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ID PMID Title PublicationDate abstract
30257550 Rheumatoid arthritis is associated with early tooth loss: results from Korea National Heal 2019 Nov BACKGROUND/AIMS: To examine the association between rheumatoid arthritis (RA) and periodontitis or tooth loss. METHODS: The study used data from the fifth and sixth Korea National Health and Nutrition Examination Surveys conducted from 2010 to 2015. RA was defined as participant-reported physician-diagnosed RA that was being treated. Periodontitis and the number of natural teeth were determined by dental examination. Periodontitis was defined according to the community periodontal index (periodontal probing depth ≥ 4 mm). The association between RA and periodontitis or tooth loss was examined after controlling for confounding variables (e.g., age, smoking status, socioeconomic status, dental caries, frequency of toothbrushing, body mass index, alcohol consumption, and diabetes) in men and women. Subgroup analyses stratified by age were also performed. RESULTS: The study enrolled 20,297 participants aged ≥ 19 years (157 RA patients and 20,140 non-RA controls). There was no association between RA and periodontitis or tooth loss in men and women. Subgroup analyses in those aged < 60 years revealed a non-significant association between RA and periodontitis (adjusted odds ratio, 1.53; p = 0.162), but they revealed a significant association between RA and tooth loss (adjusted β, 0.20; p = 0.042). CONCLUSION: RA was not associated with periodontitis, but was associated with tooth loss in younger adults. Younger RA patients are more likely to suffer tooth loss than general younger population; thus dental management is required.
31411781 Periodontal disease in Chinese patients with rheumatoid arthritis: A case-control study. 2019 Nov OBJECTIVE: To evaluate the prevalence and severity of periodontal disease in Chinese rheumatoid arthritis patients. SUBJECTS AND METHODS: This cross-sectional study included 128 RA and 109 healthy controls. Two dentists conducted periodontal status including Plaque index (PI), Gingival index (GI), pocket probing depths (PPDs), Clinical attachment level (CAL) and Bleeding on probing (BOP) independently. Sociodemographic, lifestyle, clinical parameters and use of medication were assessed. Data were analyzed by Student's t test, χ(2) test, Wilcoxin-Mann- Whitney's test, Correlational Analysis, univariate or multivariate logistic regression. RESULTS: The periodontal status was significantly worse in RA, especially the condition of dental and gingival status. RA had 4.68-fold. After adjusted potential risk factors, RA had 10.26-fold. The independent variable related to GI was DAS28 (p = .05) negatively, to the contrary, ESR (p = .013) was positively associated; the independent variable positively and related to periodontitis was educational level (p = .021) and anti-CCP positivity (p = .002). Through multivariate logistic regression, age and swollen joint were the independent variable related to periodontitis of RA (OR 1.087, p = .044) and (OR 1.560, p = .008) respectively. CONCLUSIONS: Chinese RA patients show higher odds of PD. It is important to take early interventions in combination with medical therapy.
30660077 Butyrate inhibit collagen-induced arthritis via Treg/IL-10/Th17 axis. 2019 Mar Rheumatoid arthritis (RA) is a chronic autoimmune disorder demanding the development of novel therapeutic strategy. Butyrate is a functional short-chain fatty acid produced by the anaerobic intestinal microbiota. This study aimed to investigate the attenuation of butyrate on RA. The collagen-induced arthritis (CIA) mouse model was established and butyrate was administered in drinking water along with the collagen immunization. The histopathological features, clinical score, paw swelling, as well as the production of pro-inflammatory cytokines including interleukin (IL)-1β, IL-6 and IL-17A were measured to determine the amelioration of butyrate on arthritis. The differentiation of Treg cells and Th17 cells in the splenic cells was assessed by flow cytometry. The expression of Foxp3, IL-10, Rorγt and IL-17A were detected by RT-PCR and FACS immunostaining. Anti-IL10R antibody was used in the CIA and CD4(+) cell cultures to mediate the effects of butyrate. Butyrate significantly inhibited expressions of IL-1β, IL-6 and IL-17A, but promoted the expression of IL-10. Butyrate also increased systematical Treg cells and reduced Th17 cells. Mechanism study revealed that butyrate directly enhanced the polarization of Treg cells but not Th17 cells. All effects of butyrate on RA were inversed by the co-administered anti-IL10R antibody. This study showed that butyrate administration inhibited arthritis in CIA mice model, suppressed the expression of inflammatory cytokines. The modulation may be mediated the differentiation of CD4 T cells towards Treg cells, which produce anti-inflammatory cytokine IL-10, and thus influenced the function of Th17 cells.
