OBJECTIVE: To investigate the clinical characteristics of rheumatoid arthritis (RA) patients with malignant tumor. METHODS: Retrospective summary was made of 1 562 in patients of RA from January 2011 to June 2017. In the study, 74 RA patients with malignant tumor were reviewed and analyzed, and the general conditions, tumor types, RA and tumor onset sequence, and the medication situation were analyzed. RESULTS: The incidence of malignant tumor in the patients with rheumatoid arthritis in our center was 4.16%. The 74 patients were complicated with malignant tumor, of whom 53 were female, and 21 male. The age of RA at presentation was (52.6±17.8) years. The average disease duration of malignant tumor was (63.4 ± 12.7) years. The onset time of rheumatoid arthritis was earlier than that of malignant tumors in 51 cases (51/74), with an average of (17.2±14.2) years between 2 and 60 years. The incidence of malignant tumor was earlier than that of rheumatoid arthritis in 16 cases (16/74), with an average of (6.2±5.9) years between 1 and 21 years, of which 10 cases were sex hormone related tumors. Seven cases (7/74) were diagnosed with RA at the same time, and the time interval between the two diseases was within 1 year. All the patients were over 60 years old with digestive tract tumors. All the 7 patients showed polyarthritis, significantly increased erythrocyte sedimentation rate and C-reactive protein, including 4 rheumatoid factor positive cases and 2 anti-CCP antibody positive cases. The effect of non-steroidal anti-inflammatory drugs and traditional drugs to improve the condition of the disease was poor in the 7 patients, and the condition was relieved after using low-dose glucocorticoids. Gastrointestinal tumors, breast and reproductive system tumors were the most common, followed by respiratory, urological and blood system tumors. CONCLUSION The risk in patients of rheumatoid arthritis complicated with malignant tumor is higher than that of the general population. A variety of factors play an important role in cancer risk of RA, including disease activity, some estrogen metabolites, the use of drugs and so on. Therefore, all RA patients should be screened for malignant tumor during diagnosis, and malignant tumor surveillance is mandatory for all rheumatoid arthritis patients after diagnosis.
Adult ; Aged ; Arthritis, Rheumatoid/complications* ; Autoantibodies ; C-Reactive Protein/analysis* ; Female ; Humans ; Male ; Middle Aged ; Neoplasms/immunology* ; Peptides, Cyclic ; Retrospective Studies ; Rheumatoid Factor/blood*

We aimed to investigate the value of bone scintigraphy with additional blood pool phase (BSBP), compared with conventional bone scintigraphy (CBS), in the assessment of rheumatoid arthritis (RA). A total of 242 patients (43 males, 199 females; 14-78 years) with arthralgia, and underwent BSBP were retrospectively analyzed. On the first physical examination, active arthritis was found in 128 of the 242 patients. Clinical diagnosis was made by a rheumatologist on the basis of the 1987 American College of Rheumatology (ACR) criteria, which are considered to be the gold standard. The diagnostic performances and prognostic value of BSBP and CBS were analyzed in the total patients with arthralgia and in the patients with arthritis. The sensitivity of BSBP (84.2%, 80/95) were significantly higher than that of CBS (74.8%, 72/95) in the patients with arthralgia (P = 0.039). When BSBP was interpreted with the results of elevated/positive anti-CCP antibody, its accuracy over CBS also became significantly higher (86.0%, 208/242 vs. 83.1%, 201/242 respectively, P = 0.021). The diagnostic odds ratio of BSBP positivity was higher than CBS positivity in the patients with arthralgia (26.0, 12.9-52.4 vs. 21.1, 10.8-41.3) and with arthritis (12.0, 4.9-29.4 vs. 10.0, 4.2-23.4). Both BSBP and CBS appear to provide acceptable accuracy and comparable diagnostic performance for diagnosis of RA. However, in the patients with arthralgia, BSBP was found to be more sensitive than CBS and more accurate when interpreted with the result of anti-CCP antibody. This could help physicians diagnose RA in daily clinical practice.
Adolescent ; Adult ; Aged ; Arthralgia/complications ; Arthritis, Rheumatoid/complications/*diagnosis ; Autoantibodies/blood ; Bone and Bones/diagnostic imaging ; Female ; *Gated Blood-Pool Imaging ; Humans ; Male ; Middle Aged ; Odds Ratio ; Peptides, Cyclic/immunology ; Positron-Emission Tomography ; Prognosis ; Retrospective Studies ; Sensitivity and Specificity ; Technetium/chemistry ; *Tomography, X-Ray Computed ; Young Adult

