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miR-26a regulates mouse hepatocyte proliferation via directly targeting the 3' untranslated region of CCND2 and CCNE2

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hepatobiliary & Pancreatic Diseases International 2016年第1期15卷 65-72页

作者： Jian Zhou Wei-Qiang Ju xiao-Peng Yuan xiao-Feng Zhu Dong-Ping Wang xiao-shun he Organ Transplant Center the First Affiliated HospitalSun Yat-Sen University

BACKGROUND： The deficiency of liver regeneration needs to be addressed in the fields of liver surgery, split liver transplan- tation and living donor liver transplantation. Researches of microRNAs would broaden our understandings on the mecha- nisms of various diseases. Our previous research confirmed that miR-26a regulated liver regeneration in mice; however, the relationship between miR-26a and its target, directly or in- directly, remains unclear. Therefore, the present study further investigated the mechanism of miR-26a in regulating mouse hepatocyte proliferation. METHODS： An established mouse liver cell line, Nctc-1469, was transfected with Ad5-miR-26a-EGFP, Ad5-anti-miR-26a- EGFP or AdS-EGFP vector. Cell proliferation was assessed by MTS, cell apoptosis and cell cycle by flow cytometry, and gene expression by Western blotting and quantitative real-time PCR. Dual-luciferase reporter assays were used to test targets of miR-26a. RESULTS： Compared with the Ad5-EGFP group, Ad5-anti- miR-26a-EGFP down-regulated miR-26a and increased prolif- eration of hepatocytes, with more cells entering the G1 phase of cell cycle （82.70%＋1.45% vs 75.80%＋_3.92%）, and decreased apoptosis （5.50%＋0.35% vs 6.73%_＋0.42%）. CCND2 and CCNE2 were the direct targeted genes of miR-26a, miR-26a down- regulation up-regulated CCND2 and CCNE2 expressions and down-regulated p53 expression in Nctc-1469 cells. On the con- trary, miR-26a over-expression showed the opposite results. CONCLUSIONS： miR-26a regulated mouse hepatocyte pro- liferation by directly targeting the 3＇ untranslated regions of cyclin D2/cyclin E2; miR-26a also regulated p53-mediated apoptosis. Our data suggested that miR-26a may be a promis- ing regulator in liver regeneration.

关键词： microRNA miR-26a gene expression hepatocyte proliferation regulation

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Application of extended criteria donor grafts in liver transplantation for acute-on-chronic liver failure:A retrospective cohort study

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World Journal of Gastroenterology 2023年第41期29卷 5630-5640页

作者： Jin-Long Gong Jia Yu Tie-Long Wang xiao-shun he Yun-Hua Tang xiao-Feng Zhu Department of hepatobiliary Surgery Hunan Provincial People's HospitalThe First Affiliated Hospital of Hunan Normal UniversityChangsha 410005Hunan ProvinceChina Organ Transplant Center The First Affiliated HospitalSun Yat-sen UniversityGuangzhou 510080Guangdong ProvinceChina Department of Gastroenterology Surgery The First Affiliated Hospital of University of South ChinaHengyang 421005Hunan ProvinceChina

BACKGROUND There is no consensus on the usage of extended criteria donor(ECD)grafts in liver transplantation(LT)for acute-on-chronic liver failure(ACLF)*** To summarize the experience of using ECD livers in *** A retrospective cohort study was conducted,enrolling patients who underwent LT at the First Affiliated Hospital of Sun Yat-Sen University from January 2015 to November *** patients were divided into ECD and non-ECD groups for *** A total of 145 recipients were enrolled in this study,of which ECD and non-ECD recipients accounted for 53.8%and 46.2%,*** after cardiac death(DCD)recipients accounted for the minority compared with donation after brain death(DBD)recipients(16.6%vs 83.4%).Neither overall survival nor graft survival significantly differed between ECD and non-ECD and DCD and DBD *** grafts were associated with a significantly higher incidence of early allograft dysfunction(EAD)than non-ECD grafts(67.9%vs 41.8%,P=0.002).Postoperative outcomes between DCD and DBD recipients were comparable(P>0.05).ECD graft(P=0.009),anhepatic phase(P=0.034)and recipient gamma glutamyltransferase(P=0.016)were independent risk factors for *** preoperative number of extrahepatic organ failures>2(P=0.015)and intraoperative blood loss(P=0.000)were independent predictors of poor post-LT *** Although related to a higher risk of EAD,ECD grafts can be safely used in *** main factors affecting post-LT survival in ACLF patients are their own severe preoperative disease and intraoperative blood loss.

