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Objective To evaluate the protective effect and the underlying mechanism of mesenchymal stem cell-derived extracellular vesicle (MSC-EV) on radiation-induced liver injury and liver cell line injury in mouse models. Methods C57BL/6 mice were randomly divided into the blank group, model group and MSC-EV treatment group (treatment group), with 9 mice in each group. AML12 cells were randomly divided into the control group, irradiation group and MSC-EV intervention group (intervention group). Animal and cell models with radiation-induced injury were established by one-time 15 Gy and 6 Gy X-ray irradiation, respectively. At 48 h after irradiation, liver tissues and serum samples of mice were collected and prepared for subsequent experiments. At 15 h post-irradiation, cell experiment was carried out. Serum levels of alanine aminotransferase (ALT), aspartate aminotransferase (AST) and content of malondialdehyde (MDA) in liver tissues and cells were measured. The relative expression levels of interleukin (IL)-1β, IL-6, transforming growth factor (TGF)-β and CXC chemokine ligand (CXCL)10 messenger RNA (mRNA) were detected by real-time fluorescent quantitative polymerase chain reaction (RT-qPCR). Liver tissues were prepared for hematoxylin-eosin (HE) staining to calculate liver pathological injury score. The apoptosis of liver tissues and cells was assessed by terminal deoxynucleotidyl transferase-mediated dUTP nick-end labeling (TUNEL) and propidiumiodide (PI) staining, respectively. The expression levels of glutathione peroxidase 4 (GPX4) and ferroptosis suppressor protein 1 (FSP1) proteins were detected by Western blot. The production level of reactive oxygen species (ROS) was detected by dihydroethidine (DHE) staining. The fluorescence intensity of mitochondrial permeability transition pore (mPTP) was determined. Results Compared with the blank group, serum levels of AST and ALT were up-regulated, and the relative expression levels of IL-1β, TGF-β and CXCL10 mRNA in the mouse liver tissues were up-regulated, and MDA content was increased, liver injury score was elevated, cell apoptosis rate was increased, intracellular ROS level was elevated, and the relative expression levels of GPX4 and FSP1 proteins in the mouse liver tissues were down-regulated in the model group, and the differences were statistically significant (all P<0.05). Compared with the model group, serum levels of AST and ALT were decreased, and the relative expression levels of IL-1β, TGF-β and CXCL10 mRNA in the liver tissues of mice were down-regulated, MDA content was declined, liver injury score was declined, cell apoptosis rate was decreased, intracellular ROS level was decreased, and the relative expression levels of GPX4 and FSP1 proteins in the liver tissues of mice were up-regulated in the treatment group, and the differences were statistically significant (all P<0.05). Compared with the control group, cell apoptosis rate was increased, intracellular ROS level was elevated, the fluorescence intensity of mPTP was weakened, the relative expression levels of IL-1β, TGF-β and IL-6 mRNA were up-regulated, MDA content was increased, and the relative expression levels of GPX4 and FSP1 proteins were down-regulated in the irradiation group, and the differences were statistically significant (all P<0.05). Compared with the irradiation group, cell apoptosis rate was declined, intracellular ROS level was decreased, the fluorescence intensity of mPTP was strengthened, the relative expression levels of IL-1β, TGF-β and IL-6 mRNA were down-regulated, MDA content was decreased and the relative expression levels of GPX4 and FSP1 proteins were up-regulated in the intervention group, and the differences were statistically significant (all P<0.05). Conclusions MSC-EV may effectively alleviate radiation-induced liver injury by reducing ferroptosis of liver cells, enhancing antioxidant level and decreasing the production of lipid peroxide, thereby effectively alleviating radiation-induced liver injury.
