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Science Bulletin 2024年第9期69卷 1286-1301页

作者：郦仕杰 sarun juengpanich Win Topatana 谢天傲侯丽丹朱怡远陈佳东单煜凯韩依纳陆子毅陈天恩 Charlie Topatana 张斌曹佳胜胡家豪严加费陈迎鑫顾臻俞计成蔡秀军陈鸣宇 Department of General Surgery Sir Run-Run Shaw HospitalZhejiang UniversityHangzhou 310016China School of Medicine Zhejiang UniversityHangzhou 310058China National Engineering Research Center of Innovation and Application of Minimally Invasive Instruments Sir Run-Run Shaw HospitalZhejiang UniversityHangzhou 310016China School of Materials Science and Engineering Zhejiang UniversityHangzhou 310058China Department of Chemistry Zhejiang UniversityHangzhou 310016China Department of Pathology Sir Run-Run Shaw HospitalZhejiang UniversityHangzhou 310016China International College Zhejiang UniversityHangzhou 310058China Institute of Advanced Magnetic Materials and International Research Center for EM Metamaterials College of Materials&Environmental EngineeringHangzhou Dianzi UniversityHangzhou 310018China Zhejiang Provincial Key Laboratory for Advanced Drug Delivery Systems College of Pharmaceutical SciencesZhejiang UniversityHangzhou 310058China National Key Laboratory of Advanced Drug Delivery and Release Systems Zhejiang UniversityHangzhou 310058China Liangzhu Laboratory Zhejiang UniversityHangzhou 311121China Jinhua Institute of Zhejiang University Jinhua 321299China MOE Key Laboratory of Macromolecular Synthesis and Functionalization Department of Polymer Science and EngineeringZhejiang UniversityHangzhou 310027China

Adavosertib(ADA)is a WEE1 inhibitor that exhibits a synthetic lethal effect on p53-mutated gallbladder cancer(GBC).However,drug resistance due to DNA damage response compensation pathways and high toxicity limits further ***,estrone-targeted ADA-encapsulated metal–organic frameworks(ADA@MOF-EPL)for GBC synthetic lethal treatment by inducing conditional factors are *** high expression of estrogen receptors in GBC enables ADA@MOF-EPL to quickly enter and accumulate near the cell nucleus through estrone-mediated endocytosis and release ADA to inhibit WEE1 upon entering the acidic tumor *** irradiation induces ADA@MOF-EPL to generate reactive oxygen species(ROS),which leads to a further increase in DNA damage,resulting in a higher sensitivity of p53-mutated cancer cells to WEE1 inhibitor and promoting cell death via conditional synthetic *** conditional factor induced by ADA@MOF-EPL further enhances the antitumor efficacy while significantly reducing systemic ***,ADA@MOF-EPL demonstrates similar antitumor abilities in other p53-mutated solid tumors,revealing its potential as a broad-spectrum antitumor drug.

关键词： Synthetic lethality Nanomedicine Sonodynamic therapy Gallbladder cancer Metal-organic frameworks DNA damage response

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Development of synthetic lethality in cancer:molecular and cellular classification

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Signal Transduction and Targeted Therapy 2020年第1期5卷 434-447页

作者： Shijie Li Win Topatana sarun juengpanich Jiasheng Cao Jiahao Hu Bin Zhang Diana Ma Xiujun Cai Mingyu Chen Department of General Surgery Sir Run-Run Shaw HospitalZhejiang University School of Medicine310016 HangzhouChina School of Medicine Zhejiang University310058 HangzhouChina Key Laboratory of Laparoscopic Technology of Zhejiang Province 310016 HangzhouChina Zhejiang Minimal Invasive Diagnosis and Treatment Technology Research Center of Severe Hepatobiliary Disease 310016 HangzhouChina Zhejiang Research and Development Engineering Laboratory of Minimally Invasive Technology and Equipment 310016 HangzhouChina Zhejiang University Cancer Center 310000 HangzhouChina

Recently,genetically targeted cancer therapies have been a topic of great *** lethality provides a new approach for the treatment of mutated genes that were previously considered unable to be targeted in traditional genotype-targeted *** increasing researches and applications in the clinical setting made synthetic lethality a promising anticancer treatment ***,the current understandings on different conditions of synthetic lethality have not been systematically assessed and the application of synthetic lethality in clinical practice still faces many ***,we propose a novel and systematic classification of synthetic lethality divided into gene level,pathway level,organelle level,and conditional synthetic lethality,according to the degree of specificity into its biological *** preclinical findings of synthetic lethality in recent years will be reviewed and classified under these different ***,synthetic lethality targeted drugs in clinical practice will be briefly ***,we will explore the essential implications of this classification as well as its prospects in eliminating existing challenges and the future directions of synthetic lethality.

