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Objective: The objective of this study was to explore the associations of body mass index (BMI), fat mass index (FMI), skeletal mass index (SMI) and secondary osteoporosis (OP) in patients with rheumatoid arthritis (RA)., Methods: The bone mineral density (BMD) at sites of the femur neck (Neck), total hip (Hip) and lumbar vertebrae 1-4 (L1-4) was measured by dual-energy X-ray absorptiometry. The skeletal muscle index, body fat percentage and mineral content were measured by biological electrical impedance for calculating BMI, FMI and SMI., Results: A total of 433 patient with RA and 158 healthy controls were enrolled. The BMDs at each site of the RA patients were lower compared with those of the healthy controls (p < 0.0001), and the prevalence of OP (36.1%, 160/443) and sarcopenia (65.2%, 288/443) in the RA patients were higher than those in the controls (12.7%, 20/158, p < 0.0001; 9.0%, 14/156, p < 0.0001). Significant differences in the BMD, FMI, SMI, mineral content, body fat percentage and skeletal muscle mass were found among the RA patients in the different BMI groups (p < 0.05). In RA patients with BMI < 18.5 kg/m 2 , the prevalence of OP in the RA patients with sarcopenia was similar to that in those without sarcopenia (44.4% vs. 66. 7%, χ 2  = 0. 574, p = 0.449). In the RA patients with a normal BMI or who were overweight or obese, prevalence of OP in the RA patients with sarcopenia was significantly higher than that in the RA patients without sarcopenia (42.8% vs. 21.7%, χ 2  = 10.951, p = 0.001; 61.1% vs. 13.0%, χ 2  = 26.270, p < 0.0001). In the RA patients without sarcopenia, the prevalence of OP in the RA patients in the different BMI groups was different (p = 0.039). In the RA patients with sarcopenia, there was no significant difference in the prevalence of OP among the RA patients in the different BMI groups (p = 0. 128). The linear correlation analysis showed that the SMI in RA patients was positively correlated with the BMD of each site measured and BMI and FMI (p < 0.0001). However, there was a negative linear correlation between SMI and disease duration (p = 0.048). The logistic regression analysis found that SMI (OR = 0.569, p = 0.002, 95% CI 0.399-0.810), BMI (OR = 0.884, p = 0.01, 95% CI 0.805-0.971) and gender (1 = female, 2 = male) (OR = 0.097, p < 0.0001, 95% CI 0.040-0.236) were protective factors for OP in RA, while age (OR = 1.098, p < 0.0001, 95% CI 1.071-1.125) was the risk factor., Conclusion: BMI and SMI are associated with the occurrence of OP in RA patients, and both SMI and BMI are important protective factors for OP secondary to RA., (© 2024. The Author(s).)

Objectives: The study aimed to explore the association of sarcopenia and vitamin D deficiency with glucocorticoid-induced osteoporosis (GIOP) in Chinese patients with rheumatoid arthritis (RA)., Method: Skeletal muscle mass, serum 25(OH)D levels, and bone mineral density (BMD) were assessed., Results: The prevalence of OP, sarcopenia, and vitamin D deficiency in RA patients was significantly higher than in controls (all P < 0.001). The percentage of GC use was 56.9%, and the prevalence of GIOP was 38.1% in 480 RA patients. The prevalence of OP in RA patients without sarcopenia was lower than that in RA patients with sarcopenia (P < 0.05). In RA patients with and without GC, the prevalence of OP in patients without sarcopenia was significantly lower than that in patients with sarcopenia (P < 0.001 and P < 0.05). Female sex (OR = 54.737; 95% CI: 7.103-421.809; P < 0.0001), age (OR = 1.078; 95% CI: 1.048-1.110; P < 0.0001), sarcopenia, and vitamin D deficiency (OR = 2.250; 95% CI: 1.246-64.065; P = 0.007) were risk factors for GIOP in RA patients., Conclusions: GIOP is associated with sarcopenia and vitamin D deficiency and is widespread among Chinese patients with RA. Key points ·Percentage of using GC and the prevalence of OP were all high in Chinese patients with RA. ·GIOP was widely existed in Chinese RA patients, which was associated with sarcoprnia and vitamin D deficiency., (© 2023. The Author(s), under exclusive licence to International League of Associations for Rheumatology (ILAR).)

