Search for: rheumatoid arthritis    methotrexate    autoimmune disease    biomarker    gene expression    GWAS    HLA genes    non-HLA genes   

ID PMID Title PublicationDate abstract
32899051 The efficacy and safety of Huangqi Guizhi Wuwu decoction for rheumatoid arthritis: A proto 2020 Sep 4 BACKGROUND: Rheumatoid arthritis has the characteristics of slow progression, long course, and repeated attacks. At present, western medicine commonly used in clinical practice not only reduces pain and improves symptoms, but also has more adverse reactions, affecting the health, and life of patients. In ancient China, Huangqi Guizhi Wuwu decoction was used by doctors to treat rheumatoid arthritis, with remarkable effect. In recent years, many clinical studies have also shown that Huangqi Guizhi Wuwu decoction has reliable effect in treating rheumatoid arthritis, but there is no evidence of evidence-based medicine. Therefore, this study aims to systematically evaluate the clinical efficacy and safety of Huangqi Guizhi Wuwu decoction in the treatment of rheumatoid arthritis. METHODS: Using computer to retrieve PubMed, The Cochrance Library, Embase, Web of Science, CNKI, VIP and Wanfang database, in addition manually retrieve Google academic and Baidu academic to collect all randomized controlled trials for Huangqi Guizhi Wuwu decoction in the treatment of rheumatoid arthritis, including relevant academic journal and conference papers, dissertations, from the establishment of the database to July 2020. After 2 evaluators independently screened the literature, extracted the data, and evaluated the risk of bias included in the study, RevMan5.3 software was used to analyze the data. RESULTS: This research evaluate the efficacy and safety of Huangqi Guizhi Wuwu decoction in treating Rheumatoid arthritis from the aspects of clinical efficacy rate, visual analog scale (VAS), swollen joint count (SJC), morning stiffness time, Rrythrocyte sedimentation rate (ESR), C-reactive protein (CRP), rheumatoid factor (RF), and adverse reaction incidence. CONCLUSION: This study will provide reliable evidence for the clinical application of Huangqi Guizhi Wuwu decoction in the treatment of rheumatoid arthritis. ETHICS AND DISSEMINATION: The private information from individuals will not publish. This systematic review also will not involve endangering participant rights. Ethical approval is not required. The results may be published in a peer-reviewed journal or disseminated in relevant conferences. OSF REGISTRATION NUMBER: DOI 10.17605/OSF.IO/RZY3V.
32114962 The safety of modern intravenous iron infusions in patients with rheumatoid arthritis - a 2020 Dec Objectives: To assess the evidence for the safety of intravenous iron infusions in patients with rheumatoid arthritis.Methods: A systematic literature search was performed in June 2019 on PubMed and Cochrane databases for eligible studies.Results: There is significant evidence of safety and efficacy of intravenous iron in patients with rheumatoid arthritis using newer, less immunogenic iron preparations, such as iron sucrose and low molecular weight iron dextran preparations.Discussion: Iron deficiency anaemia has a significant impact on the quality of life of patients with rheumatoid arthritis, but the use of intravenous iron is generally avoided due to concerns raisedin older studies using high molecular weight iron dextran of exacerbating the disease. However, such concerns have not been confirmed in more recent studies using newer preparations.Conclusion: We find significant evidence of safety and efficacy in more recent studies of larger cohorts of patients using newer, less immunogenic iron preparations.
33328426 Risk of New-Onset Acute Coronary Syndrome and Atrial Fibrillation in Patients With Rheumat 2021 Jan 25 BACKGROUND: Rheumatoid arthritis (RA) has extra-articular manifestations of cardiovascular diseases and is associated with a high mortality rate in Western populations. This study aimed to investigate the risk of acute coronary syndrome (ACS) and atrial fibrillation (AF) associated with RA in a Korean population.Methods and Results:Patients were selected from a senior cohort from the Korean National Health Insurance Service in 2002, and followed until 31 December 2015. Patients with newly developed ACS and AF were identified and compared with controls for a 10-year period using time-dependent propensity and risk-set matching. A total of 4,217 incident RA patients and their 8,432 controls comprised the incident RA and matched cohorts, respectively. ACS was identified during 24,642 person-years [incidence rate (IR) 402 per 10,000 person-years, 95% confidence interval (CI) 330-489] among the RA cohort. In the matched cohort, 141 ACS patients were identified during 50,011 person-years (IR 282 per 100,000 person-years, 95% CI 239-333). RA patients were 1.43-fold more likely to develop ACS than the matched controls [hazard ratio (HR) 1.43, 95% CI 1.10-1.84], but showed similar occurrence risk of AF (HR 1.06, 95% CI 0.83-1.35). CONCLUSIONS: A higher risk for ACS and a similar risk for AF were found by risk-set matched analysis in a senior RA cohort compared with the control, using Korean nationwide long-term data.
