Objective This study aimed to investigate the role of microRNA-34a (miR-34a) in regulating liver regeneration (LR) and the development of liver cancer in rats by targeting Notch signaling pathway. Methods Thirty male Sprague-Dawley (SD) rats were randomly assigned into partial hepatectomy (PH) group and sham hepatectomy (SH) group. Hematoxylin and eosin (HE) staining was used to observe the histological change in liver tissues. Enzyme-linked immunosorbent assay (ELISA) was used to measure the serum tumor necrosis factor α (TNF-α) and interleukin-6 (IL-6) levels. Dual-luciferase reporter gene assay was performed to examine whether miR-34a targeted Notch1 gene. Human liver cancer Huh7 cells were transfected and divided into blank, negative control (NC), miR-34a mimics and miR-34a inhibitors groups. MTT and flow cytometry were used to detect cell growth, and cell cycle and apoptosis, respectively. Quantitative real-time polymerase chain reaction (qRT-PCR) was applied detect to the expressions of miR-34a and Notch receptor mRNA. Western blotting was performed to detect the protein expressions of Notch receptors, P21, Bax, Bcl-2 and Bcl-xL. Tumor xenograft in nude mice was done to observe tumor formation in different groups. Results Compared to the SH group, miR-34a expression in liver tissues in the PH group decreased first and then increased to the normal level during LR. In early stage of LR, the expressions of Notch receptors and miR-34a were negatively correlated. Compared to the blank and NC groups, the cell growth was inhibited, cell cycle was mainly arrested in the G2/M phase and cell apoptosis rate increased in the miR-34a mimics group. Moreover, the expressions of miR-34a, P21 and Bax were up-regulated, while the expressions of Notch receptors, and Bcl-2 and Bcl-xL were down-regulated in this group. Additionally, the tumor growth in the miR-34a mimics group was reduced. The miR-34a inhibitors group showed contrary tendencies. Conclusion Our study demonstrates that miR-34a regulated LR and the development of liver cancer by inhibiting Notch signaling pathway.

Background Metabolic syndrome (MS) is common in kidney transplant recipients(KTRs) and associated with an increased risk of cardiovascular events. There is a need for accurate, non-invasive methods to predict MS in this population. Lipid accumulation product (LAP) is an effective marker of central lipid accumulation related to high risk of MS, cardiovascular disease(CVD) and diabetes. This study aims to assess the ability of LAP as a marker of MS in KTRs. Methods A total of 92 KTRs were included in this study. The general anthropometries and blood biochemical indexes were measured. Body mass index(BMI), waist-hip ratio (WHR), LAP, HOMA-IR and Framingham risk scores(FRS) were calculated. Results The prevalence of MS was 57.8 % in KTRs. Respectively, 64.1%, 16.3%, and 19.6% of patients with KTRs were at low, intermediate, and high risk of CVD according to FRS categorization. KTRs with MS had significantly higher LAP levels compared to those without MS. LAP was highly correlated with lipid metabolism, abdominal obesity, glucose metabolism and inflammatory factor in KTRs. Our analyses revealed that LAP is an independent risk factor for development of MS. Receiver operating characteristic curve (ROC) analysis showed that LAP was a significant discriminator for prediction of MS in KTRs. The optimal cutoff value for LAP in predicting MS was 39.72 (80.8 % sensitivity, 90 % specificity). Conclusion Our study revealed all adiposity measures of interest present themselves as easy and practical tools for evaluating MS in KTRs and LAP is the best index for the determination of MS in KTRs among them.

Viral infection seriously affects the survival and life quality of transplanted patients without an accurate diagnosis during the early stage. Herein, we aimed to develop a novel diagnostic method based on non-coding RNAs expression in peripheral blood. An immunosuppressive mouse model of viral infection after transplantation was established. Differentially expressed non-coding RNAs were distinguished by microarray analyses in the virus-infected group. After homology analysis, 46 miRNAs and 24 lncRNAs were further verified by qRT-PCR in the peripheral blood samples of transplanted patients. Compared with normal transplanted patients, miR-29b, miR-185, and NR_073415.2 were significantly downregulated in the PBMC of post-transplant patients with viral infection. Based on the expression of the above three RNAs, principal component analysis (PCA) identified a slight overlap between the two groups. A 3-non-coding-RNA detection panel was constructed by the support vector machine analysis (SVM), whose loss rate was 14.71%. The area under the curve of it was 0.909. With the optimal cut-off value (Y = 0.328), the sensitivity was 0.929 and the specificity was 0.781. Therefore, based on non-coding RNAs expressions, a detection panel for viral infection after organ transplantation was formed with high diagnostic specificity and sensitivity.