Objectives: To explore the synergistic effect of vitamin D deficiency and sarcopenia on vertebral osteoporostic fracture (VF) in patients with rheumatoid arthritis (RA)., Methods: A total of 188 patients with RA and 158 control subjects were enrolled. Bone mineral density (BMD) at the total hip, neck of femur, lumbar vertebra 1-4, and skeletal muscle mass was measured by dual energy X-ray absorptiometry (DXA) and biological electrical impedance, respectively. Serum 25(OH)D was tested by electrochemiluminescence. The prevalence of VF and osteoporosis (OP) were compared between RA and controls. The synergism of sarcopenia and vitamin D deficiency on VF in patients with RA was tested by χ 2 test and logistic regression., Results: The prevalence of OP at all measured sites and VF in RA patients were all higher than those in controls (P < 0.0001). The incidence of VF in RA either with sarcopenia or with vitamin D deficiency was higher than for those without sarcopenia or without vitamin D deficiency (χ 2  = 5.069, P = 0.027, χ 2  = 8.822, P = 0.001). Age, disease duration, C-reactive protein (CRP), erythrocyte sedimentation rate (ESR), DAS28, health assessment questionnaire (HAQ), Sharp score, and body mass index (BMI) were significantly different between RA with sarcopenia or not (P < 0.05). Logistic regression analysis found that age (OR = 1.095, 95%, CI: 1.044-1.150, P < 0.0001) was a significant risk factor for VF in patients with RA, while high skeletal muscle mass (SMI) (OR = 0.513, 95% CI: 0.327-0.804, P = 0.004) was a protective factor for VF in RA patients., Conclusions: VF, sarcopenia, and vitamin D deficiency are common in patients with RA. Sarcopenia and vitamin D deficiency may be risk factors for the incidence of VF in RA patients., Key Points: • RA patients had a higher incidence of OP and VF, also a high prevalence of sarcopenia and vitamin D deficiency. • Vitamin D deficiency and sarcopenia may might have a synergistic effect on VF in RA. • Aging and sarcopenia are risk factors for VF in RA patients, and sarcopenia were associated with disease activity and structural damage., (© 2022. The Author(s), under exclusive licence to International League of Associations for Rheumatology (ILAR).)

Patients with rheumatoid arthritis (RA) had higher incidences of sarcopenia, falls, osteoporosis, and vertebral osteoporotic fractures (VOPF). Sarcopenia was associated with longer disease duration, higher disease activity, and more severe RA. The interactive effect of sarcopenia and falls was associated with a higher risk of VOPF in patients with RA., Purpose: Whether sarcopenia and falls are a risk factor for vertebral fracture in RA patients has not been demonstrated. This study aimed to explore the incidence of vertebral osteoporotic fracture (VOPF) and its relationship with sarcopenia and falls in RA patients., Methods: A total of 474 RA patients and 156 controls were enrolled in this study. Anteroposterior and lateral X-ray examinations of the vertebral column (T4-L4) were used for the semiquantitative assessment of VOPF. Bone mineral density was measured by dual-energy X-ray absorptiometry. Skeletal muscle mass was measured by direct segmental multifrequency bioelectrical impedance analysis (DSM-BIA method)., Results: RA patients had an increased risk of sarcopenia (62.4% vs 9.0%, x 2  = 47.478, P < 0.001), falls (30.2% vs 3.2%), osteoporosis (OP) (33.5% vs 12.8%, x 2  = 134.276, P < 0.001), and VOPF (20.3% vs 3.8%, x 2  = 47.478, P < 0.001) than controls. Patients with sarcopenia were more likely to have VOPF than RA without sarcopenia (24.0% vs 14.0%, x 2  = 6.802, P = 0.009). RA with sarcopenia and prior falls had the highest incidences of VOPF (36.7%). Older age (OR = 1.056, P < 0.001, 95% CI 1.030-1.083), falls (OR = 2.043, P = 0.003, 95% CI 1.238-3.371), OP (OR = 1.819, P = 0.034, 95% CI 1.046-3.163), and usage of glucocorticoids (GCs) (OR = 1.862, P = 0.022, 95% CI 1.093-3.172) were risk factors for VOPF in RA patients, while a higher skeletal muscle index (SMI) was a protective factor (OR = 0.754, P = 0.038, 95% CI 0.578-0.984) for VOPF in RA patients., Conclusions: The interactive effect of sarcopenia and falls is associated with a higher risk of VOPF in patients with RA., (© 2021. International Osteoporosis Foundation and National Osteoporosis Foundation.)