关键词： Extended criteria donor Acute-on-chronic liver failure Liver transplantation

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Validation and performance of three scoring systems for predicting primary non-function and early allograft failure after liver transplantation

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hepatobiliary & Pancreatic Diseases International 2024年第5期23卷 463-471页

作者： Yu Nie Jin-Bo Huang Shu-Jiao he Hua-Di Chen Jun-Jun Jia Jing-Jing Li xiao-shun he Qiang Zhao General Surgery Center Department of Hepatobiliary Surgery IIResearch Center for Artificial Organ and Tissue EngineeringGuangzhou Clinical Research and Transformation Center for Artificial LiverInstitute of Regenerative MedicineZhujiang HospitalSouthern Medical UniversityGuangzhou 510515China Organ Transplant Center the First Affiliated HospitalSun Yat-sen UniversityGuangzhou 510080China Guangdong Provincial Key Laboratory of Organ Donation and Transplant Immunology Guangzhou 510080China Guangdong Provincial International Cooperation Base of Science and Technology Guangzhou 510080China Division of hepatobiliary Pancreatic Surgery the First Affiliated HospitalZhejiang University School of MedicineHangzhou 310003China

Background: Primary non-function(PNF) and early allograft failure(EAF) after liver transplantation(LT) seriously affect patient outcomes. In clinical practice, effective prognostic tools for early identifying recipients at high risk of PNF and EAF were urgently needed. Recently, the Model for Early Allograft Function(MEAF), PNF score by King's College(King-PNF) and Balance-and-Risk-Lactate(BAR-Lac) score were developed to assess the risks of PNF and EAF. This study aimed to externally validate and compare the prognostic performance of these three scores for predicting PNF and EAF. Methods: A retrospective study included 720 patients with primary LT between January 2015 and December 2020. MEAF, King-PNF and BAR-Lac scores were compared using receiver operating characteristic(ROC) and the net reclassification improvement(NRI) and integrated discrimination improvement(IDI) analyses. Results: Of all 720 patients, 28(3.9%) developed PNF and 67(9.3%) developed EAF in 3 months. The overall early allograft dysfunction(EAD) rate was 39.0%. The 3-month patient mortality was 8.6% while 1-year graft-failure-free survival was 89.2%. The median MEAF, King-PNF and BAR-Lac scores were 5.0(3.5–6.3),-2.1(-2.6 to-1.2), and 5.0(2.0–11.0), respectively. For predicting PNF, MEAF and King-PNF scores had excellent area under curves(AUCs) of 0.872 and 0.891, superior to BAR-Lac(AUC = 0.830). The NRI and IDI analyses confirmed that King-PNF score had the best performance in predicting PNF while MEAF served as a better predictor of EAD. The EAF risk curve and 1-year graft-failure-free survival curve showed that King-PNF was superior to MEAF and BAR-Lac scores for stratifying the risk of EAF. Conclusions: MEAF, King-PNF and BAR-Lac were validated as practical and effective risk assessment tools of PNF. King-PNF score outperformed MEAF and BAR-Lac in predicting PNF and EAF within 6 months. BAR-Lac score had a huge advantage in the prediction for PNF without post-transplant variables. Proper use

关键词： Primary non-function Early allograft failure Risk predicting model Liver transplantation

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Gut perforation after orthotopic liver transplantation in adults

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World Journal of Gastroenterology 2007年第14期13卷 2125-2128页

作者： Jun Xiong Shen You xiao-shun he Organ Transplantation Center 1^st Affiliated Hospital Sun Yat-Sen University Guangzhou 510080 Guangdong Province China

AIM： To describe cases of gut perforation after orthotopic liver transplantation.METHODS： Data were colleted from our center database and medical records. Six of 187 patients （3.2%）who underwent orthotopic liver transplantation from January to December 2005 developed gut *** patients were male with an average age of 46 *** piggyback liver transplantation was performed at the Organ Transplantation Center, First Affiliated Hospital, Sun Yat-Sen ***： Previous operation, steroid therapy, and prolonged portal venous cross clamp time, poor nutritional status and iatrogenic injury were found to be its ecological factors. The patients with gut perforation were found to have fever, increased leukocytes, mild abdominal pain and tenderness. The median portal venous clamp time was 63 min （range 45-72 min）,median cold ischaemia time was 11.3 h （range 7-15 h）.Median intraoperative blood loss was 500 mL （range 100-1200 mL） and median operation time was 8.8 h （range 6-12 h）. None of the six patients developed acute cellular rejection. White cell count was above 18 × 10^9/L in five patients （neutrophilic leukocytes were above 90%） and 1.5 × 10^9/L in one patient. Bacterial culture in drainage liquid revealed enterococci in five patients. Of the 6 patients undergoing orthotopic liver transplantation, 3 survived and 3 died after modified piggyback liver transplantation.CONCLUSION： Gut perforation occurs after orthotopic liver transplantation in adults. A careful and minimal dissection during OLT, longer retention of the stomach tube, and reducing the portal clamp time and steroid dose should be taken into consideration. If gut perforation is not prevented, then early diagnosis,preferably through detection of enterococci may ensure better survival.

