This paper aims to explore the activity of Codonopsis canescens extract against rheumatoid arthritis(RA) based on the Toll-like receptors(TLRs)/mitogen-activated protein kinases(MAPKs)/nuclear factor kappa B(NF-κB) signaling pathways and its mechanism. The ultra-performance liquid chromatography-quadrupole time-of-flight/mass spectrometry(UPLC-Q-TOF-MS) was used to identify the components of C. canescens extract. Forty-eight male SD rats were randomly divided into six groups, namely the normal group, the model group, the methotrexate(MTX) tablet group, and the low, medium, and high-dose C. canescens extract(ZDS-L, ZDS-M, and ZDS-H) groups, with 8 rats in each group. The model of collagen-induced arthritis in rats was induced by injection of bovine type Ⅱ collagen emulsion. MTX(2.5 mg·kg~(-1)), ZDS-L, ZDS-M, and ZDS-H(0.3 g·kg~(-1), 0.6 g·kg~(-1), and 1.2 g·kg~(-1)) were administrated by gavage. Rats in the normal group and the model group received distilled water. MTX was given once every three days for 28 days, and the rest medicines were given once daily for 28 days. Body weight, degree of foot swelling, arthritis index, immune organ index, synovial histopathological changes, and serum levels of tumor necrosis factor-α(TNF-α), interleukin-1β(IL-1β), and interleukin-6(IL-6) were observed. Protein expressions of TLR2, TLR4, NF-κB p65, p38 MAPK, and p-p38 MAPK in rats were determined by Western blot. Thirty-four main components were identified by UPLC-Q-TOF-MS, including 15 flavonoids, 7 phenylpropanoids, 4 terpenoids, 4 organic acids, 2 esters, and 2 polyalkynes. As compared with the normal group, the body weight of the model group was significantly decreased(P<0.01), and foot swelling(P<0.05, P<0.01), arthritis index(P<0.01), and the immune organ index(P<0.01) were significantly increased. The synovial histopathological injury was obviously observed in the model group. The serum levels of inflammatory factors TNF-α, IL-1β, and IL-6 were significantly increased(P<0.01), and the protein expression levels of TLR2, TLR4, NF-κB p65, p-p38 MAPK/p38 MAPK in the synovial tissue were significantly increased(P<0.01) in the model group. As compared with the model group, the body weights of the ZDS dose groups were increased(P<0.01), and the degree of foot swelling(P<0.01) and the arthritis index were decreased(P<0.05, P<0.01). The immune organ index was decreased(P<0.01) in the ZDS dose groups, and the synovial tissue hyperplasia and inflammatory cell infiltration were alleviated. The serum levels of TNF-α, IL-1β, and IL-6 were significantly decreased(P<0.05, P<0.01), and the protein expression levels of TLR2, TLR4, NF-κB p65, p-p38 MAPK/p38 MAPK were decreased(P<0.05, P<0.01) in the ZDS dose groups. C. canescens extract containing apigenin, tricin, chlorogenic acid, aesculin, ferulic acid, caffeic acid, and oleanolic acid has a good anti-RA effect, and the mechanism may be related to the inhibition of TLRs/MAPKs/NF-κB signaling pathways.
