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Decitabine induces IRF7-mediated immune responses in p53-mutated triple-negative breast cancer:a clinical and translational study

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Frontiers of Medicine 2024年第2期18卷 357-374页

作者： Haoyu Wang Zhengyuan Wang Zheng Wang Xiaoyang Li Yuntong Li Ni Yan Lili Wu Ying Liang Jiale Wu Huaxin Song Qing qu Jiahui Huang Chunkang Chang Kunwei Shen Xiaosong chen Min lu Department of General Surgery Comprehensive Breast Health CenterRuijin Hospital Affiliated to Shanghai Jiao Tong University School of MedicineShanghai200025China Shanghai Institute of Hematology State Key Laboratory of Medical GenomicsNational Research Center for Translational Medicine(Shanghai)Ruijin Hospital Affiliated to Shanghai Jiao Tong University School of MedicineShanghai200025China Department of Hematology Shanghai Institute of HematologyRuijin Hospital Affiliated to Shanghai Jiao Tong University School of MedicineShanghai200025China Department of Hematology Shanghai Jiao Tong University Affiliated Sixth People’s HospitalShanghai200025China

p53 is mutated in half of cancer ***,no p53-targeting drugs have been ***,we reposition decitabine for triple-negative breast cancer(TNBC),a subtype with frequent p53 mutations and extremely poor *** a retrospective study on tissue microarrays with 132.TNBC cases,DNMT1 overexpression was associated with p53 mutations(P=0.037)and poor overall survival(OS)(P=0.010).In a prospective DEciTabinE and Carboplatin in TNBC(DETECT)trial(NCT032.5552.,decitabine with carboplatin produced an objective response rate(ORR)of 42.in 12.patients with stage IV *** the 9 trialed patients with available TP53 sequencing results,the 6 patients with p53 mutations had higher ORR(3/6 vs.0/3)and better OS(16.0 vs.4.0 months)than the patients with wild-type *** a mechanistic study,isogenic TNBC cell lines harboring DETECT-derived p53 mutations exhibited higher DNMT1 expression and decitabine sensitivity than the cell line with wild-type *** the DETECT trial,decitabine induced strong immune responses featuring the striking upregulation of the innate immune player IRF7 in the p53-mutated TNBC cell line(upregulation by 16-fold)and the most responsive patient with *** integrative studies reveal the potential of repurposing decitabine for the treatment of p53-mutated TNBC and suggest IRF7 as a potential biomarker for decitabine-based treatments.

关键词： p53 mutation triple-negative breast cancer decitabine DNMT1 IRF7 innate immune response

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CRL2.(APPBP2.-mediated TSPYL2.degradation counteracts human mesenchymal stem cell senescence

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Science china(Life Sciences) 2024年第3期67卷 460-474页

作者： Daoyuan Huang Qian Zhao Kuan yang Jinghui Lei Ying Jing Hongyu Li chen Zhang Shuai Ma Shuhui Sun Yusheng Cai Guibin Wang Jing qu Weiqi Zhang Si Wang Guang-Hui Liu Advanced Innovation centerfor Human Brain Protection National Clinical Research Centerfor Geriatric DisordersXuanwu Hospital Capital Medical UniversityBeijing 100053China State Key Laboratory of Stem Cell and Reproductive Biology Institute of ZoologyChinese Academy of SciencesBeijing 100101China Aging Translational Medicinecenter International Centerfor Aging and CancerBejing Municipal GeriatricMedical Research CenterXuanwu HospitalCapital Medical UniversityBeijing 100053China State Key Laboratory of Membrane Biology Institute of ZoologyChinese Academy of SciencesBeijing 100101China University of Chinese Academy of Sciences Beijing 100049China beijing Institute for Stem Cell and Regenerative Medicine Beijing100101China CAS Key Laboratory of Genomic and Precision Medicine Bejing Institute of Genomics and China National Center for BioinformationChinese Academy of SciencesBeijing 100101China Institute for Stem Cell and Regeneration CASBeijing 100101China The Fifth People's Hospital of Chongqing Chongqing 400062China Sino-Danish Cllege University of Chinese Academy of SciencesBeijing101408China national Laboratory of Biomacromolecules CAS Center for Excelence in BiomacromoleculesInstitute of BiophysicsChinese Academy of SciencesBeijing100101China State Key Laboratory of Proteomics Beijing Proteome Research CenterNational Center for Protein Sciences(Beijing)Beijing Institute of LifeomicsBeijing 102206China

