Consecuencias de la artritis reumatoide en la articulación temporomandibular y su manejo odontológico / Consequences of rheumatoid arthritis in the temporomandibular joint and its dental management

Introducción: la artritis reumatoide es parte del grupo de las enfermedades autoinmunes con incidencia considerable sobre la población. Se caracteriza por la afección de las articulaciones del cuerpo que la padece; en mayor frecuencia se encuentra afectada la articulación temporomandibular por el complejo articular que ésta presenta; entre los signos y síntomas que comúnmente podemos encontrar en pacientes con este tipo de enfermedad son los chasquidos o ruidos articulares, dolor orofacial, pérdida o imposibilidad del movimiento de la mandíbula y cambios anatómicos localizados en el área de la articulación temporomandibular. Objetivo: describir las consecuencias que desencadena la artritis reumatoide sobre la articulación temporomandibular y cómo es para el odontólogo el manejo de estos pacientes en consulta, evaluar los tratamientos para cada caso sobre un correcto diagnóstico. Material y métodos: se realizó una revisión bibliográfica de artículos recientes sobre el tema, utilizando buscadores como SciELO, Elsevier y PubMed, siendo 30 las fuentes seleccionadas con idiomas en inglés y español. Resultados: esta enfermedad autoinmune se caracteriza por afectar múltiples articulaciones del cuerpo humano simétrica y bilateralmente incluyendo la articulación temporomandibular (ATM), lo cual conlleva al riesgo de desarrollar trastornos temporomandibulares (TTM). Es importante conocer los métodos para realizar un correcto diagnóstico oportuno de la ATM del paciente con artritis reumatoide (AR) con la finalidad de ofrecer un tratamiento conservador. Conclusión: los trastornos temporomandibulares desencadenantes de la artritis reumatoide son afecciones que se deben considerar para el buen manejo del paciente con este padecimiento, comprender y respaldar un diagnóstico clínico es de vital importancia para dar al paciente un tratamiento adecuado dependiendo el grado de complejidad en la que cada individuo se encuentra; conocer el manejo adecuado y encaminar al paciente a una mejor calidad de vida es clave en la consulta odontológica del día a día (AU)

Introduction: rheumatoid arthritis is part of the group of autoimmune diseases with considerable incidence in the population. It is characterized by the affection of the joints of the body that suffers from it; most frequently the temporomandibular joint is affected due to the articular complex that it presents; among the signs and symptoms that we can commonly find in patients with this type of disease are joint clicks or noises, orofacial pain, loss or impossibility of jaw movement and anatomical changes located in the temporomandibular joint area. Objective: to describe the consequences that rheumatoid arthritis triggers on the temporomandibular joint and how it is for the dentist to manage these patients in consultation, to evaluate the treatments for each case on a correct diagnosis. Material and methods: a bibliographic review of recent articles on the subject was carried out, using search engines such as SciELO, Elsevier and PubMed, with 30 sources selected in English and Spanish. Results: this autoimmune disease is characterized by affecting multiple joints of the human body symmetrical and bilaterally including the TMJ which leads to the risk of developing TMD. It is important to know the methods to make a correct diagnosis of the TMJ of the patient with RA in order to offer a conservative treatment. Conclusions: the temporomandibular disorders that trigger rheumatoid arthritis are conditions that should be considered for the proper management of the patient with this condition, understanding and supporting a clinical diagnosis is of vital importance to give the patient an adequate treatment depending on the degree of complexity in which each individual is; knowing the proper management and directing the patient to a better quality of life is key in the day-to-day dental practice (AU)

Tasa de publicaciones de trabajos presentados sobre artritis reumatoidea en congresos de Reumatología / Publication rates of papers on rheumatoid arthritis submitted to Congresses of Rheumatology

Resumen Introducción: se publica una minoría de todos los trabajos presentados en los Congresos Argentinos de Reumatología (CAR). Objetivos: analizar los temas de estudio (TDE) de los trabajos sobre artritis reumatoidea (AR) presentados en los CAR y su tasa de publicación. Materiales y métodos: se analizaron todos los resúmenes sobre AR, como motivo primario de estudio, presentados en los CAR entre 2008 y 2017. Se agruparon según TDE, y se determinaron los TDE repetidos definidos como, al menos, dos estudios similares presentados sobre el mismo tema. Se determinó la tasa de publicación, el número de estudios similares por TDE, el número de centros participantes y el número de pacientes estudiados. Resultados: sobre 346 trabajos presentados, 51 (14,7%) fueron publicados. Se publicaron 14 (11,9%) de los 118 estudios sobre TDE repetidos versus 37 (16,2%) del resto de los TDE (p=0,4). Los trabajos sobre TDE repetidos no incluyeron más pacientes ni involucraron a un número mayor de centros. Se encontraron 13 TDE repetidos con al menos tres estudios similares y ningún estudio publicado. Conclusiones: solo una minoría de los trabajos sobre AR se publicó. Un tercio de los trabajos presentados en los CAR correspondió a TDE repetidos, que no mejoraron la tasa de publicación.

