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Gut microbial metabolite targets HDAC3-FOXK1-interferon axis in fibroblast-like synoviocytes to ameliorate rheumatoid arthritis

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Bone Research 2024年第2期12卷 421-437页

作者： Hongzhen Chen Xuekun Fu Xiaohao Wu Junyi Zhao Fang Qiu Zhenghong Wang Zhuqian Wang Xinxin Chen Duoli Xie Jie Huang Junyu Fan Xu Yang Yi Song Jie Li dongyi he Guozhi Xiao Aiping Lu Chao Liang Department of Systems Biology School of Life SciencesSouthern University of Science and TechnologyGuangdong Provincial Key Laboratory of Cell Microenvironment and Disease ResearchShenzhen Key Laboratory of Cell MicroenvironmentShenzhen 518055China Institute of Integrated Bioinfomedicine and Translational Science(IBTS) School of Chinese MedicineHong Kong Baptist UniversityHong Kong SAR 999077China Department of Biochemistry School of MedicineSouthern University of Science and TechnologyGuangdong Provincial Key Laboratory of Cell Microenvironment and Disease ResearchShenzhen Key Laboratory of Cell MicroenvironmentShenzhen 518055China Division of Immunology and Rheumatology Stanford UniversityStanfordCA 94305USA VA Palo Alto health Care System Palo AltoCA 94304USA Institute of Plant and Food Science Department of BiologySouthern University of Science and TechnologyShenzhen 518055China Department of Rheumatology Guanghua Hospital Affiliated to Shanghai University of Traditional Chinese MedicineShanghai University of Traditional Chinese MedicineShanghaiChina Department of Computational Biology St.Jude Children’s Research HospitalMemphisTNUSA Department of Laboratory Medicine Peking University Shenzhen HospitalShenzhenChina Guangdong-Hong Kong-Macao Joint Lab on Chinese Medicine and Immune Disease Research Guangzhou 510006China Shanghai University of Traditional Chinese Medicine Shanghai 200032China State Key Laboratory of Proteomics National Center for Protein Sciences(Beijing)Beijing Institute of Lifeomics100850 BeijingChina

Rheumatoid arthritis(RA)is an autoimmune *** studies hold an opinion that gut microbiota is environmentally acquired and associated with RA ***,accumulating evidence demonstrates that genetics also shape the gut *** is known that some strains of inbred laboratory mice are highly susceptible to collagen-induced arthritis(CIA),while the others are resistant to ***,we show that transplantation of fecal microbiota of CIA-resistant C57BL/6J mice to CIA-susceptible DBA/1J mice confer CIA resistance in DBA/1J mice.C57BL/6J mice and healthy human individuals have enriched *** than DBA/1J mice and RA *** of *** prevents CIA in DBA/1J *** identify that *** mainly produces propionate and C57BL/6J mice and healthy human individuals have higher level of ***-like synoviocytes(FLSs)in RA are activated to undergo tumor-like *** disrupts HDAC3-FOXK1 interaction to increase acetylation of FOXK1,resulting in reduced FOXK1 stability,blocked interferon signaling and deactivation of *** treat CIA mice with propionate and show that propionate attenuates ***,a combination of propionate with anti-TNF etanercept synergistically relieves *** results suggest that *** or propionate could be an alternative or complementary approach to the current therapies.

关键词： HDAC3 cytes interferon

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类风湿关节炎治疗的进展与挑战

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中国药学杂志 2024年第3期59卷 200-209页

作者：姜平常岑许林帅时一鸣何东仪上海中医药大学附属光华医院上海200052 上海中医药大学上海201203 上海市光华中西医结合医院关节炎研究所上海200052

类风湿关节炎(rheumatoid arthritis, RA)是一种慢性、全身性、异常的炎性免疫反应。其特点是累及滑膜和多器官,并造成关节和关节软骨破坏。在过去的30年里,一些有希望的新化合物和抗体已经被开发出来用于治疗RA。而RA治疗药物的引入和... 详细信息

