[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 muscle 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 measurement 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 overlapping syndromes of low muscle mass, especially sarcopenia should be emphasized in patients with RA.
Humans ; Arthritis, Rheumatoid/physiopathology* ; Female ; Male ; Sarcopenia/complications* ; Middle Aged ; Cachexia/diagnosis* ; Malnutrition/etiology* ; Obesity/physiopathology* ; Body Composition ; Syndrome ; Hand Strength ; Adult ; Muscle, Skeletal/physiopathology* ; Surveys and Questionnaires

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.

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.

Objective:To investigate the characteristics of functional limitation and associated factors in patients with rheumatoid arthritis (RA).Methods:Consecutive patients with RA were recruited from August 2015 to June 2019 at Department of Rheumatology, Sun Yat-Sen Memorial Hospital. Demographic and clinical characteristics including age, gender, erythrocyte sedimentation rate (ESR), visual analogue scale (VAS) of pain, clinical disease activity index (CDAI), modified total Sharp score were collected. Physical function was assessed by the Stanford health assessment questionnaire disability index (HAQ-DI).Ordered logistic regression was used to analyze the related factors of HAQ-DI.Results:A total of 643 RA patients were finally recruited including 114 males and 529 females with mean age (49.7±12.9) years. There were 399 (62.1%) patients having different degrees of functional limitation, who were classified as mild (293, 45.6%), moderate (73, 11.4%) and severe (33, 5.1%). The prevalence of functional limitation was positively correlated with age and disease activity. The most restricted activity was walking [43.5% (280/643)], followed by gripping [36.1% (232/643)], reaching [35.5% (228/643)], daily activities [33.4% (215/643)], hygiene [33.0% (212/643)], dressing and grooming [29.7% (191/643)] and arising [29.1% (187/643)], and the last eating [18.4% (118/643)]. Multivariate ordered logistic regression analysis showed that age ( OR=1.019, 95% CI 1.004-1.035),pain VAS ( OR=1.820, 95% CI 1.616-2.050), ESR ( OR=1.009, 95% CI 1.001-1.017), CDAI ( OR=1.080, 95% CI 1.059-1.102) and modified total Sharp score ( OR=1.010, 95% CI 1.004-1.015) were associated factors of functional limitation. Conclusion:The majority RA patients have functional limitation. Age, pain and active disease are independent associated factors. Therefore, target treatment and control of pain should be emphasized in RA patients.

Objective To investigate the diagnostic value of intraductal ultrasonography for the quality of biliary stricture.Methods Data of the patients who had received operation because of biliary stricture after IDUS examination from 2006 to 2010 were collected.IDUS results were compared with those of operation.Results There were 43 cases of malignant strictures and 6 benign strictures in total.The sensitivity,specificity,positive predictive value,negative predictive value and diagnostic accuracy of intraductal uhrasonography for the quality of biliary stricture were 97.7％ ( 42/43 ),83.3％ ( 5/6 ),97.7％ ( 42/43 ),83.3％ (5/6) and 95.9％ (47/49),respectively,which were significantly higher than conventional imaging like ultrasound B,CT and MRCP.Twenty one cases in 32 were diagnosed as malignant biliary stricture with cytological brushing,with the diagnostic accuracy of 65.6％.All cases had been diagnosed by IDUS.Conclusion Intraductal ultrasonography is of high diagnostic value for biliary stricture.However,cytological brushing based on IDUS is of limited diagnostic value for malignant biliary stricture.

Objective To compare curve-tip angiography guide wire (loach guide wire) and ultrasmooth hydrophilic guide wire (zebra guide wire) in selective common bile duct (CBD) cannulation of endoscopic retrograde cholangiopancreatography (ERCP). Methods A total of 196 patients were randomly assigned to loach guide wire group to receive cannulation guided by loach guide wire first ( n = 98 ) and zebra guide wire group to use zebra guide wire first ( n =98). If cannulation was not successful after 10 minutes, a further attempt was made for an additional 10 minutes using the alternative guide wire. If still not successful after 10 minutes, other cannulation accessories would be used. The primary and overall selective cannulation time, success rate, and post-procedure abdominal pain and serum amylase were assessed. Results The primary success rate of selective CBD cannulation was higher in the loach guide wire group (93.9%) than that in zebra guide wire group (86. 7%, P ＜0. 05), while there was no significant difference in cannulation time between 2 groups (P ＞ 0. 05 ). The cannulation success rate after crossover was higher in loach guide wire group (76. 9% ) than that in zebra guide wire group (0. 0%, P ＜0. 05). There was no significant difference in post-procedure serum amylase or occurrence rate of post ERCP pancreatitis between 2 groups (P ＞ 0. 05 ).Conclusion Loach guide wire is superior to zebra guide wire in ERCP selective CBD cannulation, which can replace zebra guide wire in difficult cannulation.

Objective To investigate the pathological features of gastro-esophageal high-grade intraepithelial neoplasia (HGIEN) confirmed by biopsy and to compare the differences of its diagnosis after endoscopic resection. Methods Data of 147 patients with gastro-esophageal HGIEN confirmed by biopsy, who underwent EMR or ESD in recent 4 years were analyzed for the pathological findings of pre- and post- procedures. Results Among 147 cases of HGIEN diagnosed by endoscopic biopsy, 106 lesions were in esophagus and 41 in stomach. After endoscopic resection, intraepithelial neoplasia was confirmed in 97 (66%), and cancer was diagnosed in 50 (34%), of which submucosal layer was involved in 11. There were 34 cases of adenocarcinoma and 16 squamous cell carcinomas, in which 22 cases (44%) were poorly or moderately differentiated. Conclusion More than one third cases of biopsy diagnosed HGIEN are confirmed to be carcinoma after endoscopic resection, which needs active therapeutic measures.