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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 investigate the correlation between serum microRNA (miR)-15a-5p and prognosis, neoadjuvant chemotherapy (NAC) response in patients with locally advanced gastric cancer (LAGC).Methods:The clinical data of 122 patients with LAGC who underwent surgery after NAC in Eastern Theater Air Force Hospital of the Chinese People′s Liberation Army from May 2016 to April 2020 were analyzed retrospectively. The general clinical data and laboratory examination results of the patients were recorded. The expression level of serum miR-15a-5p was detected by real-time fluorescence quantitative polymerase chain reaction, and the relationship between the expression of miR-15a-5p and different clinical characteristics in patients with LAGC was analyzed. The pathological response was evaluated by Becker tumor regression grading, in which patients with grade 1a, 1b and 2 were sensitive group and patients with grade 3 were resistant group.Results:The patients with LAGC were divided into high expression (>1.038) and low expression (≤1.038) according to the median miR-15a-5p of 1.038 with 61 cases each. The expression level of serum miR-15a-5p was related to the preference for spicy food, endoscopic ultrasonography (EUS)-T stage and EUS-N stage ( P<0.01 or <0.05). According to the evaluation result of pathological reaction, there were 47 cases in resistance group and 74 cases in sensitive group. The serum miR-15a-5p in resistance group was significantly higher than that in sensitive group: 1.69 (1.39, 1.97) vs. 0.99 (0.96, 1.02), and there was statistical difference ( Z =-8.55, P<0.01). The receiver operating characteristic curve analysis result showed that the area under the curve of serum miR-15a-5p predicting NAC response was 0.959 (95% CI 0.929 to 0.990), the optimal cut-off value was 1.049, the sensitivity was 100.0%, and the specificity was 85.1%. Multivariate Logistic regression analysis result showed that miR-15a-5p was an independent risk factor for NAC response in patients with LAGC ( HR = 1 880.840, 95% CI 123.510 to 28 641.846, P<0.01). Kaplan-Meier survival curve analysis result showed that the median overall survival time and median progression free survival time in patients with high expression of miR-15a-5p were significantly shorter than those in patients with low expression of miR-15a-5p (19 months vs. 62 months and 12 months vs. 51 months), and there were statistical differences (log-rank χ2 = 41.99 and 61.97, P<0.01); the 10-year overall survival rate and 10-year progression free survival rate in patients with high expression of miR-15a-5p were significantly lower than those in patients with low expression of miR-15a-5p (4.9% vs. 52.5% and 24.6% vs. 85.2%), and there were statistical differences (log-rank χ2 = 33.70 and 45.32, P<0.01). Multivariate Cox regression analysis result showed that R 0 resection and miR-15a-5p were the independent risk factors affecting the overall survival time and progression free survival time in patients with LAGC (overall survival time: HR = 1.945 and 3.487, 95% CI 1.033 to 3.660 and 2.112 to 5.759, P<0.05 or <0.01; progression free survival time: HR = 2.427 and 6.335, 95% CI 1.069 to 5.510 and 3.341 to 12.013, P<0.05 or <0.01). Conclusions:The increase of serum miR-15a-5p level is related to NAC response and poor prognosis in patients with LAGC. It can be used as a reliable biomarker to predict the prognosis and NAC response of LAGC.
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Objective To evaluate the clinical efficacy of liver transplantation in children with Alagille syndrome (ALGS). Methods Clinical data of 12 children with ALGS were collected and retrospectively analyzed. Clinical characteristics of children with ALGS, pathological characteristics of liver tissues, characteristics of liver transplantation, postoperative complications and follow-up of children with ALGS were analyzed. Results JAG1 gene mutation and typical facial features was present in all 12 children. Jaundice was the most common initial symptom, which occurred at 7 (3, 40) d after birth. Upon liver transplantation, the Z scores of height and body weight were calculated as -2.14 (-3.11, -1.83) and -2.32 (-3.12, -1.12). Five children developed severe growth retardation and 4 children with severe malnutrition. Eight of 12 children were diagnosed with cardiovascular abnormalities. Pathological examination showed that the lobular structure of the diseased livers of 4 children was basically maintained, and 8 cases of nodular liver cirrhosis in different sizes including 1 case of single early moderately-differentiated hepatocellular carcinoma. Three children were misdiagnosed with biliary atresia and underwent Kasai portoenterostomy. Eight children underwent living donor liver transplantation, three children underwent cadaveric donor liver transplantation (two cases of split liver transplantation and one case of cadaveric total liver transplantation), and one child underwent domino liver transplantation (donor liver was derived from a patient with maple syrup urine disease). during the follow-up of 30.0(24.5, 41.7) months, the survival rates of the children and liver grafts were both 100%. During postoperative follow-up, the Z scores of height and body weight were calculated as -1.24 (-2.11, 0.60) and -0.83 (-1.65, -0.43), indicating that the growth and development of the children were significantly improved after operation. Conclusions Liver transplantation is an efficacious treatment for children with ALGS complicated with decompensated cirrhosis, severe itching and poor quality of life. For children with ALGS complicated with cardiovascular abnormalities, explicit preoperative evaluation should be delivered, and consultation with pediatric cardiologists should be performed if necessary.
