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Deciphering the pharmacological mechanism of Guan-Jie-Kang in treating rat adjuvant-induced arthritis

Hudan Pan, Yanfang Zheng, Zhongqiu Liu, Zhongwen Yuan, Rutong Ren, Hua Zhou, Ying Xie, Liang Liu

《医学前沿（英文）》 2019年第13卷第5期页码 564-574 doi: 10.1007/s11684-018-0676-2

摘要： Traditional Chinese medicine (TCM) formulas have attracted increasing attention worldwide in the past few years for treating complex disease including rheumatoid arthritis. However, their mechanisms are complex and remain unclear. Guan-Jie-Kang (GJK), a prescription modified from “Wu Tou Decoction,” was found to significantly relieve arthritis symptoms in rats with adjuvant-induced arthritis after 30-day treatment, especially in the 24 g/kg/day group. By analyzing 1749 targets related to 358 compounds in the five herbs of GJK, we identified the possible anti-arthritis pathways of GJK, including the calcium signaling and metabolic pathways. Bone damage levels were assessed by micro-computed tomography, and greater bone protective effect was observed with GJK treatment than with methotrexate. Receptor activator of nuclear factor κB ligand (RANKL)–RANK signaling, which is related to calcium signaling, was significantly regulated by GJK. Moreover, a target metabolomics assay of serum was conducted; 17 metabolic biomarkers showed significant correlations with treatment. An integrated pathway analysis revealed that pyruvate metabolism, purine metabolism, and glycolysis metabolism were significantly associated with the effects of GJK in arthritis treatment. Thus, this study establishes a new omics analytical method integrated with bioinformatics analysis for elucidating the multi-pathway mechanisms of TCM.

关键词： rheumatoid arthritis traditional Chinese medicine pharmacological mechanism metabolism adjuvant-induced arthritis omics analysis

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益生菌辅助治疗类风湿关节炎的益处：随机对照临床试验荟萃分析和系统综述 Article

潘胡丹, 李润泽, 李婷, 王俊, 刘良

《工程（英文）》 2017年第3卷第1期页码 115-121 doi: 10.1016/J.ENG.2017.01.006

摘要：

肠道和口腔菌群是影响类风湿关节炎(rheumatoid arthritis, 简称类风关) 发生、发展的重要因素。

关键词：类风湿关节炎临床试验益生菌辅助系统综述荟萃分析

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blood monocular cells by triptolid is associated with TNF-alpha-308 gene polymorphisms in rheumatoid arthritis

Xiu-Liang TAO MM, Sheng-Hao TU MD, Ri-Bo XIONG MM, Yong-Hong HU BM,

《医学前沿（英文）》 2010年第4卷第2期页码 220-224 doi: 10.1007/s11684-010-0025-6

摘要： This study examined the inhibitory effect of triptolid (TP) on tumor necrosis factor-α (TNF-α) secreted from peripheral blood monocular cells (PBMCs) and the association of the inhibitory effect with TNF-α-308 gene polymorphisms in rheumatoid arthritis (RA) patients. Gene polymorphism at A-G site 308 in the promoter region of TNF-α gene was detected in 42 RA patients by using allele specific polymerase chain reaction (AS-PCR) assay. PBMCs were harvested from these patients and treated first with lipopolysaccharides (LPS) and then with different doses of TP (1, 5.4 and 15 ng/mL). The TNF-α level in the supernatants was measured by enzyme-linked immunosorbent assay (ELISA). The results showed that TNF-α level in the supernatants of TP (1 ng/mL)-treated PBMCs was decreased by 3.80% and 4.91%, respectively, in the patients with AA and AG genotypes, when compared with those treated with LPS alone (>0.05). Moreover, the TNF-α level in the patients with GG genotype was reduced by 20.74% (<0.05). When PBMCs were treated with TP at 5.4 ng/mL, TNF-α levels in the patients with AA, AG, and GG genotypes were decreased by 20.42%, 34.73%, and 41.69%, respectively (<0.05). The TNF-α level was slightly higher in the PBMCs treated with 15 ng/mL of TP than those in the two TP groups in the patients carrying AA, AG, and GG genotypes (>0.05). It was concluded that gene polymorphism at TNF-α-308 sites may relate to the secretion of TNF-α in RA patients. TP has different inhibitory effects on the secretion of TNF-α in the patients harboring different genotypes, which may be one of the reasons for individual variation in response to TP.

关键词： arthritis rheumatoid molonuclear cells tumor necrosis factor gene polymorphisms triptolid

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传统中医药治疗类风湿性关节炎——从经验医学到循证医学 Review

潘胡丹, 肖瑶, 王婉莹, 任汝通, 梁丽娴 , 刘良

《工程（英文）》 2019年第5卷第5期页码 895-906 doi: 10.1016/j.eng.2019.01.018

摘要：

类风湿关节炎（RA）是一种常见的自身免疫性疾病，病因难以捉摸。常规和生物疾病缓解药物有时会失效或仅产生部分反应。中药（TCM）长期以来一直在中国用作RA的治疗方法，并在世界范围内得到越来越多的接受。传统上，中医治疗以中医辨证论治为指导。但是，它们仍然依赖于中医理论和医生进行经验实践

关键词：中药，类风湿关节炎，循证治疗，展望

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Genetic and clinical markers for predicting treatment responsiveness in rheumatoid arthritis

Xin Wu, Xiaobao Sheng, Rong Sheng, Hongjuan Lu, Huji Xu

《医学前沿（英文）》 2019年第13卷第4期页码 411-419 doi: 10.1007/s11684-018-0659-3

摘要： Although many drugs and therapeutic strategies have been developed for rheumatoid arthritis (RA) treatment, numerous patients with RA fail to respond to currently available agents. In this review, we provide an overview of the complexity of this autoimmune disease by showing the rapidly increasing number of genes associated with RA. We then systematically review various factors that have a predictive value (predictors) for the response to different drugs in RA treatment, especially recent advances. These predictors include but are certainly not limited to genetic variations, clinical factors, and demographic factors. However, no clinical application is currently available. This review also describes the challenges in treating patients with RA and the need for personalized medicine. At the end of this review, we discuss possible strategies to enhance the prediction of drug responsiveness in patients with RA.

