Yu-Ling Sun

Plasticity-improved Zr-Cu-Al bulk metallic glass matrix composites containing martensite phase

Zr48.5Cu46.5Al5 bulk metallic glass matrix composites with diameters of 3 and 4mm were produced through water-cooled copper mold casting. Micrometer-sized bcc based B2 structured CuZr phase containing martensite plate, together with some densely distributed nanocrystalline Zr2Cu and plate-like Cu10Zr7 compound, was found embedded in a glassy matrix. The microstructure formation strongly depends on the composition and cooling rate. Room temperature compression tests reveal significant strain hardening and plastic strains of 7.7% and 6.4% before failure are obtained for the 3-mm- and 4-mm-diam samples, respectively. The formation of the martensite phase is proposed to contribute to the strain hardening and plastic deformation of the materials.

Necessity and indications of invasive treatment for Budd-Chiari syndrome

BACKGROUNDnThe development of collaterals in Budd-Chiari syndrome has been described and these collaterals play an important role in the presentation of this disease. These collaterals are diagnostic and their use in management strategy has never been evaluated. This study aimed to investigate the indications, feasibility and necessity of invasive treatment for patients with Budd-Chiari syndrome and to determine whether such a strategy is necessary for optimal management.nnnMETHODSnTwenty-nine patients who had been treated at our unit were enrolled in this study. Based on physical and biochemical examination, and hemodynamic compensation by collaterals, 18 patients underwent radiological intervention (group A), while the other 11 had no invasive treatment (group B). The related hemodynamic parameters were acquired when percutaneous angiography was performed.nnnRESULTSnIn group A, all patients underwent successfully inferior vena cava (IVC) balloon angioplasty with or without stenting. Four patients also underwent hepatic vein angioplasty. In these patients, the mean IVC pressure before and after treatment was statistically different (29.3+/-9.2 vs 15.1+/-4.6 mmHg, P<0.01). The mean IVC pressure was much lower in group B than in group A (12.9+/-2.4 vs 29.3+/-9.2 mmHg, P<0.01), but there was no difference from that of the patients after radiological treatment (12.9+/-2.4 vs 15.1+/-4.6 mmHg, P>0.05). Median follow-up was 32.3 months (mean 21.3 months; range 3-61 months). In the course of follow-up, the patients in group A survived with good systemic status except for re-stenosis in one patient who underwent re-canalization of the IVC. In group B, 10 patients had good systemic status except one patient who had a meso-caval shunt because of deterioration.nnnCONCLUSIONSnThe rationale of early diagnosis and early treatment is not suitable for all patients with Budd-Chiari syndrome. Satisfactory survival can be achieved in some patients without invasive treatment, who are completely compensated by rich collaterals. Nonetheless, a positive treatment procedure should be performed if the patients situation worsens in the course of regular follow-up.

Stem‐like cells in hepatitis B virus–associated cirrhotic livers and adjacent tissue to hepatocellular carcinomas possess the capacity of tumorigenicity

Background and Aim:u2002 Recent investigations demonstrate that adult stem cells may be targets for malignant transformation and that the stem‐like cells in diseased livers possess the capacity of tumorigenicity in animal models. The aim of this study is to examine expression patterns of stem‐cell markers in hepatitis B virus–associated cirrhotic livers and hepatocellular carcinomas (HCC), and to investigate the stem‐like cell capacity of tumorigenicity in these tissues.

Staged management of Budd-Chiari syndrome caused by co-obstruction of the inferior vena cava and main hepatic veins

BACKGROUNDnCollateralized intra- and extra-hepatic routes in patients with Budd-Chiari syndrome (BCS) were important. This study aimed to investigate the feasibility and clinical outcomes of the staged management of BCS based on the degree of compensation provided by intra- or extra-hepatic collateral circulations.nnnMETHODSnA total of 103 adult patients with BCS caused by co-obstruction of the inferior vena cava (IVC) and main hepatic veins (MHVs) between March 2001 and October 2009 were enrolled in this study. Based on the pathological classification and degree of hemodynamic compensation by collateral circulations, treatment priority for IVC hypertension was determined in the first-stage treatment. Patients were deemed eligible for second-stage treatment when the first-stage treatment failed to relieve.nnnRESULTSnImaging results revealed that most patients had collateral circulations to different extents. Based on the degree of compensation provided by these collateral circulations, 74 patients underwent single-stage treatment for IVC hypertension, i.e., radiologic intervention (RI) for 61 patients and surgical procedures (SPs) for 13. One patient was treated for portal hypertension. Twenty-nine patients underwent second-stage treatment (25 underwent RI and SP, and 4 only SP). The general morbidity and mortality after all procedures were 8.3% and 1.5%, respectively. After a median follow-up of 35 months, 4 patients underwent second-stage treatment and 7 underwent recanalization of the IVC/MHVs. Two patients died of hepatocellular carcinoma and 1 died of graft obstruction.nnnCONCLUSIONnStaged management produces excellent outcomes for patients with BCS caused by co-obstruction of the IVC and MHVs.