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Objective@#To investigate the prevalence and association of hyperuricemia (HUA) and hypertriglyceridemic Waist (HTW) phenotype in children and adolescents aged 6-17 years in Inner Mongolia, providing a basis for the prevention and treatment of hyperuricemia in adolescents in Inner Mongolia.@*Methods@#A total of 2 175 students of primary, junior high, and senior high school students from eight counties (districts) in Inner Mongolia were chosen and received a questionnaire survey, physical examination, and laboratory test by used a multi stage stratified random sampling approach. The association between the HTW phenotype and HUA was analyzed using binary Logistic regression.@*Results@#The prevalence of the HTW phenotype was 2.1%, with boys(2.5%) higher than that of girls(1.6%) ( χ 2=14.50, P<0.05). The average SUA level of the participants was 308.00 (259.00, 371.00) mmol/L, with a statistically significant sex difference(Z=-9.87, P<0.05). The prevalence of HUA was 21.1%. The frequency of HUA in the HTW phenotype(44.4%) was higher than in other phenotypes, followed by enlarged waist (EW) phenotype. After controlling for associated variables, the EW phenotypes (OR=1.76，95%CI=1.26-2.47) and HTW phenotypes (OR=2.25, 95%CI=1.12-4.52) were associated with higher risk for HUA(P<0.05).@*Conclusion@#In Inner Mongolia, the prevalence of HUA in children and adolescents aged 6-17 years is high, and there shows a positive association between the HTW phenotype and hyperuricemia. For the prevention of hyperuricemia, more attention should be paid to children and adolescents with HTW phenotype.
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Objective@#To investigate the prevalence and association of hyperuricemia (HUA) and hypertriglyceridemic Waist (HTW) phenotype in children and adolescents aged 6-17 years in Inner Mongolia, providing a basis for the prevention and treatment of hyperuricemia in adolescents in Inner Mongolia.@*Methods@#A total of 2 175 students of primary, junior high, and senior high school students from eight counties (districts) in Inner Mongolia were chosen and received a questionnaire survey, physical examination, and laboratory test by used a multi stage stratified random sampling approach. The association between the HTW phenotype and HUA was analyzed using binary Logistic regression.@*Results@#The prevalence of the HTW phenotype was 2.1%, with boys(2.5%) higher than that of girls(1.6%) ( χ 2=14.50, P<0.05). The average SUA level of the participants was 308.00 (259.00, 371.00) mmol/L, with a statistically significant sex difference(Z=-9.87, P<0.05). The prevalence of HUA was 21.1%. The frequency of HUA in the HTW phenotype(44.4%) was higher than in other phenotypes, followed by enlarged waist (EW) phenotype. After controlling for associated variables, the EW phenotypes (OR=1.76，95%CI=1.26-2.47) and HTW phenotypes (OR=2.25, 95%CI=1.12-4.52) were associated with higher risk for HUA(P<0.05).@*Conclusion@#In Inner Mongolia, the prevalence of HUA in children and adolescents aged 6-17 years is high, and there shows a positive association between the HTW phenotype and hyperuricemia. For the prevention of hyperuricemia, more attention should be paid to children and adolescents with HTW phenotype.