类风湿关节炎(rheumatoid arthritis, RA)是一种慢性、全身性、异常的炎性免疫反应。其特点是累及滑膜和多器官,并造成关节和关节软骨破坏。在过去的30年里,一些有希望的新化合物和抗体已经被开发出来用于治疗RA。而RA治疗药物的引入和精准医学的发展也引发了与患者获得新疗法、最佳方案选择、成本效益、预后监测和疗效监测相关的几个问题,特别是在药物反应率低、耐药性和不良副作用方面。人们非常重视治疗RA的最佳药物组合,特别是在症状严重或早期进展的患者中。解决这些问题需要新的治疗方法和新的机制,并为药物选择、药物重组建立准确的指南。笔者根据美国国家医学图书馆的临床试验数据库,综述了有前景的新药,并讨论了RA药物开发的趋势和治疗中的挑战,为RA的精准治疗和未来的研究方向提供了参考。

关键词：类风湿关节炎精准医学新疗法药物开发

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Prevalence of type 2 diabetes among rheumatoid arthritis patients:a large retrospective study

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Chinese Medical Journal 2022年第20期135卷 2515-2517页

作者： Zhenge Han Qi Zhou Hairong Han Weizhen Qiao Zhonghong Qie dongyi he Department of Laboratory Guanghua Hospital of Traditional and Western MedicineShanghai 200052China Department of Rehabilitation Medicine Shanghai Xuhui Central HospitalShanghai 200031China Department of Central Laboratory Wuxi People's Affiliated of Nanjing Medical UniversityWuxiJiangsu 214023China Department of Clinical Laboratory Huadong SanatoriumWuxiJiangsu 214065China Department of Rheumatism Guanghua Hospital of Traditional and Western MedicineShanghai 200052China

To the Editor:Rheumatoid arthritis(RA)is a chronic inflammatory disease characterized by an excess of cardiovascular disease(CVD)risk,estimated to be at least 50%greater than the general population.[1]CVD has been recognized as the main cause of mortality in established RA patients,but recent data confirm this trend also in earlier stages of the disease.[2]Several factors have been evoked as determinants of this additional risk,but the most consolidated theory attributes this phenomenon to the interplay between chronic high-grade inflammation and elevated prevalence of“classical”cardiovascular risk factors,including diabetes.

关键词： patients cardiovascular diabetes

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基于DCE-MRI图像TIC分析法的类风湿关节滑膜炎定量评估

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中国医学物理学杂志 2024年第4期41卷 426-432页

作者：毛瑾玲朱中旗李英豪何东仪姜婷夏天石洁汪红志华东师范大学物理与电子科学学院/上海市磁共振重点实验室上海200062 上海市光华中西医结合医院医学影像科上海200523

目的:为了提高对评估类风湿性关节炎(RA)的诊断敏感性,对滑膜血管翳尤其是炎性血管翳的形状及数量进行量化评估和可视化呈现,为临床指导用药提供可靠依据。方法:对18例经临床病理确诊的RA患者行手腕关节DCE-MRI检查,统一对第4个时相的... 详细信息

目的:为了提高对评估类风湿性关节炎(RA)的诊断敏感性,对滑膜血管翳尤其是炎性血管翳的形状及数量进行量化评估和可视化呈现,为临床指导用药提供可靠依据。方法:对18例经临床病理确诊的RA患者行手腕关节DCE-MRI检查,统一对第4个时相的增强图像进行感兴趣区域(ROI)勾画。采用Spearman相关性分析评价该病例的时间强度曲线(TIC)参数[早期增强率(MSI)、强化幅值差(MSD)、达峰时间、拟合曲线尾部切线斜率]之间的相关性并确定其独立特征。使用独立特征定义4型曲线(Ⅰ型,缓升型;Ⅱ型,速升速降型;Ⅲ型,速升平台型;Ⅳ型,速升缓升型),并计算出ROI内每个类型TIC所占容积,再与RAMRIS评分结果进行比较确定相关性最强的TIC,基于该曲线特征进行滑膜炎的定量分级和二维多切片彩色编码显示。结果:MSI与MSD存在显著的正相关,Ⅱ型区域容积与RAMRIS评分具有极好的相关性(r=0.812),即动态增强MRI图像中,TIC为速升速降型区域符合滑膜炎性血管翳类型。结论:TIC分析法方便医生精准地进行炎性血管翳的定量分析,为RA患者疾病严重程度的诊断及用药治疗前后对比提供重要临床信息。

