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DNA damage response-related immune activation signature predicts the response to immune checkpoint inhibitors: from gastrointestinal cancer analysis to pan-cancer validation

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Cancer Biology & Medicine 2024年第3期21卷 252-266页

作者： Junya yan Shibo Wang Jing Zhang Qiangqiang Yuan Xianchun Gao Nannan Zhang yan Pan Haohao Zhang Kun Liu Jun Yu Linbin Lu Hui Liu Xiaoliang Gao Sheng Zhao Wenyao Zhang Abudurousuli Reyila Yu Qi Qiujin Zhang Shundong Cang Yuanyuan Lu yanglin Pan yan kong Yongzhan Nie State Key Laboratory of Holistic Integrative Management of Gastrointestinal Cancers and National Clinical Research Center for Digestive Diseases Xijing Hospital of Air Force Military Medical UniversityXi'an 710032China Department of Oncology Henan Provincial People's HospitalZhengzhou University People's HospitalZhengzhou 450o03China Faculty of Life Science Northwest UniversityXi'an 710069China Unit 73211 of the People's Liberation Army Nanjing 211800China Key Laboratory of Resource Biology and Biotechnology in Western China(Ministry of Education) School of MedicineNorthwest UniversityXi'an 710069China Shaanxi University of Chinese Medicine Second Clinical Medicine FacultyXi'an 712046China Key Laboratory of Carcinogenesis and Translational Research(Ministry of Education) Department of Renal Cancer and MelanomaPeking University Cancer Hospital and InstituteBeijing 100142China

Objective: DNA damage response(DDR) deficiency has emerged as a prominent determinant of tumor immunogenicity. This study aimed to construct a DDR-related immune activation(DRIA) signature and evaluate the predictive accuracy of the DRIA signature for response to immune checkpoint inhibitor(ICI) therapy in gastrointestinal(GI) cancer.Methods: A DRIA signature was established based on two previously reported DNA damage immune response assays. Clinical and gene expression data from two published GI cancer cohorts were used to assess and validate the association between the DRIA score and response to ICI therapy. The predictive accuracy of the DRIA score was validated based on one ICI-treated melanoma and three pan-cancer published cohorts.Results: The DRIA signature includes three genes(CXCL10, IDO1, and IFI44L). In the discovery cancer cohort, DRIA-high patients with gastric cancer achieved a higher response rate to ICI therapy than DRIA-low patients(81.8% vs. 8.8%;P < 0.001), and the predictive accuracy of the DRIA score [area under the receiver operating characteristic curve(AUC) = 0.845] was superior to the predictive accuracy of PD-L1 expression, tumor mutational burden, microsatellite instability, and Epstein–Barr virus status. The validation cohort demonstrated that the DRIA score identified responders with microsatellite-stable colorectal and pancreatic adenocarcinoma who received dual PD-1 and CTLA-4 blockade with radiation therapy. Furthermore, the predictive performance of the DRIA score was shown to be robust through an extended validation in melanoma, urothelial cancer, and pan-cancer.Conclusions: The DRIA signature has superior and robust predictive accuracy for the efficacy of ICI therapy in GI cancer and pancancer, indicating that the DRIA signature may serve as a powerful biomarker for guiding ICI therapy decisions.

关键词： DNA damage response-related immune activation immune checkpoint inhibitors biomarker gastrointestinal cancer pan-cancer

Vitamin D-binding protein in plasma microglia-derived extracellular vesicles as a potential biomarker for major depressive disorder

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Genes & Diseases 2024年第2期11卷 1009-1021页

作者： Gaojia Zhang Ling Li yan kong Dandan Xu Yu Bao Zhiting Zhang Zhixiang Liao Jiao Jiao Dandan Fan Xiaojing Long Ji Dai Chunming Xie Zhiqiang Meng Zhijun Zhang Department of Neurology Affiliated Zhongda HospitalResearch Institution of NeuropsychiatrySchool of MedicineSoutheast UniversityNanjingJiangsu 210009China Department of Biochemistry and Molecular Biology School of MedicineSoutheast UniversityNanjingJiangsu 210009China Shenzhen Key Laboratory of Drug Addiction Brain Cognition and Brain Disease InstituteShenzhen Institute of Advanced TechnologyChinese Academy of Sciences (CAS)ShenzhenGuangdong 518000China CAS Key Laboratory of Brain Connectome and Manipulation The Brain Cognition and Brain Disease Institute (BCBDI)Shenzhen Institute of Advanced TechnologyChinese Academy of SciencesShenzhenGuangdong 518055China Lauterbur Research Center for Biomedical Imaging Shenzhen Institute of Advanced TechnologyChinese Academy of SciencesShenzhenGuangdong 518055China Shenzhen-Hong kong Institute of Brain Sciences-Shenzhen Fundamental Research Institutions ShenzhenGuangdong 518000China Brain Cognition and Brain Disease Institute Department of Mental Health and Public HealthFaculty of Life and Health SciencesShenzhen Institute of Advanced TechnologyChinese Academy of SciencesShenzhenGuangdong 518055China