30874488 Atlantoaxial instability in a patient with neck pain and rheumatoid arthritis. 2021 May Context: The purpose of this report is to describe the clinical decision-making process for a patient with rheumatoid arthritis with neck pain with underlying atlantoaxial instability.Findings: The patient was evaluated for worsening upper neck pain that began insidiously 1 year prior. The patient denied numbness or tingling in her upper or lower extremities, dizziness or lightheadedness, difficulty maintaining balance with walking, or muscle weakness. Cervical spine range of motion was limited in all planes due to pain and apprehension. The patient's neurological examination was unremarkable. Prior flexion and extension radiographs of the cervical spine were interpreted as unremarkable with alignment preserved in flexion and extension. However, upon further inspection, the cervical spine flexion radiograph was concerning for inadequate cervical motion, which may have limited the diagnostic utility of these radiographs. Additionally, a Sharp-Purser test was performed, which was positive for excessive motion. Flexion and extension radiographs of the cervical spine were then repeated ensuring the patient adequately flexed and extended during the imaging. Severe anterior subluxation of C1 relative to C2 with cervical flexion was noted, as C1 moved as much as 8-9 mm anterior to C2 with cervical flexion. Given the degree of atlantoaxial instability, the patient subsequently underwent successful posterior fusion from the occiput to C2.Conclusion/Clinical Relevance: This case report demonstrates the importance of properly screening for upper cervical spine instability in patients with rheumatoid arthritis and neck pain and understanding the importance of obtaining adequate and appropriate diagnostic imaging.
31292392 Rheumatoid Arthritis Complicated with Nasal Septum Perforation Due to Methotrexate-associa 2019 Nov 1 A 44-year-old female with rheumatoid arthritis treated with methotrexate (MTX) and tocilizumab (TCZ) was admitted to our hospital with nasal pain. Nasal fiberscopy revealed septum perforation, while a membrane biopsy indicated granuloma and fibrinoid necrosis of the small artery. The patient was treated with prednisolone 30 mg/day after discontinuation of MTX and TCZ. Inguinal lymph node biopsy revealed diffuse infiltrations of atypical T-cells and Epstein-Barr virus-positive B cells. The patient was diagnosed with peripheral T-cell lymphoma due to MTX-associated lymphoproliferative disorder (MTX-LPD). We herein describe the case of a patient with nasal septum perforation due to MTX-LPD mimicking granulomatosis with polyangiitis.
31066587 MicroRNA-27b-3p inhibits apoptosis of chondrocyte in rheumatoid arthritis by targeting HIP 2019 Dec BACKGROUND: Understanding the mechanism of chondrocytes degeneration could provide a new potential therapeutic idea for rheumatoid arthritis (RA) treatment. MicroRNA-27b-3p (miR-27b-3p) has been shown to regulate a variety of cell behaviors in various cell types. However, the role of miR-27b-3p in RA remains unknown. MATERIALS AND METHODS: Expression of miR-27b-3p and HIPK2 in cartilage tissues and chondrocytes was characterized using qRT-PCR and Western blot. MiR-27b-3p was overexpressed or suppressed in chondrocytes to observe the potential role of miR-27b-3p. RESULTS: We found declined miR-27b-3p and elevated HIPK2 in RA tissues and cells using qRT-PCR. Dual-luciferase reporter assay validated HIPK2 is a direct target of miR-27b-3p, confirmed by Western blot results. Pearson correlation presented that there was a significantly negative correlation between miR-27b-3p and HIPK2 mRNA. Overexpression of miR-27b-3p significantly reduced the expression of pro-apoptotic protein c-caspase3 and increased the expression of anti-apoptotic Bcl-2; however, downregulation of miR-27b-3p has a significant effect of inducing apoptosis. Furthermore, overexpression of miR-27b-3p combined with recombinant HIPK2 protein showed the inhibitory effect of miR-27b-3p was abolished by HIPK2. CONCLUSION: We found declined miR-27b-3p and elevated HIPK2 in RA tissues and cells. Further in vitro studies demonstrated that miR-27b might inhibit chondrocyte apoptosis and thus attenuate RA development by directly inhibiting HIPK2 expression.