Objective: Venous thromboembolism (VTE) is one of the most important postoperative complications after total joint replacement, which seriously affects the recovery of patients. We conducted this network meta-analysis to comprehensively compare the efficacy and safety of various common anticoagulants.Methods: We used data of relevant randomized controlled trials from multiple database. Then a Bayesian network meta-analysis was performed to assess the efficacy and safety of different anticoagulant drugs or strategies by comparing seven related outcome indicators.Results: 49 eligible studies that assessed 55464 patients after total hip replacement were included into our network meta-analysis. According to our results, extended rivaroxaban and rivaroxaban combined with aspirin are nearly most effective for preventing any kinds of thrombosis but they seem to be closely related with the incidence of bleeding events. Dalteparin combined with aspirin can prevent DVT, VTE, proximal DVT, PE and reduce bleeding events significantly. UFH, TB-402 are not ideal for use as the posteroperative anticoagulants because of their non-prominent effects and relevance with the bleeding events. Dextran is the worst in the prevention of thrombosis.Conclusion: Combined anticoagulant regimes are more effective in prevention of vein thrombosis after total hip replacement than single anticoagulant, and extended duration strategies are more effective than standard duration strategies in prevention of vein thrombosis. Extended rivaroxaban and rivaroxaban combined with aspirin are both ideal choices for patients at high risk for thrombosis. But for patients who might be concerned about the bleeding risk, dalteparin combined with aspirin is the preferable option rather than rivoxaban.Funding Statement: This work was supported by the Mittal Innovation Project of Central South University (Grant No. GCX20190879Y), the Fundamental Research Funds for the Central Universities of Central South University (Grant No. 2018zzts930), the Central South University Sports Medicine Scholarship, the National College Students’ Innovation and Entrepreneurship Training Program (Grant No. 201710422116).Declaration of Interests: The authors stated: "None declared."Ethics Approval Statement: This network meta-analysis was completed in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines.

Background: Ischemia-reperfusion injury (IRI) has been considered an inevitable event in organ transplantation since the first successful kidney transplant was performed in 1954. To avoid IRI, we have established a novel procedure called ischemia-free organ transplantation. Here, we describe the first case of ischemia-free kidney transplantation (IFKT). Materials and Methods: The kidney graft was donated by a 19-year-old brain-dead donor. The recipient was a 47-year-old man with end-stage diabetic nephropathy. The graft was procured, preserved, and implanted without cessation of blood supply using normothermic machine perfusion. Results: The graft appearance, perfusion flow, and urine production suggested that the kidney was functioning well-during the whole procedure. The creatinine dropped rapidly to normal range within 3 days post-transplantation. The levels of serum renal injury markers were low post-transplantation. No rejection or vascular or infectious complications occurred. The patient had an uneventful recovery. Conclusion: This paper marks the first case of IFKT in humans. This innovation may offer a unique solution to optimizing transplant outcomes in kidney transplantation.

Cerebral ischemia reperfusion (I/R) injury is associated with a high incidence of neurological morbidity and mortality worldwide. Higenamine has anti-inflammatory, anti-oxidative and anti-apoptotic capacities and has been successfully used in myocardial and intestinal ischemia reperfusion. We hypothesized that higenamine might serve the same effects in cerebral I/R. In a rat model of cerebral I/R, higenamine improved functional state of nerves, significantly inhibited the I/R-induced increase in the serum level of tumor necrosis factor α (TNF-alpha) and interleukins (ILs) such as IL-1, IL-6 and IL-18, and CD14+ cells, while decreasing the axonal nerve degeneration. Together, the data demonstrate that higenamine has therapeutic effect in cerebral I/R injury.