Abstract Introduction: only a few articles submitted to the Argentine Congress of Rheumatology (ACOR) are published. Objectives: to analyse the topics of study (TOS) and the publication rate of articles on rheumatoid arthritis (RA) submitted to the ACOR. Materials and methods: every abstract submitted to the ACOR between 2008 and 2017, whose primary research subject was RA, was analyzed and sorted according to TOS. Repeated TOS, defined as at least two similar studies on the same topic, were identified. The publication rate and the number of similar studies according to TOS, participating centers, and patients were determined. Results: out of 346 articles submitted, 51 (14.7%) were published. Fourteen (11.9%) of the 118 studies on repeated TOS were published vs. 37 (16.2%) of the rest of the TOS (p: 0.4). The articles on repeated TOS neither included more patients nor involved a higher number of centers. Thirteen repeated TOS with at least three similar studies, but no published articles were identified. Conclusions: only a few articles on RA were published. One third of the studies submitted to the ACOR are repeated TOS, a fact that does not improve the publication rate.

A rat model of rheumatoid arthritis: TDZD-8 is associated with the protection against the induction of the synovium knee joint IL-17A/GSK3beta/ROS/alpha-SMA axis of fibrosis / Un modelo de rata de artritis reumatoide: TDZD-8 está asociado con la protección contra la inducción del eje de fibrosis de la articulación sinovial de la rodilla IL-17A/GSK3ß/ROS/α-SMA

SUMMARY: Rheumatoid arthritis (RA) that affects the synovial knee joint causes swelling of the synovial membrane and tissue damage. Interleukin-17A (IL-17A) and the enzyme glycogen synthase kinase-3β (GSK3β) are involved in the pathogenesis of RA. The link between IL-17A, GSK3β, the oxidative stress, and the profibrogenic marker alpha-smooth muscle actin (α-SMA) with and without TDZD-8, GSK3β inhibitor has not been studied before. Consequently, active immunization of rats was performed to induce RA after three weeks using collagen type II (COII) injections. The treated group received daily injection of 1 mg/kg TDZD-8 for 21 days following the immunization protocol (COII+TDZD-8). Blood and synovium tissue samples were harvested at the end of the experiment. RA development was confirmed as corroborated by a substantial increase in blood levels of the highly specific autoantibody for RA, anti-citrullinated protein antibody as well as augmentation of reactive oxidative species (ROS) levels measured as lipid peroxidation. RA induction also increased synovium tissue levels of IL-17A and the profibrogenic marker, α-SMA. All these parameters seemed to be significantly (p<0.0001) ameliorated by TDZD-8. Additionally, a significant correlation between IL-17A, ROS, and α-SMA and biomarkers of RA was observed. Thus, knee joint synovium RA induction augmented IL-17A/GSK3β/ROS/α-SMA axis mediated arthritis in a rat model of RA, which was inhibited by TDZD-8.

La artritis reumatoide (AR) que afecta la articulación sinovial de la rodilla provoca inflamación de la membrana sinovial y daño tisular. La interleucina-17A (IL-17A) y la enzima glucógeno sintasa quinasa-3β (GSK3β) están involucradas en la patogenia de la AR. No se ha estudiadol vínculo entre IL-17A, GSK3β, el estrés oxidativo y el marcador profibrogénico actina de músculo liso alfa (α-SMA) con y sin inhibidor de TDZD-8, GSK3β. En consecuencia, se realizó una inmunización activa de ratas para inducir la AR después de tres semanas usando inyecciones de colágeno tipo II (COII). El grupo tratado recibió una inyección diaria de 1 µg/ kg de TDZD-8 durante 21 días siguiendo el protocolo de inmunización (COII+TDZD-8). Se recogieron muestras de sangre y tejido sinovial al final del experimento. El desarrollo de AR se confirmó como lo corroboró el aumento sustancial en los niveles sanguíneos del autoanticuerpo altamente específico para AR, el anticuerpo antiproteína citrulinada, así como el aumento de los niveles de especies oxidativas reactivas (ROS) medidos como peroxidación lipídica. La inducción de AR también aumentó los niveles de tejido sinovial de IL-17A y el marcador profibrogénico, α-SMA. Todos estos parámetros parecían mejorar significativamente (p<0,0001) con TDZD-8. Además, se observó una correlación significativa entre IL- 17A, ROS y α-SMA y biomarcadores de AR. Por lo tanto, la inducción de AR en la sinovial de la articulación de la rodilla aumentó la artritis mediada por el eje IL-17A/GSK3β/ROS/α-SMA en un modelo de rata de AR, que fue inhibida por TDZD-8.