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Objective:To explore the safety and efficacy of camrelizumab salvage therapy for extrahepatic recurrent hepatocellular carcinoma with PD-L1 negativity in transplanted liver tissue.Methods:From May 2020 to December 2020, retrospective analysis was performed for 3 cases of camrelizumab salvage therapy for extrahepatic recurrent hepatocellular carcinoma recipients with PD-L1 negative in transplanted liver tissue.Three recipients with extrahepatic recurrence progressed after first/second-line targeted drug therapy.Camrelizumab was given as salvage therapy after normal tissue of ransplanted liver was confirmed as negative for PD-L1 by immunohistochemistry.The safety and efficacy of treatment were observed by monitoring the changes in the levels of alanine aminotransferase, aspartate aminotransferase and bilirubin, the occurrence of complications and the outcome of treatment before and after dosing.Results:During a follow-up period of 1.5 to 15.5 months, no recipients showed acute rejection symptoms such as sharp elevations of transaminase and bilirubin.Headache ( n=1), vomiting ( n=1) and fatigue & hypertension ( n=1) became relieved after treatment.As of February 28, 2022, there were one survivor and two deaths.The fatal causes were tumor progression ( n=1) and thoracic aortic rupture due to esophageal perforation ( n=1). The survival time of recipients was (11-15.5) months and the progression-free survival time (4-6) months. Conclusions:For extrahepatic recurrent hepatocellular carcinoma with PD-L1-negative liver transplantation in normal liver tissue, camrelizumab salvage therapy can control tumor progression to a certain extent and prolong the survival time of recipients.
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Biliary complications, especially the ischemic-type biliary lesions (ITBL), are the main causes of mortality and retransplantation for patients undergoing liver transplantation. In recent years, the application of marginal donor livers such as livers from donor of cardiac death and fatty liver leads to high incidence of ITBL. As a result, the treatment and prevention of ITBL after liver transplantation become a research hotspot. Based on the global research progress and the clinical experience of their liver transplantation center, the authors investigate the treatment and prevention of ITBL after liver transplantation in the donation after cardiac death era.
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Objective To establish a detection system of ultra high performance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS) for everolimus concentration in whole blood of liver transplant recipients. Methods The proteins of samples were precipitated with methanol and zinc sulfate, and everolimus-D4 was used as the internal standard. Phenomenex Kinetex PFP column was used. The mobile phase A was water (containing 2 mmol/Lammonium formate and 0.1% formic acid), and the mobile phase B was methanol (containing 2 mmol/L ammonium formate and 0.1% formic acid). The gradient elution was performed with the flow rate of 1 mL/min, the column temperature of 50 ℃ and the injection volume of 1 μL. The multi-reaction monitoring mode was used to quantitatively analyze with electrospray positive ionization. The UPLC-MS/MS detection system required only 100 μL of whole blood, and could achieve a sufficient lower limit of quantification without complicated sample preparation. The total running time was within 4.5 min. Linear regression (1/x2) analysis was performed using peak area of everolimus / peak area of everolimus-D4 (y) and concentration of everolimus/concentration of everolimus-D4 (x) to calculate the calibration function and analyze its accuracy and linear relationship. UPLC-MS/MS was used to detect the trough blood concentration of everolimus in blood samples of 5 recipients after liver transplantation. Results The accuracy of quality control was within 15%, and the linear relationship of everolimus was good in the blood concentration range of 1-100 ng /mL(R2 > 0.990). Trough blood concentration of everolimus measured in blood samples of 5 liver transplant recipients ranged from 3.77 to 9.27 ng/mL. Conclusions The detection system of UPLC-MS/MS in this study is suitable for monitoring the concentration of everolimus in whole blood of liver transplant recipients because of its high accuracy, simple sample processing method and short detection time.
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Objective To evaluate the effect of microvascular invasion (MVI) on prognosis of recipients after liver transplantation for primary liver cancer (liver cancer). Methods Clinical data of 177 recipients after liver transplantation for liver cancer were retrospectively analyzed. All patients were divided into the MVI-positive group (n=64) and MVI-negative group (n=113) according to postoperative pathological examination results. Clinical data were statistically compared of all recipients between the negative and positive MVI groups. The prognosis and risk factors of liver transplantation recipients for liver cancer were analyzed. Results Among 177 recipients, 64 cases (36.2%) were positive for MVI and 113 (63.8%) negative for MVI. Compared with the MVI-negative recipients, MVI-positive recipients had significantly lower degree of tumor differentiation, higher preoperative alpha-fetaprotein (AFP) level, larger maximal tumor diameter, a larger quantity of tumors, more satellite lesions and more recipients who did not meet the Milan criteria (all P < 0.05). The 1-, 3- and 5-year overall survival (OS) and recurrence-free survival (RFS) of recipients after liver transplantation for liver cancer were 80.2%, 62.1%, 58.5% and 66.3%, 57.5%, 51.2%, respectively. The 1-, 3- and 5-year OS and RFS of MVI-positive recipients were 70%, 39%, 35% and 53%, 39%, 33%, significantly lower than 86%, 75%, 72% and 73%, 68%, 63% of their counterparts negative for MVI (all P < 0.05). Cox regression analysis showed that the maximal tumor diameter >8 cm, preoperative AFP level ≥20 ng/mL, low degree of tumor differentiation and positive MVI were the independent risk factors for OS of recipients after liver transplantation for liver cancer (all P < 0.05). Positive MVI, low degree of tumor differentiation and preoperative down-staging failure were the independent risk factors for RFS of recipients after liver transplantation for liver cancer (all P < 0.05). Conclusions MVI is of significant clinical value in predicting clinical prognosis of recipients after liver transplantation for liver cancer.