32387584 Early discontinuation of tofacitinib in patients with rheumatoid arthritis co-treated with 2020 Oct OBJECTIVE: Rifampin is known to influence the pharmacokinetics of tofacitinib owing to drug interactions. The aim of this study was to determine the efficacy of tofacitinib on co-administration with rifampin in rheumatoid arthritis (RA) patients. METHODS: Biologic-naïve RA patients treated with tofacitinib were selected, and electronic medical reports were reviewed retrospectively. All patients underwent screening for latent tuberculosis infection (LTBI) before starting tofacitinib, and patients with positive results were treated to prevent progression to active tuberculosis. To evaluate the efficacy of tofacitinib with or without rifampin, the discontinuation rates of tofacitinib were examined during the first 6 months. Kaplan-Meier analysis was used to construct cumulative discontinuation curves, and comparisons were performed using the log-rank test. RESULTS: Among 81 patients who starting tofacitinib, 21 were LTBI-positive and 18 were administered rifampin concomitantly with tofacitinib. Additionally, 14 of the 81 patients (17.3%) discontinued tofacitinib during the follow-up, and 7 patients discontinued tofacitinib because of uncontrolled RA activity. The discontinuation rates of tofacitinib within the first 6 months were significantly higher in patients treated with rifampin for LTBI than in those not treated with rifampin (lack of efficacy: 24.7% vs. 5.1%, P<0.01; all causes: 38.9% vs. 11.2%, P<0.01). CONCLUSIONS: Discontinuation rates were higher in RA patients who started tofacitinib during chemoprophylaxis involving rifampin than in those who did not receive rifampin. Physicians should be aware that the efficacy of tofacitinib could be decreased by chemoprophylactic regimens for tuberculosis.
32334078 Radioscapholunate arthrodesis versus radiolunate arthrodesis in rheumatoid wrist surgery: 2020 Oct Radiolunate arthrodesis is a validated surgical technique in rheumatoid wrist surgery. When the radioscaphoid joint is involved or when there is radiolunate instability, a radioscapholunate arthrodesis must be preferred. The objective was to compare clinical and radiographic outcomes for both types of arthrodesis. Patients were evaluated retrospectively at a minimal follow-up of 12 months after radiolunate arthrodesis (RL-A group) or radioscapholunate arthrodesis (RSL-A group). Mean follow-up was 10.7 years (1-25 years). One hundred and one patients were included in RL-A group and 26 in RSL-A group. At follow-up, pain level was significantly reduced by 3.7 points and by 2.9 points in RL-A and RSL-A groups, respectively. Mobility in flexion/extension was significantly reduced by 25° in both groups. DASH and PRWE scores were 42.9 and 41.4 in RL-A group, 41.8 and 20.6 in RSL-A group, respectively. Larsen stage for the midcarpal joint increased significantly in both groups (+0.8 in RL-A group; +0.9 in RSL-A group), carpal height index decreased (-0.03 in RL-A group (significant); -0.02 in RSL-A group (non-significant)), carpal ulnar translation index increased (+0.038 in RL-A group; +0.037 in RSL-A group), without significant difference between both groups. Nonunion rate was significantly higher in RSL-A group (62%) than in RL-A group (30%). A pain free and functional wrist can be obtained after radiolunate and radioscapholunate arthrodesis. However, arthritis lesions and carpal deformities increased with follow-up similarly with both surgical techniques. Our results have shown that radiolunate arthrodesis remains a reliable surgical procedure for advanced rheumatoid wrist.
