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Aim: Coronavirus disease 2019 (COVID‐19) has been proposed as triggering autoimmunity. The aim of this study was to evaluate the presence and clinical significance of autoantibodies in patients with COVID‐19. Methods: We retrospectively collected data from 245 patients who were hospitalized for COVID‐19. All patients were tested for the presence of antinuclear antibody (ANA), rheumatoid factor (RF), anti‐citrullinated peptide antibody (ACPA), and anti‐cytoplasmic neutrophil antibody (ANCA). Risk factors for death and critical COVID‐19, defined as the need for invasive mechanical ventilation or extracorporeal membrane oxygenation, were analyzed. Results: Ninety (36.7%) patients tested positive for ANA, and 51 (20.8%) patients tested positive for RF. Three patients each (1.2%) tested positive for ACPA and ANCA. RF‐positive patients had higher rates of invasive mechanical ventilation and death than RF‐negative patients (70.6% vs 28.4%, P < 0.001 and 45.1% vs 18.6%, P < 0.001, respectively). Underlying lung disease, kidney disease, heart disease, quick COVID severity index (qCSI), and lactate dehydrogenase (LDH) were associated with in‐hospital death. RF (odds ratio [OR] 7.31, 95% CI 2.50–21.37, P < 0.001), qCSI (OR 1.42, 95% CI 1.19–1.69, P < 0.001), and LDH (OR 1.004, 95% CI 1.002–1.005, P < 0.001) were associated with critical COVID‐19. Combination of RF, qCSI, and LDH showed good prognostic value (area under the curve = 0.903, P < 0.001) for critical COVID‐19. Conclusions: ANA and RF were frequently detected in COVID‐19 patients. RF could be a risk factor for critical COVID‐19. The results of this study suggest immune dysfunction contributes to the complications of COVID‐19. [ABSTRACT FROM AUTHOR]

• The influence of equifinality on the hybrid model accuracy was assessed. • The hybrid model was developed by coupling SWAT with LSTM. • The two hybrid models constrained by RS-ET or not were compared. • The hybrid models showed better predictions than standalone SWAT and LSTM. • Among the hybrid models, those with RS-ET indicated enhanced performances. Hybrid models coupling process-based models with deep learning models have been widely used for estimating water quantity and quality. However, the impacts of uncertainty within process-based models on the performance of hybrid models remained largely unknown. This study focused on assessing the impact of uncertainties on a hybrid model that combines Soil and Water Assessment Tool (SWAT) with Long Short-Term Memory (LSTM) for estimating streamflow and suspended solids (SS). This study applied the output of SWAT as input for LSTM to make a hybrid model. By incorporating an additional constraint, remotely sensed evapotranspiration (RS-ET), the performance of hybrid models with and without considering RS-ET was evaluated at various temporal and spatial scales. Furthermore, various input settings (default and calibrated SWAT and inclusion/exclusion of precipitation) were considered. The results showed that the hybrid models tended to provide accurate estimations of monthly streamflow and SS compared to standalone SWAT and LSTM. The addition of precipitation to hybrid models did not make noticeable improvements for streamflow and SS. The hybrid models constrained by RS-ET tended to have improved estimations on streamflow and SS at daily and monthly scales compared to those unconstrained by RS-ET. Similar results were also observed at the sub-watershed level. These insights highlighted the potential of hybrid models to enhance hydrological estimations and underscore the importance of incorporating additional constraints to reduce uncertainties. Such advancements have practical implications for water resource management and decision-making processes, enabling more reliable and accurate estimations in applications of hybrid models. [ABSTRACT FROM AUTHOR]

