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Complementary and Alternative Medicine in Rheumatoid Arthritis

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Chinese Journal of Integrative Medicine 2011年第10期17卷 731-734页

作者： Chandrashekara S Department of Immunology and rheumatology ChanRe Rheumatology and Immunology Center and ResearchBangalore(560079)India

There are studies that have evidence for and are against to suggest that some of the complementary and alternative medicines （CAM） are effective against rheumatoid arthritis （RA）. However, there are no adequate studies that have evaluated the role that can be played by CAM in the management of RA. A focused approach in defining the role and limitation as well as the possible adverse events and safety should help in integrating both CAM and mainstream treatment of RA. This review discussed the limitations in the available literature and the direction for future research, which can accelerate the defining role of CAM in RA.

关键词： rheumatoid arthritis complementary and alternative therapy

nvolvement of collagen-binding heat shock protein 47 in scleroderma-associated fibrosis

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Protein & Cell 2015年第8期6卷 589-598页

作者： Haiyan Chu Ting Wu Wenyu Wu Wenzhen Tu Shuai Jiang Sidi Chen Yanyun Ma Qingmei Liu Xiaodong Zhoua Li Jin Jiucun Wang Ministry of Education Key Laboratory of Contemporary Anthropology and State Key Laboratory of Genetic Engineering Collaborative Innovation Center for Genetics and Development School of Life Sciences and Institutes of Biomedica Sciences Fudan University Shanghai 200438 China Division of Dermatology Huashan Hospital Fudan University Shanghai 200040 China Division of rheumatology Shanghai TCM-Integrated Hospital Shanghai 200082 China Division of rheumatology University of Texas Health Science Center at Houston Houston TX 77030 USA Institute of rheumatology Immunology and Allergy Fudan University Shanghai 20080 China

Uncontrolled fibrosis of skin and internal organs is the main characteristic of scleroderma, and collagen is a major extracellular matrix protein that deposits in the fibrotic organs. As the chaperone of collagen, heat shock protein 47 （HSP47） is closely related with the development of fbrosis. To explore the potential func- tion of HSP47 in the pathogenesis of scleroderma, the clinical, in vivo and in vitro studies were performed. In clinical, the increased mRNA level of HSP47 was observed in the skin fibroblasts and PBMC from scle- roderma patients, and the enhanced protein level of HSP47 was also detected in the skin biopsy and plasma of the above patients. Unexpectedly, the enhanced levels of HSP47 were positively correlated with the presence of anti-centromere antibody in scleroderma patients. Moreover, a high expression of HSP47 was found in the skin lesion of BLM-induced scleroderma mouse model. Further in vitro studies demonstrated that HSP47 knockdown could block the intracellular and extracellular collagen over-productions induced by exogenous TGF-13. Therefore, the results in this study provide direct evidence that HSP47 is involved in the pathogenesis of scleroderma. The high expression of HSP47 can be detected in the circulatory system of scleroderma patients, indicating that HSP47 maybecome a pathological marker to assess the progres- sion of scleroderma, and also explain the systemic fibrosis of scleroderma. Meanwhile, collagen over-ex- pression is blocked by HSP47 knockdown, suggesting the possibility that HSP47 can be a potential therapeutic target for scleroderma.

关键词： systemic sclerosis fibrosis collagenheat shock protein 47 anti-centromere antibody,therapeutic target

B1-cell-produced anti-phosphatidylserine antibodies contribute to lupus nephritis development via TLR-mediated Syk activation

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Cellular & Molecular Immunology 2023年第8期20卷 881-894页