32912305 A mobile app using therapeutic exercise and education for self-management in patients with 2020 Sep 10 BACKGROUND: Therapeutic exercise is a safe and cost-effective approach to alleviate hand rheumatoid arthritis (RA)-related symptoms. This study aims to investigate the differences in self-management between a smartphone app (CareHand), using hand exercises and educational advices, compared with a standard approach, on hand overall function, pain intensity, stiffness, and grip and pinch strength in patients with hand RA. METHODS: The project is a prospective, longitudinal, superiority, randomized controlled trial. Fifty-eight participants with hand RA will be randomly assigned into an experimental group (CareHand app) or a control group (conventional treatment). Control intervention involves a paper sheet with exercises and recommendations, and the experimental group includes the use of a smartphone app, which provides individualized exercise programs, self-management, and educational strategies to promote adherence to treatment. Both intervention protocols will last for 3 months. The principal investigator will conduct an educational session at baseline for all participants. Primary outcome comprises the overall hand function, assessed with the Michigan Hand Outcome Questionnaire (MHQ). Secondary outcomes include self-reported functional ability with the Quick DASH questionnaire, self-reported pain intensity and morning stiffness using a Visual Analogue Scale (VAS), and hand grip and pinch strength (dynamometer). Outcome measures will be collected at baseline, and at 1 month and 3-month follow-up. DISCUSSION: This study will evaluate the effectiveness of a tele-rehabilitation tool, which uses exercise and self-management strategies, compared to a conventional approach, in patients with hand RA. The smartphone app will allow to monitor the patient's status and to enhance patient-therapist communication. Some limitations may be related to the short follow-up duration and the lack of evaluation of psychosocial factors. Overall, this new way of promoting long-term effects in patients with a chronic rheumatic disease could be feasible and easy to implement in daily life clinical practice and current musculoskeletal care. TRIAL REGISTRATION: ClinicalTrials.gov NCT04263974 . Registered on 7 March 2020. Date of last update 15 April 2020. Ethics committee code: PI_RH_2018.
32251958 Analysis of serum rheumatoid factors in patients with rheumatoid arthritis in Han, Tibetan 2020 Jun OBJECTIVE: The aim of this study was to compare the sensitivities, specificities and correlations of serum rheumatoid factors across different races in RA patients. METHODS: Serum rheumatoid factors were tested in 150 subjects who were divided into 3 groups: group 1 including 25 Han RA patients (Han-RA) and 25 healthy Han control groups, group 2 including 25 Tibetan RA patients (T-RA) and 25 the healthy Tibetan control group and group 3 including 25 Hui-RA patients (Hui-RA) and 25 Hui healthy controls. RESULTS: There were significant differences in ESR, A-CCP, CRP, RF, SAA, SFe, IL-4, IL-6, IL-10 and IL-17 between RA patients and the corresponding control subjects in all 3 groups (P < 0.01 for ESR, A-CCP, CRP, RF, IL-4, IL-6, IL-10 and IL-17, P < 0.05 for SAA and SFe). In Tibetan RA, the levels of A-CCP were significantly lower than the Han-RA and Hui-RA. SAA of T-RA was significantly lower than the Han-RA (P < 0.05). CONCLUSION: ESR, CRP, RF, A-CCP, SAA, SFe and IL serum rheumatoid factors were useful biomarkers for RA detection in all three races.
