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Identification of Expression Pattern and Clinical Significance of the Small Cajal Body-specific RNA SCARNA16 in Hepatocellular Carcinoma

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Journal of Clinical and Translational Hepatology 2022年第1期10卷 104-111页

作者： Sitong Zhang Yuan Ding Zhongquan Sun Yao Ge Yanjie Li Xin Han Qianhui Xu Liuzhi Zhou Yining Chen Hao Xu Yang Bai Chang Xu Hao Ding Sheng Yan Weilin Wang Department of hepatobiliary and pancreatic Surgery The Second Affiliated HospitalZhejiang University School of Medi-cineKey Laboratory of Precision Diagnosis and Treatment for Hepatobiliary and Pancreatic Tumor of Zhejiang ProvinceRe-search Center of Diagnosis and Treatment Technology for Hepatocellular Carcinoma of Zhejiang ProvinceClinical Medicine Innovation Center of Precision Diagnosis and Treatment for Hepatobiliary and Pancreatic Disease of Zhejiang UniversityClinical Research Center of Hepatobiliary and Pancreatic Diseases of Zhejiang ProvinceZhejiang University Cancer CenterHangzhouZhejiangChina Key Laboratory of Precision Diagnosis and treatment for hepatobiliary and pancreatic Tumor of Zhejiang Province Research Center of Diagnosis and Treatment Technology for Hepatocellular Carcinoma of Zhejiang ProvinceClinical Medicine Innovation Center of Precision Diagnosis and Treatment for Hepatobiliary and Pancreatic Disease of Zhejiang UniversityClinical Research Center of Hepatobiliary and Pancreatic Diseases of Zhejiang ProvinceZhejiang University Cancer CenterHangzhouZhejiangChina

Background and Aims:For high morbidity and mortality,hepatocellular carcinoma(HCC)becomes a major health issue ***,numerous non-coding RNAs(ncRNAs)are known to regulate the occurrence and patho-genesis of *** ncRNAs have also been developed as tumor biomarkers and therapeutic ***,the potential function of the small Cajal body-specific RNA(scaRNA)SCARNA16,a newly identified ncRNA,remains to be explored in ***:In both HCC cell lines and specimens from 120 enrolled patients,the expression val-ues of SCARNA16 were *** divided patients into SCARNA16 high and low expression subgroups,and then analyzed the difference of various clinical characteristics and prognosis data between ***:Compared to paired controls,SCARNA16 was significantly down-regulated in HCC cell lines and clinical specimens(p<0.01).Besides,HCC patients with lower SCARNA16 expression commonly presented with larger and more tumor lesions,more ves-sel carcinoma emboli,more capsular invasion and higher TNM stages(p<0.05).Moreover,SCARNA16 expression was negatively correlated with postoperative prognosis of HCC patients in 5-year follow-up,including tumor-free survival(TFS)(median time of low *** subgroups:14 vs.48 months,p=0.006)and overall survival(OS)(median time of low *** subgroups:39 vs.52 months,p=0.001).Besides,SCARNA16 acted as an independent prognostic bio-marker in TFS(hazard ratio[HR]:0.578,95%CI:0.345-0.969,p=0.038)and OS(HR:0.366,95%CI:0.178-0.752,p=0.006).Conclusions:Low expression patterns of SCAR-NA16 remarkably associated with severe clinical status and poor survival of patients,suggesting that SCARNA16 pos-sesses potency as a novel biomarker for HCC.

关键词： Hepatocellular carcinoma Non-coding RNA SCARNA16 Clinical assessment Biomarker

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5′-tiRNA-Gln inhibits hepatocellular carcinoma progression by repressing translation through the interaction with eukaryotic initiation factor 4A-I

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Frontiers of Medicine 2023年第3期17卷 476-492页

作者： Chengdong Wu Dekai Liu Lufei Zhang Jingjie Wang Yuan Ding Zhongquan Sun Weilin Wang Department of hepatobiliary and pancreatic Surgery The Second Affiliated HospitalZhejiang University School of MedicineHangzhou 310009China Key Laboratory of Precision Diagnosis and treatment for hepatobiliary and pancreatic Tumor of Zhejiang Province Hangzhou 310009China Research center of Diagnosis and treatment Technology for Hepatocellular Carcinoma of Zhejiang Province Hangzhou 310009China Clinical Medicine Innovation center of Precision Diagnosis and treatment for hepatobiliary and pancreatic Disease of Zhejiang University Hangzhou 310009China Clinical Research center of hepatobiliary and pancreatic diseases of Zhejiang Province Hangzhou 310009China Cancer center Zhejiang UniversityHangzhou 310009China