关键词：滑膜炎血管翳腕关节磁共振成像 TIC分析

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脾肾论治炎症性肠病合并强直性脊柱炎探讨

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湖南中医药大学学报 2024年第8期44卷 1490-1494页

作者：高思远顾杨怡张笑沈逸程鹏常岑何东仪朱琦李黎上海中医药大学附属光华医院上海200052 上海中医药大学上海201203 上海中医药大学附属光华医院关节内科上海200052 上海市中医药研究院中西医结合关节炎研究所上海200052

炎症性肠病常合并强直性脊柱炎有肠外病变表现,现代医学目前对于该共病发病机制尚不明确,临床缺乏有效防治方法,无法从根本上改善疾病的预后和减少复发。中医学认为该共病发病多为脾肾失司,二者制化失常为其主要病机表现。临床表现或以... 详细信息

炎症性肠病常合并强直性脊柱炎有肠外病变表现,现代医学目前对于该共病发病机制尚不明确,临床缺乏有效防治方法,无法从根本上改善疾病的预后和减少复发。中医学认为该共病发病多为脾肾失司,二者制化失常为其主要病机表现。临床表现或以脾胃升降失司为主,或以肾虚温煦不足为主。治疗从脾肾论治出发,在炎症性肠病合并强直性脊柱炎共病的临床诊断和治疗中具有良好的临床效果。通过探讨从脾肾论治炎症性肠病及其肠外表现强直性脊柱炎共病的中医治疗经验,并附临床验案一则,以供临床参考借鉴。

关键词：炎症性肠病肠外病变强直性脊柱炎脾肾学说温肾健脾共病

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系统性硬化病肺间质病变临床分析

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中华风湿病学杂志 2024年第4期28卷 237-243页

作者：王蕾郗艳孔祥贞屠文震舒政陈园园孙大燕何东仪上海中医药大学附属上海市中西医结合医院风湿病科上海200082 上海中医药大学附属上海市中西医结合医院放射科上海200082 复旦大学生命科学院上海200438 首都医科大学附属北京儿童医院新生儿外科北京100045 上海中医药大学附属光华医院关节内科上海200052

目的回顾性分析202例系统性硬化病(SSc)合并肺间质病变(ILD)患者的疾病特点,研究不同分型SSc-ILD的特征及其与血管病变及抗体的相关性,加强对SSc-ILD的疾病认识。方法收集2021年5月至2022年9月在上海市中西医结合医院住院的249例SSc患... 详细信息

