OBJECTIVES: Hepatic fibrosis is a serious pathological consequence of chronic liver disease. Mycophenolate mofetil (MMF) is a commonly used immunosuppressant after organ transplant. However, the relationship between MMF and hepatic fibrosis remains unclear. This study aims to explore the effect of MMF on hepatic fibrosis in mice and the potential mechanism. METHODS: A total of 24 mice (male, 8-week old, C57BL/6) were randomly divided into a control group, a MMF group, a carbon tetrachloride (CCl₄) group and a CCl₄+MMF group (n=6 in each group). After the mice were sacrificed, the serum alanine aminotransferase (ALT) and aspartate aminotransferase (AST) levels were detected. The liver tissues were taken up for Masson staining and collagen I (COL1) immunohistochemistry. The levels of transforming growth factor-β1 (TGF-β1) and α-smooth muscle actin (α-SMA) were detected by Western blotting. Finally, the levels of mRNA for TGF-β1, α-SMA, and COL1 were detected using real-time PCR. RESULTS: Compared with the CCl₄ group, the ALT and AST levels were lower (both P<0.05), the degree of liver fibrosis was alleviated, and the deposition of COL1 in the liver was significantly decreased (P<0.01) in the CCl₄+MMF group. Compared with the CCl₄ group, the protein expression levels of TGF-β1 and α-SMA were significantly decreased (both P<0.05) and the relative expression levels of TGF-β1, α-SMA and COL1 mRNA in the liver were significantly decreased (all P<0.05) in the CCl₄+MMF. CONCLUSIONS MMF could reduce CCl₄-induced hepatic fibrosis, which might be related to the inhibition of TGF-β1. This study is expected to provide a target for the treatment of hepatic fibrosis.
Male ; Animals ; Mice ; Mice, Inbred C57BL ; Mycophenolic Acid/therapeutic use* ; Carbon Tetrachloride/toxicity* ; Transforming Growth Factor beta1/genetics* ; Liver Cirrhosis/drug therapy* ; RNA, Messenger

Objective:To develop an area under curve (AUC)-based nomogram to predict vancomycin-associated nephrotoxicity in critically ill patients.Methods:This retrospective cohort study included adult patients treated with vancomycin in the intensive care unit at a tertiary teaching hospital from January 2015 to December 2017. Baseline clinical characteristics before vancomycin treatment and pharmacokinetic parameters were collected to establish a prediction model of nephrotoxicity. Univariate analysis was used to screen variables, and multivariate logistic regression analysis was used to establish the prediction model and nomogram.Results:A total of 159 patients met the inclusion criteria, sixty-four were included in the final analysis. Sixteen patients (25%, 16/64) developed vancomycin-associated nephrotoxicity. The following variables were incorporated into the prediction model: vancomycin AUC, estimated glomerular filtration rate (GFR), and combined nephrotoxic drugs. The following equation was established to calculate the probability of nephrotoxicity: logit (P)=-4.83+0.009×AUC-2.87×1 (if GFR>60 ml/min)+2.53×1 (if number of combined nephrotoxic drugs≥2). A nomogram was generated based on the equation. The receiver-operating characteristic curve demonstrated that the AUC of the prediction model was 0.927 (95% CI 0.851-1.000). The cut-off value of the probability of nephrotoxicity was 26.48%. The sensitivity and specificity were 87.5% and 87.5% respectively. Conclusion:The incidence of vancomycin-associated nephrotoxicity is high. The AUC-based nomogram can effectively predict vancomycin-associated nephrotoxicity in critically ill patients.

