Application of a novel artificial perfusate based on oxygen-carrying nanoparticles in normothermic machine perfusion for porcine liver preservation after cardiac death / 浙江大学学报·医学版

OBJECTIVE@#To investigate the efficacy of a novel artificial perfusate based on oxygen-carrying perfluoronaphthalene-albumin nanoparticles in normothermic machine perfusion (NMP) for preservation of porcine liver donation after cardiac death.@*METHODS@#Artificial perfusate with perfluoronaphthalene-albumin nanoparticles was prepared at 5% albumin (w/v) and its oxygen carrying capacity was calculated. The livers of 16 Landrace pigs were isolated after 1 h of warm ischemia, and then they were divided into 4 groups and preserved continuously for 24 h with different preservation methods: cold preservation with UW solution (SCS group), NMP preservation by whole blood (blood NMP group), NMP preservation by artificial perfusate without nanoparticles (non-nanoparticles NMP group) and NMP preservation by artificial perfusate containing nanoparticles (nanoparticles NMP group). Hemodynamics, tissue metabolism, biochemical indices of perfusate and bile were monitored every 4 h after the beginning of NMP. Liver tissue samples were collected for histological examination (HE and TUNEL staining) before preservation, 12 h and 24 h after preservation.@*RESULTS@#The oxygen carrying capacity of nanoparticles in 100 mL artificial perfusate was 6.94 μL/mmHg (1 mmHg=0.133 kPa). The hepatic artery and portal vein resistance of nanoparticles NMP group and blood NMP group remained stable during perfusion, and the vascular resistance of nanoparticles NMP group was lower than that of blood NMP group. The concentration of lactic acid in the perfusate decreased to the normal range within 8 h in both nanoparticles NMP group and blood NMP group. There were no significant differences in accumulated bile production, alanine aminotransferase and aspartate aminotransferase in perfusate between nanoparticles NMP group and blood NMP group (all P>0.05). After 24 h perfusion, the histological Suzuki score in blood NMP group and nanoparticles NMP group was lower than that in SCS group and non-nanoparticles NMP group (all P<0.05), and the quantities of TUNEL staining positive cells in blood NMP group and non-nanoparticles NMP group was higher than those in nanoparticles NMP group and SCS group 12 h and 24 h after preservation (all P<0.05).@*CONCLUSION@#Artificial perfusate based on oxygen-carrying nanoparticles can meet the oxygen supply requirements of porcine livers donation after cardiac death during NMP preservation, and it may has superiorities in improving tissue microcirculation and alleviating ischemia-reperfusion injury.

Clinical value of preoperative nutritional support therapy in the hepatectomy of patients with nutritional risk: a prospective study / 中华消化外科杂志