To observe the serum samples and the anti-inflammatory effect of Tripterygium wilfordii in treating RA by using the pharmacokinetic-pharmacodynamic model, make a correlation analysis on concentration-time and effect-time curves, and explore RORγt, IL-17, STAT3, IL-6 mRNA transcriptional levels in rats by PCR. Methotrexate, tripterine and high-dose T. wilfordii could down-regulate RORγt, IL-17, STAT3, IL-6 mRNA transcriptional levels in AA rat lymph nodes. The study on PK-PD model showed correlations between inflammatory factors and blood concentration of T. wilfordii. T. wilfordii and its main active constituent tripterine could show the inflammatory effect and treat RA by inhibiting IL-17 cytokine.
Animals ; Arthritis, Rheumatoid ; drug therapy ; immunology ; Biomarkers ; Female ; Interleukin-17 ; antagonists & inhibitors ; genetics ; Interleukin-6 ; genetics ; Phytotherapy ; Rats ; Rats, Sprague-Dawley ; Tripterygium ; Triterpenes ; pharmacokinetics ; pharmacology

OBJECTIVETo observe the analgesic effect of electroacupuncture (EA) on collagen-induced arthritis (CIA) rats and its regulating effect on inflammation reaction and the endogenous opioid system of synovial tissues. Methods A total of 30 healthy male Wistar rats were randomly divided into a control group, a model group and an EA group, 10 rats in each one. The chronic pain model of CIA rats was made by cattle type-II collagen in the model group and EA group. Rats in the EA group were treated with EA at "Zusanli" (ST 36) and "Kunlun" (BL 60) for 30 min from 16th day after model establishment, once a day for consecutive 10 days. Rats in the control group did not receive any treatment. Rats in the model group were treated with fixation as the EA group. Threshold of pain, arthritis index, paw swelling were measured before model establishment and 16 d, 20 d, 23 d and 25 d after model establishment. The levels of beta-endorphin (β-END), met-enkephalin (met-ENK), dynorphin A (Dyn A) were measured by radioimmunoassay; the mRNA expressions of mu opioid receptor (MOR), kappa opioid receptor (KOR) and delta opioid receptor (DOR) in synovial tissues of CIA rats were detected by I quantitative polymerase chain reaction (qPCR).

RESULTSCompared with the control group, threshold of pain was reduced (all P<0. 01), arthritis index was increased (all P<0. 01) and paw swelling was increased (all P<0. 01) in the model group on the 16th day, 20th day, 23rd day, 25th day after model establishment. Compared with the model group, the threshold of pain was increased in the EA group (all P<0. 01), arthritis index and paw swelling were reduced (all P<0. 01) on the 23rd day and 25th day after model establishment. Compared with the control group, the level of Dyn A in synovial tissues of CIA rats was increased in the model group (P<0. 01); the mRNA expressions of MOR, KOR and DOR were down-regulated lower than 0. 5 fold of normal level. Compared with the model group, the level of β-END in synovial tissues of the knee joint was increased in the EA group (P<0. 05), and the mRNA expressions of MOR, KOR and DOR in synovial tissues of CIA rats were up-regulated more than 2 folds of normal level.

CONCLUSIONThe intervention of EA on chronic pain of CIA rats is superior, which is likely to be related with effects of EA on anti-inflammation and up-regulation of synovial tissue β-END and MOR, KOR, DOR.

