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Outcomes of liver transplantation for end-stage biliary disease: A comparative study with end-stage liver disease

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World Journal of Gastroenterology 2015年第20期21卷 6296-6303页

作者： Yan-Hua Lai Wei-Dong Duan Qiang Yu Sheng Ye Nian-Jun Xiao Dong-Xin Zhang Zhi-Qiang Huang Zhan-Yu Yang Jia-Hong Dong Hospital and institute of Hepatobiliary surgery Chinese PLA General Hospital institute of Hepatobiliary surgery South West HospitalThird Military Medical University

AIM: To evaluate the outcomes of patients with endstage biliary disease(ESBD) who underwent liver transplantation, to define the concept of ESBD, the criteria for patient selection and the optimal operation for ***: Between June 2002 and June 2014, 43 patients with ESBD from two Chinese organ transplantation centres were evaluated for liver transplantation. The causes of liver disease were primary biliary cirrhosis(n = 8), cholelithiasis(n = 8), congenital biliary atresia(n = 2), graft-related cholangiopathy(n = 18), Caroli's disease(n = 2), iatrogenic bile duct injury(n = 2), primary sclerosing cholangitis(n = 1), intrahepatic bile duct paucity(n = 1) and Alagille's syndrome(n = 1). The patients with ESBD were compared with an end-stage liver disease(ESLD) case control group during the same period, and the potential prognostic values of multiple demographic and clinical variables were assessed. The examined variables included recipient age, sex, pre-transplant clinical status, pre-transplant laboratory values, operation condition and postoperative complications, as well as patient and allograft survival rates. Survival analysis was performed using Kaplan-Meier curves, and the rates were compared using log-rank tests. All variables identified by univariate analysis with P values surgery compared to patients in the ESLD group(19.2 ± 6.6 vs 22.0 ± 6.5, P = 0.023 and 1.8 ± 1.3 vs 0.1 ± 0.2, P = 0.000). Moreover, theoperation time and the time spent in intensive care were significantly higher in the ESBD group than in the ESLD group(527.4 ± 98.8 vs 443.0 ± 101.0, P = 0.000, and 12.74 ± 6.6 vs 10.0 ±

关键词： Liver transplantation End-stage biliarydisease Model for end-stage liver disease Paediatricend-stage liver disease Complication

Inhalation of hydrogen gas reduces liver injury during major hepatotectomy in swine

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World Journal of Gastroenterology 2012年第37期18卷 5197-5204页

作者： Lei Xiang Jing-Wang Tan Li-Jie Huang Lin Jia Ya-Qian Liu Yu-Qiong Zhao Kai Wang Jia-Hong Dong Animal Experiment Centers PLA General Hospital Beijing 100853 China institute of Hepatobiliary surgery PLA General Hospital Beijing 100853 China

AIM： To study the effect of H2 gas on liver injury in massive hepatectomy using the Intermittent Pringle maneuver in swine. METHODS： Male Bama pigs （n = 14） treated with ketamine hydrochloride and Sumianxin Ⅱ as induc- tion drugs followed by inhalation anesthesia with 2% isoflurane, underwent 70% hepatotectomy with loss of bleeding less than 50 mL, and with hepatic pedicle occlusion for 20 min, were divided into two groups： Hydrogen-group （n = 7）, the pigs with inhalation of 2% hydrogen by the tracheal intubation during major hepa- totectomy; Contrast-group （n= 7）, underwent 70% hepatotectomy without inhalation of hydrogen. Hemo- dynamic changes and plasma concentrations of alanine aminotransferase （ALT）, aspartate aminotransferase （AST）, hyaluronic acid （HA）, tumor necrosis factor-α （TNF-α）, interleukin-6 （IL-6）, and malondialdehyde （MDA） in liver tissue were measured at pre-operation, post-hepatotectomy （PH） 1 h and 3 h. The apoptosis and proliferating cell nuclear antigen （PCNA） expres- sion in liver remnant were evaluated at PH 3 h. Then we compared the two groups by these marks to evalu- ate the effect of the hydrogen in the liver injury during major hepatotectomy with the Pringle Maneuver in the swine. RESULTS： There were no significant differences in body weight, blood loss and removal liver weight be- tween the two groups. There was no significant differ- ence in changes of portal vein pressure between two groups at pre-operation, PH 30 min, but in hydrogen gas treated-group it slightly decrease and lower than its in Contrast-group at PH 3 h, although there were no significant difference （P = 0.655）. ALT and AST in Hydrogen-group was significantly lower comparing to Contrast-group （P = 0.036, P = 0.011, vs P = 0.032, P = 0.013） at PH 1 h and 3 h, although the two groups all increased. The MDA level increased between the two group at PH i h and 3 h. In the hydrogen gas treated- group, the MDA level was not significantly significant at pre-operation and signif