No well-established biomarkers are available for the clinical diagnosis of major depressive disorder(MDD).Vitamin D-binding protein(VDBP)is altered in plasma and postmortem dorsolateral prefrontal cortex(DLPFC)tissues of MDD patients.Thereby,the role of VDBP as a potential biomarker of MDD diagnosis was further assessed.Total extracellular vesicles(EVs)and brain cell-derived EVs(BCDEVs)were isolated from the plasma of first-episode drug-naïve or drug-free MDD patients and well-matched healthy controls(HCs)in discovery(20 MDD patients and 20 HCs)and validation cohorts(88 MDD patients and 38 HCs).VDBP level in the cerebrospinal fluid(CSF)from chronic glucocorticoid-induced depressed rhesus macaques or prelimbic cortex from lipopolysaccharide(LPS)-induced depressed mice and wild control groups was measured to evaluate its relationship with VDBP in plasma microglia-derived extracellular vesicles(MDEVs).VDBP was significantly decreased in MDD plasma MDEVs compared to HCs,and negatively correlated with HAMD-24 score with the highest diagnostic accuracy among BCDEVs.VDBP in plasma MDEVs was decreased both in depressed rhesus macaques and mice.A positive correlation of VDBP in MDEVs with that in CSF was detected in depressed rhesus macaques.VDBP levels in prelimbic cortex microglia were negatively correlated with those in plasma MDEVs in depressed mice.The main results suggested that VDBP in plasma MDEVs might serve as a prospective candidate biomarker for MDD diagnosis.

关键词： Biomarker Cerebrospinal fluid Major depressive disorder Microglia derived extracellular vesicles Vitamin-D binding protein

Computerized cognitive remediation therapy on cognitive impairment and social function in patients with chronic schizophrenia

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World Journal of Psychiatry 2024年第6期14卷 884-893页

作者： Jian-Jun Hu Xi-Rong Sun Shuang-Ming Ni yan kong Department of Psychiatry Shanghai Pudong New Area Mental Health Center(Mental Health Center of Tongji UniversityShanghai Pudong New Area Psychological Counseling Center)Shanghai 200124China

BACKGROUND Patients with schizophrenia may have various disease manifestations,most of which gradually tend toward incurable chronic decline,leading to mental disability.The basic symptoms of the disease can impair social function,whereas long-term hospitalization produces hospitalization syndrome,causing serious damage to social function.AIM To investigate the effects of Computerized Cognitive Remediation Therapy(CCRT)on cognitive and social functioning in patients with chronic schizophrenia.METHODS A retrospective analysis of 120 patients with chronic schizophrenia in Shanghai Pudong New Area Mental Health Center was performed.They were divided into an intervention group(60 cases treated with CCRT combined with conventional medication)and a control group(60 cases treated with conventional medication).After treatment,effects on cognitive function and social roles were observed in both groups.The Positive and Negative Syndrome Scale(PANSS)was used to assess the patients'psychiatric symptoms.The Wisconsin Card Sorting Test(WCST)was used to assess the patients'cognitive functioning,and the Social Functioning Scale for Psychiatric Inpatients(SSPI)was used to assess the social functioning of the inpatient psychiatric patients.RESULTS No significant differences were observed in the PANSS,WCST,and SSPI intergroup scores before treatment(P>0.05).After 2,4,and 6 wk of therapy,general psychopathological factors,positive symptoms,negative symptoms,and total PANSS scores of PANSS in the intervention group were lower than in the control group(P<0.05).After 2,4,and 6 wk of treatment,the number of false responses,number of persistent bugs,and total responses in the WCST were significantly lower in the intervention group than in the control group(P<0.05),and the amount of completed classification was significantly higher than in the control group(P<0.05).After 2,4,and 6 wk of therapy,the SSPI scores were significantly greater than those of the controls(P<0.05).After 6 wk of treatment,the efficacy rates of the control and interv