Objective To investigate the clinical value of preoperative nutritional support (PNS) therapy in the hepatectomy of patients with nutritional risk.Methods The prospective study was conducted.The clinical data of 133 patients with nutritional risk who were admitted to the Drum Tower Hospital Affiliated to Nanjing University Medical School from August 2012 to June 2016 were collected.All the patients undergoing PNS and traditional therapy were divided into the PNS group and the control group by random number table method,respectively.Observation indicators:(1) comparisons of laboratory indexes between groups;(2) comparisons of postoperative situations between groups;(3) comparisons of postoperative complications between groups.Measurement data with normal distribution were represented as-x±s.Comparisons between groups were evaluated with the independent-sample t test.Comparisons of count data were analyzed using the chi-square test,and repeated measures data were analyzed by the repeated measures ANOVA.Results All the 133 patients were screened for eligibility,including 68 in the PNS group and 65 in the control group.(1) Comparisons of laboratory indexes between groups:alanine transaminase (ALT),aspartate transaminase (AST),total bilirubin (TBil),cholinesterase,albumin (Alb),prealbumin,transferrin and C-reactive protein (CRP) in the PNS group were respectively (36± 13) U/L,(29± 10) U/L,(18.5±2.4) mmol/L,(5 738± 1 824) U/L,(37.4±5.1) g/L,(155±48) mg/L,(2.2±0.5)g/L,(10±4) g/L at admission and (33 ± 9) U/L,(27 ± 8) U/L,(17.9± 1.8) mmol/L,(5 796± 2 016) U/L,(38.5 ± 4.7) g/L,(181 ± 40) mg/L,(2.4± 0.5) g/L,(8± 4) g/L before operation and (285±100)U/L,(218±93)U/L,(33.5±6.3)mmol/L,(4 847±1 044)U/L,(32.6±3.8)g/L,(105±34)mg/L,(1.3±0.4) g/L,(55±28) g/L at 1 day postoperatively and (149±84) U/L,(76±42) U/L,(22.7±4.9) mmol/L,(3 866±893) U/L,(34.2±2.4) g/L,(125±30) mg/L,(1.6±0.4) g/L,(51±34) g/L at 3 days postoperatively and (64±33) U/L,(44±18) U/L,(19.4±2.8) mmol/L,(4 257± 1 032) U/L,(37.0±2.1) g/L,(148±42) mg/L,(1.9±0.4)g/L,(16±11)g/L at 7 days postoperatively;ALT,AST,TBil,cholinesterase,Alb,prealbumin,transferrin and CRP in the control group were respectively (36± 15)U/L,(31± 12)U/L,(18.3±2.9)mmol/L,(5 762±1 693)U/L,(37.3±6.1)g/L,(162±51)mg/L,(2.3±0.5)g/L,(10±4)g/L at admission and (36±11)U/L,(30±11)U/L,(18.2±2.8)mmol/L,(5 789±1 673)U/L,(37.8±7.1)g/L,(166±57) mg/L,(2.3±0.6) g/L,(9±5) g/L before operation and (305±127) U/L,(246± 104) U/L,(34.2±7.8) mmol/L,(4 842±1 173)U/L,(32.0±4.1) g/L,(83±32) mg/L,(1.2±0.4) g/L,(61 ±31) g/L at 1 day postoperatively and (163±104)U/L,(82±62)U/L,(23.1±6.0)mmol/L,(3 672±937) U/L,(33.8±3.6) g/L,(106±30)mg/L,(1.4±0.4)g/L,(61±40)g/L at 3 days postoperatively and (77±48) U/L,(52±27) U/L,(20.2±3.5) mmol/L,(3 925±987) U/L,(36.6±2.8) g/L,(125±40) mg/L,(1.7±0.4) g/L,(22± 12) g/L at 7 days postoperatively,showing no statistically significant difference in changing trends of above indicators between groups (F =1.007,2.223,0.579,0.014,0.235,3.533,2.970,2.143,P＞0.05).Results of further analysis showed that there were statistically significant differences in the levels of ALT,AST and cholinesterase at 7 days postoperatively between groups (t=1.832,2.073,1.899,P＜0.05),and in the levels of prealbumin before operation and at 1,3 and 7 days postoperatively between groups (t =1.698,3.738,3.625,3.178,P＜0.05) and in the levels of transferrin and CRP at 3 and 7 days postoperatively between groups (t=2.917,2.709,1.667,2.990,P＜0.05).(2) Comparisons of postoperative situations between groups:time to initial exsufflation,time of initial defecation,infused volume of exogenous albumin and duration of postoperative hospital stay were respectively (46± 15)hours,(64±16)hours,(23±10)g,(9.2±2.6)days in the PNS group and (55±18)hours,(78±21)hours,(39±25)g,(11.7±5.3) days,with statistically significant differences in the above indicators between groups (t =2.830,4.157,5.044,3.497,P＜0.05).(3) Comparisons of postoperative complications between groups:23 and 33 patients in the PNS and control groups had postoperative complications,showing a statistically significant difference between groups (x2=3.915,P＜0.05).Eight and 17 patients in the PNS and control groups were respectively complicated with peritoneal effusion,with a statistically significant difference between groups (x2 =4.508,P＜ 0.05).Conclusion PNS therapy in the hepatectomy of patients with nutrition risk can effectively improve pre-and post-operative nutrition statuses,reduce liver damage,accelerate recoveries of liver and gastrointestinal functions,reduce complications,shorten duration of postoperative hospital stay and accelerate patients' recovery.

