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Polλ promotes microhomology-mediated end-joining (vol 30, pg 107, 2023)

NATURE STRUCTURAL & MOLECULAR BIOLOGY 2023年第7期30卷 1048-1048页

作者： Chandramouly, Gurushankar Jamsen, Joonas Borisonnik, Nikita Tyagi, Mrityunjay Calbert, Marissa L. Tredinnick, Taylor Ozdemir, Ahmet Y. Kent, Tatiana Demidova, Elena V. Arora, Sanjeevani Wilson, Samuel H. Pomerantz, Richard T. Department of Biochemistry and Molecular Biology Sidney Kimmel Cancer Center Thomas Jefferson University Philadelphia PA USA Department of Biochemistry and Molecular Biology University of Arkansas for Medical Sciences Little Rock AR USA Spark Therapeutics Philadelphia PA USA Cancer Prevention and Control Program Fox Chase Cancer Center Philadelphia PA USA Kazan Federal University Kazan Russian Federation Department of Radiation Oncology Fox Chase Cancer Center Philadelphia PA USA Genome Integrity and Structural Biology Laboratory National Institute of Environmental Health Sciences National Institutes of Health Research Triangle Park NC USA

The double-strand break (DSB) repair pathway called microhomology-mediated end-joining (MMEJ) is thought to be dependent on DNA polymerase theta (Polθ) and occur independently of nonhomologous end-joining (NHEJ) factors. An unresolved question is whether MMEJ is facilitated by a single Polθ-mediated end-joining pathway or consists of additional undiscovered pathways. We find that human X-family Polλ, which functions in NHEJ, additionally exhibits robust MMEJ activity like Polθ. Polλ promotes MMEJ in mammalian cells independently of essential NHEJ factors LIG4/XRCC4 and Polθ, which reveals a distinct Polλ-dependent MMEJ mechanism. X-ray crystallography employing in situ photo-induced DSB formation captured Polλ in the act of stabilizing a microhomology-mediated DNA synapse with incoming nucleotide at 2.0 Å resolution and reveals how Polλ performs replication across a DNA synapse joined by minimal base-pairing. Last, we find that Polλ is semisynthetic lethal with BRCA1 and BRCA2. Together, these studies indicate Polλ MMEJ as a distinct DSB repair mechanism.

关键词： DNA DNA damage and repair Nanocrystallography Non-homologous-end joining X-ray crystallography

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Associations of body mass index trajectories,weight change with mortality among the oldest old:do they differ from general older adults?

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Science Bulletin 2025年第7期70卷 1062-1065页

作者： Li Qi Chen Chen Jinhui Zhou Sixin Liu Jun Wang Yuan Wei Wenhui Shi Yang Li Tao Zhang Yuebin Lv Xiaoming Shi China CDC Key Laboratory of Environment and Population Health National Institute of Environmental HealthChinese Center for Disease Control and PreventionBeijing 100021China National Key Laboratory of Intelligent Tracking and Forecasting for Infectious Diseases National Institute of Environmental HealthChinese Center for Disease Control and PreventionBeijing 100021China Beijing Center for Disease Control and Prevention Beijing 100000China National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital Chinese Academy of Medical Sciences and Peking Union Medical CollegeBeijing 100005China Department of Epidemiology School of Public HealthSouthern Medical UniversityGuangzhou 510515China Department of Elderly Health Management Shenzhen Center for Chronic Disease ControlShenzhen 518020China Center for Global Health School of Public HealthNanjing Medical UniversityNanjing 211166China Department of Epidemiology and Biostatistics School of Public HealthTianjin Medical UniversityTianjin 300070China

Body mass index(BMI)is widely recognized as a reasonably good measure of general adiposity and an important predictor of mortality risk[1].Meta-analyses of cohort studies[2]have demonstrated a“U”or“J”-shaped correlation,wherein both low and high BMI values are associated with an increased risk of *** association between BMI and mortality may vary depending on *** young and middle-aged adults,obesity is associated with higher mortality risk[3];but for older adults aged over65 years,“obesity paradox”is more likely to be observed[4].One recent study observed that compared with normal weight in the oldest old(aged≥80 years),overweight and obese were associated with significantly descend risk of non-cardiovascular disease(nonCVD)and all-cause mortality,but not cardiovascular disease(CVD)mortality[5].

