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Exploring the potential of extrachromosomal DNA as a novel oncogenic driver

science China Life sciences 2025年第1期68卷 144-157页

作者： Huanbo Zhu Longtao Huangfu Junbing Chen Jiafu Ji Xiaofang Xing Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education/Beijing) Division of Gastrointestinal Cancer Translational Research LaboratoryPeking University Cancer Hospital & Institute Department of Gastrointestinal Cancer Center Peking University Cancer Hospital & Institute Department of Liver surgery & Transplantation Liver Cancer InstituteZhongshan HospitalFudan University Key Laboratory of Carcinogenesis and Cancer Invasion Ministry of Education state Key Laboratory of Holistic Integrative Management of Gastrointestinal Cancers Beijing Key Laboratory of Carcinogenesis and Translational ResearchDivision of Gastrointestinal Cancer Translational Research LaboratoryPeking University Cancer Hospital & Institute

Extrachromosomal DNA(ecDNA) is a form of circular DNA mostly found in tumor cells. Unlike the typical chromosomal DNA, ecDNA is circular, self-replicating, and carries complete or partial gene fragments. Although ecDNA occurrence remains a rare event in cancer, recent studies have shown that oncogene amplification on ecDNA is widespread throughout many types of cancer, implying that ecDNA plays a central role in accelerating tumor evolution. ecDNA has also been associated with increased tumor mutation burden, chromosomal instability, and even tumor microenvironment remodeling. ecDNA may be crucial in influencing tumor heterogeneity, drug sensitivity,oncogenic senescence, and tumor immunogenicity, leading to a worsening prognosis for tumor patients. In this way, several clinical trials have been conducted to investigate the importance of ecDNA in clinical treatment. In this review, we summarize the biogenesis, characteristics, and current research methods of ecDNA, discuss the vital role of ecDNA-caused tumor heterogeneity in cancers, and highlight the potential role of ecDNA in cancer therapy.

关键词： extrachromosomal DNA cancer therapy tumor heterogeneity drug resistance tumor evolution

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Advances in genotypic antimicrobialresistance testing: a comprehensive review

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science China Life sciences 2025年第1期68卷 130-143页

作者： Boheng Duan Xianjun Zeng Junping Peng Huan Kui College of Nanchang university Department of Imaging The Second Affiliated Hospital of Nanchang University NHC Key Laboratory of systems Biology of Pathogens National Institute of Pathogen BiologyChinese Academy of Medical Sciences & Peking Union Medical College Key Laboratory of Respiratory Disease Pathogenomics Chinese Academy of Medical Sciences & Peking Union Medical College Key Laboratory of Pathogen Infection Prevention and Control (Ministry of Education) State Key Laboratory of Respiratory Health and MultimorbidityNational Institute of Pathogen BiologyChinese Academy of Medical Sciences & Peking Union Medical College

Antimicrobial resistance(AMR) represents a substantial threat to global public health, complicating the treatment of common infections and leading to prolonged illness and escalated healthcare expenses. To effectively combat AMR, timely and accurate detection is crucial for AMR surveillance and individual-based therapy. Phenotypic antibiotic resistance testing(AsT) has long been considered the gold standard in clinical applications, serving as the foundation for clinical AMR diagnosis and optimized therapy. It has significantly contributed to ensuring patients′ health and the development of novel antimicrobials. Despite advancements in automated culture-based AsT technologies,inherent limitations impede the widespread use of phenotypic AsT in AMR surveillance. Genotypic AsT technologies offer a promising alternative option, exhibiting advantages of rapidity, high sensitivity, and specificity. With the continuous advancement and expanding applications of genotypic AsT technologies, such as microfluidics, mass spectrometry, and high-resolution melting curve analysis, new vigor has been injected into the development and clinical implementation of genotypic AsT technologies. In this narrative review, we discuss the principles, applications, and advancements of emerging genotypic AsT methods in clinical settings. The comprehensive review aims to highlight the significant scientific potential of emerging genotypic AsT technologies in clinical AMR diagnosis, providing insights to enhance existing methods and explore novel approaches.

