Chronic Systemic Disease Research Articles

Unmet needs and perspectives in rheumatoid arthritis-associated interstitial lung disease: A critical review.

Rheumatoid arthritis (RA) is a chronic systemic autoimmune disease characterized by synovitis as the most common clinical manifestation, and interstitial lung disease (RA-ILD) represents one of the most common and potentially severe extra-articular features. Our current understanding of the mechanisms and predictors of RA-ILD is limited despite the demonstration that an early identification of progressive fibrosing forms is crucial to provide timely treatment with antifibrotic therapies. While high resolution computed tomography is the gold standard technique for the diagnosis and follow-up of RA-ILD, it has been hypothesized that serum biomarkers (including novel and rare autoantibodies), new imaging techniques such as ultrasound of the lung, or the application of innovative radiologic algorithms may help towards predicting and detecting early forms of diseases. Further, while new treatments are becoming available for idiopathic and connective tissue disease-associated forms of lung fibrosis, the treatment of RA-ILD remains anecdotal and largely unexplored. We are convinced that a better understanding of the mechanisms connecting RA with ILD in a subgroup of patients as well as the creation of adequate diagnostic pathways will be mandatory steps for a more effective management of this clinically challenging entity.

Association between levels of serotonin, melatonin, cortisol and the clinical condition of patients with rheumatoid arthritis

Rheumatoid arthritis (RA) is a chronic systemic connective tissue disease of autoimmune basis. It is characterized by inflammation of joints and systemic complications. The etiopathogenesis is still unknown. Predisposing factors for the disease include genetic, immunological and environmental. Chronic disease and the stress experienced by patients disrupt the body’s homeostatic state and weaken the human immune system. Reduced immunity and endocrine disruption may influence the development of autoimmune diseases and exacerbate their course. The aim of the study was to investigate whether there is a relationship between the blood levels of hormones such as cortisol, serotonin, melatonin and the clinical status of RA patients as determined by the DAS28 index and CRP protein. A total of 165 people participated in the study of these 84 subjects had RA and the rest were the control group. All participants completed a questionnaire and had their blood drawn to determine hormones. Patients with RA had higher plasma cortisol (324.6 ng/ml vs. 292.9 ng/ml) and serotonin concentrations (67.9 ng/ml vs. 22.1 ng/ml) and lower plasma melatonin (116.8 pg/ml vs. 330.2 pg/ml) compared to controls. Patients whose CRP concentration were above normal also had elevated plasma cortisol concentration. No significant association was observed in RA patients between plasma melatonin, serotonin and DAS28 values. However, it can be concluded that those with high disease activity had lower melatonin levels as compared to patients with low and moderate DAS28 values. Significant differences were found between RA patients not using steroids and plasma cortisol (p = 0.035). In RA patients, it was observed that as plasma cortisol concentration increased, the chance of having an elevated DAS28 score, indicating high disease activity, increased.

Risk factors of severe periodontitis in kidney transplant recipients: A case-control study.

Kidney transplant recipients (KTRs) represent a vulnerable group of patients who develop a number of comorbidities. Severe periodontitis (SP) is associated with the most common chronic systemic diseases including kidney diseases. The objective of this study was to explore the risk factors for SP in KTRs. In this study, KTRs were divided into those with or without periodontitis and in relation to the severity of periodontitis. A comprehensive medical and periodontal examination was performed and evaluated. Multivariate logistic regression was performed to examine possible risk factors for SP among KTRs. A total of 100 KTRs were included in the analysis, of which 87% had periodontitis. Significant predictors of periodontitis were older age (OR=1.07, 95% CI [1.01, 1.13], p=0.016) and lower skeletal muscle mass (OR=0.88, 95% CI [0.78, 0.99], p=0.035). When examining periodontitis severity, predictors of SP (n=21, 24%) were increased levels of uric acid (OR=1.01, 95% CI [1.00, 1.02], p=0.022) and dental plaque (OR=1.04, 95% CI [1.01, 1.07], p=0.013). In the subset analysis that included only KTRs with measured advanced glycation end products (AGE) (n=47), 34% (n=16) had SP. The predictors of SP were AGE (OR=3.89, 95% CI [1.28, 11.82], p=0.017) and dental plaque (OR=1.07, 95% CI [1.01, 1.13], p=0.028). KTRs with SP had significantly higher uric acid levels and AGE, which may contribute to the systemic health status of this patient population.