Cullin-RING E3 ubiquitin ligases(CRLs),the largest family of multi-subunit E3 ubiquitin ligases in eukaryotic cells,represent core cellular machinery for executing protein degradation and maintaining ***,we asked what roles Cullin proteins play in human mesenchymal stem cell(hMSC)homeostasis and *** this end,we conducted a comparative aging phenotype analysis by individually knocking down Cullin members in three senescence models:replicative senescent hMSCs,Hutchinson-Gilford Progeria Syndrome hMSCs,and Werner syndrome *** all family members,we found that CUL2.deficiency rendered hMSCs the most susceptible to *** investigate CUL2.specific underlying mechanisms,we then applied CRISPR/Cas9-mediated gene editing technology to generate CUL2.deficient human embryonic stem cells(hESCs).When we differentiated these into h MSCs,we found that CUL2.deletion markedly accelerates hMSC ***,we identified that CUL2.targets and promotes ubiquitin proteasome-mediated degradation of TSPYL2.a known negative regulator of proliferation)through the substrate receptor protein APPBP2.which in turn downregulates one of the canonical aging marker-P2.^(waf1/cip1),and thereby delays *** work provides important insights into how CRL2.(APPBP2.-mediated TSPYL2.degradation counteracts hMSC senescence,providing a molecular basis for directing intervention strategies against aging and aging-related diseases.

关键词： Cullins stem cell senescence aging proteostasis ubiquitination APPBP2 TSPYL2

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Metal-Free Electrochemical Trifluoromethylation of Imidazole-Fused Heterocycles with Trifluoromethyl Thianthrenium Triflate

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Chinese Journal of Chemistry 2024年第15期42卷 1679-1685页

作者： Chang Ge Lipeng Qiao Yuyang Zhang Kai Sun jangzhen An Mei Peng Xiaolan chen Lingbo qu Bing Yu College of Chemistry Zhengzhou UniversityZhengzhouHenan 450001China national Engineering research {2. of Low-Carbon Processing and Utilization of Forest Biomass Nanjing Forestry UniversityNanjingJiangsu210037China School of Pharmacy Hengyang Medical SchoolUniversity of South ChinaHengyangHunan 421001China

A novel and eco-friendly electrochemical activation of trifluoromethyl thianthrenium triflate(TT-CF_(3)^(+)OTf^(-))for trifluoromethylation of imidazole-fused heteroaromatic compounds was *** method involves the direct electrolysis of TT-CF_(3)^(+)OTf^(-)without the requirement of external oxidants or catalysts,aligning with the principles of green chemistry.A wide range of imidazole-fused heteroaromatic compounds including imidazo[1,2.a]pyridines and benzo[d]imidazo[2.1-b]thiazoles have been successfully trifluoromethylated using this technique,exhibiting excellent compatibility with various functional groups and a broad substrate ***,the method's applicability for one-pot sequential reactions enables the reduction of waste and resource consumption by eliminating the need for intermediate purification steps.

关键词： Trifluoromethylation Electrochemical Metal-free Imidazole-fused heterocycles Thianthrenium

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A Localization Method of High Energy Transients for All-sky Gamma-ray Monitor

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research in Astronomy and Astrophysics 2024年第10期24卷 25-35页