关键词： obesity paradox body mass index bmi body mass index mortality weight change cohort studies oldest old

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Genome-wide enhancer RNA profiling adds molecular links between genetic variation and human cancers

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Military Medical Research 2025年第4期12卷 488-511页

作者： Yi-Min Cai Ze-Qun Lu Bin Li Jin-Yu Huang Ming Zhang Can Chen Lin-Yun Fan Qian-Ying Ma Chun-Yi He Shuo-Ni Chen Yuan Jiang Yan-Min Li Cai-Bo Ning Fu-Wei Zhang Wen-Zhuo Wang Yi-Zhuo Liu Heng Zhang Meng Jin Xiao-Yang Wang Jin-Xin Han Zhen Xiong Ming Cai Chao-Qun Huang Xiao-Jun Yang Xu Zhu Ying Zhu Xiao-Ping Miao Shao-Kai Zhang Yong-Chang Wei Jian-Bo Tian Department of Epidemiology and Biostatistics School of Public HealthResearch Center of Public HealthRenmin Hospital of Wuhan UniversityTai-Kang Center for Life and Medical SciencesWuhan UniversityWuhan 430071China Department of Gastrointestinal Oncology Zhongnan Hospital of Wuhan UniversityWuhan UniversityWuhan 430071China Department of Cancer Epidemiology Henan Engineering Research Center of Cancer Prevention and ControlHenan International Joint Laboratory of Cancer Preventionthe Affiliated Cancer Hospital of Zhengzhou University&Henan Cancer HospitalZhengzhou 450008China Department of Oncology Tongji HospitalTongji Medical CollegeHuazhong University of Science and TechnologyWuhan 430030China Department of Gastrointestinal Surgery Union HospitalTongji Medical CollegeHuazhong University of Science and TechnologyWuhan 430022China Department of Gastrointestinal Surgery Zhongnan Hospital of Wuhan UniversityWuhan UniversityWuhan 430071China Depar tment of Gastrointestinal Surgery Renmin Hospital of Wuhan UniversityWuhan 430060China Department of Epidemiology and Biostatistics School of Public HealthTongji Medical CollegeHuazhong University of Science and TechnologyWuhan 430022China Jiangsu Collaborative Innovation Center for Cancer Personalized Medicine Nanjing Medical UniversityNanjing 211166China Department of Gastrointestinal Oncology Hubei Cancer Clinical Study CenterZhongnan Hospital of Wuhan UniversityWuhan 430071China

Background:Dysregulation of enhancer transcription occurs in multiple *** RNAs(eRNAs)are transcribed products from enhancers that play critical roles in transcriptional *** the genetic basis of eRNA expression may elucidate the molecular mechanisms underlying ***:Initially,a comprehensive analysis of eRNA quantitative trait loci(eRNAQTLs)was performed in The cancer Genome Atlas(TCGA),and functional features were characterized using multi-omics *** establish the first eRNAQTL profiles for colorectal cancer(CRC)in China,epigenomic data were used to define active enhancers,which were subsequently integrated with transcription and genotyping data from 154 paired CRC ***,largescale case-control studies(34,585 cases and 69,544 controls)were conducted along with multipronged experiments to investigate the potential mechanisms by which candidate eRNAQTLs affect CRC ***:A total of 300,112 eRNAQTLs were identified across 30 different cancer types,which exert their influence on eRNA transcription by modulating chromatin status,binding affinity to transcription factors and RNA-binding *** eRNAQTLs were found to be significantly enriched in cancer risk loci,explaining a substantial proportion of cancer ***,tumor-specific eRNAQTLs exhibited high responsiveness to the development of ***,the target genes of these eRNAs were associated with dysregulated signaling pathways and immune cell infiltration in cancer,highlighting their potential as therapeutic ***,multiple ethnic population studies have confirmed that an eRNAQTL rs3094296-T variant decreases the risk of CRC in populations from China(OR=0.91,95%CI 0.88–0.95,P=2.92×10^(-7))and Europe(OR=0.92,95%CI 0.88–0.95,P=4.61×10^(-6)).Mechanistically,rs3094296 had an allele-specific effect on the transcription of the eRNA ENSR00000155786,which functioned as a transcriptional activator promoting the expression

