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Objective:To compare the expression levels of absent in melanoma 2 (AIM2) inflammasome pathways in rheumatoid arthritis (RA) and osteoarthritis (OA) synovial specimens.Methods:Synovial tissue samples were collected from 41 RA and 26 OA patients, respectively. Horseradish peroxidase immunohi stochemical staining was used to detect AIM2 inflammasome pathway-related proteins, including AIM2, apoptosis-associated speck-like protein containing a CARD(ASC), caspase-1, and interleukin-1 (IL-1β). A semi-quantitative score (H-score) was performed according to the degree of positiveness. Correlation analysis between H-score results and clinical indicators of erythrocyte sedimentation tate (ESR) and C-reactive protein (CRP) were performed. The H score between RA and OA was analyzed by t test and Spearman correlation analysis were utilized for correlation analysis between H score and ESR and CRP.Results:The H scores of AIM2 protein in RA synovial tissues was (132±7) and (54±8) in OA synovial tissues ( t=7.42, P<0.01). The H scores of ASC protein in RA synovial tissues was (107±9) and (74±6) in OA synovial tissues ( t=2.36, P<0.05). The H scores of caspase-1 protein in RA synovial tissues was (99±5) and (74±10) in OA synovial tissues ( t=2.15, P<0.05). The H scores of IL-1β protein in RA synovial tissues was (118±11) and (76±7) in OA synovial tissues ( t=3.30, P<0.05) . In the correlation analysis, AIM2 was positively correlated with ESR [ r=0.74, P<0.01, 95% CI(0.38, 0.9)], and ASC was positively correlated with ESR [ r=0.5, P<0.05, 95% CI(0.16, 0.74)], IL-1β was positively correlated with ESR [ r=0.62, P<0.05, 95% CI (0.31, 0.81)], and the difference was statistically significant ( P<0.05). At the same time, AIM2 was positively correlated with CRP [ r=0.65, P<0.05, 95% CI(0.25, 0.86)]; ACS was positively correlated with CRP [ r=0.42, P<0.05, 95% CI(0.05, 0.69)]. IL-1β was positively correlated with C-reactive Protein [ r=0.41, P<0.05, 95% CI(0.05, 0.67)] and positively correlated with C-reactive protein, and the difference was statistically significant ( P<0.05). Conclusion::The expression of AIM2 inflammasome pathway-related proteins in RA synovium, including AIM2, ASC, caspase-1, and IL-1β, is higher than that of OA and are positively correlated with disease activity. Activation of AIM2 inflammasome pathway may be associated with the pathogenesis of RA disease activity.
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Objective:To study the patterns of tocilizumab (TCZ) use, its efficacy and safety in patients with rheumatoid arthritis (RA) in routine clinical practice.Methods:A total of 407 patients with RA were enrolled from 23 centers and treated with TCZ within 8 weeks prior to the enrollment visit, and were followed for 6-month. The patterns of TCZ treatment at 6 months, the effectiveness and safety outcomes were recorded. Statistical analysis was performed using SAS version 9.4.Results:A total of 396 patients were included for analysis, in which 330 (83.3%) patients received TCZ combined with conventional synthetic disease-modifying antirheumatic drugs (csDMARDs), and 16.7%(66/396) received TCZ monotherapy. At baseline, TCZ was initiated in 56.6%(224/396) and 9.6%(38/396) of patients after failure of DMARDs and other biological agents (bDMARDs) respectively. During the 6-month follow-up period, the mean frequency of TCZ administration was (3.7±1.6), the mean TCZ dosage was (7.4±1.2) mg/kg, and the mean interval between doses was (40±13) days. 120(25.8%) patients were on TCZ treatment at the end of the study. Improvements in disease activity, systemic symptoms and patient report outcomes were observed at the end of the study. 22.7%(90/396) patients experienced at least one treatment related adverse event, and 8 patients experienced at least one serious adverse event.Conclusion:This study demonstrates that TCZ treatment is effective in patients with RA when being treated for 6 months with an acceptable safety profile. The duration of TCZ treatment needs to be extended.
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OBJECTIVE@#Autologous blood acupoint injection has practiced for treatment of various diseases, but its therapeutic mechanism remains unknown. This study aimed to explore the histological changes in the acupoint area after blood injection.@*METHODS@#Blood samples (0.1 mL) collected from donator mice was injected in the recipient mice at the acupoint of left Zusanli (ST- 36). At 0, 6, 12, 24, 48, 72 and 96 h after the injection (3 mice at each time point), peripheral blood and muscular tissue were collected from the injection site for blood cell classification and histological study with HE staining.@*RESULTS@#White blood cells and lymphocytes tended to increase but platelets tended to decrease at the acupoint after blood injection, but these changes were not statistically significant. Within 24 h after blood injection, acute inflammation occurred at the acupoint, and the injected blood components were infiltrated by neutrophils; a small number of monocytes were observed at the injection site, where red blood cells gradually disappeared. From 24 to 96 h, the injected area showed chronic inflammation with infiltration by mononuclear cells, macrophages, and lymphocytes, and the number of fibroblasts increased and neutrophils decreased gradually over time; the local muscle fibers were destroyed, and proliferation of fibrous tissue could be seen.@*CONCLUSIONS@#Blood injection at the acupoints can mimic the process of hematoma absorption in the muscular tissue, and local inflammation is initiated to engulf and clear the blood components, which may be the basis for the therapeutic effects induced by acupoint stimulation.
