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Hepatobiliary & pancreatic Diseases International 2024年第2期23卷 154-159页

作者： Badi Rawashdeh Richard Bell Abdul Hakeem Raj Prasad division of Transplant surgery Department of General SurgeryMedical College of WisconsinMilwaukeeWI53226USA Leeds Teaching Hospital LeedsUK

Colorectal cancer is a leading cause of cancerrelated mortality,with nearly half of the affected patients developing liver metastases.For three decades,liver resection(LR)has been the primary curative strategy,yet its applicability is limited to about 20%of cases.Liver transplantation(LT)for unresectable metastases was attempted unsuccessfully in the 1990s,with high rates of perioperative death and recurrence.There is now more interest in this strategy due to improvements in systemic therapies and surgical techniques.A significant study conducted by the Oslo group showed that patients receiving liver transplants had a 60%chance of survival after five years.Significantly better results have been achieved by using advanced imaging for risk stratification and further refining selection criteria,especially in the Norvegian SECA trials.This review carefully charts the development and history of LT as a treatment option for colorectal cancer liver metastases.The revolutionary path from the early days of exploratory surgery to the current situation of cautious optimism is traced,highlighting the critical clinical developments and improved patient selection standards that have made LT a potentially curative treatment for such challenging very well selected cases.

关键词： Liver transplantation Colorectal cancer liver metastases Non-resectable liver metastases

Evaluation of hepatitis B viral replication and proteomic analysis of HepG2.2.15 cell line after knockdown of HBx

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Hepatobiliary & pancreatic Diseases International 2011年第3期10卷 295-302页

作者： Hai-Yang Xie,Jun Cheng,Chun-Yang Xing,Jin-Jin Wang,Rong Su,Xu-Yong Wei,Lin Zhou and Shu-Sen Zheng Author Affiliations:Key Laboratory of Combined Multi-organ Transplantation,Ministry of Public Health Key Laboratory of Organ Transplantation Zhejiang Province and division of Hepatobiliary and pancreatic surgery,Department of surgery,First Affiliated Hospital,Zhejiang University School of Medicine,Hangzhou 310003,China Key Laboratory of Combined Multi-organ Transplantation Ministry of Public Health Key Laboratory of Organ Transplantation Zhejiang Province and division of Hepatobiliary and pancreatic surgery Department of Surgery First Affiliated Hospital Zhejiang University School of Medicine Hangzhou 310003 China

BACKGROUND:Hepatitis B virus (HBV) is one of the major pathogens of human liver disease.Studies have shown that HBV X protein (HBx) plays an important role in promoting viral gene expression and replication.In this study we performed a global proteomic profiling to identify the downstream functional proteins of HBx,thereby detecting the mechanisms of action of HBx on virion replication.METHODS:HBx in the HepG2.2.15 cell line was knocked down by the transfection of small interfering RNA (siRNA).The replication level of HBV was evaluated by microparticle enzyme immunoassay analysis of HBsAg and HBeAg in the culture supernatant,and real-time quantitative PCR analysis of HBV DNA.Two-dimensional electrophoresis combined with MALDI-TOF/TOF was performed to analyze the changes in protein expression profile after treatment with HBx siRNA.RESULTS:Knockdown of HBx disturbed HBV replication in vitro.HBx target siRNA significantly inhibited the expression of HBsAg,HBeAg and the replication of HBV DNA.Twelve significantly changed proteins (7 upregulated and 5 downregulated) were successfully identified by MALDI-TOF/TOF using proteomics differential expression analysis after the knockdown of HBx.Among these identified proteins,HSP70 was validated by Western blotting.CONCLUSION:The results of the study indicated the positive effect of HBx on HBV replication,and a group of downstream target proteins of HBx may be responsible for this effect.

