Objective:To investigate the characteristics of hand dysfunction and its associated factors in patients with rheumatoid arthritis (RA).Methods:A cross-sectional study. Patients with RA were recruited from January 2019 to April 2024 at the Department of Rheumatology and Immunology, Sun Yat-Sen Memorial Hospital, Sun Yat-Sen University. Demographic and clinical data were collected, including age, gender, active smoking, disease duration, time of morning stiffness, rheumatoid factor and anti-cyclic citrullinated peptide antibody, disease activity, radiographic indicators, and hand function assessment. Hand function was assessed by grip strength measures and self-reported items related to hand function in the Stanford Health Assessment Questionnaire. Factors related to hand function were analyzed by logistic regression analyses.Results:A total of 1 079 RA patients were recruited [mean age: (53.0±12.6) years]. Overall, 72.6% (783/1 079) patients experienced a decrease in grip strength, 57.2% (617/1 079) patients experienced a decreased grip strength in both hands, with the average grip strength of the left and right hands decreasing by 16.3% and 14.1%, respectively, compared to normal values; 39.9% (430/1 079) patients had self-reported hand dysfunction. There were 185 (17.1%) older RA patients (age ≥65 years). The proportion of older RA patients with decreased grip strength [89.7% (166/185) vs. 69.0% (617/894)] and degree of decrease in grip strength compared to normal values (left hand:-35.3%±30.6% vs. -12.3%±38.6%; right hand:-32.6%±32.3% vs. -10.3%±42.1%) were significantly higher than that in young patients, and the proportion of older patients with self-reported hand dysfunction was also significantly higher [53.0% (98/185) vs. 37.1% (332/894), all P<0.001]. Multivariate logistic regression analysis showed that pain visual analogue scale ( OR=1.375, 95% CI 1.020-1.854) was independently associated with grip strength decrease in older RA patients, while the 28-joint tender joint count ( OR=1.151, 95% CI 1.063-1.246) and provider global assessment of disease activity ( OR=1.381, 95% CI 1.171-1.628) were associated with self-reported hand dysfunction. Conclusions:Hand dysfunction is common in RA patients, especially among older RA patients, which is related to pain, joint tenderness and provider global assessment of disease activity. This result implies the importance of pain management in RA patients.

Objective:To analyze the clinical features of pachydermoperiostosis (PDP) and improve its diagnostic level.Methods:A retrospective analysis was conducted on the clinical data of four patients with PDP treated at Sun Yat-sen Memorial Hospital, Sun Yat-sen University from 2015 to 2023, including clinical manifestations, laboratory tests, imaging examinations, and genetic testing results.Results:All four patients were male with an average onset age of 15 years old (ranging from 9 to 18 years old). One patient′s uncle had PDP, and another patient′s parents were consanguineous, though neither parent showed signs of PDP. All four patients exhibited clubbing, skin thickening, and acne; three had frontal bossing and deepened nasolabial folds; two showed scalp sulci changes on head MRI, and all had periosteal thickening of the phalanges visible on X-ray. One patient accompanied with hypokalemic nephropathy, and another had gastric ulcer. One patient underwent whole exome sequencing test which revealed a homozygous mutation, SLCO2A1 gene c.1406C>T, leading to a protein change p.Pro469Leu. Computational tools REVEL, SIFT, and Polyphen2 predicted this variant as deleterious.Conclusion:In addition to skin thickening, frontal bossing, scalp sulci changes, clubbing, and periosteal proliferation, patients with PDP may also present with hypokalemic nephropathy and gastric ulcer. The SLCO2A1 gene c.1406C>T mutation may be pathogenic.