31816082 Clinical characteristics of rheumatic syndromes associated with checkpoint inhibitors ther 2019 Dec 1 Compared with conventional cancer therapies, the spectrum of toxicities observed with checkpoint inhibitors is unique and can affect any organ system. Arthralgia and myalgia were by far the most commonly reported rheumatic immune-related adverse events in clinical trials, and there is now a growing number of case series and reports describing clinical features of de novo rheumatic immune-related adverse events, which will be the focus of this review. Some patients develop genuine classic rheumatic and musculoskeletal diseases, but a number of rheumatic immune-related adverse events mimic rheumatic and musculoskeletal diseases with atypical features, mainly polymyalgia rheumatica, rheumatoid arthritis and myositis, as well as several systemic conditions, including sicca syndrome, vasculitis, sarcoidosis, systemic sclerosis and lupus.
30281780 Imatinib inhibits CSF1R that stimulates proliferation of rheumatoid arthritis fibroblast-l 2019 Feb In this study, we aimed to explore the effects of imatinib on the proliferation of rheumatoid arthritis synovial cell (RA-FLS) and inflammatory responses by regulating CSF1R. Differential genes were screened via microarray analysis, followed by being analysed through the weighted co-expression network (WGCNA) network, that included module and cluster analysis. The relationship between imatinib and genes was visualized using the Search Tool for the Retrieval of Interacting Genes (STITCH) database. Expressions of mRNA and protein were determined by reverse transcription-polymerase chain reaction (RT-PCR) and Western blot, respectively. Cell viability was examined via clone formation assay, while cell cycle and apoptosis were analysed through flow cytometry analysis. The hub gene CSF1R was ultimately determined by microarray analysis and WGCNA analysis. Colony-stimulating-factor receptor-1 (SF1R) was highly expressed in rheumatoid arthritis tissues and cells, and CSF1R over-expression could promote inflammatory responses. Moreover, CSF1R could promote RA-FLS proliferation, inhibit apoptosis and accelerate the cell cycle. The targeting relationship between imatinib and CSF1R was also validated in this study. Imatinib attenuated RA-FLS inflammation in a concentration-dependent manner. Meanwhile, imatinib could inhibit RA-FLS proliferation and promote apoptosis, ultimately reducing the damage of RA-FLS. Over-expression of CSF1R accelerated the cell cycle and proliferation of RA-FLS, while inhibiting cell apoptosis. Conversely, imatinib could significantly restrain the cell cycle and viability of RA-FLS and accelerated apoptosis via suppression of CSF1R expression. Further, histological and serological assay investigated and proved the proinflammatory effects of CSF1R in RA rabbits.
31127844 Lifetime risk of knee and hip replacement following a diagnosis of RA: findings from a coh 2019 Nov 1 OBJECTIVE: To estimate the lifetime risk of knee and hip replacement following a diagnosis of RA. METHODS: The analysis was undertaken using routinely collected data from the English NHS. Diagnosis of RA was identified using primary care records, with knee and hip replacement observed in linked hospital records. Parametric survival models were fitted for up to 15 years of follow-up, with age, sex, Charlson comorbidity score, socioeconomic status, BMI and smoking status included as explanatory variables. A decision model was used to combine and extrapolate survival models to estimate lifetime risk. RESULTS: The number of individuals with a diagnosis of RA and included in the study was 13 961. Lifetime risk of knee replacement and hip replacement was estimated to be 22% (95% CI: 16, 29%) and 17% (95% CI: 11, 26%) following a diagnosis of RA for the average patient profile (non-smoking women aged 64 with no other comorbidities, BMI of 27 and in the top socioeconomic quintile). Risks were higher for younger patients. CONCLUSION: The lifetime risk of knee and hip replacement for individuals with a diagnosis of RA is approximately double that of the general population. These findings allow for a better understanding of long-term prognosis and healthcare resource use, and highlight the importance of timely diagnosis and effective treatment.
