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Novel gold nanoparticles targeting somatostatin receptor subtype two with near-infrared light for neuroendocrine tumour therapy

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Nano Research 2022年第10期15卷 9149-9159页

作者： Qichen Chen Zilin Li Jiangyuan Yu Qing Xie Haizhen Lu Yiqiao Deng Jinghua Chen Wenjia Zhu Li Huo Yizhou Zhang Wei Song jianqiang Lan jianqiang cai Zhen Huang Zixi Wang Hong Zhao Department of Hepatobiliary Surgery State Key Laboratory of Molecular OncologyNational Cancer Center/National Clinical Research Center for Cancer/Cancer HospitalChinese Academy of Medical Sciences and Peking Union Medical CollegeBeijing 100021China Key Laboratory of Gene Editing Screening and R&D of Digestive System Tumor Drugs Chinese Academy of Medical Sciences and Peking Union Medical CollegeBeijing 100021China State Key Laboratory of Tribology Department of Mechanical EngineeringTsinghua UniversityBeijing 100084China Department of Nuclear Medicine Key Laboratory of Carcinogenesis and Translational ResearchMinistry of EducationPeking University Cancer Hospital&InstituteBeijing 100142China Department of Pathology National Cancer Center/National Clinical Research Center for Cancer/Cancer HospitalChinese Academy of Medical Sciences and Peking Union Medical CollegeNo.17Panjiayuan NanliBeijing 100021China Nuclear Medicine Department State Key Laboratory of Complex Severe and Rare DiseasesCenter for Rare Diseases ResearchBeijing Key Laboratory of Molecular Targeted Diagnosis and Therapy in Nuclear MedicinePeking Union Medical College HospitalChinese Academy of Medical Science and Peking Union Medical CollegeBeijing 100005China Department of Biochemistry and Molecular Biology State Key Laboratory of Medical Molecular BiologyInstitute of Basic Medical Sciences Chinese Academy of Medical SciencesSchool of Basic MedicinePeking Union Medical CollegeBeijing 100005China Guangdong Research Center of Organoid Engineering and Technology Accurate International Biotechnology Co.Ltd.Guangzhou 510650China

Neuroendocrine tumours(NETs)are rare cancers with positive somatostatin receptor 2(SSTR2)expression,and treatment strategies for NETs are not satisfactory.Nanomaterial-mediated therapy targeting SSTR2 in NETs is very promising.This study firstly combined mesoporous silica-coated gold nanorods(AuNRs@mSiO_(2))and targeting-SSTR2 dodecane tetraacetic acidtyrosine3-octreotate(DOTA-TATE)into AuNRs@mSiO_(2)@DOTA-TATE to investigate NETs inhibition under near-infrared light.AuNRs@mSiO_(2)@DOTA-TATE showed good photothermal conversion efficiency.In vitro,under light irradiation,the cell viability significantly decreased with increasing AuNR@mSiO_(2)@DOTA-TATE concentration;in two successfully established neuroendocrine tumour organoids with SSTR2 expression,AuNRs@mSiO_(2)@DOTA-TATE with light inhibited tumours significantly better than AuNRs@mSiO_(2) with light.In vivo,the SSTR2-targeting ability and biodistribution of AuNRs@mSiO_(2)@DOTA-TATE were confirmed with AuNRs@mSiO_(2)@64Cu-DOTA-TATE under micro-positron emission tomography/computed tomography(micro-PET/CT);in the AuNRs@mSiO_(2)@DOTA-TATE with laser group,the tumour surface temperature increased rapidly,with tumour volumes similar to those in the octreotide group and significantly lower than those in other groups.There was no significant difference in mice body weight between the AuNRs@mSiO_(2)@DOTA-TATE with laser group and other groups.No significant inflammatory lesions or cell necrosis was found in the main organs.In summary,we presented a feasible strategy to construct AuNRs@mSiO_(2)@DOTA-TATE with good photothermal conversion efficiency,targetingSSTR2 ability,significant antitumour effects,and good biocompatibility,warranting further explorations of AuNRs@mSiO_(2)@DOTA-TATE for NETs therapy applications.