Animals ; Cattle ; Male ; Rats ; Arthritis, Experimental/drug therapy* ; Arthritis, Rheumatoid/drug therapy* ; Body Weight ; Codonopsis/chemistry* ; Interleukin-6/blood* ; NF-kappa B/genetics* ; p38 Mitogen-Activated Protein Kinases/metabolism* ; Plant Extracts/therapeutic use* ; Rats, Sprague-Dawley ; Signal Transduction ; Toll-Like Receptor 2/metabolism* ; Toll-Like Receptor 4/metabolism* ; Tumor Necrosis Factor-alpha/pharmacology*

OBJECTIVE: To explore the characteristics and clinical phenotypes of rheumatoid arthritis (RA) and provide the basis for further understanding, interventions and outcomes of this disease. METHODS: RA patients attended at Peking University People's Hospital from 2018 to 2021 were enrolled in the study. Data collection included demographic data, the sites and numbers of joints involved, extra-articular manifestations (EAM), comorbidities and laboratory variables. Statistical and bioinformatical analysis was performed to establish clinical subtypes by clustering analysis based on the type of joint involved, EAM involvement and other autoimmune diseases overlapped. The characteristics of each subtype were analyzed. RESULTS: A total of 411 patients with RA were enrolled. The mean age was (48.84±15.17) years, and 346 (84.2%) were females. The patients were classified into 4 subtypes: small joint subtype (74, 18.0%), total joint subtype (154, 37.5%), systemic subtype (100, 24.3%), and overlapping subtype (83, 20.2%). The small joint subtype had no medium or large joint involvement, and 35.1% had systemic involvement. The erythrocyte sedimentation rate (ESR), C-reactive protein (CRP) levels and platelet count (PLT) were lower than those in other subtypes, and the rates of positive rheumatoid factors (RF-IgA and RF-IgG) were significantly higher in the small joint subtype. The total joint subtype had both large and small joint involvement but no systemic involvement. The rate of morning stiffness and positive antinuclear antibodies (ANA) in this subtype were lower than those in other subtypes. In the systemic subtype, interstitial lung disease and secondary Sjögren syndrome were the most common systemic involvements, with prominent levels of disease activity score 28-joint count (DAS28-ESR and DAS28-CRP). The overlapping subtype was commonly combined with Hashimoto's thyroiditis or primary Sjögren syndrome. Female in the overlapping subtype was more common than in other subtypes. This subtype was characterized by hyperglobulinemia, hypocomplementemia and high rate of positive ANA, especially spotting type. CONCLUSION Based on the clinical features, RA patients could be classified into 4 subtypes: small joint subtype, total joint subtype, systemic subtype, and overlapping subtype. Each subtype had its own clinical characteristics. They help for further understanding and a more individualized treatment strategy of RA.
Female ; Male ; Humans ; Cross-Sectional Studies ; Sjogren's Syndrome ; Rheumatoid Factor ; Arthritis, Rheumatoid ; Blood Sedimentation ; Phenotype

Abdomen ; Acupuncture Points ; Acupuncture Therapy ; Arthritis, Rheumatoid/therapy* ; Blood Sedimentation ; Humans ; Rheumatoid Factor ; Treatment Outcome

OBJECTIVE: To explore the clinical characteristics and biological treatment of juvenile Idiopathic arthritis (JIA) after adulthood. METHODS: Selected 358 patients with previous medical history diagnosed by JIA who were hospitalized in the Department of Rheumatology and Immunology, West China Hospital of Sichuan University from January 1, 2009 to January 1, 2019. Perform retrospective analysis of basic information, clinical symptoms, diagnostic indicators, treatment plans, outpatient follow-up (inpatients require outpatient follow-up treatment) and diagnosis and treatment process of 90 eligible cases included, and observe different ages and different courses of disease. The clinical characteristics of young and middle-aged idiopathic arthritis in adults and the outpatient situation of using biological agents for 6 months. RESULTS: According to age, they were divided into ≤26 years old group (42 cases) and >26 years old group (48 cases). Under examination [rheumatoid factor (RF), anti-nuclear antibody (ANA), anti-neutrophil antibody (ANCA), erythrocyte sedimentation rate (ESR), C-reactive protein (CRP), interleukin-1β (IL-1β), interleukin 6 (IL-6), hemoglobin (HGB), white blood cell count (WBC), human leukocyte antigen-B27 (HLA-B27), complement 3 (C3), etc.], concurrent in terms of symptoms, treatment and prognosis, the ≤26-year-old group was generally lighter than the >26-year-old group; that was, the older the age, the heavier the onset of inflammation and other symptoms, the more complications, the worse the treatment effect, and the worse the prognosis, and there were statistical differences academic significance (P < 0.05). According to the course of disease, they were divided into ≤19 years group (46 cases) and >19 years group (44 cases). In terms of examination (RF, ANA, ANCA, ESR, CRP, IL-1β, IL-6, HGB, HLA-B27, C3, etc.), complications, treatment and prognosis, the course of disease ≤19 years group was compared with the disease course> 19 years group Overall mild; that was, the longer the course of the disease, the more severe the onset of symptoms such as inflammation, the more complications, the worse the treatment effect, and the worse the prognosis, P < 0.05, the difference was statistically significant. After 6 months of outpatient treatment with biological agents, it was found that biological agents could improve some of the patients' clinical symptoms and delay the further development of the disease. Compared with the non-biological agent treatment group (48 cases), the biological agent group (42 cases) benefited, and the difference was statistically significant (P < 0.05). CONCLUSION Through retrospective analysis, this article believes that although adult JIA is diagnosed as connective tissue disease, it has special clinical characteristics with the course of the disease and age. Therefore, it should be recommended to give special attention to JIA patients after adulthood, require regular medical treatment in the adult rheumatology department, according to the corresponding connective tissue disease or JIA diagnosis, and standard treatment; at the same time, pay attention to the history of JIA. In the comparison of biological and non-biological treatment, it is proved that biological treatment can effectively improve some of the clinical symptoms of JIA patients after adulthood. Therefore, it is recommended that biological treatment be used as soon as possible if economic conditions permit to delay the development of the disease.