Aim: To evaluate clinical characteristics and natural history of non‐radiographic axial spondyloarthritis (nr‐axSpA) using KOrean Nonradiographic Axial SPondyloArthritis (KONASPA) data. Methods: Data were collected from 11 centers in South Korea. A total of 278 patients with nr‐axSpA from January 2018 to July 2020 were included. Demographic data, clinical features, comorbidities, disease activity, medications, and laboratory results were collected. Results: Mean age at symptom onset was 28.2 ± 14.2 years. Of 278 patients, 152 (54.7%) were male. Mean Bath Ankylosing Spondylitis Disease Activity Index at diagnosis was 3.5 ± 2.1. Dyslipidemia was the most common comorbidity (8.4%), followed by hypertension (6.1%). Mean age at diagnosis of nr‐axSpA was older in female patients than in male patients (31.8 ± 15.8 years vs 24.9 ± 12.0 years, P < 0.001). Enthesitis and uveitis were more frequently found in female patients than in male patients. Thirty‐one (11.1%) participants with nr‐axSpA progressed to ankylosing spondylitis. The median follow‐up duration was 48 months. In multivariable Cox regression analysis, age at symptom onset (hazard ratio [HR] 0.93, 95% confidence interval (CI) 0.88‐0.97, P = 0.006), body mass index (BMI) (HR 1.24, 95% CI 1.06‐1.44, P = 0.005) and sacroiliitis grade (HR 1.86, 95% CI 1.19‐2.92, P = 0.006) were associated with progression to ankylosing spondylitis. Conclusions: Results of nationwide data revealed that women with nr‐axSpA showed a late disease onset and more extra‐articular manifestations than men. Young age at symptom onset, high BMI, and presence of radiographic sacroiliitis at diagnosis were risk factors for progression to AS. [ABSTRACT FROM AUTHOR]

Ankylosing spondylitis is a male-predominant disease and previous study revealed that estrogens have an anti-inflammatory effect on the spondyloarthritis (SpA) manifestations in zymosan-induced SKG mice. This study aimed to evaluate the effect of selective estrogen receptor modulator (SERM) lasofoxifene (Laso) on disease activity of SpA. Mice were randomized into zymosan-treated, zymosan + 17β-estradiol (E2)-treated, and zymosan + Laso-treated groups. Arthritis was assessed by 18F-fluorodeoxyglucose (18F-FDG) small-animal positron emission tomography/computed tomography and bone mineral density (BMD) was measured. Fecal samples were collected and 16S ribosomal RNA gene sequencing was used to determine gut microbiota differences. Both zymosan + E2-treated mice and zymosan + Laso-treated mice showed lower arthritis clinical scores and lower 18F-FDG uptake than zymosan-treated mice. BMD was significantly higher in zymosan + E2-treated mice and zymosan + Laso-treated mice than zymosan-treated mice, respectively. Fecal calprotectin levels were significantly elevated at 8 weeks after zymosan injection in zymosan-treated mice, but it was not significantly changed in zymosan + E2-treated mice and zymosan + Laso-treated mice. Gut microbiota diversity of zymosan-treated mice was significantly different from zymosan + E2-treated mice and zymosan + Laso-treated mice, respectively. There was no significant difference in gut microbiota diversity between zymosan + E2-treated mice and zymosan + Laso -treated mice. Laso inhibited joint inflammation and enhanced BMD in SKG mice, a model of SpA. Laso also affected the composition and biodiversity of gut microbiota. This study provides new knowledge regarding that selected SpA patients could benefit from SERM treatment. [ABSTRACT FROM AUTHOR]