关键词： Orthotopic liver transplantation Gut perforation Enterococcus faecalis

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Kinetics of phytohemaglutinin-induced IFN-γ and TNF-a expression in peripheral blood mononuclear cells from patients with chronic hepatitis B after liver transplantation

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World Journal of Gastroenterology 2005年第29期11卷 4574-4578页

作者： Ying-Mei Tang Min-Hu Chen Gui-Hua Chen Chang-Jie Cai xiao-shun he Min-Giang Lu Wei-Min Bao Department of Gastroenterology the First Affiliated Hospital of Sun-Yat Sen University Guangzhou 510080 Guangdong Province China Department of Liver Transplantation Center the Third Affiliated Hospital of Sun-Yat Sen University Guangzhou 510080 Guangdong Province China Department of Organ Transplantation the First Affiliated Hospital of Sun-Yat Sen University Guangzhou 510080 Guangdong Province China

AIM： To study the association between host immunity and hepatitis B virus （HBV） recurrence after liver transplantation. METHODS： Peripheral blood mononuclear cells （PBMC） were isolated from 40 patients with hepatitis B and underwent orthotopic liver transplantation （OLT） before and 2, 4, 8 wk after surgery. After being cultured in vitro for 72 h, the levels of INF-γ and TNF-α in culture supematants were detected with ELISA. At the same time, the quantities of HBV DNA in serum and PBMCs were measured by real time PCR. RESULTS： The levels of INF-γ and TNF-α in PBMC culture supernatants decreased before and 2, 4 wk after surgery in turns （INF-γ 155.52±72.32 ng/L vs 14.76±9.88 ng/L vs 13.22±10.35 ng/L, F= 6.946, P= 0.027〈0.05; TNF-α 80.839±46.75 ng/L vs18.59±17.29 ng/L vs9.758±7.96 ng/L, F= 22.61, P = 0.0001〈0.05）. The levels of INF-γ and TNF-α were higher in groups with phytohemagglutinin （PHA） than in those without PHA before surgery. However, the difference disappeared following OLT. Furthermore, INF-γ and TNF-α could not be detected in most patients at wk 4 and none at wk 8 after OLT. The HBV detection rate and virus load in PBMC before and 2, 4 wk after surgery were fluctuated （HBV detected rate： 51.4%, 13.3%, 50% respectively; HBV DNA： 3.55±0.674 log（10） copies/mL vs 3.00±0.329 log（10） copies/mL vs 4.608±1.344 log（10） copies/mL, F= 7.582, P= 0.002〈0.05）. HBV DNA in serum was 4.48±1.463 log（10） copies/mL before surgery and 〈 10^3 copies/mL after OLT except for one with 5.72×10^6 copies/mL 4 wk after OLT who was diagnosed as HBV recurrence. The levels of INF-γ and TNF-α were lower in patients with a high HBV load than in those with a low HBV load （HBV DNA detected/undetected in PBMCs： IFN-γ 138.08±72.44 ng/L vs 164.24±72.07 ng/L, t = 1.065, P= 0.297〉0.05, TNF-α 80.75±47.30 ng/L vs 74.10±49.70 ng/L, t= 0.407, P= 0.686〉 0.05; HBV DNA positive/negative： IFN-γ 136.77±70.04 ng/L vs 175.27±71.50 ng/L, t= 1.702, P= 0.097〉0.05; TNF-α 75.37±43.02 ng/L vs 81.53±52.46 ng/L, t

关键词： Liver transplantation HBV Recurrence PBMC

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Liver transplantation using organs from deceased organ donors: a single organ transplant center experience

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hepatobiliary & Pancreatic Diseases International 2014年第4期13卷 409-415页