30988116 Efficacy and Pharmacodynamic Modeling of the BTK Inhibitor Evobrutinib in Autoimmune Disea 2019 May 15 Because of its role in mediating both B cell and Fc receptor signaling, Bruton's tyrosine kinase (BTK) is a promising target for the treatment of autoimmune diseases such as rheumatoid arthritis (RA) and systemic lupus erythematosus (SLE). Evobrutinib is a novel, highly selective, irreversible BTK inhibitor that potently inhibits BCR- and Fc receptor-mediated signaling and, thus, subsequent activation and function of human B cells and innate immune cells such as monocytes and basophils. We evaluated evobrutinib in preclinical models of RA and SLE and characterized the relationship between BTK occupancy and inhibition of disease activity. In mouse models of RA and SLE, orally administered evobrutinib displayed robust efficacy, as demonstrated by reduction of disease severity and histological damage. In the SLE model, evobrutinib inhibited B cell activation, reduced autoantibody production and plasma cell numbers, and normalized B and T cell subsets. In the RA model, efficacy was achieved despite failure to reduce autoantibodies. Pharmacokinetic/pharmacodynamic modeling showed that mean BTK occupancy in blood cells of 80% was linked to near-complete disease inhibition in both RA and SLE mouse models. In addition, evobrutinib inhibited mast cell activation in a passive cutaneous anaphylaxis model. Thus, evobrutinib achieves efficacy by acting both on B cells and innate immune cells. Taken together, our data show that evobrutinib is a promising molecule for the chronic treatment of B cell-driven autoimmune disorders.
31344123 Analysis of gene expression in rheumatoid arthritis and related conditions offers insights 2019 The era of next-generation sequencing has mounted the foundation of many gene expression studies. In rheumatoid arthritis research, this has led to the discovery of important candidate genes which offered novel insights into mechanisms and their possible roles in the cure of the disease. In the last years, data generation has outstripped data analysis and while many studies focused on specific aspects of the disease, a global picture of the disease is not yet accomplished. Here, we analyzed and compared a collection of gene expression information from healthy individuals and from patients suffering under different arthritis conditions from published studies containing the following clinical conditions: early and established rheumatoid arthritis, osteoarthritis and arthralgia. We show comprehensive overviews of this data collection and give new insights specifically on gene expression in the early stage, into sex-dependent gene expression, and we describe general differences in expression of different biotypes of genes. Many genes that are related to cytoskeleton changes (actin filament related genes) are differently expressed in early rheumatoid arthritis in comparison to healthy subjects; interestingly, eight of these genes reverse their expression ratio significantly between men and women compared early rheumatoid arthritis and healthy subjects. There are some slighter changes between men and woman between the conditions early and established rheumatoid arthritis. Another aspect are miRNAs and other gene biotypes which are not only promising candidates for diagnoses but also change their expression grossly in average at rheumatoid arthritis and arthralgia compared to the healthy condition. With a selection of intersecting genes, we were able to generate simple classification models to distinguish between healthy and rheumatoid arthritis as well as between early rheumatoid arthritis to other arthritides based on gene expression.
30334661 Drug survival rates of biological disease-modifying antirheumatic drugs and Janus kinase-i 2019 Nov Objectives: To assess long-term outcomes for seven biological disease-modifying antirheumatic drugs (bDMARDs) and one Janus kinase (JAK)-inhibitor in rheumatoid arthritis.Methods: We retrospectively analyzed data from 801 rheumatoid arthritis patients visiting our rheumatology clinic between 2003 and 2017. We determined drug survival rates, drug discontinuation, and switching rates in these patients.Results: Among the drugs administered to naïve subjects, the drug-survival rate was highest for tocilizumab, at 77.8% after 6 years, whereas the rates for golimumab, etanercept, abatacept, infliximab, and adalimumab, were 61.5%, 48.9%, 41.6%, 34.5%, and 34.4%, respectively. Switching drugs led to decreased survival rates. The discontinuation rates for all drugs due to adverse events and poor efficacy increased rapidly in the first 2 years and the first 6 months, respectively.Conclusions: This report is a long-term analysis of a large cohort of rheumatoid arthritis patients from a single rheumatology clinic in Japan. We conclude that to maximize the survival rate of antirheumatic drugs, it is important to maintain their effectiveness over long periods of time by appropriate drug choices and optimizing dosage before switching drugs.