关键词： antimicrobial resistance (AMR) genotypic antibiotic resistance testing (AsT) AsT technologies review

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TRMT6 and TRMT61A facilitated acute pancreatitis severity via regulation of neutrophil function

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science China Life sciences 2025年

作者： Yuan Dong Li su sin Man Lam Cen Yan Yalan Deng Guotao Lu Jinkui Yang Guanghou shui Yingmei Feng Beijing institute of hepatology Beijing Youan HospitalCapital Medical University Department of science and Development Beijing Youan HospitalCapital Medical University Laboratory for Clinical Medicine Capital Medical University Neuroscience Research institute Peking University Center of Medical and Health AnalysisPeking University state Key Laboratory of Molecular Developmental Biology Institute of Genetics and Developmental BiologyChinese Academy of Sciences Pancreatic Center Department of GastroenterologyAffiliated Hospital of Yangzhou UniversityYangzhou University Beijing Key Laboratory of Diabetes Research and Care Department of EndocrinologyBeijing Tongren HospitalCapital Medical University

Dear Editor,Type 2 diabetes mellitus (T2DM) has been identified as a risk factor for increased severity in acute pancreatitis (AP)(Mikóet al,2018).However,to date,no studies have simultaneously included healthy individuals,T2DM patients,and AP patients to investigate which diabetes-associated metabolites are linked to AP severity.

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single-cell omics: experimental workflow, data analyses and applications

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science China Life sciences 2025年第1期68卷 5-102页

作者： Fengying sun Haoyan Li Dongqing sun shaliu Fu Lei Gu Xin shao Qinqin Wang Xin Dong Bin Duan Feiyang Xing Jun Wu Minmin Xiao Fangqing Zhao Jing-Dong J.Han Qi Liu Xiaohui Fan Chen Li Chenfei Wang Tieliu shi Department of Clinical Laboratory the Affiliated Wuhu Hospital of East China Normal University (The Second People's Hospital of Wuhu City) Pharmaceutical Informatics institute College of Pharmaceutical SciencesZhejiang University Key Laboratory of spine and spinal Cord Injury Repair and Regeneration (Tongji university) Ministry of EducationOrthopaedic DepartmentTongji HospitalBioinformatics DepartmentSchool of Life Sciences and TechnologyTongji University Frontier science Center for stem Cells School of Life Sciences and TechnologyTongji University Translational Medical Center for stem Cell Therapy and institute for Regenerative Medicine Shanghai East HospitalBioinformatics DepartmentSchool of Life Sciences and TechnologyTongji University Research institute of Intelligent Computing Zhejiang Lab shanghai Research institute for Intelligent Autonomous systems Center for single-cell Omics School of Public HealthShanghai Jiao Tong University School of Medicine National Key Laboratory of Chinese Medicine Modernization Innovation Center of Yangtze River DeltaZhejiang University Center for Bioinformatics and Computational Biology Shanghai Key Laboratory of Regulatory Biologythe Institute of Biomedical Sciences and School of Life SciencesEast China Normal University Beijing institutes of Life science Chinese Academy of Sciences peking-Tsinghua Center for Life sciences Academy for Advanced Interdisciplinary StudiesCenter for Quantitative Biology (CQB)Peking University Zhejiang Key Laboratory of Precision Diagnosis and Therapy for Major Gynecological Diseases Women's HospitalZhejiang University School of Medicine Key Laboratory of Advanced Theory and Application in statistics and Data science-MOE School of StatisticsEast China Normal University

Cells are the fundamental units of biological systems and exhibit unique development trajectories and molecular features. Our exploration of how the genomes orchestrate the formation and maintenance of each cell, and control the cellular phenotypes of various organismsis, is both captivating and intricate. since the inception of the first single-cell RNA technology, technologies related to single-cell sequencing have experienced rapid advancements in recent years. These technologies have expanded horizontally to include single-cell genome, epigenome,proteome, and metabolome, while vertically, they have progressed to integrate multiple omics data and incorporate additional information such as spatial sc RNA-seq and CRIsPR screening. single-cell omics represent a groundbreaking advancement in the biomedical field,offering profound insights into the understanding of complex diseases, including cancers. Here, we comprehensively summarize recent advances in single-cell omics technologies, with a specific focus on the methodology section. This overview aims to guide researchers in selecting appropriate methods for single-cell sequencing and related data analysis.