Objectives: Spondyloarthritis (SpA) encompasses a group of disorders including ankylosing spondylitis, psoriatic arthritis, reactive arthritis, and enteropathic arthritis. SpA pathogenesis is still not well understood. Animal models are important for studying disease mechanisms and identifying new therapeutic agents. Recently, a β-glucan-induced SKG mouse was used as an animal model for SpA. The aim of this study was to evaluate the clinical and molecular characteristics of a zymosan-induced SKG mouse.Methods: Zymosan was injected intraperitoneally into SKG mice. Clinical arthritis scores were measured, and fluorine-18 fluorodeoxyglucose (18F-FDG) small-animal positron emission tomography/computed tomography (PET/CT) was performed to quantify joint inflammation. Histologic features of the joints, intestines, skin, and eyes were evaluated. Inflammatory cytokine and Wnt inhibitor expression was measured in mouse serum.Results: Zymosan exposure triggered SpA-like diseases in SKG mice, including peripheral arthritis, spondylitis, dactylitis, enteritis, and psoriatic skin lesions. 18F-FDG uptake was significantly higher in the zymosan-treated mice compared with controls. The expression of tumor necrosis factor α, interleukin (IL)-6, and Dickkopf-1 increased significantly, while IL-4 and sclerostin expression decreased significantly in zymosan-induced mice compared with control mice.Conclusions: Zymosan-induced SKG mice developed articular and extra-articular features as well as molecular changes that resembled those of human SpA. These findings suggest that the zymosan-induced SKG mouse is a good animal model to reflect the complex features of human SpA. [ABSTRACT FROM AUTHOR]

The soil vulnerability index (SVI) classifies vulnerability to cropland pollutant transport by surface runoff and leaching, helping to categorize areas with a high contribution of pollutant loads. This study aims to 1) adopt the SVI classification scheme in South Korea and 2) suggest a modified SVI classification scheme for surface runoff to anticipate climate change impacts. The precipitation amount was considered in an original scheme to make a modified scheme. The results with an original SVI classification scheme predicted that the SVI surface runoff vulnerability was relatively greater in areas with a steep slope than in those with a plain topography, and a high level of the SVI leaching vulnerability was frequently observed in plain areas. When a modified SVI classification scheme was applied, "High" vulnerability class increased from 44.0% to 57.4% and the greater increase rate was observed in the regions susceptible to heavy precipitation defined as a day with more than 80 mm precipitation. When compared with observational suspended solids, the results with a modified SVI classification scheme were more consistent with observations than those with an original SVI classification scheme. Relative to the baseline period, the SVI surface runoff vulnerability of "High" class increased by 47.1–88.7% during the climate change period. When the number of vulnerability classes was increased, the differences on "Very extremely high" class between the baseline and projection periods were clear with the increase rate of 16.4–343%. The results with an original SVI classification scheme matched well with the topographic characteristics, and a modified SVI classification scheme captured the impacts of regional precipitation patterns and climate change impacts. As a first approach to adopting the SVI classification system to South Korea, increasing the number of classifications in regions with excessive rainfall amounts can improve identifying those most vulnerable areas. • The SVI was developed to classify soil vulnerability classes to cropland pollutant. • The SVI classification scheme was tested on croplands across South Korea. • The SVI classification results agreed well with topographic characteristics. • An original classification scheme was modified to consider precipitation amount. • A modified classification scheme showed enhanced SVI classification results. [ABSTRACT FROM AUTHOR]

Aim: To evaluate the effect of tumor necrosis factor a inhibitors (TNFi) on spinal radiographic progression in patients with ankylosing spondylitis (AS). Methods: Subjects were selected from patients at a single tertiary hospital between 1995 and 2014. Patients who used TNFi with baseline and paired follow-up radiographic data with a minimum interval of 2 years were included. Time to start TNFi was defined as the time from symptom onset to the start of TNFi use. TNFi index was defined as the ratio of the period of TNFi use to the entire period of disease. Radiographic damage was assessed by the modified Stoke Ankylosing Spondylitis Spine Score (mSASSS). Univariable and multivariable linear regression analyses were used to identify factors associated with radiographic progression. Results: A total of 151 patients were included in the analysis. Seventeen (11.3%) patients were female and mean DmSASSS/year was 1.01 units/year. Mean X-ray follow-up duration was 102.9 ± 54.9 months. Mean time from symptom onset to start of TNFi use was 104.8 ± 83.6 months (median 84 months) and mean TNFi index was 42.9 ± 23.8% (median 40.9%). In multivariable analysis, initial mSASSS, initial C-reactive protein, body mass index, current smoker, and delayed start of TNFi use were associated with radiographic progression. Presence of peripheral arthritis and the TNFi index were negatively associated with radiographic progression. Conclusions: A delay in starting TNFi use and low TNFi index were associated with radiographic progression. Early and long-term use of TNFi appear to reduce spinal radiographic progression in patients with AS. [ABSTRACT FROM AUTHOR]