Nanoparticulate drug delivery systems for the treatment of rheumatoid arthritis: A comprehensive review

Rheumatoid arthritis (RA) is a chronic systemic autoimmune disease that affects 1% of the world's population. It is a progressive condition that causes joint inflammation, polyarticular synovitis, bone and cartilage destruction, bone erosion, and deformation, resulting in impairments, morbidity, and a lower quality of life. There is no curative therapy for rheumatoid arthritis because the complete pathogenesis is unknown. The treatment aim is to give symptomatic relief while preventing irreversible joint injury. The standard treatment involves glucocorticoids alone or in combination with nonbiologic and biologic disease-modifying anti-rheumatoid drugs (DMARDs). Treatment of RA with conventional dosage forms has limitations such as non-specificity, dose-escalation, increased frequency of administration, toleration, and systemic side effects. Through its application to medicine, nanotechnology has been able to address the drawbacks of conventional treatment and the complexity of the disease, thus offering new possibilities for the treatment of RA by achieving specificity to joints through active and passive targeting strategies, overcoming dose escalation, increased frequency of administration, and the adverse effects associated with it. This review entails a thorough understanding of various Nanoparticulate drug delivery systems, including polymeric nanoparticles such as polymeric micelles, nanocapsules, and dendrimers; lipid-based nanoparticles such as liposomes, solid lipid nanoparticles, nanostructured lipid carriers, Transferosomes, exosomes, nanoemulsions, ethosomes; and metallic nanoparticles such as gold and silver nanoparticles, quantum dots, siRNA, and peptide-based nanoparticulate delivery systems. A comprehensive review of the merits and drawbacks of nanoparticulate drug delivery systems is provided, as well as an update on their application on the pharmacotherapy, toxicity, clinical trial of Nanoparticles on rheumatoid arthritis and patents granted in this field.

Upadacitinib for the treatment of psoriatic arthritis.

Psoriatic arthritis is a chronic systemic inflammatory disease that presents with a variable clinical course and is typically associated with joint inflammation, together with cutaneous psoriasis. In recent decades, knowledge of the pathogenesis of psoriatic arthritis has advanced considerably and has allowed for development of new highly effective therapies, transforming the treatment landscape. Upadacitinib is a Janus kinase inhibitor (JAK) that is orally reversible with high selectivity for JAK1 and its signal transduction molecules. The results obtained in the phase III clinical trials (SELECT-PsA 1 and SELEC-PsA 2) demonstrated that upadacitinib was highly effective over placebo and non-inferior to adalimumab in several important domains of the disease. Improvements were observed in dactylitis, enthesitis and spondylitis as well as in physical function, pain, fatigue and overall quality of life. The safety profile of these results resembled that of adalimumab, apart from a slightly higher rate of herpes zoster infection, an increase of creatine kinase and an incidence of lymphopenia. However, none of these events was considered a serious adverse advent. Additionally, another analysis demonstrated that combining upadacitinib with methotrexate was associated with a similar efficacy to upadacitinib in monotherapy, both for patients that are naive to biologics treatment and for those previously treated with biologics. Therefore, upadacitinib is a new option for the treatment of psoriatic arthritis, presenting a series of beneficial characteristics. At this stage, it is important to collect long-term data to confirm the efficacy and safety profiles shown in clinical trials.

Sociodemographic evaluation of patients with rheumatoid arthritis in the state of roraima, extreme north of Brazil: A descriptive study

Rheumatoid arthritis (RA) is a chronic systemic autoimmune inflammatory disease. Consequently, the need for observational research, which aims at a quantitative/descriptive approach based on documentary and field research with the intention of analyzing the prevalence and incidence of rheumatoid arthritis in Brazil, especially in the state of Roraima, which are scarce. The aim of this study is to analyze the prevalence and incidence of rheumatoid arthritis in the state, as well as other epidemiological aspects such as the profile of patients. That said, 150 participants were obtained, of which women represented 92,0%. The most patients were between 50-59 (34.7%) and 60-69 (29.3%) years old, and also most declared themselves to be brown (82,0%). It was demonstrated that 65.3% of the patients were not born in the state, and 79.3% live in the urban area. In addition, the declared mean education level was complete high school (38%), and 63.3% of patients as well are unemployed. As for family income, 45.4% is between 1 and 3 minimum wages. Evidently, it is possible to relate advanced age, low income and lack of higher education with the prevalence of RA, as factors such as lack of knowledge reduce the haste with which the patient seeks health services, and low income also makes it impossible to pay for health privately, which offers faster services. Therefore, resident rheumatologists and civil servants in the city state claim that the number of patients with RA can reach up to twice the number of respondents, so the need for multicenter studies with large samples of patients over the years is evident.