B cell activating factor of TNF family (BAFF) is a member of TNF ligand superfamily and plays a key role in B cell homeostasis, proliferation, maturation, and survival. In this study, we detected BAFF level, the expressions of BAFF receptors and important molecules in NF-κB pathway in rheumatoid arthritis (RA) patients and analyzed the correlation between BAFF level and clinical variables, laboratory parameters or X-ray scores in order to elucidate the roles of BAFF in RA. A total of 50 RA patients and 50 healthy controls (HCs) were enrolled. We showed that the serum BAFF level in RA patients was significantly higher than that of HCs, and the percentages of B cell subsets (CD19 + B cells, CD19 + CD27 + B cells, CD19 + CD20 + CD27 + B cells, and CD19 + CD20 - CD27 + B cells) in the serum of RA patients were significantly increased compared with those of HCs. The percentages of CD19 + BAFFR + B cells, CD19 + BCMA + B cells, and CD19 + TACI + B cells in RA patients were significantly increased compared with those in HCs. The expression of important molecules in the NF-κB pathway (MKK3, MKK6, p-P38, p-P65, TRAF2, and p52) was significantly higher in RA patients than in HCs, but p100 level in RA patients was lower than that in HCs. The serum BAFF level was positively correlated with C-reactive protein, rheumatoid factor, disease activity score (in 28 joints), swollen joint counts, tender joint counts, and X-ray scores. When normal B cells were treated with BAFF in vitro, the percentages of the B cell subset and the expression of BAFF receptors were significantly upregulated. BAFF also promoted the expression of MKK3, MKK6, p-P38, p-P65, TRAF2, and p52. In conclusion, this study demonstrates that BAFF level is correlated with the disease activity and bone destruction of RA. BAFF is involved in the differentiation, proliferation, and activation of B cells in RA through NF-κB signaling pathway, suggesting that BAFF might be an ideal therapeutic target for RA., (© 2021. The Author(s), under exclusive licence to CPS and SIMM.)

Objectives: This study aimed to investigate the synergistic effect of sarcopenia and poor balance on osteoporotic vertebral fracture (VOPF) in Chinese patients with rheumatoid arthritis (RA)., Methods: A total of 238 RA patients and 158 normal subjects were enrolled in the case-control study. Poor balance capability (Berg balance scale (BBS) score < 40) and sarcopenia (skeletal muscle mass index (SMI) <7.0 (male)/5.7 (female)) between RA patients and normal subjects were compared. Associations of poor balance capability or sarcopenia with disease activity, structural damage, and joint function in different groups were also investigated., Results: The incidence of sarcopenia in RA was 58.4%, significantly higher than that in controls (P<0.0001). Moreover, the percentages of low balance capacity (BBS<40) in RA were 43.7%, which was higher than that in controls (P<0.0001). The prevalence of VOPF in the case group was 19.3%, which was higher than that in the controls (P<0.0001). In the RA group, compared to RA patients without VOPF, RA patients with VOPF had higher percentages of poor balance and sarcopenia (P<0.05). Compared with RA patients without sarcopenia or good balance, RA patients with sarcopenia or poor balance had a higher incidence of VOPF, higher disease activity, severer structural damage, and worse joint function (P<0.05). The incidence of VOPF in patients combined with good balance and non-sarcopenia (4.8%) was significantly lower than that in patients combined with poor balance and sarcopenia (38.2%) (P<0.0001). Logistic regression indicated that higher SMI and higher BBS scores were protective factors for VOPF in RA patients, while age was a risk factor for VOPF in RA patients (P<0.0001)., Conclusion: Sarcopenia and poor balance are popular in Chinese patients with RA, and they are associated with disease activity and structural damage. There is a synergistic effect of sarcopenia and poor balance on VOPF in RA. Key Points • Sarcopenia and balance capability were popular (about a half) in patients with RA. • Sarcopenia and poor balance had a synergistic effect on VOPF in RA., (© 2021. International League of Associations for Rheumatology (ILAR).)

