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非呼吸性PELOD-2儿童器官功能障碍评分可良好预测急性呼吸衰竭儿童病死率

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中国小儿急救医学 2014年第8期21卷 530-530页

作者： leclerc f Duhamel A Deken V 方伯梁首都医科大学附属北京儿童医院

目的急性肺损伤（acute lung injury,ALI）或急性呼吸窘迫综合征（acute respiratory distress syndrome,ARDS）患儿的主要死因为多脏器功能障碍（multiple organ dysfunction,MOD）而非呼吸衰竭。本研究旨在评估非呼吸性儿童器官功能... 详细信息

目的急性肺损伤（acute lung injury,ALI）或急性呼吸窘迫综合征（acute respiratory distress syndrome,ARDS）患儿的主要死因为多脏器功能障碍（multiple organ dysfunction,MOD）而非呼吸衰竭。本研究旨在评估非呼吸性儿童器官功能障碍评分（NRespPELOD-2）对急性呼吸衰竭（acute respiratory failure,ARf）患儿病死的预测价值。设计分析最近发布的PELOD-2数据资料。场所法国和比利时大学附属医院的9家多学科三级医疗PICU。研究对象 2006年1月至2007年10月间入住上述PICU的全部ARf患儿（除外新生儿）。干预措施无。测量方法和主要结果本研究前瞻性收集PICU住院期间PELOD-2评分所需的相关参量数据,8个收集时间点分别为PICU住院l、2、5、8、12、16、18 d及出PICU当日,选择各参量最异常数据进行最终评分。预后指标为PICU出院时生命体征状态。分别采用受试者操作特征曲线下面积（areas under receiver operating characteristic curve,AUC）及Hosmer-Lemeshow拟合优度检验评估PELOD-2和NRespPELOD-2评分辨识能力及标度,采用引导重新取样法修正乐观偏倚。共纳入1572例患儿（中位年龄20.6月,四分位数间距5.5;0.2月,病死率9.5%）。PELOD-2和NRespPELOD-2的识别力甚佳（AUC分别为0.93和0.92）,标度亦较好（拟合优度卡方检验分别为5.8,P=0.45和7.6,P=0.27）。4个NResp脏器功能障碍和病死风险密切相关（Pf患儿PICU住院期间所做NRespPELOD-2评分对患儿死亡的预测价值较高,其中94.3%患儿行无创呼吸支持。NRespPELOD-2评分可作为非呼吸性脏器衰竭定义工具,儿童ARDS国际专家指南推荐发展此评分。

关键词：急性呼吸衰竭多脏器衰竭预后评估评分方法疾病严重度指数 PELOD-2

Colon cancer stemness as a reversible epigenetic state:Implications for anticancer therapies

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World Journal of Stem Cells 2019年第11期11卷 920-936页

作者： Audrey Vincent Aicha Ouelkdite-Oumouchal Mouloud Souidi Julie leclerc Bernadette Neve Isabelle Van Seuningen Lille University Institut National de la Sante et de la Recherche MédicaleCHU LilleUMR-S 1172-Jean-Pierre Aubert Research CenterLille F-59000France Department of Biochemistry and Molecular Biology Lille University HospitalLille F-59000France

The recent discovery of cancer cell plasticity,*** ability to reprogram into cancer stem cells(CSCs)either naturally or under chemotherapy and/or radiotherapy,has changed,once again,the way we consider cancer *** cancer stemness is a reversible epigenetic state rather than a genetic identity,opportunities will arise for therapeutic strategies that remodel epigenetic landscapes of ***,the systematic use of DNA methyltransferase and histone deacetylase inhibitors,alone or in combination,in advanced solid tumors including colorectal cancers,regardless of their molecular subtypes,does not seem to be the best *** this review,we first summarize the knowledge researchers have gathered on the epigenetic signatures of CSCs with the difficulty of isolating rare populations of *** raise questions about the relevant use of currently available epigenetic inhibitors(epidrugs)while the expression of numerous cancer stem cell markers are often repressed by epigenetic *** markers include the three cluster of differentiation CD133,CD44 and CD166 that have been extensively used for the isolation of colon ***,we describe current treatment strategies using epidrugs,and we hypothesize that,using correlation tools comparing associations of relevant CSC markers with chromatin modifier expression,we could identify better candidates for epienzyme targeting.