关键词： Enhancer RNA(eRNA) eRNA quantitative trait loci(eRNAQTLs) Genome-wide association study(GWAS) ENSR00000155786 SENP7

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Transformer-based representation learning and multiple-instance learning for cancer diagnosis exclusively from raw sequencing fragments of bisulfite-treated plasma cell-free DNA

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Molecular oncology 2024年第11期18卷 2024 Oct 8页

作者： Jilei Liu Hongru Shen Yichen Yang Meng Yang Qiang Zhang Kexin Chen Xiangchun Li Tianjin Cancer Institute Tianjin's Clinical Research Center for Cancer National Clinical Research Center for Cancer Key Laboratory of Cancer Prevention and Therapy Tianjin Medical University Cancer Institute and Hospital Tianjin Medical University China. Department of Maxillofacial and Otorhinolaryngology Oncology Tianjin's Clinical Research Center for Cancer Tianjin Medical University Cancer Institute and Hospital Tianjin Medical University China. Department of Epidemiology and Biostatistics Key Laboratory of Molecular Cancer Epidemiology of Tianjin Tianjin's Clinical Research Center for Cancer Key Laboratory of Prevention and Control of Major Diseases in the Population Ministry of Education National Clinical Research Center for Cancer Key Laboratory of Cancer Prevention and Therapy Tianjin Medical University Cancer Institute and Hospital Tianjin Medical University China.

Early cancer diagnosis from bisulfite-treated cell-free DNA (cfDNA) fragments requires tedious data analytical procedures. Here, we present a deep-learning-based approach for early cancer interception and diagnosis (DECIDIA) that can achieve accurate cancer diagnosis exclusively from bisulfite-treated cfDNA sequencing fragments. DECIDIA relies on transformer-based representation learning of DNA fragments and weakly supervised multiple-instance learning for classification. We systematically evaluate the performance of DECIDIA for cancer diagnosis and cancer type prediction on a curated dataset of 5389 samples that consist of colorectal cancer (CRC; n = 1574), hepatocellular cell carcinoma (HCC; n = 1181), lung cancer (n = 654), and non-cancer control (n = 1980). DECIDIA achieved an area under the receiver operating curve (AUROC) of 0.980 (95% CI, 0.976-0.984) in 10-fold cross-validation settings on the CRC dataset by differentiating cancer patients from cancer-free controls, outperforming benchmarked methods that are based on methylation intensities. Noticeably, DECIDIA achieved an AUROC of 0.910 (95% CI, 0.896-0.924) on the externally independent HCC testing set in distinguishing HCC patients from cancer-free controls, although there was no HCC data used in model development. In the settings of cancer-type classification, we observed that DECIDIA achieved a micro-average AUROC of 0.963 (95% CI, 0.960-0.966) and an overall accuracy of 82.8% (95% CI, 81.8-83.9). In addition, we distilled four sequence signatures from the raw sequencing reads that exhibited differential patterns in cancer versus control and among different cancer types. Our approach represents a new paradigm towards eliminating the tedious data analytical procedures for liquid biopsy that uses bisulfite-treated cfDNA methylome.

