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Pre-transjugular-intrahepatic-portosystemic-shunt measurement of hepatic venous pressure gradient and its clinical application: A comparison study

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World Journal of Gastroenterology 2023年第22期29卷 3519-3533页

作者： Xi-Xuan Wang xiao-Chun Yin Li-Hong Gu Hui-Wen Guo Yang Cheng Yan Liu jiang-qiang xiao Yi Wang Wei Zhang xiao-Ping Zou Lei Wang Ming Zhang Yu-Zheng Zhu-Ge Feng Zhang Department of Gastroenterology Affiliated Drum Tower Hospital of Nanjing University Medical SchoolNanjing 210000Jiangsu ProvinceChina Medical School Southeast UniversityNanjing 210000Jiangsu ProvinceChina Department of Gastroenterology The Affiliated Jiangning Hospital of Nanjing Medical UniversityNanjing 210000Jiangsu ProvinceChina

BACKGROUND It is controversial whether transjugular intrahepatic portosystemic shunt(TIPS)placement can improve long-term survival.AIM To assess whether TIPS placement improves survival in patients with hepaticvenous-pressure-gradient(HVPG)≥16 mmHg,based on HVPG-related risk stratification.METHODS Consecutive variceal bleeding patients treated with endoscopic therapy+nonselectiveβ-blockers(NSBBs)or covered TIPS placement were retrospectively enrolled between January 2013 and December 2019.HVPG measurements were performed before therapy.The primary outcome was transplant-free survival;secondary endpoints were rebleeding and overt hepatic ence-phalopathy(OHE).RESULTS A total of 184 patients were analyzed(mean age,55.27 years±13.86,107 males;102 in the EVL+NSBB group,82 in the covered TIPS group).Based on the HVPG guided risk stratification,70 patients had HVPG<16 mmHg,and 114 patients had HVPG≥16 mmHg.The median follow-up time of the cohort was 49.5 mo.There was no significant difference in transplant-free survival between the two treatment groups overall(hazard ratio[HR],0.61;95%confidence interval[CI]:0.35-1.05;P=0.07).In the high-HVPG tier,transplant-free survival was higher in the TIPS group(HR,0.44;95%CI:0.23-0.85;P=0.004).In the low-HVPG tier,transplantfree survival after the two treatments was similar(HR,0.86;95%CI:0.33-0.23;P=0.74).Covered TIPS placement decreased the rate of rebleeding independent of the HVPG tier(P<0.001).The difference in OHE between the two groups was not statistically significant(P=0.09;P=0.48).CONCLUSION TIPS placement can effectively improve transplant-free survival when the HVPG is greater than 16 mmHg.

关键词： Hepatic venous pressure gradient Transjugular intrahepatic portosystemic shunts Cirrhosis Variceal rebleeding Survival

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Effects of xenogeneic adipose-derived stem cell transplantation on acute-on-chronic liver failure

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Hepatobiliary & Pancreatic Diseases International 2013年第1期12卷 60-67页

作者： Wei Zhu xiao-Lei Shi jiang-qiang xiao Guang-Xiang Gu Yi-Tao Ding Zheng-Liang Ma The Combination of Chinese Medicine with Western Medicine Gulou Clinical Medical College Nanjing University of Chinese Medicine Department of Anesthesiology Affiliated Drum-Tower HospitalNanjing University Medical School Department of Hepatobiliary Surgery Affiliated Drum-Tower HospitalNanjing University Medical School jiangsu Province's Key Medical Center for Hepatobiliary Disease

BACKGROUND:Adipose-derived stem cells(ADSCs) are particularly attractive in future clinical applications of stem cell-based therapy for acute-on-chronic liver failure(ACLF) This study was undertaken to evaluate the therapeutic potential of ADSCs on ACLF.METHODS:ADSCs isolated from porcine fat tissue were expanded and labeled with BrdU.Rabbit models of ACLF were created by administration of D-Gal following CCl 4-induced cirrhosis.One day after administration of D-Gal,rabbits of the ACLF/ADSCs group(n=15) were received ADSCs transplantation,while those in the ACLF/saline group(n=15) were treated with the same volume of saline.Biochemical parameters and histomorphological scoring were evaluated;the distribution and characteristics of transplanted ADSCs as well as the pathology of the liver were examined.RESULTS:ADSCs transplantation improved the survival rate and the liver function of rabbits with ACLF.Biochemical parameters of the ACLF/ADSCs group were improved compared with those of the ACLF/saline group,and histomorphological scoring of the ACLF/ADSCs group was significantly lower than that of the ACLF/saline group.ADSCs were identified in the periportal region of the liver after cell transplantation.CONCLUSION:Xenogenic ADSCs have therapeutic efficacy in the ACLF rabbit model.