Immune-mediated inflammatory diseases(IMIDs)are a broad category of chronic inflammatory disorders caused by abnormal activation of immune system,characterized by an imbalance between excessive release of proinflammatory cytokines and insufficient anti-inflammatory regulatory signals.Interleukin-6(IL-6),a pleiotropic cytokine,serves as a"molecular bridge"connecting innate immunity and adaptive immunity due to its unique"trinity"signaling mechanism(classical signaling,trans-signaling,and trans-presenting pathway).The IL-6 signaling pathway drives acute-phase inflammatory responses and participates in the activation of innate immunity and the regulation of adaptive immunity through multiple mechanisms,which is the key pathway that leads to the inflammatory responses and multi-organ damage of IMIDs.Therapeutic agents targeting the IL-6 pathway,which inhibit aberrant signaling by blocking IL-6/IL-6 receptor/gp130 signaling axis,have been widely used in the clinical practice for treating various IMIDs such as rheumatoid arthritis,juvenile idiopathic arthritis/adult-onset Still's disease,giant cell arteritis,Takayasu's arteritis and Castleman's disease.Currently approved medications in this class include tocilizumab,satralizumab,sarilumab,and siltuximab.However,IL-6 inhibitors also encounter various safety challenges in clinical applications,including increased infection risk,metabolic abnormalities and cardiovascular risks,hypofibrinogenemia,and DRESS syndrome.This review systematically elaborates on the molecular mechanism of the IL-6 signaling pathway and its pathogenic role in IMIDs,the progress in the development of targeted drugs,and the safety issues in clinical applications,aiming to promote the transformation of IL-6 targeted therapy from bench to clinic,provide a"mechanism-guided individualized"framework for optimizing treatment decisions,and point out the direction for the establishment of a long-term safety management system.

Objective:To investigate the characteristics of hand dysfunction and its associated factors in patients with rheumatoid arthritis (RA).Methods:A cross-sectional study. Patients with RA were recruited from January 2019 to April 2024 at the Department of Rheumatology and Immunology, Sun Yat-Sen Memorial Hospital, Sun Yat-Sen University. Demographic and clinical data were collected, including age, gender, active smoking, disease duration, time of morning stiffness, rheumatoid factor and anti-cyclic citrullinated peptide antibody, disease activity, radiographic indicators, and hand function assessment. Hand function was assessed by grip strength measures and self-reported items related to hand function in the Stanford Health Assessment Questionnaire. Factors related to hand function were analyzed by logistic regression analyses.Results:A total of 1 079 RA patients were recruited [mean age: (53.0±12.6) years]. Overall, 72.6% (783/1 079) patients experienced a decrease in grip strength, 57.2% (617/1 079) patients experienced a decreased grip strength in both hands, with the average grip strength of the left and right hands decreasing by 16.3% and 14.1%, respectively, compared to normal values; 39.9% (430/1 079) patients had self-reported hand dysfunction. There were 185 (17.1%) older RA patients (age ≥65 years). The proportion of older RA patients with decreased grip strength [89.7% (166/185) vs. 69.0% (617/894)] and degree of decrease in grip strength compared to normal values (left hand:-35.3%±30.6% vs. -12.3%±38.6%; right hand:-32.6%±32.3% vs. -10.3%±42.1%) were significantly higher than that in young patients, and the proportion of older patients with self-reported hand dysfunction was also significantly higher [53.0% (98/185) vs. 37.1% (332/894), all P<0.001]. Multivariate logistic regression analysis showed that pain visual analogue scale ( OR=1.375, 95% CI 1.020-1.854) was independently associated with grip strength decrease in older RA patients, while the 28-joint tender joint count ( OR=1.151, 95% CI 1.063-1.246) and provider global assessment of disease activity ( OR=1.381, 95% CI 1.171-1.628) were associated with self-reported hand dysfunction. Conclusions:Hand dysfunction is common in RA patients, especially among older RA patients, which is related to pain, joint tenderness and provider global assessment of disease activity. This result implies the importance of pain management in RA patients.