Acupuncture Analgesia ; Acupuncture Points ; Analgesics, Opioid ; immunology ; Animals ; Arthritis, Rheumatoid ; immunology ; therapy ; Cattle ; Chronic Pain ; immunology ; therapy ; Dynorphins ; genetics ; immunology ; Electroacupuncture ; Enkephalin, Methionine ; genetics ; immunology ; Humans ; Male ; Rats ; Rats, Wistar ; Receptors, Opioid, mu ; genetics ; immunology ; Synovial Fluid ; immunology ; beta-Endorphin ; genetics ; immunology

Rheumatoid arthritis (RA) and osteoarthritis (OA), two common types of arthritis, affect the joints mainly by targeting the synovium and cartilage. Increasing evidence indicates that a significant network connects synovitis and cartilage destruction during the progression of arthritis. We recently demonstrated that hypoxia-inducible factor (HIF)-2alpha causes RA and OA by regulating the expression of catabolic factors in fibroblast-like synoviocytes (FLS) or chondrocytes. To address the reciprocal influences of HIF-2alpha on FLS and chondrocytes, we applied an in vitro co-culture system using a transwell apparatus. When co-cultured with HIF-2alpha-overexpressing chondrocytes, FLS exhibited increased expression of matrix metalloproteinases and inflammatory mediators, similar to the effects induced by tumor-necrosis factor (TNF)-alpha treatment of FLS. Moreover, chondrocytes co-cultured with HIF-2alpha-overexpressing FLS exhibited upregulation of Mmp3 and Mmp13, which is similar to the effects induced by interleukin (IL)-6 treatment of chondrocytes. We confirmed these differential HIF-2alpha-induced effects via distinct secretory mediators using Il6-knockout cells and a TNF-alpha-blocking antibody. The FLS-co-culture-induced gene expression changes in chondrocytes were significantly abrogated by IL-6 deficiency, whereas TNF-alpha neutralization blocked the alterations in gene expression associated with co-culture of FLS with chondrocytes. Our results further suggested that the observed changes might reflect the HIF-2alpha-induced upregulation of specific receptors for TNF-alpha (in FLS) and IL-6 (in chondrocytes). This study broadens our understanding of the possible regulatory mechanisms underlying the crosstalk between the synovium and cartilage in the presence of HIF-2alpha, and may suggest potential new anti-arthritis therapies.
Animals ; Arthritis/genetics/*immunology/pathology ; Arthritis, Rheumatoid/genetics/immunology/pathology ; Basic Helix-Loop-Helix Transcription Factors/genetics/*immunology ; Cells, Cultured ; Chondrocytes/immunology/metabolism/*pathology ; Coculture Techniques ; Fibroblasts/immunology/metabolism/*pathology ; Gene Expression Regulation ; Interleukin-6/genetics/*immunology ; Male ; Mice ; Mice, Inbred C57BL ; Osteoarthritis/genetics/immunology/pathology ; Synovial Membrane/immunology/metabolism/*pathology ; Tumor Necrosis Factor-alpha/genetics/*immunology ; Up-Regulation

Adalimumab ; adverse effects ; therapeutic use ; Antirheumatic Agents ; adverse effects ; therapeutic use ; Arthritis, Rheumatoid ; drug therapy ; immunology ; Asian Continental Ancestry Group ; Autoantibodies ; immunology ; Female ; Humans ; Immunoglobulin A ; immunology ; Middle Aged ; Nephritis ; etiology ; immunology

OBJECTIVETo compare the diagnostic value of antibodies to mutated citrullinated vimentin (MCV) and some associated autoantibodies in juvenile idiopathic arthritis and to further analyze the relation between antibodies and inflammatory markers.

METHODAntibodies to cyclic citrullinated peptides (CCP) and anti-MCV antibodies were detected by enzyme-linked immunosorbent assay (ELISA), antiperinuclear factor (APF) and antikeratin antibody (AKA) by indirect immunofluorescent assay, as well as rheumatoid factor (RF) by latex agglutination test in serum samples from 113 patients with JIA and 56 children without rheumatoid arthritis.

