Objective To explore a reliable method of 70% hepatectomy model in liver fibrosis mice. Methods Sixty-six C57BL6 mice were randomly devided into control group (n=6), the traditional group (n=30, ligation and removal liver lobe) and improved group (n=30, removal of liver lobe after blocking blood flow). Those 60 mice were induced liver fibrosis firstly, then randomly divided into six mice in each group, and were sacrificed at preoperative, 12, 24, 48 and 72 hours after liver resection. Liver tissues and blood samples were collected. The survival rate and incidence of complications were recorded and compared between two groups. The serum levels of alanine aminotransferase (ALT) and aspartate aminotransferase (AST) were measured to observe the liver injury after 70%hepatectomy. The ratio of liver weight to body weight and the expression of proliferating cell nuclear antigen (PCNA) were also measured to observe the difference of liver regeneration between the two groups. Results (1) Compared to the pathological control group, liver fibrosis model was established successfully in both traditional group and improved group, which can be used in 70%hepatectomy. So the follow-up experiment can be undertook timely. (2) Compared to traditional group, the survival rate was improved significantly in improved group (96.67%vs. 73.33%), and the incidence of complications was significantly lower (P<0.05). (3) The ALT and AST levels were higher 12 h and 24 h after operation in traditional group than those of improved group (P<0.05), while ALT and AST levels were increased first 12 h after operation and then decreased in both groups (P<0.05). (4) The liver/body weight ratio showed a decreasing trend 12 h after hepatectomy in two groups. The expression of PCNA increased at the beginning of postoperative, and reached its peak at 48 h (P<0.05). However, there was no significant difference at each time point between the two groups. Conclusion By blocking blood flow to establish 70% hepatectomy model in liver fibrosis mice, we can significantly improve the success rate of the model, and reduce the incidence of complications.

BACKGROUND:Studies have shown that the reason of the slower liver regeneration in individuals of cirrhotic liver after partial hepatectomy compared with healthy liver may be related to the delayed synthesis and secretion of hepatocyte growth factor during liver regeneration, but the cause of this phenomenon is not clear. The hepatocyte growth factor activator inhibitor found in recent years can indirectly inhibit the activation of hepatocyte growth factor, but there is little research to explore the expression of hepatocyte growth factor activator inhibitor in the regeneration process after partial hepatectomy in cirrhotic liver and its relationship with the liver regeneration. OBJECTIVE:To investigate the expression of hepatocyte growth factor activator inhibitors (HAI-1, HAI-2) during cirrhotic and normal liver regeneration after partial hepatectomy through establishing the cirrhotic rat model, and to explore the biological effects of HAI-1, HAI-2 in cirrhotic liver during the liver regeneration after partial hepatectomy. METHODS:We used 40%CCl4 subcutaneous injection to establish the cirrhotic rat model, then we performed 70%liver resection for the experimental group. The rats in the control group only received ordinary water feeding and 70%liver resection. Rats in each group were randomly sacrificed before surgery and at 3 hours, 6 hours, 12 hours, 24 hours and 48 hours after surgery, and samples were col ected. We used RT-PCR technology to detect the expression of HAI-1 mRNA, HAI-2 mRNA in splenic tissue. RESULTS AND CONCLUSION:The expression levels of HAI-1 mRNA of two groups after partial hepatectomy were increased firstly and then decreased. The expression of HAI-1 mRNA in cirrhotic rats was sustained higher than that of the control group (P<0.05), there was no significant difference between the two groups of the expression of HAI-2 mRNA (P>0.05). The expression of HAI-1 mRNA in liver cirrhosis rats after resection was consistently higher than that in healthy rats, which may lead to the insufficient synthesis and secretion of hepatocyte growth factor activator in cirrhotic rats, then hepatocyte growth factor precursor may not be activated enough, eventual y leading to slow liver regeneration. HAI-2 may not be involved in the wound repair process of liver.