Objective:To analyze the clinical features of pachydermoperiostosis (PDP) and improve its diagnostic level.Methods:A retrospective analysis was conducted on the clinical data of four patients with PDP treated at Sun Yat-sen Memorial Hospital, Sun Yat-sen University from 2015 to 2023, including clinical manifestations, laboratory tests, imaging examinations, and genetic testing results.Results:All four patients were male with an average onset age of 15 years old (ranging from 9 to 18 years old). One patient′s uncle had PDP, and another patient′s parents were consanguineous, though neither parent showed signs of PDP. All four patients exhibited clubbing, skin thickening, and acne; three had frontal bossing and deepened nasolabial folds; two showed scalp sulci changes on head MRI, and all had periosteal thickening of the phalanges visible on X-ray. One patient accompanied with hypokalemic nephropathy, and another had gastric ulcer. One patient underwent whole exome sequencing test which revealed a homozygous mutation, SLCO2A1 gene c.1406C>T, leading to a protein change p.Pro469Leu. Computational tools REVEL, SIFT, and Polyphen2 predicted this variant as deleterious.Conclusion:In addition to skin thickening, frontal bossing, scalp sulci changes, clubbing, and periosteal proliferation, patients with PDP may also present with hypokalemic nephropathy and gastric ulcer. The SLCO2A1 gene c.1406C>T mutation may be pathogenic.

[Objective]To explore the occurrence of gasdermin D(GSDMD)-mediated pyroptosis and its effect on cell proliferation,migration and tubular formation abilities of synovial vascular endothelial cells(VEC)in rheumatoid arthritis(RA).[Methods]Synovium tissues from knee joints of 22 RA patients and 18 orthopaedic arthropathies(Orth.A)patients were collected.The level of activated GSDMD-NT segment in synovium was detected by Western blot.The clinical characteristics of RA patients were compared between high and low synovial GSDMD-NT groups.The cell localization of GSDMD in RA synovium was detected by immunofluorescence staining.RA synovial fluid was added to the culture of human umbilical vein endothelial cells(HUVEC)in vitro,and the level of apoptosis and expression of pyroptosis pathway proteins were detected.The effects of GSDMD on apoptosis,proliferation,migration and tubule formation of HUVEC cells were analyzed.[Results]GSDMD expression in RA synovium was significantly higher than that in Orth.A,and more severe joint destruction and higher microvascular count score were found in RA patients with high GSDMD-NT expression.Synovial VEC had positive expression of GSDMD.Stimulation with RA synovial fluid could induce GSDMD-mediated pyroptosis in HUVEC,increased the secretion of vascular endothelial growth factor(VEGF)and their abilities of proliferation,migration and tubule formation.Knockdown of GSDMD could reverse the above effects.[Conclusion]GSDMD-mediated pyroptosis of partial synovial VEC aggravates RA joint destruction through VEGF secretion that promotes proliferation,migration and angiogenesis of the remaining VEC,which may be a new target to block neovascularization and inhibit joint destruction in RA.

Objective:To investigate the clinical characteristics of overlapping syndromes of low mus-cle mass in Chinese patients with rheumatoid arthritis(RA)and their impact on physical function.Methods:Consecutive patients with RA were recruited from September 2019 to April 2024 at Department of Rheumatology and Immunology,Sun Yat-Sen Memorial Hospital.Clinical data including disease acti-vity,physical function and radiographic assessment were collected.All patients also finished measure-ment of body composition,grip strength,and gait speed,and overlapping syndromes of low muscle mass as well as malnutrition,sarcopenia,sarcopenic obesity,and cachexia were evaluated.The Stanford health assessment questionnaire-disability index(HAQ-DI)was used to evaluate physical function.Logistic regression was used to analyze the related factors of physical dysfunction.Results:A total of 1 016 RA patients were recruited.Their mean age was(52.4±12.5)years,and 82.5％were female.There were 557 cases(54.8％)with overlapping syndromes of low muscle mass and all of them were malnutrition.On this basis,326 cases(32.1％)exhibited sarcopenia,124(12.2％)sarcopenic obesity,and 33(3.2％)cachexia.There were 584(57.4％)of RA patients having physical dysfunction,with varying degrees of severity:421(41.4％)mild,124(12.2％)moderate,and 39(3.8％)severe.Compared with patients without overlapping syndromes of low muscle mass(n=459)or with malnutrition only(n=231),RA patients with both malnutrition and sarcopenia(n=326)had significantly higher core disease activity indicators and higher rate of physical dysfunction(69.6％vs.42.0％vs.56.6％).However,compared with patients without overlapping syndromes of low muscle mass,patients with malnutrition only had lower HAQ-DI score(median 0.0 vs.0.1)and lower rate of physical dysfunction(42.0％vs.56.6％).Multivariate Logistic regression analysis showed that simultaneously overlapping malnutrition and sarcopenia were associated factors of physical dysfunction(OR=2.021,95％CI:1.067-3.828),but malnutrition only was not.Conclusion:Simultaneously overlapping malnutrition and sarcopenia can deteriorate disease activity and physical dysfunction in RA patients.The screening and evaluation of over-lapping syndromes of low muscle mass,especially sarcopenia should be emphasized in patients with RA.

