Perceptions of Rheumatologists on Diagnosis of Psoriatic Arthritis in China.

Objective: High prevalence of undiagnosed psoriatic arthritis (PsA) and prolonged diagnostic delay are key troubles in the appropriate management of PsA. To analyze the possible causes for this phenomenon, a web-based nationwide survey was conducted to investigate rheumatologists' perceptions on PsA diagnosis in China. Methods: The electronic questionnaire consisting of 38 questions were designed by an expert panel and distributed with the online survey tool Sojump, which is a professional online survey platform. The completed questionnaires by real-name rheumatologists were collected. Results: A total of 1594 valid questionnaires were included. More than half of Chinese rheumatologists reported it was challenging to make a diagnosis of PsA. The four major challenges were "Difficulties in identification of atypical or hidden psoriasis", "Absence of diagnostic biomarkers", "No active self-report of history or family history of psoriasis" and "Various musculoskeletal manifestations". In diagnosing PsA, minor participants had incorrect knowledge of inflammatory arthropathy (13.7%), acute phase reactant (23.8%), and rheumatoid factor (28.7%). There were no significant differences in the knowledge of PsA and practice habits in diagnosing PsA between modern western medicine (WM)- and traditional Chinese medicine (TCM)-rheumatologists. The part-time rheumatologists were not as good as full-time rheumatologists in diagnosing PsA. Conclusions: About three quarters of Chinese rheumatologists are familiar with the elements in PsA diagnosis and have good practice habits in diagnosing PsA. Four main challenges in making PsA diagnosis are revealed. There was no significant difference in the knowledge of PsA between WM- and TCM-rheumatologists.

Therapeutic potential of russelioside B as anti-arthritic agent in Freund's adjuvant-induced arthritis in rats.

ETHNOPHARMACOLOGICAL RELEVANCE: Caralluma species are traditional edible herbs used in folkloric medicine as antidiabetic, antioxidant, antipyretic, antirheumatic, anti-inflammatory and anthelmintic agents. C. quadrangula was selected in this study to document the traditional use of the genus as anti-rheumatic treatment and the possible mechanisms of action. AIM OF THE STUDY: The higher mortality rates and shorter survival among the patients suffering from rheumatoid arthritis (RA) led to the increased interest on searching for new treatments for RA. Russelioside B (RB), a major pregnane glycoside found in C. quadrangula, was evaluated as a new anti-rheumatic agent. MATERIALS AND METHODS: The n-butanol fraction of C. quadrangula was chromatographed on a silica gel column to isolate RB. The adjuvant-induced arthritis (AIA) model was established in rats by intradermal injection of complete Freund's adjuvant (CFA) to evaluate its anti-arthritic effect. Ibuprofen was used as a reference drug. Forty rats were randomly divided into 5 groups (n = 8): normal (NOR); CFA model (CFA); ibuprofen, 5 mg/kg; RB, 25 mg/kg and RB, 50 mg/kg. The treatments were initiated from day 16 when AIA model was established and continued up to day 40. Serum diagnostic rheumatoid markers, inflammatory cytokines, oxidative stress biomarkers, cartilage and bone degeneration enzymes were assessed. RESULTS: RB at 50 mg/kg b. wt., showed significant decreases in the activities of hyaluronidase and ß-glucouronidase enzymes as well significant decreases in the levels of proinflammatory cytokines as nuclear factor-kappa-B (NF-κB), tumour necrosis factor-α (TNF-α), interleukin-6 (IL-6) and interleukin-1ß (IL-1ß) compared to the CFA group; 11.04 ± 0.61 pg/mg protein, 4.35 ± 0.25 pg/mg protein, 3.32 ± 0.13 pg/mg protein & 2.75 ± 0.14 pg/mg protein for RB, 50 mg/kg b. wt. group vs. 25.33 ± 2.13 pg/mg protein, 25.65 ± 2.1 pg/mg protein, 22.20 ± 1.34 pg/mg protein & 13.27 ± 1.40 pg/mg protein for the arthritic group, respectively. The total antioxidant capacity (TAC) was significantly restored to normal values in RB, 50 mg/kg treated rats (4.01 ± 0.09 nmol/mL vs. 3.71 ± 0.27 nmol/mL) and the levels of myeloperoxidase (MPO) reduced by 10-folds of the CFA arthritic group. Bone histomorphometry revealed that RB treatment significantly attenuated the CFA-induced bone loss in a dose-dependent manner. CONCLUSIONS: These findings suggested that the anti-arthritic effect of RB was mediated through the reduction of the rheumatoid markers, anti-inflammatory and antioxidant action, inhibition of cartilage and bone degenerative enzymes as well as attenuation of bone loss and osteoclastogenesis.

