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Objective:To investigate the role of signal lymphocyte activating molecule family member 5 (SLAMF5) in liver transplantation rejection in SD rats.Methods:Forty-five male SD rats without special pathogens, weight 260-300 g, aged 10-12 weeks were included. Among them, forty male SD rats (20 donors and 20 recipients respectively) were established with reference to the " two cuff" method. 15 liver transplantation model rats were randomly divided into 1 week (LT-1W) group, 2 weeks (LT-2W) group and 3 weeks (LT-3W) group, with 5 rats in each group, and 5 normal rats were taken as the normal control group. The expressions of SLAMF5, CD4 and CD8 were detected by polymerase chain reaction (PCR), Western blot and immunohistochemistry. The correlations between SLAMF5 expression in the lymphocyte infiltration area and the rejection activity index was analyzed.Results:The levels of alanine aminotransferase, aspartate aminotransferase and total bilirubin were significantly higher in LT-1W group, LT-2W group and LT-3W group than those in the normal control group (all P<0.05). PCR results showed that the relative expression of SLAMF5 mRNA were (5.44±1.11), (4.69±1.12), (2.18±0.68) respectively, which were increased in LT-1W group, LT-2W group and LT-3W group than those in normal control group (1.01±0.23), and the differences were statistically significant (all P<0.05). Immunohistochemical staining showed that SLAMF5 and CD4, CD8 positive T cells were mainly distributed in the portal area, hepatic lobule area and around the proliferative bile duct, and there was a certain overlap. Correlation analysis showed that there was a positive correlation between the expression of SLAMF5 in the lymphocyte infiltration area and the rejection activity index ( r=0.519, P=0.048). Conclusion:The expression of SLAMF5 is increased after liver transplantation in SD rats, and there is a correlation between SLAMF5 expression and liver transplantation rejection in rats.
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Objective:To study the effect of microRNA (miR)-330-3p on hepatic ischemia-reperfusion injury (IRI) in mice, meanwhile, and to determine potential molecular mechanism.Methods:Eighty male C57BL/6 mice, aged 7-8 weeks, 23-25 g, specific pathogen free, were randomly divided into 8 groups (10 mice in each group) using random number table: reperfusion 2 h group, 6 h group, 12 h group, 24 h group, sham group, miR-330-3p agomir group (preoperative injection of agonist), miR-330-3p antagomir group (preoperative injection of inhibitor) and miRNA-NC group. Except for the sham group, the hepatic IRI model were established in mice. Polymerase chain reaction (PCR), Western blot and immunohistochemistry were used to detect the expression of miR-330-3p and phosphoglycerate mutase family member 5 (PGAM5), cleave caspase-1 and GSDMD. Luciferase reporter assay was performed to investigate whether miR-330-3p directly targets PGAM5. At the same time, AML12 cells were also treated with miR-330-3p mimics/inhibitor or PGAM5 siRNA, then the expression of PGAM5, NLRP3, cleave caspase-1 and GSDMD were detected by Western blot analysis.Results:Level of miR-330-3p gradually decreased after reperfusion, however, mRNA level of PGAM5 was increased thereafter ( P<0.05) as compared with the sham group. Serum level of AST and ALT were decreased in miR-330-3p agomir group while that of were increased in miR-330-3p antagomir group as a function of time following reperfusion, and the differences were statistically significant (all P<0.05). Cleave caspase-1 expression was decreased in miR-330-3p agomir group but was increased in miR-330-5p antagomir group ( P<0.05). Luciferase reporter assay was performed to determine PGAM5 was a target gene of miR-330-3p. SiRNA-mediated knockdown of PGAM5 decreased level of GAM5 (0.24±0.09), NLRP3(0.12±0.07), cleave caspase-1 (0.15±0.07) and GSDMD (1.08±0.08) as compared with the siRNA-NC group (1.17±0.14), (0.36±0.09), (0.68±0.09), (1.36±0.08), and the differences were statistically significant (all P<0.05). Conclusion:MiR-330-3p can alleviate hepatic IRI in mice, which may be related to inhibition of PGAM5-induced pyroptosis.
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To analyzed a case of pediatric patient with propionic acidemia combined with dilated cardiomyopathy retrospectively, who underwent living donor liver transplantation at the Liver Transplantation Center, Beijing Friendship Hospital, Capital Medical University in March 2019.A 2 years and 6 months female child was admitted to hospital for propionic acidemia.The pretransplant echocardiogram showed left ventricular dilatation and systolic dysfunction, and thus dilated cardiomyopathy was considered.A living donor liver transplant was performed using her mother′s left latera-llobe.On the 14 months postoperatively, the child was on a liberated protein diet, but still required levocarnitine supplementation.Her hepatic and cardiac function returned normal, but growth retardation was still present.During the follow-up period, further propionic acidemia-related complications like metabolic decompensation, or any transplant-related complications were not reported.This case report suggested that liver transplantation is effective on pediatric propionic acidemia combined with cardiomyopathy, which reverses cardiomyopathy, improves cardiac function, relieves strict protein restriction, reduces the risk of metabolic decompensation, and significantly improves quality of life.