Objective To investigate the differential expression of hepatocyte growth factor activator (HGFA) and its inhibitors (HAI-1,HAI-2) during cirrhotic and normal liver regeneration after partial hepatectomy,and to explore the causes of the delayed liver regeneration after partial hepatectomy in cirrhotic rat model.Methods We used 40％ CCl4 subcutaneous injection to establish the cirrhotic rat model,and then performed 70％ liver resection for the experimental group together with no operation for the healthy rats as control group.Rats in each group after 3 hours,6 hours,12 hours,24 hours and 48 hours were randomly sacrificed and specimens were collected.The serum HGFA was detected by enzyme-linked immunosorbent assay (ELISA),and we used RT-PCR to detect the mRNA expressions of HAI-1 and HAI-2 in splenic tissue.Results The serum HGFA level in cirrhotic rats at each time point was all significantly lower than that in the control group (P ＜0.05).The expression of HAI-1 mRNA in cirrhotic rats was sustained at a higher level than that in the control group (P ＜ 0.05),but there was no significant difference on the HAI-2 mRNA expression between the two groups (P ＞ 0.05).Conclusions The synthesis of HGFA during the liver regeneration after partial hepatectomy in cirrhosis rats is lower compared with healthy rats,which may lead to the insufficient activation of HGF precursor,eventually causing the slow liver regeneration.HAI-2 may not be involved in the healing process of liver.

Objective To summarize the experience in one case of adult-to-adult combined liver-kidney transplantation.Method In Sep.2007,one case of adult-to-adult liver-kidney transplantation from the same living donor was performed on a patient with liver cirrhosis (liver failure decompensation) and chronic renal failure (uremia).There was a donation of the right liver with the middle hepatic vein and right kidney in the same time from the living donor.The piggyback liver transplantation and ectopic kidney transplantation were performed for the recipient.Basiliximab and methylprednisolone were given for immune induction therapy in operation.Tacrolimus,MMF and prednisone were given for anti-rejection.There were hepatoprotective treatment,anti-infection treatment and nutritional support for the donor and recipient after operation.The follow-up period has now been more than five years.Result The donor and the patient were smooth in the perioperative period.The liver and kidney function of the donor is well so far.There was no significant influence on quality of life of the donor.The transplanted liver and kidney function of the recipient is well so far.There were no significant complications for the recipient.Conclusion The living liver-kidney transplantation is an effective means for the treatment of liver and kidney failure.The safety can be ensured for the donors that donate the right liver and one kidney simultaneously.

Objective To study the promoting effects and mechanisms of interleukin-22 on liver regeneration in GCl4-induced liver fibrosis mice after partial hepatectomy.Methods One hundred and fortyfour C57/BL6 mice were randomly divided into four groups:PHX group,CCl4 group,CCl4 + PHX group,and CCl4 + IL22 + PHX group.The blood samples were taken to measure serum ALT and AST levels.ALT /AST was calculated to observe the liver injury at 3 h,6 h,12 h,24 h,48 h and 72 h after hepatectomy.The liver tissue specimens were collected at each time point after hepatectomy.We measured the hepatic lobe to calculate the liver weight ratio and conducted pathological examinations to observe the degree of fibrosis and pathological changes at each time point.The positive expression of proliferating cell nuclear antigen (PCNA) in liver tissue was tested by immunohistochemistry.The level of CyclinD1 and STAT3 (Signal transducer and activator of transcription 3) signaling pathway was detected by Western blot.Results (1) Compared with CCl4 + PHX group,the ALT/AST ratio of CCl4 + IL22 + PHX group was significantly higher at 24 h,48 h and 72 h,and the level of ALB of CCl4 + IL22 + PHX group was obviously increased at 48 h and 72 h (P ＜ 0.05).(2) The liver regeneration was significantly increased in CCl4 + IL22 + PHX group.Compared with CCl4 + PHX group (2.08 ± 0.16,2.77 ± 0.07,2.97 ± 0.14),the liver weight ratio of CCl4 + IL22 + PHX group(2.34 ± 0.07,3.23 ± 0.09,3.55 ± 0.09) dramatically increased at 24 h,48 h and 72 h.Moreover,the pathological sections displayed that the disease was alleviated (P ＜ 0.05).(3) Immunohistochemical assay and western blot revealed that compared with other three groups,the level of PCNA,STAT3 and Cyclin D1 was significantly lower in the CCl4 + PHX group.However,the level of PCNA,STAT3 and Cyclin D1 apparently increased in CCl4 + IL22 + PHX group at 24 h,48 h and 72 h (P ＜ 0.05).Conclusion Interleukin-22 may significantly promote liver regeneration and reduce liver pathological injury in liver fibrosis mice induced by administration of CCl4 after hepatectomy,which plays a positive role in the recovery of liver function.