Ansiedad, depresión y vulnerabilidad al estrés en personas con diagnóstico de artritis reumatoidea: un estudio exploratorio del Hospital de Clínicas de la Universidad Nacional de Asunción / Anxiety, depression, and vulnerability to stress in people diagnosed with rheumatoid arthritis: An exploratory study at the Hospital de Clínicas of the Universidad Nacional de Asunción

Antecedentes: Estudios observacionales han descrito una alta prevalencia de depresión y ansiedad en la artritis reumatoidea: los trastornos depresivos mayores se detectan en el 17 % de los pacientes con la patología, y la inflamación local y sistémica desempeña un papel importante en la ansiedad y la depresión. Objetivos: El objetivo general de esta investigación fue determinar la frecuencia de ansiedad, depresión y vulnerabilidad al estrés en pacientes con diagnóstico de artritis reumatoidea. Materiales y métodos: Este fue un estudio observacional, descriptivo de asociación cruzada y temporalmente prospectivo. El muestreo fue no probabilístico de casos consecutivos. Se incluyó a personas adultas con diagnóstico de artritis reumatoide que consultaron en el Departamento de Reumatología del Hospital de Clínicas, entre agosto y octubre del 2022. Para el diagnóstico psiquiátrico se utilizaron los siguientes instrumentos: Escala de Ansiedad Generalizada (GAD-7), Patient Health Questionnaire (PHQ-2) y Escala de Vulnerabilidad al Estrés de Smith y Miller. Resultados: Se incluyó a 36 pacientes, todas mujeres, con edades comprendidas entre los 20 y 77 años. El 27,8 % tenía depresión, según los puntos de corte del PHQ-2. El 22,2 % presentaba ansiedad, según los puntos de corte de GAD-7. En cuanto al estrés, el 22,2 % tenía vulnerabilidad a este y el 5,6 % era seriamente vulnerable. Conclusión: Depresión, ansiedad y vulnerabilidad al estrés son comorbilidades frecuentemente observadas en pacientes con artritis reumatoidea. Se requieren de intervenciones específicas de salud mental para abordar estas cuestiones y mejorar la calidad de vida de los pacientes afectados.

Background: Observational studies have described a high prevalence of depression and anxiety in rheumatoid arthritis: major depressive disorders are detected in 17 % of patients with the pathology, and local and systemic inflammation play an important role in anxiety and depression. Objectives: The overall objective of this research was to determine the frequency of anxiety, depression, and vulnerability to stress in patients diagnosed with rheumatoid arthritis. Materials and methods: This was an observational, descriptive, temporally prospective, cross-association study. Sampling was non-probabilistic of consecutive cases. We included adults with a diagnosis of rheumatoid arthritis who consulted at the Rheumatology Department of the Hospital de Clínicas between August and October 2022. The following instruments were used for psychiatric diagnosis: Generalized Anxiety Scale (GAD-7), Patient Health Questionnaire (PHQ-2) and Smith and Miller's Stress Vulnerability Scale. Results: Thirty-six patients, all women, aged between 20 and 77 years, were included in the study. The 27.8 % had depression, according to the cut-off points of the PHQ-2. Anxiety was present in 22.2 %, according to the GAD-7 cut-off points. Regarding stress, 22.2 % were vulnerable to stress and 5.6 % were seriously vulnerable. Conclusion: Depression, anxiety and vulnerability to stress are frequently observed comorbidities in patients with rheumatoid arthritis. Specific mental health interventions are required to address these issues and improve the quality of life of affected patients.

Acercamiento teórico al uso de la imagenología en el diagnóstico temprano de la artritis reumatoide / Theoretical approach to the use of imaging in the early diagnosis of rheumatoid arthritis

La artritis reumatoide es una enfermedad progresiva, con manifestaciones clásicas y tempranas como es la afectación de las articulaciones pequeñas de las manos y los tobillos. Se realizó una revisión bibliográfica de los documentos publicados entre 2017 y 2022. Se realizó una lectura preliminar de 37 artículos que cumplían con los criterios de inclusión, y finalmente se seleccionaron 23 artículos, de los cuales se tomó el contenido de mayor importancia. La ecografía es una técnica fiable y más sensible que la exploración clínica en el estudio de la enfermedad músculo-esquelética, pues permite una exploración multiplanar y dinámica, lo que resulta en un diagnóstico más exacto. La técnica Doppler constituye un complemento útil en el seguimiento de estos pacientes. Esta enfermedad es recurrente en las consultas de Reumatología, por tanto, en su valoración inicial, la utilidad de los medios diagnósticos, especialmente la ecografía, tiene gran importancia.