Long non-coding RNA small nucleolar RNA host gene 20 (SNHG20) has been demonstrated to play crucial regulatory roles in many types of cancer. However, the biological function of long ncRNA (lncRNA) SNHG20 in ovarian cancer is still unclear. In the present study, we found that lncRNA SNHG20 was significantly increased in ovarian cancer. In addition, lncRNA SNHG20 knockdown suppressed the ovarian cancer progression, whereas overexpression of SNHG20 showed the opposite effects. Moreover, our results also revealed that lncRNA SNHG20 knockdown inhibited Wnt/β-catenin signaling activity by suppressing β-catenin expression and reversing the downstream target gene expression. Taken together, lncRNA SNHG20 plays an pivotal role in ovarian cancer progression by regulating Wnt/β-catenin signaling.

我国自2010年开展心脏死亡器官捐献（donation after cardiac death,DCD）试点工作[1]以来,截至2016年9月,已完成8 866例器官捐献,获取各类供器官近2.5万个。由于DCD供肾功能差异较大,供肾弃用时有发生。本研究回顾性分析2011年7月至2015年9月中山大学附属第一医院器官移植三区弃用供肾的DCD供者资料,总结相关

Objective To analyze the incidence of BK virus (BKV) infection after kidney transplantation in our center and to evaluate the efficacy and safety of conversion treatment with Mizoribine (MZR) on BKV infection after kidney transplantation.Methods The information of recipients who received BK virus screening in hospital or outpatient during 2015-02 to 2016-12 in our center was retrospectively analyzed.The recipients positive for BKV were divided into experiment group (given conversion treatment with MZR) and control group (not given MZR conversion) according to the inclusion criteria.The negative rate of BKV,AR,hyperuricemia and the function of renal allograft during the conversion treatment with MZR were observed.Results 182 recipients accepted BKV screening during 2015-02 to 2016-12 and 68 cases were positive.The positive rate of BKV was 38.5 ％.The positive rate of peripheral blood specimens and midstream urine specimens was 7.1％ and 36.8％ respectively.Twelve recipients were positive for BKV in both peripheral blood specimens and midstream urine specimens.There were 27 recipients in experiment group and 36 cases in control group.Fourteen recipients positive for BKV became negative after MZR conversion in experiment group and the negative rate was up to 51.9％.The mean time of negative rate was 3.2 ± 2.7 (1-10) months after MZR conversion.During the conversion treatment with MZR,AR occurred in 1 case and was reversed by the impact therapy with Thymoglobulin in experiment group.The value of serum uric acid was maintained stable before and after MZR conversion under the action of uric-acidlowering drug.The renal function was kept stable in both experiment group and control group after renal transplantation.No deaths and renal allograft failure cases occurred in both groups during the research period.The 2-year survival rate for patients and kidneys was both 100％.Conclusion The incidence of BKV infection after kidney transplantation was high and the treatment scheme of MZR conversion was safe and effective.

OBJECTIVE To evaluate the outcomes of transplantation of deceased donor stone-bearing kidneys. METHODS A total of 32 patients who received renal transplantation at our center from July 2011 to June 2016 were included. Eight recipients received kidneys with incidental renal stone(s) (stone group). Twenty-four recipients received kidneys without renal stones (non-stone group). The transplantation outcomes of the 2 groups were compared. RESULTS There was 1 case of postoperative urinary tract infection in the stone group, and 2 cases in the non-stone group. No ureteral obstruction or hydronephrosis occurred in either group. No significant difference was found in the incidence of complications, serum creatinine level, and estimated glomerular filtration rate between the groups (all, P > .05). No deaths occurred in either group during the follow-up period. One recipient had postoperative calculi recurrence, and 4 recipients had residual calculi before transplantation. However, these patients had no symptomatic nephrolithiasis or obstruction, and their renal functions were normal. CONCLUSION Transplantation of deceased donor stone-bearing kidneys can achieve comparable outcomes of deceased donor non-stone-bearing kidneys. (C) 2017 Elsevier Inc.

