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Frontiers of Medicine 2024年第3期18卷 565-569页

作者： Jia Jia Lili Mao Jing Lin Wenyu Li Pei Yuan Lei Guo Jie Dai Caili Li Xue Bai Zhongwu Li Yu Chen Jun Guo Jianming Ying Lu Si State Key Laboratory of Molecular Oncology Department of PathologyNational Cancer Center/National Clinical Research Center for Cancer/Cancer HospitalChinese Academy of Medical Sciences and Peking Union Medical CollegeBeijing100021China Key Laboratory of Carcinogenesis and Translational Research(Ministry of Education/Beijing) Department of Melanoma and SarcomaPeking University Cancer Hospital&InstituteBeijing100142China Department of Medical Oncology Clinical Oncology School of Fujian Medical UniversityFujian Cancer HospitalFuzhou350014China Department of Pathology Peking University Cancer Hospital&InstituteBeijing100142China

Dear Editor,Extramammary Paget disease(EMPD)is a rare adenocarcinoma that originates in the apocrine gland-rich skin and usually affects the perineal skin(primary EMPD)or represents the intraepithelial spread of an underlying visceral carcinoma(secondary EMPD).Approximately half of EMPD cases are confined to the epidermis,which was defined as intraepithelial EMPD.

关键词： Paget HER2 adenocarcinoma

Cervical cancer prevention in China: where are we now, and what's next?

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cancer Biology & Medicine 2024年第3期21卷 213-217页

作者： Huijiao Yan Qiankun Wang Youlin Qiao School of Population Medicine and Public Health Chinese Academy of Medical Sciences and Peking Union Medical CollegeBejing 100730China Department of cancer Epidemiology National Cancer Center/National Clinical Research Center for Cancer/Cancer HospitalChinese Academy of Medical Sciences and Peking Union Medical CollegeBejing 100021China

Cervical cancer(CC) epidemiology CC, the fourth most frequently diagnosed malignancy in women worldwide, is a major global health challenge, particularly in low-resource regions. Approximately 88.1% of the 604,000 CC new cases occurred in low-and middle-income countries in 2020, and more than 90% of the 342,000 CC deaths occurred in low-and middle-income countries in 2020~1.

关键词： prevention Cervical epidemiology

Cinobufotalin prevents bone loss induced by ovariectomy in mice through the BMPs/SMAD and Wnt/β-catenin signaling pathways

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Animal Models and Experimental Medicine 2024年第3期7卷 208-221页

作者： Da-zhuang Lu Li-jun Zeng Yang Li Ran-li Gu Meng-long Hu Ping Zhang Peng Yu Xiao Zhang Zheng-wei Xie Hao Liu Yong-sheng Zhou Department of Prosthodontics Peking University School and Hospital of StomatologyBeijingChina National center of Stomatology BeijingChina National Clinical Research center for Oral Diseases BeijingChina Beijing Key Laboratory of Digital Stomatology BeijingChina Department of Cariology and Endodontology Peking University School and Hospital of StomatologyBeijingChina peking university International cancer Institute Peking University Health Science CenterPeking UniversityBeijingChina Central Laboratory Peking University School and Hospital of StomatologyBeijingChina National Engineering Research center of Oral Biomaterials and Digital Medical Devices BeijingChina

