Abstract Background: This study aims to determine the effectiveness of programmed exercise with telerehabilitation at home in patients with obesity and knee osteoarthritis on visual analogue scale scores, body mass index, and Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC). Methods: This research is a pre–post study in patients with obesity and knee osteoarthritis. Research subjects performed a series of exercise programs at home for 28 days. Before the program, there was an initial assessment from a psychologist and a nutritionist. During the program, there was tele-education, telemonitoring, and teleconsultation from doctors. Twenty-six female subjects participated. Results: Visual analogue scale scores decreased statistically significantly every week, until the end of the fourth week, compared with before the intervention (p<0.001). Body mass index and WOMAC scores decreased statistically significantly at the end of the fourth week compared with before the intervention (both p<0.001). Further analysis of all WOMAC components in the intervention group, including pain, stiffness, and physical function, also showed a statistically significant decrease (p<0.001). Conclusion: Programmed exercise as part of telerehabilitation at home has been statistically proven to reduce visual analogue scale scores, body mass index, and WOMAC in patients with obesity and knee osteoarthritis.
Telerehabilitation ; Knee Osteoarthritis ; Obesity ; Body Mass Index ; Visual Analogue Scale ; WOMAC

BACKGROUND

Rheumatoid arthritis (RA) is a systemic autoimmune disease characterized by inflammatory arthritis and extra-articular involvement. Comorbidities are highly prevalent in patients with RA, in particular cardiovascular disease (CVD), which is responsible for over 50% of premature deaths. This study aimed to describe cardiovascular diseases and their risk factors among patients with rheumatoid arthritis in the Philippine General Hospital (PGH).

To describe cardiovascular (CV) diseases and their risk factors among patients with rheumatoid arthritis.

A retrospective descriptive cross-sectional study was done in the University of the Philippines – Philippine General Hospital (UP-PGH) inpatient and outpatient services. The study included patients 18 years old and above diagnosed with RA and fulfills the 1987 American College of Rheumatology or 2010 American College of Rheumatology-European League Against Rheumatism (ACR/EULAR) classification criteria with no overlap features with other autoimmune connective tissue diseases and with complete records of the information required for the study from January 2019-December 2022. The primary outcomes of interest were the prevalence of CV diseases and CV risk factors. Descriptive statistics were used to summarize the data.

There were 123 patients in the study, 93.4% outpatients, and 95.1% females, with a mean age and disease duration of 51.3 and 9.8 years, respectively. Disease activity was moderate in 35% and high in 9.7%, based on disease activity score (DAS 28) or clinical disease activity index (CDAI) scores. Methotrexate (54%) was the most commonly used conventional synthetic disease-modifying antirheumatic drug (csDMARD). Glucocorticoid use was observed in 51.2%. None of the patients were receiving a biologic DMARD. There were 24 (19.5%) patients with CV diseases, namely myocardial infarction, heart failure, and stroke. There were 87 (70%) patients with at least one CV risk factor and 62 (50.4%) with multiple risk factors. The risk factors identified were: dyslipidemia (43.1%), hypertension (40.7%), elevated body mass index (35.7%), and diabetes mellitus (15.4%). There were f ive deaths in the hospitalized patients (4%), one due to a myocardial infarction.

The majority (70%) in our cohort had at least one CV risk factor, 19.5% had an identified CV disease, and one died from a myocardial infarction. Dyslipidemia was the most common CV risk factor. The high proportion of patients with CV disease and CV risk factors highlights the need to add the screening and management of CV diseases and risk factors as a priority among patients with rheumatoid arthritis.