Rheumatoid arthritis is a progressive disease, with classic and early manifestations such as involvement of the small joints of the hands and ankles. We conducted a bibliographic review of the documents published between 2017 and 2022. A preliminary reading of 37 articles that met the inclusion criteria was carried out, and 23 articles were finally selected, from which the most important content was taken. Ultrasound is a more sensitive and reliable technique than clinical examination for the study of musculoskeletal disease, since it allows a multiplanar and dynamic examination, which results in a more accurate diagnosis. Doppler technique is a useful complement in the follow-up of these patients. This disease is recurrent in Rheumatology consultations, that's why in its initial assessment, the usefulness of diagnostic means, especially ultrasound, is of great importance.

Shared epitope classification methods according to Gregersen and de Vries allow adequate characterization of patients with rheumatoid arthritis in a Colombian population

Introduction: The most important genetic association in rheumatoid arthritis (RA) is presented with some alleles from the HLA-DRB1 gene that encode the shared epitope (SE). Objectives: To apply the SE classification methods of Gregersen, de Vries, Raychaudhuri, Mattey, and Tezenas du Montcel in a group of Colombian patients with RA and determine the most common HLA-DRB1 alleles in the population. Methods: RA diagnosis, genetic study of the HLA-DRB1 region using Luminex technology in 50 RA and 50 healthy subjects. For the classification analysis, Fisher's exact test and chi-squared test were applied. Tables were created to count the RA-related alleles. We used odds ratio to determine the risk between the presence of the shared epitope (SE) and anti-cyclic citrullinated peptides (Anti-CCP). Results: Gregersen and de Vries methods were suitable for the characterization of RA in this population (p = .006). The most prevalent HLA-DRB1 alleles in the RA group were 14:02,04:04, 08:02,04:05, and 10:01. High frequencies of the 07:01, 03:01,13:02,01:02, and 12:01 HLA-DRB1 alleles were found in the healthy population. HLA-DRB1 alleles with similar distribution in both populations were 04:07, 15:01, 11:01, 16:02, and 01:01. A high frequency of SE + was observed in Anti-CCP + individuals (63.15%); however, this was not statistically significant [OR2.4 (.63-9.01); p = .19]. Conclusion: The SE classification methods of Gregersen and de Vries were adequate in characterizing RA in a Colombian population group. An equivalence of 100% was verified between the susceptibility alleles defined by de Vries and the alleles assigned as SE according to Gregersen.

Introducción: La asociación genética más importante en artritis reumatoide (AR) se presenta con algunos alelos del gen HLA DRB1 que codifican el epítope compartido (EC). Objetivos: Aplicar los métodos de clasificación de EC de Gregersen et al., de Vries et al., Raychaudhuri et al., Mattey et al., y Tezenas du Montcel et al., en un grupo de pacientes colombianos con AR, y determinar los alelos HLA DRB1 más frecuentes en esta población. Métodos: Diagnóstico para AR, estudio genético de la región HLA DRB1 por tecnología Luminex® de 50 sujetos AR y 50 sanos. Para análisis comparativos de clasificaciones EC, se aplicaron las pruebas test exacto de Fisher y Chi-cuadrado y se realizaron tablas de conteos para los alelos relacionados con AR. Se estimó la razón de odds para determinar el riesgo entre la presencia de EC y los anticuerpos antipéptidos cíclicos citrulinados (anti-PCC). Resultados: Los métodos de Gregersen et al. y de Vries et al. fueron adecuados para la caracterización de AR en esta población (p = 0,006). Los alelos HLA DRB1 más prevalentes en el grupo AR fueron 14:02, 04:04, 08:02, 04:05 y 10:01. Se encontraron altas frecuencias de los alelos HLA DRB1 07:01, 03:01,13:02, 01:02 y 12:01 en población sana. Alelos HLA DRB1 con distribución similar en ambas poblaciones fueron: 04:07, 15:01, 11:01, 16:02 y 01:01. Se observó alta frecuencia de individuos EC+ en el grupo AR anti-PCC+ (63,15%); no obstante, sin asociación estadística (OR: 2,4 [0,63-9,01]; p = 0,19). Conclusión: Los métodos de clasificación para EC de Gregersen et al. y de Vries et al. fueron adecuados caracterizando AR en un grupo de población colombiana. Se corroboró equivalencia del 100% entre los alelos de susceptibilidad definidos por de Vries y los alelos asignados como EC según Gregersen et al.