作者： Ming Han Zhi-Yong Guo Qiang Zhao xiao-Ping Wang xiao-Peng Yuan Xing-Yuan Jiao Chun-Hua Yang Dong-Ping Wang Wei-Qiang Ju Lin-Wei Wu An-Bin Hu Qiang Tai Yi Ma xiao-Feng Zhu xiao-shun he Organ Transplant Center First Affiliated HospitalSun Yat-Sen University

BACKGROUND： In 2011, a pilot program for deceased organ donation was initiated in China. We describe the first successful series of liver transplants in the pilot ***： From July 2011 to August 2012, our center performed 26 liver transplants from a pool of 29 deceased donors. All organ donation and allograft procurement were conducted according to the national protocol. The clinical data of donors and recipients were collected and summarized ***： Among the 29 donors, 24 were China Category II donors（organ donation after cardiac death）, and five were China Category III donors（organ donation after brain death followed by cardiac death）. The recipients were mainly the patients with hepatocellular carcinoma. The one-year patient survival rate was 80.8% with a median follow-up of 422（2-696） days. Among the five mortalities during the follow-up,three died of tumor recurrence. In terms of post-transplant complications, 9 recipients（34.6%） experienced early allograft dysfunction, 1（3.8%） had non-anastomotic biliary stricture,and 1（3.8%） was complicated with hepatic arterial *** of these complications resulted in patient death. Notably,primary non-function was not observed in any of the ***： With careful donor selection, liver transplant from deceased donors can be performed safely and plays acritical role in overcoming the extreme organ shortage in China.

关键词： liver transplantation organ donors tissue and organ procurement

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Steroid elimination within 24 hours after orthotopic liver transplantation:effectiveness and tolerability

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hepatobiliary & Pancreatic Diseases International 2012年第2期11卷 137-142页

作者： Lin-Wei Wu,Zhi-Yong Guo,Qiang Tai,Wei-Qiang Ju,Dong-Ping Wang,An-Bin Hu,xiao-Feng Zhu and xiao-shun he Organ Transplantation Center, First Affiliated Hospital, Sun Yat-Sen University, Guangzhou 510080, China Organ Transplantation Center First Affiliated Hospital Sun Yat-Sen University Guangzhou 510080 China Guangzhou China

BACKGROUND:Steroids have been the mainstay of immunosuppressive regimen in liver ***,the use of steroids is associated with various post-transplant *** study evaluated the efficacy and safety of reduced immunosuppressive regimen with steroids(steroid elimination within 24 hours post-transplant) in a cohort of Chinese liver transplant ***:Seventy-six patients in line with the selection criteria were enrolled in this prospective *** patients received anti-IL-2 receptor antibody induction and tacrolimusbased maintenance *** recipients were divided into two groups according to the duration of steroid use:40 transplant in a 3-month withdrawal group and the remaining 36 in a 24-hour elimination *** survival,postoperative infections,biopsy-proven acute rejection and steroidresistant acute rejection,non-healing wound,recurrence of hepatitis B virus(HBV) and hepatocellular carcinoma(HCC),de novo diabetes,hyperlipidemia and hypertension were assessed in the two ***:There was no significant difference in patient survival,incidence of acute rejection episodes and hyperlipidemia,and recurrence of HBV and HCC between the two ***,the incidence rates of post-transplant infection,non-healing wound,de novo diabetes and hypertension were significantly lower in the 24-hour elimination group than in the 3-month withdrawal group(all P values he risk of rejection.

关键词： liver transplantation immunosuppression steroid side effects

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The scoring system for patients with severe sepsis after orthotopic liver transplantation

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hepatobiliary & Pancreatic Diseases International 2006年第3期5卷 364-367页

作者： shun-Wei Huang, Xiang-Dong Guan, xiao-shun he, Juan Chen and Bin Ouyang Department of Surgical Intensive Care Unit ,and Department of Transplantation Surgery,First Affiliated Hospital, Sun Yat- Sen University, Guangzhou 510800, China Department of Surgical Intensive Care Unit First Affiliated Hospital Sun Yat-Sen University Guangzhou 510800 China. huangshunwei@***