Andrographolide sulfonate (AS) is a sulfonated derivative of andrographolide extracted from Andrographis paniculata (Burm.f.) Nees, and has been approved for several decades in China. The present study aimed to investigate the novel therapeutic application and possible mechanisms of AS in the treatment of rheumatoid arthritis. Results indicated that administration of AS by injection or gavage significantly reduced the paw swelling, improved body weights, and attenuated pathological changes in joints of rats with adjuvant-induced arthritis. Additionally, the levels of tumor necrosis factor-alpha (TNF-α), interleukin-6 (IL-6), and IL-1β in the serum and ankle joints were reduced. Bioinformatics analysis, along with the spleen index and measurements of IL-17 and IL-10 levels, suggested a potential relationship between AS and Th17 cells under arthritic conditions. In vitro, AS was shown to block Th17 cell differentiation, as evidenced by the reduced percentages of CD4⁺ IL-17A⁺ T cells and decreased expression levels of RORγt, IL-17A, IL-17F, IL-21, and IL-22, without affecting the cell viability and apoptosis. This effect was attributed to the limited glycolysis, as indicated by metabolomics analysis, reduced glucose uptake, and pH measurements. Further investigation revealed that AS might bind to hexokinase2 (HK2) to down-regulate the protein levels of HK2 but not glyceraldehyde-3-phosphate dehydrogenase (GAPDH) or pyruvate kinase M2 (PKM2), and overexpression of HK2 reversed the inhibition of AS on Th17 cell differentiation. Furthermore, AS impaired the activation of phosphatidylinositol 3-kinase (PI3K)/protein kinase B (AKT) signals in vivo and in vitro, which was abolished by the addition of lactate. In conclusion, AS significantly improved adjuvant-induced arthritis (AIA) in rats by inhibiting glycolysis-mediated activation of PI3K/AKT to restrain Th17 cell differentiation.
Animals ; Th17 Cells/immunology* ; Diterpenes/pharmacology* ; Arthritis, Rheumatoid/metabolism* ; Proto-Oncogene Proteins c-akt/immunology* ; Glycolysis/drug effects* ; Cell Differentiation/drug effects* ; Phosphatidylinositol 3-Kinases/genetics* ; Rats ; Male ; Rats, Sprague-Dawley ; Humans ; Andrographis paniculata/chemistry* ; Arthritis, Experimental/drug therapy* ; Interleukin-17/immunology* ; Signal Transduction/drug effects*

Arthritis, encompassing osteoarthritis (OA), rheumatoid arthritis (RA), and gouty arthritis (GA), is a prevalent inflammatory disease that significantly impacts quality of life. Natural products (NPs), derived from animals, plants, marine organisms, and microorganisms, have demonstrated beneficial effects in arthritis treatment both domestically and internationally. These natural compounds offer advantages in drug discovery due to their skeletal diversity, structural complexity, and multi-effect, multi-target, and low-toxicity properties compared to conventional small-molecule medicines. However, unclear mechanisms have hindered the development and clinical application of NPs. This review summarizes recent experimental studies from the past decade on natural medicine for arthritis treatment, emphasizing key NPs with therapeutic effects on OA, RA, and GA. It examines the effects and molecular mechanisms of NPs acting on different cells to treat arthritis. Furthermore, this review provides insights into the future prospects of NP research in this field, which is crucial for advancing NP-based arthritis treatments.
Humans ; Biological Products/therapeutic use* ; Animals ; Arthritis, Rheumatoid/drug therapy* ; Arthritis, Gouty/drug therapy* ; Arthritis/drug therapy* ; Osteoarthritis/drug therapy*