关键词： single-cell sequencing genome epigenome proteomics metabolomics multimodal spatial transcriptomics CRIsPR screening

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Gut microbiota-astrocyte axis: new insights into age-related cognitive decline

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Neural Regeneration Research 2025年第4期20卷 990-1008页

作者： Lan Zhang Jingge Wei Xilei Liu Dai Li Xiaoqi Pang Fanglian Chen Hailong Cao Ping Lei Haihe Laboratory of Cell Ecosystem Department of GeriatricsTianjin Medical University General HospitalTianjinChina Tianjin Geriatrics institute Tianjin Medical University General HospitalTianjinChina Department of Gastroenterology and hepatology Tianjin Medical University General HospitalNational Key Clinical SpecialtyTianjin Institute of Digestive DiseasesTianjin Key Laboratory of Digestive DiseasesTianjinChina Department of Urology Tianjin Medical University General HospitalTianjinChina Tianjin Neurological Institution Tianjin Medical University General HospitalTianjinChina

With the rapidly aging human population,age-related cognitive decline and dementia are becoming increasingly prevalent *** is considered the main risk factor for cognitive decline and acts through alterations in the composition of the gut microbiota,microbial metabolites,and the functions of *** microbiota–gut–brain axis has been the focus of multiple studies and is closely associated with cognitive *** article provides a comprehensive review of the specific changes that occur in the composition of the gut microbiota and microbial metabolites in older individuals and discusses how the aging of astrocytes and reactive astrocytosis are closely related to age-related cognitive decline and neurodegenerative *** article also summarizes the gut microbiota components that affect astrocyte function,mainly through the vagus nerve,immune responses,circadian rhythms,and microbial ***,this article summarizes the mechanism by which the gut microbiota–astrocyte axis plays a role in Alzheimer’s and Parkinson’s *** findings have revealed the critical role of the microbiota–astrocyte axis in age-related cognitive decline,aiding in a deeper understanding of potential gut microbiome-based adjuvant therapy strategies for this condition.

关键词： age aging Alzheimer’s disease astrocytes cognitive decline dementia gut microbiota gut–brain axis microbial metabolites neuroinflammation Parkinson’s disease

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Can patients with mild non-neoplastic lesions diagnosed at baseline screening be safely exempt from surveillance: evidence from multicenter community-based cohorts

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science China Life sciences 2025年第1期68卷 263-271页

作者： siyi He Zhiyi Zhang Guohui song Zhenhai Wang Chunyun Dai shipeng Yan Kun Jiang Bingbing song He Li Maomao Cao Dianqin sun Fan Yang Xinxin Yan shaoli Zhang Yi Teng Qianru Li Changfa Xia Wanqing Chen Office of Cancer screening National Cancer Center/National Clinical Research Center for Cancer/Cancer HospitalChinese Academy of Medical Sciences and Peking Union Medical College Department of Gastroenterology Gansu Wuwei Tumor Hospital Cixian Cancer institute Linzhou Cancer hospital Center for Disease Control and Prevention of sheyang County Department of Cancer Prevention and Control Hunan Cancer Hospital and The Affiliated Cancer Hospital of Xiangya School of MedicineCentral South University Luoshan Center for Disease Control and Prevention Office for Cancer Control and Research Affiliated Cancer Hospital of Harbin Medical University

surveillance recommendations for gastric cancer（GC） in current guidelines focused on advanced precancerous lesions and were based on precise diagnosis of severity/extent of baseline lesions. We aimed to develop a less endoscopy-related equipment-dependent risk-stratification tool, and assessed whether mild-precursor-lesion patients can be safely exempt from surveillance. In the multicenter communitybased cohort, 75,051 participants receiving baseline endoscopy were enrolled during 2015–2017 and followed-up until 2021. Cumulative incidence rates（CIRs） of GC for precancerous-conditions were calculated by Kaplan-Meier method and compared by Log-rank tests. Mixedeffects Cox regression models were used to detect potential factors for progression towards GC. A risk score was calculated as counts of selected factors. An independent cohort, including 26,586 participants was used for external validation. During a median follow-up of 6.25 years, CIRs of GC were 0.302%, 0.436%, and 4.756% for normal group, non-neoplastic（atrophic gastritis/intestinal metaplasia） and neoplastic lesions（low-grade/high-grade dysplasia）, respectively(Ptrends, including male, ≥60 years, smoking, and limited vegetable consumption, were selected for risk-stratification. High-risk patients（≥3 risk factors） with non-neoplastic lesions showed higher GC risks（adjusted HR=7.73, 95%CI: 4.29–13.92）, and their four-year CIR reached the one-year CIR of neoplastic lesions. Further categorizing non-neoplastic lesions by histological grade, both patients with moderate-to-severe lesions（aHR=3.07, 95%CI: 1.67–5.64） and high-risk patients with mild lesions（aHR=7.29, 95%CI: 3.58–14.86） showed higher risks. Consistent trends were observed in validation cohort. High-risk mild-precursor-lesion patients should receive surveillance within 3–5 years after baseline screening. Our study provides evidence on supplementing current guideline recommendations.