作者： Kongyang Ma Wenhan Du Shiyun Wang Fan Xiao Jingyi Li Jie Tian Yida Xing Xiaodan Kong Ke Rui Rencai Qin Xiaoxia Zhu Jing Wang Cainan Luo Haijing Wu Yun Zhang Chengping Wen Lan He Dongzhou Liu Hejian Zou Qianjin Lu Lijun Wu Liwei Lu Centre for Infection and Immunity Studies School of MedicineThe Sun Yat-sen UniversityShenzhen518107GuangdongChina Department of Pathology and Shenzhen Institute of Research and Innovation The University of Hong KongHong Kong999077China Department of rheumatology Shenzhen People’s HospitalThe Second Clinical Medical CollegeJinan UniversityShenzhenChina Chongqing International Institute for Immunology Chongqing400038China Department of rheumatology and Immunology Southwest HospitalThe First Hospital Affiliated to Army Medical UniversityChongqing400038China Department of Laboratory Medicine Affiliated Hospital and Institute of Medical ImmunologyJiangsu UniversityZhenjiangChina Department of rheumatology The Second Affiliated Hospital of Dalian Medical UniversityDalianChina Department of rheumatology Huashan HospitalFudan UniversityShanghaiChina Department of rheumatology and Immunology The First Affiliated Hospital of Xi’an Jiaotong UniversityXi’an710061ShaanxiChina Department of rheumatology and Immunology People’s Hospital of Xinjiang Uygur Autonomous RegionUrumqiChina Department of Dermatology Hunan Key Laboratory of Medical EpigenomicsSecond Xiangya HospitalCentral South UniversityChangshaHunanChina Key Laboratory of Chinese Medicine rheumatology of Zhejiang Province Institute of Basic Research in Clinical MedicineCollege of Basic Medical ScienceZhejiang Chinese Medical UniversityHangzhou310053China Centre for Oncology and Immunology Hong Kong Science ParkHong KongChina

Autoantibodies produced by B cells play a pivotal role in the pathogenesis of systemic lupus erythematosus (SLE). However, both the cellular source of antiphospholipid antibodies and their contributions to the development of lupus nephritis (LN) remain largely unclear. Here, we report a pathogenic role of anti-phosphatidylserine (PS) autoantibodies in the development of LN. Elevated serum PS-specific IgG levels were measured in model mice and SLE patients, especially in those with LN. PS-specific IgG accumulation was found in the kidney biopsies of LN patients. Both transfer of SLE PS-specific IgG and PS immunization triggered lupus-like glomerular immune complex deposition in recipient mice. ELISPOT analysis identified B1a cells as the main cell type that secretes PS-specific IgG in both lupus model mice and patients. Adoptive transfer of PS-specific B1a cells accelerated the PS-specific autoimmune response and renal damage in recipient lupus model mice, whereas depletion of B1a cells attenuated lupus progression. In culture, PS-specific B1a cells were significantly expanded upon treatment with chromatin components, while blockade of TLR signal cascades by DNase I digestion and inhibitory ODN 2088 or R406 treatment profoundly abrogated chromatin-induced PS-specific IgG secretion by lupus B1a cells. Thus, our study has demonstrated that the anti-PS autoantibodies produced by B1 cells contribute to lupus nephritis development. Our findings that blockade of the TLR/Syk signaling cascade inhibits PS-specific B1-cell expansion provide new insights into lupus pathogenesis and may facilitate the development of novel therapeutic targets for the treatment of LN in SLE.

关键词： B1 cell Anti-phosphatidylserine antibodies Lupus nephritis TLR Syk

Effect of cream, prepared with Tripterygium wilfordii Hook F and other four medicinals, on joint pain and swelling in patients with rheumatoid arthritis: a double-blinded, randomized, placebo controlled clinical trial

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Journal of Traditional Chinese Medicine 2019年第1期39卷 89-96页

作者： Jiao Juan Wei Chengchung Tang Xiaopo Gong Xun Yin Haibo Jiang Quan Department of rheumatology Guang'anmen Hospital Affiliated to China Academy of Chinese Medical SciencesBeijing 100053China Division of Allergy Immunology and RheumatologyChung Shan Medical University HospitalInstitute of MedicineChung Shan Medical UniversityGraduate Institute of Intergrated MedicineChina Medical UniversityTaichung 40201Taiwan China