关键词： adipose-derived stem cells acute-on-chronic liver failure cell transplantation

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Protective effects of ACLF sera on metabolic functions and proliferation of hepatocytes co-cultured with bone marrow MSCs in vitro

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World Journal of Gastroenterology 2011年第19期17卷 2397-2406页

作者： xiao-Lei Shi Jin-Yang Gu Yue Zhang Bing Han jiang-qiang xiao Xian-Wen Yuan Ning Zhang Yi-Tao Ding Department of Hepatobiliary Surgery the Affiliated Drum Tower Hospital of Nanjing University Medical School Nanjing 210008 Jiangsu Province China jiangsu Provin- cial Key Medical Center for Hepatobiliary Diseases Nanjing 210008 Jiangsu Province China jiangsu Key Labora- tory of Molecular Medicine Nanjing 210008 Jiangsu Province Jiangsu Province China Institute of Hepa- tobiliary Surgery Nanjing University Nanjing 210008 Jiangsu Province China Department of Hepatobiliary Surgery Drum Tower Clinical Medical College of Nanjing Medical University Nan- jing 210008 Jiangsu Province China Center for Artificial Liver Therapy Nanjing Sec- ond Hospital Naniing 210008 Jiangsu Province China

AIM:To investigate whether the function of hepatocytes co-cultured with bone marrow mesenchymal stem cells (MSCs) could be maintained in serum from acute-onchronic liver failure (ACLF) patients.METHODS:Hepatocyte supportive functions and cytotoxicity of sera from 18 patients with viral hepatitis B-induced ACLF and 18 healthy volunteers were evaluated for porcine hepatocytes co-cultured with MSCs and hepatocyte mono-layered culture,respectively.Chemokine profile was also examined for the normal serum and liver failure serum.RESULTS:Hepatocyte growth factor (HGF) and Tumor necrosis factor;tumor necrosis factor (TNF)-α were remarkably elevated in response to ACLF while epidermal growth factor (EGF) and VEGF levels were significantly decreased.Liver failure serum samples induced a higher detachment rate,lower viability and decreased liver support functions in the homo-hepatocyte culture.Hepatocytes co-cultured with MSCs could tolerate the cytotoxicity of the serum from ACLF patients and had similar liver support functions compared with the hepatocytes cultured with healthy human serum in vitro.In addition,cocultured hepatocytes maintained a proliferative capability despite of the insult from liver failure serum.CONCLUSION:ACLF serum does not impair the cell morphology,viability,proliferation and overall metabolic capacities of hepatocyte co-cultured with MSCs in vitro.

关键词：肝细胞生长因子骨髓干细胞 ACLF 体外培养人血清细胞增殖代谢功能保护作用

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Influence of chitosan nanofiber scaffold on porcine endogenous retroviral expression and infectivity in pig hepatocytes

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World Journal of Gastroenterology 2011年第22期17卷 2774-2780页

作者： Bing Han xiao-Lei Shi jiang-qiang xiao Yue Zhang Xue-Hui Chu Jin-Yang Gu Jia-Jun Tan Zhong-Ze Gu Yi-Tao Ding Department of Hepatobiliary Surgery the Affiliated Drum Tower Hospital of Nanjing University Medical SchoolNanjing 210008Jiangsu ProvinceChina Department of Hepatobiliary Surgery Drum Tower Clinical Medical College of Nanjing Medical UniversityNanjing 210008Jiangsu ProvinceChina State Key Laboratory of Bioelectronics Southeast UniversityNanjing 210000Jiangsu ProvinceChina

AIM: To investigate the influence of chitosan nanofiber scaffold on the production and infectivity of porcine endogenous retrovirus (PERV) expressed by porcine hepatocytes. METHODS: Freshly isolated porcine hepatocytes were cultured with or without chitosan nanofiber scaffold (defined as Nano group and Hep group) for 7 d. The daily collection of culture medium was used to detect reverse transcriptase (RT) activity with RT activity assaykits and PERV RNA by reverse transcription-polymerase chain reaction (PCR) and real time PCR with the PERV specific primers. And Western blotting was performed with the lysates of daily retrieved cells to determine the PERV protein gag p30. Besides, the in-vitro infectivity of the supernatant was tested by incubating the human embryo kidney 293 (HEK293) cells. RESULTS: The similar changing trends between two groups were observed in real time PCR, RT activity assay and Western blotting. Two peaks of PERV expression at 10H and Day 2 were found and followed by a regular decline. No significant difference was found between two groups except the significantly high level of PERV RNA at Day 6 and PERV protein at Day 5 in Nano group than that in Hep group. And in the in-vitro infection experiment, no HEK293 cell was infected by the supernatant. CONCLUSION: Chitosan nanofiber scaffold might prolong the PERV secreting time in pig hepatocytes but would not obviously influence its productive amount and infectivity, so it could be applied in the bioartificial liver without the increased risk of the virus transmission.

