Renal fibrosis, especially tubulointerstitial fibrosis, is the most common pathway of all chronic kidney diseases progressing to end-stage renal diseases. Several adaptive reactions occur in renal tubular epithelial cells after chronic injury, such as changes in glycolipid metabolism, unfolded protein response, autophagy and senescence, epithelial-to-mesenchymal transition and G2/M cell cycle arrest. Maladaptive repair mechanisms can induce tubulointerstitial fibrosis. This article will discuss the molecular mechanism of these adaptive responses of renal tubular epithelial cells driving renal tubulointerstitial fibrosis, and provide a basis for exploring new drug targets for renal tubulointerstitial fibrosis.

The new medical reform takes the major aim to facilitate the expansion of high-quality medical resources and balance the regional distribution of the resources so as to meet the people's growing demand for high-quality healthcare.To exem-plify the expansion and balance of the high-quality resources,this paper scrutinizes the cooperation between aiding and aided hos-pitals by taking a state-level regional medical center hospital in Guizhou Province as an example.With cooperation-oriented pro-jects,the hospital achieved a homogenized development with the hospitals in developed regions in management,personnel,tech-nology,discipline,and hospital culture by introducing the high-quality resources from those hospitals.Such homogenized devel-opments empower the high-quality development of health care services in the less-developed regions of southwest China.Further-more,the experience of the hospital offers a reference for the development of other aided hospitals of state-level regional medical centers under new circumstances.

Rapid turnover of the intestinal epithelium is a critical strategy to balance the uptake of nutrients and defend against environmental insults, whereas inappropriate death promotes the spread of inflammation. PPARα is highly expressed in the small intestine and regulates the absorption of dietary lipids. However, as a key mediator of inflammation, the impact of intestinal PPARα signaling on cell death pathways is unknown. Here, we show that Pparα deficiency of intestinal epithelium up-regulates necroptosis signals, disrupts the gut vascular barrier, and promotes LPS translocation into the liver. Intestinal Pparα deficiency drives age-related hepatic steatosis and aggravates hepatic fibrosis induced by a high-fat plus high-sucrose diet (HFHS). PPARα levels correlate with TRIM38 and MLKL in the human ileum. Inhibition of PPARα up-regulates necroptosis signals in the intestinal organoids triggered by TNF-α and LPS stimuli via TRIM38/TRIF and CREB3L3/MLKL pathways. Butyric acid ameliorates hepatic steatosis induced by intestinal Pparα deficiency through the inhibition of necroptosis. Our data suggest that intestinal PPARα is essential for the maintenance of microenvironmental homeostasis and the spread of inflammation via the gut-liver axis.

Objective: The epidemiological investigation of donor infection and the investigation of donor-derived infection(DDI)events in kidney transplantation to provide a basis for the prevention and treatment of donor infection and donor-derived infection events. Methods: We retrospectively reviewed 170 donors and corresponding 316 kidney recipients between January 2014 with December 2017, pre-harvest blood, sputum, urine positive and negative culture were systematically recorded. We also collected donors/recipients demographics, transplant characteristics and recipients infection data within one month and focused on patient data of DDI events. Outcomes were followed up 6 months after surgery. Results: Infection rate in 170 donors was 67.6 %, the positive rate of Gram-negative bacteria, Gram-positive bacteria and fungal were 48.3 %, 41.2 % and 10.4 %. Nine of 170 donors were DDI(5.29 %). Positive blood culture, urine culture and donor age were independent risk factors for DDI. Conclusions The incidence of donor infection is high. Although a few DDI events occur, the survival rate decreased. The positive blood culture and urine culture were important risk factors for the occurrence of DDI events. Therefore, it is necessary to focus on the monitoring of some high-risk strains and donors infected by high-risk infection sites.

The positive human leukocyte antigen (HLA) antibody present in kidney transplant recipients affects both surgery and rejection, and also affects the long-term survival of the transplanted kidney. During the third kidney transplant, bilateral axillary fossa and iliac vessel were destroyed. It was very difficult for selection or separation of surgical vessels because the adhesions and scar formation was easy to damage blood vessels and intestinal tubes. A case with strong positive HLA antibody undergoing the third kidney transplant in our hospital was successfully solved the problems, such as less transplant space and vascular scar adhesion. Rituximab, rabbit anti-human thymocyte immunoglobulin, and methylprednisolone treated-antibodies were used in the operation. The immune function test was used to develop individualized treatment after the operation. The postoperative creatinine and urine volume tended to be stable, and the 16-month follow-up renal function was good.
Antibodies ; Humans ; Kidney ; Kidney Diseases ; surgery ; Kidney Transplantation ; Nephrectomy ; Rituximab