tRNA-derived small RNAs(tsRNAs)are novel non-coding RNAs that are involved in the occurrence and progression of diverse ***,their exact presence and function in hepatocellular carcinoma(HCC)remain ***,differentially expressed tsRNAs in HCC were profiled.A novel tsRNA,tRNAGln-TTG derived 5′-tiRNA-Gln,is significantly downregulated,and its expression level is correlated with progression in *** HCC cells,5′-tiRNA-Gln overexpression impaired the proliferation,migration,and invasion in vitro and in vivo,while 5′-tiRNA-Gln knockdown yielded opposite results.5′-tiRNA-Gln exerted its function by binding eukaryotic initiation factor 4A-I(EIF4A1),which unwinds complex RNA secondary structures during translation initiation,causing the partial inhibition of *** suppressed downregulated proteins include ARAF,MEK1/2 and STAT3,causing the impaired signaling pathway related to HCC ***,based on the construction of a mutant 5′-tiRNA-Gln,the sequence of forming intramolecular G-quadruplex structure is crucial for 5′-tiRNA-Gln to strongly bind EIF4A1 and repress ***,5′-tiRNA-Gln expression level is negatively correlated with ARAF,MEK1/2,and STAT3 in HCC ***,these findings reveal that 5′-tiRNA-Gln interacts with EIF4A1 to reduce related mRNA binding through the intramolecular Gquadruplex structure,and this process partially inhibits translation and HCC progression.

关键词： EIF4A1 G-quadruplex hepatocellular carcinoma tRNA-derived small RNA translation initiation

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Analysis of the efficacy of transcatheter arterial infusion chemotherapy in the treatment of pancreatic carcinoma

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Journal of Interventional Medicine 2021年第1期4卷 21-26页

作者： Chunhui Nie Yuelin Zhang Guanhui Zhou Tanyang Zhou Tongyin Zhu Baoquan Wang Shengqun Chen Hongliang Wang Ziniu Yu Li Jing Junhui Sun hepatobiliary and pancreatic Interventional treatment center Division of Hepatobiliary and Pancreatic SurgeryThe First Affiliated HospitalZhejiang University School of MedicineHangzhou310003Zhejiang ProvinceChina Zhejiang Provincial Research center for Diagnosis and treatment of hepatobiliary diseases Hangzhou310003Zhejiang ProvinceChina Zhejiang Clinical Research center of hepatobiliary and pancreatic diseases Hangzhou310003Zhejiang ProvinceChina

Objective:To evaluate the clinical efficacy of infusion of gemcitabine(GEM) and fluorouracil(5-FU)through the celiac artery and superior mesenteric artery in the treatment of pancreatic carcinoma(PC).Methods:We analyzed 20 patients diagnosed clinically or pathologically with PC,without metastases,who had an estimated survival duration of>3 months in our department from May 2009 to December *** patients were treated directly without surgical resection of the tumor,while the other 11 patients were treated after *** all patients,the femoral artery was punctured using the Seldinger technique,and a catheter was placed in the opening of the celiac artery or the superior mesenteric *** administered 500 mg/m2 GEM and 500 mg/m2 *** data included data on clinical efficacy and survival rates during the follow-up period of 3-72 ***:Twenty patients were treated 85 times with transcatheter arterial infusion chemotherapy(TAI).The survival rates were 80%,40%,35%,20%,10%,and 5% at 3,6,12,24,and 72 months,***: TAI chemotherapy with GEM and 5-FU may be a therapeutic option for the treatment of PC.

关键词： Transcatheter arterial infusion Chemotherapy pancreatic carcinoma

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Mitofusin-2 mediated mitochondrial Ca2+ uptake 1/2 induced liver injury in rat remote ischemic perconditioning liver transplantation and alpha mouse liver-12 hypoxia cell line models

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World Journal of Gastroenterology 2017年第38期23卷 6995-7008页

作者： Ruo-Peng Liang Jun-Jun Jia Jian-Hui Li Ning He Yan-Fei Zhou Li Jiang Tao Bai Hai-Yang Xie Lin Zhou Yu-Ling Sun Department of hepatobiliary and pancreatic Surgery The First Affiliated Hospital of Zhengzhou University Institute of hepatobiliary and pancreatic diseases Zhengzhou University Key Lab of Combined Multi-Organ Transplantation Ministry of Public Health Division of hepatobiliary and pancreatic Surgery Department of Surgery First Affiliated Hospital Zhejiang University School of Medicine Collaborative Innovation center for Diagnosis and treatment of Infectious diseases