Objectives: This study aimed to evaluate the association of knee osteoarthritis (OA) with comorbidities and health-related quality of life (HRQOL). Methods: A total of 8,907 (weighted n = 13,687,058) participants aged ≥50 years who had undergone knee radiography were selected from the 2010–2012 Korea National Health and Nutrition Examination Survey. OA was classified into four subgroups based on the presence or absence of pain and radiographic OA (ROA): non-OA (Pain-/ROA-), pain only (Pain+/ROA-), ROA only (Pain-/ROA+), and painful ROA (Pain+/ROA+). ROA was defined as Kellgren–Lawrence grade ≥ 2. HRQOL measurements including EuroQOL visual analogue scale (EQ-VAS) scores and the five dimensions and summary index of the EuroQOL-5 dimension (EQ-5D index) were also analyzed. Multivariable logistic regression and linear regression analyses were performed. Results: After adjustment for socioeconomic and lifestyle characteristics, cardiovascular disease, malignancy, and other comorbidities were not significantly associated with OA. Pain only and painful ROA were each significantly associated with limitations in physical activity (odds ratio (OR) 2.66, 95% CI 2.07–3.44, p < 0.001 and OR 2.83, 95% CI 2.25–3.58, p < 0.001, respectively), lower EQ-VAS (β-coefficient = -10.95, p < 0.001 and β-coefficient = -9.75, p < 0.001, respectively), and EQ-5D index (β-coefficient = -0.10, p < 0.001 and β-coefficient = -0.13, p < 0.001) compared with the non-OA group, whereas ROA only was not associated with limitations in physical activity or lower HRQOL score. Conclusions: Comorbidities were not significantly associated with knee OA after adjustment. Knee OA was associated with physical activity and HRQOL. Painful knee OA, with or without ROA, was more strongly associated with decreased physical activity and lower quality of life than ROA without pain. [ABSTRACT FROM AUTHOR]

This study aimed to evaluate the prevalence of comorbidities in patients with rheumatoid arthritis (RA) compared with the non-RA population. The 2010–2012 Korea National Health and Nutrition Examination Survey (KNHANES), which assesses the general health status of populations in South Korea using interviews and basic health assessment, was analyzed retrospectively. Weighted prevalence and odds ratio (OR) of comorbidities were analyzed in patients with RA compared with the non-RA population. The overall weighted (n = 37,453,158) prevalence of RA was 1.5%. Patients with RA were older and more female predominant than subjects without RA. The prevalence of living in an urban area, college graduation, alcohol consumption and smoking was lower in patients with RA than non-RA. Patients with RA had more comorbidities including hypertension, dyslipidemia, myocardial infarction (MI) or angina, stoke, osteoarthritis, lung cancer, colon cancer, pulmonary tuberculosis, asthma, diabetes, depression, thyroid disease and chronic kidney disease. After adjusting socioeconomic and lifestyle characteristics, RA was associated with an increased prevalence of MI or angina (OR 1.86, 95% CI 1.17–2.96, p = 0.009), pulmonary TB (OR 1.95, 95% CI 1.24–3.09, p = 0.004), asthma (OR 1.97, 95% CI 1.05–3.71, p = 0.036), thyroid disease (OR 1.71, 95% CI 1.05–2.77), depression (OR 2.38, 95% CI 1.47–3.85, p < 0.001) and hepatitis B (OR 2.34, 95% CI 1.15–4.80, p = 0.020) compared with the non-RA population. Prevalence of solid cancer was not significantly associated with RA after adjustment. [ABSTRACT FROM AUTHOR]