28807652 Severity indices in rheumatoid arthritis: A systematic review. 2019 May OBJECTIVE: To identify tools designed to evaluate the severity of patients with rheumatoid arthritis (RA) in order to use them in the investigation of prognostic markers in early arthritis. METHODS: We conducted a systematic review of studies that developed/validated an index for RA disease severity. They were analyzed using the COSMIN checklist to assess their methodological quality. In addition, all the variables included were evaluated for their clarity of definition, feasibility and probability of being present in each outcome during the first 2 years of the disease course. To estimate redundancy, variables were grouped by domains. RESULTS: After reviewing 3,519 articles, 3 studies were included. The first study, the PAS, assessed whether current and lifetime treatment with disease-modifying antirheumatic drugs and/or biologics accurately predicted RA severity, as measured by the patient-reported PAS. Treatment variables did not fully distinguish patients in the highest and lowest quartiles of PAS scores. Another severity index, the Claims-Based Index for RA Severity (CIRAS), included the variables age, sex, Felty's syndrome, number of rehabilitation and rheumatology visits, test for inflammatory markers, number of chemistry panels/platelet counts ordered and rheumatoid factor test. The correlation was low (r=0.56) with an index previously validated by the same research group, the RA medical records-based index of severity (RARBIS), with Disease Activity Score-C-reactive protein (DAS28-PCR) (r=0.07) and Multidimensional Health Assessment Questionnaire (MD-HAQ) (r=0.008). Finally, the RARBIS, used to validate the CIRAS, was devised as an RA severity index based on medical records. It includes as domains surgery, radiology, extra-articular manifestations, clinical and laboratory variables, previously chosen by an expert panel. RARBIS had a weak correlation with treatment intensity (r=0.35) and with DAS28 (r=0.41). CONCLUSION: There is no index to assess the severity of RA based on the course of the first 2 years of follow-up that is adapted to the current strategy of therapeutic management of this disease. Therefore, we believe it is reasonable to develop a new ad hoc severity index for patients with early arthritis.
31277746 Does Triple Conventional Synthetic Disease-Modifying Antirheumatic Drug Therapy Improve up 2019 Aug Although many treatment options exist for the initial management of rheumatoid arthritis, there has long been discussion about whether initial treatment should be with methotrexate (MTX) as monotherapy or in combination with other conventional synthetic disease-modifying antirheumatic drugs (csDMARDs). Although studies initially showed additional benefit from combining MTX with other csDMARDs, this benefit disappears when glucocorticoids are added to MTX, a strategy recommended in current guidelines as a short-term bridging approach until MTX therapy exhibits its full efficacy. Also concomitant use of glucocorticoids, with MTX may not be inferior to combination therapy of MTX with TNF-inhibitors.
31027052 Methotrexate-associated primary hepatic lymphoma and cranial neuropathy in a patient with 2019 Apr RATIONALE: Rheumatoid arthritis (RA) shows a variable clinical expression in patients. Articular disease is common manifestation, but patients may rarely present with extra-articular manifestation such as cranial neuropathy. Also, primary hepatic lymphoma (PHL) has rarely been reported in patient treated with immunosuppressive drug such as methotrexate (MTX) for RA. We herein describe a case of cranial neuropathy and MTX-related PHL in a woman receiving MTX for RA. PATIENT CONCERNS: A 73-year-old women received MTX treatment for more than 5 years, presented with recurrent cranial neuropathies. During therapy of cranial neuropathies, liver enzyme levels were elevated. DIAGNOSES: The patient was diagnosed as RA by laboratory examination. A series of examinations had been launched to evaluate any possible cause of the extra-articular manifestation of the patient including ultrasound, computed tomography, magnetic resonance image (MRI) and positron emission tomography of the liver and MRI of the brain. Finally, the patient diagnosed as MTX-associated PHL and cranial neuropathy. INTERVENTIONS: The patient underwent 4-year MTX therapy for RA at first with prednisolone. After that, she had been treated with cyclophosphamide therapy for cranial neuropathy. The liver biopsy was performed for hepatic lesion. OUTCOMES: MTX was discontinued, but no improvement of PHL and elevated liver enzyme was observed during the 3 weeks. The patient received 6 cycles of chemotherapy for 3 months and achieved complete remission including PHL and cranial neuronal lesion with symptom. No instances of relapse have occurred in 2 years of follow-up. LESSONS: The present case is the extremely rare case in which MTX-related PHL and cranial neuropathy were involved together in the RA patient. It is necessary to examine long-term follow up hepatic and neurologic examinations that patient had a long history of receiving MTX therapy for RA.