AIM To investigate the protective mechanism of mitofusin-2 (Mfn2) in rat remote ischemic perconditioning (RIC) models and revalidate it in alpha mouse liver-12 (AML-12) hypoxia cell lines. METHODS Sprague-Dawley rats were divided into three groups (n = 6 each): sham, orthotopic liver transplantation and RIC. After operation, blood samples were collected to test alanine aminotransferase and aspartate aminotransferase. The liver lobes were harvested for histopathological examination, western blotting (WB) and quantitative real-time (qRT)-PCR. AML-12 cell lines were then subjected to normal culture, anoxic incubator tank culture (hypoxia) and anoxic incubator tank culture with Mfn2 knockdown (hypoxia + Si), and data of qRT-PCR, WB, mitochondrial membrane potential (Delta psi m), apoptosis, endoplasmic reticulum Ca2+ concentrations and mitochondrial Ca2+ concentrations were collected. RESULTS Both sham and normal culture groups showed no injury during the experiment. The RIC group showed amelioration of liver function compared with the orthotopic liver transplantation group (P < 0.05). qRTPCR and WB confirmed that Mfn2-mitochondrial Ca2+ uptake 1/2 (MICUs) axis was changed (P < 0.005). In AML-12 cell lines, compared with the hypoxia group, the hypoxia + Si group attenuated the collapse of..m and apoptosis (P < 0.005). The endoplasmic reticulum Ca2+ decrease and mitochondrial Ca2+ overloading observed in the hypoxia group were also attenuated in the hypoxia + Si group (P < 0.005). Finally, qRT-PCR and WB confirmed the Mfn2-MICUs axis change in all the groups (P < 0.005). CONCLUSION Mfn2 participates in liver injury in rat RIC models and AML-12 hypoxia cell lines by regulating the MICUs pathway.

关键词： Remote ischemic per-conditioning Ischemia-reperfusion injury Ca2+ Mitofusin-2 Mitochondrial Ca2+ uniporter

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Prevalence, diagnosis, and treatment of primary hepatic gastrointestinal stromal tumors

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World Journal of Gastroenterology 2020年第40期26卷 6195-6206页

作者： Xiao-Hui Qian Ying-Cai Yan Bing-Qiang Gao Wei-Lin Wang Department of hepatobiliary and pancreatic Surgery The Second Affiliated HospitalZhejiang University School of MedicineHangzhou 310009Zhejiang ProvinceChina Key Laboratory of Precision Diagnosis and treatment for hepatobiliary and pancreatic Tumor of Zhejiang Province Hangzhou 310009Zhejiang ProvinceChina Research center of Diagnosis and treatment Technology for Hepatocellular Carcinoma of Zhejiang Province Hangzhou 310009Zhejiang ProvinceChina Clinical Medicine Innovation center of Precision Diagnosis and treatment for hepatobiliary and pancreatic Disease of Zhejiang University Hangzhou 310009Zhejiang ProvinceChina Clinical Research center of hepatobiliary and pancreatic diseases of Zhejiang Province Hangzhou 310009Zhejiang ProvinceChina

Gastrointestinal stromal tumors(GIST), which is the most common mesenchymal tumor of the digestive tract, account for 1%-3% of gastrointestinal tumors. Primary stromal tumors outside the gastrointestinal tract are collectively referred to as extra GISTs, and stromal tumors in different regions often have different prognoses. A primary hepatic GIST is a rare tumor with an unknown origin, which may be related to interstitial Cajal-like cells. Although primary hepatic GIST has certain characteristics on imaging, it lacks specific symptoms and signs;thus, the final diagnosis depends on pathological and genetic evidence. This review summarizes all cases of primary hepatic GIST described in the literature and comprehensively analyzes the detailed clinical data of all patients. In terms of treatment, local resection alone or with adjuvant therapy was the prioritized choice to obtain better disease-free survival and longer survival time. For advanced unresectable cases, imatinib mesylate was applied as the first-line chemotherapy agent. Moreover, transcatheter arterial chemoembolization,/by-nc/4.0/Manuscript source: Unsolicited manuscript radiofrequency ablation, and microwave ablation were shown to improve overall survival for selected patients. Liver transplantation was a final treatment option after resistance to chemotherapy developed.