关键词： hepatitis B virus HBx replication proteomics

Polymorphisms of CCL3L1/CCR5 genes and recurrence of hepatitis B in liver transplant recipients

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Hepatobiliary & pancreatic Diseases International 2011年第6期10卷 593-598页

作者： Hong Li,Hai-Yang Xie,Lin Zhou,Wei-Lin Wang,Ting-Bo Liang,Min Zhang and Shu-Sen Zheng Key Laboratory of Combined Multi-Organ Transplan-tation,Ministry of Public Health,and division of Hepatobiliary pancreatic surgery,First Affiliated Hospital,Zhejiang University School of Medicine,Hangzhou 310003,China Key Laboratory of Combined Multi-Organ Transplantation Ministry of Public Health Zhejiang University School of Medicine Hangzhou 310003 China division of Hepatobiliary pancreatic surgery First Affiliated Hospital Zhejiang University School of Medicine Hangzhou 310003 China

BACKGROUND:The genetic diversity of chemokines and chemokine receptors has been associated with the outcome of hepatitis B virus infection.The aim of this study was to evaluate whether the copy number variation in the CCL3L1 gene and the polymorphisms of CCR5Δ32 and CCR5-2459A→G (rs1799987) are associated with recurrent hepatitis B in liver transplantation for hepatitis B virus infection-related end stage liver disease.METHODS:A total of 185 transplant recipients were enrolled in this study.The genomic DNA was extracted from whole blood,the copy number of the CCL3L1 gene was determined by a quantitative real-time PCR based assay,CCR5Δ32 was detected by a sizing PCR method,and a single-nucleotide polymorphism in CCR5-2459 was detected by restriction fragment length polymorphism PCR.RESULTS:No CCR5Δ32 mutation was detected in any of the individuals from China.Neither copy number variation nor polymorphism in CCR5-2459 was associated with post-transplant reinfection with hepatitis B virus.However,patients with fewer copies (<4) of the CCL3L1 gene compared with the population median in combination with the CCR5G allele had a significantly higher risk for recurrent hepatitis B (odds ratio=1.93,95% CI:1.00-3.69;P=0.047).CONCLUSION:Patients possessing the compound decreased functional genotype of both CCL3L1 and CCR5 genes might be more likely to have recurrence of hepatitis B after transplantation.

关键词： CCL3L1 chemokine receptor 5 copy number variation hepatitis B liver transplantation

Risk factors and incidence of acute pyogenic cholangitis

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Hepatobiliary & pancreatic Diseases International 2012年第6期11卷 650-654页

作者： Yun-Sheng Qin, Qi-Yong Li, Fu-Chun Yang , Shu-Sen Zheng division of Hepatobiliary and pancreatic surgery Key Laboratory of Combined Multi-organ Transplantation, Ministry of Public Health Key Laboratory of Organ Transplantation Zhejiang Province, First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou 310003, China division of Hepatobiliary and pancreatic surgery Key Laboratory of Combined Multi-organ Transplantation Ministry of Public Health and Key Laboratory of Organ Transplantation Zhejiang Province First Affiliated Hospital Zhejiang University School of Medicine Hangzhou 310003 China

BACKGROUND: Acute cholangitis varies from mild to severe form. Acute suppurative cholangitis (ASC), the severe form of acute cholangitis, is a fatal disease and requires urgent biliary decompression. Which patients are at a high risk of ASC and need emergency drainage is still unclear. The present study aimed to identify the factors for determining early-stage ASC and distinguishing ASC from acute cholangitis. METHODS: We analyzed 359 consecutive patients with acute cholangitis who had been admitted to the First Affiliated Hospital, Zhejiang University School of Medicine from January 2004 to May 2011. Emergency endoscopic retrograde cholangiopancreatography (ERCP) was carried out in all patients to decompress or clear the stones by experienced endoscopists Clinical and therapeutic data were collected, and univariate and multivariate analyses were performed to identify the potential risk factors of ASC. RESULTS: Of the 359 patients, 1 was excluded because of failure of ERCP drainage. Of the remaining 358 patients with an average age of 62.7 years (range 17-90), 162 were diagnosed with ASC, and 196 with non-ASC. ENBD catheters were placed in 343 patients (95.8%), of whom 182 patients had stones removed at the same time, and plastic stent was placed in 25 patients (7.0%) Clinical conditions were improved quickly after emergency biliary drainage in all patients. Complications were identified in 11 patients (3.1%): mild pancreatitis occurred in 8 patients and hemorrhage in 3 patients. There was no mortality. Univariate analysis showed that several variables were associated with ASC: age, fever, decreased urine output, hypotension, tachycardia abnormal white blood cell count (WBC), low platelet, high C reactive protein (CRP), and duration of the disease. Multivariateanalysis revealed that advanced age, hypotension, abnormal WBC, high CRP, and duration of the disease were independent risk factors for ASC. CONCLUSIONS: This study demonstrates that advanced age, hypotension, abnormal WBC, high CRP, and long duration of an