The beneficial effect of mesenchymal stem cells transplantation in combination with interleukin-1 receptor antagonist on post-hepatectomy liver failure / 中华肝胆外科杂志

Objective To study the synergetic effect and possible mechanism of transplanting mesenchymal stem cells (MSCs) in combination with interleukin-1 receptor antagonist (IL-1Ra) on acute liver failure (ALF).Methods MSCs transplantation combined with IL-1Ra was used for a swine model of ALF induced by 85％ total hepatectomy.The living conditions,blood samples and survival time were recorded or collected for analysis of hepatic function.Liver injury histology was analyzed.Hepatic cell regeneration and apoptosis were studied by immunohistochemistry staining of Ki67 and TUNELassays respectively.The expression levels of AKT and NF-κB were analyzed by Western blotting.Results The difference on the survival time between the model group and combined therapy group was statistically significant (P ＜ 0.05).Combined therapy displayed improvement not only in the serum biochemical conditions but also in the serum inflammatory cytokines.Furthermore,the observed hepatic histopathological score was significantly less compared to model group.In addition,the combined therapy group significantly inhibited the liver cell apoptosis and increased hepatic cell regeneration.Finally,a significant increase in AKT expression and decrease of NF-κB expression (P ＜ 0.05) were observed,which was consistent with their important roles in liver regeneration.Conclusion The combined therapy displayed a synergistic effect on liver regeneration,by promoting restoration and reconstruction of ALF,through regulation of inflammation and apoptosis signaling network.

Bioartificial liver and liver transplantation: new modalities for the treatment of liver failure / 临床肝胆病杂志

The main features of liver failure are extensive necrosis of hepatocytes,rapid disease progression,and poor prognosis,and at present,there are no effective drugs and methods for the treatment of liver failure.This article summarizes four treatment methods for liver failure,i.e.,medical treatment,cell transplantation,liver transplantation,and artificial liver support therapy,and elaborates on the existing treatment methods.The current medical treatment regimen should be optimized;cell transplantation has not been used in clinical practice;liver transplantation is the most effective method,but it is limited by donor liver shortage and high costs;artificial liver can effectively remove toxic substances in human body.Therefore,this article puts forward artificial liver as a transition for liver transplantation;artificial liver can buy time for liver regeneration or liver transplantation and prolong patients' survival time and thus has a promising future.The new treatment modality of bioartificial liver combined with liver transplantation may bring good news to patients with liver failure.

The beneficial effect of mesenchymal stem cells transplantation in combination with interleukin-1 receptor antagonist on post-hepatectomy liver failure / 中华肝胆外科杂志

Objective To study the synergetic effect and possible mechanism of transplanting mesenchymal stem cells (MSCs) in combination with interleukin-1 receptor antagonist (IL-1Ra) on acute liver failure (ALF).Methods MSCs transplantation combined with IL-1Ra was used for a swine model of ALF induced by 85％ total hepatectomy.The living conditions,blood samples and survival time were recorded or collected for analysis of hepatic function.Liver injury histology was analyzed.Hepatic cell regeneration and apoptosis were studied by immunohistochemistry staining of Ki67 and TUNELassays respectively.The expression levels of AKT and NF-κB were analyzed by Western blotting.Results The difference on the survival time between the model group and combined therapy group was statistically significant (P ＜ 0.05).Combined therapy displayed improvement not only in the serum biochemical conditions but also in the serum inflammatory cytokines.Furthermore,the observed hepatic histopathological score was significantly less compared to model group.In addition,the combined therapy group significantly inhibited the liver cell apoptosis and increased hepatic cell regeneration.Finally,a significant increase in AKT expression and decrease of NF-κB expression (P ＜ 0.05) were observed,which was consistent with their important roles in liver regeneration.Conclusion The combined therapy displayed a synergistic effect on liver regeneration,by promoting restoration and reconstruction of ALF,through regulation of inflammation and apoptosis signaling network.

Bioartificial liver and liver transplantation: new modalities for the treatment of liver failure / 临床肝胆病杂志

The main features of liver failure are extensive necrosis of hepatocytes,rapid disease progression,and poor prognosis,and at present,there are no effective drugs and methods for the treatment of liver failure.This article summarizes four treatment methods for liver failure,i.e.,medical treatment,cell transplantation,liver transplantation,and artificial liver support therapy,and elaborates on the existing treatment methods.The current medical treatment regimen should be optimized;cell transplantation has not been used in clinical practice;liver transplantation is the most effective method,but it is limited by donor liver shortage and high costs;artificial liver can effectively remove toxic substances in human body.Therefore,this article puts forward artificial liver as a transition for liver transplantation;artificial liver can buy time for liver regeneration or liver transplantation and prolong patients' survival time and thus has a promising future.The new treatment modality of bioartificial liver combined with liver transplantation may bring good news to patients with liver failure.