关键词： Cancer stem cells Colon cancer Epigenetics Chromatin modifying enzymes CD44 CD133 CD166

TRPC3 is required for the survival, pluripotency and neural differentiation of mouse embryonic stem cells(mESCs)

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Science China(Life Sciences) 2018年第3期61卷 253-265页

作者： Helen Baixia Hao Sarah E. Webb Jianbo Yue Marc Moreau Catherine leclerc Andrew L. Miller Division of Life Science and State Key Laboratory of Molecular Neuroscience HKUST Clear Water Bay Hong Kong China Department of Biomedical Sciences City University of Hong Kong Hong Kong China Centre de Biologie du Développement (CBD) Centre de Biologie Intégrative (CBI) Université de Toulouse CNRS UPS Toulouse F-31062 France

Transient receptor potential canonical subfamily member 3(TRPC3) is known to be important for neural development and the formation of neuronal networks. Here, we investigated the role of TRPC3 in undifferentiated mouse embryonic stem cells(mESCs) and during the differentiation of mESCs into neurons. CRISPR/Cas9-mediated knockout(KO) of TRPC3 induced apoptosis and the disruption of mitochondrial membrane potential both in undifferentiated mESCs and in those undergoing neural differentiation. In addition, TRPC3 KO impaired the pluripotency of mESCs. TRPC3 KO also dramatically repressed the neural differentiation of mESCs by inhibiting the expression of markers for neural progenitors, neurons, astrocytes and *** together, our new data demonstrate an important function of TRPC3 with regards to the survival, pluripotency and neural differentiation of mESCs.

关键词： transient receptor potential canonical subfamily member 3 (TRPC3) mouse embryonic stem cells (mESCs) neurondifferentiation CRISPR/Cas9 pluripotency apoptosis mitochondrial membrane potential

Identification of Ca2+ signaling components in neural stem/progenitor cells during differentiation into neurons and glia in intact and dissociated zebrafish neurospheres

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Science China(Life Sciences) 2018年第11期61卷 1352-1368页

作者： Man Kit Tse Ting Shing Hung Ching Man Chan Tiffany Wong Mike Dorothea Catherine leclerc Marc Moreau Andrew L.Miller Sarah E.Webb Division of Life Science & State Key Laboratory of Molecular Neuroscience HKUSTClear Water BayHongKongChina Centre de Biologie du Developpement(CBD) Centre de Biologie Integrative(CBI)Universite de ToulouseCNRSUPSToulouse F-31062France

The development of the CNS in vertebrate embryos involves the generation of different sub-types of neurons and glia in a complex but highly-ordered spatio-temporal manner. Zebrafish are commonly used for exploring the development, plasticity and regeneration of the CNS, and the recent development of reliable protocols for isolating and culturing neural stem/progenitor cells(NSCs/NPCs) from the brain of adult fish now enables the exploration of mechanisms underlying the induction/specification/differentiation of these cells. Here, we refined a protocol to generate proliferating and differentiating neurospheres from the entire brain of adult zebrafish. We demonstrated via RT-qPCR that some isoforms of ip3 r, ryr and stim are upregulated/downregulated significantly in differentiating neurospheres, and via immunolabelling that 1,4,5-inositol trisphosphate receptor(IP3 R) type-1 and ryanodine receptor(RyR) type-2 are differentially expressed in cells with neuron-or radial glial-like properties. furthermore, ATP but not caffeine(IP3 R and RyR agonists, respectively), induced the generation of Ca^(2+) transients in cells exhibiting neuron-or glial-like morphology. These results indicate the differential expression of components of the Ca^(2+) -signaling toolkit in proliferating and differentiating cells. Thus, given the complexity of the intact vertebrate brain, neurospheres might be a useful system for exploring neurodegenerative disease diagnosis protocols and drug development using Ca^(2+) signaling as a read-out.

关键词： Ca^2+ signaling neurospheres zebrafish neural stem/progenitor cells differentiation IP3receptors ryanodine receptors STIM and Orai

重组减毒细菌运送CD8^+T细胞表位的效应分析

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细胞与分子免疫学杂志 2006年第6期22卷 730-733页

作者：潘志明张晓明焦新安 Richard Lo-Man Claude leclerc 刘秀梵扬州大学农业部畜禽传染病学重点开放实验室江苏扬州225009 法国巴斯德研究所免疫调节生物学实验室法国巴黎75015

目的:分析重组减毒菌体外运送CD8+T细胞表位的效应。方法:以表达卵清蛋白(OVA)和淋巴细胞脉络丛脑膜炎病毒(LCMV)CD8+T细胞表位的重组菌13A(ptG2f)、25A(ptG2f)和SL7207(ptG2f)感染抗原提呈细胞(APC)LKb、LLd和骨髓源树突状细胞(BMDC),... 详细信息