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OBJECTIVE@#To compare the histopathological features of the synovium between rheumatoid arthritis (RA) and osteoarthritis (OA).@*METHODS@#We retrospectively analyzed the synovial specimens obtained after synovial surgery in 72 cases of RA and 24 cases of OA. Two independent pathologists reviewed the sections of the synovial tissues with HE staining, quantitatively scored the degree of fibroblast-like synoviocyte (FLS) hyperplasia, vascular hyperplasia, fibroplasia, and lymphocyte infiltration, and examined the presence plasma cell infiltration. The pathological morphology of the synovial tissues was evaluated in relation with the clinical data of the patients.@*RESULTS@#Pannus formation was also detected in the synovium of OA patients, which showed a lesser degree of OA-FLS hyperplasia, fibrosis and lymphocyte infiltration and a significantly lower rate of plasma cell infiltration compared with the pannus in RA patients. Vascular proliferation was also milder in the pannus of OA patients than in RA pannus, but the difference was not statistically significant. In OA patients, the pannus could be observed under a microscope and was difficult to distinguish from that in RA patients.@*CONCLUSIONS@#Pannus formation occurs also in the synovium of OA patients but with milder FLS hyperplasia, fibrosis and lymphocyte infiltration and a lower rate of plasma cell infiltration compared with the pannus in RA patients. These differences in the pannus between OA and RA can be of potential value in the diagnosis and treatment of the patients.
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Humans , Arthritis, Rheumatoid , Cells, Cultured , Osteoarthritis, Knee , Retrospective Studies , Synovial MembraneABSTRACT
Objective:To establish a synthetic cyclic citrullinated peptide induced arthritis model in mice, explore immunogenicity and arthritogenicity of this peptide. Methods: 36 DBA/1 mice were randomly divided into three groups, which were injected the type Ⅱ collagen ( CⅡ, CIA ) emulsion, cyclic citrullinated vimentin peptide ( CCit-Vim, CCV-IA ) emulsion, cyclic citrullinated vimentin peptide conjugated KLH ( CCit-Vim+KLH,CCV+K-IA) emulsion on day 0 and 21,respectively. Using arthritis index( AI) ,paw swelling to evaluate the incidence of arthritis;ELISA tested serum anti-CCit-Vim antibody,anti-CⅡantibody,anti-CCP antibody and TNF-α, IIF detected AKA;Histopathology of the ankle joint was obsearved. Results: There were three mice appeared arthritis in CCV+K-IA,the incidence rate of 25%,but arthritis occurs later time,short duration,and the incidence and extent of arthritis were lower than the CIA. CCV-IA no arthritis performance. CCV+K-IA produce anti-CCit-Vim antibody were significantly higher than those in CIA (1. 32±0. 59 vs 0. 78±0. 27,P=0. 031). While Anti-CCP antibody of CCV+K-IA were significantly lower than CIA (54. 73±7. 33 vs 64. 37±9. 91,P=0. 007). The anti-CⅡ antibody in CCV+K-IA and CCV-IA were lower than the CIA(15. 73±2. 10, 16. 71±3. 03 vs 19. 50±2. 36,P<0. 05). The TNF-α produced by CCV+K-IA and CIA were both significantly higher than the CCV-IA (645. 61±35. 26,618. 98±53. 32 vs 533. 63±79. 49,P<0. 05). The AKA positive rate of CCV+K-IA is 50% (6/12),significantly higher than CCV-IA 25% ( 3/12 ) and CIA 16. 67% ( 2/12 ) . Histopathology of the ankle showed that the CCV-IA and CCV+K-IA have a mild synovial hyperplasia,no obvious synovial pannus formation and inflammatory cell infiltration. Conclusion:The cyclic citrul-linated peptide conjugated KLH not only has stronger immunogenicity but also has arthritogenicity. It induced a higher positive rate of AKA than CⅡ.
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Objective To establish the models with human rheumatoid arthritis (RA) synovial fibroblasts (RASFs)-cartilage-severe combined immune deficient (SCID) mice for the study of the RASFs in the pathogenesis of RA.Methods The 4th passage RASFs were marked with 5-bromodexyuridine (5-Brdu)and injected into a cavity of inert sterile gel sponge,then with the normal human cartilage co-implanted in the back subcutaneously of SCID mice to set up a novel model of RA.Osteoarthritis synovial fibroblasts (OASFs)were injected as control group.Thirty days after the surgery,the mice were killed,the grafts and the knee joints were proceed with histological study and immunohistochemistry to detect the expression of 5-Brdu and Vimentin in synoviocytes.The serum level of interleukin (IL)-6 and matrix metalloproteinase (MMP)-3 were detected with enzyme-linked immunosorbent assay (ELISA).Results Twenty-three mice survived except for one mouse in the RASFs group died of anesthesia.① Only in one case in the RASFs group,the IL-6 was detected,the others were unable to be detected.The MMP-3 in the OASFs group was (40±17) pg/ml,but in RASFs group only one case was detected.② There were 4 and 3 implanted cartilages loss in the RASFs group and OASFs group respectively.The histological scores of cartilage invasion by synoviocytes and cartilage degradation in grafts were higher in RASFs groups than in OASFs groups (0.6±0.7 vs 0.3±0.5,2.3±0.8 vs 1.7±1.0 respectively).③ The histological scores of synovial hyperplasia and cartilage invasion in the knee joints was significantly higher in the RASFs group than in the OASFs group (3.1±0.8 vs 1.7±1.0,P＜0.01,1.6±1.7 vs 0.6±1.4,P＜0.05 respectively).④ During the grafts,a lot of 5-Brdu and Vimentin markers positive synovio-cytes were found in the mice subcutaneous tissue,but manipulus positive synoviocytes were found on the area of cartilage invasion in both groups.In knee joints,single positive synoviocytes could be detected in bone marrow and hyperplasic area of the synovial tissue in both groups.Conclusion The isolated RASFs can survival and have the ability to invade and degrade the cartilage in vivo without the limitation of immunity induced inflammations,and can also migrate to the synovial joints in distance and induce arthritis.