关键词： Extra gastrointestinal stromal tumor treatment Liver transplant Review

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Huge portal venous aneurysm incidentaloma caused by intrahepatic arterioportal fistula accompany with hepatobiliary stones and cholangitis

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hepatobiliary Surgery and Nutrition 2021年第2期10卷 288-290页

作者： Zheng-Hao Liu Dong-Kai Zhou Yu-Cheng Xiang Cheng Zeng Wei-Lin Wang Department of hepatobiliary and pancreatic Surgery The Second Affiliated HospitalZhejiang University School of MedicineHangzhouChina Key Laboratory of Precision Diagnosis and treatment for hepatobiliary and pancreatic Tumor of Zhejiang Province HangzhouChina Research center of Diagnosis and treatment Technology for Hepatocellular Carcinoma of Zhejiang Province HangzhouChina Clinical Medicine Innovation center of Precision Diagnosis and treatment for hepatobiliary and pancreatic Disease of Zhejiang University HangzhouChina Clinical Research center of hepatobiliary and pancreatic diseases of Zhejiang Province HangzhouChina

A 64-year-old female was admitted to our department because of abdominal discomfort and recurrent fever for 1 month,she had attended her local hospital 10 days earlier,where the sign of fever was regarded as being due to the pulmonary infection,however,moxifloxacin and peramivir had no therapeutic *** admission,the physical examinations were showed an upper abdominal thrill and auscultation heard a blood vessel murmur at the same location,lab tests were not showed any remarkable results,the tumor marker levels were within normal *** portal color contrast ultrasonography was showed a 5.4 cm×3.3 cm bright spot in the left intrahepatic bile duct,and a 0.9 cm distal bright spot in,and 0.7 cm expansion of the right intrahepatic bile duct(Figure 1A).Contrast-enhanced computed tomography(CT)were showed intrahepatic cholangiectasis,tumor-like dilatation of the left portal ramus,and left liver atrophy and cirrhosis(Figure 1B).

关键词： intrahepatic admitted Figure

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Risk factors of metabolic syndrome after liver transplantation

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hepatobiliary & pancreatic diseases International 2015年第6期14卷 582-587页

作者： Jun Zheng Wei-Lin Wang Division of hepatobiliary and pancreatic Surgery Department of SurgeryFirst Affiliated HospitalZhejiang University School of Medicine Department of Surgery The University of Hong Kong Collaborative Innovation center for Diagnosis and treatment of Infectious diseases

BACKGROUND： Liver transplantation is a treatment of choice for both acute and chronic liver failure. Accompanied with the increase of long-term survival rates of recipients, metabolic syndrome and its individual components, including obesity, hyperglycemia, hypertension and hyperlipidemia, have become more frequent post liver transplantation. Here we reviewed the literature concerning the risk factors for the development of metabolic complications in liver recipients.

关键词： liver transplantation risk factors hypertension hyperlipidemia diabetes mellitus

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A primary adenosquamous gallbladder carcinoma with sarcomatoid features

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hepatobiliary Surgery and Nutrition 2019年第6期8卷 671-673页

作者： Xiaohui Qian Yingsheng Wu Bingqiang Gao Weilin Wang Department of hepatobiliary and pancreatic Surgery The Second Affiliated HospitalZhejiang University School of MedicineHangzhou 310009China Key Laboratory of Precision Diagnosis and treatment for hepatobiliary and pancreatic Tumor of Zhejiang Province Hangzhou 310009China Research center of Diagnosis and treatment Technology for Hepatocellular Carcinoma of Zhejiang Province Hangzhou 310009China Clinical Medicine Innovation center of Precision Diagnosis and treatment for hepatobiliary and pancreatic Disease of Zhejiang University Hangzhou 310009China Clinical Research center of hepatobiliary and pancreatic diseases of Zhejiang Province Hangzhou 310009China

A 65-year-old female was admitted to our hospital complaining of abdominal pain for the past month.A physical examination revealed mild right upper quadrant tenderness without rebound pain and no palpable abdominal hepatomegaly or *** laboratory results showed mildly impaired liver function:AST 51 U/L(normal range<34 U/L),ALT 49 U/L(normal range<34 U/L),and C-reactive protein 16.5 mg/L(normal range<10 mg/L).