The efficacy and safety of warming acupuncture and moxibustion on rheumatoid arthritis: A protocol for a systematic review and meta-analysis.

BACKGROUND: Rheumatoid arthritis (RA), as an autoimmune disease, can eventually lead to joint deformity and loss of function, seriously reduce the quality of life of patients and increase economic burden. As a traditional Chinese therapy, warming acupuncture and moxibustion is safe, economical, and has few side effects. At present, some studies have shown that warming acupuncture and moxibustion has a certain effect on RA, but there is no evidence of evidence-based medicine. The purpose of this study was to evaluate the efficacy and safety of warming acupuncture and moxibustion in the treatment of rheumatoid arthritis. METHOD: Randomized controlled trials of warming acupuncture and moxibustion treating RA will be searched in the databases including PubMed, EMBASE, the Cochrane library, Web of science, China National Knowledge Infrastructure (CNKI), WanFang, the Chongqing VIP Chinese Science and Technology Periodical Database (VIP), and China biomedical literature database (CBM) from inception to July, 2020. In addition, Baidu, Google Scholar, International Clinical Trials Registry Platform, and Chinese Clinical Trials Registry will be searched to obtain the gray literature and relevant data that have not yet been published. Two qualified researchers will extract data and assess the risk of bias from included studies independently. Statistical analysis is performed in RevMan 5.3 software. RESULTS: The primary outcome is symptom evaluation including morning stiffness, pain, and joint swelling. The number of joints affected by RA, Rheumatoid factor (RF), erythrocyte sedimentation rate (ESR), C reactive protein (CRP), anti-cyclic peptide containing citrulline (A-CCP), and adverse effects, will be evaluated as secondary outcomes. CONCLUSIONS: This study will compare the efficacy and safety of warming acupuncture and moxibustion with common acupuncture in the treatment of RA, providing reliable evidence for clinical application. OSF REGISTRATION NUMBER: DOI 10.17605/OSF.IO/C8RY9.

Cervus and cucumis peptides combined umbilical cord mesenchymal stem cells therapy for rheumatoid arthritis.

Cervus and cucumis peptides (Lugua polypeptides, LG) are traditional Chinese medicine, which are active components of polypeptide extracted from Sika deer bone and melon seed, and they contain bone induced polypeptide biological factors. Umbilical cord mesenchymal stem cell, (UC-MSC) have tissue repair multiple effects, anti-inflammatory, and immune regulation function, which become a very promising start in rheumatoid arthritis (RA) treatment. Hence, LG combined UC-MSC can significantly enhance the UC-MSC treatment of rheumatoid arthritis (RA).To explore the clinical curative effect and therapeutic mechanism of LG combined UC-MSC for treating RA.119 patients were divided into control and treatment groups, and both groups were treated with methotrexate tablets, leflunomide, and UC-MSC. But, LG were added to the treatment group. In vitro, the effects of LG on UC-MSC cell secretion of anti-inflammatory factors were also performed.The Health Assessment Questionnaire; the 28 joint disease activity score; C reactive protein; the erythrocyte sedimentation rate; rheumatoid factor; and anti-cyclic citrullinated peptide antibody were significantly reduced in treatment group 1 year after treatment (P < .05). In vitro, compared with the control group, the number of hepatocyte growth factor (HGF), the secretion of prostaglandin E2 (PGE2) and tumor necrosis factor-inducible gene 6 protein (TSG6) increased significantly (P < .05).LG combined UC-MSCs can significantly improve the curative effect of RA patients, while LG may reduce inflammatory cytokines, regulate immunity, improve microcirculation, and are conducive to UC-MSCs migration and the repair of damaged tissue.

Effects of moxibustion on pain behaviors in patients with rheumatoid arthritis: A meta-analysis.

