of the recipients in all the three groups(x2=2.69,P=0.260).The cumulative survival rates at 1 and 3 years were 100.00%and 100.00%in group 1,93.74%and 77.16%in group 2,and 89.40%and 86.00%in group 3.The differences were not statistically significant when comparing the cumulative survival rates of transplanted livers in the three groups(x2=1.94,P=0.380).(3)Single-factor Kruskal-Wallis analysis showed that recipient gender and warm ischemia time were potential risk factors for transplantation liver loss,and further multifactor analysis showed that warm ischemia time was an independent risk factor for transplantation liver loss.Multifactorial analysis showed that warm ischemia time(P<0.05)was an independent risk factor for transplantation liver loss.ConclusionHypernatremic donor livers,especially very high sodium donor livers,have limited prognostic impact on the recipient,and donor liver acquisition is to be done collaboratively by a skilled liver transplantation team to minimize warm ischemia time.2.Preliminary study of CD200-regulated macrophage activation on GTKO endothelial cytotoxicityBackgroundThe shortage of donor livers seriously hinders the routine performance of liver transplantation,and xenotransplantation may be a potential solution to address this bottleneck.With the advent of GTKO gene-edited pigs,hyperacute rejection in xenotransplantation has been better controlled,but other rejection reactions such as acute vascular rejection still threaten the survival of transplanted liver products.In acute vascular rejection,macrophages and NK cells are significantly infiltrated.Previous studies have shown that expression of human CD200 molecules in wild-type porcine vascular endothelial cells can inhibit macrophage toxicity and phagocytosis,but whether expression of human CD200 protein in GTKO gene edited porcine vascular endothelial cells can inhibit macrophage toxicity and phagocytosis needs further investigation.ObjectivesTo investigate whether expression of human-derived CD200 protein in GTKO porcine endothelial cells inhibits macrophage toxicity and phagocytosis,and the polarization of macrophages.Methods1.Monocytes from human peripheral blood were extracted and induced into M0 macrophages,while lentiviral infection of GTKO porcine vascular endothelial cells to express human-derived CD200 molecules.2.GTKO endothelial cells and GTKO/hCD200 endothelial cells were directly mixed with M0 macrophages respectively and co After culturing,GTKO endothelial cells expressing CD200 were assayed by CCK-8 method to inhibit macrophage cytotoxicity.3.GTKO endothelial cells and GTKO/hCD200 endothelial cells were co-cultured directly with M0 macrophages,respectively.After culturing,the direction of macrophage polarization was observed by quantitative reverse transcription-polymerase chain reaction(qRT-PCR).Results1.The percentage of monocytes after extraction and purification was above 95%,and about 70%of GTKO porcine vascular endothelial cells successfully expressed human CD200 protein by quantitative flow cytometry.2.After co-culture with M0 macrophages,GTKO/hCD200 endothelial cells had better viability than GTKO endothelial cells(P<0.05).3.After co-culture with M0 macrophages,qRT-PCR assay revealed that TNF-α,IL-1βpro-inflammatory factors were down-regulated(P<0.05)and CD163,CD206,MSR1 anti-inflammatory factors(M2 macrophage-associated markers)were up-regulated in macrophages co-cultured with GTKO/hCD200 endothelial cells compared with those cocultured with GTKO endothelial cells,where CD206,MSR1 were significantly different(P<0.05,n=4).4.GTKO endothelial cells could be successfully colonized under the renal envelope in immunodeficient mice.ConclusionExpression of human-derived CD200 protein in GTKO porcine endothelial cells inhibits macrophage toxicity,while macrophages polarize toward suppression of inflammation.Whether human-derived CD200 protein inhibits macrophage phagocytosis needs to be further explored.The above findings need to be validated in animal models. |
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