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Objective:To explore the feasibility of using vascular graft interposition for lowering the complications of portal vein during pediatric liver transplantation.Methods:From June 1, 2013 to May 31, 2018, clinical data were collected for 297 children undergoing liver transplantation, including basic demographics, general preoperative status, preoperative tests, imaging findings, graft related profiles, surgical procedures and postoperative follow-ups, etc. Then the authors analyzed the effect of using interposition vessels upon lowering postoperative complications of portal vein reconstruction.Results:With a median age of 12 months, there were 153 boys (51.5%) and 144 girls (48.5%). The primary disease was mostly biliary atresia ( n=222, 74.7%). The median diameter of portal vein was 5 mm. There were 19 cases (6.4%) using vascular interposition. Among 20 cases of portal vein complications, there were portal vein stenosis ( n=17, 5.7%) and portal vein thrombosis ( n=3, 1.0%). After univariate analysis, binary Logistic regression analysis revealed that diameter of recipient's portal vein was an independent risk factor for the occurrence of portal vein complications after liver transplantation. Statistical analysis of children with portal vein diameter <4 mm ( n=90) was carried on and the results showed that there was no inter-group statistical difference ( χ2=3.061, P=0.080)on the occurrence of portal vein complications. Conclusions:Diameter of portal vein is an important factor affecting the strategic choice of portal vein reconstruction during pediatric liver transplantation and an independent risk factor for portal vein complications after liver transplantation. When the diameter of portal vein is ≤4 mm, using interposition vascular anastomosis shows no significant difference with other conventional modes.
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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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Objective:To review our experience in the use of "Full right-Full left" split liver transplantation in adult-to adult or adult-to adult-size child.Methods:The clinical data of liver donors to 4 recipients of full right-full left split liver transplantation performed at Beijing Friendship Hospital of Capital Medical University from January to December 2019 were reviewed. The surgical methods of split liver transplantation, cold ischemia time, operation time, intraoperative blood transfusion, and postoperative complications and prognosis were analyzed.Results:The 4 recipients of complete right hepatic-left hepatic split liver transplantation included 3 adults and 1 heavy child (45 kg). Their ages ranged from 14 to 48 years, and body weight ranged from 45 to 61 kg. The end-stage liver disease model score were 21, 12, 41, and 30 points. The ratios of graft mass to recipient's body mass ranged from 0.85% to 1.35%. The cold ischemia time was 457-650 min, and the operation time was 460-575 min. Early liver function recovered smoothly in all the 4 patients after transplantation, and no small liver syndrome occurred. Patients were followed up to 6 months after operation. One patient developed anastomotic biliary leak, which was cured by endoscopic retrograde cholangiopancreatographic treatment. Another patient developed biliary stricture presenting with repeated biliary tract infection despite percutaneous transhepatic puncture biliary drainage. A third patient died six months from lung infection.Conclusion:In properly selected patients, using full right-full left hemiliver by split liver transplantation increased organ utilization and provided patients with increased treatment opportunities.
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Gastroesophageal varices hemorrhage is a common complication of portal hypertension. Drug and endoscopic therapy have become the basic treatments for varices. Transjugular intrahepatic portal venous shunt is recommended for the management of refractory or recurrent variceal hemorrhage. Liver transplantation will be considered when variceal hemorrhage becomes fatal and traditional therapies are with high risk, contraindicated, or have unsatisfactory results. Patients who received traditional treatments can achieve short-term efficacy and even stabilize the disease for a long time. However, if these treatments lead to complications such as portal vein thrombosis and hepatorenal syndrome, it may increase the risk of liver transplantation complications and affect the patient’s prognosis. Elevated portal venous pressure has a variety of adverse effects on systemic circulation, which can cause hepatopulmonary syndrome, portal pulmonary hypertension, refractory ascites, etc. In these cases, liver transplantation should be performed as early as possible. Conventional treatments are unsatisfactory. In addition, frailty may be worsened after traditional treatment, which will significantly increase the risk of liver transplantation. With the increase of model for end-stage liver disease, the requirement for donor liver volume will also has been increased, which will also affect the implementation of living donor liver transplantation. Some patients with portal hypertension may have poor quality of life and it may also become a clinical indication for liver transplantation. These liver transplant-related issues should be evaluated when administering traditional therapies. Traditional therapies aimed at improving the patient's condition, delaying or controlling complications should not interfere with the consequent implementation of liver transplantation. Improving the long-term overall survival rate and quality of life of patients with portal hypertension is the ultimate standard of all treatments.