目的回顾性分析202例系统性硬化病(SSc)合并肺间质病变(ILD)患者的疾病特点,研究不同分型SSc-ILD的特征及其与血管病变及抗体的相关性,加强对SSc-ILD的疾病认识。方法收集2021年5月至2022年9月在上海市中西医结合医院住院的249例SSc患者的病例资料,分别通过SSc-ILD与SSc非ILD 2组间比较以及SSc-ILD组内不同分型之间的比较,分析SSc-ILD的疾病特点,及其与血管病变、自身抗体之间的相关性。统计分析方法根据数据类型,分别采用配对t检验、Wilcoxon符号秩和检验或χ^(2)检验。结果本研究中202例SSc-ILD患者中女性患者183例(90.6%),47例SSc非ILD患者中女性患者36例(76.6%),女性SSc患者出现ILD的发生率明显高于男性(χ^(2)=7.05,P=0.008)。胸部高分辨率CT(HRCT)发现磨玻璃影最常见(90.1%);小叶内间隔增厚、网状影的发生率均高达70.0%以上;其次是小叶间隔增厚、支气管牵拉,发生率均高于50.0%。普遍型间质性肺炎(UIP)组肺纤维化积分[23.77(10.69,36.54)]高于非特异性间质性肺炎(NSIP)组[12.63(3.44,17.89),Z=5.19,P<0.001];NSIP(纤维化型)(f-NSIP)组肺纤维化积分[18.55(6.52,26.06)]高于NSIP(细胞型)(c-NSIP)组[5.27(1.15,7.55),Z=7.59,P<0.001];肺纤维化积分与SSc发病年龄呈正相关(r=0.02,P=0.021)。UIP患者病程中伴发毛细血管扩张(37.5%与19.9%,χ^(2)=2.60,P=0.009)、皮肤溃疡(48.2%与31.5%,χ^(2)=2.21,P=0.027)及指骨吸收(51.8%与28.1%,χ^(2)=3.17,P=0.002)的发生率高于NSIP;f-NSIP组病程中出现毛细血管扩张(27.2%与10.8%,χ^(2)=2.26,P=0.024)与指骨吸收(35.8%与18.5%,χ^(2)=2.32,P=0.021)的发生率高于c-NSIP组。SSc-ILD患者的抗Scl-70抗体阳性率(76.2%与23.4%)明显高于SSc非ILD组患者(χ^(2)=47.61,P<0.001);而SSc非ILD组患者的抗着丝点抗体阳性率(31.9%与11.4%)明显高于SSc-ILD组患者(χ^(2)=12.42,P=0.001)。SSc-ILD组患者的抗SSB抗体阳性率(9.9%与0)具有显著性差异(P=0.025)。结论抗Scl-70抗体阳性与SSc-ILD的发生相关,抗SSB抗体阳性可能是SSc患者出现ILD的危险因素。

关键词：硬化病,系统性肺炎纤维化普遍型间质性肺炎非特异性间质性肺炎自身抗体

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类风湿关节炎患者外周血循环中淋巴细胞特异性蛋白酪氨酸激酶甲基化的特征研究

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中华风湿病学杂志 2024年第3期28卷 155-161,I0002页

作者：许玲夏常岑姜平魏凯赵佳男郑义馨单雨时一鸣金晔华沈逸郭士成何东仪刘佳上海中医药大学附属光华医院关节内科上海200052 美国威斯康辛大学麦迪逊分校医学与公共卫生学院医学遗传学系美国威斯康星麦迪逊53706

目的分析类风湿关节炎(RA)患者外周血循环的淋巴细胞特异性蛋白酪氨酸激酶(LCK)启动子区域的甲基化特征及其与临床指标的相关性。方法采用靶向甲基化测序方法分析比较RA与健康对照(HC)和骨关节炎(OA)患者外周血LCK启动子区域7个CpG位点... 详细信息