Adult ; Arthritis, Juvenile/drug therapy* ; Blood Sedimentation ; China ; Humans ; Infant ; Middle Aged ; Retrospective Studies ; Rheumatoid Factor

OBJECTIVE: To investigate the clinical characteristics and high risk factors of Rheumatoid arthritis (RA) complicated with tuberculosis infection. METHODS: Patients with rheumatoid arthritis diagnosed in the hospital of Sichuan Provincial People's Hospital from January 2007 to January 2017 was retrospectively collected, who were enrolled in the study group. A control group was randomly selected from the RA patients hospitalized in the same period without co-infection at a ratio of 1 :2. The general data, clinical data, laboratory test data, treatment plan, etc. of the two groups were collected in detail for single factor statistical analysis. Then multivariate Logistic regression was used to analyze the independent risk factors of RA complicated with tuberculosis infection with statistical significance in univariate analysis. RESULTS: The clinical manifestations of fever (83.3%) were most common, followed by cough (69%) and body mass loss (45.2%). In the infected group, pulmonary tuberculosis accounted for 73.3%. In the infected group the chest CT showed two or more cases, accounting for 59%. There were 9 cases (33.3%) occurring in the typical tuberculosis occurrence site. Compared with the control group, the erythrocyte sedimentation rate (ESR), C-reaction protein (CRP) levels, and the daily average dose of glucocorticoid in 1 year in the infected group were higher than those in the control group. And those differences were statistically significant(P < 0.05). There were no significant differences in gender, age, disease duration, disease activity score, white blood cell (WBC), platelet (PLT), hemoglobin (Hb), immunoglobulin G (IgG), complement (C), Anti cyclic citrullinated peptide antibody (anti-CCP), CD4⁺T cell count, and immunosuppressant use (P > 0.05). Multivariate Logistic regression analysis showed that CRP levels(OR=1.016, 95%CI:1.002-1.031) and the daily average dose of glucocorticoid in 1 year(OR=1.229, 95%CI:1.066-1.418)were the independent risk factors of RA complica-ted with tuberculosis infection. CONCLUSION RA patients with tuberculosis infection are mainly phthisis. The clinical manifestations of RA combined with tuberculosis infection are lack of specificity, and the chest imaging features of pulmonary tuberculosis are diverse, which are easy to be misdiagnosed. CRP levels and the daily average dose level of glucocorticoid in 1 year were risk factors for RA and tuberculosis infection.