RESULT(1) The positive rate of anti-MCV antibodies, anti-CCP antibodies, and RF was 16.8%, 14.2%, and 21.2% in the JIA. In the other group, the positive rate was 2.2%, 2.2%, and 6.5%. There was a significant difference between the two groups (χ(2)=8.105, 6.337, 7.036, P<0.05). The positive rate of AKA and APF were not significantly different. The area under the ROC curve of anti-MCV antibodies, anti-CCP antibodies, RF, AKA, APF was 0.579, 0.561, 0.578, 0.539, 0.505. (2) The positive rate of anti-MCV antibodies and anti-CCP antibodies were higher than other antibodies. In the RF-positive polyarticular disease patients, they were higher than those in the other subtypes (P<0.05). Antibody levels were not significantly different (P>0.05) from other subtypes. (3) The swollen joint counts and tender joint counts had a low correlation to anti-MCV antibodies, anti-CCP antibodies, RF, AKA and APF. No correlation was found between ESR, CRP and anti-MCV antibodies, anti-CCP antibodies, RF, AKA and APF.

CONCLUSIONThe diagnostic value of anti-MCV antibodies is low for JIA. The positive rate of anti-MCV antibodies was higher than the other antibodies in the classification of JIA. There was a low correlation between anti-MCV antibodies, anti-CCP antibodies, RF, AKA, APF and swollen joint counts, tender joint counts.

Antibodies, Antinuclear ; blood ; Arthritis, Juvenile ; blood ; Arthritis, Rheumatoid ; Autoantibodies ; blood ; Biomarkers ; blood ; Child ; Enzyme-Linked Immunosorbent Assay ; Fluorescent Antibody Technique, Indirect ; Humans ; Peptides, Cyclic ; immunology ; ROC Curve ; Rheumatoid Factor ; blood ; Vimentin ; immunology

OBJECTIVETo study the effect of bitter-cold herbs easing dampness method (BCHEDM) plus Sanhuang Yilong Decoction (SYD) combined with methotrexate (MTX) on expression levels of interleukin-1 (IL-1), IL-6, and IL-17 in rheumatoid arthritis (RA) patients of accumulated dampness-heat syndrome (ADHS).

METHODSFrom January 2011 to January 2013 recruited were 90 RA inpatients of ADHS at Department of Integrative Medicine on Rheumatoid Disease, General Hospital of Chengdu Military Region. They were assigned to the treatment group (45 cases) and the control group (45 cases) according to the random digit table produced by SPSS 11.5 Software. Patients in the treatment group were treated by heavy bitter-cold herbs plus SYD combined with MTX, while those in the control group were treated by MTX alone. Expressional levels of IL-1, IL-6, and IL-17 in serum were detected by enzyme linked immunosorbent assay (ELISA) before treatment, at week 2 and 4 after treatment. Erythrocyte sedimentation rate (ESR), C-reactive protein (CRP), and disease activity score in 28 joints (DAS28) were detected as well.

RESULTSAfter two or four weeks of treatment, ESR, CRP, and DAS28 decreased more in the treatment group than in the control group with statistical difference (P < 0.05, P < 0.01). After four weeks of treatment, IL-1, IL-6, IL-17, ESR, CRP, and DAS28 in the treatment group were all lower than before treatment and those of the control group at corresponding time points with statistical difference (P < 0.01).

CONCLUSIONSYD combined MTX could play roles of improving inflammatory indices within 2 weeks, and inhibiting the expression of IL-1, IL-6, and IL-17 within 4 weeks.

Arthritis, Rheumatoid ; blood ; drug therapy ; immunology ; Blood Sedimentation ; C-Reactive Protein ; Drug Therapy, Combination ; Drugs, Chinese Herbal ; therapeutic use ; Hot Temperature ; Humans ; Interleukin-1 ; blood ; Interleukin-17 ; blood ; Interleukin-6 ; blood ; Methotrexate ; therapeutic use ; Syndrome ; Treatment Outcome

