Optimal diagnosis and treatment for renal allograft fibrosis / 器官移植

Renal allograft fibrosis is one of the common and severe complications after kidney transplantation, which seriously affects the function and survival rate of renal allograft, and may even lead to organ failure and patient death. At present, the researches on renal allograft fibrosis are highly complicated, including immunity, ischemia-reperfusion injury, infection and drug toxicity, etc. The diagnosis and treatment of renal allograft fibrosis remain extremely challenging. In this article, the latest research progress was reviewed and the causes, novel diagnosis and treatment strategies for renal allograft fibrosis were investigated. By improving diagnostic accuracy and optimizing treatment regimen, it is expected to enhance clinical prognosis of kidney transplant recipients, aiming to provide reference for clinicians to deliver proper management for kidney transplant recipients.

Research progress on the role of macrophages in post-transplantation chronic rejection / 器官移植

Organ transplantation is the optimal treatment for end-stage organ failure. Nevertheless, rejection remains an important factor affecting the allograft survival. At present, acute rejection may be effectively treated, whereas no effective interventions are available for post-transplantation chronic rejection. Long-term chronic rejection may lead to graft failure and severely affect long-term survival rate of allografts. In recent years, the role of macrophages in post-transplantation chronic rejection has gradually captivated increasing attention. In this article, main pathological changes of chronic rejection, the diversity and functional differences of macrophages involved in chronic rejection, and the role and mechanism of macrophages in chronic rejection were reviewed, and research progresses on macrophage-related treatment for chronic rejection were summarized, aiming to provide reference for the study of macrophages in post-transplantation chronic rejection.

A comparative histological analysis of early and late graft dysfunction in different time zones following living donor liver transplantation

Background: Liver biopsy plays a crucial role in evaluating allograft dysfunction. Comprehensive analysis of the histological spectrum of complications, particularly rejection, in different time zones is lacking. Aim: To evaluate the histological spectrum of rejection, in four time zones, in a large Living donor liver transplant series. Patients and Methods: Retrospective analysis of 313 biopsies for the last 10 years of living donor liver transplantation (LDLT) recipients. 123 of which had rejection as diagnosis, were redistributed in four time zones [1-early (<3), 2-intermediate (3–6), 3 and 4-late (6–12 and > 12) months] and were assessed for sixteen histological parameters. Results: Biopsies in time zone 1 (26.5%), 2 (20.7%), 3 (24.6%), and 4 (28.1%)] were nearly equal. Multiple coexistent complications existed in 12% of the cases. Rejection diagnosed in time zone groups: 1 = 22 (17.9%), 2 = 27 (22%), 3 = 36 (29.3%), and 4 = 38 (30.9%). Portal inflammation mixed type (P < 0.000), portal vein (P = 0.001) and hepatic vein endothelialitis (P < 0.000), portal eosinophils (P = 0.001), and lymphocytic bile duct damage (P = 0.01) were most pronounced in group 1. Perivenulitis without hepatic vein endothelialitis was observed (P = 0.03) in groups 3, whereas bile duct atypia (P = 0.01) and duct loss (P < 0.000) were observed in group 4. Multiple episodes of rejection displayed significant association with central perivenulitis (P = 0.002) and bile duct loss (P < 0.001). Conclusions: Histological analysis in large series of LDLT recipients highlights the spectrum of complications in different time zones. Late acute and chronic rejection occurred as early as 3 months posttransplant. Central perivenulitis and bile duct atrophy were associated with repeated episodes of rejection and deterioration.