IL-27: a novel cytokine mediating immune related diseases / 生理学报

Interleukin 27 (IL-27) is a pleiotropic cytokine that is involved in the regulation of the body's innate and adaptive immunity. Previous studies have shown that IL-27 mediates a variety of inflammatory responses in vivo. With the development of animal models and technical tools, several studies have shown that it is also closely associated with autoimmune diseases and other immune related diseases, and is considered as an important candidate for the treatment of viral disease, autoimmune diseases, tumors and obesity. Therefore, this paper reviews recent progress on the role of IL-27 in acquired immunodeficiency syndrome (AIDS), rheumatoid arthritis, tumors and obesity, with the aim of providing new ideas for the treatment of immune related diseases.

Osteoimmunology research in rheumatoid arthritis: From single-cell omics approach / 中华医学杂志(英文版)

Cellular immune responses as well as generalized and periarticular bone loss are the key pathogenic features of rheumatoid arthritis (RA). Under the pathological conditions of RA, dysregulated inflammation and immune processes tightly interact with skeletal system, resulting in pathological bone damage via inhibition of bone formation or induction of bone resorption. Single-cell omics technologies are revolutionary tools in the field of modern biological research.They enable the display of the state and function of cells in various environments from a single-cell resolution, thus making it conducive to identify the dysregulated molecular mechanisms of bone destruction in RA as well as the discovery of potential therapeutic targets and biomarkers. Here, we summarize the latest findings of single-cell omics technologies in osteoimmunology research in RA. These results suggest that single-cell omics have made significant contributions to transcriptomics and dynamics of specific cells involved in bone remodeling, providing a new direction for our understanding of cellular heterogeneity in the study of osteoimmunology in RA.

Berberine inhibits autophagy and promotes apoptosis of fibroblast-like synovial cells from rheumatoid arthritis patients through the ROS/mTOR signaling pathway / 南方医科大学学报

OBJECTIVE@#To evaluate the regulatory effect of berberine on autophagy and apoptosis balance of fibroblast-like synoviocytes (FLSs) from patients with in rheumatoid arthritis (RA) and explore the mechanism.@*METHODS@#The inhibitory effect of 10, 20, 30, 40, 50, 60, 70, and 80 μmol/L berberine on RA-FLS proliferation was assessed using CCK-8 method. Annexin V/PI and JC-1 immunofluorescence staining was used to analyze the effect of berberine (30 μmol/L) on apoptosis of 25 ng/mL TNF-α- induced RA-FLSs, and Western blotting was performed to detect the changes in the expression levels of autophagy- and apoptosis-related proteins. The cells were further treated with the autophagy inducer RAPA and the autophagy inhibitor chloroquine to observe the changes in autophagic flow by laser confocal detection of mCherry-EGFP-LC3B. RA-FLSs were treated with the reactive oxygen species (ROS) mimic H2O2 or the ROS inhibitor NAC, and the effects of berberine on ROS, mTOR and p-mTOR levels were observed.@*RESULTS@#The results of CCK-8 assay showed that berberine significantly inhibited the proliferation of RA-FLSs in a time- and concentration-dependent manner. Flow cytometry and JC-1 staining showed that berberine (30 μmol/L) significantly increased apoptosis rate (P < 0.01) and reduced the mitochondrial membrane potential of RA-FLSs (P < 0.05). Berberine treatment obviously decreased the ratios of Bcl-2/Bax (P < 0.05) and LC3B-II/I (P < 0.01) and increased the expression of p62 protein in the cells (P < 0.05). Detection of mCherry-EGFP-LC3B autophagy flow revealed obvious autophagy flow block in berberine-treated RA-FLSs. Berberine significantly reduced the level of ROS in TNF-α-induced RA-FLSs and upregulated the expression level of autophagy-related protein p-mTOR (P < 0.01); this effect was regulated by ROS level, and the combined use of RAPA significantly reduced the pro-apoptotic effect of berberine in RA-FLSs (P < 0.01).@*CONCLUSION@#Berberine can inhibit autophagy and promote apoptosis of RA-FLSs by regulating the ROS-mTOR pathway.

Mechanism of artesunate on bone destruction in experimental rheumatoid arthritis based on transcriptomics and network pharmacology / 中国中药杂志