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Objective:To explore the clinical value of serum IgE detection in patients with systemic lupus erythematosus (SLE).Methods:From January 2018 to June 2019, 62 SLE patients in Rizhao Central Hospital were selected as the observation group, 30 healthy volunteers were selected in the control group, and 30 patients with allergic diseases were selected in the allergic diseases group.The difference of IgE level among the observation group, the healthy control group and the allergic disease group was detected and compared.The difference of IgE level between active and remission SLE patients was compared.The complement C3, C4 and anti ds-DNA in active and remission SLE patients and healthy controls were detected and compared.The correlation between the level of IgE and the disease activity of SLE was analyzed.Results:The levels of IgE were (126.5±51.6)kU/L, (31.2±9.9)kU/L, (316.5±152.6)kU/L in the observation group, control group and the allergic disease group, respectively, the difference was statistically significant ( F=91.263, P<0.05). The level of IgE in the allergic disease group was the highest, which was significantly higher than that in observation group and healthy control group; and the IgE level of the observation group was significantly higher than that of the control group, the differences were statistically significant ( t=14.375, 18.593, 7.210, all P<0.05). The level of IgE in active SLE patients was (201.65±75.5)kU/L, which was significantly higher than that in remission SLE patients [(35.6±13.5)kU/L], the difference was statistically significant ( t=12.241, P<0.05). The C3 and C4 levels in active SLE patients were (0.55±0.20)g/L and (0.13±0.04)g/L, respectively, which were significantly lower than those in the remission SLE patients [(0.86±0.35)g/L, (0.28±0.10)g/L] and the control group [(0.92±0.39)g/L, (0.30±0.12)g/L], and the percentage of anti ds-DNA antibody [(36.97±12.52)%] was significantly higher than that of SLE patients and control group, the differences were statistically significant ( F=11.303, 29.993, 197.902, all P<0.05). The C3, C4 and anti ds-DNA between the remission SLE patients and the control group had no statistically significant differences (all P>0.05). The IgE level was positively correlated with SLEDAI score and anti ds-DNA ( r=0.842, 0.823, all P<0.05). IgE level was negatively correlated with C3 and C4 levels ( r=-0.798, -0.807, all P<0.05). Conclusion:The level of IgE in SLE patients is higher than that in allergic patients.The level of IgE is related to disease activity.
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Purpose@#Microtubule-associated protein 1 light chain 3B (LC3B) serves as a key component of autophagy,which is associated with the progression of carcinoma. Yet, it is still unclear whetherLC3B is also an independent risk factor for intrahepatic cholangiocarcinoma (ICC). We aimto explore the predictive value of LC3B on prognosis of ICC, and to establish a novel andavailable nomogram to predict relapse-free survival (RFS) and overall survival (OS) for thesepatients after curative-intent hepatectomy. @*Materials and Methods@#From August 2004 to March 2017, 105 ICC patients were eligibly enrolled in the ThirdAffiliated Hospital of Sun Yat-sen University. Preoperative clinical information of enrolledpatients was collected. Expression LC3B in the ICC specimen was detected by immunohistochemistry. @*Results@#The 5-year RFS and OS in this cohort were 15.7% and 29.6%, respectively. On multivariateCox regression analysis, independent risk factors for 5-year OS were cancer antigen 125,microvascular invasion, LC3B expression and lymph node metastasis. Except for the above4 factors, neutrophil/lymphocyte ratio and tumor differentiation were independent factorsfor 5-year RFS. The area under the curve of nomograms for OS and RFS were 0.820 and0.747, respectively. @*Conclusion@#The nomograms based on LC3B can be considered as effective models to predict postoperativesurvival for ICC patients.
