Objective To explore the cause and treatment strategy of chronic graft rejection characteristic of jaundice in patients with liver transplantation. MethodsPrimary disease, immunosuppressive protocol were reviewed in nine cases surviving more than 1 year after liver transplantation. The pathology examination, choledochoscopy and ultrasound examination were performed. The dosage of immunosuppressive agent was adjusted. Four cases underwent operation. Results Chronic rejection was well controlled in 6 out of the 9 cases with total bilirubin level decreased from 200 ?mol/L to less than 100 ?mol/L. Bile flocculus and bile slush became less obvious or disappeared after flushing and dilataltion of the common bile duct. Three cases died in spite of aggressive therapy. ConclusionsInsufficient immunosuppressive strength is one of the most important causes for chronic rejection. Immunological injury results in hepatocellular damage, bile slush, inflamed thick bile duct.

BACKGROUND:Matrix metal oproteinases (MMPs) have been shown to break the balance between the production and degradation of extracel ular matrix by degrading col agen, gelatin, elastin and other macromolecules, which is the leading cause of bone and cartilage damage in rheumatic arthritis.
OBJECTIVE:To determine the expression levels of MMP-2 and MM-9 in the rabbit knee osteoarthritis cartilage, and to analyze whether they are related to the early MRI performance.
METHODS:Fifty healthy Japanese white rabbits free from osteoarthritis were enrol ed and randomly divided into control group (n=10) and model group (n=40). The anterior and posterior cruciate ligament amputation was adopted to establish the model of osteoarthritis. Subsequently, MRI examination and the expression levels of MMP-2 and MMP-9 were detected at 1, 3, 5 and 7 weeks (n=10 at each time point), respectively.
RESULTS AND CONCLUSION:MRI examination showed that more damaged cartilage appeared with time in the rabbit model of osteoarthritis, and significantly different from MRI classification (P<0.05). The expression levels of MMP-2 and MMP-9 mRNA in the model group were always significantly higher than those in the control group (P<0.05);MMP-2 level reached the highest at 3 weeks after modeling (P<0.01), and then presented a slight decline;MMP-9 level peaked at 5 weeks after modeling (P<0.01) and slightly decreased at 7 weeks. MRI classification of cartage injury and expressions of MMP-2 (R2=0.119, P=0.119) and MMP-9 (R2=0.466, P=0.466) were shown to have the correlation. These results il ustrate that the serum levels of MMP-2 and MMP-9 are related to the early destruction of articular cartilage in patients with osteoarthritis, and can be used as predictors for early osteoarthritis.

Objective To explore the relationship between immune functions of patients with acute leukemia (AL) and invasive fungat infection (IFI). Methods T lymphocyte subpopulations and natural killer (NK) cells in 61 AL patients complicated with IFI at first visit, AL remission, the time of IFI onset and 4 weeks after antifungal treatment were measured by flow cytometry. Meanwhile,levels of IgG, IgM and IgA were detected by immunoturbidimetry. The statistical analysis was done using ANOVA, t test and chi-square test. Results CD3+ , CD3+ CD4+ , CD8+ CD28+ T lymphocyte as well as CD4+/CD8+ ratio at the time of IFI onset in AL patients were all lower than those at first visit, AL remission and 4 weeks after antifungal treatment (F= 25.6,26.6,13. 1,167.9; all P＜0.05), while CD8+ CD28- T lymphocyte were higher than those at first visit, AL remission and 4 weeks after antifungal treatment (F= 220.2,P＜0.01). CD3+ , CD3+ CD4+ and CD4 + /CD8+ ratio of patients who responded effectively to antifungal treatment were all higher than those of non-responders (t=3.75,8. 61,3.17; all P＜0.05). The serum levels of IgG, Igm and IgA at first visit, ALremission, the time of IFI onset and 4 weeks after treatment were similar (F=0.78,0.72,0.81; all P ＞0.05). The effect rate of antifungal therapy in AL remission group was higher than that in nonremission group (87% vs 53%,x2 = 7.62, P＜0.05). Conclusions The cellular immune functions are impaired severely in AL patients complicated with IFI, while the levels of IgG, IgM and IgA are similar during IFI. Therefore, the efficacy of antifungal therapy may partly depend on the recovery of cellular immune functions and remission of AL.