作者： Yi Zhao Wangchen Xue Shaolin Xiong Qi luo Yuanhao Wang Jiacong Liu Heng Yu Xiaoyun Zhao Yue Huang Jinyuan Liao Jianchao Sun Xiaobo Li Qibin Yi Ce Cai Shuo Xiao Shenglun Xie Chao Zheng Yanqiu Zhang chenwei Wang {2. Tan Zhiwei Guo Chaoyang Li Zhenghua An gang chen Yanqi du Min Gao Ke Gong Dongya Guo Jiang He Jianjian He Bing Li gang Li Xinqiao Li Jing Liang Xiaohua Liang Yaqing Liu Xiang Ma Rui Qiao Liming Song Xinying Song Xilei Sun Jin Wang Ping Wang Xiangyang Wen Hong Wu Yanbing Xu Sheng yang Dali Zhang Fan Zhang Hongmei Zhang Peng Zhang Shu Zhang Zhen Zhang Shijie Zheng Keke Zhang Xingbo Han Haiyan Wu Hu Tai Hao Geng Gaopeng lu Wei Xu Fanchao Lyu Hongbo Zhang Fangjun lu Shuangnan Zhang Department of Astronomy Beijing Normal UniversityBeijing 100875China Key Laboratory of Particle Astrophysics Institute of High Energy PhysicsChinese Academy of SciencesBeijing 100049China University of Chinese Academy of Sciences Beijing 100049China School of Physics and Optoelectronics Xiangtan UniversityXiangtan 411105China College of Physics Hebei Normal UniversityShijiazhuang 050024China Guizhou Provincial Key Laboratory of Radio Astronomy and Data Processing Guizhou Normal UniversityGuiyang 550001China School of Physics and Electronic Science Guizhou Normal UniversityGuiyang 550001China Institute of Astrophysics Central China Normal UniversityWuhan 430079China College of physics Sciences Technology Hebei UniversityBaoding 071002China Physics and Space Science College China West Normal UniversityNanchong 637002China School of Computing and Artificial Intelligence Southwest Jiaotong UniversityChengdu 611756China College of Electronic and information Engineering Tongji UniversityShanghai 201804China Innovation Academy for Microsatellites of Chinese Academy of Sciences Shanghai 201304China national Space Science center Chinese Academy of SciencesBeijing 100190China School of Earth and Space Sciences University of Science and Technology of ChinaHefei 230026China Electronic Information School Wuhan UniversityWuhan 430072China Key Laboratory of Transportation Meteorology of china Meteorological Administration Nanjing Joint Institute for Atmospheric SciencesNanjing 210000China Key Laboratory of Middle Atmosphere and Global Environment Observation Institute of Atmospheric PhysicsChinese Academy of SciencesBeijing 100029China

Fast and reliable localization of high-energy transients is crucial for characterizing the burst properties and guiding the follow-up *** based on the relative counts of different detectors has been widely used for all-sky gamma-ray *** are two major methods for this count distribution localization:χ^(2.minimization method and the Bayesian *** we propose a modified Bayesian method that could take advantage of both the accuracy of the Bayesian method and the simplicity of the χ^(2.*** comprehensive simulations,we find that our Bayesian method with Poisson likelihood is generally more applicable for various bursts than the χ^(2.method,especially for weak *** further proposed a location-spectrum iteration approach based on the Bayesian inference,which could alleviate the problems caused by the spectral difference between the burst and location *** method is very suitable for scenarios with limited computation resources or timesensitive applications,such as in-flight localization software,and low-latency localization for rapidly follow-up observations.

关键词： methods:data analysis methods:analytical (stars:)gamma-ray burst:general

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Distribution of Traditional Chinese Medicine syndromes in diabetic kidney disease chronic kidney disease 1-5: a correlation study

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Journal of Traditional Chinese Medicine 2024年第3期44卷 572-580页

作者： LI Shuang duAN Shuwei DONG Zheyi qu Yilun luO Yayong KE Jianghua WANG Conghui PENG yangzhi ZHOU Xuefeng chen Xiangmei Department of Nephrology First Medical Center of Chinese PLA General HospitalNephrology Institute of the Chinese People's Liberation ArmyNational Key Laboratory of Kidney DiseasesNational Clinical Research Center for Kidney DiseasesBeijing Key Laboratory of Kidney Disease ResearchBeijing 100853China School of Clinical Medicine Guangdong Pharmaceutical Universityjuangzhou510006China Basic Medical College Chengdu University of Traditional Chinese MedicineChengdu610075China