A 58-year-old male patient with angioimmunoblastic T-cell lymphoma developed a rash and skin tightness on the face, limbs, and trunk together with joint stiffness and dysfunction after 6 months of treatment with the programmed cell death protein-1 inhibitor camrelizumab. Laboratory tests revealed progressive eosinophilia over 6 months, with the eosinophil count increasing from 0.07×10 9/L to 3.3×10 9/L. Magnetic resonance imaging showed thickened skin of both forearms, while T 2-weighted imaging showed markedly increased signal intensity within the myofascia. Skin biopsy of the right forearm showed thickened and fibrosed fascia and infiltration of inflammatory cells, including lymphocytes, plasma cells, and eosinophils. The patient was diagnosed with immune checkpoint inhibitor (ICI)-induced eosinophilic fasciitis (EF). After beginning treatment with methylprednisolone (40 mg daily), methotrexate (10 mg/week), and baricitinib (4 mg daily), his symptoms of skin tightness and joint dysfunction significantly improved within 1 month, and his peripheral blood eosinophil count decreased to 0.17×10 9/L. ICI-induced EF is a rare immune-related adverse reaction. To date, only 20 cases have been reported in published foreign literature, and their clinical characteristics are summarized here. The time from ICI treatment to EF was 12 (8,15) months, and the main clinical manifestations included skin involvement ( n=19), joint dysfunction ( n=11), myalgia/muscle weakness ( n=9), and peripheral eosinophilia ( n=16). After treatment, the clinical symptoms of EF improved in 17 patients, and eosinophil counts returned to normal after 3 (1,8) months. EF is a dysfunctional adverse response to ICI therapy. Tumor patients undergoing immunotherapy should be monitored for symptoms of EF. Early treatment is essential for preventing complications.