The present study investigated the mechanism of artesunate in the treatment of bone destruction in experimental rheumatoid arthritis(RA) based on transcriptomics and network pharmacology. The transcriptome sequencing data of artesunate in the inhibition of osteoclast differentiation were analyzed to obtain differentially expressed genes(DEGs). GraphPad Prism 8 software was used to plot volcano maps and heat maps were plotted through the website of bioinformatics. GeneCards and OMIM were used to collect information on key targets of bone destruction in RA. The DEGs of artesunate in inhibiting osteoclast differentiation and key target genes of bone destruction in RA were intersected by the Venny 2.1.0 platform, and the intersection target genes were analyzed by Gene Ontology(GO)/Kyoto Encyclopedia of Genes and Genomes(KEGG) enrichment. Finally, the receptor activator of nuclear factor-κB(RANKL)-induced osteoclast differentiation model and collagen-induced arthritis(CIA) model were established. Quantitative real time polymerase chain reaction(q-PCR), immunofluorescence, and immunohistochemistry were used to verify the pharmacological effect and molecular mechanism of artesunate in the treatment of bone destruction in RA. In this study, the RANKL-induced osteoclast differentiation model in vitro was established and intervened with artesunate, and transcriptome sequencing data were analyzed to obtain 744 DEGs of artesunate in inhibiting osteoclast differentiation. A total of 1 291 major target genes of bone destruction in RA were obtained from GeneCards and OMIM. The target genes of artesunate in inhibiting osteoclast differentiation and the target genes of bone destruction in RA were intersected to obtain 61 target genes of artesunate against bone destruction in RA. The intersected target genes were analyzed by GO/KEGG enrichment. According to the results previously reported, the cytokine-cytokine receptor interaction signaling pathway was selected for experimental verification. Artesunate intervention in the RANKL-induced osteoclast differentiation model showed that artesunate inhibited CC chemokine receptor 3(CCR3), CC chemokine receptor 1(CCR1) and leukemia inhibitory factor(LIF) mRNA expression in osteoclasts in a dose-dependent manner compared with the RANKL-induced group. Meanwhile, the results of immunofluorescence and immunohistochemistry showed that artesunate could dose-dependently reduce the expression of CCR3 in osteoclasts and joint tissues of the CIA rat model in vitro. This study indicated that artesunate regulated the CCR3 in the cytokine-cytokine receptor interaction signaling pathway in the treatment of bone destruction in RA and provided a new target gene for the treatment of bone destruction in RA.

Application of microneedle-assisted percutaneous drug delivery system in treatment of rheumatoid arthritis:a review / 中国中药杂志

Rheumatoid arthritis(RA) is a chronic degenerative joint disease characterized by inflammation. Due to the complex causes, no specific therapy is available. Non-steroidal anti-inflammatory agents and corticosteroids are often used(long-term, oral/injection) to interfere with related pathways for reducing inflammatory response and delaying the progression of RA, which, however, induce many side effects. Microneedle, an emerging transdermal drug delivery system, is painless and less invasive and improves drug permeability. Thus, it is widely used in the treatment of RA and is expected to be a new strategy in clinical treatment. This paper summarized the application of microneedles in the treatment of RA, providing a reference for the development of new microneedles and the expansion of its clinical application.

Mechanism of active ingredients in Periploca forrestii compound against rheumatoid arthritis based on integrative metabolomics and network pharmacology / 中国中药杂志

In this study, an ultra-performance liquid chromatography-quadrupole time-of-flight high resolution mass spectrometer(UPLC-Q-TOF-HRMS) was used to investigate the effects of the active ingredients in Periploca forrestii compound on spleen metabolism in rats with collagen-induced arthritis(CIA), and its potential anti-inflammatory mechanism was analyzed by network pharmacology. After the model of CIA was successfully established, the spleen tissues of rats were taken 28 days after administration. UPLC-Q-TOF-HRMS chromatograms were collected and analyzed by principal component analysis(PCA), orthogonal partial least squares discriminant analysis(OPLS-DA), and MetPA. The results showed that as compared with the blank control group, 22 biomarkers in the spleen tissues such as inosine, citicoline, hypoxanthine, and taurine in the model group increased, while 9 biomarkers such as CDP-ethanolamine and phosphorylcholine decreased. As compared with the model group, 21 biomarkers such as inosine, citicoline, CDP-ethanolamine, and phosphorylcholine were reregulated by the active ingredients in P. forrestii. Seventeen metabolic pathways were significantly enriched, including purine metabolism, taurine and hypotaurine metabolism, glycerophospholipid metabolism, and cysteine and methionine metabolism. Network pharmacology analysis found that purine metabolism, glycerophospholipid metabolism, and cysteine and methionine metabolism played important roles in the pathological process of rheumatoid arthritis. This study suggests that active ingredients in P. forrestii compound can delay the occurrence and development of inflammatory reaction by improving the spleen metabolic disorder of rats with CIA. The P. forrestii compound has multi-target and multi-pathway anti-inflammatory mechanism. This study is expected to provide a new explanation for the mechanism of active ingredients in P. forrestii compound against rheumatoid arthritis.