关键词： neuroendocrine tumours somatostatin receptor 2 nanoparticles photothermal therapy

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Prognostic relevance of number and ratio of metastatic lymph nodes in resected carcinoma of the ampulla of Vater

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Chinese Journal of Cancer Research 2013年第6期25卷 735-742页

作者： Jianguo Zhou Qian Zhang Peng Li Yi Shan Dongbing Zhao jianqiang cai Department of Abdominal Surgery Cancer HospitalChinese Academy of Medical Sciences & Peking Union Medical College Department of General Surgery Aerospace Central Hospital

Objectives： To explore the prognostic relevance of the number and ratio of metastatic lymph nodes in resected Carcinoma of the ampulla of Vater （CAV）. Methods： The clinical data of 155 patients who underwent pancreaticoduodenectomy （PD） for cancer of the ampulla of Vater between January 1990 and December 2010 were retrospectively analyzed. Kaplan- Meier method was used in survival analysis and Log rank method in comparison. Multivariate analysis was performed using Cox proportional hazards model. Results： Among these 155 patients, the in-hospital mortality rate was 4.5%, lymph node positive disease was 21.3%, and the 5-year survival rate was 51.6%. Patients with a lymph node ratio （LNR）〉20% were more likely to have tumor differentiation, depth of duodenal involvement, depth of pancreatic invasion, T-stage and TNM-Stage. The number of the metastatic lymph nodes is important prognostic factors of the CAV. Univariate analysis showed that the factors associated with the prognosis included tumor size （P=0.036）, tumor differentiation （P=0.019）, LNR （P=0.032）, mtmber of metastatic lymph nodes （P=0.024）, lymph node metastasis （P=0.03）, depth of pancreatic invasion （P=0.001）, T-stage （P=0.002）, TNM stage （P=0.001）, elevated CA 19-9 （P=0.000）, and jaundice （P=0.021）. Multivariate analysis showed that the factors associated with the prognosis were the number of metastatic lymph nodes （P=0.032; RR： 1.283; 95% CI： 1.022-1.611）, tumor size （P=0.043; RR： 1.736; 95% CI： 1.017-2.963）, and elevated CA 19-9 （P=0.003; RR： 3.247; 95% CI： 1.504-7.010）. Conclusions： LNR is a useful factor for predicting the prognosis of the radical treatment for CAV,, whereas the number of metastatic lymph nodes is the most important factor. Further research on the locations, number, and LNR will be clinically meaningful to improve survival in patients with CAV.

关键词： Ampulla of vater lymph nodes metastasis carcinoma prognosis

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肝癌综合治疗新格局

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中华消化外科杂志 2024年第2期23卷 204-208页

作者：蔡建强赵宏陈晓国家癌症中心国家肿瘤临床医学研究中心、中国医学科学院、北京协和医学院肿瘤医院肝胆外科北京100021

外科手术是肝癌最主要的根治性治疗方式。我国中晚期肝癌比例高,初诊时手术切除率低,且术后复发率高,严重威胁人民生命健康。随着新型治疗药物的问世和治疗理念的更新,肝癌综合治疗进入全新时代。以靶向治疗、免疫治疗为代表的系统治疗... 详细信息

外科手术是肝癌最主要的根治性治疗方式。我国中晚期肝癌比例高,初诊时手术切除率低,且术后复发率高,严重威胁人民生命健康。随着新型治疗药物的问世和治疗理念的更新,肝癌综合治疗进入全新时代。以靶向治疗、免疫治疗为代表的系统治疗,以介入、放疗为代表的非手术局部治疗,以及系统治疗和局部治疗的联合,显著提高了治疗有效率,为患者带来希望。笔者回顾既往研究,总结团队诊断与治疗经验,系统阐述靶向、免疫治疗时代以外科治疗为主的肝癌综合治疗策略。