Arthritis, Rheumatoid/complications* ; Autoantibodies ; Blood Sedimentation ; Humans ; Peptides, Cyclic ; Retrospective Studies ; Rheumatoid Factor ; Tuberculosis/epidemiology*

OBJECTIVE: To detect the levels of Dickkopf-1 (DKK-1) in the plasma of patients with rheumatoid arthritis (RA), and to analyze their correlation with peripheral blood T cell subsets and clinical indicators. METHODS: Enzyme-linked immunosorbent assay (ELISA) was used to detect plasma DKK-1 levels in 32 RA patients and 20 healthy controls, and to record the various clinical manifestations and laboratory indicators of the RA patients, and flow cytometry to detect peripheral blood T cell subsets in the RA patients (Including Treg, nTreg, aTreg, sTreg, Teff, Tfh, CD4⁺CD161⁺T, CD8⁺T, CD8⁺CD161⁺T cells). The plasma DKK-1 levels between the two groups were ompared, and its correlation with peripheral blood T cell subsets and clinical indicators analyzed. RESULTS: (1) The plasma DKK-1 concentration of the RA patients was (124.97±64.98) ng/L. The plasma DKK-1 concentration of the healthy control group was (84.95±13.74) ng/L. The plasma DKK-1 level of the RA patients was significantly higher than that of the healthy control group (P < 0.05), and the percentage of CD8⁺CD161⁺T cells in the peripheral blood of the RA patients was significantly higher than that of the healthy control group (P < 0.05). (2) The plasma DKK-1 level was positively correlated with erythrocyte sedimentation rate (r=0.406, P=0.021), DAS28 score (r=0.372, P=0.036), immunoglobulin G(r=0.362, P=0.042), immunoglobulin A(r=0.377, P=0.033); it had no correlation with age, course of disease, C-reactive protein, rheumatoid factor, anti-cyclic citrullinated peptide antibody, immunoglobulin M, complement C3, complement C4, white blood cell, neutrophil ratio. (3) The plasma DKK-1 level in the RA patients was positively correlated with the percentage of peripheral blood CD161⁺CD8⁺T cells (r=0.413, P=0.019);it had no correlation with Treg, nTreg, aTreg, sTreg, Teff, Tfh, CD4⁺CD161⁺T, CD8⁺T cells. (4) The percentage of CD161⁺CD8⁺T cells was negatively correlated with erythrocyte sedimentation rate (r=-0.415, P=0.004), C-reactive protein (r=-0.393, P=0.007), DAS28 score(r=-0.392, P=0.007), rheumatoid factor (r=-0.535, P < 0.001), anti-citrullinated protein antibody (r=-0.589, P < 0.001), immunoglobulin G(r=-0.368, P=0.012) immunoglobulin M (r=-0.311, P=0.035); it had no correlation with age, disease course, immunoglobulin A, complement C3, complement C4, white blood cell, and neutrophil ratio. CONCLUSION RA patients' plasma DKK-1 levels and the percentage of CD8⁺CD161⁺T cells in T cell subsets in peripheral blood increase, which may be related to the secretion of proinflammatory cytokines in patients; DKK-1 is involved in the regulation of bone homeostasis and can be used as a marker of bone destruction in RA.
Arthritis, Rheumatoid ; Blood Sedimentation ; Humans ; Intercellular Signaling Peptides and Proteins/blood* ; Plasma ; Rheumatoid Factor ; T-Lymphocyte Subsets

BACKGROUND: Several factors, including clinical manifestations and laboratory data, have been used to evaluate the disease activity of Sjögren's syndrome (SS). We investigated saliva indicators of disease activity in primary SS patients. METHODS: We enrolled 138 Taiwanese patients with primary SS and 100 Taiwanese normal controls. Interleukin (IL)-6, IL-17A, tumor necrosis factor-alpha (TNF-α), and rheumatoid factor (RF)-IgA levels in saliva samples were measured using ELISA or fluorescent enzyme-linked immunoassay. Serum IgG, IgA, and IgM levels were measured by nephelometry. Erythrocyte sedimentation rate (ESR) was measured with an automatic ESR analyzer. The t-test and Pearson correlation test were used. RESULTS: IL-6 level was higher in primary SS patients than in normal controls (14.23±14.77 vs 9.87±7.32, P=0.012), but there were no significant differences in IL-17A, TNF-α, and RF-IgA levels. In primary SS patients, IL-6 level correlated weakly with ESR and IgG levels (r=0.252, P=0.015, and r=0.248, P=0.017, respectively), and TNF-α level correlated weakly with IgG level (r=0.231, P=0.024). CONCLUSIONS: IL-6 may play a role in SS pathogenesis. Saliva IL-6 might be an indicator of disease activity in primary SS patients.