Objectives: This study aimed to investigate the relationship of serum hemoglobin (HB) level with disease activity and structural damage in Chinese patients with rheumatoid arthritis (RA)., Methods: A total of 890 RA patients and 890 normal subjects were enrolled in the case-control study. A HB threshold of< 110 g/L (women) and < 120 g/L (men) was used to determine anemia. All the patients were divided into three groups: non-anemia group (HB ≥ 120 g/L (male) or 110 g/L (female)), mild anemia group ((90 g/L < HB < lower limit of normal), and medium to severe anemia group (HB ≤ 90 g/L). Serum HB level and anemia prevalence between RA patients and normal subjects were compared. Associations of HB level with disease activity, structural damage, and function of joint in different groups were also investigated., Results: The average of HB level in RA was (109.08 ± 17.96)g/l, which was lower than that in controls (136.75 ± 14.57)g/l (P < 0.001). Anemia was observed in 47% of the RA patients, while prevalence of anemia in control group was only 4.4%. In RA group, percentages of non-anemia, mild anemia, and medium to severe anemia were 47%, 38%, and 15%. Compared with non-anemia RA patients, RA patients with anemia had higher disease activity, severer structural damage and worse function of joint (P < 0.001). With the increase of anemia, the disease activity, structural damage, and dysfunction of joints increased significantly (P < 0.05-0.001). Linear regression analysis showed that HB level was negatively correlated with disease activity parameters, degree of joint destruction, and function (P < 0.05-0.001). Logistic regression indicated that serum HB level was protective factors for disease activity and structural damage in RA (P < 0.001)., Conclusion: HB level was significantly related to disease activity and structural damage in RA patients.Key Points• Inflammatory anemia was popular (about a half) in patients with RA.• HB level was related to disease activity and structural damage in RA patients.

Objectives: To explore the prevalence and risk factors of osteoporosis (OP) and vertebral osteoporotic fracture (VOPF) in patients with rheumatoid arthritis (RA)., Methods: Anteroposterior and lateral X-ray examination of the vertebral column (T4-L4) was used for the semi-quantitative assessment of VOPF. Bone mineral density was measured by dual-energy X-ray absorptiometry., Results: Of 865 RA patients, the prevalence of OP and VOPF was 33.6% and 20.2%, respectively. Patients with OP or VOPF were older, and had longer term use and a larger daily amount and cumulative dose of glucocorticoids (GCs), longer disease duration, and higher Health Assessment Questionnaire (HAQ) scores and Sharp scores than patients without OP or VOPF (P < 0.05). OP was also correlated with higher disease activity. The patients treated with GCs had higher incidences of OP and VOPF than the patients without GCs (P < 0.05). The cutoff values in the area under curve (AUC) of the daily dose or treatment course of GCs-VOPF were 9 mg and 37.5 days. Older age, female sex, and a higher Sharp score were risk factors for OP in RA patients, while higher BMI was a protective factor. Older age and a high GC daily dose were risk factors for VOPF in RA patients., Conclusions: RA patients have a high prevalence of OP and VOPF. Older age, female sex, lower BMI, and higher activity and severity of RA are closely related with OP. Older age and a higher GC daily dose are risk factors for VOPF in RA patients. Key Points • Older age, female sex, lower BMI, and a higher Sharp score were risk factors for OP in RA patients. • Older age and a high GC daily dose were risk factors for VOPF in RA patients. • OP and VOPF in RA patients were correlated with longer disease duration and higher severity of RA.

Osteoporosis Self-Assessment Tool for Asians (OSTA) is an indicator for assessing osteoporosis in postmenopausal women. The aim of this study was to investigate the value of OSTA index on predicting osteoporosis in elderly Chinese patients with established rheumatoid arthritis (RA). A total of 320 patients with RA and 158 normal individuals were recruited from January 2015 to October 2017. Bone mineral density (BMD) at the femur and lumbar spine was measured by dual-energy X-ray absorptiometry. RA group and control group were divided into low risk (values≥-1), medium risk (values between -4 and -1), and high risk (values ≤-4) group according to the value of OSTA index. One-way analysis of variance showed that BMD at all detected regions among the 3 groups were obviously different (p < 0.0001). Incidences of osteoporosis among different OSTA groups were 21.76% (47/216), 56.41% (44/78), and 80.77% (21/26), separately (x 2  = 67.389, p < 0.0001). In RA group including premenspausal or postmenspausal female subgroup, prevalences of osteoporosis among different OSTA groups were different (p < 0.05-0.0001). We also found a positive linear correlation between OSTA index and BMD (p < 0.0001) both in RA and in control groups. Logistic regression revealed OSTA index (odds ratio = 0.734, p < 0.0001, 95% confidence interval: 0.657-0.819) was a protective factor for occurrence of RA-induced osteoporosis. OSTA had the highest discriminatory power, with an estimated Area Under Curve (AUC) of 0.750 (95% confidence interval 0.694-0.807, p < 0.0001), sensitivity of 76.9% and specificity of 66.5%. Our findings indicated that OSTA index was closely associated with BMD in RA patients, the degree of correlation was much stronger than age or BMI. OSTA index was a predictor for osteoporosis in RA, but it might have little relationship with disease status in RA., (Copyright © 2018 The International Society for Clinical Densitometry. Published by Elsevier Inc. All rights reserved.)