关键词： Computerized cognitive correction therapy Schizophrenia Cognitive function Social function Psychopathological factors

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技术寄生视角下技术进化的原动力追问

科学学研究 2024年第1期42卷 38-45页

作者：丁飞孔燕新疆师范大学马克思主义学院新疆乌鲁木齐830017 中国科学技术大学人文与社会科学学院安徽合肥230026

技术寄生理论指出,技术间的寄生有助于两种或多种技术共生发展;宿主技术中的寄生技术不成比例的增长将促进复杂技术系统的发展;拥有较多寄生技术的宿主技术比拥有较少寄生技术的宿主技术进化快;宿主技术的进化不独立于与它相关联的技术... 详细信息

技术寄生理论指出,技术间的寄生有助于两种或多种技术共生发展;宿主技术中的寄生技术不成比例的增长将促进复杂技术系统的发展;拥有较多寄生技术的宿主技术比拥有较少寄生技术的宿主技术进化快;宿主技术的进化不独立于与它相关联的技术。技术寄生发生的初期,外部环境的影响是寄生发生的外在条件,技术内部的差异是寄生发生的内在限制,这显示出寄生具有选择性。在中期,寄生技术与宿主技术相互促进,共同进化,预示寄生具有互惠性。在后期,寄生技术交替寄生于宿主技术,表明寄生具有替代性。结合技术进化的普遍规律,“双S曲线”能够从技术内部反映技术从寄生到共生的进化规律。技术寄生理论启示应该摒弃描述进化现象,注重解释联结机制;在创新管理中初期突出多样性和基础性,中后期注重灵活性和导向性。

关键词：技术寄生技术进化双S曲线创新管理

人工智能伦理原则的实践进路——基于德国人工智能伦理标签的启示

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自然辩证法研究 2024年第2期40卷 89-95页

作者：彭玥孔燕中国科学技术大学人文与社会科学学院合肥230026 西南科技大学外国语学院绵阳621010

人工智能伦理标签是德国反思伦理原则实践困境之后提出的新理念,标志着德国人工智能伦理由原则到实践的重要转向。该标签的核心价值在于细化伦理标准参数、简化伦理风险场景以及嵌入能效标签的规范形式,从而实现伦理原则可评估、可操作... 详细信息

人工智能伦理标签是德国反思伦理原则实践困境之后提出的新理念,标志着德国人工智能伦理由原则到实践的重要转向。该标签的核心价值在于细化伦理标准参数、简化伦理风险场景以及嵌入能效标签的规范形式,从而实现伦理原则可评估、可操作与可解释。通过梳理与分析人工智能伦理标签的主要内涵,为我国当下人工智能伦理实践进路提供了重要启示:深入人工智能应用情景的伦理案例研究,提升伦理原则的实践有效性;扩展多元化的人工智能伦理规范形式,增加伦理原则的道德接受度;构建完善的指标评估体系,提高伦理原则的系统阐释性;推进伦理标准认证项目发展,增强未来市场监管规则的竞争力。

关键词：人工智能伦理标签德国实践进路启示

共价有机框架膜阳离子基团密度调控实现快速阴离子传导

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科学通报 2024年第9期69卷 1111-1113页

作者：孔彦吕博晖吴洪姜忠义天津大学化工学院天津300072

离子交换膜是目前众多电化学应用的核心部件,如燃料电池、电解槽、电化学氢气压缩机等[1].其中,离子传导率是离子交换膜的核心性能指标,决定了相关电化学装置的输出功率、能量转化效率等关键指标.因此,开发高离子传导率的离子交换膜对... 详细信息

离子交换膜是目前众多电化学应用的核心部件,如燃料电池、电解槽、电化学氢气压缩机等[1].其中,离子传导率是离子交换膜的核心性能指标,决定了相关电化学装置的输出功率、能量转化效率等关键指标.因此,开发高离子传导率的离子交换膜对于高性能电化学的应用至关重要.根据导电离子种类,离子交换膜主要分为质子交换膜和阴离子交换膜.

