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Improving the value of molecular testing:current status and opportunities in colorectal cancer precision medicine

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Cancer Biology & Medicine 2024年第1期21卷 21-28页

作者： Haiyun Li Linwei Guo Chenchen Wang Xin Hu ye xu Department of Colorectal Surgery Fudan University Shanghai Cancer CenterShanghai 200032China Department of Oncology Shanghai Medical CollegeFudan UniversityShanghai 200032China Department of Gastrointestinal Medical Oncology Fudan University Shanghai Cancer CenterShanghai 200032China Precision Cancer Medical Center Affiliated with Fudan University Shanghai Cancer Center Shanghai 201315China

Colorectal cancer(CRC)is the second leading cause of cancer-related deaths *** radical resection with adjuvant chemotherapy remains the primary treatment choice for CRC,but the 5-year postoperative survival rate is only approximately 60%,and approximately one-third of patients with CRC experience recurrence within 2 years of ***,the transformation of high-throughput sequencing has accelerated the development of precision *** example,KRAS mutations indicate resistance to anti-epidermal growth factor receptor(EGFR)-targeted therapies in ***,molecular-guided individualized therapy has brought new promise in major clinical areas and challenges,such as novel biomarkers predicting sensitivity and resistance to immunotherapy for microsatellite stable(MSS)CRC.

关键词： cancer chemotherapy colorectal

An in-situ study of static recrystallization in Mg using high temperature EBSD

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Journal of Magnesium and Alloys 2024年第4期12卷 1419-1430页

作者： xu ye Zhe Suo Zhonghao Heng Biao Chen Qiuming Wei Junko Umeda Katsuyoshi Kondoh Jianghua Shen School of Aeronautics Northwestern Polytechnical UniversityXi’anShaanxiChina Shaanxi Key Laboratory of Impact Dynamic and Its Engineering Application Xi’anShaanxiChina School of Mechanical Engineering Qinghai UniversityXiningQinghaiChina School of Materials Science and Engineering Northwestern Polytechnical UniversityXi’anShaanxiChina Department of Mechanical Engineering University of North Carolina at CharlotteCharlotteNCUSA Joining and Welding Research Institute Osaka University11-1 MihogaokaOsakaJapan

It has been a common method to improve the mechanical properties of metals by manipulating their microstructures via static recrystallization,i.e.,through heat ***,the knowledge of recrystallization and grain growth is critical to the success of the *** the present work,by using in-situ high temperature EBSD,the mechanisms that control recrystallization and grain growth of an extruded pure Mg were *** experimental results revealed that the grains of priority for dynamic recrystallization exhibit fading competitiveness under static *** is also found that grain boundary movement or grain growth is likely to show an inverse energy gradient effect,i.e.,low energy grains tend to swallow or grow into high energy grains,and grain boundaries of close to 30°exhibit superior growth advantage to *** finding is that{10-12}tensile twin boundaries are sites of hardly observed for recrystallization,and are finally swallowed by adjacent recrystallized *** above findings may give comprehensive insights of static recrystallization and grain growth of Mg,and may guide the design of advanced materials processing in microstructural engineering.

关键词： Pure Mg In-situ HT-EBSD Recrystallization Grain growth

VLBI with SKA:Possible Arrays and Astrometric Science

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Research in Astronomy and Astrophysics 2024年第7期24卷 1-33页

作者： Yingjie Li ye xu Jingjing Li Shuaibo Bian Zehao Lin Chaojie Hao Dejian Liu Purple Mountain Observatory Chinese Academy of SciencesNanjing 210023China University of Science and Technology of China Hefei 230026China

The next generation of very long baseline interferometry(VLBI)is stepping into the era of microarcsecond(μas)astronomy,and pushing astronomy,especially astrometry,to new *** with the Square Kilometre Array(SKA),SKA-VLBI,will increase current sensitivity by an order of magnitude,and reach astrometric precision routinely below 10μas,even challenging 1μ*** advancement allows precise parallax and proper motion measurements of various celestial *** improvements can be used to study objects(including isolated objects,and binary or multiple systems)in different stellar stages(such as star formation,main-sequence stars,asymptotic giant branch stars,pulsars,black holes,white dwarfs,etc.),unveil the structure and evolution of complex systems(such as the Milky Way),benchmark the international celestial reference frame,and reveal cosmic ***,the theory of general relativity can also be tested with SKA-VLBI using precise measurements of light deflection under the gravitational fields of different solar system objects and the perihelion precession of solar system objects.