BACKGROUND: Pain is the main symptom of patients with rheumatoid arthritis (RA). Reports of the effects of moxibustion on patients with rheumatoid arthritis have reached various conclusions. The aim of this meta-analysis was to evaluate the effect of moxibustion on pain in patients with RA. METHODS: A systematic search of MEDLINE, EMBASE, the Cochrane Library, and the Chinese databases Wan Fang Med Database, CNKI, and VIP (until November, 2018) was used to identify studies reporting pain (on a visual analogue scale (VAS)), erythrocyte sedimentation rate (ESR), C-reactive protein (CRP) and rheumatoid factor (RF) levels, response rate, and the ACR50 rate in patients with RA. Results were expressed as mean difference (MD) and 95% confidence intervals (CI). RESULTS: Six studies involving 281 participants were included. Moxibustion had significant effects on pain (VAS: MD = -0.53, 95% CI [-0.94, -0.12], P =.01). Moreover, moxibustion had effects on CRP (MD = -2.84, 95% CI [-5.13, -0.55], P =.01), ESR (MD = -8.44, 95% CI ([-13.19, -3.68], P =.0005), and RF (MD = -6.39, 95% CI [-18.57, 5.79], P =.30). Additionally, it had effects on response rate (n = 249, RR = 1.26, 95% CI [1.11, 1.43], P =.0004) and ACR50 rate (n = 140, RR = 1.44, 95% CI [1.11, 1.88], P =.007). CONCLUSION: We found that moxibustion with Western medicine therapy is superior to Western medicine therapy alone for pain in patients with RA. Moxibustion had significant effects on pain in patients with RA, but the effects of moxibustion on inflammatory factors in RA were unclear.

Moxibustion for rheumatoid arthritis: Protocol for a systematic review.

BACKGROUND: Rheumatoid Arthritis (RA) is a serious chronic disease which will result in serious syndrome such as joints stiffness, disability, and death. The major medications treating RA usually make sense and side effects, while moxibustion is known as a safe and effective treatment for RA. This review aims to systematically evaluate the effect and safety of moxibustion for treating RA. METHODS: The following databases will be searched from their inception to March 2019: PubMed, Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE, EMBASE, Wan-Fang Databases, China National Knowledge Infrastructure (CNKI), Chinese Biomedical Literature Database (CBM), Citation Information by National Institute of Informatics, Chinese Scientific Journal Database (VIP Database). Two reviewers will search these databases, select data and measure the quality of studies independently. The methodological quality will be assessed by the Cochrane risk of bias tool. Data will be synthesized by either the fixed-effects or random-effects model according to a heterogeneity test. The primary outcome is symptom evaluation including morning stiffness, pain and joint swelling. The number of joints affected by RA, adverse effects, quality of life, erythrocyte sedimentation rate (ESR), C reactive protein (CRP), and Rheumatoid factor (RF) will be evaluated as secondary outcomes. Risk ratio for dichotomous data and mean differences with a 95% confidence interval for continuous data will be adopted to express the effect and safety of acupuncture for RA. RESULTS: This study will provide a high-quality synthesis of current evidence of moxibustion for asthma from several aspects including morning stiffness, pain and joint swelling. The number of joints affected by RA, adverse effects, quality of life, erythrocyte sedimentation rate (ESR), C reactive protein (CRP), and Rheumatoid factor (RF). CONCLUSION: The conclusion of our study will provide updated evidence to judge whether moxibustion is an effective and safe intervention for patients with RA. ETHICS AND DISSEMINATION: As individuals will not be involved, the ethical approval will not be required. This review will be published in a peer-reviewed journal or at a relevant conference. PROSPERO REGISTRATION NUMBER: CRD42019126685.

Systemic treatment with resveratrol reduces the progression of experimental periodontitis and arthritis in rats.

Rheumatoid arthritis and periodontitis are chronic inflammatory diseases which has been closely associated due to the nature of immune-inflammatory imbalance response. Resveratrol is a naturall product with biological proprieties that may promote immunomodulatory effects on host response. This study investigated resveratrol continuous administration effect on experimental periodontitis and arthritis progression in rats. Thirty-five rats were assigned to the following groups: 1-experimental arthritis + experimental periodontitis + placebo (RA+EP +PL) (n = 12); 2 -RA+EP+ ibuprofen (RA+PE+IB) (n = 11); 3-RA+EP+ resveratrol (RA+PE+RSV) (n = 11). After euthanasia, the specimens were processed for morphometric analysis of bone loss, and the gingival tissue surrounding the first molar was collected for quantification of inflammatory markers using a Luminex/MAGpix assay and anti-citrullinated protein antibody (ACCPA) levels were measured by ELISA assay. Serum level of rheumatoid factor (RF) was measured by ELISA assay. Paw edema was analyzed using a plethysmometer. Higher bone loss was observed in PL group, when compared to IB and RSV groups. RSV group presented higher IL-4 concentration than PL and IB groups. Resveratrol reduced RF serum levels and both IB and RSV decreased ACCPA gingival levels. Besides, paw swelling level was significantly lower in IB and RSV groups in the 21th day and only in RSV group in the 28th day. Histological analyzes showed smooth articular surface and higher width of the subchondral cortical in RSV group. Resveratrol showed modulatory effect and seems to reduce the inflammatory signs of arthritis and articular damage throughout the time.