Immunophenotypic shift of memory CD8 T cells identifies the changes of immune status in the patients after liver transplantation

Abstract Objective: Chronic or acute rejection is a leading cause of allograft loss after solid organ transplantation and the presence of memory T cells is associated with increased propensity for allograft rejection. The purpose of this study was to investigate the correlation between immunophenotypic shift of memory CD8+ T cells and immune status in the patients after liver transplantation. Material and methods: Seventy-three blood samples were collected and varied compartments of memory CD8+ T cells were analysed in non-rejected and rejected patients. Results: The results show that with time elapsed, the immunophenotypes of memory CD8+ cells shifted from naive T cells to central or intermediate memory cells, and then to effector or terminal memory cells in non-rejected patients. This course was correlated with the expression of CD127 on CD8+ T cells. In rejected patients, the main proportion of CD8+ cells were dominated by naive CD8+ cells and then rapidly restored to the immunophenotypes of memory T cells after effective treatment. Conclusion: These results demonstrated that immunophenotypic shift of memory CD8+ T cells was closely related to the change of the immune status in the patients after liver transplantation. Monitoring the immunophenotypic shift of memory CD8+ T cells is of great importance in the prediction for allograft rejection and treatment effectiveness after liver transplantation.

Withdrawal of immunosuppression in liver transplantation and the mechanism of tolerance

BACKGROUNDnImmunosuppression reagents have side effects and cause considerable long-term morbidity and mortality in patients after liver transplantation. Sufficient evidences showed that minimization or withdrawal of immunosuppression reagents does not deteriorate the recipients immune response and physiological function and therefore, is feasible in some recipients of liver transplantation. However, the mechanisms are not clear. The present review was to update the current status of immunosuppression in liver transplantation and the mechanism of minimization or withdrawal of immunosuppression in liver recipients.nnnDATA SOURCESnWe searched articles in English on minimization or withdrawal of immunosuppression in liver transplantation in PubMed. We focused on the basic mechanisms of immune tolerance in liver transplantation. Studies on immunosuppression minimization or withdrawal protocols and biomarker in tolerant recipients were also analyzed.nnnRESULTSnMinimization or withdrawal of immunosuppression can be achieved by the induction of immune tolerance, which may not be permanent and can be affected by various factors. However, accurately evaluating immune status post-transplant is a prerequisite to achieve individualized immunosuppression. Numerous mechanisms for immune tolerance have been found, including immunophenotypic shift of memory CD8+ T cells and CD4+ T cell subsets. Activation of the inflammasome through apoptosis-associated speck-like protein containing a C-terminal caspase recruitment domain (ASC) in dendritic cells is associated with rejection after liver transplantation.nnnCONCLUSIONSnMinimization or withdrawal of immunosuppression can be achieved by the induction of immune tolerance via different mechanisms. This process could be affected by immunophenotypic shift of memory CD8+ T cells and CD4+ T cell subsets, which may be correlated with activation of the inflammasome through ASC in dendritic cells.

Compensation by collateral circulation determines invasive therapeutic indications for patients with Budd-Chiari syndrome

We read with interest the comprehensive review article by Rossle and Gerbes that details the management of ascites in patients with liver cirrhosis and concludes that the transjugular intrahepatic portosystemic shunt (TIPS) could manage refractory ascites more effectively than large-volume paracentesis.1 However, there is an important issue regarding the management of ascites, which is caused by Budd-Chiari syndrome (B-CS), that the authors failed to address.nnIn patients with chronic course, the formation of intra and extrahepatic collaterals leads to improvement of liver function and may silence this disease and make it asymptomatic.2 Thus, collateral circulation …

Mitofusin-2 mediated mitochondrial Ca2+ uptake 1/2 induced liver injury in rat remote ischemic perconditioning liver transplantation and alpha mouse liver-12 hypoxia cell line models