目的:分析重组减毒菌体外运送CD8+T细胞表位的效应。方法:以表达卵清蛋白(OVA)和淋巴细胞脉络丛脑膜炎病毒(LCMV)CD8+T细胞表位的重组菌13A(ptG2f)、25A(ptG2f)和SL7207(ptG2f)感染抗原提呈细胞(APC)LKb、LLd和骨髓源树突状细胞(BMDC),应用体外抗原提呈试验检测APC对重组菌运送的CD8+T细胞表位的提呈效应。结果:感染试验证实,减毒菌13A、25A和SL7207对LKb细胞或LLd细胞均具有良好的侵袭能力,BMDC对重组菌具有很好的摄取功能。抗原提呈试验结果显示,在感染的早期(2h),LKb、LLd细胞和BMDC均可提呈重组菌13A(ptG2f)或SL7207(ptG2f)运送的T细胞表位;在感染的晚期(48h),LKb细胞对OVA257-264CD8+T细胞表位的提呈效应降低,LLd细胞对LCMV118-132CD8+T细胞表位的提呈效应增强。3种APC均不能提呈25A(ptG2f)运送的T细胞表位。另外,在同样的作用条件下,BMDC对减毒菌运送的抗原表位的提呈效应要强于LKb和LLd细胞。结论:重组菌能运送CD8+T细胞表位,为基于减毒细菌的新型基因工程疫苗的分子设计提供了有益借鉴。

关键词： CD8^+T细胞表位减毒大肠杆菌减毒鼠伤寒沙门氏菌体外抗原提呈试验

Loss of Notch signaling in skeletal stem cells enhances bone formation with aging

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Bone Research 2023年第4期11卷 737-750页

作者： Lindsey H.Remark Kevin leclerc Malissa Ramsukh Ziyan Lin Sooyeon Lee Backialakshmi Dharmalingam Lauren Gillinov Vasudev V.Nayak Paulo El Parente Margaux Sambon Pablo J.Atria Mohamed A.E.Ali Lukasz Witek Alesha B.Castillo Christopher Y.Park Ralf H.Adams Aristotelis Tsirigos Sophie M.Morgani Philipp Leucht Department of Orthopaedic Surgery NYU Robert I.Grossman School of MedicineNew YorkNYUSA Applied Bioinformatics Laboratories NYU Grossman School of MedicineNew YorkNYUSA Institute of Comparative Molecular Endocrinology Ulm UniversityUlmGermany Max Planck Institute for Molecular Biomedicine Department of Tissue Morphogenesisand University of MünsterFaculty of MedicineD-48149 MünsterGermany Department of Biochemistry and Molecular Biology University of Miami Miller School of MedicineMiamiFLUSA Department of Pathology NYU Robert I.Grossman School of MedicineNew YorkNYUSA Biomaterials Division New York University College of DentistryNew YorkNYUSA Hansjörg Wyss Department of Plastic Surgery NYU Grossman School of MedicineNew York UniversityNew YorkNYUSA Department of Biomedical Engineering Tandon School of EngineeringNew York UniversityBrooklynNYUSA Department of Cell Biology NYU Robert I.Grossman School of MedicineNew YorkNYUSA

Skeletal stem and progenitor cells(SSPCs) perform bone maintenance and repair. With age, they produce fewer osteoblasts and more adipocytes leading to a loss of skeletal integrity. The molecular mechanisms that underlie this detrimental transformation are largely unknown. Single-cell RNA sequencing revealed that Notch signaling becomes elevated in SSPCs during aging. To examine the role of increased Notch activity, we deleted Nicastrin, an essential Notch pathway component, in SSPCs in vivo. Middle-aged conditional knockout mice displayed elevated SSPC osteo-lineage gene expression, increased trabecular bone mass, reduced bone marrow adiposity, and enhanced bone repair. Thus, Notch regulates SSPC cell fate decisions, and moderating Notch signaling ameliorates the skeletal aging phenotype, increasing bone mass even beyond that of young mice. finally, we identified the transcription factor Ebf3 as a downstream mediator of Notch signaling in SSPCs that is dysregulated with aging, highlighting it as a promising therapeutic target to rejuvenate the aged skeleton.