Regenerative Potential of Bone Morphogenetic Protein 7-Engineered Mesenchymal Stem Cells in Ligature-Induced Periodontitis.

Periodontitis is an oral disease caused by bacterial infection that has stages according to the severity of tissue destruction. The advanced stage of periodontitis presents irreversible destruction of soft and hard tissues, which finally results in loss of teeth. When conventional treatment modalities show limited results, tissue regeneration therapy is required in patients with advanced periodontitis. In the present study, we aimed to evaluate the effect of bone marrow-derived mesenchymal stem cells (BM-MSCs) delivering bone morphogenetic protein 7 (BMP7) on tissue regeneration in a periodontitis model. BMP7 is a member of the BMP family that shows bone-forming ability; however, BMPs rapid clearing and degradation and unproven efficacy make it difficult to apply it in clinical dentistry. To overcome this, we established BMP7-expressing engineered BM-MSCs (BMP7-eBMSCs) that showed superior osteogenic differentiation potential when subcutaneously transplanted with a biphasic calcium phosphate scaffold into immunocompromised mice. Furthermore, the efficacy of BMP7-eBMSC transplantation for periodontal tissue regeneration was evaluated in a rat ligature-induced periodontitis model. Upon measuring two-dimensional and three-dimensional amounts of regenerated alveolar bone using microcomputed tomography, the amounts were found to be significantly higher in the BMP7-eBMSC transplantation group than in the eBMSC transplantation group. Most importantly, fibrous periodontal ligament (PDL) tissue regeneration was also achieved upon BMP7-eBMSC transplantation, which was evaluated by calculating the modified relative connective tissue attachment. The amount of connective tissue attachment in the BMP7-eBMSC transplantation group was significantly higher than that in the ligature-induced periodontitis group, although the increase was comparable between the BMP7-eBMSC and human PDL stem cell transplantation groups. Taken together, our results suggested that sustainable release of BMP7 induces periodontal tissue regeneration and that transplantation of BMP7-eBMSCs is a feasible treatment option for periodontal regeneration. Impact Statement Periodontitis is the second most common human dental disease affecting chronic systemic diseases. Despite the tremendous efforts trying to cure the damaged periodontal tissues using tissue engineering technologies, a definitive regenerative method has not been in consensus. Researchers are seeking more feasible and abundant source of mesenchymal stem cells (MSCs), and furthermore, how to use reliable growth factors under more efficient control are the issues to be solved. In this study, we aimed to evaluate the effect of bone morphogenetic protein 7 (BMP7) gene delivering bone marrow-derived MSCs on periodontal tissue regeneration to evaluate the efficacy of BMP7 and engineered BMSCs for periodontal tissue regeneration.

Recommendations for individual comorbidity risk assessment in adult patients with psoriasis

It has long been known that chronic inflammatory systemic diseases, such as psoriasis, pose ahigh risk of developing comorbidities. In everyday clinical practice, it is therefore of particular importance to identify patients who have an individually increased risk profile. In patients with psoriasis, the comorbidity patterns "metabolic syndrome", "cardiovascular comorbidity" and "mental illness" were identified as particularly relevant in epidemiological studies depending on the duration and severity of the disease. In the everyday care of patients with psoriasis in dermatological practice, the use of an interdisciplinary checklist for risk analysis and the initiation of professional follow-up care has proven valuable. On the basis of an existing checklist, the contents were critically evaluated by an interdisciplinary group of experts and aguideline-oriented update was prepared. In the opinion of the authors, the new analysis sheet represents apracticable, factually focused and updated tool for comorbidity risk assessment in patients with moderate and severe psoriasis.