Gut microbiota and its implications in small bowel transplantation / 医学前沿

The gut microbiota is mainly composed of a diverse population of commensal bacterial species and plays a pivotal role in the maintenance of intestinal homeostasis, immune modulation and metabolism. The influence of the gut microbiota on solid organ transplantation has recently been recognized. In fact, several studies indicated that acute and chronic allograft rejection in small bowel transplantation (SBT) is closely associated with the alterations in microbial patterns in the gut. In this review, we focused on the recent findings regarding alterations in the microbiota following SBTand the potential roles of these alterations in the development of acute and chronic allograft rejection. We also reviewed important advances with respect to the interplays between the microbiota and host immune systems in SBT. Furthermore, we explored the potential of the gut microbiota as a microbial marker and/or therapeutic target for the predication and intervention of allograft rejection and chronic dysfunction. Given that current research on the gut microbiota has become increasingly sophisticated and comprehensive, large cohort studies employing metagenomic analysis and multivariate linkage should be designed for the characterization of host-microbe interaction and causality between microbiota alterations and clinical outcomes in SBT. The findings are expected to provide valuable insights into the role of gut microbiota in the development of allograft rejection and other transplant-related complications and introduce novel therapeutic targets and treatment approaches in clinical practice.

Role of mTOR C1/C2 pathways involve in abrogation of chronic rejection in rat heart transplantation model / 国际生物医学工程杂志

Objective To study the expression of the components of the mammalian rapamycin target protein (mTOR) pathway in T lymphocytes in rats with chronic rejection (CR),and to explore the role of mTOR pathway in the inhibition of CR.Methods ACI rat recipients received intraperitoneal ectopic cardiac transplantation with Wistar-Furth rat hearts.In the experimental group,a mutated class Ⅰ major histocompatibility complex (MHC Ⅰ) that can eliminate CR was delivered into recipients prior-operation,and a sub-therapeutic cyclosporine A (CsA) (10 mg/kg,3 d) was also administered.In the experimental control group,the heart allograft recipients were treated with sub-therapeutic CsA (10 mg/kg,3 d).The blank controls were the untreated recipients.Each group was divided into three subgroups (5 rats in each subgroup) according to the sacrifice time on the postoperative 1st,3rd and 7th days.The spleen samples were taken for T cell extraction and Western blot analysis.Results Western blot results showed that rat heart allografts with abolished CR exhibited downregulation of the RAPAsensitive mTORC 1 elements including mTOR and Raptor,and down-regulation of the RAPA-insensitive mTORC2 elements including Rictor and Sin1.Conclusions Abrogation of CR in rat model system involves modulation of mTOR C1 and mTOR C2 pathways.The mTOR C1 pathway regulates cellular proliferation and the mTORC2 pathway regulates T-cell motility.Selective targeting of T-cell actin cytoskeletal pathways shows potential for pathway-targeted immunosuppression therapies.

Patología del trasplante hepático, aspectos más relevantes del período postrasplante tardío / Most Relevant Pathology Issues in the Late Post Liver Transplant Period

La sobrevida de los pacientes postrasplante hepático supera el 90% al año y el 75% a los 5 años. Entender las causas de pérdida del injerto, o inclusive la muerte del paciente, es esencial para mejorar aún más los resultados a largo plazo. La evaluación de las biopsias hepáticas tiene un papel importante en la explicación y manejo de la disfunción del injerto de hígado, que ocurre después del primer año del trasplante. La interpretación de estas biopsias puede ser muy difícil, en especial por la alta incidencia de enfermedades recurrentes que pueden mostrar un cuadro clínico y unas características histopatológicas que semejan varias condiciones, especialmente cuando el rechazo agudo o crónico pueden sobreponerse a una patología ya existente o presentarse de manera simultánea y contribuir a la disfunción tardía del injerto, por lo que el análisis de la biopsia puede ayudar a determinar el componente principal de la lesión. Es indispensable la correlación clínico patológica, teniendo en cuenta la enfermedad original, el tipo de inmunosupresión, las pruebas de función hepática, las serologías virales, los autoanticuerpos y los hallazgos radiológicos. En este artículo comentaré las patologías más frecuentes y las que causan más problemas en su diagnóstico durante el período postrasplante tardío

