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Chinese Medical Journal 2024年第2期137卷 140-151页

作者： Minghao Lin Xiaosu Zhao Yingjun Chang Xiangyu Zhao Peking University People’s Hospital Peking University Institute of HematologyNational Clinical Research Center for Hematologic DiseaseBeijing Key Laboratory of Hematopoietic Stem Cell TransplantationBeijing 100044China

Chimeric antigen receptor(CAR)-modified T-cell therapy has achieved remarkable success in the treatment of acute lymphoblastic leukemia(ALL).Measurable/minimal residual disease(MRD)monitoring plays a significant role in the prognostication and management of patients undergoing CAR-T-cell *** MRD detection methods include flow cytometry(FCM),polymerase chain reaction(PCR),and next-generation sequencing(NGS),and each method has advantages and *** has been well documented that MRD positivity predicts a poor prognosis and even disease ***,how to perform prognostic evaluations,stratify risk based on MRD status,and apply MRD monitoring to guide individual therapeutic decisions have important implications in clinical *** review assesses the common and novel MRD assessment *** addition,we emphasize the critical role of MRD as a prognostic biomarker and summarize the latest studies regarding MRD-directed combination therapy with CAR-T-cell therapy and allogeneic hematopoietic stem cell transplantation(allo-HSCT),as well as other therapeutic strategies to improve treatment ***,this review discusses current challenges and strategies for MRD detection in the setting of disease relapse after targeted therapy.

关键词： Measurable/minimal residual disease Acute lymphoblastic leukemia Chimeric antigen receptor-modified T-cell therapy Allogeneic hematopoietic stem cell transplantation Relapse

Targeting N4-acetylcytidine suppresses hepatocellular carcinoma progression by repressing eEF2.mediated HMGB2.mRNA translation

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Cancer Communications 2024年第9期44卷 1018-1041页

作者： Hailing Liu Lei Xu Shiwei Yue Hongfei Su Xing Chen Qiumeng Liu Hui Li Huifang Liang Xiaoping Chen Jiefeng He Zeyang Ding Bixiang Zhang Hepatic Surgery Center Tongji HospitalTongji Medical CollegeHuazhong University of Science and TechnologyWuhanHubeiP.R.China Hubei key laboratory of Hepato‑Pancreatic‑Biliary Diseases Tongji HospitalTongji Medical CollegeHuazhong University of Science and TechnologyWuhanHubeiP.R.China Department of Hepatopancreatobiliary Surgery Zhejiang Cancer HospitalHangzhou Institute of Medicine(HIM)Chinese Academy of SciencesHangzhouZhejiangP.R.China Department of Hepatobiliary Pancreatic Tumor Center Chongqing University Cancer HospitalSchool of MedicineChongqing UniversityChongqingP.R.China key laboratory of {2. transplantation Ministry of EducationWuhanHubeiP.R.China Department of Hepatobiliary Surgery Key Laboratory of Hepatobiliary and Pancreatic Diseases of Shanxi Province(Preparatory)Shanxi Bethune HospitalShanxi Academy of Medical SciencesShanxi Medical UniversityTaiyuanShanxiP.R.China

Background:N4-acetylcytidine(ac4C)represents a novel messenger RNA(mRNA)modification,and its associated acetyltransferaseN-acetyltransferase 10(NAT10)plays a crucial role in the initiation and progression of tumors by regulating mRNA ***,its role in hepatocellular carcinoma(HCC)development and prognosis is largely *** study aimed to elucidate the role of NAT10-mediated ac4C in HCC progression and provide a promising therapeutic ***:The ac4C levels were evaluated by dot blot and ultra-performance liquid chromatography-tandem mass spectrometry with harvested HCC *** expression of NAT10 was investigated using quantitative real-time polymerase chain reaction,western blotting,and immunohistochemical staining across 91 cohorts of HCC *** explore the underlying mechanisms of NAT10-ac4C in HCC,we employed a comprehensive approach integrating acetylated RNA immunoprecipitation and sequencing,RNA sequencing and ribosome profiling analyses,along with RNA immunoprecipitation,RNA pulldown,mass spectrometry,and site-specific mutation *** drug affinity responsive targets stability,cellular thermal shift assay,and surface plasmon resonance assays were performed to assess the specific binding of NAT10 and ***,the efficacy of targeting NAT10-ac4C for HCC treatment was elucidated through in vitro experiments using HCC cells and in vivo HCCmouse ***:Our investigation revealed a significant increase in both the ac4C RNA level and NAT10 expression in ***,elevated NAT10 expression was associated with poor outcomes in HCC ***,silencing NAT10 suppressed HCC proliferation and metastasis in vitro and in ***,NAT10 stimulates the ac4C modification within the coding sequence(CDS)of high mobility group protein B2.HMGB2.,which subsequently enhances HMGB2.translation by facilitating eukaryotic elongation factor 2.eEF2.binding to the ac4C sites on HMGB2.mRNA’s C