Objective To deepen the understanding of chronic disseminated candidiasis(CDC)in patients with acute leukemia(AL).Methods CDC was investigated in 119 AL patients who received induction chemotherapy from August 2004 to May 2005.Clinical manifestations,laboratory tests,imaging modalities,diagnosis and treatment were investigated retrospectively.Results Three patients(2.5%) were identified to be suffering from CDC.All the three patients had an absolute neutrophil count (ANC)＜0.5 × 109/L for more than 15 days.Two patients had normal ANC when they were diagnosed to have CDC.The common manifestations in these three patients were persistent fever,splenohepatomegalia and percussion pain in hepatic region.Meanwhile,2 of them were accompanied with cough,expectoration and dyspnoea.The abnormal laboratory test observed during the course of infection in two of them was increase of alkaline phosphatase.Computed tomography scan showed multiple hypodense lesions in the liver and spleen in all the three patients:two of them showed multiple nodular patchy shadOW$in lungs.Nuclear magnetic resonance imaging showed multiple abnormal signal in liver,spleen and kidneys in one of the patients.Two patients had positive bleed fungal cultures and histologic examination in one of the patients were positive for Candida tropicalis.Two patients received amphotericin B therapy empirically,but it was replaced by amphotericin B colloid dispersion (ABCD) later in one and combined with voficonazole in another because of unresponsiveness to the drug.One patient took a favorable turn after receiving ABCD therapy for 45 d,which was replaced by voriconazole because of the emergence of fever after disconfinuation of ABCD.All the three patients received further chemotherapy smoothly after the diagnosis of CDC.Conclusion The diagnosis of CDC remains difficult.Fungal blood cultares and histologic examination have been considered in many studies as the golden standard for the diagnosis of CDC.Amphotericin B is the cornerstone of treatment in patients with CDC and lipid formulations of amphotericin B can be used in CDC patients who are intolerant of or refractory to conventional amphotericin B.Voriconazole has a favorable response for refrectory/relapse patients and could be used for second line trectment.The development of CDC in patients with acute leukemia does not preclude further chemotherapy.

BACKGROUND:At present, there are a number of articles about hypothermic machine perfusion versus static cold storage of kidney alografts; however, the conclusions are various. Furthermore, due to the limitation of single sample size, there is a lack of objective evaluation on the merits and demerits of hypothermic machine perfusion. OBJECTIVE: To compare the prognostic outcomes of hypothermic machine perfusion and static cold storage of kidney alografts. METHODS: A computer-based search of PubMed, sinoMed, EMbase, Web of Science, the Cochrane Central Register of Controled Trials (CENTRAL), Wanfang and CNKI databases were searched from their establishment to March 4, 2015 to screen the randomized controled trials (RCTs) about hypothermic machine perfusion versus static cold storage for kidney transplantation. Meanwhile, the references of included RCTs were also searched by hand. After study selection, RCTs screening, data extraction and quality assessment were conducted by two reviewers independently. Meta-analyses were performed by using the RevMan5.3.0 software. The quality of evidence was assessed by using the GRADEpro3.6 software. RESULTS AND CONCLUSION: Six articles were included, involving 619 cases undergoing hypothermic machine perfusion and 620 cases undergoing static cold storage. The results of Meta-analyses showed that the incidence of primary graft non-function, incidence of delayed graft function of functional kidney alografts, and incidence of delayed graft function were significantly lower in the hypothermic machine perfusion group than the static cold storage group (P < 0.05 or 0.01). There were no differences in the 1-year recipient survival rate and 1-year alograft survival rate between the two groups (P > 0.05). These findings indicate that the hypothermic machine perfusion only can reduce the incidence of postoperative complications to maintain the function of kidney, but cannot improve the 1-year recipient survival rate and 1-year alograft survival rate. Hypothermic machine perfusion has no advantage on the long-term preservation of donor organ compared with the static cold storage.