关键词： cell‐free DNA early cancer diagnosis weakly supervised learning

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Outcome measures of phase III anticancer drug trials in China

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Chinese Medical Journal 2023年第8期136卷 992-994页

作者： Lanwei Guo Huiyao Huang Yue Yu Jun Wang Le Wang Shuhang Wang Dawei Wu Yuan Fang Ning Jiang Shaokai Zhang Yu Tang Ning Li Department of Cancer Epidemiology and Prevention Henan Engineering Research Center of Cancer Prevention and ControlHenan International Joint Laboratory of Cancer PreventionThe Affiliated Cancer Hospital of Zhengzhou University&Henan Cancer HospitalZhengzhouHenan 450008China Clinical Trials Center National Cancer Center/National Clinical Research Center for Cancer/Cancer HospitalChinese Academy of Medical Sciences and Peking Union Medical CollegeBeijing 100021China National Center for Drug Evaluation National Medical Products AdministrationBeijing 100022China Department of Cancer Prevention The Cancer Hospital of the University of Chinese Academy of Sciences(Zhejiang Cancer Hospital)HangzhouZhejiang 310022China

To the Editor:Phase III clinical trials have been used to provide evidence in support of the approval of most new agents in the treatment of cancer.[1]The selection of the primary endpoint is critical to the outcome of phase III clinical trials and the launch of the cancer *** the present study,we performed a crosssectional study to describe the endpoint information and analyze the trends over time in the research and development of cancer drugs tested in phase III clinical trials in China.

关键词： clinical drug drugs

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Cardiovascular toxicities associated with novel cellular immune therapies

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Blood Advances 2024年第24期8卷 6282-6296页

作者： Munir, Malak Sayed, Ahmed Addison, Daniel Epperla, Narendranath Department of Medicine Ain Shams University Faculty of Medicine Cairo Egypt Department of Cardiology Houston Methodist DeBakey Heart & Vascular Center Houston TX United States Division of Cancer Prevention and Control Department of Internal Medicine College of Medicine The Ohio State University Columbus OH United States Division of Epidemiology College of Public Health The Ohio State University Columbus OH United States Division of Hematology and Hematologic Malignancies Huntsman Cancer Institute The University of Utah Salt Lake City UT United States

Over the past decade, T-cell–directed therapies, including chimeric antigen receptor T-cell (CAR-T) and bispecific T-cell engager (BTE) therapies, have reshaped the treatment of an expanding number of hematologic malignancies, whereas tumor-infiltrating lymphocytes, a recently approved cellular therapy, targets solid tumor malignancies. Emerging data suggest that these therapies may be associated with a high incidence of serious cardiovascular toxicities, including atrial fibrillation, heart failure, ventricular arrhythmias, and other cardiovascular toxicities. The development of these events is a major limitation to long-term survival after these treatments. This review examines the current state of evidence, including reported incidence rates, risk factors, mechanisms, and management strategies of cardiovascular toxicities after treatment with these novel therapies. We specifically focus on CAR-T and BTE therapies and their relation to arrhythmia, heart failure, myocarditis, bleeding, and other major cardiovascular events. Beyond the relationship between cytokine release syndrome and cardiotoxicity, we describe other potential mechanisms and highlight key unanswered questions and future directions of research. © 2024 by The American Society of Hematology.

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Challenges oncologists face when caring for hispanics living in puerto rico with colorectal cancer and multiple chronic conditions

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BMC cancer 2025年第1期25卷 1-12页

作者： Castañeda-Avila, Maira A. Latoni-Guillermety, Daniela Sabatino, Meagan Ortiz-Ortiz, Karen J. Lapane, Kate L. Division of Epidemiology Department of Population and Quantitative Health Sciences University of Massachusetts Chan Medical School 55 Lake Ave North Worcester 01655 MA United States Duquesne University Pittsburgh PA United States Cancer Control and Population Sciences Program The University of Puerto Rico Comprehensive Cancer Center San Juan Puerto Rico Department of Health Services Administration Graduate School of Public Health Medical Sciences Campus University of Puerto Rico San Juan Puerto Rico