30810221 Genetic and epigenetic alteration of the programmed cell death 1 in rheumatoid arthritis. 2019 Oct BACKGROUND: Rheumatoid arthritis (RA) is an autoimmune disease where both genetics and epigenetics are contributing factors. In order to discover genetic and epigenetic associations with RA and its phenotypes, we analysed RNA expression, DNA variations and DNA methylation of programmed cell death 1 (PDCD1) in a cohort of RA patients and healthy controls. METHODS: RA patients (n = 206) and healthy controls (n = 234) were included for analysis of PDCD1 expression, PDCD1 polymorphisms and PDCD1 methylation. Differences in continuous variables between groups were compared by applying t tests. Associations between phenotypes and genotypes were evaluated with contingency tables. Sensitivity analyses were conducted to confirm the robustness of results, considering potential confounding factors and different treatment response definitions. Odds ratio (OR) and 95% confidence interval (95% CI) were calculated. RESULTS: Higher expression of PDCD1 was found in RA compared to controls (P < 0.001), with similar PDCD1 polymorphisms in RA and controls. rs36084323 decreased inadequate response to conventional synthetic disease-modifying antirheumatic drugs (OR = 0.37, 95% CI = 0.19-0.72, P = 0.003), and rs41386349 increased rheumatoid factor seropositivity (OR = 11.89, 95% CI = 1.57-89.87, P = 0.003). Sensitivity analysis adjusting for further potential confounders and using different treatment response definition indicated similar results. Additionally, DNA methylation change at regulatory region of PDCD1 was detected in RA (P = 0.036). CONCLUSION: Altogether, this was the first study to suggest genetic and epigenetic changes of PDCD1 in RA subsets and RA. Independent prospective cohorts are awaited to address the implications of these genetic and epigenetic changes in disease pathogenesis and phenotypes of RA.
31672652 Serum profile of transferrin isoforms in rheumatoid arthritis treated with biological drug 2019 Dec BACKGROUND: In the chronic inflammation process in the course of rheumatoid arthritis (RA), many alterations in the expression of plasma proteins, as well as their posttranslational modifications (including glycosylation) can occur. Taking into account the disturbances in protein glycosylation and the emerging new treatment regimens, the aim of this study was to assess the serum profile of transferrin isoforms in RA patients treated with biological drugs. METHODS: The study included 20 patients (16 females and 4 males; mean age: 53.4 years; range: 24-67) with rheumatoid arthritis treated with rituximab. Serum samples were taken 3 times: before and 3 and 6 months during treatment. The isoforms of transferrin were separated by capillary electrophoresis (MINICAP electrophoretic system, Sebia, France) into five major fractions: asialo-, disialo-, trisialo-, tetrasialo- and pentasialotransferrin. The results were calculated as relative concentrations of each fraction. RESULTS: The median trisialotransferrin relative concentrations after 3 and 6 months treatment (4.40% and 4.10%, respectively) were significantly higher (p = 0.013, p = 0.009, respectively) than before treatment (3.50%). The levels of serum pentasialotransferrin were also increased 3 and 6 months following treatment (16.5% and 17.7%, p = 0.005 and p = 0.006, respectively) as compared to those before therapy (14.5%), while tetrasialotransferrin concentrations were lower (80.3% and 78.4%, p = 0.009 and p = 0.008, respectively) than before treatment (81.5%). Trisialotransferrin relative concentration correlated with Hb (p = 0.019), whereas pentasialotransferrin with PLT (p = 0.036) after treatment. CONCLUSIONS: This study indicates that treatment with rituximab of RA patients alters the serum profile of transferrin isoforms. Tri-, tetra- and pentasialotransferrin relative concentrations measurements can be a useful tool to monitor therapy.