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Objective The use of split liver transplantation (SLT) from deceased donors in children is gradual increasing.This study analyzed the outcomes of SLT in pediatric recipients at a single center in China.Methods From July 2017 to September 2018,42 SLTs in 41 pediatric recipients were performed.There were 24 adult donors with age ranged from 19 to 52 years and 10 pediatric donors with age ranged from 4 years to 16 years.In adult donors,the livers were divided to left lateral segment (LLS) and extended right lobe (ERL) grafts,and 24 LLS and 1 ERL graft were used.Among 10 pediatric donors,the same split technique was used.Further reduction of the grafts was done on 1 ERL and 3 LLS grafts.There were 34 children with biliary atresia,accounting for 82.9％ of the total patients.Twenty-four patients (58.5％) were less than one year old.For pediatric receptor PELD score,5 cases had 0-14 scores,21 cases had 15-29 scores and 16 cases had more than 30 scores.GRWR was 1.65％-4.39％ in children.The cold ischemia time of grafts was 3-13 h.Results The operations were completed successfully in 41 children.During the follow-up period of 2 months to 4 years and 3 months,38 children recovered and discharged.The incidence of complications of hepatic artery,portal vein and biliary tract was 4.8％,7.1％ and 9.5％oo respectively.There were 3 perioperative deaths and 2 recurrent deaths during the follow-up period.The 1-and 2-year survival rates were 90.25％ and 87.8％ respectively,and the graft survival rates were 88.1％ and 85.7％ respectively.Conclusions Under the background of organ donation in China,we should attach importance to the application of splitting technique in pediatric liver transplantation.Grasping the selection criteria of donors and recipients and fine operation can achieve a satisfactory result.
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Objective To evaluate the safety and efficacy of individualized treatment of splenorenal shunt during liver transplantation. Methods Clinical data of 2 recipients who underwent orthotopic liver transplantation and splenorenal shunt intraoperatively were retrospectively analyzed. According to the perfusion status after splenorenal shunt and donor liver reflow, the left renal vein ligation and splenorenal shunt vessel ligation were performed in two recipients during liver transplantation. The general postoperative conditions of the recipients were observed, including surgical related complications, peak portal blood flow velocity, liver and renal function indexs. The postoperative conditions of the recipients were monitored by abdominal ultrasound. Results No intraoperative or postoperative complications occurred in two recipients. The changes of peak portal blood flow velocity before and after splenorenal shunt in two recipients were 22.9-35.1 cm/s and 24.3-58.8 cm/s respectively. No delayed recovery of alanine aminotransferase (ALT) level was observed in two patients after operation. Case 1 experienced a transient increase in the serum creatinine (Scr), which was recovered to normal at postoperative 13 d. During the postoperative follow-up, ultrasound examination demonstrated that the direction and velocity of portal blood flow were normal and liver perfusion was excellent. Conclusions It is safe and effective to selectively ligate the left renal vein or splenorenal shunt vessels of the recipients with severe splenorenal shunt during liver transplantation.
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Objective To explore the clinical and technical essentials of hepatic arterial segmentation and reconstruction during split liver transplantation using pediatric deceased donor .Methods The clinical data were retrospectively analyzed for 15 pediatric deceased donor aged 4 .6-16 .3 years undergoing split liver transplantation from July 2017 to March 2019 .The donors were DBD (donation after brain death ,n=13) and DCD(donor after cardiac death ,n=2) .Thirty split liver transplantations were performed using these 15 pediatric deceased donors .The receptors were adult + child (n=5) and child + child recipients (n=10) . According to the Michels' classification ,the clinical types were I (n= 13) ,V (n= 1) and VI (n= 1) . Hepatic arterial segmentation :In type I hepatic arterial type donor liver ,proper hepatic artery was retained in right trilobar liver (n=8) ,low-age (< 7 years) donor liver (n=5) ,retaining proper hepatic artery in left liver & reconstructing right trilobe directly using right hepatic artery trunk (n= 4) .Methods of hepatic artery reconstruction :8-0 Prolene string was utilized under 4 .5 times magnifying glass for reconstructing hepatic artery in recipients aged under 4 years .Results Hepatic arterial segmentation and reconstruction were successfully completed .Hepatic arterial thrombosis occurred in 2 ./25 ecipients .The overall incidence of hepatic arterial complications was 6 .67％ .Conclusions For reducing the occurrence of arterial complications , arterial segmentation and reconstruction in pediatric deceased donor should be performed according to the size of donor liver and the characteristics of hepatic arterial classification .