关键词： specificity drugs synthetic

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Prognostic factors and predictors of postoperative adjuvant transcatheter arterial chemoembolization benefit in patients with resected hepatocellular carcinoma

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World Journal of Gastroenterology 2020年第10期26卷 1042-1055页

作者： Ming-Yu Chen sarun juengpanich Jia-Hao Hu Win Topatana Jia-Sheng Cao Chen-Hao Tong Jian Lin Xiu-Jun Cai Department of General Surgery Sir Run-Run Shaw HospitalZhejiang University School of MedicineHangzhou 310000Zhejiang ProvinceChina School of Medicine Zhejiang UniversityHangzhou 310016Zhejiang ProvinceChina Engineering Research Center of Cognitive Healthcare of Zhejiang Province Hangzhou 310000Zhejiang ProvinceChina Department of General Surgery Shaoxing People’s HospitalZhejiang UniversityShaoxing 312000Zhejiang ProvinceChina Department of General Surgery Longyou People’s HospitalQuzhou 314400Zhejiang ProvinceChina

BACKGROUND Postoperative adjuvant transcatheter arterial chemoembolization (PA-TACE) has improved overall survival (OS) in patients with hepatocellular carcinoma (HCC).However,the prognostic and predictive factors remain *** To assess the prognostic factors and the predictors of PA-TACE benefit for OS in patients with resected *** Univariate and multivariate analyses were performed to identify the potential prognostic factors for *** order to assess the predictive factors of PA-TACE benefit,the interaction variables between treatments for each subgroup were evaluated using the Cox proportional hazards regression *** A total of 378 patients (PA-TACE vs surgery alone,189:189) from three centerswere included after a propensity-score 1:1 matching *** to the group receiving surgery alone,PA-TACE prolonged the OS rate in patients with resected HCC (P <0.001).The Barcelona Clinic Liver Cancer system and ferritinto-hemoglobin ratio (FHR) were used as the prognostic factors for OS in both *** (P=0.023) and microscopic vascular invasion (MVI)(P=0.002) were also identified in the PA-TACE group,while gender (P=0.027),hepatitis B virus(P=0.034) and albumin-bilirubin grade (P=0.027) were also selected in the surgery alone *** addition,PA-TACE resulted in longer OS than surgery alone across subgroups [all hazard ratios (PA-TACE-to-surgery alone)<1].Notably,a significantly prolonged OS following PA-TACE was observed in patients with high FHR (P=0.038) and without MVI (P=0.048).CONCLUSION FHR and Barcelona Clinic Liver Cancer stages were regarded as prognostic factors for ***,high FHR and the absence of MVI were important predictive factors,which can be used to assist clinicians in selecting which patients could achieve a better OS with PA-TACE.

关键词： Postoperative adjuvant transcatheter arterial chemoembolization Hepatocellular carcinoma Prognostic factors Predictive factors Overall survival

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Promising key genes associated with tumor microenvironments and prognosis of hepatocellular carcinoma

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World Journal of Gastroenterology 2020年第8期26卷 789-803页

作者： Long Pan Jing Fang Ming-Yu Chen Shu-Ting Zhai Bin Zhang Zhi-Yu Jiang sarun juengpanich Yi-Fan Wang Xiu-Jun Cai Key Laboratory of Laparoscopic Technique Research of Zhejiang Province Department of General SurgerySir Run Run Shaw HospitalZhejiang University School of MedicineHangzhou 310016Zhejiang ProvinceChina Zhejiang Province Medical Research Center of Minimally Invasive Diagnosis and Treatment of Abdominal Diseases Hangzhou 310016Zhejiang ProvinceChina