目的分析类风湿关节炎(RA)患者外周血循环的淋巴细胞特异性蛋白酪氨酸激酶(LCK)启动子区域的甲基化特征及其与临床指标的相关性。方法采用靶向甲基化测序方法分析比较RA与健康对照(HC)和骨关节炎(OA)患者外周血LCK启动子区域7个CpG位点的甲基化水平,并与临床信息进行相关性分析和ROC曲线构建。结果采用非参数检验分析发现,与HC[0.53(0.50,0.57)]和OA患者[0.59(0.54,0.62)]相比,RA患者[0.63(0.59,0.68)]的整体甲基化水平升高(H=47.17,P<0.001)。同时与HC组[0.38(0.35,0.41)、0.59(0.55,0.63)、0.60(0.55,0.64)、0.59(0.55,0.63)、0.58(0.53,0.62)、0.45(0.43,0.49)、0.57(0.54,0.61)]相比,RA组cg0535031560、cg0535031580、cg0535031595、cg05350-315101、cg05350315104、cg05350315128和cg05350315142CpG位点的甲基化水平都显著升高[0.46(0.42,0.49)、0.70(0.65,0.75)、0.70(0.66,0.76)、0.70(0.65,0.75)、0.69(0.64,0.74)、0.55(0.51,0.59)、0.68(0.63,0.73)],差异具有统计学意义(Z=-5.63,-5.89,-5.91,-5.89,-5.98,-5.95,-5.95,均P<0.001)。与OA组相比[0.65(0.59,0.69)、0.65(0.60,0.69)、0.64(0.58,0.68)、0.50(0.45,0.54)、0.63(0.58,0.67)],RA组cg0535-031595、cg05350315101、cg05350315104、cg05350315128、cg05350315142的CpG位点甲基化水平都显著升高[0.70(0.66,0.76)、0.70(0.65,0.75)、0.69(0.64,0.74)、0.55(0.51,0.59)、0.68(0.63,0.73)],差异具有统计学意义(Z=-3.56、-3.52、-3.60、-3.67、-3.62,P=0.036、0.042、0.031、0.030、0.030)。此外,利用Pearson相关分析发现该区域整体甲基化水平与CRP(r=0.19,P=0.004)和ESR(r=0.14,P=0.035)呈正相关。CRP(低)组[0.63(0.58,0.68)]的LCK启动子区域整体甲基化水平高于CRP(高)组[0.65(0.61,0.70)],差异有统计学意义(Z=2.60,P=0.009)。最后,通过构建ROC曲线,验证外周血LCK启动子区域甲基化水平作为RA患者,特别是血清阴性RA患者与HC、OA组的鉴别效能,曲线下面积(AUC)值(95%CI)为0.78(0.63,0.93)。结论本研究提供了RA患者外周血LCK启动子区域甲基化状态和甲基化单倍型模式特征,该区域整体甲基化水平与炎症水平呈正相关,同时可用于鉴别血清阴性RA患者与HC、OA患者。

关键词：关节炎类风湿甲基化淋巴细胞特异蛋白质酪氨酸激酶p56(LCK) cg05350315

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Honeycomb-like biochar framework coupled with Fe_(3)O_(4)/FeS nanoparticles as efficient heterogeneous Fenton catalyst for phenol degradation

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Journal of Environmental Sciences 2024年第2期136卷 390-399页

作者： Aihua Cheng Yi he Xiaohe Liu Chi he Department of Environmental Engineering College of Geology and EnvironmentXi’an University of Science and TechnologyXi’an 710054China State Key Laboratory of Multiphase Flow in Power Engineering School of Energy and Power EngineeringXi’an Jiaotong UniversityXi’an 710049China National Engineering Laboratory for VOCs Pollution Control Material and Technology University of Chinese Academy of SciencesBeijing 101408China

Achieving an efficient and stable heterogeneous Fenton reaction over a wide pH range is of great significance for wastewater ***,a pollen-derived biochar catalyst with a unique honeycomb-like structure,coupled with the dispersion of magnetic Fe_(3)O_(4)/FeS(Fe/S)nanoparticles,was synthesized by simple impregnation precursor,followed by *** prepared Fe/S-biochar catalyst demonstrated outstanding phenol degradation efficiency across a wide pH range,with 98%of which eliminated even under neutral conditions(pH 7.0).The high catalytic activity was due to the multilevel porous structure of pollenderived biochar provided enough active sites and allowed for better electron transfer,then increases oxidation ability to promote the ***,the acid microenvironment formed by SO_(4)^(2-)group from Fe/S composite extended the pH range for Fenton reaction,and S^(2-)facilitated the conversion of≡Fe^(3+)to≡Fe^(2+),resulting in remarkable degradation ***,biochar can effectively promote cycling stability by limiting Fe *** work may provide a general strategy for designing 3D framework biochar-based Fe/S catalysts with excellent performance for heterogeneous Fenton reactions.