OBJECTIVE: To investigate the effectiveness a cream onjoint pain and swelling in patients with rheumatoid arthritis(RA). The cream, topically used, in was prepared with Tripterygium wilfordii Hook F(TwHF), Mangxiao(Nalrii Sulfas), Chuanxiong(Rhizoma Chuanxiong), stir-frying with liquid adjuvant Ruxiang(Olibanum), and stir-frying with liquid adjuvant Moyao(Myrrh).METHODS: Patients were 1∶1 randomized to addon TwHF cream twice a day or placebo for 4 *** primary endpoint was achievement rate of20% improvement in American College of Rheuma-tology criteria(ACR20) at week 4. Secondary endpoints were ACR50, 28-joint count Disease Activity Score(DAS28) improvement and safety *** analyses were performed using intention to treat analysis(ITT) ***: A total of 70 active RA patients were enrolled. At week 4, the ACR20 was 34.3%(12/35) in TwHF cream group and 11.4%(4/35) in placebo group(P = 0.015). Similarly, a higher ACR50 responder proportion was seen in TwHF cream group with 17.1%(6/35) comparing to it in placebo group with 2.9%(1/35)(P = 0.046). The TwHF cream group also had more improvement than the placebo group on DAS28-ESR(1.1 vs 0.5, P = 0.001), DAS28-CRP(1.4 vs 0.7, P = 0.001), tender joint count(5.5 vs2.6, P = 0.018), swollen joint count(3.5 vs 1.6, P =0.003) and Physician's global assessment(25.8 vs13.0, P = 0.002), as well as C-reactive protein(11.2 vs 2.7, P = 0.048). Except 2 skin allergy events in TwHF cream group, no other substantive adverse events were ***: On the short term, TwHF cream is likely to be an effective and safety complimentary treatment in patients with active RA.

关键词： Tripterygium wilfordii Arthritis,rheumatoid External therapy Randomized controlled trial

Gene mutations and clinical phenotypes in 15 Chinese children with cryopyrin-associated periodic syndrome(CAPS)

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Science China(Life Sciences) 2017年第12期60卷 1436-1444页

作者： Caifeng Li Xiaohua Tan Junmei Zhang Shipeng Li Wenxiu Mo Tongxin Han Weiying Kuang Yifang Zhou Jianghong Deng Department of rheumatology and Immunology Beijing Children's HospitalCapital Medical UniversityNational Center for Children"s HealthBeijing 100045China

The aim of our study is to explore the features of clinical manifestations and genetic mutations in Chinese CAPS patients. Fifteen confirmed patients with CAPS were enrolled. The onset time ranges from 2 days after birth to 6 years and 1 month. Recurrent urticaria rash(93.3%) with fever(100%) were two dominant characteristics of these patients that were presented as either acute or chronic process. Systemic involvements were found in all patients except for one with only rash and fever. The top three symptoms were fever(100%), rash(93.3%) and myalgia(76%). Other clinical manifestations include arthritis(11 cases), lung involvement(seven cases), optical dysfunction(seven cases), nerve deafness(six cases), nervous system involvement(five cases), hepatomegaly, splenomegaly and lymphadenectasis(five cases). Also, four patients had heart involvement and one patient suffered kidney involvement. The laboratory inflammation index such as leukocyte counts, platelet counts, erythrocyte sedimentation rate(ESR), C-reactive protein(CRP), serum amyloid A(SAA) and fibrinogen(FIB) increased significantly at initial stage, but decreased after therapy. As for gene mutation detection, Twelve out of 15 patients were confirmed with mutation in NLRP3, including 11 mutant site: c1789 A>G, c.1703 T>A, c.913 G>A, c.1710 G>C, c.1057 G >T, c.2335 C>T, c.932 T>C,c.296 G>C, c.663 C>T, t.1702 T>A, 299 G>A. Mutation sites c.1703 T>A, c.2335 C>T, c.296 G>C, c.663 C>T, and 299 G>A were newly identified. The association between gene mutation and clinical manifestation shows that D305 N was highly associated with severe organs involvements, and therefore, the time of therapy and regimen were critical for the prognosis of disease. As the largest cohort study of Chinese CAPS patients, we confirmed that all patients presented typical clinical manifestations, identified five new mutation sites on NLRP3 and analyzed the correlation between the genotypes and phenotypes. We also raise concerns for one case