关键词：肝肿瘤新辅助治疗转化治疗外科手术多学科团队疗效

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Validity of distress thermometer for screening of anxiety and depression in family caregivers of Chinese breast cancer patients receiving postoperative chemotherapy

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Chinese Journal of Cancer Research 2020年第4期32卷 476-484页

作者： Min Yang Fei Ma Bo Lan jianqiang cai Xiaoying Sun Binghe Xu Comprehensive Oncology Department National Cancer Center/National Clinical Research Center for Cancer/Cancer HospitalChinese Academy of Medical Sciences and Peking Union Medical CollegeBeijing 100021China Department of Medical Oncology National Cancer Center/National Clinical Research Center for Cancer/Cancer HospitalChinese Academy of Medical Sciences and Peking Union Medical CollegeBeijing 100021China Department of Hepatobiliary Surgery National Cancer Center/National Clinical Research Center for Cancer/Cancer HospitalChinese Academy of Medical Sciences and Peking Union Medical CollegeBeijing 100021China Department of Medical Oncology Cancer Hospital of Huanxing Chaoyang DistrictBeijing 100122China

Objective:Family caregivers(FCs)of breast cancer patients play a vital role throughout the treatment process.Psychological distress of FCs is common and often ignored.A simple and effective instrument for screening psychological distress would help in selecting those FCs requiring special attention and intervention.Here,the validity of distress thermometer(DT)in FCs of Chinese breast cancer patients receiving postoperative chemotherapy was assessed,and the prevalence of anxiety and depression was evaluated.Methods:We recruited 200 FCs of hospitalized breast cancer patients in this cross-sectional descriptive study.Before the first cycle of adjuvant chemotherapy,the levels of anxiety and depression among FCs were assessed using DT and Hospital Anxiety and Depression Scale(HADS).In total,191 valid cases were analyzed.HADS was used as the diagnostic standard to assess the effectiveness of DT as a screening tool for anxiety and depression as well as to analyze the diagnostic efficiency of DT at various cutoff points.Results:The definitive prevalence of both anxiety and depression was 8.90%.The mean level of anxiety and depression among FCs was 5.64±3.69 and 5.09±3.85,respectively,both of which were significantly higher than corresponding Chinese norms(P<0.01).The areas under receiver operating characteristic curves of DT for the diagnoses of FCs'anxiety and depression were 0.904 and 0.885,respectively.A cutoff value of 5 produced the best diagnostic effects of DT for anxiety and depression.Conclusions:The levels of both anxiety and depression were higher in the FCs of Chinese breast cancer patients receiving postoperative chemotherapy than the national norm.DT might be an effective tool to initially screen psychological distress among FCs.This process could be integrated into the palliative care of breast cancer patients and warrant further research.

关键词： Breast cancer distress thermometer anxiety depression

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Neoadjuvant radiotherapy for resectable hepatocellular carcinoma with portal vein tumor thrombus:a systematic review

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Hepatobiliary Surgery and Nutrition 2022年第5期11卷 709-717页

作者： Zhewen Wei Jianjun Zhao Xinyu Bi Yefan Zhang Jianguo Zhou Zhiyu Li Zhen Huang Hong Zhao jianqiang cai Department of Hepatobiliary Surgery National Cancer Center/National Clinical Research Center for Cancer/Cancer HospitalChinese Academy of Medical Sciences and Peking Union Medical CollegeBeijingChina