32669452 Gastrointestinal perforations in patients with rheumatoid arthritis treated with biologica 2020 Jul OBJECTIVES: To compare incidence rates of gastrointestinal (GI) perforations between patients with RA and the general population, and between patients treated with tumour necrosis factor inhibitors (TNFi) and non-TNFi biologics. METHODS: In this nationwide cohort study, a total of 63 532 patients with RA, with 26 050 biological treatment episodes (TNFi, rituximab, abatacept or tocilizumab) and 76 304 general population controls, were followed between 2009 and 2017 until the first outcome event. The main outcome was hospitalisation or death due to lower GI perforations, identified according to a prespecified list of ICD-10 (International Classification of Diseases, 10th revision) codes. Inverse probability of treatment weighting was used for adjustment. RESULTS: The sex-standardised and age-standardised incidence rates of lower GI perforations were 1.1 (95% CI 1.0 to 1.3) events per 1000 person-years among general population controls, 1.6 (1.5-1.7) among bionaïve patients and ranged from 1.8 (1.4-3.6) (TNFi) to 4.5 (2.7-10.4) (tocilizumab) among biologics-treated patients. After adjustment for glucocorticoid use, the risk in bionaïve, TNFi-treated, abatacept-treated or rituximab-treated patients with RA was no longer different from the general population, while for tocilizumab it remained significantly higher. Comparing tocilizumab to TNFi, the adjusted HR for lower GI perforations was 2.2 (1.3-3.8), corresponding to one additional GI perforation per 451 patient-years treated with tocilizumab instead of TNFi. CONCLUSION: Tocilizumab was associated with a higher risk of lower GI perforations compared with alternative biologics. In absolute numbers, the risk remained low on all biologics commonly used to treat RA, but the accumulated evidence across settings and outcome definitions supports that this risk should be considered in treatment guidelines for RA.
32360348 Flaccidoside II ameliorates collagen-induced arthritis in mice. 2020 Aug 5 Flaccidoside II (FLA II), the primary active constituent from Anemone flaccida rhizome, was proven to exert therapeutic effect against collagen-induced arthritis (CIA). In this study, a research based on the CIA mouse model was carried out in order to elucidate its therapeutic mechanisms preliminarily. The mice were immunized with porcine type-II collagen to induce CIA and administrated intragastrically with FLA II daily from day 7-42 of the first collagen immunization. The arthritis scores as reflected by the severity of paw swelling and erythema were significantly reduced in FLA II (32 mg/kg) from day 33 onwards. On day 42, the joints of FLA II-treated mice exhibited obvious reductions of inflammatory cells infiltration, synovial hyperplasia and bone destruction. When the concentration of FLA II was no less than 40 nmol/ml, the treatment notably inhibited T and B lymphocyte proliferative responses. As compared to the model group, in FLA II groups, the serum levels of pro-inflammatory cytokines (IL-1β, IL-6 and TNF-α) were significantly decreased while those of Th2 type cytokines (IL-4 and IL-10) were clearly enhanced. In addition, FLA II treatment showed little regulatory effect on the levels of Th1 type cytokines (IFN-γ and IL-2). The severity of mice CIA was improved by FLA II, further confirming its potential value for the safe treatment of rheumatoid arthritis. The main mechanisms likely involve the inhibition of lymphocyte proliferation and pro-inflammatory cytokine secretion, and the modulation of Th1/Th2-related cytokine balance in CIA.
31982791 Lycopene used as Anti-inflammatory Nanodrug for the Treatment of Rheumathoid Arthritis: An 2020 Apr Lycopene is a carotenoid drug that has demonstrated several properties, including antioxidant and anti-inflammatory activity. The absorption in human body is very low (10-30 % only). In order to increase the bioavailability, lycopene nanoemulsion was formulated and characterized (atomic force microscopy, thermogravimetric analysis dynamic light scattering and differential scanning calorimetry). Also in vitro assay to evaluate the at-binding with MPR1 was performed. Finally, in vivo assay in animals inducted with rheumathoid arthritis were performed. The results showed that the formulated nanolycopene had superior efficacy when compared with the conventional lycopene (not nano-formulated) in inducted animals (rheumatoid arthritis). The results support the use of nanolycopene as an anti-inflammatory agent for rheumatoid arthritis therapy.