OBJECTIVE: To analyze the distribution of Traditional Chinese medicine(TCM) syndromes in patients with diabetic kidney disease(DKD) and its related ***: We enrolled 435 patients with DKD, who were not undergoing dialysis, admitted to the Department of Nephrology, First Medical center, Chinese PLA General Hospital from April 2.2. to August *** of their TCM syndromes and related factors was carried ***: The 435 patients included 109, 117, 86, and 12. chronic kidney disease(CKD) 1-2. CKD3, CKD4, and CKD5 cases, respectively. With the progression of CKD1-5, the proportion of Yin deficiency and dry heat syndrome,and that of Qi and Yin deficiency syndrome showed a downward trend, whereas the proportion of spleen-kidney yang deficiency, blood deficiency, blood stasis, water stagnation, and phlegm turbidity syndromes showed an upward trend;the differences were statistically significant(P 2., P = 0.005], albumin(OR = 1.058, P = 0.006), and estimated glomerular filtration rate(eGFR)(OR = 1.02.,P 2.7, P = 0.004). Qi and Yin deficiency syndrome was positively correlated with albumin(OR = 1.056, P 2.) but negatively correlated with age(OR = 0.977, P = 0.02.). Liver-kidney Yin deficiency syndrome was positively correlated with age(OR = 1.02., P = 0.02.) and glycosylated hemoglobin(OR = 1.2.3, P = 0.007) but negatively correlated with total cholesterol(OR = 0.792. P = 0.006).Spleen-kidney yang deficiency syndrome was negatively correlated with hemoglobin(OR = 0.977, P luSION: With CKD1-5 progression, TCM syndromes changed from Yin deficiency and dry

关键词： diabetic nephropathies syndrome and complex hemoglobins albumins glomerular filtration rate correlation of data

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Multiomics analysis reveals metabolic subtypes and identifies diacylglycerol kinase α (DGKA) as a potential therapeutic target for intrahepatic cholangiocarcinoma

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Cancer Communications 2024年第2期44卷 226-250页

作者： Weiren Liu Huqiang Wang Qianfu Zhao chenyang Tao Weifeng qu Yushan Hou Run Huang Zimei Sun Guiqi Zhu Xifei Jiang Yuan Fang Jun Gao Xiaoling Wu Zhixiang yang Rongyu Ping Jiafeng chen Rui yang Tianhao Chu Jian Zhou Jia Fan Zheng Tang Dong yang Yinghong Shi Department of Liver Surgery and Transplantation Liver Cancer InstituteZhongshan HospitalFudan UniversityKey Laboratory of Carcinogenesis and Cancer Invasion of Ministry of EducationShanghaiP.R.China research Unit of Liver cancer Recurrence and Metastasis Chinese Academy of Medical SciencesBeijingP.R.China State Key Laboratory of Medical Proteomics Beijing Proteome Research CenterNational Center for Protein Sciences(Beijing)Beijing Institute of LifeomicsBeijingP.R.China

Background:Intrahepatic cholangiocarcinoma(iCCA)is a highly heteroge-neous and lethal hepatobiliary tumor with few therapeutic *** metabolic reprogramming of tumor cells plays an essential role in the develop-ment of tumors,while the metabolic molecular classification of iCCA is largely ***,we performed an integrated multiomics analysis and metabolic classification to depict differences in metabolic characteristics of iCCA patients,hoping to provide a novel perspective to understand and treat ***:We performed integrated multiomics analysis in 116 iCCA samples,including whole-exome sequencing,bulk RNA-sequencing and proteome *** on the non-negative matrix factorization method and the protein abundance of metabolic genes in human genome-scale metabolic models,the metabolic subtype of iCCA was *** and prognostic gene analy-ses were used to compare overall survival(OS)differences between metabolic *** proliferation analysis,5-ethynyl-2.-deoxyuridine(Edu)assay,colony formation assay,RNA-sequencing and Western blotting were performed to investigate the molecular mechanisms of diacylglycerol kinaseα(DGKA)in iCCA ***:Three metabolic subtypes(S1-S3)with subtype-specific biomarkers of iCCA were *** metabolic subtypes presented with distinct prog-noses,metabolic features,immune microenvironments,and genetic *** S2.subtype with the worst survival showed the activation of some special metabolic processes,immune-suppressed microenvironment and Kirsten ratsar-coma viral oncogene homolog(KRAS)/AT-rich interactive domain 1A(ARID1A)*** the S2.subtype-specific upregulated proteins,DGKA was further identified as a potential drug target for iCCA,which promoted cell proliferation by enhancing phosphatidic acid(PA)metabolism and activating mitogen-activated protein kinase(MAPK)***:Viamultiomics analyses,we identified three metabolic subtypes of iCCA,revealing

关键词： diacylglycerol kinaseα intrahepatic cholangiocarcinoma MAPK signaling metabolic classifi-cation multiomics analysis phosphatidic acid metabolism

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Mapping the Characteristics of Respiratory Infectious Disease Epidemics in china Based on the Baidu Index from November 2.2. to January 2.2.