Background:The prognosis of hepatocellular carcinoma(HCC)with portal vein tumor thrombus(PVTT)is extremely poor.The clinical outcome of preoperative radiotherapy(RT)is still controversial.This study aimed to compare the clinical outcomes of combined neoadjuvant RT and hepatectomy with hepatectomy alone for HCC with PVTT.Methods:Comprehensive database searches were performed in PubMed,the Cochrane Library,EMBASE,and the Web of Science to retrieve studies published from the database creation to July 1,2020.Only comparative studies that measured survival between neoadjuvant RT followed by hepatectomy and hepatectomy alone were included.The characteristics of the included studies and patients were extracted,and the included data are presented as relative ratio(RR)estimates with 95%confidence intervals(CIs)for all outcomes.The RRs of each study were pooled using a fixed or random effects model with Review Manager(the Cochrane Collaboration,Oxford,UK)version 5.3.The response rate to RT and the overall survival(OS)rate in neoadjuvant RT followed by hepatectomy and hepatectomy alone were measured.Results:One randomized and two non-randomized controlled trials with 302 patients were included.Most patients were classified as Child-Pugh A,and Type II and III PVTT were the most common types.After RT,29(22.8%)patients were evaluated as partial response(PR)and had a positive RT response,but nine(7.1%)had progressive disease(PD).Neoadjuvant RT followed by hepatectomy was received by 127(42.1%)patients after excluding 15(5.0%)patients with severe complications or PD after RT,and 160(53.0%)patients received hepatectomy alone.In the randomized controlled trial(RCT),the 1-year OS rate in the neoadjuvant RT group and the surgery alone group was 75.2%and 43.1%,respectively(P<0.001).In the two non-randomized studies,a meta-analysis with a fixed effects model showed a longer OS in patients undergoing neoadjuvant RT followed by hepatectomy compared with hepatectomy alone at 1-year follow-up(RR=2.02;95%CI:1.45-2.80;P<0.0001).Conclusions:

关键词： Hepatocellular carcinoma(HCC) portal vein tumor thrombosis neoadjuvant radiotherapy hepatectomy

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Simultaneous hepatic resection benefits patients with synchronous colorectal cancer liver metastases

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Chinese Journal of Cancer Research 2016年第5期28卷 528-535页

作者： Yuan Li Xinyu Bi Jianjun Zhao Zhen Huang Jianguo Zhou Zhiyu Li Yefan Zhang Hong Zhao jianqiang cai Department of Abdominal Surgery Cancer HospitalChinese Academy of Medical Sciences and Peking Union Medical College

Objective： The safety of the simultaneous resection of synchronous colorectal cancer liver metastases （SCRLM） is still being debated. However, this simultaneous operative approach is more commonly adopted at present than in the past. Therefore, we compared simultaneous hepatic resection with delayed hepatic resection in this study.Methods： All patients with SCRLM diagnosed before initial treatment between January 2009 and September 2013 were retrospectively included in our study. Short-term and long-term outcomes were compared in patients who underwent simultaneous colorectal and hepatic resection and those treated by delayed hepatectomy.Results： Among the 73 patients diagnosed with SCRLM, simultaneous coloreetal and hepatic resection was performed in 60 patients （82.2%）, while delayed hepatic resection was performed in 13 patients （17.8%）. The mortality rate was zero. The postoperative complication rate after delayed resection was higher than, but not significantly different from, that after simultaneous resection （46% vs. 23%, P=0.166）. The duration of operating time （240 vs. 420 min, P〈0.05） and postoperative hospital stay time （11 vs. 18 days, P〈0.05） were shorter in the simultaneous resection group. After the initial treatments were given, the 1-, 2-, and 3-year survival rates in the simultaneous resection group were 77%, 59%, and 53%, respectively, whereas those in the delayed resection group were 67%, 42%, and 10%, respectively. The 5-year survival rate in the simultaneous resection group was 23%; overall survival differed significantly between the two groups （P=0.037）. Median disease-free survival （DFS） times were 19.1 months in the simultaneous resection group and 8.8 months in the delayed resection group. DFS differed significantly between the two groups. Coenclusions： Simultaneous colorectal and hepatic resection is safe and exhibits advantages in the longtime survival of patients.