关键词：猪内源性逆转录病毒纳米纤维肝细胞壳聚糖感染性 Western印迹法支架 HEK293细胞

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Evaluation of a novel hybrid bioartificial liver based on a multi-layer flat-plate bioreactor

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World Journal of Gastroenterology 2012年第28期18卷 3752-3760页

作者： xiao-Lei Shi Yue Zhang Xue-Hui Chu Bing Han Jin-Yang Gu jiang-qiang xiao Jia-Jun Tan Zhong-Ze Gu Hao-Zhen Ren Xian-Wen Yuan Yi-Tao Ding Department of Hepatobiliary Surgery Jiangsu Province's Key Medical Center for Hepatobiliary Disease The Affiliated Drum Tower Hospital of Nanjing University Medical School Nanjing 210008 Jiangsu Province China State Key Laboratory of Bioelectronics Southeast University Nanjing 210008 Jiangsu Province China

AIM: To evaluate the efficacy and safety of a hybrid bioartificial liver (HBAL) system in the treatment of acute liver failure. METHODS: Canine models with acute liver failure were introduced with intravenous administration of D-galactosamine. The animals were divided into: the HBAL treatment group (n = 8), in which the canines received a 3-h treatment of HBAL; the bioartificial liver (BAL) treatment group (n = 8), in which the canines received a 3-h treatment of BAL; the non-bioartificial liver (NBAL) treatment group (n = 8), in which the canines received a 3-h treatment of NBAL; the control group (n = 8), in which the canines received no additional treatment. Biochemical parameters and survival time were determined. Levels of xenoantibodies, RNA of porcine endogenous retrovirus (PERV) and reverse transcriptase (RT) activity in the plasma were detected. RESULTS: Biochemical parameters were significantly decreased in all treatment groups. The TBIL level in the HBAL group was lower than that in other groups (2.19 ± 0.55 mmol/L vs 24.2 ± 6.45 mmol/L, 12.47 ± 3.62 mmol/L, 3.77 ± 1.83 mmol/L, P < 0.05). The prothrombin time (PT) in the BAL and HBAL groups was significantly shorter than the NBAL and control groups (18.47 ± 4.41 s, 15.5 ± 1.56 s vs 28.67 ± 5.71 s, 21.71 ± 3.4 s, P < 0.05), and the PT in the HBAL group was shortest of all the groups. The albumin in the BAL and HBAL groups significantly increased and a significantly higher level was observed in the HBAL group compared with the BAL group (27.7 ± 1.7 g/L vs 25.24 ± 1.93 g/L). In the HBAL group, the ammonia levels significantly decreased from 54.37 ± 6.86 to 37.75 ± 6.09 after treatment (P < 0.05); there were significant difference in ammonia levels between other the groups (P < 0.05). The levels of antibodies were similar before and after treatment. The PERV RNA and the RT activity in the canine plasma were all negative. CONCLUSION: The HBAL showed great efficiency and safety in the treatment of acute liver failure.

关键词：生物人工肝混合型生物反应器评价猪内源性逆转录病毒肝功能衰竭平板基础

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Effect evaluation of interleukin-1 receptor antagonist nanoparticles for mesenchymal stem cell transplantation

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World Journal of Gastroenterology 2013年第12期19卷 1984-1991页

作者： xiao-Lei Shi Wei Zhu Jia-Jun Tan jiang-qiang xiao Lin Zhang Qian Xu Zheng-Liang Ma Yi-Tao Ding Department of Hepatobiliary Surgery the Affiliated Drum Tower Hospital of Nanjing University Medical School Key Medical Center of jiangsu Province for Hepatobiliary Diseases Gulou Clinical Medical College of Combined TCM and Western Medicine Nanjing University of Chinese Medicine Department of Anesthesiology the Affiliated Drum Tower Hospital of Nanjing University Medical School School of Public Health Southeast University