Liver resection (LR) and liver transplantation (LT) are potential curative treatment methods for early hepatocellular carcinoma (HCC). However, it is controversial which treatment is more beneficial to patients with solitary HCC meeting the United Network for Organ Sharing (UNOS) criteria (single lesion, diameter <= 50mm, no vascular invasion, no extrahepatic metastasis). We retrieved patients with solitary HCC meeting UNOS criteria diagnosed between 2004-2013 from the Surveillance Epidemiology and End Results (SEER) database. Multivariate Cox proportional hazards regression models were used to evaluate the impact of surgery type (LR/LT) on overall survival (OS) and disease-specific survival (DSS) in both the whole study group and subgroups. Our analyses show that LT Patients had significantly superior OS (Adjusted HR (95% CI): 0.39 [0.26-0.59]) and DSS (Adjusted HR (95% CI): 0.19 [0.10-0.35]) than those receiving LR, although compared with the 288 patients receiving LR, the 258 patients receiving LT had younger age, smaller tumor size, and higher fibrosis score (P<0.001). Subgroup analyses identified significant interactions between surgery type (LR/LT) and gender (Male/Female) in both OS (P = 0.02) and DSS (P = 0.02). Male patients benefit more from LT compared with LR in both OS (Adjusted HR (95% CI): 0.29 [0.18-0.47]) and DSS (Adjusted HR (95% CI): 0.10 [0.05-0.21]), but there is no difference between patients receiving LT and LR in female patients. In conclusion, LT is associated with superior survival than LR in patients with solitary HCC meeting UNOS criteria. Moreover, male patients benefits more from LT than LR, while female patients do not show different outcomes between the two procedures.

Transplantation centers have given much attention to donor availability. However, no reliable quantitative methods have been employed to accurately assess graft quality before transplantation. Here, we report that the indocyanine green (ICG) clearance test is a valuable index for liver grafts.

Rhabdomyolysis in deceased donors usually causes acute renal failure (ARF), which may be considered a contraindication for kidney transplantation. From January 2012 to December 2016, 30 kidneys from 15 deceased donors with severe rhabdomyolysis and ARF were accepted for transplantation at our center. The peak serum creatinine (SCr) kinase, myoglobin, and SCr of the these donors were 15569 +/- 8597U/L, 37092 +/- 42100 mu g/L, and 422 +/- 167 mu mol/L, respectively. Two donors received continuous renal replacement therapy due to anuria. Six kidneys exhibited a discolored appearance (from brown to glossy black) due to myoglobin casts. The kidney transplant results from the donors with rhabdomyolysis donors were compared with those of 90 renal grafts from standard criteria donors (SCD). The estimated glomerular filtration rate at 2 years was similar between kidney transplants from donors with rhabdomyolysis and SCD (70.3 +/- 14.6 mL/min/1.73m(2) vs 72.3 +/- 15.1 mL/min/1.73m(2)). We conclude that excellent graft function can be achieved from kidneys donors with ARF caused by rhabdomyolysis.