关键词： CAPS genetic mutation clinical phenotTpe NLRP3

Correlation of Thl7 cells and CD4＋CD25＋ regulatory T cells with clinical parameters in patients with systemic sclerosis

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Chinese Medical Journal 2014年第20期127卷 3557-3561页

作者： Jiang Nan Li Mengtao Zeng Xiaofeng Department of Internal Medicine Department of rheumatology

Background Systemic sclerosis （SSc） is an autoimmune disease that has three major components： inflammation, fibrosis, and vasculopathy. T-helper 17 cell （Th17） and regulatory T cell （Treg） are considered to be critical for autoimmune disease pathogenesis. The role of Th17 and Treg in SSc is still unclear. The aim of this study was to detect the presence of Th17s and CD4＊CD25~ Tregs in peripheral blood samples from SSc patients and to investigate the possible roles of these two T cell subsets in SSc pathogenesis. Methods Th17s （CD4 and IL-17 positive） and CD4＊CD25~ Tregs （CD4, CD25 and Foxp3 positive） in the peripheral blood mononuclear cells of 53 SSc patients and 27 healthy controls were counted by flow cytometry. The differences between SSc and control patients were analyzed. Clinical parameters, including disease duration, duration of the second symptoms, Modified Rodnan Skin Score （MRSS）, anti-topoisomerase I antibody, anti-U1 ribonucleoprotein （RNP） antibody, systemic involvements, pulmonary function test （PFT） and high resolution computed tomography （HRCT） score were prospectively collected following EUSTAR （EULAR scleroderma trial and research group） protocols. The correlations between the experimental and clinical data were investigated. Results The ratio of Th17 in SSc patients was significantly elevated compared to healthy controls （8.74% vs. 4.41%, P 〈0.001）. The amount of Th17 was positively correlated with disease duration （R=-0.531, P=-0.013） and duration of the second symptoms （R=-0.505, P=0.023）. The ratio of CD4＊CD25＊ Treg in SSc patients also significantly differed from the healthy controls （3.04% vs. 2.24%, P=0.018）. Elevated Tregs were more frequently observed in patients with a high interstitial lung disease （ILD） score on computed tomography （24/36） compared with patients with normal ILD scores （4/12, ,P=-0.043）. Elevated Tregs were also more often observed in patients with low carbon monoxide diffusing capacity （DLCO）（24/34） compared with pat

关键词： scleroderma, systemic Thl 7 cells T-lymphoeytes, regulatory

Drug-containing serum of Xinfeng capsules protect against H9C2 from death by enhancing miRNA-21 and inhibiting toll-like receptor 4/phosphorylated p-38(p-p38)/p-p65 signaling pathway and proinflammatory cytokines expression

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Journal of Traditional Chinese Medicine 2018年第3期38卷 359-365页

作者： Cao Yunxiang Guo Yunke Zong Ruikai Huang Chuanbing Wang Yue Liu Jian First Clinical School Nanjing University of Traditional Chinese Medicine Department of rheumatology The First Affiliated Hospital of Anhui University of Traditional Chinese Medicine

