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Pathogenic conversion of regulatory B10 cells into osteoclastpriming cells in rheumatoid arthritis

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Pathogenic conversion of regulatory B10 cells into osteoclas...

第十届全国免疫学学术大会

作者： Hongjiang Liu Fanlei Hu Xia Zhang Liling Xu Yingni Li yuquan qian Yuqin Yang Limin Ren Jian Zhang Zhanguo Li Yuan Jia 北京大学人民医院风湿免疫研究所

Objective: Regulatory B10 cells were proved to be functionally impaired in rheumatoid arthritis(RA), with the potential of converting into pathogenic cells. A recent study suggested that B cells were a major source of Receptor activator of nuclear factor kappa B ligand(RANKL) in the joints of RA patients. Whether B10 could produce RANKL ectopically to perpetuate bone destruction remains unknown. The aim of this study was to characterize RANKL-producing B10 cells and reveal their bone-destructive capacities in ***: RANKL expression in healthy control and RA patient CD19CD24hi CD27 B10 cells, as well as other B cell subsets, including CD19 B cells, CD19CD27 memory B cells, CD19CD27CD27 non-B10 cells was evaluated by flow cytometry and seminested PCR & q PCR. The role of tumor necrosis factor alpha(TNF-α) and interleukin-1β(IL-1β) in inducing RANKL expression in B10 cells was evaluated by in vitro stimulation assay. The correlation between RANKL-producing B10 cells and clinical features of RA patients was analyzed using Spearman’s rank test. The bone destructive role of these RANKL-producing B10 cells in RA was revealed by osteoclast differentiation ***: Human B10 cells could ectopically express RANKL, which might be termed as RANKL-producing B10 *** RA circumstance, these RANKL-producing B10 cells expanded dramatically, which was partially induced by TNF-α. The frequencies of these cells correlated positively with RA disease activity and tender joint counts. Strikingly,RANKL-producing B10 cells from RA patients, but not healthy individuals could significantly promote osteoclast differentiation in vitro, thus perpetuating the bone ***: In RA, B10 cells demonstrated the potential of converting into RANKL-producing cells, thus promoting osteoclast formation and exacerbating bone destruction. Modulating the status of B10 cells might provide novel therapeutic strategies for RA

关键词： Rheumatoid arthritis Regulatory B10 cells RANKL Osteoclast

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物联网技术在医院中的应用

中国医院建筑与装备 2017年第5期18卷 97-99页

作者：刘玉泉钱强江苏省中西医结合医院南京210028

文章总结了物联网技术在医院中的具体应用,根据物联网应用针对的不同对象,对各种应用进行了简单的分类,提出了物联网在医院中应用时需要注意的问题。

关键词：物联网医院感知层

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轻板框架板——柱抗震节点的强度

武汉建材学院学报 1985年第1期 93-105页

作者：熊丹安茅玉泉钱康玲兵器工业部第六设计院兵器工业部第六设计院工程师

石家庄市 KQ-79型轻板框架板柱节点,不同于通常的梁-柱节点或板-柱节点.本文根据该节点抗震性能的试验结果,分析了节点的抗弯强度和节点核心区的抗剪强度。结合节点的特点,提出了节点传递极限弯矩和节点核心区抗剪能力的计算公式。

关键词：形板试件极限弯矩危险截面核心区

Nanoparticles targeting tumor-associated macrophages:A novel anti-tumor therapy

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Nano Research 2022年第3期15卷 2177-2195页

作者： Siyuan Chen Furong Qin Manni Wang yuquan Wei Zhiyong qian Xiawei Wei Laboratory of Aging Research and Cancer Drug Target State Key Laboratory of BiotherapyNational Clinical Research Center for GeriatricsWest China HospitalSichuan UniversityChengdu 610041China

The immunosuppressive tumor microenvironment(TME)is crucial in the occurrence of tumorigenesis,metastasis,and drug *** all stromal cells,tumor-associated macrophages(TAMs)are recognized as vital components causing the TME to be favorable for cancer cells and are also main targets in cancer *** date,nanoparticle(NP)-based drug delivery systems,as new technology platforms,have exhibited considerable advantages,such as targeted drug delivery at tumor sites,enhanced drug transport efficiency,and controllable drug release profiles,which provide new approaches for cancer *** TAM-targeting nanoparticles,various therapeutic strategies have been developed by varying their design,namely,by blocking TAM recruitment,promoting TAM transformation,and directly diminishing existing *** the current review,we provide a brief overview of the role of TAMs in the tumor microenvironment and their functions and highlight strategies for TAM ***,the applications of nanoparticles in targeting TAMs to improve cancer therapeutic efficiency are summarized.