A RARE ENTITY OF BILATERAL MEDIAL MEDULLARY SYNDROME IN SLE

Medial medullary syndrome is a rare type of ischemic stroke and represents <1% of posterior circulation strokes, in which bilateral infarcts are even rare and can rarely occur in young patients. It usually presents with quadriplegia, dysarthria , dysphagia , impaired sensations. SLE is chronic systemic autoimmune disease often effects young women and is characterized by multisystem involvement. It has eightfold higher risk of stroke, but it rarely occurs as initial manifestation of disease. The CNS involvement in SLE leads to increased rates of mortality, morbidity and disability. Cerebrovascular disease may be attributed to disease, as manifestation of Neuropsychiatric SLE

Investigating the correlation of the NF-κB and FoxP3 gene expression with the plasma levels of pro- and anti-inflammatory cytokines in rheumatoid arthritis patients.

Rheumatoid arthritis (RA) is a chronic inflammatory systemic autoimmune disease. Cytokines regulate a wide range of inflammatory processes involved in RA pathogenesis. Anti-inflammatory cytokines (i.e., TGF-β and lL-10) and pro-inflammatory cytokines, like IL-6, were found to be potentially implicated in RA pathogenesis. Besides, NF-κB and FoxP3 are critical transcription factors regulating the inflammatory events occurring in RA patients. This study intends to assess the plasma levels of IL-6, IL-10, and TGF-β1 cytokines, as well as the expression of NF-κB and FoxP3 genes in RA patients, compared to the healthy controls. Peripheral blood was collected from 50 RA patients (25 new case and 25 under-treatment) and 25 age- and gender-matched healthy subjects. The disease activity was determined using the DAS-28 and ESR criteria. Also, plasma levels of TGF-β1, lL-10, and IL-6 were measured by enzyme-linked immunosorbent assay (ELISA) technique, and the gene expression of NF-κB and FoxP3 was evaluated using the real-time PCR method. Our results showed a significant up-regulation of Rel-A and NF-κB1, and also a down-regulation of FoxP3 gene expression in under-treatment RA patients compared to the controls (P=0.031, P=0.014, and P=0.011, respectively). Moreover, there was a significant reduction of Rel-A and FoxP3 in the under-treatment RA patients compared to new case RA patients (P=0.005 and P=0.015, respectively). Also, plasma levels of TGF-β1 were significantly increased in both the new case and under-treatment RA patients relative to controls (P<0.001). In conclusion, classical NF-κB (P65/P50) and FoxP3 may have significant pro- and anti-inflammatory roles in RA pathogenesis, respectively. Key Point •NF-κB (P65/P50) has a contribution to the early phase of RA.

MiR-383-5p, miR-181a-5p, and miR-181b-5p as Predictors of Response to First-Generation Somatostatin Receptor Ligands in Acromegaly.

Acromegaly is a chronic systemic disease caused in the vast majority of cases by growth hormone (GH)-secreting adenoma, with surgery being the first-line treatment. When a cure is not attained with surgery, first-generation somatostatin receptor ligands (fg-SRLs) are the most common medication prescribed. Predictors of response to fg-SRLs have been studied; however, they cannot fully predict the response to fg-SRL. MicroRNAs are small RNAs, the main role of which is messenger RNA (mRNA) post-transcriptional regulation. This study aimed to identify the microRNAs involved in resistance to treatment with fg-SRLs in acromegaly. Ten patients with acromegaly undergoing treatment with fg-SRLs were selected to undergo miRNA sequencing: five controlled and five uncontrolled with treatment. Bioinformatic analysis was performed to detect differentially expressed miRNAs. Then, the same 10 samples were used for validation by qPCR and an additional 22 samples were analyzed, totaling 32 samples. e We found 59 differentially expressed miRNAs in the first analysis. miR-181a-5p and miR-181b-5p were downregulated, and miR-383-5p was upregulated in the uncontrolled group. Receiver operating characteristic (ROC) curve analysis of miR-383-5p showed an NPV of 84.3% and a PPV of 84.5%. In summary, miR-181a-5p, miR-181b-5p, and miR-383-5p are biomarkers of response to fg-SRLs, and they can be used individually or included in prediction models as tools to guide clinical decisions.

Investigating the Interplay Between Gut Microbiome and Immune Landscape in Sarcoidosis

Sarcoidosis is a chronic systemic inflammatory disease characterized by granulomatous infiltration of affected organs, predominantly the lungs, with unclear etiology. Prior studies implicate microbial antigens as a trigger for inflammation driving granuloma formation. Considering potential cross-interactions along the lung-gut axis, we examine the relationship between gut microbiome and host immunity in sarcoidosis.