The association between omega-3 fatty acid biomarkers and inflammatory arthritis in an anti-citrullinated protein antibody positive population.

Objectives: Higher circulating omega-3 fatty acids (n-3 FAs) are associated with a lower prevalence of anti-CCP antibodies and RF in subjects without RA. We examined whether, in anti-CCP+ subjects, n-3 FAs also play a role in development of inflammatory arthritis (IA). Methods: At Colorado-based health fairs from 2008 to 2014, participants without a previous diagnosis of RA who were anti-CCP3+ (n = 47) were recruited into a follow-up study; symptom assessments and joint examinations were conducted every 6 months for the determination of IA. We measured n-3 FAs as a percentage of total lipids in red blood cell membranes (n-3 FA%) at each visit. Results: We detected IA in 10 anti-CCP3+ subjects (21%) at the baseline visit. Increased total n-3 FA% in red blood cell membranes [odds ratio (OR) = 0.09, 95% CI: 0.01, 0.76], specifically docosapentaenoic acid (OR = 0.16, 95% CI: 0.03, 0.83) and docosahexaenoic acid (OR = 0.23, 95% CI: 0.06, 0.86), was associated with a lower odds of IA at the baseline visit, adjusting for n-3 FA supplement use, current smoking, RF+, elevated CRP+ and shared epitope. We followed 35 of the anti-CCP3+ subjects who were IA negative at baseline and detected 14 incident IA cases over an average of 2.56 years of follow-up. In a time-varying survival analysis, increasing docosapentaenoic acid significantly decreased risk of incident IA (hazard ratio = 0.52, 95% CI: 0.27, 0.98), adjusting for age at baseline, n-3 FA supplement use, RF+, CRP+ and shared epitope. Conclusion: n-3 FAs may potentially lower the risk of transition from anti-CCP positivity to IA, an observation that warrants further investigation.

Anti-arthritic activity of aqueous-methanolic extract and various fractions of Berberis orthobotrys Bien ex Aitch.

BACKGROUND: The roots and stem bark of Berberis orthobotrys (Berberidaceae) have long been used traditionally to treat joint pain. Though, it has not been pharmacologically assessed for rheumatoid arthritis. The current study explores anti-arthritic activity and phytochemical analysis of aqueous-methanolic extract (30:70) and fractions (ethyl acetate, n-butanol, and aqueous) of Berberis orthobotrys roots. METHODS: Anti-arthritic potential was evaluated in vitro using protein denaturation (bovine serum albumin and egg albumin) and membrane stabilization methods at 12.5-800 µg/ml concentration and in vivo via turpentine oil, formaldehyde and Complete Freund Adjuvant (CFA) models at 50, 100 and 150 mg/kg doses. Also, in vitro antioxidant ability was appraised by reducing power assay. Moreover, total flavonoid content, Fourier transform infrared spectroscopy and High performance liquid chromatography of n-butanol fraction were performed. RESULTS: The results revealed concentration dependent inhibition of albumin denaturation and notable RBC membrane stabilization, with maximum results obtained at 800 µg/ml. Similarly, plant exhibited dose dependent anti-arthritic effect in turpentine oil and formaldehyde models, with maximum activity observed at 150 mg/kg. The results of CFA model depicted better protection against arthritic lesions and body weight alterations. Also, B.orthobotrys remarkably ameliorated altered hematological parameters, rheumatoid factor and positively modified radiographic and histopathological changes. Additionally, plant exhibited remarkable anti-oxidant activity. Moreover, phytochemical analysis revealed polyphenols and flavonoids. CONCLUSION: Taken together, these results support traditional use of B.orthobotrys as potent anti-arthritic agent that may be proposed for rheumatoid arthritis treatment.

[Clinical efficacy of moxibustion as supplement on rheumatoid arthritis and the exploration on its mechanism].