This study aimed to evaluate the association between rheumatoid arthritis (RA) and hearing impairment in the Korean adult population. Audiometric and laboratory test data from the 2010–2012 Korean National Health and Nutrition Examination Survey (KNHANES) were used for analysis. The relationship between RA and hearing impairment was analyzed, adjusting for various known risk factors associated with hearing impairment. RA was defined in the questionnaire as “RA diagnosed by a physician (yes/no) through a standardized interview.” We defined hearing impairment according to 2 categories of frequency (low/mid and high) as follows (average values in kHz): low/mid frequency, 0.5, 1.0, and 2.0, and high frequency, 3.0, 4.0, and 6.0. Of the subjects, 15,158 (weighted n = 32,035,996) completed the audiometric tests. The overall weighted prevalence of RA was 1.5%. The prevalence of hearing impairment was higher in the subjects with RA than in those without RA, in both, the low/mid- and high-frequency categories (21.1% vs 7.5%, p < 0.001 and 43.3% vs. 26.2%, p < 0.001, respectively). In the multivariable logistic analysis, RA (odds ratios [OR] 1.47, 95% confidence interval [CI] 1.05–2.06, p = 0.025) was an independent risk factor of low/mid-frequency hearing impairment along with age (OR 1.12, 95% CI 1.12–1.13, p < 0.001), current smoking (OR 1.27, 95% CI 1.03–1.56, p = 0.026), and college graduation (OR 0.53, 95% CI 0.39–0.72, p < 0.001). In the multivariable analysis of high-frequency hearing impairment, RA did not show any association with hearing impairment. This study suggests that RA is associated with low/mid-frequency hearing impairment after adjustment for various known risk factors. Further study is needed to verify the hearing impairment in RA. [ABSTRACT FROM AUTHOR]

Aim To evaluate the clinical characteristics and outcomes of nonradiographic axial spondyloarthritis (nr-axSpA) in Korean patients. Methods A retrospective analysis evaluated 155 patients with nr-axSpA at a single tertiary hospital between January 2001 and January 2011. Baseline characteristics and clinical courses were reviewed and compared with those of patients with ankylosing spondylitis ( AS). Results The mean age at disease onset was 29.5 ± 10.8 years and 52 (33.5%) patients were female. The mean age at symptom onset was older (29.5 ± 10.8 vs 25.9 ± 9.2, respectively, P < 0.001) and the male-to-female ratio was lower (2 : 1 vs 5 : 1, respectively, P = 0.001) in patients with nr-axSpA compared with patients with AS. The proportion of females was higher among patients with late onset SpA than early-onset nr-axSpA (55.0% vs 30.1%, respectively, P = 0.029). Among 74 patients with nr-axSpA, whose follow-up duration was more than 1.5 years, 29 (39.2%) patients progressed to AS during the follow-up period. The proportion of females was lower in progressors that that of non-progressors (13.8% vs 44.4%, respectively, P = 0.010). Presence of syndesmophyte and minimal X-ray changes at baseline were frequently observed in progressors compared with non-progressors (26.7% vs 0.0%, P = 0.006 and 69.0 vs 35.6%, P = 0.005, respectively). Conclusions The predominance of male patients is more prominent among Korean patients with SpA compared with Caucasians. Female nr-axSpA patients had late symptom onset and less progression to AS. X-ray changes at baseline were associated with radiographic progression. [ABSTRACT FROM AUTHOR]