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china CDC weekly 2024年第37期6卷 939-945,I0001-I0007页

作者： Dazhu Huo Ting Zhang Xuan Han Liuyang yang Lei Wang Ziliang Fan Xiaoli Wang Jiao yang Qiangru Huang Ge Zhang Ye Wang Jie Qian Yanxia Sun Yimin qu Yugang Li Chuchu Ye luzhao Feng Zhongjie Li Weizhong yang chen Wang School of Health Policy and Management Chinese Academy of Medical Sciences&Peking Union Medical CollegeBeijingChina School of Population Medicine and Public Health Chinese Academy of Medical Sciences(CAMS)&Peking Union Medical CollegeBeijingChina Yichang center for Disease Prevention and Control Yichang CityHubei ProvinceChina Weifang center for Disease Prevention and Control Weifang CityShandong ProvinceChina beijing center for Disease Prevention and Control BeijingChina School of Public Health Dali UniversityDali CityYunnan ProvinceChina Shanghai Pudong New Area center for Disease Control and Prevention ShanghaiChina

Introduction:Infectious diseases pose a significant global health and economic burden,underscoring the critical need for precise predictive *** Baidu index provides enhanced real-time surveillance capabilities that augment traditional ***:Baidu search engine data on the keyword“fever”were extracted from 2.5 cities in china from November 2.2. to January *** and peak dates for influenza epidemics were identified by testing various criteria that combined thresholds and consecutive ***:The most effective scenario for indicating epidemic commencement involved a 90th percentile threshold exceeded for seven consecutive days,minimizing false *** detection was optimized using a 7-day moving average,balancing stability and ***:The use of internet search data,such as the Baidu index,significantly improves the timeliness and accuracy of disease surveillance *** innovative approach supports faster public health interventions and demonstrates its potential for enhancing epidemic monitoring and response efforts.

关键词： faster precise false

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Two-year longitudinal change in choroidal and retinal thickness in school-aged myopic children:exploratory analysis of clinical trials for myopia progression

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Eye and Vision 2024年第4期10卷 1-10页

作者： Meiping Xu Xinping Yu Minghui Wan Kemi Feng Junxiao Zhang Meixiao Shen BjÖrn Drobe Hao chen Jia qu Jinhua Bao Eye Hospital and School of Ophthalmology and Optometry Wenzhou Medical UniversityWenzhouZhejiangChina national Clinical research {2. for Ocular Diseases WenzhouZhejiangChina. WEiRC WMU-Essilor International Research CenterWenzhouZhejiangChina R&D Vision Sciences AMERA EssilorInternationalSingaporeSingapore

Background:With increasing axial length(AL)and myopia progression,the micro-structure of the retina and choroid gradually *** study describes the longitudinal changes in retinal and choroidal thickness in school-aged children with myopia and explores the relationship between changes in choroidal thickness and myopia ***:An exploratory analysis of a randomized trial was ***(n=168,aged 7 to 12.years)with myopia from-0.75 diopter(D)to-4.00 D were enrolled in this prospective longitudinal *** refraction,AL,retinal and choroidal thicknesses were measured at baseline and at 1-and 2.year follow-ups."Rapid progression myopia"was defined as increasing in myopia>1.00 D and'"stable progression myopia"was≤1.00 D during the 2.year *** affecting the changes in choroidal thickness were analysed using linear mixed ***:AL significantly increased by 0.67±0.2. mm with a myopic shift of-1.50±0.64 D over the 2.*** overall retinal thickness increased from 2.1.12.15.91μm at baseline to 2.3.47±15.74μm at the 2.year followup(F=2..785,P2.1.03±54.04μm at baseline to 2.6.53±59.71μm at the 2.year follow-up(F=73.358,P3.579μm/mm,P=0.002.and sex(β=-17.2.8,P=0.001).Choroidal thickness continued to decrease in subjects with rapid progression(F=92.06,P2.2.,P=0.119).Conclusion:Significant choroidal thinning was observed and was associated with rapid progression and *** findings indicate a need to understand the role of the choroid in eye growth and myopia ***/Precis:The macular choroidal thickness of myopic children is relevant to different degrees of myopic progression in this 2.year longitudinal *** findings suggest that control of choroidal thickness might work to regulate human ocular growth.