OBJECTIVE: To explore the clinical efficacy of moxibustion on rheumatoid arthritis (RA) in the patients and the impacts on the inflammatory indices. METHODS: Forty RA patients were randomized into an observation group and a control group, 20 cases in each one. In the control group, diclofenac sodium sustained release tablets were used, 0.3 g each time, twice a day; methotrexate tablets were used, 10 mg each time, once a week; folic acid was used, 5 mg each time, once a week. In the observation group, on the basis of the treatment as the control group, moxibustion was added specially on the swelling and painful joints, once a day, 15-20 min each time till: the local skin turned slightly red. The treatment was given once a day, at the interval of 1 day after every 6 treatments. In the two groups, the efficacy was observed after 30-day treatment. Before and after treatment, the rheumatoid factor (RF), high sensitivity C-reactive protein (hs-CRP), erythrocyte sedimentation rate (ESR), disease activity score-28 (DAS-28) and the score of joint symptom and physical signs were observed. RESULTS: Compared with those before treatment, the levels of RF, hs-CRP, ESR, DAS-28 and the symptom scale score were all reduced in the RA patients of the two groups after treatment (all P < 0.05). Compared with the control group, the levels of RF, hs-CRP, ESR, DAS-28 and the symptom scale score in the observation group were improved much apparently (all P < 0.05). The total effective rate was 85.0% (17/20) in the observation group and was 80.0% (16/20) in the control group. The total effective rate in the observation group was apparently better than that in the control group (P < 0.05). CONCLUSION: Moxibustion as supplement relieves the joint symptoms, reduces the inflammatory reactive indices and improves the clinical efficacy in the RA patients.

Effect of denosumab on Japanese patients with rheumatoid arthritis: a dose-response study of AMG 162 (Denosumab) in patients with RheumatoId arthritis on methotrexate to Validate inhibitory effect on bone Erosion (DRIVE)-a 12-month, multicentre, randomised, double-blind, placebo-controlled, phase II clinical trial.

OBJECTIVES: To evaluate efficacy and safety of three different regimens of denosumab, a fully human monoclonal antibody to receptor activator of nuclear factor kappa B (RANK) ligand (RANKL), for Japanese patients with rheumatoid arthritis (RA). METHODS: In this multicentre, randomised, placebo-controlled phase II study, 350 Japanese patients with RA between 6 months and <5 years, stratified by glucocorticoid use and rheumatoid factor status, were randomly assigned to subcutaneous injections of placebo or denosumab 60 mg every 6 months (Q6M), every 3 months (Q3M) or every 2 months (Q2M). All patients basically continued methotrexate treatment and had a supplement of calcium and vitamin D throughout the study. The primary endpoint was change in the modified Sharp erosion score from baseline to 12 months. RESULTS: Denosumab significantly inhibited the progression of bone erosion at 12 months compared with the placebo, and the mean changes of the modified Sharp erosion score at 12 months from baseline were 0.99, 0.27 (compared with placebo, p=0.0082), 0.14 (p=0.0036) and 0.09 (p<0.0001) in the placebo, Q6M, Q3M and Q2M, respectively. Secondary endpoint analysis revealed that denosumab also significantly inhibited the increase of the modified total Sharp score compared with the placebo, with no obvious evidence of an effect on joint space narrowing for denosumab. As shown in previous studies, denosumab increased bone mineral density. No apparent difference was observed in the safety profiles of denosumab and placebo. CONCLUSIONS: Addition of denosumab to methotrexate has potential as a new therapeutic option for patients with RA with risk factors of joint destruction. TRIAL REGISTRATION NUMBER: JapicCTI-101263.

The Effect of SHH-Gli Signaling Pathway on the Synovial Fibroblast Proliferation in Rheumatoid Arthritis.