Objectives To evaluate the clinical courses and outcomes of patients with monoarthritis and to investigate the predictive factors of clinical outcomes. Methods A retrospective analysis was performed of 171 patients with chronic monoarthritis at a single tertiary hospital between January 2001 and January 2011. Baseline characteristics, radiographic findings and the clinical course were reviewed. Results The most commonly involved joints were the knees (24.0%), followed by the wrists (22.8%) and ankles (18.7%). A final diagnosis was established in 74 (43.3%) patients. Thirty-one (18.1%) patients were diagnosed with rheumatoid arthritis ( RA), 23 (13.5%) with peripheral spondyloarthritis (SpA), and 19 (11.1%) with Behçet's disease ( BD). Among 108 patients who were initially undiagnosed, 85 (78.7%) patients remained with undiagnosed monoarthritis, with relatively shorter symptom durations and requiring less treatment. The initially involved joint was a predictive factor for the final diagnosis: the wrist joint for RA (odds ratio [ OR] 11.58, P < 0.001), the ankle joint for SpA ( OR 6.19, P < 0.001), and the knee joint for BD ( OR 3.43, P = 0.014). Bony erosion at baseline was associated with progression to oligo- or polyarthritis ( OR 2.88, P = 0.030) and with radiographic progression. Conclusions In patients presenting with monoarthritis, a final diagnosis was established in less than half of the patients, and a majority of undiagnosed patients showed benign clinical courses. The initially involved joint and the presence of erosion at baseline were predictors of the final diagnosis and of clinical outcomes. [ABSTRACT FROM AUTHOR]

Abstract: Objectives: To investigate the effects of benzo[a]pyrene (B[a]P), a major toxic component of cigarette smoke, on the expression of Slug and to determine the effect of B[a]P/Slug on the invasive properties of rheumatoid arthritis (RA) fibroblast-like synoviocytes (FLS). Method: The expression of Slug was measured by real-time PCR following the stimulation of FLS with different concentrations of B[a]P or EGF. The phosphorylation of the key enzymes in the signaling pathway was analyzed by western blots. Inhibitors of PI3K/Akt/mTOR pathway were used to confirm the critical pathway for Slug expression. An in vitro cell invasion assay was performed using RA FLS treated with Slug cDNA, Slug small interference RNA, or control. Results: Slug expression increased significantly following treatment with B[a]P or EGF in a dose-dependent manner. The stimulation of FLS with B[a]P or EGF induced the phosphorylation of Akt kinase, but not in ERK, JNK and p38. The Slug mRNA expression induced by B[a]P and EGF decreased significantly following the treatment with PI3K/Akt/mTOR inhibitors. Slug overexpression using Slug cDNA upregulated the invasive function of FLS, and Slug depletion using siRNA showed the opposite effect compared with the control. In addition, the stimulation with B[a]P increased the invasive function of the control siRNA-treated FLS but not in the Slug siRNA-treated FLS. Conclusion: Our data showed that B[a]P regulates the invasive properties of RA FLS through Slug expression. This mechanism may provide a novel molecular link underlying the association between smoking and increased radiographic progression in RA. [Copyright &y& Elsevier]

The aim of this study is to investigate the effects of CIP2A (Cancerous inhibitor of protein phosphatase 2A) on the apoptosis of RA FLS. Proliferation and apoptotic activity of RA FLS following treatment with CIP2A siRNA or control siRNA were analyzed using MTT assays and Cell Death Detection kit. RA FLS was treated with CIP2A siRNA or control siRNA in 3-, 6-, and 9-day intervals for a Western blot analysis to determine C-Myc expression. To evaluate the signal transduction pathways engaged in apoptosis, caspase-3 activity, caspase-9 activity, PARP, and phosphorylation of the Akt kinase were analyzed by Western blot. Cell viability of RA FLS was significantly lower in the CIP2A siRNA-treated group compared with the control after 7 days ( p = 0.022). Apoptosis of RA FLS was significantly higher in the CIP2A siRNA-treated group compared with the control when incubated for 3, 6, and 9 days ( p = 0.029, p = 0.021, p = 0.043, respectively). C-Myc expression did not change with the different incubation periods. CIP2A siRNA-treated FLS expressed higher level of activated caspase-3, caspase-9, and PARP ( p = 0.014, p = 0.020, p = 0.021, respectively) and lower level of phosphorylated Akt ( p = 0.001) compared with those treated with the control siRNA. Our data show that CIP2A expression in RA FLS is an important mediator of dysfunctional apoptosis independent of c-Myc stabilization. Expression of CIP2A may contribute to apoptotic resistance of RA FLS through the activation of Akt and deactivation of caspase-3, caspase-9, and PARP. Inhibition of CIP2A may therefore constitute a novel, promising therapeutic target in RA. [ABSTRACT FROM AUTHOR]