A discolored/black kidney has 5 major differential diagnoses: massive microthrombi and/or severe cortical necrosis, hemosiderosis, lipofuscin or melanin pigment deposits, and oculocutaneous albinism. Renal hemosiderosis is an indicator of severe intravascular hemolysis.1 Lipofuscin or melanin pigment deposits can also cause black kidney.2,3 In addition, oculocutaneous albinism can result in black kidneys due to accumulation of ceroid-like material in the lysosomes of the kidney.4 Herein, we report 2 black kidneys which resulted from a donation after cardiac death (DCD) donor with severe rhabdomyolysis which were successfully transplanted. An 18-year-old man was severely injured in a motor vehicle accident. His medical history was unremarkable, without chronic anemia, oculocutaneous albinism or other related syndromes. He was hospitalized in the intensive care unit for 26 days before donation. His initial laboratory results were as follows: serum creatinine (SCr), 0.6 mg/dL; creatine phosphokinase (CPK), 433 units/L; and serum myoglobin, 540 μg/L. His peak CPK was 22 408 units/L, peak serum myoglobin was 119 617 μg/L, and peak SCr 4.4 mg/dL. At the time of organ procurement, his SCr was 1.3 mg/dL, CPK was 439 units/L, and serum myoglobin was 353 μg/L. Urine output for the 24 hours before organ procurement was 3550 mL, and the terminal urine output was 150 mL/h. Organs were donated through the procedure of DCD. The functional warm ischemic time (starts when the systolic blood pressure has a sustained fall below 50 mm Hg and extends up to the onset of cold in situ perfusion) was 6 minutes. The time from oxygen saturation falls below 70% to the onset of cold in situ perfusion was 15 minutes. After finishing cold in situ perfusion, the kidneys looked black (Figure 1A). Based on the black appearance, other centers turned down the kidneys. Wedge biopsy was performed on the right kidney, and frozen section showed normally structured glomeruli and tubules, mild edema of tubular epithelial cells, and no microthrombosis in the vessel loop of the glomeruli. The right kidney was preserved by static cold storage, and the left kidney was preserved by a LifePort Organ Recovery Systems, the pump perfusion lasted for 16 hours with terminal flow 141 mL/min and resistance 0.16 mm of Hg/(mL/min). Based on the donor’s history, the renal biopsy pathological results, and the pump characteristics, the 2 kidneys were accepted for transplantation at our center.FIGURE 1: A, Black appearance of the kidneys after bench surgery. B, Casts were evident after Masson Trichrome staining (original magnification, ×400). C, Casts stained for myoglobin (original magnification, ×400).In recipient 1, immediate graft function was observed with a cold ischemia time of 24 hours. His SCr reached a nadir value of 1.0 mg/dL on postoperative day 5. Recipient 2 also achieved immediate graft function with a cold ischemia time of 28 hours. His SCr reached a nadir value of 1.1 mg/dL on postoperative day 7. Both recipients received induction therapy with thymoglobulin 1.5 mg/kg per day for 4 days. Subsequent maintenance immunosuppression consisted tacrolimus, mycophenolate mofetil, and prednisone.5 Six months posttransplant, both recipients are doing well with stable SCr of 0.9 and 1.1 mg/dL, respectively. Final paraffin section pathological results showed massive casts in the distal convoluted tubules and immunohistochemical staining of the casts for myoglobin was positive (Figures 1B, C). Rhabdomyolysis is common in trauma patients with acute renal injury, and it is not a contraindication for kidney donation,6-8 even though the donor may be anuric from acute kidney injury.8 However, discoloration of the kidneys has not been mentioned in prior reports.6-8 The myoglobin generated after rhabdomyolysis will lead to blocking and damage of the glomerulus and kidney tubule, with pathological changes similar to acute tubular necrosis. The black appearance of the kidneys in this case was caused by massive myoglobin casts in the distal convoluted tubules. Patients with renal hemosiderosis can have normal renal function or can have renal failure.1 Myoglobin casts cannot be differentiated from renal hemosiderosis based on a frozen section. Moreover, rhabdomyolysis is a clinical diagnosis based on serum CPK levels and is not generally made on the basis of biopsy findings.9 Pump parameters and frozen section biopsy results are helpful for determining the acceptability of kidneys from marginal donors. We usually pump 1 kidney and perform a wedge biopsy on the other kidney from the same DCD donor because we are concerned that the biopsy procedure may cause a leakage of the pump solution and result in overestimation of the pump flow. Generally, we accept kidneys with a resistance less than 0.4 mm Hg/(mL/min) when a biopsy excludes microthrombi or glomerular thrombi, cortical necrosis, and chronic lesions. We conclude that kidneys with a black appearance from severe rhabdomyolysis may be suitable for transplantation.

It has been reported that microRNAs (miRs) can regulate renal response to acute injury and members of them are believed to be important in maintenance of renal function and development of renal injury. We investigated the actions of microRNA423- 5p (miR-423-5p) and glutathione-S-transferase (GST) M1 after acute kidney injury. MiR-423-5p was up-regulated and GSTM1 was down-regulated in human kidney (HK-2) cells subjected to hypoxia/reoxygenation (H/R) and in rat kidneys subjected to ischemia/reperfusion (I/R) injury. Dual luciferase assays revealed miR-423-5p binding to the 3' untranslated region of GSTM1. Proliferation was lower and apoptosis, ER stress and oxidative stress were all higher in H/R-treated HK-2 cells transfected with or without miR-423-5p mimics and GSTM1 siRNA than in the same cells transfected with miR-423-5p inhibitors and a GSTM1 expression vector. Increased miR-423-5p and decreased GSTM1 mRNA and protein levels were observed in rat kidneys on days 1, 2 and 7 after I/R. Levels had normalized by days 14 and 21. On day 3 after treatment, rats receiving I/R or I/R plus miR-423-5p mimics exhibited higher serum creatinine and urea nitrogen levels than rats receiving I/R plus a miR423- 5p inhibitor. MiR-423-5p and lower GSTM1 mRNA and protein levels were higher in the I/R and I/R plus miR-423-5p mimic groups than in the I/R plus miR-423-5p inhibitors group. These findings demonstrate that after acute kidney injury, miR-4235p induces ER stress and oxidative stress by inhibiting GSTM1and suppresses repair.