BACKGROUND: Because of the complicated pathological features after liver transplantation, severe sepsis is difficult to treat and often leads to death. This study was undertaken to analyze the role of orthotopic liver transplantation (OLT) in patients with severe sepsis and to evaluate the effect of the scoring system. METHODS: Fifty-six patients conformed to the inclusion criteria. They were divided into two groups: non-OLT group (group A) and OLT group (group B). Besides the general data of the patients, the surveillance of blood lactate, the number of failed organs, acute physiology and chronic health evaluationⅡ(APACheⅡ) and mutiple organ dysfunction score (MODS) were evaluated at the 1st, 3rd and 7th day after OLT. RESULTS: The mortality during hospitalization was 30% in the non-OLT group and 57.6% in the other group. The level of blood lactate at the 1st day of OLT increased more significantly in the OLT group than in the non-OLT group (Pher than that in the non-OLT group in the seven days after OLT. The number of failed organs in the OLT group was greater than that in the non-OLT group (Phe continuous score of APACheⅡwas not significantly different in the two groups. But the continuous MODS in the OLT group was higher than that in the non-OLT group (Phe number of failed organs. CONCLUSIONS: The persistently higher level of blood lactate during 7 days may be a dependent risk factor. Immunosuppression may be another risk factor for OLT patients. The mortality of OLT in patients with severe sepsis in 28 days is almost double that in non-OLT patients. The MODS score is better than the APACheⅡscore in the assessment of organ failure in OLT patients with severe sepsis. The standard scoring system could be improved or a new scoring system that includes the blood lactate score should be established for liver transplantation.

关键词： orthotopic liver transplantation systemic inflammatory response syndrome severe sepsis blood lactate acute physiology and chronic healthevaluationⅡ mutiple organ dysfunction score

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Investigating the level structure of ^(206)Rn:evolution from seniority regime to collective dynamics

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Chinese Physics C 2024年第11期48卷 75-85页

作者： Rui Guo Li-Hua Zhu Jing-Bin Lu Guan-Jian Fu Meng Wang Bao-Hua Sun Gao-Long Zhang Zhen Ren Yi-heng Wu Yun Zheng Chuang-Ye he Jin-Long Wang xiao-Guang Wuand shun-he Yao School of Physics Beihang UniversityBeijing 100191China College of Physics Jilin UniversityChangchun 130012China School of Physics Science and Engineering Tongji UniversityShanghai 200092China School of Electronic Engineering and Intelligent Manufacturing An Qing Normal UniversityAnqing 246133China China Institute of Atomic Energy Beijing 102413China

Excited states of ^(206)Rn have been examined via the 197 Au(^(14)N,5n)^(206)Rn fusion reaction at a beam energy of 78 MeV.A number of transitions and levels are identified by the γ-γ coincidence measurement,further enriching the level scheme of ^(206)*** fullconfiguration shell model and nucleon-pair approximation(NPA)were utilized to investigate the single-particle configurations and seniority structures in ^(206)*** results of these two calculations suggest that 2_(1)^(+) and 4_(1)^(+) states exhibit only a 50%component of a seniority-two state associated with a broken neutron *** collectivity of these two states primarily arises from configuration mixing due to residual proton-neutron ***,6_(1)^(+) and 8_(1)^(+) states are predominantly characterized by a seniority-two state marked by a broken proton pair.

关键词： γ-γcoincidence measurement levels shell model nucleon-pair approximation seniority collectivity

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Graft-verse-host disease after liver transplantation:A report of two cases and review of literature

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World Journal of Gastroenterology 2008年第6期14卷 974-979页

作者： Zhi-Yong Guo xiao-shun he Lin-Wei Wu xiao-Feng Zhu Wei-Qiang Ju Dong-Ping Wang Shen You Yi Ha Guo-Dong Wang Jie-Fu Huang Organ Transplantation center First Affiliated Hospital Sun Yat-Scn University Guangzhou 510080 Guangdong Province China

Graft-verse-host disease (GVHD) is an uncommon fatal complication following liver transplantation (LTx). In China's Mainland, only six cases have been reported with a morbidity rate up to 1%-2%. Definitive diagnosis was achieved by molecular techniques (HLA typing or PCR-STR) in only two cases and the remaining cases were diagnosed based on typical clinical features with exclusion of other possible causes. All patients died of septic shock or multiple organ failure even after administration of increased corticosteroids and supportive therapy, and reduced immunosuppressive agents. In our center, two cases of GVHD were found among 128 (1.56%) patients. One case was diagnosed by detecting lymphocyte macrochimerism through DNA-STR. Both of them died even after aggressive treatment. In China, the incidence of GVHD is similar to that reported by foreign centers except for an extremely bad prognosis. Rapid diagnosis is crucial for a better prognosis. In China, only 37.5% of cases are diagnosed by molecular methods. We recommend detecting lymphocyte macrochimerism through DNA-STR to get a rapid diagnosis, and interleukin 2-receptor antibody (basiliximab or daclizumab) therapy seems to be a good choice for the disease.

关键词： Graft-versus-host disease Liver transplantation Prognosis Diagnosis Treatment

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