One year survival rates of liver transplant patients exceed 90% while five year survival rates exceed 75%. Understanding the causes of graft losses and patient deaths is essential for further improvement of long-term results. Evaluation of liver biopsies has an important role in explaining liver graft dysfunction that occurs more than one year after transplantation, and thus is key for post-transplant patient management. The interpretation of these biopsies can be very difficult especially because of the high incidence of recurrent diseases that sometimes have clinical and histopathological features that resemble various other conditions. This is especially true for acute and chronic rejection which can overwhelm an existing condition and which can develop simultaneously with other conditions that contribute to late graft dysfunction. Analysis of the biopsy can help determine the main component of a lesion. Clinical findings must be correlated to pathological findings, and the correlation must take into account the original disease, the type of immunosuppression, liver function tests, viral serology, autoantibodies and radiological findings. In this article I will discuss the most common diseases and those that cause the most problems for diagnosis during the late post-transplant period

Prognostic factors for the evolution and reversibility of chronic rejection in pediatric liver transplantation

OBJECTIVE: Chronic rejection remains a major cause of graft failure with indication for re-transplantation. The incidence of chronic rejection remains high in the pediatric population. Although several risk factors have been implicated in adults, the prognostic factors for the evolution and reversibility of chronic rejection in pediatric liver transplantation are not known. Hence, the current study aimed to determine the factors involved in the progression or reversibility of pediatric chronic rejection by evaluating a series of chronic rejection cases following liver transplantation. METHODS: Chronic rejection cases were identified by performing liver biopsies on patients based on clinical suspicion. Treatment included maintaining high levels of tacrolimus and the introduction of mofetil mycophenolate. The children were divided into 2 groups: those with favorable outcomes and those with adverse outcomes. Multivariate analysis was performed to identify potential risk factors in these groups. RESULTS: Among 537 children subjected to liver transplantation, chronic rejection occurred in 29 patients (5.4%). In 10 patients (10/29, 34.5%), remission of chronic rejection was achieved with immunosuppression (favorable outcomes group). In the remaining 19 patients (19/29, 65.5%), rejection could not be controlled (adverse outcomes group) and resulted in re-transplantation (7 patients, 24.1%) or death (12 patients, 41.4%). Statistical analysis showed that the presence of ductopenia was associated with worse outcomes (risk ratio=2.08, p=0.01). CONCLUSION: The presence of ductopenia is associated with poor prognosis in pediatric patients with chronic graft rejection.

Progress of immunologic mechanisms of Vδ2-γδT cell in cytomegalovirus infection / 国际儿科学杂志

Recently,an unconventional T cell population (collectively designated as Vδ2 -γδT cell ) has been characterized during the anti-cytomegalovirus immune response in all organ transplant recipients,neo-nates,and healthy individuals.These cytomegalovirus-induced Vδ2 -γδT cells undergo a dramatic and stable ex-pansion after cytomegalovirus infection,in a conventional adaptive way.Similarly,as cytomegalovirus-specific CD8 +αβT cells,they exhibit an effector/memory TEMRA phenotype and cytotoxic effect or functions.This paper reviews the researchs and reports about cytomegalovirus induced-Vδ2 -γδT cell,including its location,phe-notype,and activation,as well as its immunologic mechanism in cytomegalovirus infection,acute or chronic re-jection,and anti-cancer function.

Clinical and pathological analysis of rejection cases after kidney transplantation / Шинэ санаа Шинэ нээлт