Blood Sedimentation ; Enzyme-Linked Immunosorbent Assay ; Humans ; Immunoassay ; Immunoglobulin A ; Immunoglobulin G ; Immunoglobulin M ; Interleukin-17 ; Interleukin-6 ; Interleukins ; Nephelometry and Turbidimetry ; Rheumatoid Factor ; Saliva ; Tumor Necrosis Factor-alpha

OBJECTIVE: To examine the relationship of serum/plasma YKL-40 levels with rheumatoid arthritis (RA) and their correlation with RA activity and rheumatoid factor (RF) level. METHODS: We performed a meta-analysis comparing the serum/plasma YKL-40 levels between patients with RA and controls and examined the correlation coefficients of the circulating YKL-40 level with the RF level and RA activity based on the 28-joint disease activity score (DAS28), erythrocyte sedimentation rate (ESR), and C-reactive protein (CRP) level. RESULTS: Nine studies (707 patients with RA and 1,041 controls) were included in the meta-analysis. The YKL-40 levels were significantly higher in the RA group than in the control group (standardized mean difference [SMD]=1.071, 95% confidence interval [CI]=0.726~1.417, p<0.001). Stratification by ethnicity showed significantly elevated YKL-40 levels in the RA groups from European, Asian, North American, and Arab populations. The YKL-40 level was significantly higher in the RA group than in the control group in both age- and sex-matched and only age-matched populations (SMD=0.937, 95% CI=0.554~1.320, p<0.001; SMD=2.951, 95% CI=1.389~4.512, p<0.001, respectively). Subgroup analysis by sample size showed significantly increased YKL-40 levels in the RA group in both small (n<100) and large (n>100) populations. Meta-analysis of correlation coefficients showed a significant positive correlation between the YKL-40 levels and DAS28, ESR, CRP level, and RF level (DAS28: correlation coefficient=0.381, 95% CI=0.044~0.640, p=0.028; RF level: correlation coefficient=0.341, 95% CI=0.176~0.487, p<0.001). CONCLUSION: The circulating YKL-40 levels are high in patients with RA and positively correlate with RA activity and RF level.
Arabs ; Arthritis, Rheumatoid ; Asian Continental Ancestry Group ; Blood Sedimentation ; C-Reactive Protein ; Humans ; Rheumatoid Factor ; Sample Size

OBJECTIVE: To evaluate the value of anti-carbamylated protein (CarP) antibody in the diagnosis of rheumatoid arthritis-associated intersitial lung diseas (RA-ILD). METHODS: Clinical and laboratory data and serum samples of patients with RA between December 2017 and June 2019 in Department of Rheumatology, General Hospital of Ningxia Medical University were collected. The patients were subclassified as RA-ILD and RA-without ILD based on computed tomography scans of the chest, Enzyme 1inked immunosorbent assay (ELISA) was used to assess anti-CarP antibody in the serum of each group. The occurrence of ILD and other laboratory indexes were analyzed. Comparison of measurement data between the 2 groups was performed by two independent sample t-test or Mann-Whitney U nonparametric test, while the count data were compared by Chi square test; Receiver operating characteristic curve (ROC) was drawn to determine the cut-off value of anti-CarP antibody to RA-ILD diagnosis and to analyze its diagnostic efficacy. RESULTS: The anti-CarP antibody level in the RA-ILD group was 21.14 (12.29, 29.75), which was significantly higher than that in the RA-without ILD group 11.6 (6.66, 19.05) (P=0.000). The difference was statistically significant (P<0.05). The positive rate of anti-CarP antibody in RA-ILD group (53%) was significantly higher than that in RA-without ILD group (16%) (P<0.05); There was no significant differences in the levels of rheumatoid factor (RF) and anti-cyclic citrullinated peptide (CCP) between the two groups (P>0.05). The age and disease activity score (DAS28) in the RA-ILD group were significantly higher than those in the RA-withhout ILD group (P<0.05). The proportion of men and smoking in the RA-ILD group was higher than that in the RA-without ILD group, but the difference was not statistically significant. The ROC curve showed that the anti-CarP antibody had a cut off value of 20.56 U/mL, with the sensitivity of 53.50%, and specificity of 84.20%, the area under the ROC curve were 0.76. Spearman correlation analysis showed that rheumatoid factor (RF) and age were positively correlated with anti-CarP antibody (r=0.172, P=0.043; r=0.200, P=0.006). Anti-CarP antibody level was not associated with the DAS28 score, erythrocyte sedimentation rate (ESR), C-reactive protein (CRP), anti-CCP antibody, swollen joint count, and tender joint count (P>0.05). CONCLUSION The anti-CarP antibody level in RA-ILD patients is higher than that in RA-without ILD, suggesting that anti-CarP antibody may have a role in the development of RA-ILD.