BACKGROUND: Pulmonary microvascular endothelial cells (PMVECs) were not complex, and the endothelial barrier was destroyed in the pathogenesis progress of acute lung injury (ALI)/acute respiratory distress syndrome (ARDS). Previous studies have demonstrated that hepatocyte growth factor (HGF), which was secreted by bone marrow mesenchymal stem cells, could decrease endothelial apoptosis. We investigated whether mTOR/STAT3 signaling acted in HGF protective effects against oxidative stress and mitochondria-dependent apoptosis in lipopolysaccharide (LPS)-induced endothelial barrier dysfunction and ALI mice. METHODS: In our current study, we introduced LPS-induced PMEVCs with HGF treatment. To investigate the effects of mammalian target of rapamycin (mTOR)/signal transducer and activator of transcription 3 (STAT3) pathway in endothelial oxidative stress and mitochondria-dependent apoptosis, mTOR inhibitor rapamycin and STAT3 inhibitor S3I-201 were, respectively, used to inhibit mTOR/STAT3 signaling. Moreover, lentivirus vector-mediated mTORC1 (Raptor) and mTORC2 (Rictor) gene knockdown modifications were introduced to evaluate mTORC1 and mTORC1 pathways. Calcium measurement, reactive oxygen species (ROS) production, mitochondrial membrane potential and protein, cell proliferation, apoptosis, and endothelial junction protein were detected to evaluate HGF effects. Moreover, we used the ALI mouse model to observe the mitochondria pathological changes with an electron microscope in vivo. RESULTS: Our study demonstrated that HGF protected the endothelium via the suppression of ROS production and intracellular calcium uptake, which lead to increased mitochondrial membrane potential (JC-1 and mitochondria tracker green detection) and specific proteins (complex I), raised anti-apoptosis Messenger Ribonucleic Acid level (B-cell lymphoma 2 and Bcl-xL), and increased endothelial junction proteins (VE-cadherin and occludin). Reversely, mTOR inhibitor rapamycin and STAT3 inhibitor S3I-201 could raise oxidative stress and mitochondria-dependent apoptosis even with HGF treatment in LPS-induced endothelial cells. Similarly, mTORC1 as well as mTORC2 have the same protective effects in mitochondria damage and apoptosis. In in vivo experiments of ALI mouse, HGF also increased mitochondria structural integrity via the mTOR/STAT3 pathway. CONCLUSION In all, these reveal that mTOR/STAT3 signaling mediates the HGF suppression effects to oxidative level, mitochondria-dependent apoptosis, and endothelial junction protein in ARDS, contributing to the pulmonary endothelial survival and barrier integrity.
Animals ; Apoptosis ; Calcium/metabolism* ; Endothelial Cells/metabolism* ; Endothelium/metabolism* ; Hepatocyte Growth Factor/metabolism* ; Lipopolysaccharides/pharmacology* ; Mammals/metabolism* ; Mechanistic Target of Rapamycin Complex 1/metabolism* ; Mechanistic Target of Rapamycin Complex 2/metabolism* ; Mice ; Mitochondria/metabolism* ; Oxidative Stress ; Reactive Oxygen Species/metabolism* ; Respiratory Distress Syndrome ; Sirolimus/pharmacology* ; TOR Serine-Threonine Kinases/metabolism*

Diabetes mellitus is one of the most common complications after liver transplantation. The survival rate of recipients after liver transplantation with diabetes mellitus and the long-term survival rate of grafts are significantly lower than those of their counterparts without diabetes mellitus. In recent years, diabetes mellitus after liver transplantation has attracted widespread attention along with the rapid development of liver transplantation in China. Although post-transplantation diabetes mellitus (PTDM) has been extensively investigated in the past two decades, multiple problems remain to be further resolved. The study was designed to review the latest research progress upon diabetes mellitus after liver transplantation, covering the definition and diagnostic criteria of PTDM, risk factors, prevention and treatment of diabetes mellitus after liver transplantation, aiming to deepen the understanding of diabetes mellitus following liver transplantation, deliver effective prevention and management, improve the long-term survival rate and enhance the quality of life of the recipients.

Renal transplantation is one of the most effective treatment methods for end-stage renal diseases. However, some recipients present with fatigue symptoms after renal transplantation. Fatigue not only affects the quality of life, but also reduces the compliance of recipients with immunosuppressive agents. To strengthen the attention of medical staff to the fatigue, make early diagnosis and deliver effective interventions for renal transplant recipients, the current situation, risk factors and intervention methods of fatigue in renal transplant recipients were reviewed in this article.