Establishment of a porcine model of acute liver failure after 85% hepatectomy / 中国实验动物学报

Objective To establish a porcine model of liver failure after different percent hepatectomy.Methods The porcine models of liver failure 75%,85%,95% hepatectomy were developed and the living conditions and survival time were recorded.The blood samples of pre-surgery,post-hepatectomy d1,d3,d5 and post-hepatectomy 1 week,2 weeks,and 3 weeks were collected for hepatic function analysis.Histological examination of liver tissues was performed using HE staining.Liver injury histology was interpreted and scored in the terminal samples.Results The average survival time of pigs with post-hepatectomy liver failure after 75%,85%,95% hepatectomy was 19.0±5.6 days,17.3±5.5 days,1.3±1.5 days,respectively.Their pathological scores were 5.67±0.52,8.17±0.82 and 8.50±0.71,respectively.With the increase of percent hepatic resection,the incidence of hepatic failure was increasing.ALT,AST,ALP,LDH and TBA were dramatically increased in the pigs after 85% hepatectomy.Conclusions The pig model of acute liver failure by 85% hepatectomy is successfully established,which can cause typical acute liver failure in Bama miniature pigs.

Development of research hospital's humanistic system at Nanj ing Drum Tower Hospital / 中华医院管理杂志

In the practice of building its humanistic environment of a research hospital,Nanjing Drum Tower hospital adheres to such humanistic characteristics of the hospital as humanistic concept,planning, environment,management,service,and quality.Furthermore,the hospital upholds such keys as learning, innovation, cooperation, undertaking, competition and development. High focus, high starting point planning,persistence,and down-to-earth efforts,effectively promoting hospital development.

Transplantation routes and mechanism of mesenchymal stem cell therapy in porcine models with acute liver failure / 中华肝胆外科杂志

Objective To explore the most effective route of mesenchymal stem cell transplantation (MSCs) in D-galactosamine (D-gal) induced porcine model with acute liver failure (ALF) and the potential mechanism.Methods BA-MA mini-pigs with D-gal-induced ALF were transplanted with porcine mesenchymal stem cells (MSCs) through four routes:intraportal injection (InP),peripheral intravenous injection (PV),hepatic intra-arterial injection (AH) and intrahepatic injection (IH).The survival time was recorded.The blood samples before and after MSC transplantation were collected for detecting liver function.Liver histology was interpreted and scored.Hepatic apoptosis and regeneration were detected by Terminal Deoxynucleotidyl Transferase dUTP Nick End Labeling (TUNEL) assay and Ki-67 assay.The protein expression of cleaved caspase-3,survivin,AKT and ERK were analyzed by Western blot.Results The average survival time in each group was (10.7 ±1.6) days (InP),(6.0 ±0.9) days (AH),(4.7 ±1.4) days (PV),(4.3 ± 0.8) days (IH) when compared with D-gal group [(3.8 ± 0.8) days].The histopathological scores revealed a significantly decrease in InP group (3.17 ± 1.04,P ＜0.05) and AH group (8.17 ± 0.76,P ＜ 0.05) when compared with that in D-gal group (11.50 ± 1.32).The apoptosis rate in InP group (25.0 ± 3.4％,P ＜ 0.05) and AH group (40.5 ± 1.0％,P ＜ 0.05) was lower than that in D-gal group (70.6 ± 8.5％).The expression of active caspase-3 was inhibited,while the expression of survivin,AKT and ERK was elevated in InP group.Conclusions The intraportal injection was superior to other pathways for MSCs transplantation.Intraportal MSC transplantation could improve liver function,inhibit cell apoptosis,promote cell proliferation and prolong the survival in porcine ALF model.