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Objective@#To investigate the clinical value of Bayesian network in predicting survival of patients with advanced gallbladder cancer(GBC)who underwent curative intent surgery.@*Methods@#The clinical data of patients with advanced GBC who underwent curative intent surgery in 9 institutions from January 2010 to December 2015 were analyzed retrospectively.A median survival time model based on a tree augmented naïve Bayes algorithm was established by Bayesia Lab software.The survival time, number of metastatic lymph nodes(NMLN), T stage, pathological grade, margin, jaundice, liver invasion, age, sex and tumor morphology were included in this model.Confusion matrix, the receiver operating characteristic curve and area under the curve were used to evaluate the accuracy of the model.A priori statistical analysis of these 10 variables and a posterior analysis(survival time as the target variable, the remaining factors as the attribute variables)was performed.The importance rankings of each variable was calculated with the polymorphic Birnbaum importance calculation based on the posterior analysis results.The survival probability forecast table was constructed based on the top 4 prognosis factors. The survival curve was drawn by the Kaplan-Meier method, and differences in survival curves were compared using the Log-rank test.@*Results@#A total of 316 patients were enrolled, including 109 males and 207 females.The ratio of male to female was 1.0∶1.9, the age was (62.0±10.8)years.There was 298 cases(94.3%) R0 resection and 18 cases(5.7%) R1 resection.T staging: 287 cases(90.8%) T3 and 29 cases(9.2%) T4.The median survival time(MST) was 23.77 months, and the 1, 3, 5-year survival rates were 67.4%, 40.8%, 32.0%, respectively.For the Bayesian model, the number of correctly predicted cases was 121(≤23.77 months) and 115(>23.77 months) respectively, leading to a 74.86% accuracy of this model.The prior probability of survival time was 0.503 2(≤23.77 months) and 0.496 8(>23.77 months), the importance ranking showed that NMLN(0.366 6), margin(0.350 1), T stage(0.319 2) and pathological grade(0.258 9) were the top 4 prognosis factors influencing the postoperative MST.These four factors were taken as observation variables to get the probability of patients in different survival periods.Basing on these results, a survival prediction score system including NMLN, margin, T stage and pathological grade was designed, the median survival time(month) of 4-9 points were 66.8, 42.4, 26.0, 9.0, 7.5 and 2.3, respectively, there was a statistically significant difference in the different points(P<0.01).@*Conclusions@#The survival prediction model of GBC based on Bayesian network has high accuracy.NMLN, margin, T staging and pathological grade are the top 4 risk factors affecting the survival of patients with advanced GBC who underwent curative resection.The survival prediction score system based on these four factors could be used to predict the survival and to guide the decision making of patients with advanced GBC.
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Objective To investigate the influence of preoperative splenectomy on the prognosis after liver transplantation.Methods The retrospective cohort study was conducted.The clinical data of 95 patients who underwent liver transplantation in the Third Affiliated Hospital of Sun Yat-sen University between January 2004 and January 2014 were collected.Thirty-five patients undergoing preoperative splenectomy and pericardial devascularization and 60 undergoing spleen-preserving liver transplantation were allocated into the study group and control group,respectively.All patients received modified piggyback liver transplantation by the same team.Observation indicators:(1) intra-and post-operative situations;(2) follow-up and survival.The follow-up using telephone interview and outpatient examination was performed once every a week within 3 months postoperatively,once every one month within 6 months postoperatively and once every 3 months after 1 year postoperatively up to January 2016,including routine blood test,plasma-drug concentration of immunosuppressive agent and function of liver and kidney.Ultrasound and abdominal CT were used to monitor the long-term complication and survival.The measurement data with normal distribution were represented as (x)±s,and comparison between groups was done by the t test.Comparison of count data was done by the chi-square test.Results (1) Intra-and post-operative situations:all patients underwent successful liver transplantation.The operation time,volumes of intraoperative blood loss and blood transfusion were (483 ± 136) minutes,(5 683±2 950) mL,(4 887±3 682) mL in the study group and (392± 103)minutes,(3 522± 1 885)mL,(3 455±2 630)mL in the control group,respectively,with statistically significant differences between groups (t=3.683,4.358,2.202,P＜0.05).Six patients in the study group had intraoperative portal vein thrombosis (PVT),including 4 in level 1,1 in level 2 and 1 in level 3,and no patients in the control group,showing a statistically significant difference between groups (x2 =1.979,P＜0.05).Five patients with PVT in level 1 or 2 