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.

Objective To determine the clinical value of MRCP for peroperative evaluation of donor biliary system in living donor liver transplantation (LDLT). Methods A total of 60 living donors for the LDLT were enrolled in this study. Of the 60 donors with a mean age of 32.2 (19-60), 50were male and 10 female. MRCP was performed before and cholangiography was done during the right lobectomy in these donors. The results of MRCP were compared with those of cholangiography to determine the value of MRCP for typing the biliary system in the donors. Results The preoperative MRCP showed that 40 donors were of type Ⅰ biliary tract, 12 of type Ⅱ , 5 of type Ⅲ and 3 of other types. The intraoperative cholangiography showed that the accordance rate of MRCP was 97.4%,91% and 89% for type Ⅰ , type Ⅱ and other types, respectively. The overall rate of accuracy of MRCP was 95% (57/60). Conlusion MRCP can show types of biliary tract in living donors for liver transplantation to provide evidence for plan of surgery.

Objective To investigate the effects of different hepatic perfusion procedures for small-for-size liver transplantation in rats. Methods A total of 156 rats were randomly divided into two groups: portal vein perfusion group (groupⅠ, n=78) and abdominal aorta perfusion group (groupⅡ, n=78). After harvesting graft, the left lobe of the liver and the middle lobe were resected and the remaining approximately 30%volumes of the liver were transplanted in groupⅠand groupⅡ. The body weights of donor and acceptor, the weight of graft, the time of operating in donor, the cold ischemia time, anhepatic phase, the blocking time of inferior hepatic vena cava and the time of operating in receptor were recorded in two groups. The serum levels of alanine aminotransferase (ALT), aspartate aminotransferase (AST), pathological HE staining and 7-day survival rate in 6 h, 1 d, 3 d and 7 d after operation were compared between two groups. Results The serum levels of ALT and AST were decreased gradually in two groups, but the levels decreased slowly in groupⅠ. The serum levels of ALT and AST were significantly higher in groupⅠthan those of groupⅡ(P<0.05). HE staining showed greater damage of mi-crostructure of liver tissue at early stage in group Ⅰthan that in groupⅡ. The 7-day survival rate was lower in group Ⅰthan that of groupⅡ(χ2=4.050,P=0.044). Conclusion There is a higher survival rate and mild liver damage in small-for-size liver transplantation in rats using perfusion by abdominal aorta.

Objective To study the clinical treatment and prognosis of de novo liver cancer following renal transplantation.Methods The clinical data of 15 patients who developed de novo liver cancer after renal transplantation carried out prior to treatment of liver cancer at the First Center Hospital of Tianjin between June 2006 and June 2016 were retrospectively studied.These patients were diagnosed to have liver cancer ranging from 23 to 98 months after renal transplantations,with an average of (42.5 ± 29.7) months.Two patients were diagnosed within 2 years,7 within 5 years,and 6 over 5 years after renal transplantation.Results Three patients underwent transcatheter arterial chemoembolization (TACE) and 12 patients underwent surgical resection which included right/left hemihepatectomy (n =5),hepatic segment resection (n =4),and tumor enucleation (n =3).Postoperative histopathology confirmed hepatocellular carcinoma in 8 patients,cholangiocarcinoma in 1 patient,and mixed liver cancer in 3 patients.Among the 12 patients who initially underwent'curative'surgery,3 patients died from recurrent cancer 8,16,25 months after surgery,respectively.The remaining 9 patients were still alive with a follow-up which ranged from 0.6 to 65-month.The 3 patients who underwent TACE were alive for 4,7 and 13 months,respectively.Conclusions De novo liver cancer were usually asymptomatic and had a rapid onset.The optimal clinical management which includes early diagnosis,appropriate therapy with immunosuppression and renal function preservation can result in good long-term survival.