BACKGROUND Despite significant advances in multimodality treatments,hepatocellular carcinoma(HCC)remains one of the most common malignant *** of novel prognostic biomarkers and molecular targets is urgently *** To identify potential key genes associated with tumor microenvironments and the prognosis of *** The infiltration levels of immune cells and stromal cells were calculated and quantified based on the ESTIMATE *** expressed genes(DEGs)between high and low groups according to immune or stromal scores were screened using the gene expression profile of HCC patients in The Cancer Genome Atlas and were further linked to the prognosis of *** genes were validated in four independent HCC ***-related key genes were identified by a LASSO Cox regression *** HCC patients with a high immune/stromal score had better survival benefits than patients with a low score.A total of 899 DEGs were identified and found to be involved in immune responses and extracellular matrices,147 of which were associated with overall ***,52 of 147 survival-related DEGs were validated in additional ***,ten key genes(STSL2,TMC5,DOK5,RASGRP2,NLRC3,KLRB1,CD5L,CFHR3,ADH1C,and UGT2B15)were selected and used to construct a prognostic gene signature,which presented a good performance in predicting overall *** This study extracted a list of genes associated with tumor microenvironments and the prognosis of HCC,thereby providing several valuable directions for the prognostic prediction and molecular targeted therapy of HCC in the future.

关键词： Hepatocellular carcinoma Tumor microenvironment Differentially expressed genes Overall survival

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Biologic therapy for Crohn’s disease over the last 3 decades

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World Journal of Clinical Cases 2022年第2期10卷 594-606页

作者： Ji-Liang Shen Zheng Zhou Jia-Sheng Cao Bin Zhang Jia-Hao Hu Jia-Ying Li Xiao-Ming Liu sarun juengpanich Ming-Song Li Xu Feng Department of General Surgery Sir Run-Run Shaw HospitalZhejiang University School of MedicineHangzhou 310016Zhejiang ProvinceChina Department of Gastroenterology Nan Fang HospitalSouthern Medical UniversityGuangzhou 510515Guangdong ProvinceChina Department of Gastroenterology Third Affiliated Hospital of Guangzhou Medical UniversityGuangzhou 510000Guangdong ProvinceChina

BACKGROUND Despite the overload of publications on Crohn’s disease(CD),no comprehensive analysis of biologic therapy for CD has been *** To determine knowledge gaps and identify areas of interest of biologic therapy for *** The top 100 highest-cited original articles were identified from January 1991 to December 2020 in the Clarivate Analytics Web of Science Core Collection *** conducted a bibliometric analysis of biologic therapy for CD based on total citations,summarized the bibliographic information of the articles related to CD biologic therapy,and explored the research *** The top 100 highest-cited original articles were identified with total citations ranging from 307 to *** 2000s(Period II,n=66)yielded the most influential original articles and saw the most dramatic *** the top 10 countries,including 8 European countries and 2 North American countries,the United States(n=37)and Belgium(n=20)contributed the most *** the top 10 institutions,the University Hospital Gasthuisberg in Belgium(n=23),the University of Chicago in the United States(n=20),and the Mayo Clinic in the United States(n=17)published the most *** authors,Rutgeerts P in Belgium(n=32),Sandborn WJ in the United States(n=23),and Feagan BG in Canada(n=18)published the highest number of *** cooperation relationships between the United States and Europe were most ***(impact factor=22.682)published the most articles on biologic therapy for CD(n=32)with 17654 total ***-tumor necrosis factor biologics and monoclonal antibodies were the most studied *** The bibliometric analysis emphasized the key contributions to the development of the specialized *** data would provide useful research insights into biologic therapy for CD for clinicians and researchers.

关键词： Biologic therapy Crohn’s disease Bibliometric analysis Most influential Insight

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Laparoscopic surgery for early gallbladder carcinoma:A systematic review and meta-analysis

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World Journal of Clinical Cases 2020年第6期8卷 1074-1086页

作者： Xu Feng Jia-Sheng Cao Ming-Yu Chen Bin Zhang sarun juengpanich Jia-Hao Hu Win Topatana Shi-Jie Li Ji-Liang Shen Guang-Yuan Xiao Xiu-Jun Cai Hong Yu Department of General Surgery Sir Run-Run Shaw HospitalZhejiang UniversityHangzhou 310016Zhejiang ProvinceChina Department of General Surgery Jiaxing Hospital of Traditional Chinese MedicineJiaxing 314000Zhejiang ProvinceChina