关键词： Massive hepatotectomy Hydrogen gas, An-ti-oxidant Hyperperfusion Malondialdehyde Oxidativestress

Inflammasome links traumatic brain injury, chronic traumatic encephalopathy, and Alzheimer's disease

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Neural Regeneration Research 2025年第6期20卷 1644-1664页

作者： Gabriela Seplovich Yazan Bouchi Juan Pablo de Rivero Vaccari Jennifer C.Munoz Pareja Andrew Reisner Laura Blackwell Yehia Mechref Kevin K.Wang J.Adrian Tyndall Binu Tharakan Firas Kobeissy Department of surgery Morehouse School of MedicineAtlantaGAUSA Department of Neurobiology Center for NeurotraumaMultiomics&Biomarkers(CNMB)Neuroscience InstituteMorehouse School of MedicineAtlantaGAUSA Department of Neurological surgery and the Miami Project to Cure Paralysis University of Miami Miller School of MedicineMiamiFLUSA Division of Pediatric Critical Care Department of PediatricsUniversity of Miami Miller School of MedicineMiamiFLUSA Department of Pediatrics Emory UniversityAtlantaGAUSA Department of Neurosurgery Children’s Healthcare of AtlantaAtlantaGAUSA Department of Chemistry and Biochemistry Texas Tech UniversityLubbockTXUSA Morehouse School of Medicine AtlantaGAUSA

Traumatic brain injury, chronic traumatic encephalopathy, and Alzheimer's disease are three distinct neurological disorders that share common pathophysiological mechanisms involving neuroinflammation. One sequela of neuroinflammation includes the pathologic hyperphosphorylation of tau protein, an endogenous microtubule-associated protein that protects the integrity of neuronal cytoskeletons. Tau hyperphosphorylation results in protein misfolding and subsequent accumulation of tau tangles forming neurotoxic aggregates. These misfolded proteins are characteristic of traumatic brain injury, chronic traumatic encephalopathy, and Alzheimer's disease and can lead to downstream neuroinflammatory processes, including assembly and activation of the inflammasome complex. Inflammasomes refer to a family of multimeric protein units that, upon activation, release a cascade of signaling molecules resulting in caspase-induced cell death and inflammation mediated by the release of interleukin-1β cytokine. One specific inflammasome, the NOD-like receptor protein 3, has been proposed to be a key regulator of tau phosphorylation where it has been shown that prolonged NOD-like receptor protein 3 activation acts as a causal factor in pathological tau accumulation and spreading. This review begins by describing the epidemiology and pathophysiology of traumatic brain injury, chronic traumatic encephalopathy, and Alzheimer's disease. Next, we highlight neuroinflammation as an overriding theme and discuss the role of the NOD-like receptor protein 3 inflammasome in the formation of tau deposits and how such tauopathic entities spread throughout the brain. We then propose a novel framework linking traumatic brain injury, chronic traumatic encephalopathy, and Alzheimer's disease as inflammasomedependent pathologies that exist along a temporal continuum. Finally, we discuss potential therapeutic targets that may intercept this pathway and ultimately minimize long-term neurological decline.