Background:Osteoporosis is a chronic bone disease characterized by bone loss and decreased bone strength.However,current anti-resorptive drugs carry a risk of various complications.The deep learning-based efficacy prediction system(DLEPS)is a forecasting tool that can effectively compete in drug screening and prediction based on gene expression changes.This study aimed to explore the protective effect and potential mechanisms of cinobufotalin(CB),a traditional Chinese medicine(TCM),on bone loss.Methods:DLEPS was employed for screening anti-osteoporotic agents according to gene profile changes in primary osteoporosis.Micro-CT,histological and morphological analysis were applied for the bone protective detection of CB,and the osteogenic differentiation/function in human bone marrow mesenchymal stem cells(hBMMSCs)were also investigated.The underlying mechanism was verified using qRT-PCR,Western blot(WB),immunofluorescence(IF),etc.Results:A safe concentration(0.25mg/kg in vivo,0.05μM in vitro)of CB could effectively preserve bone mass in estrogen deficiency-induced bone loss and promote osteogenic differentiation/function of hBMMSCs.Both BMPs/SMAD and Wnt/β-catenin signaling pathways participated in CB-induced osteogenic differentiation,further regulating the expression of osteogenesis-associated factors,and ultimately promoting osteogenesis.Conclusion:Our study demonstrated that CB could significantly reverse estrogen deficiency-induced bone loss,further promoting osteogenic differentiation/function of hBMMSCs,with BMPs/SMAD and Wnt/β-catenin signaling pathways involved.

关键词： BMPs/SMAD bone loss cinobufotalin hBMMSCs osteogenesis osteoporosis Wnt/β-catenin signaling pathways

Epigenetic regulators as the foundation for molecular classification of colorectal cancer

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cancer Biology & Medicine 2024年第7期 547-552页

作者： Zhenyu Liu Xin Zhou Fuchou Tang School of Life Sciences Biomedical Pioneering Innovation Center Department of General Surgery Third Hospital Peking University Beijing Advanced Innovation center for Genomics (ICG) Ministry of Education Key Laboratory of Cell Proliferation and Differentiation peking university third hospital cancer center Academy for Advanced Interdisciplinary Studies Peking University

Colorectal cancer （CRC） accounts for approximately 10% of newly diagnosed cancer cases and cancer-related deaths worldwide1. The identification of molecular subtypes of CRCs has significantly advanced treatment stra...

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Plant-based dietary patterns and risk of esophageal cancer:A prospective cohort study spanning 17 years

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Chinese Journal of cancer Research 2024年第1期36卷 36-45页

作者： Xiaorui Zhang Feifan He Jiayue Li Ru Chen Xinqing Li Li Li Fen Liu Shaoming Wang Wenqiang Wei Department of Epidemiology and Health Statistics School of Public HealthBeijing Municipal Key Laboratory of Clinical EpidemiologyCapital Medical UniversityBeijing 100069China National Central cancer Registry office National Cancer Center/National Clinical Research Center for Cancer/Cancer HospitalChinese Academy of Medical Sciences and Peking Union Medical CollegeBeijing 100021China Department of cancer Epidemiology National Cancer Center/National Clinical Research Center for Cancer/Cancer HospitalChinese Academy of Medical Sciences and Peking Union Medical CollegeBeijing 100021China

Objective: Plant-based diets have multiple health benefits for cancers;however, little is known about the association between plant-based dietary patterns and esophageal cancer(EC).This study presents an investigation of the prospective associations among three predefined indices of plant-based dietary patterns and the risk of EC.Methods: We performed endoscopic screening for 15,709 participants aged 40-69 years from two high-risk areas of China from January 2005 to December 2009 and followed the cohort until December 31, 2022. The overall plant-based diet index(PDI), healthful plant-based diet index(h PDI), and unhealthful plant-based diet index(u PDI), were calculated using survey responses to assess dietary patterns. We applied Cox proportional hazard regression to estimate the multivariable hazard ratios(HRs) and 95% confidence intervals(95% CIs) of EC across 3plant-based diet indices and further stratified the analysis by subgroups.Results: The final study sample included 15,184 participants in the cohort. During a follow-up of 219,365person-years, 176 patients with EC were identified. When the highest quartile was compared with the lowest quartile, the pooled multivariable-adjusted HR of EC was 0.50(95% CI, 0.32-0.77) for h PDI. In addition, the HR per 10-point increase in the h PDI score was 0.42(95% CI, 0.27-0.66) for ECs. Conversely, u PDI was positively associated with the risk of EC, and the HR was 1.80(95% CI, 1.16-2.82). The HR per 10-point increase in the u PDI score was 1.90(95% CI, 1.26-2.88) for ECs. The associations between these scores and the risk of EC were consistent in most subgroups. These results remained robust in sensitivity analyses.Conclusions: A healthy plant-based dietary pattern was associated with a reduced risk of EC. Emphasizing the healthiness and quality of plant-based diets may be important for preventing the development of EC.