Dupilumab Efficacy in Children With Atopic Dermatitis Aged 6 Months to 5 Years With and Without Atopic Comorbidities

Atopic dermatitis (AD) is a chronic inflammatory systemic disease that frequently occurs with atopic comorbidities. Here, we evaluate the efficacy of dupilumab with concomitant topical corticosteroids (TCS) for moderate-to-severe AD in children with and without asthma, allergic rhinitis, and food allergies.

DOP13 Plasma metabolite fingerprint could discriminate inflammatory bowel disease patients from healthy subjects

Abstract Background Inflammatory bowel diseases (IBD, Crohn’s disease [CD], ulcerative colitis [UC]) are chronic immune-mediated systemic diseases with unknown aetiology. In the past few years, experimental studies revealed associations of human serum and plasma metabolites’ with IBD with a possible discriminative power between IBD and healthy subjects. Our study focused on the utility of plasma metabolome profiling as a diagnostic marker in patients with different phenotypes. Methods IBD patients were enrolled in a double-centre prospective cohort study. Large number of healthy subjects were included to reduce methodological bias. Blood samples were obtained at baseline and stored at –20°C and plasma metabolites were measured by high performance liquid chromatography coupled with tandem-mass spectrometry (HPLC-MS/MS). Logistic regression, minimum redundancy maximal relevance (mRMR), principal component analysis (PCA), and linear discriminant analysis (LDA) were used to calculate discriminative power. Results Plasma metabolome profile of 26 IBD (13 UC and 12 CD) patients and 168 HC participants were analyzed, and 388 metabolites were measured. 33 and 58% of CD patients and 31 and 39% of UC patients had clinical and endoscopic activity based on clinical (mean pMayo: 2.8±3.4, CDAI: 56±62) and endoscopic (mean PanMayo: 7.4±13.3 and SES-CD: 7.3±8.2) indices. Low plasma level of cysteine (CV=-0.36; p&amp;lt;0.01), triglycerides (CV=-0.19; p&amp;lt;0.01) and hexosylceramide (HexCer(d18:1/23:0); CV=-0.18; p&amp;lt;0.01), while high level of arginine (CV=0.3; p&amp;lt;0.24), hexosylceramide (HexCer(d18:2/23:0); CV=0.2; p=0.02), glutamate (CV=0.19; p&amp;lt;0.01) and lactate (CV=0.16; p=0.01) were significantly associated with IBD. According to mRMR analysis, cysteine (p&amp;lt;0.001), triglyceride (p&amp;lt;0.01), and HexCer(d16:1/22:0); (p&amp;lt;0.001) ranked highest in terms of feature importance (discriminative power). Based on the 16 metabolites considered to be of the highest discriminative power, the healthy and the IBD groups were well separated (PC1=18.2%, PC2=14.7%; Figure 1.). Conclusion Based on our results, plasma metabolite levels may help to discriminate IBD and healthy subjects. Integrative analysis of different biological samples may potentially predict IBD and could promote achieving personalized medicine. Further sample collections and analysis within this study can reveal discriminative metabolite fingerprints among IBD subtypes and correlations with activity as well.

Clinical characteristics of 683 children and adolescents, aged 0–18 years, newly diagnosed with type 1 diabetes mellitus in Henan Province: a single-center study

BackgroundType 1 diabetes mellitus (T1DM) is a common chronic systemic disease that threatens the health of children worldwide. Diabetic ketoacidosis (DKA) is the most severe acute complication of diabetes and can lead to death. This study aimed to explore the epidemiological features, clinical manifestations, and risk factors for DKA in children and adolescents newly diagnosed with T1DM in the Department of Endocrinology of the Children’s Hospital of Henan Province.MethodsMedical records of 683 children and adolescents newly diagnosed with T1DM in our center from March 2014 to November 2021 were retrospectively analyzed. The data included the general condition, laboratory indexes, and clinical symptoms. The patients were divided into three groups according to age: Group I, 0–3 years; Group II, 4–9 years; and Group III, 10–18 years.ResultsThe incidence of DKA was 62.96% and was highest in Group I. Group I had the lowest C-peptide and hemoglobin A1c, but the highest blood glucose at first diagnosis, and 25-hydroxyvitamin D3 levels, hospitalization lengths, and medical costs. 25.5% of the children were delayed in diagnosis. Logistic regression analysis showed that elevated HbA1c levels and hyperglycemia were independent risk factors for DKA. On the other hand, C-peptide and 25- hydroxyvitamin D were protective factors for DKA.ConclusionsThe incidence of DKA among children and adolescents in the Henan Province is very high. Moreover, DKA can be easily delayed in diagnosis. Newly diagnosed infants with T1DM are more likely to present with DKA, suffer more severe metabolic disorders, endure longer hospital stays, and accrue higher medical costs.