BACKGROUND There is a controversy as to whether laparoscopic surgery leads to a poor prognosis compared to the open approach for early gallbladder carcinoma (GBC)We hypothesized that the laparoscopic approach is an alternative for early *** To identify and evaluate the safety and feasibility of laparoscopic surgery in the treatment of early *** A comprehensive search of online databases,including MEDLINE (PubMed),Cochrane libraries,and Web of Science,was performed to identify noncomparative studies reporting the outcomes of laparoscopic surgery and comparative studies involving laparoscopic surgery and open surgery in early GBC from January 2009 to October 2019.A fixed-effects meta-analysis was performed for 1-and 5-year overall survival and postoperative complications,while 3-year overall survival,operation time,blood loss,the number of lymph node dissected,and postoperative hospital stay were analyzed by random-effects *** The review identified 7 comparative studies and 8 non-comparative studies.1068 patients (laparoscopic surgery:613;open surgery:455) were included in the meta-analysis of 1-,3-,and 5-year overall survival with no significant differences observed [(HR=0.54;95%CI:0.29-1.00;12=0.0%;P=0.051),(HR=0.75;95%CI:0.34-1.65;I^2=60.7%;P=0.474),(HR=0.71;95%CI:0.47-1.08;I^2=49.6%;P=0.107),respectively].There were no significant differences in operation time[weighted mean difference (WMD)=18.69;95%CI:-19.98-57.36;I^2=81.4%;P=0.343],intraoperative blood loss (WMD=-169.14;95%CI:-377.86-39.57;I2=89.5%;P=0.112),the number of lymph nodes resected (WMD=0.12;95%CI:-2.95-3.18;I^2=73.4%;P=0.940),and the complication rate (OR=0.69;95%CI:0.30-1.58;I2=0.0%;P=0.377) between the two groups,while patients who underwent laparoscopic surgery had a reduced length of hospital stay (WMD=-5.09;95%CI:-8.74--1.45;I2=91.0%;P=0.006).CONCLUSION This systematic review and meta-analysis confirms that laparoscopic surgery is a safe and feasible alternative to open sur

关键词： Laparoscopic surgery Open surgery Early gallbladder carcinoma Survival Meta-analysis

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Artificial intelligence in gastroenterology and hepatology:Status and challenges

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World Journal of Gastroenterology 2021年第16期27卷 1664-1690页

作者： Jia-Sheng Cao Zi-Yi Lu Ming-Yu Chen Bin Zhang sarun juengpanich Jia-Hao Hu Shi-Jie Li Win Topatana Xue-Yin Zhou Xu Feng Ji-Liang Shen Yu Liu Xiu-Jun Cai Department of General Surgery Sir Run-Run Shaw HospitalZhejiang UniversityHangzhou 310016Zhejiang ProvinceChina Zhejiang University School of Medicine Zhejiang UniversityHangzhou 310058Zhejiang ProvinceChina School of Medicine Wenzhou Medical UniversityWenzhou 325035Zhejiang ProvinceChina College of Life Sciences Zhejiang UniversityHangzhou 310058Zhejiang ProvinceChina

Originally proposed by John McCarthy in 1955,artificial intelligence(AI)has achieved a breakthrough and revolutionized the processing methods of clinical medicine with the increasing workloads of medical records and digital *** are paying attention to AI technologies for various diseases in the fields of gastroenterology and *** review will illustrate AI technology procedures for medical image analysis,including data processing,model establishment,and model ***,we will summarize AI applications in endoscopy,radiology,and pathology,such as detecting and evaluating lesions,facilitating treatment,and predicting treatment response and prognosis with excellent model *** current challenges for AI in clinical application include potential inherent bias in retrospective studies that requires larger samples for validation,ethics and legal concerns,and the incomprehensibility of the output ***,doctors and researchers should cooperate to address the current challenges and carry out further investigations to develop more accurate AI tools for improved clinical applications.

关键词： Artificial intelligence Gastroenterology Hepatology Status Challenges

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Adhesive cryogel particles for bridging confined and irregular tissue defects

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Military Medical Research 2023年第6期10卷 763-777页

作者： Yao-Ting Xue Ming-Yu Chen Jia-Sheng Cao Lei Wang Jia-Hao Hu Si-Yang Li Ji-Liang Shen Xin-Ge Li Kai-Hang Zhang Shu-Qiang Hao sarun juengpanich Si-Bo Cheng Tuck-Whye Wong Xu-Xu Yang Tie-Feng Li Xiu-Jun Cai Wei Yang Department of Engineering Mechanics Zhejiang UniversityHang‑zhou 310027China Key Laboratory of Soft Machines and Smart Devices of Zhejiang Province Zhejiang UniversityHangzhou 310027China Center for X‑Mechanics Department of Engineering MechanicsZhejiang Univer‑sityHangzhou 310027China Department of General Surgery Sir Run-Run Shaw HospitalZhejiang UniversityHangzhou 310016China Soft Intelligent Materials Co. LtdSuzhou 215123China School of Biomedical Engineering and Health Sciences and Advanced Membrane Technology Research Centre Universiti Teknologi Malaysia81310 SkudaiMalaysia