关键词： tumors immunotherapy tumor-associated macrophages nanoparticles

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商业建筑色彩与造型设计要点研究

城市建筑 2014年第6期11卷 15-15页

作者：钱昱全中国建筑西南设计研究院有限公司 610041

本文针对商业建筑色彩与造型设计要点进行了探讨。商业建筑的外观造型与色彩有着很好的名片效果,能够给来往的顾客带来直观的视觉冲击。笔者结合自己的工作经验,对商业建筑的造型、色彩设计两方面内容做出了详细的分析。

关键词：商业建筑色彩与造型设计要点

Nanovaccines for cancer immunotherapy:Current knowledge and future perspectives

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Chinese Chemical Letters 2023年第8期34卷 57-68页

作者： Yiming Wu Zhe Zhang yuquan Wei Zhiyong qian Xiawei Wei Laboratory of Aging Research and Cancer Drug Target State Key Laboratory of Biotherapy and Cancer CenterNational Clinical Research Center for GeriatricsWest China HospitalSichuan UniversityChengdu 610041China

Cancer immunotherapy harnesses the immune system to attack tumors and has received extensive attention in recent *** vaccines as an important branch of immunotherapy are designed for delivering tumor antigens to antigen-presenting cells(APCs)to stimulate a strong immune response to against tumors,representing a potentially therapeutic and prophylactic effect with the long-term anticancer ***,the disappointing outcomes of their clinical use might be attributed to dilemma in antigen selection,immunogenicity,lymph nodes(LNs)targeting ability,lysosomal escape ability,immune evasion,***,aiming to overcome these barriers,has been utilized in cancer vaccine development for *** preclinical and clinical studies demonstrate positive results in nanomaterials-based cancer vaccines with considerable improvement in the vaccine *** this review,we systematically introduced the characteristics of nanovaccines and highlighted the different types of nanomaterials used for cancer vaccine *** addition,the opportunities and challenges of the emerging nanotechnology-based cancer vaccines were discussed.

关键词： Cancer immunotherapy Cancer vaccines Nanoparticles Antitumor immune response Clinical transformation

PEG400-mediated nanocarriers improve the delivery and therapeutic efficiency of mRNA tumor vaccines

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Chinese Chemical Letters 2024年第5期35卷 314-319页

作者： Wen Xiao Fazhan Wang Yangzhuo Gu Xi He Na Fan qian Zheng Shugang Qin Zhongshan He yuquan Wei Xiangrong Song Department of Critical Care Medicine Frontiers Science Center for Disease-related Molecular NetworkState Key Laboratory of BiotherapyWest China HospitalSichuan UniversityChengdu 610041China Medical Research Center The First Affiliated Hospital of Zhengzhou UniversityZhengzhou UniversityZhengzhou 450000China

Dendritic cell(DC)-targeted delivery of mRNA is a prominent method to boost the efficacy of mRNA tumor *** targeting ligands are often modified on nanocarriers by polyethylene glycol(PEG)linker in mRNA delivery *** the PEG linker length influences the targeting delivery efficiency of mRNA nanocarrier in vivo remains ***,we designed and constructed DC-targeted mRNA delivery systems modified by mannose via different PEG linker lengths(100/400/1000/2000)(MPn-LPX).The top candidate MP_(400)-LPX(the linker was PEG400)showed the optimal mRNA expression and antigen presentation owing to the highly efficient uptake by ***,MP_(400)-LPX could better inhibited tumor growth and extended survival in the E.G7-OVA lymphoma and TC-1 cervical tumor mouse ***,these results demonstrated that PEG400 was the optimal linker for the PEGylated DC-targeted mRNA *** findings provided a new platform for the rational design of targeted mRNA nanovaccines with shorter-length PEG.