Rheumatoid arthritis (RA) is a chronic autoimmune disease characterized by chronic synovitis. This study aims to investigate the role of sonic hedgehog (SHH)-Gli signaling pathway in synovial fibroblast proliferation in rheumatoid arthritis. The expression of serum SHH in RA patients group was significantly increased compared with the systemic lupus erythematosus (SLE), ankylosing spondylitis (AS), and healthy subject (healthy control, HC) groups, respectively; serum SHH expression of RA patients was positively correlated with rheumatoid factor (RF) and anti-cyclic citrullinated peptide antibodies (anti-CCP Ab), while there was no significant correlation between SHH expression and erythrocyte sedimentation rate (ESR). SHH, Ptch, Smo, and Gli molecules were highly expressed in rat RA-synovial fibroblast (RA-SF); after blocking the SHH-Gli signaling pathway with a Gli specific inhibitor, Gli-antagonist 61 (GANT61), RA-SF proliferation was inhibited in a dose-dependent manner and the apoptosis rate of RA-SF was increased as well; the expression levels of fibroblast growth factor receptor 1 (FGFR1) and FGFR3 declined in SF cells after GANT61 treatment. Our results suggest that SHH-Gli pathway is involved in the pathogenesis of RA, and blocking SHH-Gli pathway inhibits RA-SF cell proliferation and increases cell apoptosis, which may shed light on developing new ideas for RA treatment.

Effects of Vitamin K on Matrix Metalloproteinase-3 and Rheumatoid Factor in Women with Rheumatoid Arthritis: A Randomized, Double-Blind, Placebo-Controlled Trial.

OBJECTIVES: Rheumatoid arthritis (RA) is an autoimmune disease characterized by an increase in some autoantibodies and proteolytic enzymes, leading to joint destruction. Although recent investigations have considered vitamin K as an anti-inflammatory nutrient with an important role in bone metabolism, there is currently limited information on its efficacy in RA. We aimed to examine the effects of vitamin K1 (phylloquinone) on the biomarker of joint destruction and autoantibody in patients with RA. MATERIALS AND METHODS: This was a randomized clinical trial in which 64 women with RA who fulfilled the eligibility criteria were randomly allocated to an intervention or a control group. Vitamin K1 or placebo was administered to the participants for 8 weeks. Baseline characteristics and anthropometric measures were obtained. Clinical status using disease activity score in 28 joints (DAS-28), serum levels of matrix metalloproteinase-3 (MMP-3), and rheumatoid factor (RF) were assessed before and after the intervention. RESULTS: The serum level of MMP-3 compared with the baseline values did not change significantly in the groups. However, the serum concentration of RF decreased significantly in the vitamin K1 group (p = 0.041). Intergroup comparison showed no significant change in RF serum level after adjusting for relevant confounders (p > 0.05). CONCLUSIONS: Vitamin K1 supplementation at 10 mg/day for 8 weeks did not alter joint destruction and immune status in the patients with RA compared with the controls.

Biomarkers in Remission According to Different Criteria in Patients with Rheumatoid Arthritis.

OBJECTIVE: Remission is the primary aim in the treatment of patients with rheumatoid arthritis (RA). In this study, we aimed to evaluate biomarker profiles of patients in remission by different criteria and compare these profiles with controls. METHODS: Serum levels of calprotectin, interleukin 6 (IL-6), type II collagen helical peptide, C-terminal crosslinking telopeptide of type I collagen generated by matrix metalloproteinases (ICTP), matrix metalloproteinase 3 (MMP-3), resistin, and leptin were measured by ELISA in 80 patients. The patients were in Disease Activity Score at 28 joints with erythrocyte sedimentation rate (DAS28-ESR) remission, and had these characteristics: female/male 54/26, mean age 51.4 ± 12.1 years, mean disease duration 11.4 ± 8.1 years, rheumatoid factor positivity 68.7% (n = 55), anticyclic citrullinated peptide positivity 60.7% (n = 48). These patients were also evaluated for the American College of Rheumatology/European League Against Rheumatism (Boolean) and Simple Disease Activity Index (SDAI) remissions. Additionally, 80 age-, sex-, and comorbidity-matched individuals without rheumatic diseases were included in the study as controls. RESULTS: At recruitment of 80 patients in DAS28 remission, 33 patients (41.2%) were found in Boolean remission and 39 patients (48.7%) were in SDAI remission. Serum MMP-3, ICTP, resistin, and IL-6 levels of the 80 patients in DAS28 remission were statistically significantly higher than the controls. Patients in Boolean and SDAI remissions had significantly higher serum ICTP, resistin, and IL-6 levels in comparison with the controls. CONCLUSION: The 3 commonly used remission criteria of RA are almost similar with regard to patients' biomarker levels. Biomarker profiles of patients may provide complementary information to clinical evaluation of remission and may help to determine the patients under the risk of progression.

Antinociceptive and anti-inflammatory activities of Schefflera octophylla extracts.