underwent thrombectomy and then end-to-end anastomosis of PV.One patient with PVT in level 1 had PVT recurrence and was cured by postoperative thrombolytic therapy.One patient with PVT in level 3 received PV reconstruction using artificial blood vessels,and had PVT recurrence and then was cured.There was no PV stenosis between groups.The levels of platelet at 1,3 and 7 days postoperatively were (75±60)× 109/L,(71± 45)×109/L,(111±73)×109/L in the study group and (57±32) ×109/L,(52±46) ×109/L,(87±53)×109/L in the control group,respectively,with statistically significant difference between groups (t =1.909,1.957,1.848,P＜ 0.05).The levels of platelet at 14 and 30 days postoperatively were respectively (230± 152)× 109/L,(310± 140)× 109/L in the study group and (193± 125)× 109/L,(286±62)× 109/L in the control group,with no statistically significant difference between groups (t=1.284,1.199,P＞0.05).The cases with postoperative infection,acute rejection,new-onset PVT in level 1-2 and 3-4 and PV stenosis were respectively 23,0,2,0,2 in the study group and 35,1,2,0,1 in the control group,with no statistically significant difference between groups (x2 =1.171,0.590,0.547,1.184,P＞0.05).Patients with postoperative infection and acute rejection were improved by symptomatic treatment.Two patients in the study group with PVT underwent anticoagulant and thrombolytic therapy,including 1 receiving interventional thrombectomy therapy.Two patients in the control group with new-onset PVT were cured by anticoagulant and thrombolytic therapy.Three patients with PV stenosis underwent percutaneous transhepatic portography (PTA) for balloon dilation,including 1 in the study group with good improvement after stent implantation.(2) Follow-up and survival:95 patients were followed up for 3-24 months,with an average time of 18 months.During the follow-up,the rate of chronic rejection in study and control groups was 5.7％(2/35) and 5.0％(3/60),showing no statistically significant difference between groups (x2 =0.023,P＞0.05).The 1-and 2-year accumulative survival rates were respectively 91.4％ (32/35),82.9％ (29/35) in the study group and 93.3％ (56/60),76.7％(46/60) in the control group,with no statistically significant difference between groups (x2 =0.780,P＞0.05).Conclusion The splenectomy before liver transplantation is easy to form PVT,increase time and difficulty of transplantation surgery,however,it doesn't increase complication risk after transplantation and affect postoperative survival.
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Objective To evaluate the clinical efficacy of application of hepatitis B surface antigen (HBsAg)-positive donor liver in adult liver transplantation. Methods Clinical efficacy of 28 recipients with liver diseases induced by virus B hepatitis (hepatitis B) undergoing liver transplantation using HBsAg-positive donor liver from July 2012 to October 2015 was retrospectively analyzed. Clinical prognosis and postoperative complications of the recipients were summarized. The changing features of serum levels of HBsAg and hepatitis B virus (HBV) DNA was investigated. Results After liver transplantation, 28 recipients were orally administered with entecavir to prevent the recurrence of hepatitis B. During perioperative period, 2 recipients died from sepsis and acute heart failure. During postoperative follow-up, 2 cases died from the recurrence of hepatocellular carcinoma (liver cancer). The remaining 24 patients were followed up for 12-26 months. Throughout the follow-up, 24 recipients were positive for serum HBsAg. After treatment, the titre of HBV DNA was significantly declined to <1×102 copies/mL at postoperative 12 months. No graft dysfunction induced by hepatitis B recurrence occurred in 24 recipients alive. Conclusions As a marginal donor liver, HBsAg-positive liver graft is safe for liver transplantation in the recipients with hepatitis B-related liver diseases. Postoperatively, anti-HBV treatment should be strengthened and intimate follow-up should be delivered.
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Objective To explore the features of peripheral blood immune cells in long-term survival recipients after liver transplantation.Methods The expression of T subsets (Th1,Th2,Th17,Th22,Tregs),NK cells,NKt cells,Bregs,MDSC in long-term survival recipients (postoperative follow-up time ≥5 years,30 cases),short-term survival recipients(postoperative follow-up time ≤1 year,15 cases) and healthy control (15 cases) were determined by flowcytometry.Results Th17 cells were significantly higher in the long-term group compared with short-term group and healthy control group(P ＜0.01).Tregs in long-term group compared with short-term group were significantly higher (P ＜ 0.01),but the difference was not statistically significant compared with healthy control group (P ＞ 0.05).NK cells were significantly higher in long-term group compared with short-term group and healthy control group (P ＜ 0.01).MDSC were significantly higher in long-term group compared with short-term group and healthy control group (P ＜0.01).Conclusions Th17,Tregs,NK cells and MDSC were significantly higher in long-term survival of liver recipients,which may be related to immune tolerance.