关键词： N4-acetylcytidine N-acetyltransferase 10 hepatocellular carcinoma mRNA translation targeted therapy

Immune response triggered by the ablation of hepatocellular carcinoma with nanosecond pulsed electric field

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Frontiers of Medicine 2021年第2期15卷 170-177页

作者： Jianpeng Liu Xinhua Chen Shusen Zheng Division of Hepatobiliary Pancreatic Surgery Department of SurgeryFirst Affiliated HospitalSchool of MedicineZhejiang UniversityHangzhou 310003China key laboratory of {2. multi-organ transplantation Ministry of Public HealthKey Laboratory of the Diagnosis and Treatment of Organ TransplantationCAMSKey Laboratory of Organ TransplantationHangzhou 310003China Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases Hangzhou 310003China

Nanosecond pulsed electric field(nsPEF)is a novel,nonthermal,and minimally invasive modality that can ablate solid tumors by inducing *** animal experiments show that nsPEF can induce the immunogenic cell death of hepatocellular carcinoma(HCC)and stimulate the host’s immune response to kill residual tumor cells and decrease distant metastatic ***-induced immunity is of great clinical importance because the nonthermal ablation may enhance the immune memory,which can prevent HCC recurrence and *** review summarized the most advanced research on the effect of *** possible mechanisms of how locoregional nsPEF ablation enhances the systemic anticancer immune responses were *** stimulates the host immune system to boost stimulation and prevail ***,nsPEF increases the dendritic cell loading and inhibits the regulatory responses,thereby improving immune stimulation and limiting immunosuppression in HCC-bearing ***,nsPEF has excellent potential for HCC treatment.

关键词： nanosecond pulsed electric fields(nsPEF) hepatocellular carcinoma(HCC) immune response recurrence metastasis

Lower tacrolimus trough levels in the late period after living donorliver transplantation contribute to improvements in long-term clinicaloutcomes

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Hepatobiliary & Pancreatic Diseases International 2018年第3期17卷 204-209页

作者： lei geng li-dong wang jun-jie huang tian shen zhuo-yi wang bing-yi lin yu-fu ye shu-sen zheng Division of Hepatobiliary and Pancreatic Surgery Department of SurgeryThe First Affiliated HospitalZhejiang University School of MedicineHangzhou 310003China key laboratory of {2. multi-organ transplantation Ministry of Public HealthKey Laboratory of Organ TransplantationHangzhou 310003China key laboratory of {2. transplantation Hangzhou 310003China Collaborative Innovation Center for Diagnosis Treatment of Infectious Diseases Hangzhou 310003China

Background： Previous studies have emphasized the need to reduce tacrolimus （TAC） trough levels in theearly post-liver transplantation （LT） period. However, whether late-period TAC trough levels influence the long... 详细信息

关键词： Liver transplantation Complications Immunosuppression

Oncogenic role of microRNA-42.-5p in hepatocellular carcinoma

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Hepatobiliary & Pancreatic Diseases International 2015年第6期14卷 613-618页

作者： Li-Ming Wu Jian-Song Ji Zhe Yang Chun-Yang Xing Ting-Ting Pan Hai-Yang Xie Feng Zhang Li Zhuang Lin Zhou Shu-Sen Zheng Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases key laboratory of {2. multi-organ transplantation Ministry of Public Health key laboratory of {2. transplantation of Zhejiang Province Division of Hepatobiliary and Pancreatic Surgery First Affiliated HospitalZhejiang University School of Medicine Lishui Hospital of Zhejiang University

BACKGROUND： It has been found that microRNA-42.-5p （miR42.-Sp） is an oncogenic factor and frequently upregulated in gastric carcinoma. However, the involvement of miR42.- 5p in hepatocellular carcinoma （HCC） has been rarely reported. The aim of this study was to assess whether miR42.-Sp is aberrantly expressed in HCC tissues, and to characterize its roles in the cancerous biology of HCC.