关键词： acute cholangitis suppurative endoscopic retrograde cholangiopancreatography

Circularly polarized light emission and detection by chiral inorganic semiconductors

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Frontiers of Optoelectronics 2024年第2期17卷 43-49页

作者： Zha Li Wancai Li Dehui Li Wei Tang Huageng Liang Huaibing Song Chao Chen Liang Gao Jiang Tang Wuhan National Laboratory for Optoelectronics Huazhong University of Science and TechnologyWuhan 430074China School of Optical and Electronic Information Huazhong University of Science and TechnologyWuhan 430074China International Health Care Center National Center for Global Health and MedicineTokyo 162‑8655Japan Hepato‑Biliary‑pancreatic surgery division Department of SurgeryThe University of Tokyo HospitalTokyo 113‑8655Japan Department of Urology Union HospitalTongji Medical CollegeHuazhong University of Science and TechnologyWuhan 430074China Faculty of Materials Science and Chemistry China University of GeosciencesWuhan 430074China

Chiral inorganic semiconductors with high dissymmetric factor are highly desirable,but it is generally difficult to induce chiral structure in inorganic semiconductors because of their structure rigidity and symmetry.In this study,we introduced chiral ZnO film as hard template to transfer chirality to CsPbBr3 film and PbS quantum dots(QDs)for circularly polarized light(CPL)emission and detection,respectively.The prepared CsPbBr_(3)/ZnO thin film exhibited CPL emission at 520 nm and the PbS QDs/ZnO film realized CPL detection at 780 nm,featuring high dissymmetric factor up to around 0.4.The electron transition based mechanism is responsible for chirality transfer.

关键词： High dissymmetric factor Circularly polarized light emission Semiconductor Hard template,Chirality

SERPINE2 promotes liver cancer metastasis by inhibiting c-Cbl-mediated EGFR ubiquitination and degradation

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Cancer Communications 2024年第3期44卷 384-407页

作者： Shiyu Zhang Xing Jia Haojiang Dai Xingxin Zhu Wenfeng Song Suchen Bian Hao Wu Shinuo Chen Yangbo Tang Junran Chen Cheng Jin Mengqiao Zhou Haiyang Xie Shusen Zheng Penghong Song division of Hepatobiliary and pancreatic surgery Department of SurgeryThe First Affiliated HospitalZhejiang University School of MedicineHangzhouZhejiangP.R.China National Health Commission Key Laboratory of Combined Multi-organ Transplantation HangzhouZhejiangP.R.China Key Laboratory of the Diagnosis and Treatment of Organ Transplantation Research Unit of Collaborative Diagnosis and Treatment for Hepatobiliary and Pancreatic CancerChinese Academy of Medical SciencesHangzhouZhejiangP.R.China Key Laboratory of Organ Transplantation Research Center for Diagnosis and Treatment of Hepatobiliary DiseasesHangzhouZhejiangP.R.China State Key Laboratory for Diagnosis and Treatment of Infectious Diseases First Affiliated HospitalZhejiang University School of MedicineHangzhouZhejiangP.R.China