BACKGROUND/AIMS: To evaluate the impact on mortality of anti-tumor necrosis factor (anti-TNF) treatment of rheumatoid arthritis-associated interstitial lung disease (RA-ILD). METHODS: We retrospectively reviewed the medical records of 100 RA-ILD patients who visited our tertiary care medical center between 2004 and 2011, identified those treated with an anti-TNF agent, divided patients into non-survivor and survivor groups and evaluated their clinical characteristics and causes of death. RESULTS: A total of 24 RA-ILD patients received anti-TNF therapy, of whom six died (25%). Mean age at initiation of anti-TNF therapy was significantly higher in the nonsurvivor versus survivor group (76 years [range, 66 to 85] vs. 64 years [range, 50 to 81], respectively; p = 0.043). The mean duration of anti-TNF treatment in the non-survivor group was shorter (7 months [range, 2 to 14] vs. 23 months [range, 2 to 58], respectively; p = 0.030). The duration of anti-TNF therapy in all nonsurviving patients was < 12 months. Pulmonary function test results at ILD diagnosis, and cumulative doses of disease-modifying drugs and steroids, did not differ between groups. Five of the six deaths (83%) were related to lung disease, including two diffuse alveolar hemorrhages, two cases of acute exacerbation of ILD, and one of pneumonia. The sixth patient died of septic shock following septic arthritis of the knee. CONCLUSIONS: Lung complications can occur within months of initial anti-TNF treatment in older RA-ILD patients; therefore, anti-TNF therapy should be used with caution in these patients.
Adult ; Aged ; Aged, 80 and over ; Antirheumatic Agents/adverse effects/*therapeutic use ; Arthritis, Rheumatoid/complications/diagnosis/*drug therapy/immunology/mortality ; Female ; Humans ; Lung Diseases, Interstitial/diagnosis/etiology/*mortality ; Male ; Middle Aged ; Republic of Korea ; Retrospective Studies ; Risk Assessment ; Risk Factors ; Tertiary Care Centers ; Time Factors ; Treatment Outcome ; Tumor Necrosis Factor-alpha/*antagonists & inhibitors

Eupatilin is the main active component of DA-9601, an extract from Artemisia. Recently, eupatilin was reported to have anti-inflammatory properties. We investigated the anti-arthritic effect of eupatilin in a murine arthritis model and human rheumatoid synoviocytes. DA-9601 was injected into collagen-induced arthritis (CIA) mice. Arthritis score was regularly evaluated. Mouse monocytes were differentiated into osteoclasts when eupatilin was added simultaneously. Osteoclasts were stained with tartrate-resistant acid phosphatase and then manually counted. Rheumatoid synoviocytes were stimulated with TNF-alpha and then treated with eupatilin, and the levels of IL-6 and IL-1beta mRNA expression in synoviocytes were measured by RT-PCR. Intraperitoneal injection of DA-9601 reduced arthritis scores in CIA mice. TNF-alpha treatment of synoviocytes increased the expression of IL-6 and IL-1beta mRNAs, which was inhibited by eupatilin. Eupatilin decreased the number of osteoclasts in a concentration dependent manner. These findings, showing that eupatilin and DA-9601 inhibited the expression of inflammatory cytokines and the differentiation of osteoclasts, suggest that eupatilin and DA-9601 is a candidate anti-inflammatory agent.
Animals ; Anti-Inflammatory Agents/pharmacology/*therapeutic use ; Arthritis, Experimental/chemically induced/*drug therapy ; Arthritis, Rheumatoid/drug therapy/pathology ; Cell Differentiation/*drug effects ; Cells, Cultured ; Collagen Type II ; Cytokines/biosynthesis ; Disease Models, Animal ; Drugs, Chinese Herbal/therapeutic use ; Female ; Flavonoids/pharmacology/*therapeutic use ; Humans ; Inflammation/drug therapy/immunology ; Interleukin-1beta/genetics/metabolism ; Interleukin-6/genetics/metabolism ; Lymph Nodes/cytology ; Mice ; Mice, Inbred DBA ; Monocytes/cytology ; Osteoclasts/*cytology ; Plant Extracts/pharmacology ; RNA, Messenger/biosynthesis ; Synovial Membrane/cytology ; T-Lymphocytes, Regulatory/cytology/immunology ; Tumor Necrosis Factor-alpha/pharmacology