Advance of indocyanine-green in fluorescent staining tumor in surgical operation / 国际外科学杂志

Surgery is so far the most widely used and effective treatment of neoplastic diseases.However,residual tumour cells during surgery remain a major trigger of cancer recurrence and matastasis.Although intraoperative rapid pathological R0 resection can be achieved based on preoperative imageological examination,but for small satellite lesions and the naked eye can not find the error quickly and so often cause pathological presence of residual tumour cells.Thus,quick and accurate identification of residual cancer cells is crucial for prognosis of cancer patients.Indocyanine green (ICG) is a new type of fluorochrome that can stain tumours under the near-infrared fluorescence during surgery,the paper will be reviewed latest developments in the reagent for fluorescence in tumours.

Effect of anti-PMN serum treatment on D-GalN-induced ALF rats / 西安交通大学学报(医学版)

ABSTRACT:Objective To investigate changes in the neutrophils in rats with D-galactosamine (D-GalN)-induced acute liver failure (ALF)and to explore the therapeutic effect of interventions treatment of neutrophils on ALF.Methods Liver function,the expressions of inflammatory cytokines TNF-αand IL-1β,and the changes of neutrophils in the peripheral blood and the liver were observed in rats with D-GalN (intraperitoneal injection)-induced ALF.SD rats were randomly divided into three groups when treated with intervention of neutrophils:control group,ALF group (intraperitoneal injection of D-GalN),and treatment group (intravenous injection of anti-PMN serum via tail vein 24 h before modeling).Biochemical analysis was used to detect serum ALT,AST, TBIL and blood ammonia.Hematology analyzer was applied to analyze the number and percentage of peripheral blood neutrophils.The number of neutrophils in the liver was evaluated by immunohistochemistry.Liver RT-PCR was adopted to detect the mRNA expression of inflammatory cytokines TNF-αand IL-1β.Results We found that 6 h after D-GalN injection,serum ALT,AST,TBIL and blood ammonia in ALF rats were significantly increased (P <0.05).The mRNA expression levels of inflammatory cytokines TNF-αand IL-1βin the liver reached the peak at 6 h after modeling (P <0.001),and it was still notably higher at 24 h than before modeling (P <0.001 ).The number and percentage of peripheral blood neutrophils and the number of neutrophils in the liver were all markedly increased 12 h after modeling (P <0.001 ),and the increase continued at least until 24 h (P <0.001 ).24 h after intravenous injection of anti-PMN serum via tail vein,ALF rats had a distinct decrease in the number of peripheral blood neutrophils and neutrophils in the liver 24 h after modeling (P <0.001).Meanwhile,serum ALT,AST,TBIL and blood ammonia were all greatly decreased compared with those in ALF group (P <0.05);a significant reduction of hepatocyte apoptosis was observed.Also,the expressions of TNF-α and IL-1β in the liver were remarkably decreased after treatment (P <0.05).Conclusion Neutrophils accumulated in peripheral blood and liver of rats with D-GalN-induced ALF.The treatment of anti-PMN serum may have a therapeutic effect on liver function and immune microenvironment in ALF rats.

Effects of structured triglyceride on postoperative recovery of patients with primary liver cancer after hepatectomy: a prospective study / 中华消化外科杂志