Kidney transplantation is the best alternative treatment for end-stage renal disease and health-related quality of life and survival of the patients are improved compared with dialysis. Worldwide, more than 1.4 million patients with CKD receive renal replacement therapy with incidence growing by approximately 8% annually.1 Unfortunately, despite significant improvement in graft function, kidney transplants can still fail due to acute rejection and chronic allograft nephropathy.2 Kidney biopsy after transplantation, which has evaluated by Banff 09 classification is usefull method for diagnose of transplanted kidney disease.3,4Kidney graft rejection was diagnosed in 10 renal allograft biopsy specimens (bs) obtained from transplant patients followed up at our institute between 2015 and 2016. All specimens were evaluated as satisfactory which show more than 8 glomerulus under the light microscopy. Each renal cortical tissue was divided into two tips: one piece for routine H&E stain and special stains, including Masson’s trichrome, and PAS stain; another piece for immunofluorescence by frozen section, which were stained with IgA, IgM, IgG and complement component (C3, C4, C1q, C4d). All the renal biopsies were examined by the same pathologist.Out of 117 transplantations, 10 episodes of rejection selected. Among the 10 patients, 30% had an acute T cell rejection and 70% had a chronic allograft nephropathy. Interstitial inflammation (i1-7) was present in 7 bs (70%), tubulitis (t1-4,t2-2) in 6 bs (60%), transplant glomerulitis (g1-1, g2-2, g3-1) in 4 bs (40%), transplant interstitial fibrosis (ci1-2, ci2-2, ci3-2) in 6 bs (60%), tubular atrophy (ct1-6, ct2-2, ct3-1) in 9 bs (90%), mesangial matrix increase (mm1-5) in 5 bs (50%), vascular fibrosis intimal thickeness (cv1-3) in 3 bs (30%), arteriolar hyaline thickening (ah1-5) in 5 bs (50%), tubulitis (ti1-6, ti2-3, ti3-1) in 10 bs (100%) and peritubular capillaritis (ptc1-1, ptc2-2, ptc3-1) in 4 bs (40%). C4d deposition was present very mild in wall of the vessels and peritubular capillaries. Because of not good working Methenamin silver stain, we couldn’t demostrate glomerular basement membrane changes (cg) fully.We suggest that histopathological changes of transplant glomerulopathy might be accompanied by inflammation of the microvasculature, such as transplant glomerulitis and peritubular capillaritis. C4d deposition in the wall of the vessels and peritubular capillaritis is not always present in biopsy specimens of transplant glomerulopathy.

Manufacture and comparison of chronic rejection model of orthotopic and heterotopic intestinal ;transplantation in rats / 器官移植

Objective To compare the modeling effect of chronic rejection following orthotopic and heterotopic intestinal transplantation in rats.Methods F344 (RT1 1 vr )rats were used as the donors and Lewis (RT1 1 )rats were used as the recipients.Models of allogeneic heterotopic and orthotopic intestinal transplantation in rats (8 rats in each model) were established,and subcutaneous injection of ciclosporin was given at 0 ~1 4 d after operation.Changes in body weight and survival time of the recipients were observed after operation.In addition,pathological changes in intestinal tissue were observed by hematoxylin-eosin (HE)staining.Changes in collagenous fibers and elastic fibers in intestinal tissue were observed after alcohol and hematoxylin staining.Finally,success rate of modeling of recipients in two groups was calculated.Results Rats in heterotopic and orthotopic intestinal transplantation groups were able to survive for a long time,most of which were more than 90 d.For the rats in orthotopic intestinal transplantation group,normal diet could be recovered at the 3 rd d after operation.Their body weight could recover preoperative level at about the 1 4th d after operation,and then grew slowly.However,most of the rats in orthotopic intestinal transplantation group continued weight loss from the 1 50th d after operation,which could not be reversed with ciclosporin.For the rats in heterotopic intestinal transplantation group,normal diet could be recovered at the 1 st d after operation,and their body weight could recover preoperative level within 25-30 d after operation and gradually rose and remained at a high level within 30-90 d after operation.No pathological changes of chronic rejection and obvious mesangial fibrosis in intestinal tissue were observed at the 90th d after operation,but intestinal tissue developed chronic rejection and obvious mesangial fibrosis at the 1 63 rd d and 200th d after operation in orthotopic intestinal transplantation group.Typical pathological changes of chronic rejection and mesangial fibrosis in intestinal tissue were observed at the 90th d and 200th d after operation for rats in heterotopic intestinal transplantation group.All the rats in heterotopic intestinal transplantation group showed characteristic pathological changes.The success rate of modeling was 1 00% in heterotopic intestinal transplantation group,which was not of statistical significance,compared with the success rate of modeling of 75% in the orthotopic intestinal transplantation group (P >0.05).Conclusions Chronic rejection will occur at different time points with small dose of ciclosporin after operation if models of orthotopic and heterotopic intestinal transplantation are established in combination of F344 → Lewis rats.Compared with orthotopic intestinal transplantation,the rat model of heterotopic intestinal transplantation holds the advantages of simple modeling,shorter chronic rejection and relatively consistent degree of pathological changes,which is more suitable for experimental study.