Objectives: Recent evidence has demonstrated that UBASH3A play a pivotal role in multiple autoimmune diseases. In this study, we explored the association between UBASH3A gene single-nucleotide polymorphisms (SNPs) and rheumatoid arthritis (RA) in a Chinese Han population. We also comparatively evaluated the UBASH3A expression profile in peripheral blood mononuclear cells (PBMCs) from patients with RA and healthy controls., Methods: Four UBASH3A polymorphisms (rs1893592, rs11203203, rs2277798, and rs3788013) were studied in 553 patients with RA and 587 controls in a Chinese population. Genotyping was performed using the Fluidigm 192.24 Dynamic Array Integrated Fluidic Circuit (IFC). For gene expression study, UBASH3A mRNA levels of 30 RA patients and 31 healthy individuals were assessed by real-time quantitative polymerase chain reaction (RT-qPCR). Data were analyzed by SPSS 19.0 software., Results: A significant association between rs1893592 polymorphism and RA was found under all genetic models (all p<.05). We also discovered a significant association between rs3788013 polymorphism and RA in the allele and genotype distributions, as well as the recessive model (all p<.05). Moreover, we found the genotype distribution and allele frequency of rs1893592 were significantly associated with RF phenotype in the RA patients (χ 2  = 6.786, p=.034; χ 2  = 4.534, p=.033; respectively). We also found the genotype distribution and allele frequency of rs2277798 were significantly associated with anti-CCP phenotype in the RA patients (χ 2  = 7.873, p=.020; χ 2  = 4.473, p=.034; respectively). However, we did not detect any significant associations between rs11203203 and RA susceptibility and autoantibody profiles (all p>.05). The mRNA expression of UBASH3A was increased in PBMCs of patients with RA when compared to healthy controls (p=.001)., Conclusions: Our observations suggested that the dysregulation of UBASH3A might be associated with the pathogenesis of RA, and UBASH3A gene polymorphisms (rs1893592 and rs3788013) might contribute to RA susceptibility in Chinese Han population.

Usage of glucocorticoid (GC) is a strong risk factor of osteoporosis (OP) and osteoporotic fracture (OPF) in Chinese patients with rheumatoid arthritis (RA). Controlling GC daily dosage and shortening GC course are helpful in preventing glucocorticoid-induced osteoporosis (GIOP) and OPF for Chinese patients with RA., Introduction: This study aims to investigate the prevalence and risk factors of GIOP, and also identify influences of GC daily dosage and GC treatment course for GIOP in Chinese patients with RA., Methods: Seven hundred and ninety patients with RA and 158 normal subjects were enrolled in the study. Clinical and laboratory features and medications of GC were recorded in detail. Bone mineral density (BMD) was measured by dual energy X-ray absorptiometry in all subjects., Results: BMD at all measured sites in RA was significantly lower than that in control group. Prevalence of OP was obviously higher in RA with GC group (41.6%), compared with RA without GC group (29.4%). Prevalence of OPF in group of RA with GC (21.0%) was higher than that in group of RA without GC (13.3%). Usage of GC, female, and age were risk factors for the occurrence of OP and OPF in RA, while body mass index (BMI) was the protective factor of OP. Prevalence of GIOP and OPF had statistical significance among groups of different treatment courses with GC, whereas no statistical difference was found among groups with different daily dosages of GC., Conclusions: GIOP exists generally in Chinese patients with RA, which relates to treatment course not daily dosage of GC. Usage of GC is also the risk factor for the happening of OPF in Chinese patients with RA.