关键词： Alzheimer's disease caspase-1 chronic traumatic encephalopathy inflammasomes neurodegeneration neuroinflammation NLRP1 NLRP3 pyroptosis tauopathy traumatic brain injury

Growth-inhibitory effects of MOB2 on human hepatic carcinoma cell line SMMC-7721

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World Journal of Gastroenterology 2012年第48期18卷 7285-7289页

作者： Jian-Jun Leng Hua-Min Tan Ke Chen Wei-Gan Shen Jing-Wang Tan institute of Hepatobiliary surgery PLA General Hospital Department of general surgery Fuzhou General Hospital of Nanjing Military Command Department of Hepato-bilio-pancreatic surgery Northern Jiangsu People's Hospital Department of Molecular Biology Laboraoty Medical College of Yangzhou University

AIM:To investigate the growth-inhibiting and apoptosis-inducing effects of the gene MOB2 on human hepatic carcinoma cell line ***:The full-length cDNA of the MOB2 gene was amplified from human umbilical vein endothelial *** correct full-length MOB2 cDNA was subcloned into the eukaryotic expression vector *** lipofection of the MOB2 gene into cancer cells,the levels of MOB2 protein in the cancer cells were detected by *** transfect the recombined plasmid vector pEGFP-CI-MOB2 into SMMC-7721 cells,the cells were cultured in Dulbecco's Modified Eagle'sMedium with 10% fetal calf serum and glutamine,and then mixed with liposomes,Lipofectamine 2000 and the plasmid vector ***:We observed the growth and proliferation of SMMC-7721 cells containing pEGFP-CI-MOB2 and analyzed their apoptosis and growth cycle phases by flow *** successfully transfected the recombined plasmid vector pEGFP-CI-MOB2 into SMMC-7721 cells and screened for a single clone cell containing *** transfection,MOB2 enhanced growth suppression,induced apoptosis,increased the ratio of G0/G1,significantly inhibited the advance of cell cycle phase,and arrested cells in G0/G1 ***:MOB2 overexpression induces apoptosis and inhibits the growth of human hepatic cancer cells,which may be useful in gene therapy for hepatic carcinoma.

关键词： Gene expression SMMC-7721 Growth inhibition Apoptosis

Extracorporeal continuous portal diversion plus temporal plasmapheresis for “small-for-size” syndrome

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World Journal of Gastroenterology 2013年第33期19卷 5464-5472页

作者： Peng Hou Chao Chen Yu-Liang Tu Zi-Man Zhu Jing-Wang Tan institute of Gastroenterology The First Affiliated Hospital of Chinese PLA General Hospital institute of Hepatobiliary surgery The First Affiliated Hospital of Chinese PLA General Hospital

AIM:To investigate the effect of plasmapheresis via the portal vein for"small-for-size"syndrome(SFSS)aided by extracorporeal continuous portal diversion(ECPD).METHODS:Extensive or total hepatectomy in the pig is usually adopted as a postoperative liver failure(PLF)or SFSS *** this study,animals which underwent85%-90%hepatectomy were randomized into either the Systemic group(n=7)or the Portal group(n=7).In the Systemic group,all pigs received temporal plasmapheresis(PP)via the extracorporeal catheter circuit(systemic to systemic circulation)from 24 to 30 h posthepatectomy(PH);in the Portal group,all pigs received ECPD to divert partial portal vein flow(PVF)to the systemic circulation after hepatectomy,then converted to temporal PP from 24 to 30 h PH,and subsequently converted to ECPD again until 48 h *** the Portal group,the PVF was preserved at 3.0-3.3 times that of the baseline value,similar to that following 70%hepatectomy,which was regarded as the optimal PVF to the hypertrophic liver *** 48 h PH,all pigs were re-opened and the portal vein pressure(PVP),PVF,and HAF(hepatic artery flow)were measured,and then diversion of the portal venous flow was ***1 h the PVP,PVF,and HAF were *** portal hemodynamic changes,liver injury,liver regeneration and bacterial/lipopolysaccharide(LPS)translocation were evaluated in the two ***:The PVP in the Portal group was significantly lower than that in the Systemic group during the time period from 2 to 49 h PH(P<0.05).Serum alanine aminotransferase(ALT),total bilirubin(TB)and ammonia were significantly reduced in the Portal group compared with the Systemic group from 24 to 48 h PH(P<0.05).The Portal group may have attenuated sinusoidal endothelial injury and decreased the level of HA compared with the Systemic *** the Systemic group,there was significant sinusoidal dilation,hydropic changes in hepatocytes and hemorrhage into the hepatic parenchyma,and the sinusoidal endothelial