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Objective:To study the hepatic hemodynamics changes and pathophysiological mechanisms of the use of a functional shunt after auxillary liver transplantation to treat portal hypertension associated with a small-for-size graft.Methods:A retrospective analysis of the clinical data of patients with portal hypertension treated with functional shunting of small-volume grafts from a living donor liver at the Beijing Friendship Hospital, Capital Medical University from July 2014 to December 2018, and a total of 6 patients were included as the research objects, including 4 males and 2 females, with a median age of 35.5 (29.0-52.0) years old. Blood flow monitoring data were collected during and after operation, and the characteristics of liver hemodynamics were analyzed.Results:The portal venous blood flow of the remnant native liver gradually decreased to no flow. As a buffer response, the flow velocity of hepatic artery increased. The portal venous blood flow of the graft gradually increased in the early postoperative period and then gradually decreased from post-operation Day 5 to 10 due to gradual increase in portal venous resistance. However, the portal venous perfusion gradually increased from Day 10 after the operation, reached to a level and declined to a stable level about 1 month after the operation. The volume of abdominal drainage slowly decreased after the peak level at Day 5-10 after the operation, and disappeared completely at Day 30 after operation.Conclusions:When using auxiliary liver transplantation for functional shunting to treat portal hypertension, autologous residual liver can act as a guide buffer for the pressure gradient of portal vein hyperperfusion in liver transplantation, and reach a steady state of blood flow distribution about 1 month after surgery, while relying on autologous remnant liver hepatic artery buffer response prevents small liver syndrome.
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There are significant differences in origin and development between pediatric liver malignancies and adult liver malignancies, and even for the same type of liver cancer, there are still differences in its development, progression, therapies, and treatment outcome between children and adults. The histological manifestation and anatomical location of pediatric liver malignancies can reflect the characteristics of invasion and metastasis, the difficulty in surgical treatment, and the sensitivity of drug therapy. Therefore, treatment modalities should be selected based on these characteristics. Pediatric liver malignancies are more sensitive to adjuvant therapy such as chemotherapy, and the combination with adjuvant therapies, such as chemotherapy, before or after liver transplantation may achieve satisfactory results and thus expand the indications for liver transplantation. Among pediatric liver malignancies, hepatoblastoma, hepatocellular carcinoma, and undifferentiated embryonal sarcoma is more common and can be treated by liver transplantation with satisfactory prognosis. Liver transplantation should be considered for children with malignant liver tumors confined to the liver and poor response to liver resection.
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Objective According investigate the expression of NLRP3 in liver tissues of mice with hepatic ischemia-reperfusion injury (HIRI),to determin the role of NLRP3 in the process of HIRI.Methods Established mice model of partial HIRI.Forty-two male C57BL/6 mice (aged 7 to 8 weeks,weight 20 to 25 g) were respectively divided into 7 groups:no-treatment control group,sham operation group,HIRI groups (2、6、12、24 h) and CY-09 group,6 mice in each group.The injury of the hepatic tissues in the 7 groups was analyzed based on detecting the levels of alanine transaminase (ALT),aspartate transaminase (AST),interleukin-1β (IL-1β),interleukin-18 (IL-18),tumor necrosis factor-α (TNF-α) by ELISA.HE and TUNEL staining were used to observe the pathological changes of liver tissues after HIRI.Western blotting assay were carried out to detect the expressions of NLRP3 and Caspase-1.Measurement data were expressed as mean ± standard deviation (Mean ± SD),and one-way variance analysis was used for comparison between groups.If the variance was not uniform,Dunnett C test was used.Results Serum ALT,AST,IL-1 β,IL-18 and TNF-α of mice detected in HIRI groups were higher than no-treatment control group and sham operation group at all endpoints (P ＜ 0.05).The relative expression of NLRP3 and Caspase-1 in the liver tissues of mice in the HIRI groups were significantly higher than that in the no-treatment control group and sham operation group.Serum ALT,AST,IL-1β,IL-18 and TNF-α of mice detected in CY-09 group were lower than HIRI groups at all endpoints (P ＜ 0.05).Less hepatocellular necrosis were exhibited in CY-09 group,comparing to HIRI groups.The hepatocyte apoptosis rate of mice in the CY-09 group was significantly lower than that in the 12 h HIRI group (P ＜ 0.05).The relative expression of NLRP3 in the liver tissues of mice in the CY-09 group was significantly lower than that in other groups.The relative expression of Caspase-1 in the liver tissues of mice in the CY-09 group was significantly lower than that in other groups except the no-treatment control group and sham operation group.Conclusions HIRI cause an increase in NLRP3 expression.The inhibition of NLRP3 can reduce HIRI.