31145222 Effect of a Dynamic Exercise Program in Combination With Mediterranean Diet on Quality of 2020 Oct OBJECTIVE: To assess the effect of a dynamic exercise program (DEP) in combination with a Mediterranean diet (MD) on health-related quality of life in women with rheumatoid arthritis (RA). METHOD: A randomized clinical trial including 144 women with RA diagnosis was performed. Patients were randomized into 4 groups: (1) MD + DEP (n = 36), (2) DEP (n = 37), (3) MD (n = 40), and (4) control (n = 31). All patients received conventional disease-modifying antirheumatic drugs. Health-related quality of life was assessed with 36-item Short Form Health Survey v2 (0-100 score) and disability with Health Assessment Questionnaire Disability Index at enrollment and after 24 weeks. Between-groups comparisons of the change in the quality of life scores from baseline to follow-up were performed using analysis of covariance in which baseline-to-follow-up was the dependent variable, and the intervention group was the independent variable. RESULTS: All patients had low disease activity at the time of enrollment, with a mean 28-joint Disease Activity Score of less than 3.2. Patients who were included in the MD + DEP and DEP groups showed 15 points of increase in health-related quality of life global punctuation versus 3.5 in the MD group and -4.6 in the control group (p = 0.01). Also the scores in the physical component after 24 weeks of intervention in the MD + DEP group improved (15.5), in the DEP group (12) and MD group as well (5.1), whereas the control group showed a decrease of the score (-1.7) (p = 0.03 between groups). CONCLUSIONS: The combination of MD + DEP could improve the quality of life in RA patients with low disease activity receiving conventional disease-modifying antirheumatic drugs.
33788444 [Effect of moxibustion on expression of autophagy related molecules in synovial tissues of 2020 Oct 25 OBJECTIVE: To observe the effect of moxibustion on expression of autophagy related gene(Atg), serine/threonine protein kinase-uncoordinated 51 like kinase-1 (ULK1), Beclin1 and microtubule associated proteins light chain 3 (LC3) and ultrastructure of synovium in rheumatoid arthritis (RA) rats, so as to explore its mechanisms underlying improvement of RA. METHODS: Forty SD rats were randomly divided into normal control, RA model, moxibustion, cigarette-roasting and medication groups (n=8 rats in each group). The RA model was established by keeping the rats in wind, cold and wet environment for 12 h, once a day for 20 days and subcutaneous injection of Freund's adjuvant complete into the sole of the left hind paw. Moxibustion was applied to the left "Zusanli" (ST36) for 20 min, once a day for 15 days. Rats of the cigarette-roasting group was treated by ignited cigarettes instead of moxa strips. Rats of the medication group was treated by gavage of Tripterygium wilfordii polyglycoside tablet suspension (0.8 mg/100 g) once a day for 15 days. The rats' paw volume of the left hindlimb was measured by using a water-based paw plethysmometer. The synovial tissue of the left plantar joint was harvested at the end of experiments for observing changes of the ultrastructure with transmission electron microscope, and the expression of ULK1, Atg3, Atg5, and Atg12 mRNAs was detected with quantitative real-time PCR and the expression of LC3-Ⅱ and Beclin-1 proteins were detected with Western blot. RESULTS: Following modeling, the paw volume of the left hindlimb was significantly increased (P<0.01), while the expression levels of Atg3, Atg5, Atg12 and ULK1 mRNAs, and LC3-Ⅱ and Beclin-1 proteins of the synovial tissue were notably down-regulated in the model group relevant to the normal control group (P<0.01). The increase of the paw volume in the moxibustion and medication groups and the down-regulation of synovial Atg3, Atg12 and ULK1 mRNAs in the 3 intervention groups, and Atg5 mRNA , and LC3-Ⅱ and Beclin-1 proteins in both moxibustion and medication groups were considerably suppressed (P<0.01, P<0.05). The therapeutic effect of moxibustion was apparently superior to that of cigarette-roasting in down-regulating the paw volume, and up-regulating the expression levels of Atg3, Atg5, Atg12 and ULK1 mRNAs, and LC3-Ⅱ and Beclin-1 proteins (P<0.05, P<0.01), and notably weaker than that of medication in up-regulating Atg3 and ULK1 mRNAs (P<0.01), but was comparable to that of medication in up-regulating the expression levels of Atg5 and Atg12 mRNAs, LC3-Ⅱand Beclin-1 proteins (P>0.05). Results of the ultrastructural observation showed an obvious injury of synovial cells, such as unclear and incomplete nuclear membrane, chromatin condensation, swollen mitochondria with broken crests, cavitation-like degeneration of cytoplasma, and appearance of autophagosomes and lysosomes in the model group, which was relatively milder in the 3 intervention groups. CONCLUSION: Moxibustion can reduce the paw edema and inflammatory injury of the plantar synovial tissue in RA rats, which may be related to its effects in up-regulating Atg3, Atg5, Atg12 and ULK1 mRNAs, and LC3-Ⅱ and Beclin-1 proteins to enhance the cellular autophagy. The therapeutic effect of moxibustion is obviously superior to that of cigarette-roasting and medication in relieving swelling.