关键词： Biomass Biochar Fenton reaction Fe_(3)O_(4)/FeS(Fe/S) Phenol degradation

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Antigen-presenting effects of effector memory Vγ9Vδ2 T cells in rheumatoid arthritis

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Cellular & Molecular Immunology 2012年第3期9卷 245-254页

作者： Chaoying Hu Liu Qian Yi Miao Qiuyu Huang Ping Miao Ping Wang Qiwen Yu Hong Nie Jiying Zhang dongyi he Rong Xu Xuehua Chen Bingya Liu Dongqing Zhang Shanghai Institute of Immunology Shanghai Jiao Tong University School of MedicineShanghaiChina Central laboratory Shanghai Xuhui Central HospitalShanghaiChina Guanghua Rheumatoid Arthritis Specialized Hospital ShanghaiChina Shanghai Jiao Tong University School of Medicine Ruijin HospitalShanghaiChina

Rheumatoid arthritis is an autoimmune disease that primarily affects the limbs, but the pathogenic mechanism remains unclear. 78 T cells, a T-cell subpopulation, are characterized by multiple biological functions and associated with a variety of diseases. This study investigated the antigen-presenting effects of γδ2 cells and their relationship with rheumatoid arthritis development. We found that Vγ9Vδ2 T cells （the predominant subtype of γδ T cells in peripheral blood） were activated by isopentenyl pyrophosphate to continuously proliferate and differentiate into effector memory cells. The effector memory Vγ9Vδ2 T cells exhibited phenotypic characteristics of specific antigen-presenting cells, including high HLA-DR and CD80/86 expression. These Vγ9Vδ2 T cells could present soluble antigens and synthetic peptides to CD4＋ T cells. Vγ9Vδ2 T cells with different phenotypes showed different cytokine secretion patterns. Effector memoryVγ9Vδ2 T cells simultaneously secreted not only interferon （IFN）-γbut also IL-17. The peripheral blood and joint synovial fluid from RA patients contained numerous heterogeneous γδ T cells that were predominantly effector memory Vγ9Vδ2 T cells with the ability to secrete inflammatory factors. We also found that γδ T cells had a similar antigen-presenting capability to B cells. These results suggest that during the development of rheumatoid arthritis, 78 T cells can aggravate immune dysfunction and produce abnormal immune damage by secreting cytokines and inducing inflammatory cells to participate in synergistic inflammatory responses. Furthermore, γδ T cells can behave similarly to B cells to present viral peptides and autoantigen peptides to CD4＋ T cells, thus sustaining CD4＋ T-cell activation.

关键词： antigen-presenting function rheumatoid arthritis γδT cell TEM Vγ9Vδ2 T cell

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Distributed Optimal Variational GNE Seeking in Merely Monotone Games

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IEEE/CAA Journal of Automatica Sinica 2024年第7期11卷 1621-1630页

作者： Wangli he Yanzhen Wang IEEE the Key Laboratory of Smart Manufacturing in Energy Chemical Process Ministry of EducationEast China University of Science and TechnologyShanghai 200237China

In this paper, the optimal variational generalized Nash equilibrium(v-GNE) seeking problem in merely monotone games with linearly coupled cost functions is investigated, in which the feasible strategy domain of each agent is coupled through an affine constraint. A distributed algorithm based on the hybrid steepest descent method is first proposed to seek the optimal v-GNE. Then, an accelerated algorithm with relaxation is proposed and analyzed, which has the potential to further improve the convergence speed to the optimal v-GNE. Some sufficient conditions in both algorithms are obtained to ensure the global convergence towards the optimal v-GNE. To illustrate the performance of the algorithms, numerical simulation is conducted based on a networked Nash-Cournot game with bounded market capacities.

关键词： Distributed algorithms equilibria selection generalized Nash equilibrium(GNE) merely monotone games

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