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Objective To evaluate the effect of donor-derived infection on the clinical prognosis of the recipients undergoing liver transplantation. Methods Clinical data of 75 donors and recipients undergoing liver transplantation were retrospectively analyzed. According to the culture results of donor organ lavage fluid, all recipients were divided into the positive group (n=26) and negative group (n=49). Clinical parameters of the recipients during perioperative period were observed in the positive and negative groups. The sputum and peritoneal drainage fluid of the recipients undergoing liver transplantation were cultured. The incidence of postoperative infection of the recipients was observed. The 1.5-year survival curve of the recipients was analyzed by Kaplan-Meier method. Results In the positive group, the incidence of portal vein stenosis and thrombosis was significantly higher than that in the negative group (P < 0.05). Among 75 recipients undergoing liver transplantation, 33 cases (44%) developed postoperative infection mainly in the lung and abdominal cavity. The infection rate significantly differed between the positive group (77%) and negative group (27%, P < 0.05). In the positive group, sputum culture was positive in 10 recipients and peritoneal drainage culture was positive in 11 recipients. The sputum culture outcomes of 4 recipients were consistent with those of the organ lavage fluid culture of their donors. The peritoneal drainage culture results of 6 recipients were consistent with those of the organ lavage fluid culture of their donors. After anti-infection treatment, 2 recipients in the positive group died at postoperative 5 and 12 d, and the culture results of the remaining recipients were negative. In the negative group, 7 recipients were positive for sputum culture and 6 recipients were positive for peritoneal drainage culture. The culture results of all recipients were negative following anti-infection therapy. Two recipients died from graft failure at postoperative 1 month and 1 year. The 1.5-year survival rate did not significantly differ between the positive and negative groups (P > 0.05). Conclusions The effect of donor-derived infection on the early prognosis of liver transplant recipients cannot be neglected, whereas it exerts mild impact on the intermediate- and long-term clinical prognosis of the recipients.
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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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Hepatocellular carcinoma (HCC) is the most important cause of adult liver transplantation in China. HCC recurrence after liver transplantation is a common clinical problem. It is imperative to explore its metastasis and recurrence mechanism and to develop effective prevention and treatment strategies. This article describes the basic prevention and treatment strategies for recurrent HCC after liver transplantation. During the pre-transplant period, the clinical and pathological information of HCC, such as tumor staging, general morphology, pathological features, tumor markers and tumor molecular biological characteristics, should be collected and analyzed carefully in order to determine the risk of recurrent HCC; Design and implement a comprehensive program of prevention and treatment. Currently, sorafenib and capecitabine are common candidate drugs for prevention and control of recurrence of HCC after liver transplantation. Substitution of m-TOR inhibitors for CNI-like drugs can be used as an immunosuppressive drug to prevent and control recurrence of HCC. HCC recurrence after liver transplantation will significantly reduce the cure rate, but active treatment often can effectively control the progression of the disease and improve the prognosis. However, available effective measures to prevent the progress of HCC can also be used to treat HCC recurrence after liver transplantation. Surgical treatment is preferred for recurrent lesions that can be resected, and local treatment is available for recurrent lesions that cannot be resected. Drug treatment can inhibit tumor growth to a certain extent, but it is difficult to achieve a satisfying prognosis by single drug, commonly used as adjuvant therapy.
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Objective To investigate the effect of miRNA-30a-3p on the proliferation,invasion and metastasis of liver cancer cells by targeting Atg3-mediated autophagy pathway.Methods The immunohistochemical staining was used to detect content of miRNA-30a-3p and Atg3 and their correlation in human hepatocellular carcinoma.Liver cancer cells were cultured in vitro and hunger environment was used to induce autophagy.RFP-GFP-LC3 double-labeled adenovirus infected hepatoma cells were used to detect autophagosomes in hepatoma cells.The expressions of autophagy-related proteins (autophagocytosis associated protein (Atg3),polyubiquitin-binding protein p62,autophagy microtubule-associated protein light chain 3 (LC3)) and EMT-related proteins (N-cadherin,vimentin,snail,ZO-1) were detected by Western blot.Platelet cloning assay and transwell assay were carried out to detect the proliferation,invasion and metastasis of carcinoma cell.CCK-8 kit was used to detect hepatocarcinoma cells' viability.Results The expression of miRNA-30a-3p was down-regulated.The expression of Atg3,E-cadherin and N-cadherin in miRNA-30a-3p high-expressed hepatocellular carcinoma was lower than that in miRNA-30a-3p low-expressed hepatocellular carcinoma.Increasing the expression of miRNA-30a-3p in hepatocellular carcinoma cells can decrease the expression of Atg3 and LC3,increase the expression of p62 and inhibit the formation of autophagosomes;otherwise,Atg3 and LC3 were increased,p62 was decreased and the formation of autophagosomes was promoted.Inhibition of Atg3 expression could decrease the expression of EMT-related proteins.When miRNA-30a-3p was inhibited,the cell viability of HCC was increased at each time point (F1 =10.314,P ＜0.05).When miRNA-30a-3p and Atg3 were inhibitor together,the cell viability of HCC was decreased at each time point(F2 =6.599,P ＜ 0.05).Conclusion miRNA-30a-3p can inhibit Atg3-mediated autophagy pathway and reduce cell autophagy activity,thus inhibiting the proliferation,invasion and metastasis of hepatocarcinoma cells.