关键词： Small-for-size syndrome Postoperative liver failure Extracorporeal portal diversion Plasmapheresis Hepatectomy

Poor prognosis for hepatocellular carcinoma with transarterial chemoembolization pre-transplantation:Retrospective analysis

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World Journal of Gastroenterology 2015年第12期21卷 3599-3606页

作者： Hai-Lin Li Wen-Bin Ji Rui Zhao Wei-Dong Duan Yong-Wei Chen Xian-Qiang Wang Qiang Yu Ying Luo Jia-Hong Dong Department of Hepatobiliary surgery Qilu Hospital Shandong University Hospital and institute of Hepatobiliary surgery Chinese PLA General Hospital

AIM: To investigate whether transarterial chemoembolization(TACE) before liver transplantation(LT) improves long-term survival in hepatocellular carcinoma(HCC) ***: A retrospective study was conducted among 204 patients with HCC who received LT from January 2002 to December 2010 in PLA general Hospital. Among them, 88 patients received TACE before LT. Prognostic factors of serum α-fetoprotein(AFP), intraoperative blood loss, intraoperative blood transfusion, disease-free survival time, survival time with tumor, number of tumor nodules, tumor size, tumor number, presence of blood vessels and bile duct invasion, lymph node metastasis, degree of tumor differentiation, and preoperative liver function were determined in accordance with the Child-TurcottePugh(Child) classification and model for end-stage liver disease. We also determined time of TACE before transplant surgery and tumor recurrence and metastasis according to different organs. Cumulative survival rate and disease-free survival rate curves were prepared using the Kaplan-Meier method, and the logrank and χ2 tests were used for ***: In patients with and without TACE before LT, the 1, 3 and 5-year cumulative survival rate was 70.5% ± 4.9% vs 91.4% ± 2.6%, 53.3% ± 6.0% vs 83.1% ± 3.9%, and 46.2% ± 7.0% vs 80.8% ± 4.5%, respectively. The median survival time of patients with and without TACE was 51.857 ± 5.042 mo vs 80.930 ± 3.308 mo(χ2 = 22.547, P < 0.001, P < 0.05). The 1, 3 and 5-year disease-free survival rates for patients with and without TACE before LT were 62.3% ± 5.2% vs98.9% ± 3.0%, 48.7% ± 6.7% vs 82.1% ± 4.1%, and 48.7% ± 6.7% vs 82.1% ± 4.1%, respectively. The median survival time of patients with and without TACE before LT was 50.386 ± 4.901 mo vs 80.281 ± 3.216 mo(χ2 = 22.063, P < 0.001, P < 0.05). TACE before LT can easily lead to pulmonary or distant metastasis of the primary tumor. Although there was no significant difference between the two groups, the chance of met

关键词： Liver transplantation Hepatocellular carcinoma Tra

Gut microbiota and its implications in small bowel transplantation

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Frontiers of Medicine 2018年第3期12卷 239-248页

作者： Chenyang Wang Qiurong Li Jieshou Li Research institute of general surgery Jinling Hospital Medical School Nanjing University Nanjing 210002 China

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 metabofism. 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 SBT and 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 allografl 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.

关键词： gut microbiota small bowel transplantation acute rejection chronic rejection mucosal immunity biomarker microbiota-targeted therapy

Biomarkers for response to immunotherapy in hepatobiliary malignancies

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Hepatobiliary & Pancreatic Diseases International 2022年第5期21卷 413-419页

作者： Zhi-Fei Lin Lun-Xiu Qin Jin-Hong Chen Department of general surgery Huashan HospitalCancer Metastasis InstituteFudan UniversityShanghai 200040China