ETHNOPHARMACOLOGICAL RELEVANCE: Schefflera octophylla (Lour.) Harms, a traditional Chinese herb mainly distributed in Southeast Asia, is extensively prescribed to alleviate pain and treat rheumatoid arthritis (RA), influenza, throat swelling, pain, etc. In this paper, the antinociceptive and anti-inflammatory activities of the ethanol extract and its five different polar fractions of this plant were evaluated. Furthermore, the anti-rheumatoid arthritis activity of the ethanol extract and its active fraction (CHCl3 fraction) were evaluated. And the chemical constituents of the CHCl3 active fraction displayed significant antinociceptive and anti-inflammatory activities were investigated. MATERIALS AND METHODS: Antinociceptive and anti-inflammatory activities were investigated by hot plate test, acetic acid-induced abdominal writhing test and formalin test, xylene-induced ear edema test. The anti-rheumatoid arthritis activity was evaluated through the model of adjuvant-induced arthritis (AA) in rats, paw swelling, pain response, arthritis index and histopathological changes of ankle, the levels of TNF-α, IL-1ß, IL-6 and rheumatoid factor (RF) of rats were detected. The chemical constituents of the CHCl3 fraction were isolated using chromatographic techniques. Their structures were elucidated by spectroscopic data analysis. RESULTS: The results showed that the ethanol extract of S. octophylla has significant dose-dependent anti-inflammatory and antinociceptive activities. And its five different polar fractions especially the CHCl3 fraction significantly inhibited the abdominal writhing induced by acetic acid and ear edema induced by xylene, also increased pain threshold in hot plate test in 120 min and reduced ticking times in formalin test. The ethanol extract of S. octophylla and the CHCl3 fraction demonstrated an anti-RA effect in a dose-dependent manner. The levels of TNF-α, IL-1ß and IL-6 in ethanol extract (600 mg/kg) and CHCl3 fraction (300 mg/kg) groups were significantly lower than those of the model group. The chemical constituents study of the CHCl3 fraction from S. octophylla led to six triterpenoids which were identified as taraxerone (1), 3-epi-taraxerol (2), aleuritolic acid (3), 3-oxofriedelan-28-oic acid (4), 3ß,19α -dihydroxy-urs-12-ene- 24,28-dioic acid (5) and asiatic acid (6). Compounds 1-5 were obtained from this plant for the first time. CONCLUSION: This study proved the antinociceptive, anti-inflammatory and anti-rheumatoid arthritis activities of S. octophylla. Triterpenoids obtained from its CHCl3 fraction may be responsible for those activities. These results could support the fact that S. octophylla is used traditionally to cure inflammatory and pain diseases.

Animal models of rheumatoid arthritis: How informative are they?

Animal models of arthritis are widely used to de-convolute disease pathways and to identify novel drug targets and therapeutic approaches. However, the high attrition rates of drugs in Phase II/III rates means that a relatively small number of drugs reach the market, despite showing efficacy in pre-clinical models. There is also increasing awareness of the ethical issues surrounding the use of animal models of disease and it is timely, therefore, to review the relevance and translatability of animal models of arthritis. In this paper we review the most commonly used animal models in terms of their pathological similarities to human rheumatoid arthritis as well as their response to drug therapy. In general, the ability of animal models to predict efficacy of biologics in man has been good. However, the predictive power of animal models for small molecules has been variable, probably because of differences in the levels of target knockdown achievable in vivo.

[Evaluation of Basic Performance of "Point Strip ferritin-3000" for Simple and Rapid Quantification of Serum Ferritin].

Serum ferritin is an excellent marker for total iron content in the body and is essential for the diagnosis of iron deficiency or iron overload. Recently, a simple and rapid method, which utilizes immunochromatography for the quantification of serum ferritin, was developed. However, the range of measurement in previous reagents was limited (10-500 ng/mL). This range is rather narrow and is not fully helpful for the diagnosis of iron overload which sometimes occurs as a result of prolonged transfusions, or for monitoring iron contents during iron chelation therapy against iron overload. In the present study we evaluated the basic performance of the newly developed "Point Strip ferritin-3000", which can measure serum ferritin in the range of 300-3,000 ng/mL. Coefficient of variation (CV) s of within and inter-day assays were in the ranges of 7.3-11.1% and 2.1-5.2%, respectively. Using 87 serum samples obtained from the patients with written informed consents, the correlation coefficient was calculated to be 0.93 compared to the control method. In addition, the quantification of serum ferritin by "Point Strip ferritin-3000" was not influenced by bilirubin, hemoglobin, chyle, rheumatoid factor, or ascorbic acid. From our data, "Point Strip ferritin-3000" is reliable reagent in the range of 300-3,000 ng/mL, and is therefore considered to be useful for the diagnosis of iron overload, as well as for monitoring iron contents during iron chelation therapy. In addition, this quantification method can be easily performed using a small desktop equipment without any special technique, making this system applicable for epidemiological surveys and clinical studies.