AIM To investigate the protective mechanism of mitofusin-2 (Mfn2) in rat remote ischemic perconditioning (RIC) models and revalidate it in alpha mouse liver-12 (AML-12) hypoxia cell lines. METHODS Sprague-Dawley rats were divided into three groups (n = 6 each): sham, orthotopic liver transplantation and RIC. After operation, blood samples were collected to test alanine aminotransferase and aspartate aminotransferase. The liver lobes were harvested for histopathological examination, western blotting (WB) and quantitative real-time (qRT)-PCR. AML-12 cell lines were then subjected to normal culture, anoxic incubator tank culture (hypoxia) and anoxic incubator tank culture with Mfn2 knockdown (hypoxia + Si), and data of qRT-PCR, WB, mitochondrial membrane potential (ΔΨm), apoptosis, endoplasmic reticulum Ca2+ concentrations and mitochondrial Ca2+ concentrations were collected. RESULTS Both sham and normal culture groups showed no injury during the experiment. The RIC group showed amelioration of liver function compared with the orthotopic liver transplantation group (P < 0.05). qRT-PCR and WB confirmed that Mfn2-mitochondrial Ca2+ uptake 1/2 (MICUs) axis was changed (P < 0.005). In AML-12 cell lines, compared with the hypoxia group, the hypoxia + Si group attenuated the collapse of ΔΨm and apoptosis (P < 0.005). The endoplasmic reticulum Ca2+ decrease and mitochondrial Ca2+ overloading observed in the hypoxia group were also attenuated in the hypoxia + Si group (P < 0.005). Finally, qRT-PCR and WB confirmed the Mfn2-MICUs axis change in all the groups (P < 0.005). CONCLUSION Mfn2 participates in liver injury in rat RIC models and AML-12 hypoxia cell lines by regulating the MICUs pathway.

Total closure of pancreatic section for end-to-side pancreaticojejunostomy decreases incidence of pancreatic fistula in pancreaticoduodenectomy

BACKGROUNDnPostoperative pancreatic fistula (POPF) is a serious complication and results in prolonged hospitalization and high mortality. The present study aimed to evaluate the safety and effectiveness of total closure of pancreatic section for end-to-side pancreaticojejunostomy in pancreaticoduodenectomy (PD).nnnMETHODSnThis was a prospective randomized clinical trial comparing the outcomes of PD between patients who underwent total closure of pancreatic section for end-to-side pancreaticojejunostomy (Group A) vs those who underwent conventional pancreaticojejunostomy (Group B). The primary endpoint was the incidence of pancreatic fistula. Secondary endpoints were morbidity and mortality rates.nnnRESULTSnOne hundred twenty-three patients were included in this study. The POPF rate was significantly lower in Group A than that in Group B (4.8% vs 16.7%, P<0.05). About 38.3% patients in Group B developed one or more complications; this rate was 14.3% in Group A (P<0.01). The wound/abdominal infection rate was also much higher in Group B than that in Group A (20.0% vs 6.3%, P<0.05). Furthermore, the average hospital stays of the two groups were 18 days in Group A, and 24 days in Group B, respectively (P<0.001). However, there was no difference in the probability of mortality, biliary leakage, delayed gastric emptying, and pulmonary infection between the two groups.nnnCONCLUSIONnTotal closure of pancreatic section for end-to-side pancreaticojejunostomy is a safe and effective method for pancreaticojejunostomy in PD.

Hepatocyte Differentiation of Human Fibroblasts from Cirrhotic Liver in vitro and in vivo

BACKGROUNDnMesenchymal stem cells (MSCs) and fibroblasts have intimate relationships, and the phenotypic homology between fibroblasts and MSCs has been recently described. The aim of this study was to investigate the hepatic differentiating potential of human fibroblasts in cirrhotic liver.nnnMETHODSnThe phenotypes of fibroblasts in cirrhotic liver were labeled by biological methods. After that, the differentiation potential of these fibroblasts in vitro was characterized in terms of liver-specific gene and protein expression. Finally, an animal model of hepatocyte regeneration in severe combined immunodeficient (SCID) mice was created by retrorsine injection and partial hepatectomy, and the expression of human hepatocyte proteins in SCID mouse livers was checked by immunohistochemical analysis after fibroblast administration.nnnRESULTSnSurface immunophenotyping revealed that a minority of fibroblasts expressed markers of MSCs and hepatic epithelial cytokeratins as well as alpha-smooth muscle actin, but homogeneously expressed vimentin, desmin, prolyl 4-hydroxylase and fibronectin. These fibroblasts presented the characteristics of hepatocytes in vitro and differentiated directly into functional hepatocytes in the liver of hepatectomized SCID mice.nnnCONCLUSIONSnThis study demonstrated that fibroblasts in cirrhotic liver have the potential to differentiate into hepatocyte-like cells in vitro and in vivo. Our findings infer that hepatic differentiation of fibroblasts may serve as a new target for reversion of liver fibrosis and a cell source for tissue engineering.