Comprehensive analysis of long noncoding RNAs and lncRNA-mRNA networks in snakehead (Channa argus) response to Nocardia seriolae infection

Evidence has been demonstrated that lncRNAs are involved in a variety of immune responses in vertebrate. It has been demonstrated that immune-related lncRNAs play vital functions in immune regulation against infections in teleost. Nocardia seriolae, as one of the Gram-positive bacteria, can cause chronic systemic granulomatous disease for snakehead (Channa argus). However, how lncRNAs function in the immune regulation process once snakehead was infected with N. seriolae infection has not been studied so far. Accordingly, transcription landscapes of lncRNAs and mRNAs in snakehead were investigated. A total of 1,991 lncRNA were obtained. Totally, we predicted 57,584 co-expression and 16,047 co-location lncRNA-mRNA pairs. To further analyze the potential function of these lncRNAs, GO enrichment analysis and KEGG signal pathways were performed on the target mRNAs of these differently expressed lncRNAs, suggesting that lncRNAs may play essential roles in modulating mRNA expression levels, and subsequently trigger downstream immune signaling pathways to regulate the immune response in snakehead. In addition, 9 DEmRNA and 3 lncRNAs were randomly selected for qRT-PCR analyzed, which confirmed the accuracy of transcriptome data. These results can provide novel knowledge about lncRNAs in immune responses process in snakehead, and can serve as important resources for further investigating the roles of lncRNAs during pathogen infections in teleost.

Could Periodontitis Aggravate Psoriasis?—An Update by Systematic Review

(1) Background: Psoriasis is a chronic and inflammatory systemic disease that has been associated with periodontal pathologies, specifically periodontitis. The aim of this research is to answer the following question: Could periodontitis aggravate psoriasis? (2) Methods: We carried out a systematic review following the PRISMA guide using PubMed, Embase, Scopus, and WOS; (3) Results: A total of 111 studies were identified in the databases and 11 were obtained after screening. The selection included nine case–control studies, one cross-sectional study, and one cohort study. Most of the publications report an increase in bleeding on probing and the presence of periodontal pockets in patients with psoriasis, confirming that inflammation caused by periodontitis can contribute to systemic inflammation worsening psoriasis. To summarize, the scientific literature indicates that local periodontal inflammation could aggravate psoriasis.

Sjogren’s Syndrome with Interstitial Lung Disease

Sjogren’s syndrome (SS) is an autoimmune disease affecting exocrine glands with known properties to cause chronic systemic multi-organ disease involvement. It produced the typical features of sicca syndrome, but due to insidious onset of the disease, patient may present with complications of the condition at the initial presentation. We present a case of primary Sjogren’s syndrome (SS) who first presented with pulmonary manifestations and was subsequently diagnosed as Lymphocytic Interstitial Pneumonia (LIP). The patient was extensively investigated and received appropriate treatment modalities.