32936426 Ankylosing spondylitis coexists with rheumatoid arthritis and Sjögren's syndrome: a case 2021 May Rheumatoid arthritis (RA), ankylosing spondylitis (AS), and Sjögren's syndrome (SS) are the most common rheumatic diseases. However, a coexistence of AS and RA or SS in the same patient is rare. What' s more, the case of AS coexists with RA, and SS is not be found yet. Here, we present a 65-year-old male patient who develop typical clinical symptoms of AS, RA, and SS successively (such as inflammatory low back pain, symmetrical small joint swelling and pain, and severe dryness of mouth and eyes) and was finally diagnosed with AS coexisting with RA and SS.
30850962 Detection of rheumatoid arthritis from hand radiographs using a convolutional neural netwo 2020 Apr INTRODUCTION: Plain hand radiographs are the first-line and most commonly used imaging methods for diagnosis or differential diagnosis of rheumatoid arthritis (RA) and for monitoring disease activity. In this study, we used plain hand radiographs and tried to develop an automated diagnostic method using the convolutional neural networks to help physicians while diagnosing rheumatoid arthritis. METHODS: A convolutional neural network (CNN) is a deep learning method based on a multilayer neural network structure. The network was trained on a dataset containing 135 radiographs of the right hands, of which 61 were normal and 74 RA, and tested it on 45 radiographs, of which 20 were normal and 25 RA. RESULTS: The accuracy of the network was 73.33% and the error rate 0.0167. The sensitivity of the network was 0.6818; the specificity was 0.7826 and the precision 0.7500. CONCLUSION: Using only pixel information on hand radiographs, a multi-layer CNN architecture with online data augmentation was designed. The performance metrics such as accuracy, error rate, sensitivity, specificity, and precision state shows that the network is promising in diagnosing rheumatoid arthritis.
32840033 Third-Generation Anti-Cyclic Citrullinated Peptide Antibodies Improve Prediction of Clinic 2020 Nov OBJECTIVE: To 1) determine the prevalence of anti-cyclic citrullinated peptide 3 (anti-CCP3) antibodies in anti-CCP2 antibody-positive (anti-CCP2+) at-risk individuals, and 2) explore the additional value of anti-CCP3 antibodies in anti-CCP2+ at-risk individuals for predicting progression to inflammatory arthritis. METHODS: Stored serum samples obtained from 347 anti-CCP2+ (BioPlex 2200; Bio-Rad) at-risk individuals without clinical synovitis were tested for anti-CCP3 antibodies. Anti-CCP2 titers were categorized as low or high, and anti-CCP3 titers were categorized as negative, low, or strong. Progression to inflammatory arthritis was defined as the development of clinical synovitis in ≥1 joint. Only subjects with ≥1 follow-up visit were included in the progression analysis (n = 291). RESULTS: In the 347 samples included, anti-CCP3 antibody titers tended to be either negative (n = 138 [39.7%]) or strongly positive (n =189 [54.4%]), with very few subjects showing a low titer (n = 20 [5.7%]). In contrast, for anti-CCP2 antibodies, more low titers were observed (n = 103 [29.7%]). Eighty-eight of 291 subjects (30.2%) developed inflammatory arthritis. The rate of progression to inflammatory arthritis in the low-titer anti-CCP2 group and the high-titer anti-CCP2 group fell from 7.5% to 3.3% and from 38.9% to 9.8%, respectively, when anti-CCP3 was negative. Progression in the high-titer anti-CCP2 group increased from 38.9% to 48.4% when anti-CCP3 was strongly positive. The area under the curve was 0.72 for anti-CCP2 (95% confidence interval [95% CI] 0.66, 0.78) and 0.76 for anti-CCP3 (95% CI 0.70, 0.81) for assessment of progression. In the multivariable analysis, the odds ratio for the development of inflammatory arthritis in anti-CCP3+ subjects was 1.73 (95% CI 1.20, 2.51) (P < 0.01). CONCLUSION: Anti-CCP3 antibodies improve the prediction of inflammatory arthritis in anti-CCP2+ at-risk individuals. The impact of anti-CCP3 antibody status for the risk stratification of individuals with high-titer anti-CCP2 is particularly notable.