关键词： astrometry-parallaxes-stars kinematics and dynamics-ISM kinematics and dynamics-Galaxy kinematics and dynamics-galaxies kinematics and dynamics-gravitation

The Largest Chinese Cohort Study Indicates Homologous Recombination Pathway Gene Mutations as Another Major Genetic Risk Factor for Colorectal Cancer with Heterogeneous Clinical Phenotypes

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Research 2024年第3期6卷 191-203页

作者： Yun xu Kai Liu Cong Li Minghan Li Fangqi Liu Xiaoyan Zhou Menghong Sun Megha Ranganathan Liying Zhang Sheng Wang Xin Hu ye xu Department of Colorectal Surgery Fudan University Shanghai Cancer CenterShanghaiP.R.China Department of Pathology Fudan University Shanghai Cancer CenterShanghaiP.R.China Department of Pathology Tissue BankFudan University Shanghai Cancer CenterShanghaiP.R.China Department of Medicine Memorial Sloan Kettering Cancer CenterNew YorkNYUSA Department of Pathology and Laboratory Medicine David Geffen School of MedicineUniversity of CaliforniaLos AngelesCAUSA Precision Cancer Medical Center Fudan University Shanghai Cancer CenterShanghaiP.R.China

While genetic factors were associated with over 30% of colorectal cancer (CRC) patients, mutations in CRC-susceptibility genes were identified in only 5% to 10% of these patients. Besides, previous studies on hereditary CRC were largely designed to analyze germline mutations in patients with single genetic high-risk factor, which limited understanding of the association between genotype and phenotypes. From January 2015 to December 2018, we retrospectively enrolled 2,181 patients from 8,270 consecutive CRC cases, covering 5 categories of genetic high-risk factors. Leukocyte genomic DNA was analyzed for germline mutations in cancer predisposition genes. The germline mutations under each category were detected and analyzed in association with CRC susceptibility, clinical phenotypes, and prognoses. A total of 462 pathogenic variants were detected in 19.3% of enrolled CRC patients. Mismatch repair gene mutation was identified in 9.1% of patients, most prevalent across all high-risk groups. Homologous recombination (HR) gene mutations were detected in 6.5% of cases, penetrated in early-onset and extra-colonic cancer risk groups. Mutations in HR genes, including BARD1, RAD50, and ATM, were found to increase CRC risk with odds ratios of 2.8-, 3.1-, and 3.1-fold, respectively. CRC patients with distinct germline mutations manifested heterogeneous phenotypes in clinicopathology and long-term prognoses. Thus, germline mutation screenings should be performed for CRC patients with any of those genetic risk factors. This study also reveals that HR gene mutations may be another major driver for increased CRC risk.

关键词： susceptibility category Major

Sulforaphane ameliorates non-alcoholic steatohepatitis by KLF4-mediated macrophage M2 polarization

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Food Science and Human Wellness 2024年第5期13卷 2727-2740页

作者： Xianghui Huang Jia xu ye xu Bingxin Huangfu Feng Zhang Yanzhou Hu Ruxin Gao Xinxin Ren Boyang Zhang Kunlun Huang Xiaoyun He Key Laboratory of Precision Nutrition and Food Quality Key Laboratory of Functional DairyMinistry of EducationCollege of Food Science and Nutritional EngineeringChina Agricultural UniversityBeijing 100083China Key Laboratory of Safety Assessment of Genetically Modified Organism(Food Safety) the Ministry of Agriculture and Rural Affairs of the P.R.ChinaBeijing 100083China

Non-alcoholic fatty liver disease (NAFLD) has become a global issue and a severe threat to public ***, to date, no approved therapeutic drugs have been developed. Dietary interventions with naturalproducts have shown promise in preventing and treating NAFLD. Sulforaphane (SFN) is a phytocompoundwith antioxidant and anti-inflammatory properties, and previous research has demonstrated that SFN canameliorate hepatic lipid accumulation and inflammation. However, the molecular mechanisms underlying thesebeneficial effects remain unclear. In this study, we confirmed the protective effects of SFN on excessive lipidaccumulation and inflammatory injury in a high-fat, high-fructose diet-induced non-alcoholic steatohepatitis(NASH) mouse model. We found that SFN attenuates the inflammatory injury in a macrophage cell line andthe liver of NASH mice, owing to the promotion of M1-type macrophage polarization toward the M2-type andthe regulation of inflammatory mediators. Further analysis demonstrated that this SFN-induced macrophageM2-type polarization occurs in a Krüppel-like factor 4 (KLF4)-dependent manner. In summary, we uncovereda new mechanism of action underlying SFN activity and provide evidence that dietary intervention with SFNmight be protective against NASH.