关键词： hepatocellular carcinoma miR42.-5p proliferation invasion oncogene

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 {2. 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 72. patients with primary LT between January 2.15 and December 2.2.. 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 72. patients, 2.(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

Reassessment of palliative surgery in conversion therapy of previously unresectable hepatocellular carcinoma: Two case reports and review of literature

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World Journal of Gastrointestinal Surgery 2024年第10期16卷 3312-3320页

作者： Yang-Bo Zhu Jia-Yi Qin Ting-Ting Zhang Wen-Jin Zhang Qi Ling Division of Hepatobiliary and Pancreatic Surgery Department of SurgeryThe First Affiliated HospitalZhejiang University School of MedicineHangzhou 310003Zhejiang ProvinceChina key Lab of combined {2.-organ transplantation Ministry of Public HealthThe First Affiliated HospitalZhejiang University School of MedicineHangzhou 310003Zhejiang ProvinceChina Department of Clinical Pharmacy The First Affiliated HospitalZhejiang University School of MedicineHangzhou 310003Zhejiang ProvinceChina Department of Medical Imaging The First Affiliated HospitalZhejiang University School of MedicineHangzhou 310003Zhejiang ProvinceChina

BACKGROUND Most patients with hepatocellular carcinoma(HCC)have lost the opportunity for direct surgery at the time of *** chemoembolization(TACE)combined with immune checkpoint inhibitors or tyrosine kinase inhibitors(TKI)can partially transform some unresectable HCC and improve the prognosis ***,based on the promising prospects of combined targeted and immunotherapy for the effective treatment of HCC,the positive role of palliative surgery in the conversion treatment of advanced HCC urgently needs further in-tensive *** SUMMARY In this study,we describe two successful cases of"conversion therapy for un-resectable HCC"achieved mainly by palliative surgery combined with TACE plus immunotherapy and TKIs.A 48-year-old patient with newly diagnosed HCC,presenting with a 6-cm mass in the segment VII/VIII of the right liver with mul-tiple intrahepatic metastases,could not undergo one-stage radical surgical *** underwent palliative surgery with radiofrequency of metastatic lesions and the palliative resection of the primary mass,and received subsequent TACE treatments twice in the early postoperative period(2.weeks and 6 weeks),in addition to targeted and immune combination therapy with sintilimab injection and oral *** evidence of recurrence was observed during the 11-month follow-up period after *** other patient was a 47-year-old patient with massive HCC(18 cm×15 cm×4.5 cm)in the left liver with severe *** left portal branch was occluded and a tumor thrombus formed,and the tumor partly involved the middle hepatic *** patient underwent palliative surgery of left hemihepatectomy(including resection of the middle hepatic vein)for HCC,followed by three TACE procedures and oral TKIs 2.weeks after *** months later,the re-examination via computed tomography revealed no tumour activity in the remaining right liver,while magnetic resonance imaging revealed slight local tumor enh

关键词： Hepatocellular carcinoma Transarterial chemoembolization Immunotherapy Conversion Therapy Tyrosine kinase inhibitors Case report

''Minimizing tacrolimus' ' strategy and long-term survival after liver transplantation

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World Journal of Gastroenterology 2014年第32期20卷 11363-11369页

作者： Jun-Jun Jia Bin-Yi Lin Jiang-Juan He Lei Geng Dhruba Kadel Li Wang Dong-Dong Yu Tian Shen Zhe Yang Yu-Fu Ye Lin Zhou Shu-Sen Zheng key laboratory of {2. multi-organ transplantation Ministry of Public Health Depart-ment of Hepatobiliary and Pancreatic Surgery First Affiliated Hospital of Zhejiang University School of Medicine

AIM: To investigate the effect of the ‘‘minimizing tacrolimus' ' strategy on long-term survival of patients after liver transplantation(LT).METHODS: We conducted a retrospective study of 319 patients who received LT between January 2.09 and December 2.11 at the First Affiliated Hospital of Zhejiang University School of Medicine. Following elimination of ineligible patients, 2.5 patients were included in the study. The relationship between early tacrolimus(TAC)exposure and survival period was analyzed by Kaplan Meier curves. Adverse effects related to TAC were eval-uated by the χ2.test. Routine monitoring of blood TAC concentration(TC) was performed using the PRO-TracTM Ⅱ Tacrolimus Elisa Kit(Diasorin, United States). RESULTS: Of 2.5 subjects enrolled in the study, 12.(52.8%) experienced adverse effects due to TAC. When evaluating mean TC, the survival time of patients with a mean TC 2..3 ± 47.8 d, 911.3 ± 131.6 d vs 1343.2.± 83.1 d, P 2.4 was significantly longer than that in the other groups(1388.8 ± 45.4 d vs 102..6 ± 131.3 d, 1388.8 ± 45.4 d vs 12.4.9 ± 57.0 d, P 2.and SD > 4, the survival time was not statistically different. Adverse effects experienced in all three groups were not statistically different. In Cox regression analysis, male patients and those with a primary diagnosis of benign disease, mean TC > 5 ng/mL and TC SD 2.4 had better ***: The early ‘‘minimizing tacrolimus' ' strategy with a mean TC of 5-10 ng/mL and SD of 2.4 was beneficial in terms of long-term survival after LT.