The relation between epithelial-mesenchymal transition and bronchiolitis obliterans post lung transplantation in rats / 中华胸心血管外科杂志

Objective To imitate the pathological process of bronchiolitis obliterans(BO) post lung transplantation and in-vestigate the phenomenon of epithelial-mesenchymal transition ( EMT ) in small airway epithelial cells and its relation to BO . Methods We established the rat model of allogeneic orthotropic left lung transplantation with grafts from F 344 rats transplanted to Lewis rats by the Tri-cuff anastomosis.Then rats were daily injected intraperitoneally with cyclosporine (5 mg· kg-1 · d-1 ) for 10 days, intratracheally applied with lipopolysaccharide(0.5 mg/kg) at the 28th day and killed at the 90th day post-surger-y.We observed the histological structure of the lung grafts by HE and Masson staining , detected E-cadherin and Vimentin ex-pression in lung grafts and normal ones of F344 rats by immunohistochemistry, then analyzed the relation between small airway remodeling and the alterations in EMT markers expression .Enumeration data was analyzed with Fisher exact test and Spearman rank correlation was applied in correlation analysis .Results We found inflammatory cell infiltration , fibroplasia of bronchiole walls and significant lumen stenosis in lung graft mesenchyma.In lung grafts, the positive expression of E-cadherin was 5(total 13), which was significantly lower than that in normal lungs(7/8, P<0.05), and conversely the positive expression of Vim-entin was higher than normal ones(10/13 vs 2/8, P <0.05).The Spearman rank correlation analysis demonstrated that E-cadherin expression bear a negative correlation with Vimentin expression(r=-0.750, P<0.01).Conclusion Our study established a disease model imitating the pathological process of BO .And EMT was observed in small airway epithelial cells of the BO-exhibited lung grafts, indicating that EMT was involved in the process of BO airway remodeling .Thus it may reveal no-vel therapeutic targets for BO post lung transplantation by further investigation into the mechanism and pathological significance of EMT in small airway epithelial cells.

Rechazo en trasplante pulmonar: ¿cómo evaluarlo por tomografía computada multidectector? / Lung Transplant Rejection: How to Evaluate by Multidetector Computed Tomography?

El trasplante pulmonar es una opción terapéutica válida para mejorar la sobrevida de pacientes con enfermedades respiratorias en fase avanzada. La supervivencia tras el trasplante de pulmón ha mejorado en gran medida como resultado de los avances en la técnica quirúrgica, la cuidadosa preservación de órganos de donantes, las mejoras en la terapia inmunosupresora y el reconocimiento precoz de complicaciones con el uso de técnicas de imagen. Nuestro objetivo es proporcionar una guía radiológica del rechazo agudo y crónico del trasplante pulmonar. Se describirán los hallazgos por tomografía computada multidetector (TCMD).

Lung transplantation is a valid therapeutic option to prolong survival in patients with end-stage pulmonary disease. Survival after lung transplantation has greatly improved as a result of advances in surgical techniques, careful preservation of donor organs, progress in immunosuppressive therapy, and the use of imaging techniques for an early recognition of complications. Our goal is to provide a radiology guide of acute and chronic rejection of lung transplants. The fndings of multidetector computed tomography (MDCT) studies are described.

Advances in research on animal models of chronic rejection after lung transplantation / 中国实验动物学报

The most important cause of late mortality after lung transplantation is obliterative bronchiolitis ( OB) . It is clear that a good animal model is indispensable to further unravel and clarify the pathogenesis of bronchiolitis obliterans syndrome ( BOS) .Many animal models have been developed to study BOS, however, so far, none of these models truly mimics the human condition.In recent years mouse models of orthotopic lung transplantation have been established, which provide potential possibilities for further studies of OB/BOS after lung transplantation.The aim of this article was to review the pros and cons of those animal models, and discuss the possible approaches to establish animal models of chronic rejec-tion after lung transplantation.