AIM: To study the efficacy of marrow mesenchymal stem cells (MSCs) transplantation combined with interleukin-1 receptor antagonist (IL-1Ra) for acute liver failure (ALF). METHODS: Chinese experimental miniature swine were randomly divided into four groups (n = 7), and all animals were given D-galactosamine (D-gal) to induce ALF. Group A animals were then injected with 40 mL saline via the portal vein 24 h after D-gal induction;Group B animals were injected with 2 mg/kg IL-1Ra via the ear vein 18 h, 2 d and 4 d after D-gal induction; Group C received approximately 1 × 108 green fluorescence protein (GFP)-labeled MSCs (GFP-MSCs) suspended in 40 mL normal saline via the portal vein 24 h after D-gal induction; Group D animals were injected with 2 mg/kg IL-1Ra via the ear vein 18 h after D-gal induction, MSCs transplantation was then carried out at 24 h after D-gal induction, and finally 2 mg/kg IL-1Ra was injected via the ear vein 1 d and 3 d after surgery as before. Liver function, serum inflammatory parameters and pathological changes were measured and the fate of MSCs was determined.RESULTS: The optimal efficiency of transfection (97%) was achieved at an multiplicity of infection of 80, as observed by fluorescence microscopy and flow cytometry (FCM). Over 90% of GFP-MSCs were identified as CD44+ CD90+ CD45-MSCs by FCM, which indicated that most GFP-MSCs retained MSCs characteristics. Biochemical assays, the levels of serum inflammatory parameters and histological results in Group D all showed a significant improvement in liver injury compared with the other groups (P < 0.05). The number of GFP-MSCs in Group D was also greater than that in Group B, and the long-term cell proliferation rate was also better in Group D than in the other groups.CONCLUSION: MSCs transplantation is useful in ALF, IL-1Ra plays an important role in alleviating the inflammatory condition, and combination therapy with MSCs transplantation and IL-1Ra is a promising treatment for ALF.

关键词： Interleukin-1 receptor antagonist Mesenchymal stem cells Cell transplantation Acute liver failure Inflammatory environment

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Current understanding of ELF4 deficiency:a novel inborn error of immunity

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World Journal of Pediatrics 2024年第5期20卷 444-450页

作者： Hong-qiang Du xiao-Dong Zhao Department of Rheumatology&Immunology National Clinical Research Center for Child Health and DisordersMinistry of Education Key Laboratory of Child Development and DisordersChongqing Key Laboratory of Child Rare Diseases in Infection and ImmunityChildren’s Hospital of Chongqing Medical UniversityZhongshan Er Road 136Yuzhong DistrictChongqingChina

Background ELF4 deficiency has been recently recognized as a novel disorder within the spectrum of inborn errors of immunity(IEIs),specifically categorized as a“disease of immune dysregulation.”Cases of this condition,reported by our team and others,are very limited worldwide.As such,our current knowledge of this new disease remains preliminary.This review aims to provide a brief overview of the clinical manifestations,pathogenesis,and treatment strategies for this novel IEI.Data sources A comprehensive review was conducted after an extensive literature search in the PubMed/Medline database and websites concerning transcriptional factor ELF4 and reports concerning patients with ELF4 deficiency.Our search strategy was“ELF4 OR ETS-related transcription factor Elf-4 OR EL4-like factor 4 OR myeloid Elf-1-like factor”as of the time of manuscript submission.Results The current signature manifestations of ELF4 deficiency disorder are recurrent and prolonged oral ulcer,abdominal pain,and diarrhea in pediatric males.In some cases,immunodeficiency and autoimmunity can also be prominent.Targeted Sanger sequencing or whole exome sequencing can be used to detect variation in ELF4 gene.Western blotting for ELF4 expression of the patient’s cells can confirm the pathogenic effect of the variant.To fully confirm the pathogenicity of the variant,further functional test is strongly advised.Glucocorticoid and biologics are the mainstream management of ELF4 deficiency disorder.Conclusions Pediatric males presenting with recurring ulcerations in digestive tract epithelium with or without recurrent fever should be suspected of DEX.When atypical presentations are prominent,variations in ELF4 gene should be carefully evaluated functionally due to the complex nature of ELF4 function.Experience of treating DEX includes use of glucocorticoid and biologics and more precise treatment needs more patients to identify and further mechanistic study.

关键词： ELF4 transcription factor Immune dysregulation Inborn errors of immunity Mechanism Recurrent infections

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Gelfand-Kirillov Dimension and Reducibility of Scalar Generalized Verma Modules for Classical Lie Algebras

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Acta Mathematica Sinica,English Series 2024年第3期40卷 658-706页

作者： Zhan qiang BAI Jing jiang School of Mathematical Sciences Soochow UniversitySuzhou 215006P.R.China E-mail:zqbai@*** jjsd6514@***

Let g be a classical complex simple Lie algebra and q be a parabolic subalgebra.Let M be a generalized Verma module induced from a one dimensional representation of q.Such M is called a scalar generalized Verma module.In this paper,we will determine the reducibility of scalar generalized Verma modules associated to maximal parabolic subalgebras by computing explicitly the Gelfand-Kirillov dimension of the corresponding highest weight modules.