30875504 Design, synthesis and evaluation of novel 7H-pyrrolo[2,3-d]pyrimidin-4-amine derivatives a 2019 May 1 A series of 7H-pyrrolo[2,3-d]pyrimidine derivatives were designed and synthesized as reversible BTK inhibitors, and evaluated their kinase selectivity, anti-proliferation against the B-cell lymphoma cell lines (Ramos, Jeko-1) and cell line BTK enhanced (Daudi) in vitro. Among them, compound 28a exhibited the most excellent potency (IC(50) = 3.0 nM against BTK enzyme, 8.52 μM, 11.10 μM and 7.04 μM against Ramos, Jeko-1, Daudi cells, respectively), good kinase selectivity and inhibited BTK Y223 auto-phosphorylation and PLCγ2 Tyr1217 phosphorylation. Importantly, 28a showed efficacy anti-arthritic effect on collagen-induced arthritis (CIA) model in vivo. 28a 60 mg/kg dose level once a day group displayed markedly reduced joint damage and cellular infiltration without any bone and cartilage morphology change.
31762208 A wide-targeted urinary and serum metabolomics strategy reveals the effective substance of 2020 Feb As an important Chinese medicine decoction, Wu-tou decoction has been used to treat rheumatic arthritis for more than a thousand years. We previously reported that the Wu-tou decoction could change the urinary and serum metabolites in adjuvant-induced arthritis rats significantly. The purpose of this research was to confirm the potential biomarkers obtained by previous non-targeted metabolomics study through quantitative analysis by liqui chromatography with tandem mass spectrometry, in the meantime, to further study the effective material basis of Wu-tou decoction. Firstly, the important compounds in the tryptophan metabolism pathway, the arginine and proline metabolism pathway, the amino acid metabolism pathway, the tricarboxylic acid cycle, the vitamin B(6) metabolism pathway, and the phenylalanine metabolism pathway, which were identified as potential biomarkers in previous study, were selected for quantitative analysis. Then the linearity, limit of detection, limit of quantification, selectivity, accuracy, precision, stability, recovery, and matrix effect of the quantitative method were examined. Finally, ten and eighteen metabolites were quantitatively analyzed in the serum and urine, respectively. The results showed that seven out of ten serum potential biomarkers and ten out of eighteen urine potential biomarkers were confirmed as real biomarkers. This research provides a powerful reference for the study on effective material basis of Wu-tou decoction.
31153706 Impact of the pattern of interstitial lung disease on mortality in rheumatoid arthritis: A 2019 Dec OBJECTIVE: An important extra-articular manifestation of rheumatoid arthritis (RA) is interstitial lung disease (ILD). The relationship between the usual interstitial pneumonia (UIP) pattern and mortality in patients with RA is unclear. The purpose of this study was to complete a systematic literature review and meta-analysis on the association between RA-ILD pattern and mortality risk. METHODS: We performed a systematic literature review through December 12, 2018. Study characteristics, unadjusted and adjusted relative risks (RR) of mortality for ILD pattern were extracted from the identified studies and quality assessments were performed. RR for mortality (RA-UIP vs. other RA-ILD) was pooled using inverse variance weighting and random effects models. RESULTS: Ten retrospective cohort studies met our eligibility criteria. A total of 1256 RA-ILD patients were included with 484 total deaths. Meta-analysis yielded a pooled RR of 1.66 (95% confidence interval1.07 to 2.56) for death among those with UIP RA-ILD compared with other patterns. In sub-group analysis when pooling studies comparing UIP to NSIP pattern of RA-ILD, the RR was 2.39 (95% CI 0.86-6.68). CONCLUSION: Through a systematic literature review and meta-analysis, we found UIP pattern to be associated with a higher mortality risk in RA-ILD compared to other patterns of RA-ILD although more recent studies emphasize the importance of pulmonary physiology and the extent of lung involvement as significant predictors of mortality rather than the pattern of RA-ILD. Recognizing the small number of studies satisfying eligibility and inconsistent accounting for confounders, further study of mortality risk in RA-ILD is needed with standardized assessment of various RA, ILD, and patient-related factors.