Orthotopic liver transplantation (OLT) was first implemented by Starzl in 1963.With the development of liver transplantation,Tzaris was the first to report piggyback liver transplantation (PBLT) in 1989.The fundamental difference between OLT and PBLT:end to end vascular anastomosis between the donor and recipient is performed after diseased liver resection with the posthepatic inferior vena cava in OLT,while PBLT is to preserve the recipient's hepatic vein and end to end vascular anastomosis between interior vena cava of donor and shaped hepatic vein is performed.However in the clinical practice,the above two techniques cannot meet the needs of clinical liver transplantation technology.Since 1993 the author has implemented a series of improvements in liver transplantation technology based on PBLT and performed ameliorated piggyback liver transplantation (APBLT).This article focuses on the technical characteristics and clinical application of APBLT.

Objective To investigate the clinical efficacy of vena cava-atrium anastomosis liver transplantation (VCAALT) for Budd-Chiari syndrome (BCS).Methods The retrospective descriptive study was conducted.The clinicopathological data of 18 BCS patients who underwent VCAALT in the Zhongnan Hospital of Wuhan University (6 cases),the Third Xiangya Hospital of Central South University (8 cases) and Tongji Hospital Affiliated to Tongji Medical College of Huazhong University of Science and Technology (4 cases) from May 1996 to December 2012 were collected.All the 18 patients were males,aged from 29 to 61 years,with an average age of 42 years.According to characteristics and invasion extent of hepatic vein and vena cava after preoperative examinations,patients were performed different surgical procedures of VCAALT,including bridge piggyback liver transplantation (BPBLT),hanging atrium liver transplantation (HALT) and cava vena resection bridge liver transplantation (CVRBLT).Observation indicators:(1) surgical and postoperative situations;(2) typical case analysis;(3) follow-up situations.Follow-up using outpatient examination and telephone interview was performed to detect patients' survival up to December 2018.Measurement data with normal distribution were represented as Mean±SD and measurement data with skewed distribution were described as M (range).Results (1) Surgical and postoperative situations:of 18 patients,11 underwent BPBLT,3 underwent HALT,4 underwent CVRBLT.The operation time and volume of intraoperative blood loss were (6.0± 1.3)hours and (1 264±435)mL.One patient died of bilateral pulmonary diffuse inflammation and sepsis due to severe infection.The duration of postoperative hospital stay was (18±5) days.(2) Typical case analysis:one 47-year-old male BCS patient was detected retrohepatic vena cava plaques and thrombus and hepatic venous thrombus by exploratory laparotomy,and underwent BPBLT.A 43-year-old male BCS patient was detected hepatic and retrohepatic vena cava plaques,thrombus,concomitant cavernous transformation,and underwent HALT.A 32-year-old male BCS patient was detected plaques and thrombus with red thrombus in the hepatic vein,from right renal vein to right atrium,and underwent CVRBLT.All the 3 patients underwent VCAALT successfully with a satisfactory recovery.(3) Followup situations:18 patients were followed up for 3.0-60.0 months,with a median time of 51.7 months.During the follow-up,3 patients died of acute rejection,biliary complications and chronic graft dysfunction at 1,3,5 years postoperatively.The 1-,3-,5-year survival rates were 16/18,15/18,14/18,respectively.Conclusion Different surgical procedures of VCAALT for BCS are selected according to different situations of patients,which are safe and feasible with a satisfactory efficacy and beneficial to long-term survival of patients.

Objective To explore the effects of WeChat-based peer supports upon medication adherence and quality-of-life in liver transplant recipients .Methods A total of 63 patients with liver transplantation were conveniently divided into intervention group (n=32) and control group (n=31) depending upon their different follow-up periods .In control group ,routine outpatient health guidance was offered while intervention group received 6-week WeChat-based peer supports . Medication compliance and quality-of-life of two groups were evaluated at Month 3/6/12 post-intervention . Results At Month 3 post-intervention ,as compared with control group ,only non-punctual medication improved significantly in intervention group (P<0 .01);at Month 6 post-intervention ,all aspects of drug adherence improved in intervention group (P< 0 .05) ,at Month 12 post-intervention ,drug adherence ,non-punctual medication and missed dosing improved in intervention group ( P> 0 .05 ) . However , inter-group quality-of-life was not statistically significant at Month 3/6/12 post-intervention .Conclusions WeChat-based peer supports may partially improve the immediate compliance of patients with liver transplantation .However ,long-term outcomes and effects on quality-of-life are worth further researches .

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 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.