Traditional Chinese medicine therapy for rheumatoid arthritis: a review / 中国中药杂志

Rheumatoid arthritis(RA) is an autoimmune disease that seriously affects the physical and mental health of patients, but its pathogenesis is still unclear. At present, clinical treatment drugs include conventional synthetic disease modifing anti-rheumatic drugs(csDMARDs), nonsteroid anti-inflammtory drugs(NSAIDs), hormones, small molecule targeted drugs, biological agents, etc. These drugs can relieve the clinical symptoms of most patients with RA to a certain extent, but there are still many limitations, such as drug adverse reactions and individual differences in drug efficacy. Therefore, the research on drug treatment targets and the development of low-toxicity drugs helps further improve the precise prevention, diagnosis, and treatment of RA. There is an urgent need for efficient and low-toxic treatments to delay the clinical progress of RA. As a treasure of Chinese culture, traditional Chinese medicine(TCM) is widely used as an alternative therapy in the treatment of various diseases, and has a significant clinical efficacy. TCM therapy(including monomer traditional Chinese medicine, classical compounds, and non-drug therapies) has a significant curative effect on RA. Based on the literature research in recent years, this paper reviewed the clinical and mechanism research of TCM therapy in the treatment of RA, and provided more in-depth thinking for the wide application of TCM therapy in clinical practice.

Continuation, reduction, or withdrawal of tofacitinib in patients with rheumatoid arthritis achieving sustained disease control: a multicenter, open-label, randomized controlled trial / 中华医学杂志(英文版)

BACKGROUND@#Rheumatoid arthritis (RA), a chronic systemic autoimmune disease, is characterized by synovitis and progressive damage to the bone and cartilage of the joints, leading to disability and reduced quality of life. This study was a randomized clinical trial comparing the outcomes between withdrawal and dose reduction of tofacitinib in patients with RA who achieved sustained disease control.@*METHODS@#The study was designed as a multicenter, open-label, randomized controlled trial. Eligible patients who were taking tofacitinib (5 mg twice daily) and had achieved sustained RA remission or low disease activity (disease activity score in 28 joints [DAS28] ≤3.2) for at least 3 months were enrolled at six centers in Shanghai, China. Patients were randomly assigned (1:1:1) to one of three treatment groups: continuation of tofacitinib (5 mg twice daily); reduction in tofacitinib dose (5 mg daily); and withdrawal of tofacitinib. Efficacy and safety were assessed up to 6 months.@*RESULTS@#Overall, 122 eligible patients were enrolled, with 41 in the continuation group, 42 in the dose-reduction group, and 39 in the withdrawal group. After 6 months, the percentage of patients with a DAS28-erythrocyte sedimentation rate (ESR) of <3.2 was significantly lower in the withdrawal group than that in the reduction and continuation groups (20.5%, 64.3%, and 95.1%, respectively; P  < 0.0001 for both comparisons). The average flare-free time was 5.8 months for the continuation group, 4.7 months for the dose reduction group, and 2.4 months for the withdrawal group.@*CONCLUSION@#Withdrawal of tofacitinib in patients with RA with stable disease control resulted in a rapid and significant loss of efficacy, while standard or reduced doses of tofacitinib maintained a favorable state.@*TRIAL REGISTRATION@#Chictr.org, ChiCTR2000039799.

Diffuse lung involvement in rheumatoid arthritis: a respiratory physician's perspective / 中华医学杂志(英文版)

The lungs are one of the most common extra-articular organs involved in rheumatoid arthritis (RA), which is reported to occur in up to 60% to 80% of RA patients. Respiratory complications are the second leading cause of death due to RA. Although there is a wide spectrum of RA-associated respiratory diseases, interstitial lung disease is the most common manifestation and it impacts the prognosis of RA. There has been progress in understanding the management and progression of rheumatoid arthritis-associated interstitial lung disease (RA-ILD) and RA-associated respiratory diseases recently, for example, opportunistic pulmonary infectious diseases and toxicity from RA therapies. From a chest physicians' perspective, we will update the diagnosis and treatment of RA-associated ILD, methotrexate-associated lung disease, and the complication of Pneumocystis jiroveci pneumonia in RA in this review.

Role of ceRNA network in inflammatory cells of rheumatoid arthritis / 中南大学学报(医学版)

Rheumatoid arthritis (RA) is a chronic inflammatory autoimmune disease caused by inflammatory cells. Various inflammatory cells involved in RA include fibroblast-like synoviocytes, macrophages, CD4+T-lymphocytes, B lymphocytes, osteoclasts and chondrocytes. The close interaction between various inflammatory cells leads to imbalance of immune response and disorder of the expression of mRNA in inflammatory cells. It helps to drive production of pro-inflammatory cytokines and stimulate specific antigen-specific T- and B-lymphocytes to produce autoantibodies which is an important pathogenic factor for RA. Competing endogenous RNA (ceRNA) can regulate the expression of mRNA by competitively binding to miRNA. The related ceRNA network is a new regulatory mechanism for RNA interaction. It has been found to be involved in the regulation of abnormal biological processes such as proliferation, apoptosis, invasion and release of inflammatory factors of RA inflammatory cells. Understanding the ceRNA network in 6 kinds of RA common inflammatory cells provides a new idea for further elucidating the pathogenesis of RA, and provides a theoretical basis for the discovery of new biomarkers and effective therapeutic targets.