OBJECTIVE: To investigate effect of drug-containing serum of Xinfeng capsules on myocardial cell ***: Drug-containing serum of Xinfeng capsules rat models were established by intragastricly administrated Xinfeng capsules. MTT assay wasused to evaluated H9C2 cells viability. H9C2 cells were divided into normal control group, triptolide group, lipopolysaccharide(LPS) group, drug-containing serum group and mi RNA-21 inhibitor group. micro RNA-21(mi RNA-21) inhibitor was structured and transfected into H9C2 cells. Western blot and immunofluorescence assay were applied to examine toll-like receptor 4(TLR4), phosphorylated p-38(p-p38) and p-p65 expression. Quantitative real-time PCR(q RT-PCR) was used to evaluated m RNA levels of mi RNA-21. Enzyme linked immunosorbent(ELISA) was used to measure tumor necrosis factor α(TNF-α), IL-6 and IL-17 ***: Drug-containing serum treatment significantly increased cell viability compared to LPS treated group. q RT-PCR results indicated that mi RNA-21 levels were significantly decreased in drugcontaining serum group compared to LPS *** and late apoptosis in drug-containing serum group were significantly decreased compared to LPS group. Western blot and immunofluorescence assay results showed that TLR4, p-p38 and p-p65 levels in drug-containing serum group were significantly decreased compared to LPS group. ELISA findings indicated that drug-containing serum significantly decreased inflammatory cytokine levels of TNF-α, IL-6 and ***: Drug-containing serum of Xinfeng capsules protect against lipopolysaccharide instructed H9C2 cells from death by enhancing mi RNA-21 and inhibiting TLR4/p-p38/p-p65 signaling pathway and proinflammatory cytokines expression.

关键词： Drug-containing serum Xinfeng cap-sules MicroRNAs Proinflammatory cytokines Toll-like receptor 4 Myocardial cell Apoptosis

COVID-19,liver dysfunction and pathophysiology:A conceptual discussion

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World Journal of Gastroenterology 2022年第6期28卷 683-688页

作者： Jucier Gonçalves Júnior Department of Internal Medicine Division of RheumatologySão Paulo UniversitySão Paulo 01246-903StateBrazil

The intra and extracellular pathways of hepatic injury by coronavirus disease 2019(COVID-19)are still being *** them is important to treat this viral disease and other liver and biliary tract ***,this paper aims to present three hypotheses about liver injury caused by COVID-19:(1)The interactions between severe acute respiratory syndrome coronavirus 2 spike protein and membrane receptors in the hepatocyte;(2)The dysbiosis and"gutliver axis"disruption in patients with serious clinical presentations of COVID-19;and(3)The inflammatory response exacerbated through the production of interleukins such as ***,despite these new perspectives,the pathophysiological process of liver injury caused by COVID-19 is still complex and ***,understanding all these variables is a challenge to science but also the key to propose individualized and effective patient therapies.

关键词： COVID-19 Intracellular signaling peptides and proteins Immunopathology Liver diseases Liver injury SARS-CoV-2

Immunohistochemical study of Fas antigen expression in synovial tissues from patients with rheumatoid arthritis

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Chinese Medical Journal 1998年第3期000卷 19-21页

作者：于清宏刘湘源施桂英 Department of rheumatology General Hospital of PLA Beijing 100853 China

Objective To investigate the location and expression of Fas (Apo 1, CD 95) antigen in synovial tissue from rheumatoid arthritis (RA). Methods Immunohistochemical technique was used to identify the location and expression of Fas antigen in synovial tissues from 27 RA, 11 osteoarthritis (OA), 7 ankloysing spondylitis (AS), 3 pigmented villo hyperplastic synovitis, 1 juvenile rheumatoid (JRA) patients and 5 “normal” control subjects. Results Fas was strongly expressed by synoviocytes and infiltrated lymphocytes in approximately two thirds of RA patients (16/27). However, only weak expression occurred on lymphocytes in 3 of 11 OA, 1 of 7 AS patients and 1 of 5 “normal” subjects. The stain positive substance in the forms of rings, granules, or dust was deposited on the cell membrane and in cytoplasm. Conclusion The expression of Fas may be involved in the mechanism of synovium proliferation and abnormal activation of local lymphocytes in RA.

关键词：于清宏 synovial antigen tissues arthritis rheumatoid 刘湘 Fas