关键词： rheumatoid arthritis gene clinical markers therapy

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血清鸟氨酸水平下降与类风湿关节炎缓解情况密切相关——从青藤碱的一项随机双盲临床试验中得到的启示 Article

石颖, 潘胡丹, 伍建林, 邹庆华, 谢昕怡, 李红刚, 周华, 卞西清, 冷文飞, 王灿坚, 王亚峰, 方勇飞, 刘良

《工程（英文）》 2022年第16卷第9期页码 93-99 doi: 10.1016/j.eng.2021.04.014

摘要：

青藤碱（SIN）是中国类风湿关节炎（RA）治疗的常用药物，但目前尚无SIN单药治疗疗效的文献报道。本研究旨在探讨SIN治疗RA的有效性和安全性，并分析鸟氨酸水平与RA患者疾病活动情况的相关性。本项目设计为24周的多中心、随机、安慰剂对照、双盲临床试验，轻中度活动度的RA患者按照1∶1∶1随机分配接受SIN（120 mg，每日两次）、甲氨蝶呤（MTX）（每周10 mg）或SIN + MTX治疗。项目以24周达到ACR50标准的受试者比例，以及根据临床疾病活动指数(CDAI)显示改善的受试者比例为主要疗效指标，并进一步分析24周治疗后的RA受试者疾病活动变化是否与血清鸟氨酸水平相关。在135名受试者中，38名、39名和36名分别接受了SIN、MTX和SIN + MTX的治疗。在SIN治疗组中，52.63%的受试者在治疗24周后达到ACR50标准，与MTX治疗组和SIN + MTX治疗组的结果相当。患者不良反应以肝功能损害和胃肠功能紊乱为主，但SIN组肝功能损害的发生率（1/38）明显低于MTX组（10/39）和SIN + MTX组（8/36）。采用超高效液相-四极杆飞行时间质谱仪（UHPLC-Q-TOF/MS），测定了三个治疗组4个随访时间点共计221份血清样本中的鸟氨酸、瓜氨酸和精氨酸的含量。治疗24周后，血清鸟氨酸水平随着疾病活动度的降低而下降，敏感度为80%，提示鸟氨酸水平可一定程度上预测治疗应答情况。综上所述，SIN对RA患者的疗效与MTX相当，副作用更少，且首次发现血清鸟氨酸水平与类风湿关节炎的缓解密切相关，提示鸟氨酸具有成为类风湿关节炎疗效评价指标的潜在价值。

关键词：类风湿关节炎青藤碱有效性安全性炎性因子

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血清淀粉样蛋白各亚型在类风湿性关节炎发病机制中的作用 Article

梁丽娴, 赖焕玲, 李润泽, 潘胡丹, 江泽波, 李莹, 段富刚, 徐家辉, 张懿中, 石阿西, 魏春莉, 张方圆, 姚小军, 刘良

《工程（英文）》 2022年第10卷第3期页码 174-182 doi: 10.1016/j.eng.2020.08.018

摘要：前期研究通过全外显子组测序，在类风湿性关节炎（rheumatoid arthritis, RA）患者中发现一种新的致病突变发生在SAA1.2 的序列中。

关键词：血清淀粉样蛋白类风湿性关节炎发病机制关节内注射

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between cold and hot pattern in traditional Chinese medicine and gene expression profiles in rheumatoid arthritis

Miao Jiang, Cheng Xiao, Gao Chen, Cheng Lu, Qinglin Zha, Xiaoping Yan, Weiping Kong, Shijie Xu, Dahong Ju, Pu Xu, Youwen Zou, Aiping Lu

《医学前沿（英文）》 2011年第5卷第2期页码 219-228 doi: 10.1007/s11684-011-0133-y

摘要： Clinical manifestations of rheumatoid arthritis (RA) are diversified, and based on the manifestations, the patients with RA could be classified into different patterns under traditional Chinese medicine. These patterns decide the selection of herbal prescription, and thus they can help find a subset of rheumatoid arthritis patients for a type of therapy. In the present study, we combine genome-wide expression analysis with methods of systems biology to identify the functional gene networks for the sets of clinical symptoms that comprise the major information for pattern classification. Clinical manifestations in rheumatoid arthritis were clustered with factor analysis, and two factors (similar to cold and hot patterns in traditional Chinese medicine) were found. Microarray technology was used to reveal gene expression profiles in CD4 T cells from 21 rheumatoid arthritis patients. Protein-protein interaction information for these genes from databases and literature data was searched. The highly-connected regions were detected to infer significant complexes or pathways in this protein-protein interaction network. The significant pathways and function were extracted from these subnetworks using the Biological Network Gene Ontology tool. The genes significantly related to hot and cold patterns were identified by correlations analysis. MAPK signalling pathway, Wnt signaling pathway, and insulin signaling pathway were found to be related to hot pattern. Purine metabolism was related to both hot and cold patterns. Alanine, aspartate, and tyrosine metabolism were related to cold pattern, and histindine metabolism and lysine degradation were related to hot pattern. The results suggest that cold and hot patterns in traditional Chinese medicine were related to different pathways, and the network analysis might be used for identifying the pattern classification in other diseases.

关键词： gene expression profile pathway rheumatoid arthritis traditional Chinese medicine systems biology