Background:The advent of immune checkpoint inhibitors(ICIs)has revolutionized the therapeutic options of hepatobiliary ***,the clinical benefit provided by immunotherapy seems limited to a small subgroup of patients with hepatobiliary *** identification of reliable predictors of the response to immunotherapy is urgently *** sources:Literature search was conducted in Pub Med for relevant articles published up to May *** of clinical trials was obtained from https://***/.Results:Biomarkers for ICI response of hepatobiliary malignancies remain in the exploration stage and lack compelling *** programmed death-ligand 1(PD-L1)expression is the most widely studied biomarker in hepatocellular carcinoma(HCC)and biliary tract cancers(BTCs),but there are conflicting results on its predictive *** mutational burden(TMB)is generally low both in HCC and BTCs,and the clinical trials of TMB are rare in hepatobiliary ***,mismatch repair deficiency(dMMR)/high microsatellite instability(MSI-H)may be a predictive biomarker of response to antiPD-1 therapy in ***,some emerging biomarkers,such as gut microbiota,show predictive potential in the preliminary *** and liquid-biopsy biomarkers,including circulating tumor cells,circulating tumor DNA(ct DNA)and exosomal PD-L1 provide a quick and non-invasive approach for monitoring the ICI response,showing a new promising ***:Multiple potential biomarkers for predicting ICI response of hepatobiliary malignancies have been explored and tried to apply in *** there is no robust evidence to prove their clinical value in predicting immunotherapeutic response for patients with hepatobiliary *** identification of predictors for response to ICIs is an urgent need and major *** studies are warranted to validate the role of emerging biomarkers in predicting immunotherapeut

关键词： Biomarker Immunotherapy Hepatocellular carcinoma Biliary tract cancers

Hepatocellular carcinoma with child Pugh-A Cirrhosis treated with stereotactic body radiotherapy

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World Journal of Gastrointestinal surgery 2017年第12期9卷 256-263页

作者： Shaakir Hasan Ngoc Thai Tadahiro Uemura Vijay Kudithipudi Paul Renz Stephen Abel Alexander V Kirichenko Division of Radiation Oncology Allegheny General Hospital Cancer Institute Division of Transplant surgery Allegheny General Hospital Cancer Institute

AIM To evaluate the control, survival, and hepatic function for Child Pugh(CP)-A patients after Stereotactic body radiotherapy(SBRT) in hepatocellular carcinoma(HCC).METHODS From 2009 to 2016, 40 patients with Barcelona Liver Clinic(BCLC) stages 0-B HCC and CP-A cirrhosis completed liver SBRT. The mean prescription dose was 45 Gy(40 to 50 Gy in 4-5 fractions). Local relapse, defined as recurrence within the planning target volume was assessed with intravenous multiphase contrast computed tomography or magnetic resonance imaging every 4-6 mo after completion of SBRT. Progression of cirrhosis was evaluated by CP and Model for End Stage Liver Disease scores every 3-4 mo. Toxicities were graded per the Common Terminology Criteria for Adverse Events(v4.03). Median follow-up was 24 *** Forty-nine HCC lesions among 40 patients were analyzed in this IRB approved retrospective study. Median tumor diameter was 3.5 cm(1.5-8.9 cm). Six patients with tumors ≥ 5 cm completed planned selected transarterial chemoembolization(TACE) in combination with SBRT. Eight patients underwent orthotropic live transplant(OLT) with SBRT as a bridging treatment(median time to transplant was 12 mo, range 5 to 23 mo). The Pathologic complete response(PCR) rate in this group was 62.5%. The 2-year in-field local control was 98%(1 failure). Intrahepatic control was 82% and 62% at 1 and 2 years, respectively. Overall survival(OS) was 92% and 60% at 1 and 2 years, with a median survival of 41 mo per Kaplan Meier analysis. At 1 and 2 years, 71% and 61% of patients retained CPA status. Of the patients with intrahepatic failures, 58% developed progressive cirrhosis, compared to 27% with controlled disease(P = 0.06). Survival specific to hepatic failure was 92%, 81%, and 69% at 12, 18, and 24 mo. There was no grade 3 or higher toxicity. On univariate analysis, gross tumor volume(GTV) < 23 cc was associated with freedom from CP progression(P = 0.05), hepatic failure-specific survival(P = 0.02), and tr

关键词： Stereotactic body radiotherapy Hepatocellular carcinoma Child-Pugh A Cirrhosis Hepatoma Local control Radiotherapy Radiation