关键词： Colorectal cancer synchronous liver metastases simultaneous resection survival

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鸡蛋里面挑骨头呕心沥血育新苗:刘允怡院士组织开展临床研究培训纪实

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中华消化外科杂志 2024年第1期23卷 98-101页

作者：卢绮萍蔡建强高强朱鹏梁霄赵宏中国人民解放军中部战区总医院普通外科武汉430070 国家癌症中心国家肿瘤临床医学研究中心、中国医学科学院、北京协和医学院肿瘤医院肝胆外科北京100021 复旦大学附属中山医院、复旦大学肝癌研究所上海200032 华中科技大学同济医学院附属同济医院肝脏外科武汉430030 浙江大学医学院附属邵逸夫医院肝胆胰外科杭州310020

香港中文大学教授、中国科学院刘允怡院士积极倡导用"种果树""育果林"模式开展临床研究,培养造就一支临床实践、临床研究双馨人才队伍,切实提高我国临床医学科学技术水平,在国际医学科学领域发出响亮的中国声音,更好地为人类健康事业服... 详细信息

香港中文大学教授、中国科学院刘允怡院士积极倡导用"种果树""育果林"模式开展临床研究,培养造就一支临床实践、临床研究双馨人才队伍,切实提高我国临床医学科学技术水平,在国际医学科学领域发出响亮的中国声音,更好地为人类健康事业服务。为此,他在应邀参加中国医师协会外科医师分会肝胆青年专家工作组举办的"肝胆不一样"青年医师学者论坛上,亲自组织举办临床研究培训班。培训班在3期活动中,围绕一个鲜明主题:如何提升我国临床研究水平,在国际上更好地发出中国声音;汇集了一批多维度专家,分别来自外科临床医学、方法学、管理学等领域,不仅有知名专家,更有一批青年才俊;采取了一种生动活泼的教学模式,将引导性报告与互动性讨论辩论会紧密结合,穿插进行;大力倡导了一种风清气正的学术精神:采取国际法则,对7项预备进行的临床研究项目和4篇已发表在国际高影响力期刊的论文进行"鸡蛋里面挑骨头"式的对事不对人的深入剖析、尖锐批评,以一种全新的指导模式为青年医师开展临床研究引路导航、指点迷津,使全体参会代表深感教育深刻,获益满满。该场培训活动,不仅为推进我国消化外科临床研究实现科学化、标准化、规范化、国际化奠定了一块铺路基石,而且对如何用科学精神培养造就一批中青年临床医学科学家展示了一条正确路径。

关键词：临床研究培训诊断治疗消化外科青年学者

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Correction: AHR mediates the Aflatoxin B1 toxicity associated with hepatocellular carcinoma

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Signal Transduction and Targeted Therapy 2022年第1期7卷 331-332页

作者： Qing Zhu Yarui Ma Junbo Liang Zhewen Wei Mo Li Ying Zhang Mei Liu Huan He Chunfeng Qu jianqiang cai Xiaobing Wang Yixin Zeng Yuchen Jiao State Key Laboratory of Molecular Oncology National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital Chinese Academy of Medical Sciences and Peking Union Medical College Beijing China Key Laboratory of Gene Editing Screening and R&D of Digestive System Tumor Drugs Chinese Academy of Medical Sciences Peking Union Medical College Beijing China State Key Laboratory of Oncology in South China Collaborative Innovation Center for Cancer Medicine Sun Yat-sen University Cancer Center Guangzhou China Department of Clinical Laboratory National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital Chinese Academy of Medical Sciences and Peking Union Medical College Beijing China State Key Laboratory of Medical Molecular Biology Institute of Basic Medical Sciences Chinese Academy of Medical Sciences School of Basic Medicine Peking Union Medical College Beijing China Department of Hepatobiliary Surgery National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital Chinese Academy of Medical Sciences and Peking Union Medical College Beijing China

Correction to:Signal Transduction and Targeted Therapy https://***/10.1038/s41392-021-00713-1 z published online 9 August 2021 After online publication of the article^(1),the authors noticed one inadvertent mistake occurred during the production process in Fig.7 that needs to be corrected.The correct data are provided as follows.The key findings of the article are not affected by these corrections.The original article has been corrected.