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Objective To investigate the safety and effectiveness of anatomical partial splenectomy during liver transplantation in pediatric patients to prevent postoperative refractory hypersplenism.Methods From January 2015 to August 2018,7 pediatric patients with preoperative severe hypersplenism underwent anatomical subtotal splenectomy together with liver transplantation at our institution.Clinical informations,including operative time,intraoperative bleedinh,postoperative hospital stay,postoperative complications,platelet counts,leukocyte counts and the length and thickness of spleen determined by abdominal ultrasound,were collected retrospectively and statistically analyzed.Results The median total operation time was 495 min (320-768 min),the median intraoperative blood loss was 350 mL (300-1300 mL) and the median hospital stay was 19 days (14-55 days).Patients were followed up for 7.0-36.6 months (median 20.1 months).The length and thickness of spleen were reduced immediately from (18.89 ± 1.77) to (11.13 ± 2.28) cm (P＜0.001)and from (6.31 ± 0.53) to (4.97 ± 1.29) cm (P＜0.05),respectively.During the follow-up period of the first week,the mean platelet counts and leukocyte counts increased from (46.71 ± 18.91) × 109/L to (173.71 ± 73.15) × 109/L (P＜0.001) and from (1.59 ± 0.42) × 109/L to (11.12 ± 4.17) × 109/L (P＜0.001),respectively.During the one-year follow-up period,there was no residual splenic regrowth,and the peripheral blood cell counts remained normal.All patients survived to date with no procedure-related complications.Conclusions The anatomical subtotal splenectomy during liver transplantation in pediatric transplant recipients with preoperative severe splenomegaly and hypersplenism is a feasible option for the prevention of posttransplant refractory hypersplenism.
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Hypersplenism is a common and serious complication in patients with cirrhosis and portal hypertension. Currently, the therapeutic options for severe hypersplenism mainly include total splenectomy, partial splenic embolization, local thermal ablation, splenic artery ligation, surgical shunt, and partial splenectomy. This article discussed the current progress in the relative mechanisms and invasive treatment of severe secondary hypersplenism in the patients with cirrhosis and portal hypertension.
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Hypersplenism is a common and serious complication in patients with cirrhosis and portal hypertension.Currently,the therapeutic options for severe hypersplenism mainly include total splenectomy,partial splenic embolization,local thermal ablation,splenic artery ligation,surgicat shunt,and partial sple-nectomy.This article discussed the current progress in the relative mechanisms and invasive treatment of severe secondary hypersplenism in the patients with cirrhosis and portal hypertension.
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Objective To analyze the donor specific antibody (DSA) in liver transplantation,and discuss the therapeutic schemes.Methods We retrospectively analyzed prospectively collected samples from 139 cases of liver transplantation from September 1,2013 to July 1,2015.Luminex assays were applied to determine human leukocyte antigen,panel reactive antibody (PRA).For PRA positive cases,DSA,C1q and C4d were detected,and liver biopsy was done.Results Of 139 cases enrolled,there were 12 cases positive for DSAs,including 2 cases of PreDSA:1 case of Ⅰ DSA (HLA-A mismatch),and 1 case of Ⅱ DSA (HLA-DQ mismatch).Ten cases of de novo DSA (including 1 case of PreDSA) all were HLA-DQ mismatch.The liver biopsy on 5 cases showed hepatic fibrosis,early rejection and intrahepatic cholestasis,and only 2 cases showed positive C4d.Of 6 cases of DSA,5 cases showed positive C1q.In the patients positive for DSA,tacrolimus dose was adjusted postoperatively,adding mycophenolatemofetil or increasing its dose,or methylprednisolone and immunoglobulin given.Conclusion DSAs are important indicators of sensitized recipients in liver transplantation,associated with trends toward worse outcomes in patients or allografts.The monitoring of DSA is requisite in order to adjust the immunosuppressant.
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Objective:To detect the expression level of microRNA-634 (miR-634) in hepatocellular carcinoma (HCC) and its regulatory effect on the common biological behavior of hepatocellular carcinoma cells .Methods: Real-time fluorescence quantitative PCR (RT qPCR) method was used to detect HCC cell lines (HepG2, SMMC7721, BEL7402, bel7404, SNU739), 69 cases of HCC tissues and matching relative quantification of miR-634 paracancerous tissues and analysis of relationship between miR-634 expression and HCC patients gender, age, tumor size, degree of differentiation, child Pugh classification, BCLC staging, portal vein tumor thrombus and liver metastasis , while building a miR-634 eukaryotic expression vector and transfected into hepatocellular carcinoma cell lines, using live cell counting kit-8 CCK-8, flow cytometric annexin V/PI double staining and Transwell experiment to detect the transfection miR-634 on cell proliferation , apoptosis and invasion effects .Results:Compared with the normal human liver cell line L-02 and hepatocellular carcinoma cells miR-634 were decreased ( PSNU739>Bel7402>Bel7404>SMMC7721;69 cases of hepatocellular carcinoma ( HCC ) of miR-634 level ( 0.253 ±0.019 ) and lower than that of the matched paracancerous tissues ( P<0.05 ) , and related with the tumor size , degree of differentiation , BCLC stage , portal vein tumor thrombus and liver metastasis ( P<0.05 ) .Over expression in the transfected group 24-96 h after miR-634 level continues to rise , control group and blank vector transfected group differences were statistically significant ( P<0.05 );and the control transfection group and blank group compared to transfection proliferation inhibition rate , apoptosis rate was increased , but wear the number of cell membrane decreased, the difference was statistically significant (P<0.05).Conclusion:miR-634 in hepatocellular carcinoma tissues and cells were low expression and related to clinical pathological parameters , raised its level can inhibit the proliferation and invasion of hepatocellular carcinoma cells and induce apoptosis , for the prevention and treatment of liver cancer has an important reference value .