Objective To investigate the long-term clinical efficacy of simplified multivisceral transplantation in patients with end-stage liver disease and type 2 diabetes.Methods The clinical data of 31 cases of simplified multivisceral transplantations between 2009 to 2017 were retrospectively analyzed.Results Median post-transplant follow-up was currently 13 ± 26 (0-86) months.Two recipients died of multiple organ dysfunction system (MODS) followed by severe sepsis on postoperative day (POD) 15 and 18,respectively.One recipient died from severe pneumonia with pyemia on POD 37.One recipient died of graft versus host disease (GVHD) on POD 40.One recipient died from acute myelogenous leukemia.Two recipients died of tumor recurrence at postoperative month (POM) 9 and 26,respectively.No biliary complication or diabetes recurrence was observed during follow-up.Condusion Donation after citizen's death is becoming the only organic source in China.Our results indicate that combined en-bloc liver-pancreas transplantation is technically feasible and leads to excellent long-term control of glucose metabolism and satisfactory quality of life in recipients with end—stage liver disease and diabetes mellitus.

Background Suicide through taking poison organophosphate, the most widely used pesticide in China, is an infrequent cause of death in organ donors. The transplant colleagues may hesitate to use these organs due to concerning the quality and safety of the organs. We want to investigate the effect of kidney transplantation from donors died from suicide through taking organophosphate. Method Kidney transplantation from donors died of suicide by taking organophosphate were retrospectively reviewed. Results There were 6 donors died of poisoning of organophosphate. Pre-implant wedge biopsy of donor kidneys showed normal glomerular and tubunar morphology in 3 donors, normal glomerular morphology with mild acute tubular necrosis (ATN) in 2 donors, mild ATN and 4% glomerulosclerosis in 1 donor (Table 1). All kidneys showed favorable pump parameters in hypothermic pulsatile machine perfusion (flow: 115 ± 26 ml/min, resistance: 0.25 ± 0.09 mmHg/[ml/min]). Twelve cases of kidney transplantation were performed with cold ischemic time of 9.2 ± 3.8 h. No case of delayed graft function or acute rejection occurred. After a follow-up of 13-62 months, all recipients survived with excellent renal graft function, with 12 months eGFR of 75.8 ± 14.1 ml/min/1.73m2. Conclusion Kidneys from donors dying of poisoning of organophosphate are suitable for transplantation and can achieve excellent graft function.

Rhabdomyolysis in deceased donors usually causes acute renal failure (ARF), which may be considered a contraindication for kidney transplantation. From January 2012 to December 2016, 30 kidneys from 15 deceased donors with severe rhabdomyolysis and ARF were accepted for transplantation at our center. The peak serum creatinine (SCr) kinase, myoglobin, and SCr of the these donors were 15 569±8597 U/L, 37 092±42 100 μg/L, and 422±167 μmol/L, respectively. Two donors received continuous renal replacement therapy due to anuria. Six kidneys exhibited a discolored appearance (from brown to glossy black) due to myoglobin casts. The kidney transplant results from the donors with rhabdomyolysis donors were compared with those of 90 renal grafts from standard criteria donors (SCD). The estimated glomerular filtration rate at 2 years was similar between kidney transplants from donors with rhabdomyolysis and SCD (70.3±14.6 mL/min/1.73 m2 vs 72.3±15.1 mL/min/1.73 m2). We conclude that excellent graft function can be achieved from kidneys donors with ARF caused by rhabdomyolysis.