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Objective To investigate the donor-related risk factors for long-term biliary complications after liver transplantation (LT) from organ donation by citizens after death.Methods The clinical data of 140 donors who donated the organs after death for LT in the Third Affiliated Hospital of Sun Yat-sen University between April 2016 and April 2017 were retrospectively analyzed.The incidence of long-term biliary complications after LT in the recipients was observed,and the relationship between the incidence and the clinical indexes of the donors was analyzed.The influencing factors for long-term biliary complications after LT were analyzed using univariate and multivariate logistic regression analysis.Results The incidence of long-term biliary complications after LT in the recipients was 9.29％ (13/140).The incidence of donation after cardiac death (DCD) group and donation after brain death (DBD) group was 9.68％ (6/62) and 8.97％ (7/78) respectively.There was no significant difference between the two groups.Univariate logistic regression analysis revealed the long-term biliary complications after LT was related with cerebrovascular accident cause,the second warm ischemia time,steatosis of liver,history of cardiopulmonary resuscitation,dosage of dopamine before procurement and hypoproteinemia.Multivariate logistic regression analysis (removing warm ischemia time) revealed the independent influencing factors for long-term biliary complications after LT from organ donation were the second warm ischemia time (OR =1.106,95％ CI:1.034-1.181;P＜0.05),steatosis of liver (OR =5.319,95％ CI:1.020-27.752;P＜0.05) and dosage of dopamine before procurement (OR =1.279,95％ CI:1.021-1.601;P ＜ 0.05).Conclusion Postoperative long-term biliary complication is one of the major complications after LT from organ donation.The independent risk factors should be strictly controlled,as the second warm ischemia time,steatosis of liver and dosage of dopamine before procurement are contributed to the incidence of long-term biliary complications.
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Objective To explore the safety of programmed death receptor (PD)-1 monoclonal antibody for treatment of hepatocellular carcinoma (HCC)recurrence after liver transplantation.Methods Clinical data of 1 case with acute immune hepatitis induced by PD-1 monoclonal antibody (pembrolizumab)therapy for recurrent HCC after liver transplantation was retrospectively analyzed.Results The patient who received liver transplantation for primary HCC was diagnosed with lung metastasis at 4 months after the transplantation,and treated with the pembrolizumab (1 50 mg intravenous infusion of once)at 1 2 months after transplantation.Liver dysfunction was found at 5 th d after treatment,and liver biopsy was conducted which showed pathological changes of mild to moderate acute rejection.It was diagnosed to be acute immune hepatitis based on the patient 's clinical manifestations,laboratory examination and pembrolizumab drug instructions.After adrenal cortical hormone and intensive immunosuppressive therapy,the patient was followed up for 8 months,which showed that the patient survived with tumor,but the liver function remained abnormal.Conclusions PD-1 monoclonal antibody and other immune checkpoint inhibitors are not suitable for the immunologic suppression after liver transplantation due to the risk of inducing immune hepatitis.
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Objective To investigate the curative effect of liver transplantation on acute liver failure of pregnancy.Methods Clinical data of 2 patients with acute liver failure of pregnancy undergoing liver transplantation in the Third Affiliated Hospital of Sun Yat-sen University from March 2004 to June 201 5 were retrospectively studied.Results The patient of case 1 developed subacute liver failure and underwent emergency liver transplantation,because chronic viral hepatitis B (HBV)progressed quickly after natural delivery.The patient of case 2 developed acute liver failure with unknown etiology,and underwent subtotal hysterectomy by the obstetrician on the following day of emergency liver transplantation because the intrauterine fetus was dead. The two patients were given tacrolimus (FK506 ) and adrenocortical hormone as the postoperative early immunosuppressive regimen.Anti-HBV treatment was enhanced for the patient of case 1 with the antivirus regimen of entecavir combined with hepatitis B immune globulin.The patient of case 1 was willing to continue pregnancy,so the minimal dose of a single immunosuppressant was used when the graft function was stable.The patient of case 2 had no ability of pregnancy and underwent routine postoperative management.The two patients were followed up till the date of submission and they recovered well.The patient of case 1 had no recurrence of HBV and delivered a baby boy successfully.Conclusions Liver transplantation on acute liver failure of pregnancy may obtain good curative effect.