Therapeutic effects and possible mechanisms of sirolimus on nephritic mice with chronic rejection / 国际药学研究杂志

Objective To explore the therapeutic effects of sirolimus on nephritic mice with chronic rejection, and the possible mechanisms. Methods B6D2F1 mice transplanted with cell mixture of spleen, thymus, and lymph nodes from DBA/2 spleen, thymus, and lymph nodes cell mixture were used to construct murine model with chronic rejection, and the transplanted mice were randomly divided into two groups. Mice in the sirolimus-treated group were given sirolimus orally in a dose of 1 mg(kg*d) for 12 consecutive weeks, while mice in the control group were administered with equal amounts of olive oil. Nephritis in mice was confirmed by urine protein determination and histopathological analysis. Enzyme immunoassay was used to detect the serum levels of anti-DNA antibodies including anti-ds DNA IgG, anti-ds DNA IgG1, anti-ds DNA IgG2a, anti-ss DNA IgG, anti-ss DNA IgG1, and anti-ss DNA IgG 2a. Real-time PCR analysis was conducted to evaluate the gene expression of interleukin-6 (IL-6), tumor necrosis factor-α (α), interferon-γ (IFN-γ), interleukin-1 β (IL-lβ), monocyte chemoattractant protein 1 (MCP-1), regulated upon activation n T cell expressed and secreted (RANTES), B lymphocyte chemoattractant (BLC), transforming growth factor βi (TGF-βi), and gen I. The proportion and activation of T and B lymphocytes in peripheral blood or spleen were determined by flow cytometric ana Results At the end of observation period, the incidence of nephritis in mice treated with sirolimus was significantly lower than t mice treated with olive oil (P < 0. 05). Histopathological evaluation of kidney specimen showed evident vascular intimal hyper and mononuclear cell infiltration in control group. In contrast, no obvious kidney lesions was observed in sirolimus-treated mice. thermore, the levels of anti-DNA antibodies and the transcriptional expression of lupus IL-6, TNF-α, IFN-γ, IL-lβ, MCP-1, ] TES, BLC, TGF-βi, and collgen I were significantly down-regulated in sirolimus-treated group as compared with control group. cytometric analysis indicated that both of the proportion of activated/memory T cells in peripheral blood and the expression level o face activation markers on T and B lymphocytes in spleen were significantly decreased in mice exposed to sirolimus as comparec those exposed to olive oil (P <0. 05). On the other hand, the proportion of CD4 + FOXP3 + regulatory T cells in spleen was si cantly upregulated in sirolimus-treated group as compared with control group. Conclusion Sirolimus may inhibit the proliferatio activation of effector cells and downregulate the expression of chemokines and inflammatory factors through up-regulation of (FOXP3 3T cells, thus effectively ameliorating the progression of nephritis in mice.

Clinical efficacy of tertiary liver transplantation / 中华消化外科杂志

Objective To investigate the efficacy of tertiary liver transplantation.Methods The clinical data of 4 patients with hepatobiliary disease who were admitted to the General Hospital of Chinese People's Armed Police Forces from April 2002 to December 2012 were retrospectively analyzed.All the patients received orthotopic liver transplantation,and received tacrolimus + mycophenolate mofetil (MMF) + hormone after operation.All the patients were followed up till May 2014,and their prognosis was learned.The measurement data were analyzed using the t test.Results Three patients with benign hepatic disease received tertiary liver transplantation due to biliary complications and chronic rejection,and 1 patient with hepatic cancer received tertiary liver transplantation because of hepatic cancer recurrence.The average interval between the primary and secondary liver transplantation was 16.0 months,which was shorter than 22.5 months of the interval between the secondary and tertiary liver transplantation.The mean operation time in the secondary liver transplantation was (11.4 ± 1.0)hours,which was significantly shorter than (14.1 ± 2.2) hours in the tertiary liver transplantation (t =3.644,P ＜ 0.05).The median volumes of blood loss in the secondary and tertiary liver transplantation were 1 300 mL and 1 800 mL,and the median volumes of blood transfusion were 1 400 mL and 3 100 mL.The hepatic function of the 4 patients recovered smoothly at the early time after liver transplantation.Two patients (3 cases) were complicated with infection postoperatively (1 patient was infected by pseudomonas aeruginosa within 30 days after liver transplantation,and was cured by active antimicrobial treatment),and they were cured after anti-infectional treatment.One patient died of hepatic failure at the 80th month after the primary liver transplantation,1 died of hepatic cancer recurrence complicated by pulmonary,bone and retroperitoneal lymph node metastasis at the 107th month after the primary liver transplantation,and the other 2 patients survived for 104 months and 26 months after the primary liver transplantation,respectively.Conclusion Tertiary liver transplantation is effective for the treatment of biliary complications and chronic rejection after liver transplantation,and it can extend the life span of patients with hepatic cancer recurrence if there are insufficient donor resources.