Arthritis, Rheumatoid ; Autoantibodies ; Blood Sedimentation ; Humans ; Lung Diseases ; Male ; Peptides, Cyclic ; Rheumatoid Factor

OBJECTIVE: Antibodies against carbamylated protein (anti-CarP) were found to be a promising marker to evaluate joint damage and disease activity in patients with rheumatoid arthritis (RA). However, whether anti-CarP antibodies were present in systemic lupus erythematosus (SLE) remained ambiguity. We have therefore undertaken this study to assess the levels of serum anti-CarP antibodies and to evaluate their clinical value in SLE. METHODS: Serum levels of antibodies against carbamylatedfibrinogen (anti-CarP) were measured by enzyme-linked immunosorbent assay (ELISA) in 105 SLE patients and 73 healthy controls. Other clinical and laboratory measurements of the SLE patients were collected from medical records. Data analyses between anti-CarP antibodies and other laboratory measurements were performed using SPSS software for Windows 24.0. RESULTS: The levels of serum anti-CarP antibodies in the patients with SLE were significantly higher than those in the healthy controls (P<0.05). There were significant differences between the anti-CarP-positive group and anti-CarP-negative group in many clinical features. The disease duration, values of ESR, CRP, RF, anti-cardiolipin, anti-dsDNA, D-dipolymer, IgA and IgG were significantly higher in the anti-CarP-positive group compared with the negative group (P<0.05). Conversely, the values of complement 3, complement 4, peripheral blood RBC, and hemoglobin were significantly lower in anti-CarP-positive group than in the negative group(P<0.05). Moreover, the incidence of increase of erythrocyte sedimentation rate (ESR), C-reactive protein (CRP), rheumatoid factor (RF), D-dipolymer, decrease of peripheral blood RBC, hemoglobin, complement 3, complement 4, and positive rate of anti-dsDNA were significant different between the two groups(P<0.05). The positive rate of anti-CarP (21.9%) was higher than that of anti-Sm (15.24%), and close to anti-ribosomal P protein (22.86%) in our SLE patients. In addition, anti-CarP antibody was present in the SLE patients lacking the disease specific antibodies, including anti-Sm (anti-CarP positive rate 20.2%, 18/89), anti-dsDNA (anti-CarP positive rate 9.3%, 4/43), anti-nucleosome (anti-CarP positive rate 12.5%, 6/48), and anti-ribosomal P protein antibody (anti-CarP positive rate 20.9%, 17/81). Moreover, the high levels of anti-CarP antibodies were correlated with short disease duration, low C3, C4, RBC, and hemoglobin (P<0.05), high ESR, CRP, IgA, IgG, RF, anti-cardiolipin, anti-dsDNA, and D-dipolymer (P<0.05). CONCLUSION The level of anti-CarP antibody was increased in the serum of patients with SLE. There were correlations between anti-CarP antibodies and clinical and laboratory indicators of SLE patients.
Autoantibodies ; Blood Sedimentation ; Enzyme-Linked Immunosorbent Assay ; Fibrinogen ; Humans ; Lupus Erythematosus, Systemic ; Rheumatoid Factor