Objective To investigate the effects of structured triglyceride on hepatic function,nutritional status,inflammatory reaction and immunologic function of patients with primary liver cancer after hepatectomy.Methods A prospective,double-blind,randomized,controlled clinical trial was conducted based on the clinical data of 80 patients with primary liver cancer who underwent hepatectomy at the Drum Tower Hospital from January 2011 to December 2012.All the 80 patients were allocated into the testing group (40 patients) and the control group (40 patients) based on a random number table,and received isometrical nitrogen and isocaloric parenteral nutritional support therapy for 7 days after operation.Structured triglyceride (STG) and physical mixed medium chain/long chain triglycerides (MCT/LCT) were applied to the patients in the testing group and the control group,respectively.The hepatic function,nutritional status,inflammatory reaction,immunologic function and prognosis of patients were compared between the 2 groups.The measurement data with normal distribution were presented as (x) ± s.The comparision between groups was evaluated with an independent sample t test.The trend analyses for variables were done using the repeated measures ANOVA.The measurement data with skew distribution were described as M(P25,P75) and analyzed by the analysis of variance.The count data were analyzed using the chi-square test.Results All the 80 patients who were screened for eligibility were randomly divided into the testing group (40 patients) and the control group (40 patients).The alanine transaminase (ALT),aspartate transaminase (AST),prealbumin,choline esterase,C-reactive protein,IgG,IgM,IgA,CD3 +,CD4 +,CD8 + and CD4 +/CD8 + in the 2 groups showed a range of variations before operation and at postoperative day 5 and 7.The ALT,AST,prealbumin,choline esterase,C-reactive protein,IgG,IgM,IgA,CD3 +,CD4 +,CD8 + and CD4+/CD8 + from preoperation to postoperative day 7 were from (36 ± 10)U/L,(37 ± 13)U/L,(233 ±42)mg/L,(154±32)U/L,(8.1 ±1.6)mg/L,(14±5)g/L,(3.2±1.3)g/L,(2.1 ±1.3)g/L,55.6％±6.8％,37.5％±2.0％,25.9％±2.9％ and 1.5 ±0.5 to (83 ±33)U/L,(63 ±42)U/L,(208 ±37)mg/L,(145 ±26)U/L,(30.3 ±8.6)mg/L,(12 ±3)g/L,(2.8 ±1.6)g/L,(2.0 ±1.2)g/L,46.2％±3.9％,33.4％±3.1％,27.9％±3.0％ and 1.2 ±0.4 in the control group,and from (36 ± 12)U/L,(36 ± 14)U/L,(231 ±45)mg/L,(149 ±25)U/L,(7.6 ± 1.8)mg/L,(13 ±5)g/L,(3.3 ±0.7)g/L,(2.1 ± 1.1)g/L,54.2％±6.3％,37.6％±3.5％,24.8％±3.4％ and 1.5 ±0.4 to (43 ±30)U/L,(40 ±33)U/L,(255 ±44)mg/L,(153 ±27)U/L,(21.7 ±11.2)mg/L,(17 ±4)g/L,(4.1 ± 1.7)g/L,(2.4 ± 1.9)g/L,57.9％±3.2％,39.2％ ± 2.9％ 22.7％ ± 3.4％ and 1.7 ± 0.4 in the testing group,respectively,showing significant differences between the 2 groups (F =94.71,86.40,64.22,16.77,8.18,37.23,11.52,22.58,50.30,26.44,13.16,44.84,P ＜ 0.05).There were no significant differences in the level of ALT,AST,prealbumin,choline esterase,C-reactive protein,IgA,CD8 + and CD4 +/CD8 + at postoperative day 5 between the 2 groups (t =1.24,1.03,0.91,1.02,0.53,0.68,1.61,0.98,P＞0.05).There were significant differences in the IgG,IgM,CD3+and CD4 + at postoperative day 5 between the 2 groups (t =2.58,3.15,3.87,2.46,P ＜ 0.05).There were significant differences in the levels of ALT,AST,prealbumin,choline esterase,C-reactive protein,IgG,IgM,IgA,CD3 +,CD4 +,CD8 + and CD4 +/CD8 + at postoperative day 7 between the 2 groups (t =4.83,2.79,5.58,2.12,3.10,2.53,4.17,2.35,3.45,2.98,3.12,3.75,P ＜0.05).The body weight of patients at postoperative day 7 and duration of hospital stay in the control group were (57 ± 6) kg and (9.9 ± 1.5) days,which were significantly different from (61 ± 8) kg and (8.8 ± 1.3) days in the testing group (t =3.67,2.71,P ＜ 0.05).Conclusion Structured triglyceride can effectively improve the recovery of hepatic function,nutrition status and immunologic function and reduce inflammatory reaction for the patients with primary liver cancer after hepatectomy.