Background: Colorectal cancer (CRC) is the leading cause of cancer-related death in Puerto Rico, posing significant challenges for patients with multiple chronic conditions (MCC). This qualitative study aimed to explore oncologists’ perspectives regarding the care of patients with CRC and MCC in Puerto Rico. Methods: We conducted semi-structured interviews in Spanish with nine oncologists providing care for patients with CRC in Puerto Rico. We reached data saturation. We performed thematic analysis to identify key patterns and themes within the interview data. The coding scheme evolved through team discussions, with discrepancies addressed for consistency. Quotes were translated from Spanish to English. Results: Five key themes were: (1) social determinants of health, (2) diagnosis pathways, (3) factors influencing treatment decisions, (4) survivorship and end-of-life care, and (5) care coordination and communication. Oncologists treating patients with CRC and MCC identified the lack of a social support network as a notable care coordination challenge. The health insurance system’s pre-authorization requirements for procedures and treatments further complicated care delivery, particularly for older adults, who faced challenges navigating these administrative processes without sufficient support. A lack of transportation and local specialized care services was a noted barrier to comprehensive patient care. Communication between patients, physician and caregivers proved challenging when multiple physicians and procedures were involved with patient’s care, often requiring patients to schedule appointments with different specialists themselves. Inter-provider communication primarily relied on phone calls or notes sent with the patient. Conclusions: Oncologists caring for Hispanic older adults with CRC and MCC encounter complex challenges influenced by unmet social needs and the presence of comorbidities. Tailored approaches, culturally sensitive care, and improved coord

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Japanese Encephalitis in China in the Period of 1950–2018:From Discovery to control

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Biomedical and Environmental Sciences 2021年第3期34卷 175-183页

作者： CHEN Xiao Jing WANG Huan Yu LI Xiao Long GAO Xiao Yan LI Ming Hua FU Shi Hong HE Ying LI Fan YIN Qi Kai XU Song Tao WU Dan LI Yi Xing YIN Zun Dong YANG Guang LIANG Guo Dong Department of Arbovirus NHC Key Laboratory of BiosafetyNational Institute for Viral Disease Control and PreventionChinese Center for Disease Control and PreventionBeijing 102206China State Key Laboratory for Infectious Disease Prevention and Control Chinese Center for Disease Control and PreventionBeijing 102206China Department of Epidemiology School of MedicineJinan UniversityGuangzhou 510632GuangdongChina Department of Environmental and Global Health College of Public Health and Health ProfessionsUniversity of FloridaGainesvilleUSA Department of Science and Technology Beijing Tiantan HospitalCapital Medical UniversityBeijing 100070China Department of Microbiology University of PennsylvaniaPhiladelphiaPA 19104USA National Immunization Program Chinese Center for Disease Control and PreventionBeijing 102206China

Japanese encephalitis(JE)was first discovered in Japan in 1871;in 1924,a major outbreak occurred,with 6,000 JE cases reported and a mortality rate of approximately 60%[1,2].Later studies showed that JE is caused by th... 详细信息

关键词： encephalitis Japanese JEV

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Immunogenicity of Short-Course,High-Dose Hepatitis B Vaccination in Patients with Chronic Kidney Disease-Shanxi Province,China,2019-2020

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China CDC weekly 2024年第50期6卷 1331-1336,I0002-I0005页

作者： Linying Gao Xufeng Cui Xinyuan Mo Zhaoyue Men Xiuyang Xu Tian Yao Jianmin Wang Hongting Liu Hongping Guo Guowei Chai Liming Liu Fuzhen Wang Xiaofeng Liang Suping Wang Yongliang Feng School of Public Health Shanxi Medical UniversityTaiyuan CityShanxi ProvinceChina Key Laboratory of Coal Environmental Pathogenicity and Prevention(Shanxi Medical University) Ministry of EducationTaiyuan CityShanxi ProvinceChina Center of Clinical Epidemiology and Evidence Based Medicine Shanxi Medical UniversityTaiyuan CityShanxi ProvinceChina First Hospital/First Clinical Medical College of Shanxi Medical University Taiyuan CityShanxi ProvinceChina Department of Nephrology Linfen Central HospitalLinfen CityShanxi ProvinceChina Department of Nephrology Yuncheng Central HospitalYuncheng CityShanxi ProvinceChina Department of Nephrology Linfen People’s HospitalLinfen CityShanxi ProvinceChina Department of Nephrology Houma People’s HospitalHouma CityShanxi ProvinceChina National Immunization Program Chinese Center for Disease Control and PreventionBeijingChina Institute of Vaccine Industry Jinan UniversityGuangzhou CityGuangdong ProvinceChina Institute of Disease Control and Prevention Jinan UniversityGuangzhou CityGuangdong ProvinceChina Chinese Preventive Medicine Association BeijingChina