关键词： Non-alcoholic steatohepatitis(NASH) Krüppel-like factor 4 Nuclear translocation Chemokine Lipid metabolism

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职业教育数字教材建设的内涵、问题及路径探究

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中国职业技术教育 2024年第20期 12-18页

作者：徐晔教育部课程教材研究所

随着教育数字化的推进,职业教育数字教材作为数字技术与职业教育教学深度融合的产物,深刻影响着职业教育人才培养质量。在理清职业教育数字教材边界的基础上,深入分析职业教育数字教材存在的问题,包括教材建设整体规划不够、教材标准规... 详细信息

随着教育数字化的推进,职业教育数字教材作为数字技术与职业教育教学深度融合的产物,深刻影响着职业教育人才培养质量。在理清职业教育数字教材边界的基础上,深入分析职业教育数字教材存在的问题,包括教材建设整体规划不够、教材标准规范缺失、教材内容的知识图谱缺位、教材质量监控体系不足。聚焦职业教育数字教材的生命周期,提出职业教育数字教材建设的路径:统筹规划职业教育数字教材建设,一体化开发职业教育数字教材,建立职业教育数字教材监控体系,系统推动职业教育数字教材建设,助力职业教育人才培养质量全面提升。

关键词：职业教育数字教材教材管理教材开发教材监控

计及相似日的VMD-FE-LSTM光伏出力组合预测模型研究

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太阳能学报 2024年第5期45卷 490-499页

作者：王涛李薇许野王旭王鑫鹏华北电力大学核科学与工程学院北京102206

针对光伏出力的随机性和波动性导致预测精度偏低的问题,构建一套融合相似日理论、变分模态分解法、模糊熵计算方法和深度学习算法的光伏出力组合预测模型。在运用灰色关联分析法确定影响光伏出力的关键气象因素和使用综合相似距离法选... 详细信息

针对光伏出力的随机性和波动性导致预测精度偏低的问题,构建一套融合相似日理论、变分模态分解法、模糊熵计算方法和深度学习算法的光伏出力组合预测模型。在运用灰色关联分析法确定影响光伏出力的关键气象因素和使用综合相似距离法选定待预测日的历史相似日的基础上,利用模糊熵对变分模态分解的光伏出力分量进行重组,得到若干规律性较强的新序列;然后,分别构建各重组序列的长短期记忆神经网络预测模型;最终,对重组序列的预测值进行求和得到预测结果。该组合模型在云南某光伏电站的应用结果表明,对比其他模型,所提出的组合预测模型精度更高,具有很好的应用前景。

关键词：光伏发电预测模型变分模态分解长短期记忆神经网络综合相似距离模糊熵

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交往行动理论视野中学校文化建设的现实困境与变革路径

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教学与管理 2024年第18期 41-44页

作者：徐烨佳华中师范大学教育学院武汉430079

学校文化建设是我国文化强国战略的重要组成部分。当前,我国学校文化建设正遭遇着由系统殖民引起的离境之忧、主体中心逻辑造就的生成之困和从“成人”到“治人”的体用之殇。哈贝马斯交往行动理论为重塑学校文化生态提供了有益启示。... 详细信息

学校文化建设是我国文化强国战略的重要组成部分。当前,我国学校文化建设正遭遇着由系统殖民引起的离境之忧、主体中心逻辑造就的生成之困和从“成人”到“治人”的体用之殇。哈贝马斯交往行动理论为重塑学校文化生态提供了有益启示。其主要观点将以语言为媒介的交互活动作为系统进化的动力源泉,将“U”“D”原则作为系统优化的外部保障,将“非强迫共识”作为系统规范的本质属性。基于此提出我国学校文化建设的变革路径,要强化其底层逻辑,完善其对话规则,遵循其人本指向。

关键词：交往行动理论学校文化建设言语交互以人为本文化认同度

Tislelizumab in previously treated,locally advanced unresectable/metastatic microsatellite instability-high/mismatch repair-deficient solid tumors

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Chinese Journal of Cancer Research 2024年第3期36卷 257-269页