关键词： Cancer immunotherapy mRNA vaccines DC-targeted delivery PEGylated liposomes Cellular uptake

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软组织肉瘤免疫联合靶向治疗研究进展

中国肿瘤临床与康复 2024年第10期31卷 598-609页

作者：曹杨王伟钱玉泉王明昭陈彤陈燕超徐海荣牛晓辉刘雨桃国家癌症中心、国家肿瘤临床医学研究中心、中国医学科学院、北京协和医学院肿瘤医院内科北京100021 国家骨科医学中心、首都医科大学附属北京积水潭医院北京100035

软组织肉瘤(STS)是一种发生在软组织的异质性肿瘤,涵盖众多组织学亚型。对于局部晚期或转移性STS,传统的手术和化疗效果欠佳,迫切需要开发新的治疗策略。近年来,免疫检查点抑制剂(ICIs)在晚期STS治疗中具有显著的抗肿瘤活性,同时,靶向... 详细信息

软组织肉瘤(STS)是一种发生在软组织的异质性肿瘤,涵盖众多组织学亚型。对于局部晚期或转移性STS,传统的手术和化疗效果欠佳,迫切需要开发新的治疗策略。近年来,免疫检查点抑制剂(ICIs)在晚期STS治疗中具有显著的抗肿瘤活性,同时,靶向药物的发展提高了治疗的精准性,靶向治疗与免疫治疗的联合应用为STS治疗开辟了新的可能。文章综述了靶向治疗与免疗治疗联合应用在STS治疗中的最新进展。

关键词：软组织肉瘤免疫治疗靶向治疗免疫检查点抑制剂

Sodium alginate coating simultaneously increases the biosafety and immunotherapeutic activity of the cationic mRNA nanovaccine

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Acta Pharmaceutica Sinica B 2023年第3期13卷 942-954页

作者： Xing Duan Yi Zhang Mengran Guo Na Fan Kepan Chen Shugang Qin Wen Xiao qian Zheng Hai Huang Xiawei Wei yuquan Wei Xiangrong Song Department of Critical Care Medicine Department of Clinical PharmacyFrontiers Science Center for Disease-related Molecular NetworkState Key Laboratory of Biotherapy and Cancer CenterWest China HospitalSichuan UniversityChengdu 610041China West China Hospital Sichuan UniversityChengdu 610041China

The extraordinary advantages associated with mRNA vaccines,including their high efficiency,relatively low severity of side effects,and ease of manufacture,have enabled them to be a promising immunotherapy approach against various infectious diseases and ***,most mRNA delivery carriers have many disadvantages,such as high toxicity,poor biocompatibility,and low efficiency in vivo,which have hindered the widespread use of mRNA *** further characterize and solve these problems and develop a new type of safe and efficient mRNA delivery carrier,a negatively charged SA@DOTAP-mRNA nanovaccine was prepared in this study by coating DOTAP-mRNA with the natural anionic polymer sodium alginate(SA).Intriguingly,the transfection efficiency of SA@DOTAP-mRNA was significantly higher than that of DOTAP-mRNA,which was not due to the increase in cellular uptake but was associated with changes in the endocytosis pathway and the strong lysosome escape ability of SA@*** addition,we found that SA significantly increased the expression of LUC-mRNA in mice and achieved certain spleen ***,we confirmed that SA@DOTAP-mRNA had a stronger antigen-presenting ability in E.G7-OVA tumor-bearing mice,dramatically inducing the proliferation of OVA-specific CLTs and ameliorating the antitumor ***,we firmly believe that the coating strategy applied to cationic liposome/mRNA complexes is of potential research value in the field of mRNA delivery and has promising clinical application prospects.

关键词： Negatively charged mRNA vaccine Sodium alginate Cationic liposome DOTAP Lysosomes escape Cancer Immunotherapy Toxicity