OBJECTIVE: To analyze the clinical features of chronic myeloid leukemia (CML) with T315 I mutation (CML-T315I) and compare the effectiveness of different treatments. METHODS: We retrospectively analyzed the clinical data and outcomes of 19 patients with CML-T315I receiving different treatments. The T315 I mutations in these patients were detected by examination of BCR-ABL kinase domain (KD) mutation by RTQ-PCR and Sanger sequencing. The relapse following the treatments, defined as hematological, cytogenetic and molecular biological recurrences, were analyzed in these patients. RESULTS: Of the 19 patients with CML-T315I, 14 (73.7%) were in CML-CP stage at the initial diagnosis, and 13 (81.2%) were high-risk patients based on the Sokal scores. All the 19 patients were treated with TKI after the initial diagnosis, and during the treatment, 15 (78.9%) patients were found to have additional chromosomal aberrations, and 10 (52.6%) had multiple mutations; 13 (68.4%) of the patients experienced disease progression (accelerated phase/blast crisis) before the detection of T315I mutation, with a median time of 40 months (5-120 months) from the initial diagnosis to the mutation detection. After detection of the mutation, 12 patients were treated with ponatinib and 7 were managed with the conventional chemotherapy regimen, and their overall survival rates at 3 years were 83.3% and 14.2%, respectively ( < 0.001). CONCLUSIONS CML patients resistant to TKI are more likely to have T315I mutations, whose detection rate is significantly higher in the progressive phase than in the chronic phase. These patients often have additional chromosomal aberrations and multiple gene mutations with poor prognoses and a high recurrence rate even after hematopoietic stem cell transplantation. Long-term maintenance therapy with ponatinib may improve the prognosis and prolong the survival time of the patients.
Drug Resistance, Neoplasm ; Fusion Proteins, bcr-abl ; Humans ; Imidazoles ; Leukemia, Myelogenous, Chronic, BCR-ABL Positive ; Mutation ; Pyridazines ; Retrospective Studies

Hepatic artery thrombosis (HAT) is the most frequent vascular complication following with liver transplantation,whichis the foremost cause of primary graft nonfunction,graft loss and recipient's death.Hepatic artery thrombosis after liver transplantation wasdivided into early hepatic artery thrombosis (E-HAT) and late hepatic artery thrombosis (L-HAT).And the etiologywascomplex,clinical presentations were diversity,treatment effects were controversial,therefore,the early detection,early diagnosis and early treatment of hepatic artery thrombosis after liver transplantation are very important.In this paper,the progress in the diagnosis and treatment of hepatic artery thrombosis after liver transplantation were reviewed.

To explore the efficacy of sorafenib combined with chemotherapy and donor lymphocyte infusion (DLI) in patients with FLT3-positive acute myeloid leukemia (AML) relapsed after allogeneic hematopoietic stem cell transplantation (allo-HSCT).Of the 14 patients relapsed after allo-HSCT,9 achieved complete remission after salvage therapy of sorafenib combined with chemotherapy and DLI,6 with complete molecular remission,2 with partial remission,and 3 with no response.With a median follow up of 220 (range,30-1 782) days after post-transplantation relapse,7 patients were still alive and 7 died.Salvage therapy of sorafenib combined with chemotherapy and DLI shows a decent therapeutic effect for FLT3-positive AML relapsed after allo-HSCT.

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.

Objective To sum up the experiences in liver transplantations from donation after brain death (DBD),and compare the clinical effect,complications and influential factors with international situation.Methods The retrospective descriptive study was adopted.All the data of 66 DBD liver donors and the matched recipients from authors' affiliations during June 2010 and June 2013 were collected.Original articles,meta-analysis and data reports with high academic influence were read and data were analyzed with SPSS 22.0.Results The incidence of serious complications,vascular complications and biliary complications during the first year among 66 recipients was 21.2％,10.6％,and 6.1％,respectively.Compared to international situation,graft 1-,3-,and 5-year survival rate was similar (P＞0.05) (83％,80％ and 73％ respectively),similar to that of recipients.There was no statistically significant difference in primary nonfunction and vascular complications between our center and other centers.As for biliary complications,morbidity was lower in our center (P＜0.05).The 3-and 5-year survival rate of recipients was also similar (P＞0.05),though the 1-year survival rate was slightly lower (P＜ 0.05).Conclusion These findings provide evidence that patient's prognosis under DBD liver transplantation in our center is acceptable,and long-term survival rate has reached international level.Still,1-year survival rate of recipients is unsatisfactory.In order to achieve a good clinical efficacy,we need to find out disadvantages during donor maintenance,recipient selection,surgical procedure and postoperative management.