关键词： Notch skeletal elevated

Matrix可脱弹簧圈作为血管内治疗脑内血管瘤的新方法:早期血管造影和临床预后的分析

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世界核心医学期刊文摘（神经病学分册） 2006年第3期2卷 45-46页

作者： Taschner C.A. leclerc X. Rachdi H. 牛亚利 Service de Neuroradiologic H■pital Roger Salengro C.H.R.U. Lille Rue Emile Laine F-59037 Lille Cedex France

Background and Purpose -Endovascular coil embolization has become an accepted alternative for the treatment of intracranial aneurysms. The purpose of this st udy was to evaluate the clinical safety and the angiographic stability of aneury sm occlusion with a new class of biologically active platinum coils after a 6-m onth period. Methods -Twenty-five patients with 25 intracranial aneurysms were treated by selective embolization with a new coated bioactive coil (Matrix; Bos ton Scientific Neurovascular). Matrix coils were used alone in 6 patients and in combination with Guglielmi detachable coils (GDCs; Boston Scientific Neurovascu lar) in 19. Angiographic results, procedure-related complications, and adverse neurological events during the follow-up period were recorded. Magnetic resonan ce angiography was performed at 6 months in all patients. Results -Initial angi ographies demonstrated complete occlusion in 17 patients, residual neck in 7, an d a persisting aneurysm in 1. The clinical follow-up showed stable results in a ll patients. The grade of aneurysm occlusion at 6 months improved in 4 patients, remained stable in 15, and deteriorated in 6. Three patients needed retreatment because of a major aneurysm recanalization. Angiographic recurrences in cases o f aneurysms treated with a combination of Matrix coils and GDCs occurred within the expected range for bare platinum coils. Two of 3 patients needing retreatmen t had been treated with Matrix coils alone. Conclusion -Stable results were obt ained predominantly when Matrix coils were combined with bare platinum coils. A prospective, randomized study is necessary to assess the potential benefit of Ma trix coils for patients treated by endovascular techniques.

关键词：血管内治疗 Matrix 血管瘤可脱弹簧圈血管造影磁共振血管成像临床安全性复查时间造影复

重组减毒细菌运送CD8+ T细胞表位的效应分析

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重组减毒细菌运送CD8+ T细胞表位的效应分析

减毒大肠杆菌对真核表达的CD8+T细胞表位的运送研究

全国人畜共患病学术研讨会

作者：潘志明张晓明焦新安 Richard Lo-Man Claude leclerc 刘秀梵扬州大学农业部畜禽传染病学重点开放实验室法国巴斯德研究所免疫调节生物学实验室

目的:分析重组减毒菌体外运送CD8T细胞表位的效应。方法:以表达OVA和LCMV CD8T细胞表位的重组菌13A(ptG2f)、25A(ptG2f)、SL7207(ptG2f)感染抗原提呈细胞LK、LL和骨髓源树突状细胞(BMDC),应用体外抗原提呈试验检测抗原提呈细胞对重组菌... 详细信息

目的:分析重组减毒菌体外运送CD8T细胞表位的效应。方法:以表达OVA和LCMV CD8T细胞表位的重组菌13A(ptG2f)、25A(ptG2f)、SL7207(ptG2f)感染抗原提呈细胞LK、LL和骨髓源树突状细胞(BMDC),应用体外抗原提呈试验检测抗原提呈细胞对重组菌运送的CD8T细胞表位的提呈效应。结果:感染试验证实,减毒菌13A、25A和SL7207对LK细胞或L细胞均具有良好的侵袭能力,BMDC对重组菌具有很好的摄取功能。抗原提呈试验结果显示,在感染早期(2h),LK、LL和BMDC细胞均可提呈重组菌13A(ptG2f)或SL7207(ptG2f)运送的T细胞表位;在感染晚期(48h),LK细胞对OVA257-264 CD8T细胞表位提呈效应降低,LL细胞对LCMV 118-132 CD8T细胞表位提呈效应增强。三种抗原提呈细胞均未对25A(ptG2f)运送的T细胞表位产生提呈效应。另外,在同样的作用条件下,BMDC对减毒菌运送的抗原表位的提呈效应要强于LK和LL细胞。结论:在体外证实了重组菌能运送CD8T细胞表位,为基于减毒细菌的新型基因工程疫苗的分子设计提供了有益借鉴。

关键词： CD8+T细胞表位减毒大肠杆菌减毒鼠伤寒沙门氏菌体外抗原提呈试验

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减毒大肠杆菌对真核表达的CD8+T细胞表位的运送研究