Sjögren's syndrome (SS) is an autoimmune disease characterized primarily by oral and periocular dryness. Astragalus-Salvia (AS) and Ophiopogon-Dendrobium (OD) represent two frequently utilized herb pairs in SS treatment. While the combination of AS-OD herb pairs demonstrates clinical efficacy in alleviating SS symptoms, its underlying mechanism remains unclear. This investigation sought to assess the therapeutic effects and elucidate the potential mechanisms of AS-OD in non-obese diabetic (NOD)/Ltj mice with SS. The study utilized NOD/Ltj mice as SS models, administering AS-OD treatment for 10 weeks at doses of 113.1, 226.2, and 339.3 mg·d^-1·20 g^-1. Results demonstrated that AS-OD improved SS symptoms, evidenced by enhanced salivary flow rate, decreased anti-SSA/Ro and anti-SSB/La antibody levels, increased swimming duration, and reduced lactate (LA) and blood urea nitrogen (BUN) levels in NOD/Ltj mice. AS-OD reduced lymphocyte infiltration, enhanced Aquaporin-5 (AQP5) expression in the submandibular gland, decreased inflammatory cytokine levels in the submandibular gland, and reduced the T helper type 17/regulatory T lymphocyte (Th17/Treg) cell ratio in the spleen. Transcriptomic and proteomic analyses indicated AS-OD's involvement in regulating phosphatidylinositol-3-kinase/protein kinase B (PI3K/AKT) and Janus kinase 3/signal transducer and activator of transcription 3 (JAK1/STAT3) pathways, with inhibitory effects validated in both NOD/Ltj mice submandibular gland and A-253 cells. Furthermore, AS-OD enhanced cell viability and reduced A-253 cell apoptosis through the PI3K/AKT pathway. In A-253 cells, AS-OD reduced inflammatory cytokine levels, CXC chemokine ligand 9/10 (CXCL9/10), and T-cell chemotaxis by inhibiting the JAK1/STAT3 pathway. AS-OD mitigates SS by suppressing inflammation and immune responses through the PI3K/AKT and JAK1/STAT3 pathways.
Animals ; STAT3 Transcription Factor/genetics* ; Sjogren's Syndrome/immunology* ; Mice, Inbred NOD ; Proto-Oncogene Proteins c-akt/genetics* ; Phosphatidylinositol 3-Kinases/genetics* ; Mice ; Drugs, Chinese Herbal/administration & dosage* ; Signal Transduction/drug effects* ; Janus Kinase 1/genetics* ; Humans ; Female ; Astragalus Plant/chemistry* ; Male

Introduction: Autoimmune polyendocrine syndrome (APS) type 4 is a clustering of at least 2 or more organ-specific autoimmune diseases in a single patient, which do not fall into other categories of APS, in combination with at least one more endocrine or non-endocrine organs. The multitude of autoimmune comorbidities and their associated treatment may contribute to osteoporosis and fracture. Case Description: A 35-year-old female with bilateral distal femoral pathologic fracture from an inch fall underwent bilateral, minimally invasive plate osteosynthesis. Pathologic fracture from secondary osteoporosis resulted from rheumatoid arthritis, chronic steroid use from rheumatoid arthritis (prednisone 10 mg for 24 months), premature ovarian failure since 20 years old without hormone replacement therapy, and possible Turner syndrome. She had persistently elevated thyroid-stimulating hormone in spite of high levothyroxine (4.25 μg/kg/day) dose; hence, gastric malabsorption from possible atrophic gastritis was likewise considered. Benefits and risks associated with treatment were reviewed to manage the patient holistically. Conclusion APS is a rare complex syndrome which may lead to various complications. Presence of hypogonadism, rheumatoid arthritis, and chronic steroid use further predisposes the development of secondary osteoporosis. Early screening and treatment of osteoporosis would have decreased the risk of development of fracture.
Fractures, Spontaneous ; Primary Ovarian Insufficiency ; Arthritis, Rheumatoid