作者： Jian Li ye xu Aimin Zang Yunong Gao Quanli Gao Yanqiao Zhang Dong Wang Jianming xu Ying Yuan Haiping Jiang Jieer Ying Chunmei Shi Yanhong Deng Jing Wang Tianshu Liu Yi Huang Xiaoping Qian Yueyin Pan Ying Cheng Sheng Hu Jin Wang Mengyue Shi Ke Wang Han Hu Lin Shen State Key Laboratory of Holistic Integrative Management of Gastrointestinal Cancers Beijing Key Laboratory of Carcinogenesis and Translational ResearchDepartment of Gastrointestinal OncologyPeking University Cancer Hospital&InstituteBeijing 100142China Department of Oncology Fudan University Shanghai Cancer CenterShanghai 200032China Department of Medical Oncology Affiliated Hospital of Hebei UniversityBaoding 071000China Key Laboratory of Carcinogenesis and Translational Research(Ministry of Education/Beijing) Department of GynecologyPeking University Cancer Hospital&InstituteBeijing 100142China Department of Immunotherapy Henan Cancer HospitalZhengzhou 450001China Department of Gastrointestinal Oncology Affiliated Cancer Hospital of Harbin Medical UniversityHarbin 150086China Department of Gastrointestinal Oncology Chongqing University Cancer HospitalChongqing 400030China Department of Gastrointestinal Oncology the Fifth Medical CenterChinese PLA General HospitalBeijing 100048China Department of Medical Oncology the Second Affiliated HospitalZhejiang University School of MedicineHangzhou 310009China Department of Medical Oncology the First Affiliated HospitalZhejiang University School of MedicineHangzhou 310003China Department of Medical Oncology Cancer Hospital of the University of Chinese Academy of SciencesHangzhou 310022China Department of Medical Oncology Fujian Medical University Union HospitalFuzhou 350001China Department of Oncology the Sixth Affiliated HospitalSun Yat-sen UniversityGuangzhou 510655China Department of Medical Oncology Hunan Cancer HospitalChangsha 410013China Department of Medical Oncology Zhongshan HospitalFudan UniversityShanghai 200032China Department of Immunotherapy Hubei Cancer HospitalWuhan 430079China Department of Medical Oncology the Affiliated Hospital of Nanjing University Medical SchoolNanjing 210008China Department of Medical Oncology Anhui Provincial HospitalHefei 230001China Department of Medical Oncology Jilin Cancer Hospital

Objective:The open-label,phase II RATIONALE-209 study evaluated tislelizumab(anti-programmed cell death protein 1 antibody)as a tissue-agnostic monotherapy for microsatellite instability-high(MSI-H)/mismatch repair-deficient(dMMR)***:Adults with previously treated,locally advanced unresectable or metastatic MSI-H/dMMR solid tumors were *** received tislelizumab 200 mg intravenously every 3 *** response rate(ORR;primary endpoint),duration of response(DoR),and progression-free survival(PFS)were assessed by independent review committee(Response Evaluation Criteria in Solid Tumors v1.1).Results:Eighty patients were enrolled and treated;75(93.8%)patients had measurable disease at *** had metastatic disease and received at least one prior therapy for advanced/metastatic disease(n=79;98.8%).At primary analysis(data cutoff July 8,2021;median follow-up 15.2 months),overall ORR[46.7%;95%confidence interval(95%CI),35.1−58.6;one-sided P<0.0001]and ORR across tumor-specific subgroups[colorectal(n=46):39.1%(95%CI,25.1–54.6);gastric/gastroesophageal junction(n=9):55.6%(95%CI,21.2−86.3);others(n=20):60.0%(95%CI,36.1−80.9)]were significantly greater with tislelizumab vs.a prespecified historical control ORR of 10%;five(6.7%)patients had complete *** DoR,PFS,and overall survival were not reached with long-term follow-up(data cutoff December 5,2022;median follow-up 28.9 months).Tislelizumab was well tolerated with no unexpected safety ***-related adverse events(TRAEs)of grade≥3 occurred in 53.8%of patients;7.5%of patients discontinued treatment due to ***:Tislelizumab demonstrated a significant ORR improvement in patients with previously treated,locally advanced unresectable or metastatic MSI-H/dMMR tumors and was generally well tolerated.

关键词： Biomarkers DNA mismatch repair immune checkpoint inhibitors microsatellite instability phase II clinical trials programmed cell death 1 receptor