Osteoporosis (OP) is one of the signs of bone damage in rheumatoid arthritis (RA). The 14-3-3η protein is an inflammatory protein, which has been reported to be associated with rheumatoid arthritis (RA). This is to determine the serum levels of 14-3-3η protein, evaluate its diagnostic value in early RA, and clear out its significance in RA with secondary osteoporosis. Two hundred fifty-nine RA patients and 80 age and sex-matched healthy controls were included. Assays of serum 14-3-3η protein were done for all participants by enzyme-linked immunosorbent assay (ELISA). Dual-energy X-ray absorptiometry (DEXA) was used to measure bone mineral density (BMD). Serum 14-3-3η protein level was significantly high in RA (2.49/4.72), compared with controls (P < 0.0001). Positive rate of 14-3-3η protein in RA was 97.3%, which was higher than that in controls (χ 2  = 276.641, P < 0.0001). Serum 14-3-3η protein level in early RA was significantly higher than that in established RA (3.91/4.82 vs 2.01/3.29, Z = 2.624, P < 0.05). The positive rate among three groups (normal control, early RA group, established RA group) differed from each other (χ 2  = 131.396, P < 0.0001). Results of ROC curve indicated the cutoff point of 14-3-3η protein for diagnosis of early RA was 0.879 ng/ml (P < 0.0001). Linear correlation analysis found that serum 14-3-3η protein positively correlated with VAS and HAQ (P < 0.0001), negatively correlated with BMD at lumbar spine and femur in RA (P < 0.0001). Serum 14-3-3η protein among groups of bone mass normal (2.73/3.79), osteopenia (3.15/4.86), and osteoporosis (6.34/6.42) was different in early RA patients (χ 2  = 7.974, P < 0.05). Serum 14-3-3η protein levels increase significantly in patients with RA (especially in early RA). There are close relationships between serum 14-3-3η protein and clinical symptoms and osteoporosis in patients with RA.

Introduction: Chicken type II collagen (CCII) is a protein extracted from the cartilage of chicken breast and exhibits intriguing possibilities for the treatment of autoimmune diseases by inducing oral tolerance. A 24-week, double-blind, double-dummy, randomized, methotrexate (MTX)-controlled study was conducted to evaluate the efficacy and safety of CCII in the treatment of rheumatoid arthritis (RA)., Methods: Five hundred three RA patients were included in the study. Patients received either 0.1 mg daily of CCII (n = 326) or 10 mg once a week of MTX (n = 177) for 24 weeks. Each patient was evaluated for pain, morning stiffness, tender joint count, swollen joint count, health assessment questionnaire (HAQ), assessments by investigator and patient, erythrocyte sedimentation rate (ESR), and C-reactive protein (CRP) by using the standard tools at baseline (week 0) and at weeks 12 and 24. Additionally, rheumatoid factor (RF) was evaluated at weeks 0 and 24. Measurement of a battery of biochemical parameters in serum, hematological parameters, and urine analysis was performed to evaluate the safety of CCII., Results: Four hundred fifty-four patients (94.43%) completed the 24-week follow-up. In both groups, there were decreases in pain, morning stiffness, tender joint count, swollen joint count, HAQ, and assessments by investigator and patient, and all differences were statistically significant. In the MTX group, ESR and CRP decreased. RF did not change in either group. At 24 weeks, 41.55% of patients in the CCII group and 57.86% in the MTX group met the American College of Rheumatology 20% improvement criteria (ACR-20) and 16.89% and 30.82%, respectively, met the ACR 50% improvement criteria (ACR-50). Both response rates for ACR-20 and ACR-50 in the CCII group were lower than those of the MTX group, and this difference was statistically significant (P < 0.05). The DAS28 (disease activity score using 28 joint counts) values of the two treatment groups were calculated, and there was a statistically significant difference between the two treatment groups (P < 0.05). Gastrointestinal complaints were common in both groups, but there were fewer and milder side effects in the CCII group than in the MTX group. The incidence of adverse events between the two groups was statistically significant (P < 0.05)., Conclusions: CCII is effective in the treatment of RA and is safe for human consumption. CCII exerts its beneficial effects by controlling inflammatory responses through inducing oral tolerance in RA patients., Clinical Trial Registration Number: ChiCTR-TRC-00000093.