Primary clinical study of a novel bioartificial liver combined with liver transplantation in patients with liver failure / 中华器官移植杂志

Objective To investigate the safety and therapeutic effects of the novel bioartificial liver (BAL) combined with liver transplantation in patients with liver failure.Method Twenty-two patients with liver failure were admitted.Ten of them were treated with the novel BAL 24 h before liver transplantation,while the rest 12 served as controls and received liver transplantation only.The clinical signs and symptoms,liver function,ammonia,coagulation function and complete blood count were evaluated before,during and after the treatment.Levels of xenoantibodies (IgG and IgM) were detected by ELISA kit.Titers of complement were quantified by CH50 kit.DNA in the collected PBMCs was extracted for PCR with PERV specific primers and the porcine specific primer Sus scrofa cytochrome B.The RT activity was detected as well.The operation related information was recorded,such as operation success rate,operative time,cold ischemia time,bleeding volume in operation and liver function.Result All treatment procedures were completed successfully without any adverse reaction.In the BAL group,the clinical symptoms such as acratia,anorexia and abdominal distension were improved,as well as the stage of hepatic encephalopathy and the results of experimental tests such as liver function,ammonia,and coagulation function.No PERV infection and no obvious changes of the IgG,IgM and CH50 levels were detected in patients plasma.All patients were successfully bridged to modified pig-back liver transplantation and recovered.There were no differences in operative time and cold ischemia time (P＞0.05).However,bleeding volume was different in these two groups (P＜0.05).The liver function was improved significantly in BAL group than the control group after liver transplantation (P＜0.01).Conclusion The novel BAL could improve the internal environment of patients with liver failure,and enhance the safety and efficiency of liver transplantation.The novel BAL combined with liver transplantation could be an effective therapy for patients with liver failure.

Research progress in promoting stem cell function and differentiation via electrical stimulation / 国际生物医学工程杂志

Nowadays,stem cells are recognized as the most promising seed cells of tissue engineering due to their self replication ability and multilineage differentiation potential.In order to apply them to tissue engineering,a variety of physical and biochemical methods were tried to promote the proliferation,function and differentiation,and good effects were achieved.Recently,as a rising method of physical stimulation,electrical stimulation received more and more attention and had been proved to have good effects on stem cell proliferation and differentiation.This paper summarized the advances in promoting effects of electrical stimulation on stem cell proliferation and differentiation,and discussed the possible mechanisms of stem cell differentiation induced by electrical stimulation.

Recent advance in liver grafts from marginal donor / 中华肝胆外科杂志

The lack of organ donors is a major obstacle against the application of liver transplantation.Recently,how to expand the source of liver donors has become a focus of transplantation research.The use of marginal donor may help solve current dilemma between the increasing waiting recipients and the relatively few donors.However,marginal donors always comes with elevated risk of primary nonfunction,initial poor function,delayed graft function loss and infection.Research on risk factors and complication preventing strategies of marginal donor transplantation is important in improving our understanding of liver transplantation.In the present article,we summarized recent progress in the research of marginal donors.And based on the experience from our center,we believe that the use of marginal donors in liver transplantation may help improve the situation of donor shortage,and isehemia-reperfusion injury remains the core topic of marginal donor transplantation and represents the direction of future study.

The factors influencing the transfer of porcine endogenous retroviruses across the membrane in bioartificial livers / 中华肝胆外科杂志

ObjectiveTo identify the factors influencing the transfer of porcine endogenous retroviruses across the membrane of a new bioartificial liver (BAL),which is a necessary caution to consider for BALs carrying porcine hepatocytes.MethodsA novel porcine BAL composed of two circuits was constructed using a plasma filter with membrane pore size of 500 nm and a plasma component separator with membrane pore sizes 10 nm,20 nm,30 nm,and 35 nm.Co-cultured cells of porcine hepatocytes and mesenchymal stem cells or single porcine hepatocytes were incubated in the bioreactors.The BAL was continuously worked for 72 hours during which the supernatant was collected from the internal and external circuits every 12 hours.PERV RNA,reverse transcriptase (RT) activity,and in vitro infectivity from the supernatant were detected.ResultsIn the plasma filter group,the PERV RNAlevels were the same in both circuits,suggesting little to no effect of the plasma filter on the PERV RNA's crossing.With plasma component separators,PERV RNA was found in the external circuits at different times without positive RT activity and HEK293 cell infection,but its level was reduced significantly.The larger the membrane pore size was,the earlier and the more RNA was detected.ConclusionsThe membrane pore size,the treatment time and the viral level in the internal circuit are contributing factors influencing the transfer of PERV RNA across the membrane in a BAL.