OBJECTIVE: To carry out genetic testing and clinical phenotypic characterization on a four-generation Chinese pedigree affected with Stickler syndrome type I and explore its genotype-phenotype correlation. METHODS: A child presented at the Second Affiliated Hospital of Guangzhou University of Traditional Chinese Medicine in February 2023 for micrognathia, glossoptosis and cleft palate and his family members were selected as the study subjects. Clinical data were collected from the affected members, and peripheral blood samples were obtained from 17 participants (including 4 patients and 13 asymptomatic individuals). Whole exome sequencing (WES) was carried out. Candidate variant was verified by Sanger sequencing. Genotype-phenotype correlation was analyzed by integrating the sequencing data with evidence from existing literature. This study has bee granted by the Ethics Committee of Guangdong Provincial Hospital of Traditional Chinese Medicine and Guangzhou Women and Children's Medical Center (Ethics No.: 2022-406B00). RESULTS: The four-generation pedigree has comprised 19 members. In addition to the proband, 5 affected individuals had manifested with high myopia, congenital cataracts, and progressive vision loss. Two deceased members reportedly exhibited similar ocular manifestations. Among the four living patients, two had developed retinal detachment, while two others presented with chronic joint pain onset between 35 ~ 40 years of age. One patient required hip replacement surgery at age 42 secondary to femoral head necrosis. The proband, the youngest affected member, exhibited characteristic phenotypes including congenital micrognathia and cleft palate, consistent with Pierre-Robin syndrome. Genetic analysis revealed a heterozygous nonsense mutation in COL2A1 (NM_001844.5: c.2668C>T; p.Gln890Ter) segregating with the disease in all four symptomatic patients. This variant was absent in asymptomatic family members and unaffected controls. While the mutation is listed in ClinVar, no clinical case report has associated it with this phenotypic spectrum. It was not recorded in population databases (gnomAD v4.1.0, 1000 Genomes Project, or ExAC), supporting its potential pathogenicity. CONCLUSION This study has diagnosed a four-generation Chinese pedigree with Stickler syndrome type I attributed to the pathogenic COL2A1 variant c.2668C>T (p.Gln890Ter), which is a rare nonsense mutation associated with ocular predominance and variable skeletal involvement. Notably, this family exhibited marked clinical heterogeneity despite sharing the identical genotype, which highlighted the challenges in phenotype-genotype correlation. The autosomal dominant transmission pattern observed in this pedigree has provided critical insights into COL2A1-related collagenopathies and underscored the necessity of ultrasonographic monitoring for ocular anomalies during prenatal diagnosis. Above findings have advanced our understanding of the pleiotropic effects in type Ⅱ collagen disorders and laid the foundation for precision-based genetic counseling, enabling targeted cascade screening and implementation of tertiary prevention strategies against congenital disabilities for high-risk families.
Adolescent ; Adult ; Child ; Child, Preschool ; Female ; Humans ; Male ; Middle Aged ; Arthritis/genetics* ; Collagen Type II/genetics* ; Connective Tissue Diseases/genetics* ; Exome Sequencing ; Genetic Association Studies ; Genotype ; Hearing Loss, Sensorineural/genetics* ; Mutation ; Pedigree ; Phenotype ; Retinal Detachment/genetics* ; East Asian People/genetics*

OBJECTIVE: To evaluate the differential expression of RNA in blood monocytes in patients with Juvenile idiopathic arthritis (JIA) treated with TNF antagonists (TNFi), and to explore the effect and mechanism of gene expression on the efficacy of JIA. METHODS: A total of 29 children with JIA treated with methotrexate (MTX) and TNFi in Guangzhou Women and Children's Medical Center of Guangzhou Medical University from April 2021 to November 2023 were enrolled. After 6 months, the children were divided into two groups according to the treatment effect, i.e., 13 cases in the ineffective group and 16 cases in the effective group, the peripheral blood of the children was collected, the blood mononuclear cells were isolated for transcriptome sequencing, the differentially expressed genes between the groups were analyzed, the signaling pathways and metabolic pathways related to the efficacy of TNFi were analyzed by GO and KEGG enrichment, and the mechanism related to the efficacy of TNFi was explored. This study was approved by Medical Ethics Committee of the Guangzhou Women and Children's Medical Center of Guangzhou Medical University (Ethics No.: 2023-330B00). RESULTS: There was a statistically significant difference in the gender and age distribution between the two groups of children (P < 0.05), while no statistically significant differences were observed in disease duration, rheumatoid antibody levels, or JIA subtypes (P > 0.05). After sequencing data quality control and comparison of reference genomes, a total of 18 523 protein-coding genes were identified in all children's samples. A total of 705 differentially expressed genes (DEGs) were identified between the effective group and the invalid group through differential analysis, of which 579 were up-regulated in the effective group and 126 in the inactive group. GO function and KEGG pathway enrichment analysis showed that DEG was significantly enriched in 55 GO entries and 32 KEGG metabolic pathways, which were mainly related to IL-1β production and regulation, cytokine production and regulation, cytokine-cytokine receptor interaction, immune response regulation, and Toll-like receptor signaling pathway. CONCLUSION DEG between the effective and ineffective groups of TNFi treatment may be involved in the biological processes such as cytokine production and regulation, cytokine-receptor interaction, and immune response regulation, which will be helpful to predict the efficacy and prognosis of TNFi treatment for JIA.
Humans ; Arthritis, Juvenile/blood* ; Female ; Male ; Child ; Methotrexate/therapeutic use* ; Child, Preschool ; Tumor Necrosis Factor-alpha/antagonists & inhibitors* ; Transcriptome ; Adolescent ; RNA/genetics* ; Signal Transduction ; Gene Expression Profiling