关键词： correction finding corrected

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Expert consensus on organizing the multidisciplinary team(MDT) diagnosis and treatment of hepato-pancreato-biliary diseases in China

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Science China(Life Sciences) 2022年第5期65卷 1036-1039页

作者： Binhao Zhang Jian Zhou Weifen Xie Kaishan Tao Shichun Lu Xianglin Yuan Lianxin Liu Weilin Wang Yilei Mao Ping Bie Jingfeng Liu Xinyu Bi Zhiwei Zhang Changhong Liang jianqiang cai Zhixiang Jian Yi Lv Peng Zhu Wei Zhang Hongqiang Yang Weiping Zhou Bixiang Zhang Xiaoping Chen Tongji Hospital Tongji Medical College of Huazhong University of Science and TechnologyWuhan 430030China Zhongshan Hospital Fudan UniversityShanghai 200032China Shanghai Changzheng Hospital Shanghai 200003China Xijing Hospital of Air Force Medical University Xi’an 710032China Chinese PLA General Hospital Beijing 100048China The First Affiliated Hospital of University of Science and Technology of China Hefei 230001China The Second Affiliated Hospital of Medical College of Zhejiang University Hangzhou 310009China Peking Union Medical College Hospital Beijing 100140China The Third Affiliated Hospital of Chongqing Medical University Chongqing 400016China Fujian Medical University Cancer Hospital Fuzhou 350005China Cancer Hospital Chinese Academy of Medical Sciences Beijing 100021China Guangdong Provincial People’s Hospital Guangzhou 510080China The First Affiliated Hospital of Xi’an Jiaotong University Xi’an 710061China The First Affiliated Hospital of Chengdu Medical College Chengdu 610599China The Eastern Hepatobiliary Surgery Hospital Second Military Medical UniversityShanghai 201805China

Multidisciplinary team(MDT) discussion has been well established in some European countries and widely carried out in various clinical professional fields(Festen et al.,2021;Fleissig et al.,2006).Many studies have reported the benefits of MDT,including improving survival and quality of cancer care(Munro et al.,2015;Nixon et al.,2021;Tsai et al.,2020).

关键词： diagnosis MDT

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AHR mediates the aflatoxin B1 toxicity associated with hepatocellular carcinoma

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Signal Transduction and Targeted Therapy 2021年第9期6卷 2809-2821页

作者： Qing Zhu Yarui Ma Junbo Liang Zhewen Wei Mo Li Ying Zhang Mei Liu Huan He Chunfeng Qu jianqiang cai Xiaobing Wang Yixin Zeng Yuchen Jiao State Key Laboratory of Molecular Oncology National Cancer Center/National Clinical Research Center for Cancer/Cancer HospitalChinese Academy of Medical Sciences and Peking Union Medical CollegeBeijingChina State Key Laboratory of Medical Molecular Biology Institute of Basic Medical Sciences Chinese Academy of Medical SciencesSchool of Basic Medicine Peking Union Medical CollegeBeijingChina Department of Hepatobiliary Surgery National Cancer Center/National Clinical Research Center for Cancer/Cancer HospitalChinese Academy of Medical Sciences and Peking Union Medical CollegeBeijingChina Key Laboratory of Gene Editing Screening and R&D of Digestive System Tumor Drugs Chinese Academy of Medical SciencesPeking Union Medical CollegeBeijingChina State Key Laboratory of Oncology in South China Collaborative Innovation Center for Cancer MedicineSun Yat-sen University Cancer CenterGuangzhouChina Department of Clinical Laboratory National Cancer Center/National Clinical Research Center for Cancer/Cancer HospitalChinese Academy of Medical Sciences and Peking Union Medical CollegeBeijingChina

Aflatoxin exposure is a crucial factor in promoting the development of primary hepatocellular carcinoma(HCC)in individuals infected with the hepatitis virus.However,the molecular pathways leading to its bioactivation and subsequent toxicity in hepatocytes have not been well-defined.Here,we carried out a genome-wide CRISPR-Cas9 genetic screen to identify aflatoxin B1(AFB1)targets.Among the most significant hits was the aryl hydrocarbon receptor(AHR),a ligand-binding transcription factor regulating cell metabolism,differentiation,and immunity.

关键词： aflatoxin metabolism hepatocellular

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