Current Issues in the Treatment of Chronic Antibody-Mediated Rejection in Kidney Transplantation / 한양의대학술지

Circulating alloantibodies are found in a substantial number of renal allograft recipients, and can induce chronic allograft injury, which is represented microscopically as transplant glomerulopathy and diffuse C4d deposition in peritubular capillaries (PTCs). Development of these injuries is significantly correlated with late allograft loss, and in this regard, it was included as a new disease entity named chronic antibody-mediated rejection (cAMR) in the updated Banff 05 classification. Usually, the prognosis of cAMR is poor and conventional immunosuppressants mainly targeting T cell-mediated immunity cannot prevent or reverse it. Therefore, some researchers have suggested that therapies directed at the humoral response may be required for the treatment of cAMR. Recently, some reports have suggested that the combined use of rituximab and intravenous immunoglobulin (IVIg) therapy may be useful for the treatment of cAMR. Our previous study also showed that rituximab and IVIg combination therapy effectively delayed the progression of cAMR. We administered rituximab and IVIg combination therapy to 18 biopsy-proven cAMR patients and found that it significantly slowed the decline of the estimated glomerular filtration rate. However, this effect was limited in patients with heavy proteinuria, and dissipated in all patients by 1 year post-treatment. Recently, new drugs targeting the humoral immune system, such as bortezomib and eculizumab, have been tested for the treatment of cAMR. However, the studies still lack definitive data in terms of successful treatment of cAMR. We speculate that those therapies will compensate for the limitation of previous anti-humoral therapies for cAMR.

Experimental study of platelet derived growth factor expression in small bowel transplantation of rats / 中国综合临床

Objective To investigate the expression of platelet derived growth factor(PDGF) in small bowel transplantation of rats.Methods Isogeneic and allogeneic small bowel transplantation were performed in rats by microsurgical technology.All rats were divided into two groups:isogeneic control group and allogeneic test group.Transplanted tissues were test on 7th,28th and 90th after surgery.Positioning using immunohistochemical method the expression of PDGF.Real time PCR and immunohistochemical staining were also performed to detect the expression of PDGF.Results The unique feature including intestinal graft fibrosis was showed in tissues.Immunohistochemistry results showed PDGF expression was higher in intestinal glands.PDGF mRNA levels in transplanted tissues showed a gradual upward trend,and the top levels is in POD90.Conclusion PDGF expression was significantly higher in the late of intestinal transplantation,which showed an guideline for chronic rejection of intestinal transplantation.

The rat model of graft cholangiopathies established by cold preservation or chronic rejection / 中华肝胆外科杂志