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Objective To investigate the role of interferon regulatory factor-1 (IRF-1) in liver ischemia/reperfusion (IR) injury and its underlying mechanism,and identify effective managements in alleviating liver IR injury.Methods Three groups of mice models with liver IR injury were well established,including control group (S),warm liver IR injury group (IR) and recombinant IRF-1 group (IRF-1).The levels of mRNA and protein,liver function and pathological changes of liver tissue were detected in group S and group IR.Additionally,the marker of IRF-1,p-Stat1,p-P38,PARP1 and Caspase-3 were measured and PCNA expression was determined in group IR and group IRF-1 mice with 6-hour liver IR injury.Results IRF-1 mRNA and protein and the levels expression of proteins were significantly elevated with peak occurred after 6-hour IR injury,which was statistic difference compare to the group S (t2h =-3.512,t6h =-4.247,t12h =-4.088,t24h =-3.851;P ＜ 0.05).Serum ALT and AST of mice detected in group IR were higher than group S at all endpoints (tALT =4.931,4.592,4.277,4.809;tAST =4.980,4.617,4.336,4.915;P ＜ 0.05).Furthermore,pathological damage change was more distinct compared with group S.The elevated levels of IRF-1,p-Statl,p-P38,PARP1 and Caspase-3 and decreased PCNA expression were determined in mice models with recombinant IRF-1 intervention.Conclusion IRF-1 expression could be closely correlated with liver IR injury,and its underlying mechanism may be attributed to activation of JNK MAPK protein and inhibition of PCNA expression.
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This article introduced the main biological mechanisms of acupuncture promoting nerve function recovery after spinal cord injury, which include inhibition of inflammation and oxidative stress, alleviation of neuropathic pain, increase of neurotrophic active sub-stance, regulation of cell survival/apoptosis gene and neural regeneration pathway.
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Objeetive To analyze the clinical efficacy of liver transplantation (OLT) for patients with hepatopulmonary syndrome (HPS).Methods From 2008 to 2013,420 adult patients underwent liver transplantation in our hospital.There were 91 patients with,and 329 patients without,HPS.The 5-year survival and mortality rates after OLT for the two groups were retrospectively analyzed.Results There were no significant differences between patients without and with HPS in age,primary disease,Child-Pugh score,MELD score,cold ischemia time and warm ischemia time.However,the differences on serum albumin [(29.6 ± 1.2) g/L vs.(26.4 ± 1.6) g/L] and blood oxygen pressure [(61.0 ±9.0) mmHg (1 mmHg =0.133 kPa) vs.(87.0 ± 6.0) mmHg] were significantly different (P ＜ 0.05).The 1-year cure rate was 65.9％ (60/91) in 91 patients with HPS after liver transplantation.The 1,3,5-year cumulative survival rates for patients without HPS were 97.3％,90.9％ and 80.3％,respectively,and the main causes of death were primary graft dysfunction,recurrent cardiovascular events and primary disease recurrence or tumors.The 1,3,5-year cumulative survival rates for patients with HPS were 65.9％,59.3％ and 56.0％,and the main causes of death were multiple-organ failure,pulmonary infection and cerebrovascular events.Kaplan-Meier survival curve analysis showed that the survival of patients with HPS was significantly lower than that of patients without HPS (P ＜ 0.05).Conclusions Liver transplantation is the most effective treatment for patients with HPS,but the short-term mortality rate is relatively high.We still need to learn more about HPS to improve the survival rate of patients with HPS after liver transplantation.
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Evoked potentials can reflect the integrity of spinal sensory and motor conduction pathway.Evoked potential exami-nation not only provides relatively objective index for patients with spinal cord injury in preoperative diagnosis,intraoperative monitoring and prognosis judging,but also plays an irreplaceable role in evaluating animal models for spinal cord injury.This pa-per systematically reviews evoked potential in the clinical exami-nation of spinal cord injury and its application in evaluating ani-mal models.