关键词： stomach neoplasms precancerous conditions cancer screening cumulative incidence risk stratification

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Antithetical impacts of deleterious LRP1B mutations in non-squamous and squamous NsCLCs on predicting benefits from immune checkpoint inhibitor alone or with chemotherapy over chemotherapy alone: retrospective analyses of the POPLAR/OAK and CHOICE-01 trial

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science China Life sciences 2025年第1期68卷 249-262页

作者： Jinliang Wang Wenyong Zhou Yu Xu Jianchun Duan Qiaoxia Zhou Guoqiang Wang Leo Li Chunwei Xu Wenxian Wang shangli Cai Zhijie Wang Jie Wang Department of Oncology The Fifth Medical Center of Chinese PLA General Hospital Department of Thoracic surgery Shanghai Chest HospitalSchool of MedicineShanghai Jiao Tong University Burning Rock Biotech CAMs Key Laboratory of Translational Research on Lung Cancer State Key Laboratory of Molecular OncologyDepartment of Medical OncologyNational Cancer Center/National Clinical Research Center for ancer/Cancer HospitalChinese Academy of Medical Sciences and Peking Union Medical College institute of Basic Medicine and Cancer (IBMC) Chinese Academy of Sciences Department of Clinical Trial The Cancer Hospital of the University of Chinese Academy of Sciences (Zhejiang Cancer Hospital)

In non-small cell lung cancers,the non-squamous and squamous subtypes（nsqNsCLC and sqNsCLC） exhibit disparities in pathophysiology,tumor immunology,and potential genomic correlates affecting responses to immune checkpoint inhibitor（ICI）-based *** our inhouse training cohort（n=85）,the presence of the LRP1B deleterious mutation（LRP1B-del） was associated with longer and shorter progression-free survival（PFs） on ICIs alone in nsqNsCLCs and sqNsCLCs,respectively(Pinteraction=0.008).These results were validated using a larger public ICI cohort(n=208,Pinteractionscence staining revealed an association between LRP1B-del and increased and decreased numbers of tumor-infiltrating CD8+T cells in nsqNsCLCs（P=0.040） and sqNsCLCs（P=0.014）,*** the POPLAR/OAK cohort,nsqNsCLCs with LRP1B-del demonstrated improved PFs benefits from atezolizumab over docetaxel(hazard ratio（HR）=0.70,P=0.046),whereas this benefit was negligible in those without LRP1B-del（HR=1.05,P=0.64）.Conversely,sqNsCLCs without LRP1B-del benefited more from atezolizumab（HR=0.60,P=0.002） than those with LRP1B-del（HR=1.30,P=0.31）.Consistent results were observed in the in-house CHOICE-01 cohort,in which nsqNsCLCs with LRP1B-del and sqNsCLCs without LRP1B-del benefited more from toripalimab plus chemotherapy than from chemotherapy alone(Pinteraction=0.008).This multi-cohort study delineates the antithetical impacts of LRP1B-del in nsqNsCLCs and sqNsCLCs on predicting the benefits from ICI alone or with chemotherapy over chemotherapy *** findings highlight the distinct clinical utility of LRP1B-del in guiding treatment choices for nsqNsCLCs and sqNsCLCs,emphasizing the necessity for a detailed analysis based on pathological subtypes when investigating biomarkers for cancer therapeutics.

关键词： non-squamous NsCLC squamous NsCLC LRP1B deleterious mutations predictive biomarker immune checkpoint inhibitor

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α-2-Hs-glycoprotein is a potential marker predicting hepatitis B e antigen seroconversion in patients with chronic hepatitis B during treatment with pegylated interferon alfa-2b

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science China(Life sciences) 2011年第1期54卷 39-47页

作者： MA Hui WANG JiangHua GUO Fang WEI Lai peking university people's hospital Peking University Hepatology Institute Beijing 100044 China