Background:Liver cancer is a malignancy with high morbidity and mortality rates.Serpin family E member 2(SERPINE2)has been reported to play a key role in the metastasis of many tumors.In this study,we aimed to investigate the potential mechanism of SERPINE2 in liver cancer metastasis.Methods:The Cancer Genome Atlas database(TCGA),including DNA methy-lation and transcriptome sequencing data,was utilized to identify the crucial oncogene associated with DNA methylation and cancer progression in liver can-cer.Data from the TCGA and RNA sequencing for 94 pairs of liver cancer tissues were used to explore the correlation between SERPINE2 expression and clin-ical parameters of patients.DNA methylation sequencing was used to detect the DNA methylation levels in liver cancer tissues and cells.RNA sequencing,cytokine assays,immunoprecipitation(IP)and mass spectrometry(MS)assays,protein stability assays,and ubiquitination assays were performed to explore the regulatory mechanism of SERPINE2 in liver cancer metastasis.Patient-derived xenografts and tumor organoid models were established to determine the role of SERPINE2 in the treatment of liver cancer using sorafenib.Results:Based on the public database screening,SERPINE2 was identified as a tumor promoter regulated by DNA methylation.SERPINE2 expression was significantly higher in liver cancer tissues and was associated with the dismal prognosis in patients with liver cancer.SERPINE2 promoted liver cancer metas-tasis by enhancing cell pseudopodia formation,cell adhesion,cancer-associated fibroblast activation,extracellular matrix remodeling,and angiogenesis.IP/MS assays confirmed that SERPINE2 activated epidermal growth factor receptor(EGFR)and its downstream signaling pathways by interacting with EGFR.Mechanistically,SERPINE2 inhibited EGFR ubiquitination and maintained its protein stability by competing with the E3 ubiquitin ligase,c-Cbl.Additionally,EGFR was activated in liver cancer cells after sorafenib treatment,and SER-PINE2 knockdown-induced EGFR downregulation sig

关键词： liver cancer metastasis DNA methylation SERPINE2 EGFR c-Cbl ubiquitination

Liver transplantation in Crigler-Najjar syndrome type I disease

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Hepatobiliary & pancreatic Diseases International 2012年第5期11卷 545-548页

作者： Zhen-Hua Tu, De-Sheng Shang, Jin-Cai Jiang, Wu Zhang, Min Zhang, Wei-Lin Wang, Hai-Yan Lou,Shu-Sen Zheng division of Hepatobiliary and pancreatic surgery, Department of surgery, First Affiliated Hospital, Zhejiang University School of Medicine, Key Laboratory of Combined Multi-Organ Transplantation, Ministry of Public Health & Key Laboratory of Organ Transplantation of Zhejiang Province Department of Radiology,First Affiliated Hospital,Zhejiang University School of Medicine, Hangzhou 310003, China division of Hepatobiliary and pancreatic surgery Department of Surgery First Affiliated Hospital Zhejiang University School of Medicine Key Laboratory of Combined Multi-Organ Transplantation Ministry of Public Health & Key Laboratory of Organ Transplantation of Zhejiang Province Hangzhou 310003 Hangzhou China Department of Radiology First Affiliated Hospital Zhejiang University School of Medicine Hangzhou 310003 Hangzhou China

BACKGROUND: Crigler-Najjar syndrome type I (CNS I) is a very rare autosomal recessive inherited disease that liver transplantation can properly deal with. METHODS: We present one case of an 18-month-old child with CNS I diagnosed by clinical findings and genetic detecting LTx was performed 5 days after kernicterus broke out and neurological symptoms were successfully reversed. RESULT: Magnetic resonance imaging and magnetic resonance spectroscopy showed encouraging results that brain pathology had a trend to return to normal in 1-year follow-up, combined with electroencephalogram and motor development estimate studies. CONCLUSIONS: Liver transplantation can cure CNS I with reversible neurological symptoms to some extent in time Magnetic resonance spectroscopy may be a future option of predicting brain conditions and selecting suitable patients with CNS I for transplantation.

关键词： Crigler-Najjar liver transplantation inborn error of metabolism magnetic resonance imaging hyperbilirubinemia

Effects of suppressing glucose transporter-1 by an antisense oligodeoxynucleotide on the growth of human hepatocellular carcinoma cells

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Hepatobiliary & pancreatic Diseases International 2011年第1期10卷 72-77页

作者： Tian-Qi Liu,Jun Fan,Lin Zhou and Shu-Sen Zheng Key Laboratory of Combined Multi-organ Trans-plantation,Ministry of Public Health Key Laboratory of Organ Trans-plantation,Zhejiang Province and division of Hepatobiliary and pancreatic surgery,Department of surgery State Key Laboratory for Diagnosis and Treatment of Infectious Disease,First Affiliated Hospital,Zhejiang University School of Medicine,Hangzhou 310003,China Department of Hepatobiliary surgery,the People’s Hospital of Guangxi Zhuang Autonomous Region, Nanning 530021,China Key Laboratory of Combined Multi-organ Transplantation Ministry of Public Health Key Laboratory of Organ Transplantation Zhejiang Province and division of Hepatobiliary and pancreatic surgery Department of Surgery Zhejiang University School of Medicine Hangzhou 310003 China Department of Hepatobiliary surgery the People's Hospital of Guangxi Zhuang Autonomous Region Nanning 530021 China State Key Laboratory for Diagnosis and Treatment of Infectious Disease First Affiliated Hospital Zhejiang University School of Medicine Hangzhou 310003 China