关键词： Esophageal cancer diet dietary pattern epidemiology nutrition prospective cohort study

CircPTEN-MT from PTEN regulates mitochondrial energy metabolism

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Journal of Genetics and Genomics 2024年第5期51卷 531-542页

作者： Danhui Ruan Jiancheng Xu Yang Liu Juan Luo Xuyang Zhao Yuhua Li Guangxi Wang Jiawen Feng Hui Liang Yue Yin Jianyuan Luo Yuxin Yin Institute of Systems Biomedicine Department of PathologySchool of Basic Medical SciencesBeijing Key Laboratory of Tumor Systems BiologyPeking University International Cancer InstitutePeking-Tsinghua Center of Life SciencesPeking University Health Science CenterBeijing 100191China Institute of Precision Medicine Peking University Shenzhen HospitalShenzhenGuangdong 518036China Department of Pharmacology School of Basic Medical SciencesPeking University Health Science CenterBeijing 100191China Department of Medical Genetics Center for Medical GeneticsSchool of Basic Medical SciencesPeking University Health Science CenterBeijing 100191China Soochow university cancer Institute SuzhouJiangsu 215127China

Phosphatase and tensin homolog(PTEN)is a multifunctional gene involved in a variety of physiological and pathological processes.Circular RNAs(circRNAs)are generated from back-splicing events during mRNA processing and participate in cell biological processes through binding to RNAs or proteins.However,PTEN-related circRNAs are largely unknown.Here,we report that circPTEN-mitochondria(MT)(hsa_circ_0002934)is a circular RNA encoded by exons 3,4,and 5 of PTEN and is a critical regulator of mitochondrial energy metabolism.CircPTEN-MT is localized to mitochondria and physically associated with leucine-rich pentatricopeptide repeat-containing protein(LRPPRC),which regulates posttranscriptional gene expression in mitochondria.Knocking down circPTEN-MT reduces the interaction of LRPPRC and steroid receptor RNA activator(SRA)stem-loop interacting RNA binding protein(SLIRP)and inhibits the polyadenylation of mitochondrial mRNA,which decreases the mRNA level of the mitochondrial complex I subunit and reduces mitochondrial membrane potential and adenosine triphosphate production.Our data demonstrate that circPTEN-MT is an important regulator of cellular energy metabolism.This study expands our understanding of the role of PTEN,which produces both linear and circular RNAs with different and independent functions.

关键词： Circular RNA LRPPRC Mitochondrial energy metabolism mtDNApost-transcriptional regulation

DNA damage chemotherapeutic drugs suppress basal-like breast cancer growth by down-regulating the transcription of the FOXO1-KLF5 axis

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Genes & Diseases 2024年第1期11卷 91-94页

作者： Qiuxia Cui Jian Sun Jingping Yuan Juanjuan Li Chuanyu Yang Guangshi Du Chengang Zhou Pu Qiu Jidong Gao Yuanqi Zhang Dewei Jiang Ceshi Chen Affiliated hospital of Guangdong Medical university Science&Technology of China ZhanjiangGuangdong 524000China Department of Breast Surgical Oncology National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital and Shenzhen HospitalChinese Academy of Medical Sciences and Peking Union Medical CollegeShenzhenGuangdong 518116China Key Laboratory of Animal Models and Human Disease Mechanisms of the Chinese Academy of Sciences and Yunnan Province Kunming Institute of ZoologyChinese Academy of SciencesKunmingYunnan 650223China Department of Pathology Renmin Hospital of Wuhan UniversityWuhanHubei 430060China Department of Breast and Thyroid Surgery Renmin Hospital of Wuhan UniversityWuhanHubei 430060China Translational Medicine Research center of Guizhou Medical university GuiyangGuizhou 550025China Department of Breast Surgical Oncology National Cancer Center/National Clinical Research Center for Cancer/Cancer HospitalChinese Academy of Medical Sciences and Peking Union Medical CollegeBeijing 100021China Yunnan cancer hospital and the third Affiliated hospital of Kunming Medical university and Yunnan cancer center KunmingYunnan 650500China Academy of Biomedical Engineering Kunming Medical UniversityKunmingYunnan 650500China