关键词： Tacrolimus Liver transplantation Outcome Minimizing tacrolimus Immunosuppressive drug

Liver transplantation and resection in patients with hepatocellular cancer and portal vein tumor thrombosis: Feasible and effective?

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Hepatobiliary & Pancreatic Diseases International 2024年第2期23卷 123-128页

作者： Prashant Bhangui Institute of Liver transplantation and Regenerative Medicine Medanta–The MedicitySector 38GurgaonDelhi NCR 122001India

Patients with locally advanced hepatocellular cancer(HCC)and portal vein tumor thrombosis(PVTT)have a dismal prognosis since limited treatment options are available for *** recent years,effective systemic therapy,and advances in the understanding of technicalities and effectiveness of ablative therapies especially radiotherapy,have given some hope to prolong survival in *** review summarized recent evidence in literature regarding the possible role of liver resection(LR)and liver transplantation(LT)in patients with locally advanced HCC and PVTT with no extrahepatic *** therapies have helped make curative resection or LT a reality in selected *** review emphasizes on the key points to focus on when considering surgery in these patients,who are usually relegated to palliative systemic therapy *** patient selection based on tumor biology,documented downstaging based on imaging and decrease in tumor marker levels,and an adequate waiting period to demonstrate stable disease,may help obtain satisfactory long-term outcomes post LR or LT in an intention to treat strategy in patients with HCC and PVTT.

关键词： Hepatocellular carcinoma Portal vein tumour thrombosis Downstaging therapies Living donor liver transplantation and resection Outcomes

Gut liver brain axis in diseases:the implications for therapeutic interventions

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Signal Transduction and Targeted Therapy 2024年第1期9卷 79-104页

作者： Mengyao Yan Shuli Man Benyue Sun Long Ma Lanping Guo Luqi Huang Wenyuan Gao State key laboratory of Food Nutrition and Safety Key Laboratory of Industrial MicrobiologyMinistry of EducationTianjin Key Laboratory of Industry MicrobiologyNational and Local United Engineering Lab of Metabolic Control Fermentation TechnologyChina International Science and Technology Cooperation Base of Food Nutrition/Safety and Medicinal ChemistryCollege of BiotechnologyTianjin University of Science&Technology300457 TianjinChina National Resource Center for Chinese Materia Medica China Academy of Chinese Medical Sciences100700 BeijingChina Tianjin key laboratory for Modern Drug Delivery&High-Efficiency School of Pharmaceutical Science and TechnologyTianjin UniversityWeijin Road300072 TianjinChina

Gut-liver-brain axis is a three-way highway of information interaction system among the gastrointestinal tract,liver,and nervous *** the past few decades,breakthrough progress has been made in the gut liver brain axis,mainly through understanding its formation mechanism and increasing treatment *** this review,we discuss various complex networks including barrier permeability,gut hormones,gut microbial metabolites,vagus nerve,neurotransmitters,immunity,brain toxic metabolites,β-amyloid(Aβ)metabolism,and epigenetic regulation in the gut-liver-brain *** therapies containing antibiotics,probiotics,prebiotics,synbiotics,fecal microbiota transplantation(FMT),polyphenols,low FODMAP diet and nanotechnology application regulate the gut liver brain ***,some special treatments targeting gut-liver axis include farnesoid X receptor(FXR)agonists,takeda G protein-coupled receptor 5(TGR5)agonists,glucagon-like peptide-1(GLP-1)receptor antagonists and fibroblast growth factor 19(FGF19)*** gut-brain axis embraces cognitive behavioral therapy(CBT),antidepressants and tryptophan metabolism-related *** liver-brain axis contains epigenetic regulation and Aβmetabolism-related *** the future,a better understanding of gut-liver-brain axis interactions will promote the development of novel preventative strategies and the discovery of precise therapeutic targets in multiple diseases.

关键词： metabolism therapeutic immunity