[Comparative study of the influence of melatonin and diclofenac on some hematologic indices of experimental rheumatoid arthritis in rats].

Pineal hormone melatonin (1 and 5 mg/kg) and diclofenac (8 mg/kg) significantly limited hematologic indices of inflammation and immunologic reactivity in rats with experimental adjuvant arthritis. The effect of melatonin was more pronounced than that of diclofenac.

Vitamin D deficiency and low bone mineral density in native Chinese rheumatoid arthritis patients.

OBJECTIVE: We aimed to examine the risk factors related to the development of osteoporosis in rheumatoid arthritis (RA) patients and whether there is an association among the changes in bone mineral density (BMD), disease activities (modified DAS28), serum 25-hydroxyvitamin D (25OHD) levels, and disease duration. METHODS: There were 110 patients with RA and 110 age- and sex-matched healthy controls who were concurrently studied. All of the patients underwent the following measurements: erythrocyte sedimentation rate, C-reactive protein, rheumatoid factor, and serum 25OHD. Dual-energy X-ray absorptiometry (DEXA) was also used to measure the BMD of the left femur at the time of recruitment. Patients taking vitamin D supplement or corticosteroids were excluded. RESULTS: The incidences of osteopenia (45.6% vs. 36.4%, P = 0.170) and osteoporosis (33.6% vs. 5.45%, P = 0.000) were higher in the RA patients than in the healthy controls. There was a significant negative correlation between vitamin D levels and DAS28 (r = -0.325, P = 0.001) and a significant positive correlation between vitamin D levels and BMD (r = 0.422, P = 0.000). The multiple regression analysis revealed that 25OHD levels were significantly correlated with disease activity and BMD (F = 11.087, P = 0.000). Stepwise multiple regression analysis showed that serum 25OHD levels were the significant predictors for low BMD and high disease activity (DAS28) in RA patients. CONCLUSION: The incidences of osteoporosis and osteopenia were higher in RA patients compared to the age- and gender-matched healthy controls. Low serum 25OHD levels correlate with low BMD and high disease activity in RA patients.

Tongue diagnosis of traditional Chinese medicine for rheumatoid arthritis.

Rheumatoid arthritis (RA) is a chronic, systemic autoimmune disease with unknown aetiology that causes the immune system to attack the joints (synoviums), leading to chronic inflammation. According to the traditional Chinese medicine (TCM), RA falls into the category of Impediment disease ("Bi" syndrome), that is, poor circulation of qi and blood (stasis). Tongue diagnosis is an important method of TCM to detect blood stasis. In this study, 74 RA patients, meeting the pre-set criteria, were recruited via rheumatology outpatient clinic and examined by experienced rheumatology physicians. Two images-one of the tongue and the other, sublingual vessels-of the same patient were taken by a Canon digital camera in a darkroom with uniform lighting conditions. Relevant features of the tongue were extracted by utilising image processing techniques. Every tongue was classified into corresponding patterns based on the features identified. The subjects included 62 females and 12 males with an average age of 49.86 ± 13.81 years old, an average morbidity period of 4.56 ± 3.92 years, an average rheumatoid factor (RF) of 225.3 ± 373.8 IU/mL and an average erythrocyte sedimentation rate of (ESR) 40.9 ± 31.9 m/hr. According to our study, 86% of the patients with RA have tongues with sublingual vessels with a width of more than 2.7 mm, a length of more than 3/5 from tongue tipto sublingual caruncle, or a count of sublingual vessels more than 2. Moreover, since RA index is highly correlated with blood stasis in TCM, a logistic regression is conducted to predict the probability of presence of RA using RF and ESR as explanatory variables. Also, the logistic regression analysis of RA with respect to the conventional tongue diagnosis criteria was performed. Based on the aforementioned studies, we concluded that tongue diagnosis is helpful in detecting blood stasis of RA.