31893540 Sinomenine hydrochloride loaded thermosensitive liposomes combined with microwave hyperthe 2020 Feb 25 The conventional medications are still facing a huge challenge for the treatment of rheumatoid arthritis (RA). Thus, looking for an effective therapy of RA has became an urgent issue nowadays. In this study, a novel thermosensitive liposome loaded with sinomenine hydrochloride (SIN-TSL) was developed by a pH gradient method. The SIN-TSL had a mean particle size of around 100 nm, and an high entrapment efficiency and drug loading capacity. The results also suggested that SIN-TSL had a thermosensitive drug release behaviour, with the drug release rate at 43 °C was much faster than the one at 37 °C. The SIN-TSL could be effectively taken up by lipopolysaccharide-activated HUVECs, without any cytotoxicity was observed. In addition, both in vitro and in vivo studies indicated that the SIN-TSL combined with microwave hyperthermia exhibited superior anti-rheumatoid arthritis effect. Overall, these results suggest that SIN-loaded thermosensitive liposomes combined with microwave hyperthermia could provide an optional strategy for alleviating the clinical symptoms of RA.
33244818 An interdigitated aptasensor to detect interleukin-6 for diagnosing rheumatoid arthritis i 2021 Dec Rheumatoid arthritis (RA) is an autoimmune disorder causing chronic inflammation in the small joints of the articular bone and destruction of articular cartilage. RA causes stiffness, pain, joint destruction, substantial comorbidity, and functional disability. Early-stage diagnosis of RA can help in the treatment of the disease and expand the patient life span. Interleukins are a group of inflammatory cytokines; in particular, an abundance of interleukin-6 (IL-6) was found in the synovial fluid and serum. In RA patients, the levels of IL-6 have been found to be correlated with the disease, and this work focused on detecting IL-6 by its aptamer with the help of a biotin-streptavidin strategy on an interdigitated electrode. A sensitivity of 1 fM (0.021 pg/mL) and a limit of detection of 10 fM (0.21 pg/mL) were found by a linear regression [y = 0.6413x - 0.6249; R² = 0.952] of the linear range from 1 fM to 100 pM. This method enhanced the immobilization of higher aptamer molecules for recognizing RA in serum-containing samples and is applicable to other diseases.
31830886 Psychosomatic Features, Compliance and Complementary Therapies in Rheumatoid Arthritis. 2020 This review highlights the issue of psychosomatic conditions in rheumatoid arthritis, paying special attention to new researches and trends in this field. Emerging concepts in all the major parts of the problem are covered consecutively, from the impact of chronic musculoskeletal pain on the emotional state to disease influence over quality of life, socio-psychological, and interpersonal relationships. Chronic pain is closely related to emotional responses and coping ability, with a pronounced positive effect of psychotherapeutic interventions, family and social support on it. Psychosexual disorders, anxiety, depression also commonly coexist with rheumatoid arthritis, leading to further decrease in quality of life, low compliance, and high suicide risk. Influence of psychosomatic conditions on the overall treatment effect is usually underestimated by rheumatologists and general practitioners. Psychosomatic considerations are of great importance for up-to-date management of rheumatoid arthritis, as they strongly influence the quality of life, compliance, and thereby disease outcomes. Two major approaches of psychological rehabilitation exist, both coping with pain through the regulation of emotion and psychotherapeutic intervention, which not only helps patients in coping with the disease, but also aimed at improving the overall adaptation of the patient. It includes techniques of relaxation, cognitive-behavioral therapy, and biofeedback therapy. Current data about the efficacy of the additional correcting therapies for patients with rheumatoid arthritis, both emerging and common ones, are discussed in the review.