Background Reconstruction of damaged tissues requires both surface hemostasis and tissue *** with damage resulting from physical trauma or surgical treatments may have arbitrary surface topographies,making tissue bridging *** This study proposes a tissue adhesive in the form of adhesive cryogel particles(ACPs) made from chitosan,acrylic acid,1-ethyl-3-(3-dimethylaminopropyl) carbodiimide(EDC) and N-hydroxysuccinimide(NHS).The adhesion performance was examined by the 180-degree peel test to a collection of tissues including porcine heart,intestine,liver,muscle,and *** of ACPs was evaluated by cell proliferation of human normal liver cells(LO2)and human intestinal epithelial cells(Caco-2).The degree of inflammation and biodegradability were examined in dorsal subcutaneous rat *** ability of ACPs to bridge irregular tissue defects was assessed using porcine heart,liver,and kidney as the ex vivo ***,a model of repairing liver rupture in rats and an intestinal anastomosis in rabbits were established to verify the effectiveness,biocompatibility,and applicability in clinical *** ACPs are applicable to confined and irregular tissue defects,such as deep herringbone grooves in the parenchyma organs and annular sections in the cavernous *** formed tough adhesion between tissues[(670.9±50.1) J/m^(2) for the heart,(607.6±30.0) J/m^(2) for the intestine,(473.7±37.0) J/m^(2) for the liver,(186.1±13.3) J/m^(2) for the muscle,and(579.3±32.3) J/m^(2) for the stomach].ACPs showed considerable cytocompatibility in vitro study,with a high level of cell viability for 3 d[(98.8±1.2)%for LO2 and(98.3±1.6)%for Caco-2].It has comparable inflammation repair in a ruptured rat liver(P=0.58 compared with suture closure),the same with intestinal anastomosis in rabbits(P=0.40 compared with suture anastomosis).Additionally,ACP-based intestinal anastomosis(less than 30 s) was remarkably faster than the convention

关键词： Tissue reconstruction Wet adhesion Adhesive hydrogel Bioadhesive

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2013至2015年浙江地区人感染 H7 N9禽流感病毒蛋白关键位点分子特征分析

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中华临床感染病杂志 2016年第4期9卷 330-335页

作者：孙海燕童海江崔大伟 juengpanich sarun Pimpakan Aojanepong 浙江省绍兴第二医院检验科 312000 浙江大学医学院附属第一医院检验科浙江省临床体外诊断技术重点实验室杭州310003 浙江大学医学院杭州310058

目的：分析浙江地区人感染H7 N9禽流感病毒的分子特征，为更好地预防与治疗人感染H7N9禽流感提供科学依据。方法从全球禽流感共享数据库（GISAID）中下载浙江地区2013至2015年分离的人感染H7N9病毒株（共30株）和同时期禽源性病毒株（1... 详细信息

目的：分析浙江地区人感染H7 N9禽流感病毒的分子特征，为更好地预防与治疗人感染H7N9禽流感提供科学依据。方法从全球禽流感共享数据库（GISAID）中下载浙江地区2013至2015年分离的人感染H7N9病毒株（共30株）和同时期禽源性病毒株（15株）的基因序列，运用MEGA 6．0软件比较分析人H7N9流感病毒基因的分子进化特征、受体结合位点、毒力相关位点、耐药性位点的变异情况。结果进化树分析显示，浙江地区人感染H7 N9代表株与禽源性参考株的HA、NA蛋白差异较小，同源性分别为98．0％～100．0％和97．4％～100．0％。病毒氨基酸变异分析显示，30株H7N9代表株的HA蛋白均发生了226位（ Q226L／I）和186位（ G186V）突变，且2015年分离株出现A134V突变；有1株NA蛋白出现R294K耐药位点的变异；19株PB2蛋白发生了E627K突变，2株发生D701N突变；所有代表株M2蛋白均发生了S31N突变；HA的裂解位点均为PEIPKGR↓GLF，仍为低致病性毒株。结论2013至2015年浙江地区人感染H7N9流感病毒与同时期的禽源性病毒株具有高度同源性，部分氨基酸位点存在变异，所有代表株对离子通道抑制剂（金刚烷胺类药物）耐药，个别菌株出现对神经氨酸酶抑制剂（奥司他韦）耐药。

关键词：流感病毒A型,H7N9亚型分子流行病学进化树突变

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