Objective To study the influence of CYP3A5 genetic polymorphism on tacrolimus metabolism in renal transplantation recipients and evaluate the methods of detecting CYP3A5* 3 polymorphism. Methods Ninety-seven renal recipients receiving the triple immunosuppressive (tacrolimus + mycophenolate mofetil + prednison) were genotyped for CYP3A5* 3 polymorphisms by the Pyrosequencing TM assays. Tacrolimus trough concentration of the patients was measured by enzyme multiplied immunoassay technique, and concentration/adjusted dose ratio (C/D) was investigated at the 7th day, 14th day, 1st month, 3rd month and 6th month after renal transplantation. Results The Pyrosequencing TM assays allowed for quick and accurate detection of CYP3A5* 3 genotypes. There were CYP3A5* 1/* 1 genotype in 17 cases (17. 5%), * 1/* 3 in 35cases (36. 1 %) and *3/* 3 in 45 cases (46.4 %) identified in 97 renal recipients. The C/D of CYP3A5 * 1/* 1 and * 1/* 3 patients was significantly lower than that of * 3/* 3 patients (P<0. 01)after renal transplantation. Conclusion The CYP3A5* 3 polymorphisms are significantly correlated with tacrolimus pharmacokinetic in renal transplant recipients. Detecting the CYP3AS* 3 genotype of the recipient before the transplantation by the Pyrosequencing TM assays can be used to help determine the optimal initial dosage after transplantation, resulting in individualized drug therapy.

The change and the role of MAPK cascade pathway and P53 pathway after liver transplantation were explored. Thirty-four punctured donor liver specimens and 10 normal liver specimens were classified as group A (no rejection, n= 10), group B (mild/moderate acute rejection, n = 10), group C (serious acute rejection, n = 8), group D (chronic rejection/fibrosis, n = 6) and group E (control, n= 10). By using tmmunohistochemistry, the expression levels of mitogen activated protein kinase (MAPK), Ras and P53 proteins, and by in situ hybridization, MAPK and ras mRNA expression levels were detected. The results showed that the expression levels of MAPK and Ras proteins were increased by turns in groups A, B and C, and decreased by turns in groups D and E. The protein expression of P53 was higher in the treated groups. The expression of Ras,HSP70 mRNA was identical as that of protein. It is suggested that the MAPK cascade pathway and P53 pathway can protect the hepatocytes by different mechanisms after liver transplantation.MAPKs cascade pathway repairs hepatocyte injury or accelerates hepatocytes into proliferation or differentiation. P53 pathway blocks cell cycle within G1 phase to make hepatocyte repair or apoptosis to reduce disorder differentiation.

Composite tissue allotransplantation (CTA) is a novel transplantation discipline to treat functional tissue or limb defects. Since a majority of CTA grafts were vascularized grafts, it is also known as vascularized composite allotransplantation (VCA). The grafts of CTA/VCA consist of two or more types of allogeneic skin, subcutaneous tissue, bone, muscle, nerve and vessel, etc. Most of CTA/VCA grafts contain skin tissues, which possess the highest antigenicity. Acute rejection after transplantation is the primary obstacle leading to CTA/VCA graft failure and primary graft dysfunction. Hence, histopathological characteristics of skin rejection in CTA/VCA grafts have become the primary hotspot. In this article, pathological features of CTA/VCA rejection, Banff classification in 2007 and related research progress were reviewed, aiming to provide reference for the diagnosis and treatment of rejection and other complications of CTA/VCA.

Objective To investigate the diagnosis and treatment of antibody-mediated rejection after liver transplantation.Methods The clinical data of 1 case of antibody-mediated rejection after liver transplantation were collected.The patient had autoimmune liver disease (de-compensated stage) and received a liver transplantation with ABO-compatible.Triple immunosuppressive regimen of tacrolimus + mycophenolate mofetil + prednisone was used after operation.The valley of tacrolimus concentration was maintained at 8-10 μg/L.One month after transplantation,the liver function recovered to normal.Alanine aminotransferase was 16 U/L,aspartate aminotransferase was 37 U/L and total bilirubin was 17.3 U/L.Results Three months after operation,the liver function index increased sharply (total bilirubin was 186.3 U/L).The first pathological examination of liver biopsy at 14th week after operation showed the histological findings of acute rejection.Combining the data of clinical features,steroid pulse therapy was given,but the effect was poor.The biopsy of the retransplanted liver at 18th week after operation showed necrosis of minority hepatic cells and obvious attachment of lymphocytes in the central venous branch wall.Panel reactive antibodies test revealed that the HLA_ Ⅱ antibodies were intensively positive,suggesting the diagnosis of AMR.After treatment with plasma exchange and adjusting the immunosuppressant dosage,the function of the transplanted liver recovered gradually.Conclusion For liver transplantation with compatible blood type and recipient with autoimmune liver disease,we should alert the occurrence of acute AMR.Timely liver biopsy and PRA detection should be performed for definite diagnosis.Plasmapheresis is effective in treating acute AMR after liver transplantation.