关键词： Axial length Choroidal thickness Children Myopia Spectral-domain optical coherence tomography

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A Blood Hepatocellular Carcinoma Signature Recognizes Very Small Tumor Nodules with Metastatic Traits

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Journal of Clinical and Translational Hepatology 2024年第6期12卷 551-561页

作者： Kun chen Junxiao Wang Liping Jiang Fei Zhao Ruochan Zhang Zhiyuan Wu Dongmei Wang Yuchen Jiao Hui Xie Chunfeng qu State Key Lab of Molecular Oncology Department of ImmunologyNational Cancer Center/National Clinical Research Center for Cancer/Cancer HospitalChinese Academy of Medical Sciences and Peking Union Medical CollegeBeijingChina Senior Department of Oncology Fifth Medical Center of Chinese PLA General HospitalBeijingChina Aerospace Medical center/Aerospace center Hospital Peking University Aerospace Clinical CollegeBeijingChina State Key Lab of Molecular Oncology National Cancer Center/National Clinical Research Center for Cancer/Cancer HospitalChinese Academy of Medical Sciences and Peking Union Medical CollegeBeijingChina

Background and Aims:Hepatocellular carcinoma(HCC)cases with small nodules are commonly treated with radi-ofrequency ablation(RFA),but the recurrence rate remains *** study aimed to establish a blood signature for identifying HCC with metastatic traits ***:Data from HCC patients treated between 2.10 and 2.17 were retrospectively collected.A blood signature for meta-static HCC was established based on blood levels of alpha-fetoprotein and des-γ-carboxy-prothrombin,cell-free DNA(cfDNA)mutations,and methylation changes in target genes in frozen-stored plasma samples that were collected before RFA *** HCC blood signature was validated in patients prospectively enrolled ***:Of 2.1 HCC patients in the retrospective study,33.9% experienced recurrence within 1 year *** HCC blood signature identified from these patients included des-γ-carboxy-prothrombin≥40mAU/mL with cfDNA mutation score,where cfDNA mutations occurred in the genes of TP53,CTNNB1,and TERT *** signature effectively predicted 1-year post-RFArecurrence of HCC with 92. specificity and 91% sensitivity in the retrospective dataset,and with 87% specificity and 76% sensitivity in the prospective dataset(n=32.patients).Among 14 cases in the prospective study with biopsy tissues available,positivity for the HCC blood signature was associated with a higher HCC tissue score and shorter distance between HCC cells and ***:This study established an HCC blood signature in pre-RFA blood that potentially reflects HCC with metastatic traits and may be valuable for predicting the disease’s early recurrence post-RFA.

关键词： Liquid biopsy Liver dysplastic nodules Radiofrequency ablation Hepatocellular carcinoma Recurrence prediction Metastatic nodules

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The associations between the environmental exposure to polychlorinated biphenyls (PCBs) and breast cancer risk and progression

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Science china Chemistry 2010年第5期53卷 974-979页

作者： LIU SiJin ,ZHANG ShuPing,qu chen,LIU Wei & du YuGuo State Key Laboratory of Environmental Chemistry and Ecotoxicology research {2. for Eco-Environmental Sciences,Chinese Academy of Sciences,beijing 100085,china State Key Laboratory of Environmental Chemistry and Ecotoxicology Research Center for Eco-Environmental Sciences Chinese Academy of Sciences Beijing China

Polychlorinated biphenyls(PCBs) are chlorinated biphenyl compounds with wide applications in the *** spite of a ban on their production in the late 1970s,PCBs,as a group of POPs,are still persistent and widely spread in the environment,posing potential threats to human *** role of PCBs as etiologic agents for breast cancer has been intensively explored in a variety of in vivo,animal and epidemiologic *** investigations indicated higher levels of PCBs in mammary tissues or sera corresponded to the occurrence of breast cancer,but later studies showed no positive association between PCB exposure and breast cancer *** recent data suggested that the CYP1A1 m2.polymorphisms might add increased risk to the etiology of breast cancer in women with environmental exposure to *** are implicated in advancing breast cancer progression,and our unpublished data reveals that PCBs activate the ROCK signaling to enhance breast cancer ***,the correlation between PCB exposure and breast cancer risk warrants further careful investigations.

关键词： Polychlorinated biphenyls (PCBs) environmental exposure CYP1A1 polymorphisms breast cancer risk tumor progression

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