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Objective To explore the efficacy and safety of different synchronization chemotherapy for mid-dle -advanced cervical cancer.Methods 96 patients with middle -advanced cervical cancer were selected as the research objects.According to the digital table,they were divided into the observation group and control group, 48 cases in each group.The observation group was used radiotherapy combined with nedaplatin chemotherapy,The control group was used radiotherapy cisplatin and 5 -fluorouracil chemotherapy,The efficacy,transfer rate,pelvic recurrence rate,4 year survival rate and side effect of the two groups were compared.Results The effective rate in the observation group was 91.8%,87.5% in the control group,there was no significant difference between the two groups (χ2 =0.446 5,P >0.05);The rate of distant metastasis,pelvic recurrence and 4 year survival rates between the two groups had no significant difference(χ2 =1.200 0,1.338 0,1.523 8,all P >0.05);The incidence rate of Ⅲneutropenia in the observation group was 4.2%,which was lower than 22.9% in the control group(χ2 =7.206 7,P <0.05);The incidence rate Ⅲ gastrointestinal reaction of the observation group was 20.8%,which was lower than 47.9% of the control group(χ2 =7.803 8,P <0.05).Conclusion The two schemes of radiotherapy clinical cura-tive effect of chemotherapy in the treatment of middle -advanced cervical cancer has a same effect,and the patients of nedaplatin chemoradiotherapy has better tolerability,safety,which is worth of clinical application.
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Objective To investigate the feasibility of non-invasive quantitative evaluation of portal pressure (Pp) by contrast enhanced ultrasonography (CEUS).Methods 18 portal hypertension patients (PTH group) were performed with CEUS within one week before splenectomy and pericardial devascularization,and 20 healthy volunteers as controls were recruited in this study (control group).Hepatic-right kidney sectionwas chosen to calculate the area under curve of portal vein/hepatic artery (Qp/Qa) and the perfusion intensity of portal vein/hepatic artery (Ip/Ia) through time intensity curves (TIC) of liver parenchyma generated from CEUS images.Pp was measured by intra-operative mesenteric vein catheter,and the correlation betweenPp and Qp/Qa,Ip/Ia were analyzed by Pearson correlation test.Results The levels of Qp/Qa and Ip/Ia in the PTH group were 2.28 ± 0.66 and 0.35 ± 0.14 respectively,which were both significantly declined than that in the controlgroup (5.72 ± 3.69 and 1.97 ± 0.17).In the PTH group,the correlation coefficient were-0.747 and-0.617,and the linear regression equations were Y =-83 X + 5.013 andY =-15X + 0.837,which indicated that Qp/Qa and Ip/Ia had significant correlation with Pp.Conclusions CEUS parameters,including Qp/Qa and Ip/Ia,are significantly correlated to Pp in portal hypertension patients,which indicate that CEUS could be a new non-invasive clinical method for evaluating Pp.
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Objective To investigate the protective effect of human umbilical cord mesenchymal stem cells (huc-MSC) on the ischemia-reperfusion injury (IRI) of moderately fatty liver in rats. Methods The rat fatty liver model was established by fat-rich diet feeding. 60 female SD rats were randomly divided into MSC-treated and control groups (n = 30). MSC-treated group was infused with MSC (2 x 106 cells resuspended in 1.5 ml of sterile phosphate-buffered saline solution, PBS) by intra-venous injection through the tail vein. The first dose was administered on day 1 before IRI, followed by another dose on day 3 postIRI. The control group was injected with sterile PBS alone at the same intervals. Blood and liver samples were collected at day 1,4 and 7 (10 rats at each time point) post-IRI respectively to test enzyme activities,biochemical and histological changes. Serum alanine aminotransferase (ALT), aspartate aminotransferase (AST), superoxide dismutase (SOD), malondialdehyde (MDA) and tumor necrosis factor α (TNF-α) in liver tissue were measured. The pathological changes of liver tissue and apoptosis of hepatocytes were also assessed. Results Compared to the control group, the levels of ALT, AST, TNF-α, and MDA declined in the MSC-treated group on day 1 and day 4 post-IRI ( P ＜ 0. 05 ), while no difference was observed on day 7 post-IRI ( P ＞ 0. 05). There was no difference of the level of SOD between the two groups on day 1,4 and 7 post-IRI (P ＞0. 05). Pathological examination revealed inflammatory injury in the MSC-treated group was alleviated compared with that in the control group. Conclusion huc-MSC effects protection on the IRI of fatty liver in rats.