ESULTS OF X-RAY EXAMINATION AND DETERMINATION OF BODY MASS INDEX IN PATIENTS WITH RHEUMATOID ARTHRITIS

Rheumatoid arthritis (RA) is a chronic progressive systemic disease of the connective tissue affecting the joints, mainly small, of the erosive-destructive polyarthritis type, and frequent systemic inflammatory damage to internal organs. The disease is registered in all countries of the world with a frequency from 0.4 to 1.5 %. Along with drug therapy, non-drug treatment of patients with rheumatoid arthritis is also used. In particular, an important role is given to the means of physical therapy. Determining the level of functional and organic disorders is important in the treatment and physical therapy of patients with rheumatoid arthritis, taking into account the International classification of functioning, limitations of life and health (ICF).&#x0D; The purpose is to determine the level of functional and organic disorders of the affected joints in patients with rheumatoid arthritis at different stages of the disease, in order to form a personalized approach to rehabilitation.&#x0D; Materials and methods. Analysis and generalization of data from scientific and methodological field-related literature, survey, medical history taking, objective examination, instrumental research methods (X-rays), determination of body mass index (Quetelet index), as well as methods of mathematical statistics. The study was conducted on the basis of the rheumatology department of the Municipal Enterprise “Rivne Regional Clinical Hospital named after Yuriy Semeniuk” in Rivne throughout the period from 2016 to 2018. 216 young and middle-aged patients with rheumatoid arthritis took part in the examination.&#x0D; Results. The authors suggested a scheme (algorithm) of the rehabilitation examination that included a survey, medical history taking, objective examination, the results of instrumental research methods (primarily X-rays), determination of the clinical form of rheumatoid arthritis, the disease stage and degree, as well as the course of the disease. During the initial examination of the patients with rheumatoid arthritis, a predominance of women was found, namely 82%. The main complaints of the patients were: stiffness in the joints of the upper and lower limbs after sleep, pain in the joints, swelling in the small joints of the hands, numbness of the fingers and toes, limitation of movements, periodic pains in the lumbar region. The radiological stage of rheumatoid arthritis was determined according to O. Steinbrocker et al. (1949). Stage I of rheumatoid arthritis was diagnosed in 50 patients (23%), stage II – in 102 patients (47%), and stage III – in 64 cases (30%). Patients with rheumatoid arthritis of the IV radiological stage were not included in the study. All patients underwent BMI (Quetelet index) during the initial examination. It was found that among young people (25 – 44 years old), the average BMI is 25.42, for middle-aged patients (45 – 49 years old) it amounts to 27.27, which corresponds to excess body weight. This is a negative factor in the development and progression of rheumatoid arthritis and a factor to which a comprehensive program of physical therapy will be directed.&#x0D; Conclusions. During the initial examination, it was established that the majority of patients (47 %), have the II radiological stage of the disease with characteristic radiological symptoms. One of the risk factors for the development of rheumatoid arthritis is the increased body weight [4, 6]. There is an urgent need to develop and study the effectiveness of a physical therapy program that could reduce the symptoms of the disease, the level of functional and organic disorders and improve the quality of life of patients.

Effect of a combination of Atractylodes macrocephala extract with strychnine on the TLR4/NF-κB/NLRP3 pathway in MH7A cells.

Rheumatoid arthritis (RA) is now widely recognized as a chronic systemic inflammatory autoimmune disease characterized by swelling, pain and stiffness, which are often disabling. Although the number of drugs available for the treatment of RA has increased in recent years, they are generally expensive, leave patients prone to relapse and can result in severe effects when discontinued. Thus, there is a need for an inexpensive drug with fewer side effects that can be adhered to relieve pain and slow down the progression of the disease. Strychnine, a traditional Chinese medicine, was often used in ancient times to treat swollen and painful joints; however, because of its somewhat toxic nature, it is often combined with Atractylodes macrocephala to reduce its toxicity for safer therapeutic action. The present study performed high-performance liquid chromatography (HPLC)-tandem mass spectrometry (MS/MS) analysis to confirm whether the use of strychnine with Atractylodes macrocephala had the effect of reducing strychnine content. MH7A cells were induced using IL-1β to study the effect of strychnine with Atractylodes macrocephala on the Toll-like receptor 4 (TLR4)/NF-κB/NLR family pyrin domain-containing 3 (NLRP3) pathway in order to verify its role in the treatment of RA. The results indicated that the combined application of HPLC-MS/MS strychnine and Atractylodes macrocephala had a reducing effect on the strychnine content. From the subsequent experimental results, it can be inferred that Strychnine combined with Atractylodes macrocephala extract could promote the apoptosis of synovial cells, and could inhibit the expression levels of TLR4, NF-κB and NLRP3 in the cells as well as reducing the MH7A-positive cells. The expression levels of TLR4, IκB kinase β, NF-κB and NLRP3 were significantly reduced after treatment with each administration group, resulting in a decrease in the phosphorylation levels of TLR4 and NF-κB, indicating that the combination potently inhibited their phosphorylation. The combination of strychnine and atractylenolide II was also revealed to be the main active ingredient in the treatment of RA.