ObjectiveTo determine the mechanism of Yitangkang in correcting excessive apoptosis of skeletal muscle cells to improve insulin resistance （IR） by inhibiting the advanced glycation end product （AGE）/receptor for the advanced glycation end product （RAGE） signaling pathway. Method① In vitro experiments. Yitangkang-medicated serum was prepared. C2C12 cells were divided into a blank group， a model group， high-， medium-， and low-dose Yitangkang-medicated serum groups （40， 20， and 10 g·kg^-1）， and a RAGE inhibitor group. The IR model was induced by palmitic acid in C2C12 cells except for those in the blank group. After the corresponding intervention methods were conducted，the cell viability and glucose consumption level of each group were determined. In addition，the apoptosis rate was determined using flow cytometry. The mRNA and protein expression levels of the important apoptotic proteins ［B-cell lymphoma 2 （Bcl-2）， Bcl-2-associated X protein （Bax）， p53， cysteinyl aspartate-specific protease-3 （Caspase-3）， and cysteinyl aspartate-specific protease-9 （Caspase-9）］ were determined using Real-time fluorescence quantitative polymerase chain reaction （Real-time PCR） and Western blot. ② In vivo experiments. Ninety-six eligible Wistar rats were divided into a blank group， a model group， high-，medium-，and low-dose Yitangkang groups （40， 20， and 10 g·kg^-1）， and a western medicine group （pioglitazone hydrochloride，1.35 mg·kg^-1）. The IR model was induced using high-glucose and high-fat feed for diabetes combined with intraperitoneal injection of low-dose streptozotocin （STZ） in animals and verified by the hyperinsulinemic-euglycemic clamp （HEC） test. After the model was determined successfully， the rats in each group were given intragastric administration of drugs as required. Terminal deoxynucleotidyl transferase dUTP nick end labeling （TUNEL） assay was performed to determine the number of positive apoptotic cells in the skeletal muscle tissues of rats in each group，while Real-time polymerase chain reaction（Real-time PCR） and Western blot were performed to determine the mRNA and protein expression levels of the important apoptotic proteins Bcl-2， Bax， p53， Caspase-3， and Caspase-9. Result① In vitro experiments. compared with the blank group， the model groups showed increased apoptosis rate of C2C12 cells and decreased cell viability and glucose consumption （P<0.01）. Compared with the model group， the Yitangkang-medicated serum groups and the RAGE inhibitor group showed decreased apoptosis rate of C2C12 cells and increased cell viability and glucose consumption （P<0.01）. Compared with the blank group， the model group showed decreased expression levels of Bcl-2 mRNA and protein in C2C12 cells and increased mRNA and protein expression levels of Bax， p53， Caspase-3， and Caspase-9 （P<0.01）. Compared with the model group， the Yitangkang-medicated serum groups and the RAGE inhibitor group showed increased expression levels of Bcl-2 mRNA and protein in C2C12 cells （P<0.01） and decreased mRNA and protein expression levels of Bax， p53， Caspase-3， and Caspase-9 （P<0.05， P<0.01）. ② In vivo experiments. The number of positive apoptotic cells in the skeletal muscle tissues of rats in the model group significantly increased as compared with that in the blank group （P<0.01）. The number of positive apoptotic cells in the skeletal muscle tissues of rats in the Yitangkang groups and the western medicine group decreased as compared with that in the model group （P<0.01）. Compared with the blank group， the model group showed decreased expression levels of Bcl-2 mRNA and protein in skeletal muscle tissues of rats and increased mRNA and protein expression levels of Bax， p53， Caspase-3， and Caspase-9 （P<0.01）. Compared with the model group， the Yitangkang groups and the western medicine group showed increased expression levels of Bcl-2 mRNA and protein in skeletal muscle tissues of rats （P<0.01） and decreased mRNA and protein expression levels of Bax， p53， Caspase-3， and Caspase-9 （P<0.05， P<0.01）. The medium-dose Yitangkang showed a similar effect as RAGE inhibitor， and the effect was equivalent to that of pioglitazone hydrochloride. ConclusionYitangkang can inhibit skeletal muscle cell apoptosis by inhibiting the AGE/RAGE signaling pathway.

Objective:To investigate the prevalence of hypertension and its associated factors in rheumatoid arthritis (RA) patients.Methods:Consecutive Chinese patients with RA were recruited from August 2015 to September 2019 at Department of Rheumatology, Sun Yat-sen Memorial Hospital. Demo-graphic data and clinical data were collected including indicators of disease activity, functional assessment and radiographic assessment, comorbidities and previous medications. Logistic regression analysis was used to evaluate the related factors of hypertension in RA patients.Results:There were 674 RA patients recruited with 82.3%(555/674) female and mean age (50±13) years. The prevalence rate of hypertension was 32.9% (222/674), followed by dyslipidemia (9.9%, n=67), type 2 diabetes (8.8%, n=59), hyperuricemia (8.5%, n=43), fatty liver disease (8.0%, n=54), cardiovascular disease (6.2%, n=42) and chronic kidney disease (3.3%, n=22). Compared with those without hypertension, RA patients with hypertension had advanced age with longstanding disease duration, higher disease activity indicators, worse joint destruction, and higher proportions of comorbidities. Multivariate logistic regression analysis showed that comorbidities including hyperuricemia [ OR=1.977, 95% CI(1.002, 3.900)], dyslipidemia [ OR=1.903, 95% CI(1.102, 3.288)] and fatty liver disease [ OR=2.335, 95% CI(1.278, 4.265)] were risk factors of hypertension after adjustment for age and gender. Conclusion:Hyperten-sion is the most common comorbidity in RA patients which is associated with comor-bidities including hyperuricemia, dyslipidemia and fatty liver disease. Detection and management of hyperten-sion and other cardiovascular disease related comorbidities in RA patients should be emphasized.