32964059 Selective Increment of Synovial Soluble TYRO3 Correlates with Disease Severity and Joint I 2020 OBJECTIVE: To investigate the role of TAM receptors in rheumatoid arthritis (RA) by determining synovial tissue TAM receptor expression, synovial fluid levels of soluble TAM receptors, and the relationship between soluble TAM receptors, joint inflammation and disease activity. METHODS: TAM receptor expression was determined by immunohistochemistry on the synovium from RA and osteoarthritis (OA) patients. Soluble (s) Tyro3, sAxl, sMer, and their ligand Gas6 were measured by ELISA in the synovial fluid of RA (n = 28) and OA (n = 12) patients and cytokine levels by multiplex immunoassay in RA samples. Correlation analyses were performed among sTAM receptors with local cytokine levels; systemic disease parameters like erythrocyte sedimentation rate (ESR), rheumatoid factor (RF), and anticyclic citrullinated peptide antibodies (ACPA); and disease activity scores (DAS28-ESR) in RA patients. RESULTS: TAM receptors were expressed on different locations in the synovial tissue (lining, sublining, and blood vessels), and a similar expression pattern was observed in RA and OA patients. Synovial fluid sTyro3 and sMer were significantly enhanced in RA compared to OA patients, whereas no significant differences in sAxl and Gas6 levels were found. In RA samples, sTyro3 levels, but not sMer, correlated positively with proinflammatory local cytokines and the systemic factor erythrocyte sedimentation rate. Moreover, stratification analysis showed high sTyro3 levels positively correlated with higher DAS28-ESR and in RF and ACPA double positive RA patients. CONCLUSION: sTyro3 in the synovial fluid of RA patients correlates with local inflammatory molecules and systemic disease activity. These findings suggest that the reduced negative control of cell activation by TAM receptors due to their shedding in the synovial fluid, mainly sTyro3, favoring joint inflammation in RA patients.
32242853 ASSOCIATIONS BETWEEN EFFICACY OF THE THERAPY AND CIRCADIAN FLUCTUATIONS OF ENDOTHELIAL NIT 2020 Feb Despite significant progress in treatment of rheumatoid arthritis (RA), a considerable part of patients remains resistant to the current therapy, apparently for the reasons of undefined mechanisms of its pathogenesis. Recently, the disturbances of circadian regulation of inflammatory processes in RA have been highlighted as important ones. Endothelial nitric oxide synthase (NOS3) and soluble toll-like receptors 2 (sTLR2) take part in the regulation of angiogenesis, osteoclastogenesis, immune responses but their circadian rhythms and predictive significance in RA patients are still unknown. Aim - to estimate the associations between efficacy of treatment and the circadian rhythms of NOS3 and sTLR2, and NOS3 polymorphism in females with rheumatoid arthritis, Ukraine. 97 RA patients (100% female) aged 46.3±8.89 years with disease duration 8.44±6.52 years were examined. All patients as a disease-modifying therapy received methotrexate (MTX) orally in a dose ≤15 mg/week, folic acid 5 mg/week, NSAIDs and corticosteroids (CS) ≤10 mg/day by prednisone. Doses of MTX, NSAIDs and CS were stable 4 weeks prior to the enrolment and during the whole period of study. The efficacy end points included DAS28, RAID and American College of Rheumatology response criteria (ACR20/50/70). Serum levels of NOS3 and sTLR2 were determined at 08:00 and 20:00 using Cloud-Clone Corp kits (USA). NOS3 T-786С polymorphism was determined by Real-Time PCR. The SPSS22 software package was used for statistical processing of the results. The study was performed in accordance to the bioethical standards. After 12-week treatment among RA patients were revealed 52.6% ACR 20 responders and 47.4% non-responders. Opposite diurnal variation of NOS3 and sTLR2 serum levels were found in RA patients. There were significant differences in NOS3/sTLR2 ratio at 08:00 accordingly to NOS3 T786C genotype. The disturbances in daily variability of NOS3 or sTLR2 serum levels were more significant in non-responders compare to responders. Decrease of NOS3/sTLR2 ratio was a predictor of non-response to treatment in RA patients (β=0.366, р=0.000). In RA patients the disturbances of circadian rhythms of endothelial nitric oxide synthase or toll-like receptors 2 expression are associated with an increase of resistance to disease-modifying therapy with methotrexate.