BACKGROUND:The glucose transporter-1(Glut-1),a key ratelimiting factor in the transport and metabolism of glucose in cancer cells,is over-expressed in many human cancer cells and this overexpression is correlated with poor biological behavior. The increased levels of Glut-1 expression in hepatocellular carcinoma(HCC)cells functionally affect tumorigenicity.This study was undertaken to investigate effects of suppressing Glut-1 by an antisense oligodeoxynucleotide(AS-ODN)on the growth of human hepatocellular carcinoma(HepG-2)cells. METHODS:We used AS-ODN targeting against the Glut-1 gene in a HepG-2 cell line.There were four experimental groups: empty pcDNA3.1 vector(mock transfection),pcDNA3.1-anti-Glut(+),pcDNA3.1-Glut(+),and non-transfected HepG-2 cells. The Glut-1 mRNA expression was detected by RT-PCR and the Glut-1 protein expression by Western blotting after cell culture, and the glucose uptake was detected after glucose stimulation in each group. RESULTS:Compared with non-transfected HepG-2 or Glut-1 pcDNA3.1,a down-regulation of Glut-1 mRNA in HepG-2 cells transfected with anti-Glut-1 pcDNA3.1 was noted(P<0.05).Glut-1 protein in HepG-2 cells transfected with Glut-1 AS-ODN was decreased compared with non-transfected HepG-2,Glut-1 pcDNA3.1,or empty vectors. Glucose uptake by the HepG-2 cells transfected with AS-ODN was decreased at 1 hour after glucose stimulation.CONCLUSIONS:The application of Glut-1 AS-ODN can down-regulate the expression of Glut-1 at mRNA and protein,and inhibit glucose uptake partially in HepG-2 cells.The Glut-1 gene maybe a potential therapeutic target for HCC.

关键词： hepatocellular carcinoma HepG-2 cell glucose transporter-1 therapeutic target

Hepatocellular carcinoma presenting as an extrahepatic mass:A case report and review of literature

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World Journal of Gastrointestinal Oncology 2024年第5期16卷 2241-2252页

作者： Wei Kelly Wu Krutika Patel Chandrasekhar Padmanabhan Kamran Idrees Department of surgery Vanderbilt University Medical CenterNashvilleTN 37232United States Department of Pathology Microbiology and ImmunologyVanderbilt University Medical CenterNashvilleTN 37232United States division of Surgical Oncology and Endocrine surgery Department of SurgeryVanderbilt University Medical CenterNashvilleTN 37232United States

BACKGROUND Hepatocellular carcinoma(HCC)is a primary liver tumor generally diagnosed based on radiographic findings.Metastatic disease is typically associated with increased tumor diameter,multifocality,and vascular invasion.We report a case of a patient who presented with extrahepatic HCC metastasis to a portocaval lymph node with occult hepatic primary on computed tomography(CT).We review the literature for cases of extrahepatic HCC presentation without known hepatic lesions and discuss strategies to differentiate between metastatic and ectopic HCC.CASE SUMMARY A 67-year-old male with remotely treated hepatis C was referred for evaluation of an enlarging portocaval,mixed cystic-solid mass.Serial CT evaluations demonstrated steatosis,but no cirrhosis or liver lesions.Endoscopic ultrasound demonstrated a normal-appearing pancreas,biliary tree,and liver.Fine needle aspiration yielded atypical cells.The differential diagnosis included duodenal or pancreatic cyst,lymphoproliferative cyst,stromal or mesenchymal lesions,nodal involvement from gastrointestinal or hematologic malignancy,or duodenal gastrointestinal stromal tumor.After review by a multidisciplinary tumor board,the patient underwent open surgical resection of a 5.2 cm×5.5 cm retroperitoneal mass with pathology consistent with moderately-differentiated HCC.Magnetic resonance imaging(MRI)subsequently demonstrated a 1.2 cm segment VIII hepatic lesion with late arterial enhancement,fatty sparing,and intrinsic T1 hyperintensity.Alpha fetoprotein was 23.3 ng/mL.The patient was diagnosed with HCC with portocaval nodal involvement.Review:We surveyed the literature for HCC presenting as extrahepatic masses without history of concurrent or prior intrahepatic HCC.We identified 18 cases of extrahepatic HCC ultimately found to represent metastatic lesions,and 30 cases of extrahepatic HCC found to be primary,ectopic HCC.CONCLUSION Hepatocellular carcinoma can seldomly present with extrahepatic metastasis in the setting of occult primary.In patients with risk factors fo