Rheumatoid arthritis (RA) is an autoimmune disease characterized by complex pathogenesis, with its development closely linked to immune dysregulation. Regulatory T cells (Tregs), as specialized immunomodulatory cells, play a pivotal role in negatively regulating immune responses and maintaining autoimmune tolerance. In recent years, extensive research has focused on the relationship between Tregs and RA pathogenesis, with the functional role of CD8⁺ Tregs as a critical area of investigation. This review summarizes the alterations in CD8⁺ Tregs during RA progression and their potential mechanisms of action. By elucidating the diversity of CD8⁺ Treg subsets and their intricate roles in modulating immune responses, this analysis provides novel insights and therapeutic strategies for RA diagnosis and treatment.
Arthritis, Rheumatoid/pathology* ; Humans ; T-Lymphocytes, Regulatory/immunology* ; CD8-Positive T-Lymphocytes/immunology* ; Animals

Objective To explore the expression of coagulation indexes in rheumatoid arthritis (RA) and dry syndrome (pSS) and their relationships with inflammation and immune function. Methods A total of 61 patients with RA who were hospitalized in the Department of Rheumatology of Anhui Provincial Hospital of Traditional Chinese Medicine from March 12 to September 9, 2024 were selected as the RA group. And 61 patients with pSS who were hospitalized in the Department of Rheumatology of the same hospital September 4, 2023, to August 17, 2024, were selected as the pSS group. 61 healthy individuals who underwent routine medical checkups at the Physical Examination Center of Anhui Provincial Hospital of Traditional Chinese Medicine during the same period were included as the control group. Baseline clinical indexes before treatment were collected from patients in each group, including prothrombin time(PT), international normalized ratio(INR), thrombia time(TT), fibrinogen(FBG), activated partial thromboplastin time(APTT), fibrin (ogen) degradation products(FDP) and D-Dimer(D-D). Results The expression levels of PT, FBG, TT, FDP, and D-D in the RA group, the pSS group, and the normal group were significantly different. The expression levels of PT, FBG, FDP, and D-D in the RA group were all higher than those in the pSS group and the control group, respectively. And the expression level of TT in the pSS group was lower than that in control group. ROC curve analysis showed that the AUC of PT was 0.638, the AUC of FBG was 0.899, the AUC of FDP was 0.866, and the AUC of D-D was 0.919 in the RA group compared with the normal group. And the AUC of coagulation indexes for joint diagnosis of RA was higher than that of the indexes detected individually. pSS group had an AUC of PT of 0.618 compared with that of the normal group. The AUC of TT was 0.645, and the AUC of coagulation indexes for the joint diagnosis of pSS was higher than the AUC of each index detected separately. Association rule analysis showed that elevated D-D in RA patients had a significant correlation with elevated hs-CRP, CCP and RF, and elevated FBG had a significant correlation with elevated hs-CRP, ESR, RF and CCP. Elevated D-D in pSS patients had a correlation with elevated hs-CRP and anti-SSA, and elevated INR has correlation with elevated hs-CRP, anti-SSA and anti-SSB. Correlation analysis showed that PT, INR, FBG, FDP, and D-D were positively correlated with CRP and ESR, and TT was negatively correlated with CRP and ESR in the RA group. FBG, FDP, and D-D were positively correlated with CRP and ESR in the pSS group. Moreover, coagulation indexes were positively correlated with immune indexes in RA group and pSS group which were all significant. The results of multiple linear regression analysis showed that FBG was a positive correlate of hs-CRP and ESR in RA patients. For PSS patients, FBG and FDP were positive correlates of hs-CRP. APTT and FBG were positive correlates of ESR. Conclusion Compared with pSS, coagulation indexes (especially PT, FBG, FDP and D-D) are more informative for the early diagnosis of RA and the judgment of the degree of the disease, and can be used as an important predictor for the confirmation of the diagnosis of RA.
Humans ; Female ; Male ; Arthritis, Rheumatoid/diagnosis* ; Middle Aged ; Fibrin Fibrinogen Degradation Products/analysis* ; Blood Coagulation ; Adult ; Fibrinogen/metabolism* ; Partial Thromboplastin Time ; Prothrombin Time ; Aged ; Inflammation/immunology* ; ROC Curve