Most basal-like breast cancers(BLBCs)have a poor prognosis and high crossover with triple-negative breast cancers(TNBCs).However,approximately 50%of TNBC patients develop chemoresistance.^(1) Dexamethasone reportedly induces Krüppel-like factor 5(KLF5)and can cause docetaxel and cisplatin resistance in TNBC.A super-enhancer can maintain the transcription of KLF5.

关键词： FOXO1 drugs damage

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World Journal of Gastroenterology 2024年第9期30卷 1224-1236页

作者： Hai-Yang Li Lin-Lin Zheng Nan Hu Zhi-Hao Wang Chang-Cheng Tao Ya-Ru Wang Yue Liu Zulihumaer Aizimuaji Hong-Wei Wang Rui-Qi Zheng Ting Xiao Wei-Qi Rong 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 Hepatobiliary Hernia Surgery Liaocheng Dongcangfu People’s HospitalLiaocheng 252000Shandong ProvinceChina State Key Laboratory of Molecular Oncology Department of Etiology and CarcinogenesisNational Cancer Center/National Clinical Research Center for Cancer/Cancer HospitalChinese Academy of Medical Sciences and Peking Union Medical CollegeBeijing 100021China

BACKGROUND As a critical early event in hepatocellular carcinogenesis,telomerase activation might be a promising and critical biomarker for hepatocellular carcinoma(HCC)patients,and its function in the genesis and treatment of HCC has gained much attention over the past two decades.AIM To perform a bibliometric analysis to systematically assess the current state of research on HCC-related telomerase.METHODS The Web of Science Core Collection and PubMed were systematically searched to retrieve publications pertaining to HCC/telomerase limited to“articles”and“reviews”published in English.A total of 873 relevant publications related to HCC and telomerase were identified.We employed the Bibliometrix package in R to extract and analyze the fundamental information of the publications,such as the trends in the publications,citation counts,most prolific or influential writers,and most popular journals;to screen for keywords occurring at high frequency;and to draw collaboration and cluster analysis charts on the basis of coauthorship and co-occurrences.VOSviewer was utilized to compile and visualize the bibliometric data.RESULTS A surge of 51 publications on HCC/telomerase research occurred in 2016,the most productive year from 1996 to 2023,accompanied by the peak citation count recorded in 2016.Up to December 2023,35226 citations were made to all publications,an average of 46.6 citations to each paper.The United States received the most citations(n=13531),followed by China(n=7427)and Japan(n=5754).In terms of national cooperation,China presented the highest centrality,its strongest bonds being to the United States and Japan.Among the 20 academic institutions with the most publications,ten came from China and the rest of Asia,though the university of Paris Cité,Public Assistance-hospitals of Paris,and the National Institute of Health and Medical Research(INSERM)were the most prolific.As for individual contributions,Hisatomi H,Kaneko S,and Ide T were the three most prolific authors.Kaneko S ranked first by H-index,G-index,

关键词： Telomerase Bibliometric analysis Telomerase reverse transcriptase Prognosis Treatment Hepatocellular carcinoma

Advances in functional MRI research in bipolar disorder:from the perspective of mood states

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General Psychiatry 2024年第1期37卷 33-43页

作者： Yankun Wu Yun-Ai Su Linlin Zhu Jitao Li Tianmei Si Department of Clinical Psychopharmacology Peking University Sixth HospitalPeking University Institute of Mental HealthNHC Key Laboratory of Mental Health(Peking University)National Clinical Research Center for Mental Disorders(Peking University Sixth Hospital)BeijingChina peking university Sixth hospital Peking University Institute of Mental HealthNHC Key Laboratoryof Mental Health(Peking University)National Clinical Research Centerfor Mental Disorders(Peking University Sixth Hospital)BeijingChina