What is already known about this topic?As one of the populations at high risk of hepatitis B virus(HBV)infection,patients with chronic kidney disease(CKD)require rapid and effective development of hepatitis B surface antibodies(anti-HBs).What is added by this report?The short-course,high-dose regimen of hepatitis B vaccination rapidly induced comparable immunological responses to the routine regimen,achieving a seroconversion rate of 88.5%,a high-response rate of 64.1%,and anti-HBs geometric mean concentrations of 824.1 mIU/*** are the implications for public health practice?The short-course,high-dose regimen represents an effective rapid immunization strategy for CKD patients,particularly when administered prior to immunosuppressive *** study provides compelling evidence for optimizing immunization protocols in the CKD population.

关键词： routine Kidney Shanxi

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Guidelines for cervical cancer screening in China

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Gynecology and Obstetrics Clinical Medicine 2023年第4期3卷 189-194页

作者： Mingzhu Li Lihui Wei Long Sui Ding Ma Beihua Kong Xiaohua Wu Peng Wu Youlin Qiao Fanghui Zhao Linhong Wang Chinese Society for Colposcopy and Cervical Pathology of China Healthy Birth Science Association(CSCCP) China Chinese Society of Gynecologic Oncology Chinese Medical AssociationChina Chinese Gynecological Cancer Society(CGCS) China Branch of Women's Health Medicine of China International Exchange and Promotive Association for Medical and Health Care China National Cervical Cancer Prevention Consortium of Cancer Foundation of China China Branch of Cancer Prevention and Control Chinese Preventive Medicine AssociationChina Chinese Association for Maternal and Child Health Studies China Department of Obstetrics and Gynecology Peking University People's HospitalBeijingChina Diagnosis and Treatment Center of Cervical Disease Obstetrics&Gynecology Hospital of Fudan UniversityShanghaiChina Department of Obstetrics and Gynecology Tongji HospitalTongji Medical College of HUSTWuhanChina Department of Obstetrics and Gynecology Qilu Hospital of Shandong UniversityJinanChina Department of Gynecological Oncology Fudan University Shanghai Cancer CenterShanghaiChina Department of Cancer Epidemiology National Cancer Center/National Clinical Research Center for Cancer/Cancer HospitalChinese Academy of Medical Sciences and Peking Union Medical CollegeBeijingChina National Center for Chronic and Noncommunicable Disease Control and Prevention Chinese Center for Disease Control and PreventionBeijingChina Center for Global Health School of Population Medicine and Public HealthChinese Academy of Medical Sciences&Peking Union Medical CollegeBeijingChina

In response to the incidence of cervical intraepithelial neoplasia and cervical cancer in China and global screening strategies,a collaborative effort was undertaken by seven Chinese medical associations to develop this guideline for cervical cancer *** guideline recommends high-risk human papillomavirus(hr-HPV)testing as the preferred method for primary screening,which should have been approved by authoritative institutions and clinically validated for primary *** areas without access to HPV testing,cytology can be used as an ***,it is recommended to replace cytology with HPV-based screening as conditions ***(HPV testing in combination with cytology)is recommended for areas with sufficient medical resources,opportunistic screening populations,and partial special *** guideline recommends that individuals with a cervix initiate cervical cancer screening at the age 25 years and undergo HPV testing alone or cotesting every five years,or cytology alone every three *** over the age of 65 who have had documented adequate negative prior screening in the past may terminate *** screening programs are proposed for different special *** development of these guidelines is an important step in the effort to eliminate cervical cancer in China.

关键词： Cervical cancer Primary screening Cervical cytology HPV testing Guideline

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