Primary clinical study of a novel multi-layer flat-plate bioartificiai liver for patients with liver failure / 中华器官移植杂志

Objective To investigate the safety and therapeutic effects ot a novel multi-layer flat-plate bioartificial liver (BAL) for patients with liver failure.Methods Thirty-eight patients with liver failure from Dec.2010 to Dec.2011 were treated with a novel BAL based on multi-layer flatplate bioreactor and the co-cultured cells of the porcine hepatocytes and mesenchymal stem cells.A total of 48 treatments was performed,4 h each time.The clinical signs and symptoms,liver function,ammonia,coagulation function and complete blood count were evaluated before,during and after the treatment.DNA in the collected PBMCs was extracted for PCR with PERV specific primers and the porcine specific primer Sus scrofa cytochrome B.The RT activity was detected as well.Levels of xenoantibodies (IgG,IgM) were determined by using ELISA kit. Titers of complement were quantified by CH50 kit.Results All treatment procedures were completed successfully without any adverse reaction. All samples presented negative PERV DNA and RT activity. The levels of antibodies were similar before and after treatment.Treatment was associated with a temporary decline in levels of complement,and then the levels were recovered quickly.The clinical symptoms such as acratia,anorexia and abdominal distension were improved.The stage of hepatic encephalopathy in 16 patients was decreased. The liver function and ammonia was reduced disproportionately. Seven patients in all were bridged to liver transplantation,2 patients died and 2 patients gave up the treatment,and the others were turned better.After the outcome judgment according to the standard developed by the Artificial Liver Group,and Chinese Association of Infectious and Parasitic Diseases,there were 9 patients with clinical healing,25 patients with improvement and 4 patients with no effect,and the cure-improvement rate was 89.5％.Conclusion The novel multi-layer flat-plate BAL could be used as a safe and effective therapy for patients with liver failure.

Membrane molecular weight cut off impacts immunological safety of a novel bioartificial liver system / 中华肝胆外科杂志

Objective To investigate the influence of membrane molecular weight cut off in our bioartificial liver(BAL)system.Methods Beagle dogs were used for a model of acute liver failure through D-galactosamine administration.The acute liver failure Beagles were divided into two groups by the membrane molecular weight cut off.Group A was treated with BAL containing 200 kDa retention rating membrane.Group B was treated with BAL containing 1200 kDa retention rating membrane.Each group underwent two six-hour BAL treatments that were performed on day 1 and day 21.BAL medium were examined and levels of IgG,IgM,and complement hemolytic unit of 50％(CH50)antibodies were measured in all Beagles and.Results BAL treatment was associated with a significant decline in levels of CH50.1200 kDa group experienced a significant increase in levels of IgG and IgM after two BAL treatments.Significant levels of canine proteins were detected in BAL medium from 1200 kDa group.Conclusions Xenogeneic immune response in the BAL system was influenced by membrane molecular weight cut off.

Reconstruction of portal vein in liver surgery / 中华肝胆外科杂志

As an essential technique involved in complicated liver surgery,portal vein reconstruction results in eradication of macro- or microscopic tumor residual on surgical margins when combined with precise hepatectomy,improving both the living quality and the survival rate of patients.The application of this reconstruction technique needs precise evaluation of pre-operational image data,clearly dissection of portal vessels and tremendous amount of collaborative effort by the surgery team. Other techniques performed during the surgical procedure include intra-operative ultrasound scan,revitalizing the cryopreserved vessels,and angioplasty.

Evidence based therapy for primary liver cancer / 中华肝胆外科杂志

Progress in multi-disciplinary therapy for primary liver cancer (PLC) increases the 5-year survival rate from 2.6％ to 20.6％.However,the overall survival rate failed to increase significantly in the past twenty years because of lack of standardization in treatment of PLC.It is important to establish clinical guidelines which are based on randomized controlled trials,meta analysis,or systematic reviews.This review summarizes the pertinent clinical trials on PLC therapies published before October 2010.The articles were selected by a comprehensive literature search using the terms ‘liver neoplasms',‘ hepatectomy',‘ liver transplantation',‘ transarterial chemoembolization',‘ radiofrequency ablation',‘ percutaneous ethanol injection',‘ radiotherapy',‘ biological therapy',‘ chemotherapy',or ‘ Chinese herbs’.