Abstract: Aim: Chronic periaortitis (CP) is a disease characterized by a fibro‐inflammatory periaortic cuff and adventitia‐predominant fibrosis. CP encompasses idiopathic retroperitoneal fibrosis and inflammatory abdominal aortic aneurysm (AAA), and recent studies have documented overlap between CP and immunoglobulin G4‐related disease (IgG4‐RD). This study aimed to investigate clinical characteristics and treatment outcomes of patients with CP. Method: CP patients were identified by retrospective review of 1245 patients with International Classification of Diseases 10th edition code of aortitis or aortic disease. Patients were further classified into IgG4‐related and non‐IgG4‐related CP according to the criteria proposed by a Japanese study. Results: A total of 61 CP patients were identified. Patients showed a male predominance (70%) with median age of 61 at diagnosis. The abdominal aorta was most commonly involved (84%), while the thoracic aorta was affected in 46% of patients. Twenty‐three (38%) patients had accompanying aortic aneurysm. Approximately 60% of patients achieved remission without further relapse during the course. Ten patients were classified as IgG4‐related and 25 as non‐IgG4‐related. There was no significant difference in clinical features and outcomes between groups, with the exception of older age and greater pancreas involvement in IgG4‐related patients. Conclusion: We documented 61 CP patients including 10 IgG4‐related cases. CP involved the abdominal aorta in most patients and the thoracic aorta in approximately 50% of patients. IgG4‐related CP patients were older and had greater pancreas involvement, but disease outcomes appeared to be similar between IgG4‐related and non‐IgG4‐related CP. [ABSTRACT FROM AUTHOR]

Aim To investigate the effects of Tubastatin A, a selective histone deacetylase-6 inhibitor, on synovial inflammation and joint destruction in a collagen antibody-induced arthritis ( CAIA) mouse model. Methods Collagen antibody-induced arthritis mice were given daily intraperitoneal injections of various concentrations of Tubastatin A (0, 10, 50, 100 mg/kg). The clinical score and paw thickness were measured. Mice were sacrificed on day 15, and the expression of tumor necrosis factor ( TNF)-α, interleukin ( IL)-1 and IL-6 in the serum were analyzed using enyme-linked immunosorbent assay ( ELISA). Two pathologists independently measured the synovitis score. Micro-computed tomography ( CT) scans of the joints were performed to quantify joint destruction. The expression of IL-6 from human fibroblast-like synoviocytes ( FLSs) after incubation with various doses of Tubastatin A (0, 0.75, 1.5, 3 μmol/L) was measured using ELISA. Results The clinical arthritis score was significantly attenuated and paw thickness was lower in the group treated with 100 mg/kg Tubastatin A compared with those treated with vehicle alone. The synovitis score was significantly reduced in the 100 mg/kg Tubastatin A-treated group compared with the control group. Micro- CT showed that quantitative measures of joint destruction were significantly attenuated in the 100 mg/kg Tubastatin A-treated group compared with the control. The expression of IL-6 in the sera was lower in the mice treated with Tubastatin A compared with the control. The expression of IL-6 in human FLSs decreased dose-dependently after incubation with Tubastatin A without affecting cell viability. Conclusions Tubastatin A successfully ameliorated synovial inflammation and protected against joint destruction in CAIA mice, at least in part, by modulating IL-6 expression. [ABSTRACT FROM AUTHOR]