Objective To develop rat models of graft cholangiopathies and evaluated their values.Methods Four groups were constructed.The long-term cold preservation group(n=24) contained homogeneic inbred rat liver orthotopic transplantations (ROLT) performed in a rat combination of ♂ Wistar→ ♂ Wistar with the donor liver preserved in 4℃ UW for 12 h,the vessels reconstructed by the two-cuff method,and the hepatic artery and extrahepatic bile duct rebuilt by a stent.The chronic rejection group (n=24)(CsA 1 mg · kg-1 · d-1,cold preserved for 1 h) was allogeneic inbred ♂ DA→♂ Lewis rats induced for ROLT,and the revascularization methods were the same as the longterm cold preservation group.The control group (n=24) (cold preserved for 1 h) was homogeneic inbred ♂ Wistar→♂ Wistar rats with ROLT techniques the same as above.The sham group (n=24)was ♂ Wistar rats that had an exploratory laparotomy.The animals were followed for 16 weeks,complications were compared,and liver tissues were harvested.Histopathological and morphometric techniques were used to construct a time course of histological changes after liver transplantation.Results In both the long-term cold preservation group and chronic rejection group,the rats recovered slowly,the incidence of complications and mortality were higher than those of other groups,and the intrahepatic bile duct proliferation and immune cell infiltration were noticeable after the operation.In 16 weeks,the hepatic lobules were separated by the proliferating bile ducts,the normal structure of hepatic lobules disappeared,many biliary epithelial cells necrosed with disappearing cytoplasms,and there was immune cell infiltration and obliterative arteriopathy.Conclusions The rat models of graft cholangiopathies induced by long-term cold preservation or chronic rejection donor livers are stable and easily standardized.This model is ideal for studying the pathogenesis and prevention of graft cholangiopathies.

The expression and significance of decorin in chronic rejection of liver transplantion / 国际外科学杂志

Objective To investigate expression and significance of decorin(DCN)in liver tissue and serum of liver transplant patients with chronic rejection(CR).Methods Immunohistochemistry(SP method)was used to detect expression of DCN in liver tissue of 16 normal controls, 20 patients with cirrhosis, 46 liver translantion patients without CR and 8 patients with CR.Enzyme-linked immunosorbent assay method(ELISA method)was used to determined the content of DCN in serum of all research subjects.Results The expression of DCN was negative in normal hepatic tissues and with/without CR, cirrhosis tissues showed strong expression of DCN.The positive expression rate and the average optical density value of DCN in liver transplant tissues with CR had significant difference comparing with Cirrhosis tissues(25% vs 55%, 0.1249 ±0.0039 vs 0.2357 ±0.0396, P <0.01,while no statistic siqnificance compared to normal liver tissues and those without CR.The level of DCN in serum was significantly higher in liver transplant patients with CR, with significant difference comparing with normal people, liver cirrhosis and transplant liver patients without CR(54.0833 ± 6.0325)μg/L vs(1.0232 ± 0.9105)μg/L,(12.6202 ± 1.5370)μg/L,(17.7102 ± 2.3562)μg/L, P < 0.01).The concentration of DCN in serum showed a positive correlation with the degree of CR.Conclusions DCN showed negative expression in liver tissue and increased significantly in serum of liver transplantation patients with CR.This suggests that DCN may be involved in occurrence and development of CR.At the same time the determination of DCN in serum maybe become an important indicator of the early diagnosis, development and prognosis of CR for liver transplant patients.

n-3 PUFA can inhibit the apoptosis of intestinal epithelial cells of chronic rejection after small intestinal transplantation / 肠外与肠内营养

Objective: The aim of our work was to investigate the effects of n-3 polyunsaturated fatty acids on apoptosis, granzyme B and perforin expression of intestinal epithelial cells of chronic rejection after small intestinal transplantation. Methods: Small bowel transplantation was performed and rats were divided into three groups: Group 1, Lewis-to-Lewis, group 2, F344-to-Lewis, dietary corn oil, Group 3, F344-to-Lewis, dietary fish oil. All recipients were killed after 16 weeks of posttransplantation. The apoptosis rate of mucosal cells were evaluated by flow cytometry. The expressions of granzyme B and perforin were analyzed by reverse transcriptase RT-PCR. Results: A high apoptotic rate was observed when the allografts demonstrated one or more histological features of chronic rejection. N-3 polyunsaturated fatty acids decreased the rate of the apoptosis and inhibitted the expressions of granzyme B and perforin. Conclusion: N-3 polyunsaturated fatty acids can suppress the chronic rejection in small intestinal transplantation.