Mechanism of Gentisic Acid on Rheumatoid Arthritis Based on miR-19b-3p/RAF1 Axis / 中国结合医学杂志

OBJECTIVE@#To investigate the therapeutic effect of gentisic acid (GA) on rheumatoid arthritis (RA) based on the miR-19b-3p/RAF1 axis.@*METHODS@#The cell counting kit-8 method was used to detect the growth inhibitory effect of different concentrations of GA on MH7A cells, and the drug concentration of GA was determined in the experiment. The quantificational real-time polymerase chain reaction (qRT-PCR) was used to detect the expression of miR-19b-3p and RAF1. RAF1, extracellular regulated protein kinases1/2 (ERK1/2) and phospho-ERK1/2 (p-ERK1/2) were examined by Western blotting. Three methods (dual-luciferase assay, qRT-PCR and Western blot analysis) were used to verify miR-19b-3p targeting RAF1. Flow cytometry was performed to detect MH7A cell apoptosis. Transwell and wound healing assays were used to determine the invasion and migration capacities of MH7A cells.@*RESULTS@#The growth of MH7A cells was gradually inhibited with increasing GA concentration. When the GA concentration exceeded 80 mmol/L, GA was significantly cytotoxic to MH7A cells, so the half maximal inhibitory concentration of GA for MH7A cells was calculated as 67.019 mmol/L. GA upregulated miR-19b-3p expression, downregulated RAF1 expression, inhibited ERK1/2 phosphorylation, induced MH7A cell apoptosis and suppressed MH7A cell invasion and migration (P<0.05 or P<0.01). RAF1 was identified as the target of miR-19b-3p and reversed inhibitory effects on miR-19b-3p expression (P<0.05 or P<0.01). The miR-19b-3p inhibitor upregulated RAF1 expression and ERK1/2 phosphorylation, suppressed MH7A cell apoptosis and induced MH7A cell invasion and migration (P<0.01).@*CONCLUSION@#GA regulated miR-19b-3p/RAF1 axis to mediate ERK pathway and inhibit the development of RA.

Role of Interleukin-36 in inflammatory joint diseases / 浙江大学学报·医学版

Interleukin (IL)-36 is a family of cytokines that belongs to the larger IL-1 superfamily. IL-36 agonist/antagonist binds to the interleukin-36 receptor involving in physiological inflammation regulation and pathogenesis of many inflammatory diseases. In inflammatory joint diseases, the expression of IL-36 changes, and some studies have initially explored the role of IL-36 in these diseases. In psoriatic arthritis, IL-36 signal mediates plasma cell and fibroblast-like synoviocyte crosstalk presenting IL-36 agonist/antagonist imbalance. In rheumatoid arthritis, IL-36 agonists induce fibroblast-like synoviocyte to produce pro-inflammatory factors, while IL-36 antagonist deficiency leads to lesion progression. In osteoarthritis, IL-36 agonists induce chondrocytes to produce catabolic enzymes and pro-inflammatory factors. This article reviews the expression and function of IL-36 in different inflammatory joint diseases to provide a reference for revealing their pathogenic mechanisms and discovering therapeutic targets.

The expression of long non-coding RNA human leukocyte antigen complex P5(lncRNA HCP5) in synovial tissue of patients with rheumatoid arthritis is up-regulated and correlated with immune cell infiltration / 细胞与分子免疫学杂志

Objective To identify the potential long non-coding RNA (lncRNA) expressed in rheumatoid arthritis (RA) synovium key to RA onset and investigate its association with immune cell infiltration. Methods RA synovium data were downloaded from the GEO database and normalized. The lncRNAs key to RA onset were identified using multiple machine learning methods. Infiltration of 22 immune cell populations in RA synovium was measured by cell-type identification by estimating relative subsets of RNA transcripts (CIBER-SORT). The relationship between the key lncRNA and infiltrating immune cells was analyzed. Finally, real-time quantitative PCR was applied to validate the expression of the key lncRNA in RA synovial cells. Results lncRNA human leukocyte antigen complex P5(HCP5) was identified as the key lncRNA associated with RA onset. Infiltration analysis revealed increased abundance of CD8+ T cells, γδ T cells, and M1 macrophages while decreased abundance of M2 macrophages in RA synovial tissue. Correlation analysis demonstrated that the lncRNA HCP5 expression was positively associated with the infiltration abundance of CD8+ T cells, γδ T cells, and M1 macrophages in RA synovial tissue. Furthermore,the expression of lncRNA HCP5 in RA synovial cells was up-regulated. Conclusion lncRNA HCP5 expression is up-regulated in RA synovial tissue and potentially associated with immune cells infiltration.