Bipolar disorder is characterised by recurrent and alternating episodes of mania/hypomania and depression.Current breakthroughs in functional MRI techniques have uncovered the functional neuroanatomy of bipolar disorder.However,the pathophysiology underlying mood instability,mood switching and the development of extreme mood states is less well understood.This reviewpresents a comprehensive overviewof current evidence from functional MRI studies from the perspective of mood states.We first summarise the disrupted brain activation patterns and functional connectivity that have been reported in bipolar disorder,irrespective of the mood state.We next focus on research that solely included patients in a single mood state for a better understanding of the pathophysiology of bipolar disorder and research comparing patients with different mood states to dissect mood state-related effects.Finally,we briefly summarise current theoretical models and conclude this review by proposing potential avenues for future research.A comprehensive understanding of the pathophysiology with consideration of mood states could not only deepen our understanding of how acute mood episodes develop at a neurophysiological level but could also facilitate the identification of biological targets for personalised treatment and the development of new interventions for bipolar disorder.

关键词： anatomy bipolar functional

Genomic characterization of peritoneal lavage cytology-positive gastric cancer

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Chinese Journal of cancer Research 2024年第1期36卷 66-77页

作者： Zhouqiao Wu Tingfei Gu Changxian Xiong Jinyao Shi Jingpu Wang Ting Guo Xiaofang Xing Fei Pang Ning He Rulin Miao Fei Shan Yuan Zhou Ziyu Li Jiafu Ji Key Laboratory of Carcinogenesis and Translational Research(Ministry of Education/Beijing) Gastrointestinal Cancer CenterPeking University Cancer Hospital&InstituteBeijing 100142China Department of Biomedical Informatics Department of Physiology and PathophysiologyCenter for Noncoding RNA MedicineMOE Key Lab of Cardiovascular SciencesSchool of Basic Medical SciencesPeking UniversityBeijing 100191China State Key Laboratory of Holistic Integrative Management of Gastrointestinal cancers Beijing Key Laboratory of Carcinogenesis and Translational ResearchGastrointestinal Cancer CenterPeking University Cancer Hospital&InstituteBeijing 100142China

Objective: Positive peritoneal lavege cytology(CY1) gastric cancer is featured by dismal prognosis, with high risks of peritoneal metastasis. However, there is a lack of evidence on pathogenic mechanism and signature of CY1and there is a continuous debate on CY1 therapy. Therefore, exploring the mechanism of CY1 is crucial for treatment strategies and targets for CY1 gastric cancer.Methods: In order to figure out specific driver genes and marker genes of CY1 gastric cancer, and ultimately offer clues for potential marker and risk assessment of CY1, 17 cytology-positive gastric cancer patients and 31matched cytology-negative gastric cancer patients were enrolled in this study. The enrollment criteria were based on the results of diagnostic laparoscopy staging and cytology inspection of exfoliated cells. Whole exome sequencing was then performed on tumor samples to evaluate genomic characterization of cytology-positive gastric cancer.Results: Least absolute shrinkage and selection operator(LASSO) algorithm identified 43 cytology-positive marker genes, while Mut Sig CV identified 42 cytology-positive specific driver genes. CD3G and CDKL2 were both driver and marker genes of CY1. Regarding mutational signatures, driver gene mutation and tumor subclone architecture, no significant differences were observed between CY1 and negative peritoneal lavege cytology(CY0).Conclusions: There might not be distinct differences between CY1 and CY0, and CY1 might represent the progression of CY0 gastric cancer rather than constituting an independent subtype. This genomic analysis will thus provide key molecular insights into CY1, which may have a direct effect on treatment recommendations for CY1and CY0 patients, and provides opportunities for genome-guided clinical trials and drug development.

关键词： Cytology gastric carcinoma peritoneal metastasis whole exome sequencing