关键词： Extrahepatic Metastasis Portocaval Lymph node Case report

Ischemic preconditioning enhances hepatocyte proliferation in the early phase after ischemia under hemi-hepatectomy in rats

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Hepatobiliary & pancreatic Diseases International 2012年第5期11卷 521-526页

作者： Li-Ming Jin, Shui-Fang Jin, Yuan-Xing Liu, Lin Zhou, Hai-Yang Xie, Sheng Yan, Xiao Xu , Shu-Sen Zheng Department of General surgery and Intensive Care Unit, First Affiliated Hospital, Zhejiang Chinese Medical University, Hangzhou 310006, China Key Laboratory of Combined Multi-organ Transplantation, Ministry of Public Health, Key Laboratory of Organ Transplantation, Zhejiang Province, and division of Hepatobiliary and pancreatic surgery, First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou 310003, China Department of General surgery First Affiliated Hospital Zhejiang Chinese Medical University Hangzhou 310006 Hangzhou China Intensive Care Unit First Affiliated Hospital Zhejiang Chinese Medical University Hangzhou 310006 Hangzhou China Key Laboratory of Combined Multi-organ Transplantation Ministry of Public Health Key Laboratory of Organ Transplantation Zhejiang Province and Division of Hepatobiliary and Pancreatic Surgery First Affiliated Hospital Zhejiang University School of Medicine Hangzhou 310003 Hangzhou China

BACKGROUND: Ischemia/reperfusion (I/R) injury is an important barrier to liver surgery and transplantation because it impairs remnant liver/reduced-size-graft regeneration. Ischemic preconditioning (IPC), as an effective measure to overcome I/R injury, has been shown to enhance the regenerative capacity of hepatocytes. However, investigations have always focused on regeneration in the late phase after reperfusion. This study aimed to investigate whether IPC enhances hepatocyte proliferation in the early phase after reperfusion and possible underlying mechanisms. METHODS: A total of 90 rats were divided into three groups: hemi-hepatectomy alone (PHx group), 60 minutes of ischemia plus hemi-hepatectomy (I/R group), and a cycle of 10 minutes of alternating I/R prior to 60 minutes of ischemia plus hemi-hepatectomy (IPC group). Each group was divided into five subgroups sacrificed after 0.5, 2, 6, 12 or 24 hours (n=6/ subgroup). Subsequently, serum concentrations of alanine aminotransferase (ALT), aspartate aminotransferase (AST), tumor necrosis factor-alpha (TNF-α), and interleukin-6 (IL-6) were measured; caspase-3 and proliferating cell nuclear antigen (PCNA) proteins were also determined by Western blotting. Furthermore, PCNA was detected by immunohistochemistry to identify the expression site.RESULTS: Serum ALT and AST levels after 2-24 hours of reperfusion in the PHx and IPC groups were remarkably decreased compared to the I/R group, and the serum TNF-α was relatively lower. A significant increase of serum IL-6 levels was found in the PHx and IPC groups compared with the I/R group at each time point. Furthermore, PCNA expression was remarkably increased in the IPC group after 6-12 hours of reperfusion, and in the earlier 0.5 and 6 hours time points after reperfusion have shown the massive PCNA-positive hepatocytes. At the same time, the expression of liver p-JNK was higher in the IPC group in the early phase after reperfusion than that of the I/R group and its expression was consistent with the PCNA. CONCLUSION:

关键词： reperfusion injury ischemic preconditioning hepatocytes proliferation hemi-hepatectomy