关键词：质子交换膜离子交换膜燃料电池离子传导率能量转化效率电化学装置氢气压缩机阳离子基团

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马克思主义新闻观中的主体性问题

西北师大学报（社会科学版） 2024年第1期61卷 22-31页

作者：齐爱军孔岩上海大学新闻传播学院上海200444

主体性问题是马克思主义主体性思想在新闻传播领域的主体化呈现与表达,但在马克思主义新闻观研究中却是一个长期未被凸显的学术命题。在马克思主义新闻观下,主体性的建构体现在政治主体性、传媒主体性以及新闻生产者主体性三个层面,三... 详细信息

主体性问题是马克思主义主体性思想在新闻传播领域的主体化呈现与表达,但在马克思主义新闻观研究中却是一个长期未被凸显的学术命题。在马克思主义新闻观下,主体性的建构体现在政治主体性、传媒主体性以及新闻生产者主体性三个层面,三个层面均存在其主体化的独特逻辑,并落实在相应的话语行动中,即从党性、人民性相统一,到人民报刊,再到群众办报、专业办报和政治家办报的传媒现代性实践。延安时期塑造的这一马克思主义新闻观中国化主体性的初始架构,至今犹有深远的影响力,我们目前看到的改变,依然是在这个主体性的场域中展开。在今后的研究中,学术共同体需要把主体性问题带回到马克思主义新闻观中来。

关键词：马克思主义新闻观传媒现代性主体性

遂宁市农产品冷链物流高质量发展路径的研究——基于SWOT分析

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四川职业技术学院学报 2024年第1期34卷 96-102页

作者：孔燕四川职业技术学院质量管理处督导室四川遂宁629000

随着人民对高品质生活的追求,农产品冷链物流的需求量呈现爆发式增长。遂宁市作为国家陆港型物流枢纽承载城市,在农产品冷链物流高质量发展过程中有自身的优劣势。本文采用SWOT分析方法,分析了遂宁市农产品冷链物流的政策优势、资源优... 详细信息

随着人民对高品质生活的追求,农产品冷链物流的需求量呈现爆发式增长。遂宁市作为国家陆港型物流枢纽承载城市,在农产品冷链物流高质量发展过程中有自身的优劣势。本文采用SWOT分析方法,分析了遂宁市农产品冷链物流的政策优势、资源优势、交通优势;冷链物流的硬件建设、冷链物流技术和冷链物流设施设备劣势;冷链物流发展迎来成渝经济圈发展战略和市场繁荣的机遇;冷链物流被成渝极核虹吸、区域竞争压力巨大的威胁。提出“打通最先一公里”、夯实冷链物流交通网络和依托“一主四辅”枢纽布局,打造差异化配送中心的冷链物流高质量发展路径。

关键词： SWOT分析农产品冷链物流发展路径

环状RNA编码蛋白在疾病发生机制中的作用研究进展

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中华医学遗传学杂志 2024年第7期41卷 872-880页

作者：焦娇徐丹丹孔岩张志珺东南大学医学院南京210009 东南大学附属中大医院神经内科神经精神研究所南京210009 中国科学院深圳先进技术研究院深圳518055

随着研究的进展,非编码RNA被发现突破了传统的定义,可通过编码序列元件,与核糖体结合,直接编码功能性蛋白。circRNA编码蛋白的功能在非编码RNA中研究最为广泛。本研究以"circRNA"、"encode"和"translation"作为关键词,对PubMed以及Web o... 详细信息

随着研究的进展,非编码RNA被发现突破了传统的定义,可通过编码序列元件,与核糖体结合,直接编码功能性蛋白。circRNA编码蛋白的功能在非编码RNA中研究最为广泛。本研究以"circRNA"、"encode"和"translation"作为关键词,对PubMed以及Web of Science数据库进行检索,对文献进行筛选和引用检索,对circRNA的翻译机制、相关研究方法以及与疾病的相关性进行综述。circRNA可通过非帽依赖途径翻译蛋白质。多种分子技术、尤其是蛋白质谱分析对circRNA编码蛋白独特肽段的鉴定,对于证实circRNA编码蛋白的存在具有重要的价值。CircRNA编码蛋白参与消化、神经、泌尿、乳腺等多个系统疾病的调控,具有成为疾病诊断和治疗新靶标的潜力。本文对circRNA翻译领域的理论基础、现有实验方法和疾病相关研究进行了全面的归纳,为后续的诊断和治疗靶标开发提供了线索。

关键词：环状RNA 翻译蛋白疾病