关键词： gallbladder female liver

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Longitudinal gut fungal alterations and potential fungal biomarkers for the progression of primary liver disease

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Science China(Life Sciences) 2024年第6期67卷 1183-1198页

作者： Shiman Jiang Lvwan Xu Yanfei Chen Zheyue Shu Longxian Lv Yuxi Zhao Kefan Bi Sisi Yang Qiangqiang Wang Lanjuan Li State Key Laboratory for Diagnosis and treatment of Infectious diseases National Clinical Research Center for Infectious DiseasesNational Medical Center for Infectious DiseasesCollaborative Innovation Center for Diagnosis and Treatment of Infectious DiseasesThe First Affiliated HospitalZhejiang University School of MedicineHangzhou 310003China Division of hepatobiliary and pancreatic Surgery Department of SurgeryThe First Affiliated HospitalZhejiang University School of MedicineHangzhou 310003China

Liver disease,a major health concern worldwide,is a serious and progressive ***,we not only established a mouse model of DEN+CCl4-induced primary liver disease but also collected clinical human samples to investigate longitudinal alterations in the gut *** liver disease advanced,gut integrity was disrupted,and the mycobiota was disturbed in the mouse *** metabolites associated with hepatocellular carcinoma(HCC)differed from those associated with the cirrhotic phase as follows:levels of stercobilin and aflatoxin B1 dialcohol were reduced,while levels of triterpenoids,bafilomycin A1,and DHEA were increased in the HCC *** abundance of the phylum Chytridiomycota increased as the chronic liver disease progressed and was then replaced by the phylum Ascomycota in *** on the results from clinical human samples,the genus Candida(Ascomycota)(in humans)and the genus Kazachstania(Ascomycota)(in mice)occupied a dominant position in the HCC group,while other fungi were *** increased abundance of *** and depletion of *** may be hallmarks of the progression of liver cirrhosis to early ***,the administration of *** and *** in the LC-HCC progression could accelerate or retard the progression of ***,gut fungi have the potential to serve as a noninvasive clinical biomarker and even a treatment method.

关键词： gut mycobiome liver disease longitudinal studies hepatocarcinogenesis fungal biomarker

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Metastatic solitary fibrous tumor of the pancreas in a patient with Doege-Potter syndrome

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hepatobiliary Surgery and Nutrition 2020年第1期9卷 112-115页

作者： Xiaohui Qian Dongkai Zhou Bingqiang Gao Weilin Wang Department of hepatobiliary and pancreatic Surgery The Second Affiliated HospitalZhejiang University School of MedicineHangzhou 310009China Key Laboratory of Precision Diagnosis and treatment for hepatobiliary and pancreatic Tumor of Zhejiang Province Hangzhou 310009China Research center of Diagnosis and treatment Technology for Hepatocellular Carcinoma of Zhejiang Province Hangzhou 310009China Clinical Medicine Innovation center of Precision Diagnosis and treatment for hepatobiliary and pancreatic Disease of Zhejiang University Hangzhou 310009China Clinical Research center of hepatobiliary and pancreatic diseases of Zhejiang Province Hangzhou 310009China

A 46-year-old man was admitted to our hospital with a 6-month history of recurrent hypoglycemia with an unknown cause. Four months back, he was diagnosed with a complex ulcer in the stomach and duodenum in a local hospital. Physical examination revealed that the liver was swollen with a hard texture and located 5 cm below the costal margin of the abdomen. On admission, his random blood glucose level was 1.6 mmol/L, and routine laboratory tests, including those for liver enzymes, showed normal findings. The levels of tumor markers, including carcinoembryonic antigen, alpha-fetoprotein, carbohydrate antigen 19-9, and neuron-specific enolase, were normal. Magnetic resonance imaging (MRI) of the brain and pituitary gland showed no abnormalities. However, abdominal MRI revealed solid components in the pancreas and multiple masses on the liver (Figure 1A,B,C). We first considered functional neuroendocrine cancer of the pancreas with multiple liver metastases. For blood glucose control, the patient first received multiple transarterial chemoembolization (TACE) sessions to reduce the tumor burden. This resulted in amelioration of the symptoms of hypoglycemia, although they occasionally manifested. Whole-body fluorodeoxyglucose (FDG) positron emission tomography (PET)/computed tomography (CT) revealed a slightly hypodense lesion measuring 7.0×6.1 cm2 in diameter in the body of the pancreas. The lesion exhibited significantly different degrees of FDG uptake [ Figure 1D;maximum standardized uptake (SUVmax): 4.74].

关键词： pancreas admitted routine

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