The efficacy of interferon (IFN) is limited in about 1/3 of patients with chronic hepatitis B (CHB). We used two-dimensional electrophoresis (2-DE)-based proteomic strategies to identify potential serum markers predicting hepatitis B e antigen (HBeAg) seroconversion in these patients during IFN therapy. Two groups of patients were enrolled: training and validation. In the training group, 2-DE experiments and subsequent identification of altered levels of proteins showed that α-2-Hs-glycoprotein, leucine-rich α-2-glycoprotein, and haptoglobin were significantly upregulated as compared with baseline levels in the HBeAg seroconversion group, whereas apolipoprotein C-III precursor, leucine-rich α-2-glycoprotein, and α-albumin were downregulated in the non-seroconversion group. For patients with HBeAg seroconversion in the training group, Western blot analyses showed that α-2-Hs-glycoprotein levels in 75% of patients were significantly upregulated at the end of the treatment as compared with baseline levels. subsequent experiments in the validation group showed that α-2-Hs-glycoprotein levels were significantly increased at week 4 in 83.33% of patients in the HBeAg seroconversion group. Dynamic changes in the serum level of α-2-Hs-glycoprotein may be a potential early marker for predicting HBeAg seroconversion during IFN treatment for CHB.

关键词： α-2-Hs-glycoprotein pegylated interferon alfa-2b chronic hepatitis B

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Novel approaches towards conquering hepatitis B virus infection

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World Journal of Gastroenterology 2007年第6期13卷 830-836页

作者： Guo-Yi Wu Hong-song Chen hepatology institute People's Hospital Peking University Beijing 100044 China

Currently approved treatments for hepatitis B virus （HBV） infection include the immunomodulatory agent, IFN-α, and nucleos（t）ide analogues. Their efficacy is limited by their side effects, as well as the induction of viral mutations that render them less potent. It is thus necessary to develop drugs that target additional viral antigens. Chemicals and biomaterials by unique methods of preventing HBV replication are currently being developed, including novel nucleosides and newly synthesized compounds such as capsid assembling and mRNA transcription inhibitors. Molecular therapies that target different stages of the HBV life cycle will aid current methods to manage chronic hepatitis B （CriB） infection. The use of immunomodulators and gene therapy are also under consideration. This report summarizes the most recent treatment possibilities for CHB infection. Emerging therapies and their potential mechanisms, efficacy, and pitfalls are discussed.

关键词： Hepatitis B virus Antiviral drugs Drugevaluation Immunomodulatory agents Gene therapy

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Comparison analysis between haplo identical stem cell transplantation and matched sibling donor stem cell transplantation for high-risk acute myeloid leukemia in first complete remission

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science China(Life sciences) 2019年第5期62卷 691-697页

作者： Yang Liu Xiaojun Huang Qian Fei Lanping Xu Xiaohui Zhang Kaiyan Liu Yuhong Chen Huan Chen Yu Wang peking university people's hospital Peking University Institute of Hematology

In order to compare the effect between haploidentical(HID) stem cell transplantation(HsCT) and matched sibling donor(MsD)stem cell transplantation for high-risk acute myeloid leukemia(AML) in first complete remission status(CR1), we retrospectively studied 170 cases who received stem cell transplantation from Jan 2008 to Jul 2015 in peking university people's hospital. We divided all cases into MsD group(43 cases) and HID(127 cases) group. Patients in HID and MsD group displayed similar baseline characteristics except for age distribution. There were no statistic differences for overall survival(Os), cumulative incidence of relapse, leukemia free survival(LFs), transplantation related mortality(TRM) between HID and MsD group. The 3-year Os, LFs for all patients was 63.9% and 59.7% respectively. Multivariate analysis showed that grade III-IV acute graft versus host disease(aGVHD) was an independent risk factor for treatment related mortality(HR=8.134, 95% CI:3.210–20.611, Psomy/complex chromosomal karyotype and white blood cell count more than 50×109 L-1 were two independent factors for relapse(HR=1.533, 95% CI: 1.040–2.260, P=0.031)(HR=1.004, 95% CI: 1.001–1.008, P=0.015).Grade III-IV aGVHD was an independent factor for mortality(HR=3.184, 95% CI: 1.718–5.902, Pse results demonstrated some risk factors for high-risk AML leukemia transplantation and indicated for AML patients in CR1 status, haplo stem cell transplantation could have the same therapeutic effect as MsD transplantation.

关键词： high risk AML haplo stem cell transplantation matched sibling donor transplantation complex/monosomy chromosomal karyotype

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