关键词： Generalized Verma module Gelfand-Kirillov dimension Young tableau

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Severe liver injury and clinical characteristics of occupational exposure to 2-amino-5-chloro-N,3-dimethylbenzamide: A case series

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Hepatobiliary & Pancreatic Diseases International 2024年第2期23卷 186-194页

作者： Meng-xiao Feng Hua Zou Yuan-qiang Lu Department of Emergency Medicine The First Affiliated HospitalZhejiang University School of MedicineHangzhou 310003China Key Laboratory for Diagnosis and Treatment of Aging and Physic-chemical Injury Diseases of Zhejiang Province Hangzhou 310003China Occupational Health and Radiation Protection Institute Zhejiang Provincial Center for Disease Control and PreventionHangzhou 310051China

Background:The 2-amino-5-chloro-N,3-dimethylbenzamide is a key intermediate in the synthesis of pesticides and pharmaceuticals.However,no literature currently exists on 2-amino-5-chloro-N,3-dimethylbenzamide poisoning in humans.This study aimed to reveal the health hazard of this chemical for humans and summarize the clinical characteristics of patients with occupational 2-amino-5-chloro-N,3-dimethylbenzamide poisoning.Methods:This observational study included four patients with 2-amino-5-chloro-N,3-dimethylbenzamide poisoning from June 2022 to July 2022.The entire course of the incidents was described in detail.Blood 2-amino-5-chloro-N,3-dimethylbenzamide concentrations were detected by a mass spectrometer.Hema-toxylin and eosin staining was performed to assess liver injury,and immunofluorescence was used to evaluate hepatic mitophagy.Results:The 2-amino-5-chloro-N,3-dimethylbenzamide powder(99%purity)entered the human body mainly via the skin and respiratory tract due to poor personal protective measures.The typical course of 2-amino-5-chloro-N,3-dimethylbenzamide poisoning was divided into latency,rash,fever,organic dam-age,and recovery phases in accordance with the clinical evolution.Rash and fever may be the important premonitory symptoms for further organ injuries.The chemical was detected in the blood of all patients and caused multiple organ injuries,predominantly liver injury,including kidney,myocardium,and micro-circulation.Three patients recovered smoothly after comprehensive treatments,including artificial liver therapy,continuous renal replacement therapy,glucocorticoids,and other symptomatic and supportive treatments.One patient survived by liver transplantation.The postoperative pathological findings of the removed liver showed acute liver failure,and immunofluorescence staining confirmed the abundance of mitophagy in residual hepatocytes.Conclusions:This study is the first to elaborate the clinical characteristics of patients with 2-amino-5-chloro-N,3-dimethylbenzamide poisoning.The chemical enter

关键词： 2-amino-5-chloro-N,3-dimethylbenzamide Poisoning Clinical characteristics Liver injury

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Ceramic-lined compound copper pipe prepared by SHS process

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中国有色金属学会会刊：英文版 2004年第Z1期14卷 106-110页

作者： FU Han-guang jiang Zhi-qiang ZHANG xiao-hong Department of Mechanical Engineering Tsinghua University Beijing 100084 China Department of Industrial Engineering Zhengzhou Institute of Aeronautics Zhengzhou China Taiyuan Iron and Steel (Group) Company Taiyuan China

Self-propagating high-temperature synthesis(SHS) is a new kind of material synthesis technique, and has characteristics with respect to low energy consumption, short synthetizing time, high production quantity, high product purity and no environmental pollution. When SHS combines with centrifugal casting, ceramic-lined compound copper pipe(CLCCP) can be produced, the inner surface of copper pipe can produce ceramic coatings having good wear and corrosion resistance. In order to increase the densification degree, combining strength and toughness of ceramic layer, the effects of additives such as SiO2, CrO3, Na2B4O7 and ZrO2 are researched, adding SiO2 and CrO3 in thermite, the densification degree of ceramic layer increases, adding Na2 B4 O7 in thermite can increase combining strength, adding ZrO2 in thermite can increase the toughness of ceramic layer. CLCCP is used in tubular billet crystallizer, having excellent service effects and decreasing the production cost of tubular billet.

关键词： SHS ceramic lining compound copper pipe crystallizer

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