[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 observe the clinical effects of cognitive behavioral therapy (CBT) combined with pulmonary rehabilitation on the treatment of patients with pneumoconiosis. Methods A total of 108 patients with pneumoconiosis were selected as the research subject using convenient sampling method. They were randomly divided into control group and CBT group, with 54 cases in each group. Patients in the control group were treated with conventional symptomatic treatment and pulmonary rehabilitation treatment for 12 weeks. While patients in the CBT group were treated with CBT treatment in addition to treatments of the control group. The therapeutic effect was analyzed. Results Before treatment, there was no statistical difference on score of Montreal Cognitive Assessment (MoCA), percentage of forced expiratory volume in one second to the predicted value (FEV₁%), forced expiratory volume in one second to force vital capacity ratio (FEV₁/FVC%), score of the Modified Medical Research Council Dyspnea Scale (mMRC), six minute walk distance (6MWD), Hospital Anxiety and Depression Scale (HADS) subscale scores of anxiety (HADS-A) and depression (HADS-D), and scores of Chronic Obstructive Pulmonary Disease Assessment Test (CAT), St. George's Respiratory Questionnaire (SGRQ), and serum levels of leptin, interleukin-6 (IL-6) and C-reactive protein (CRP) between the two groups (all P>0.05). After treatment, the score of MoCA, FEV₁%, FEV₁/FVC% and 6MWD increased (all P<0.05), while the scores of mMRC, HDS-A, HDS-D, CAT and SGRQ decreased (all P<0.05), and the levels of serum leptin, IL-6 and CRP decreased (all P<0.05) in the CBT group compared with the control group. Conclusion The combined treatment of CBT and pulmonary rehabilitation can better improve the cognitive ability, respiratory function, motor function, negative emotion and quality of life, and alleviate inflammatory response in patients with pneumoconiosis. It is of certain clinical application value.

BACKGROUND:Parkinson's disease is a neurodegenerative disease,and its pathogenesis involves mitochondrial dysfunction.Exercise has a potential ameliorative effect on mitochondrial dysfunction related to Parkinson's disease,but there is no comprehensive review and in-depth analysis in this field. OBJECTIVE:To comprehensively review and analyze mitochondrial dysfunction related to Parkinson's disease and the potential ameliorative effect of exercise,thereby providing new ideas and methods for the treatment and prevention of Parkinson's disease. METHODS:We searched the Web of Science,PubMed,CNKI,WanFang,and VIP databases with the keywords of"mitochondria,mitochondrial function,mitochondrial disease,mitochondrial dysfunction,Parkinson's disease,Parkinson,exercise,physical activity,exercise training,exercise therapy,mitochondrial impairment,mitochondrial damage,mitochondrial defects"in Chinese and"mitochondria,Parkinson's disease,Parkinson disease,physical exercise,exercise,physical activity,mitochondrial dysfunction,mitochondrial damage,mitochondrial impairment,athletic training,exercise training,rehabilitation"in English.A total of 89 articles were included for review and analysis. RESLUTS AND CONCLUSION:Parkinson's disease is closely related to mitochondrial dysfunction,including mitochondrial biogenesis inhibition,reduced autophagy,increased apoptosis,abnormal elevation of Ca2+ concentration,and increased oxidative stress in Parkinson's disease patients.Exercise has a positive effect on mitochondrial dysfunction related to Parkinson's disease,by promoting mitochondrial biogenesisand autophagy,regulating mitochondrial morphology,altering the plasticity of the mitochondrial respiratory chain,and reducing oxidative stress,thus helping to improve the development and progression of Parkinson's disease.However,the detailed mechanism between mitochondrial dysfunction and the ameliorative effect of exercise is still not fully understood,and future clinical studies can be conducted to validate the results of animal models and gain insights into the benefits and mechanisms of exercise in patients with Parkinson's disease.

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.

Purpose: From the perspective of positive psychology, our study aimed to explore depressive symptomsand psychological well-being among Chinese nurses, as well as analyze the impacts of characterstrengths, self-efficacy and social support on the mental health of nurses. Methods: A cross-sectional and descriptive design using five self-reported questionnaires was used toinvestigate a cohort of 4238 nurses during 2018. A structural equation modeling analysis was used toverify a hypothetical model linking character strengths, self-efficacy, social support, depressive symptoms,and psychological well-being. Results: The prevalence of depression among this cohort of Chinese nurses was 58.1%. The mean scoresfor caring, inquisitiveness, and self-control were 19.93 (SD = 2.82), 15.94 (SD = 3.00), and 16.34(SD = 2.95), respectively. The hypothesized model was a good fit of the data (x2/df = 1.77, p = .183, rootmean square error of approximation = 0.04, goodness of fit index = 1.00, comparative fit index = 1.00,TuckereLewis index = 1.00). Except for the path from self-control to depression, the other hypotheticalpaths investigated were statistically significant. Conclusion Character strengths were directly and positively associated with psychological well-being.Inquisitiveness was the strongest direct protective factor for depression. In addition, characterstrengths indirectly alleviated depression and increased psychological well-being through mediatingvariables of social support and self-efficacy. This study should alert nurse managers that more attentionshould be paid to the character strengths and mental health of nurses. This study provides evidence forinterventions based on character strengths as a management strategy to support the mental health ofnurses.

Objective:To analyze the clinical course and targeted therapy of pyogenic sterile arthritis, pyoderma gangrenosum, and acne (PAPA) syndrome.Methods:The clinical history of a 6-year-old boy with PAPA syndrome, who was admitted to Hong Kong University Shenzhen Hospital in September 2017, was reviewed. His genetic diagnosis was confirmed by whole exome sequencing. The response to targeted therapy was evaluated by comparing the inflammatory markers (erythrocyte sedimentation rate (ESR) and C reactive protein (CRP) and serum cytokines (interleukin (IL)-1, IL-6 and tumor necrosis factor-α (TNF-α)) before and after biological agents treatment. For literature review, "PAPA syndrome" and"PSTPIP1 gene"were used as keywords to retrieve papers published from January 1997 to December 2019 from Pubmed, Wanfang and CNKI database.Results:The patient was a 6-year-old boy, admitted to the hospital due to recurrent joint swelling and pain for more than 4 years. Before treatment, the CRP (256 mg/L), ESR (105 mm/1 h) and cytokines including serum TNF-α (7.43 ng/L), IL-1 (<5 ng/L), IL-6 (301 ng/L) were significantly elevated. Culture of the joint effusion was negative, but the IL-6 level was above 1 000 ng/L. MRI showed osteomyelitis at the lower end of the right femur. Gene detection found a heterozygous variation of PSTPIP1 gene (c.748G>A, p.E250K). Arthralgia once alleviated after the initiation of tocilizumab and infliximab, but recurred after 1 year of treatment. Thereafter, the anti-IL-1 receptor antagonist (Anakinra) was commenced, followed by a significant improvement of the arthralgia, and a complete remission during the follow-up. Besides, the level of CRP, ESR, serum TNF-α, IL-1 and IL-6 were all decreased to normal on the last followed up in December 2019. Literature review found 29 articles and 87 patients in total. The initial symptoms included those of arthritis ( n=58), pyoderma gangrenosum ( n=33), and acne ( n=24). Among all the cases, 13 genotypes were confirmed, and 47 variations involved amino acid p.E250. Steroid and/or biological agents were used in most patients. Conclusions:PAPA syndrome should be suspected in children with recurrent pyogenic sterile arthritis, and an early diagnosis could be achieved by genetic test. Targeted treatment with biological agent may control the symptoms effectively. Biological agents can control symptoms of this disorder effectively.

Purpose: From the perspective of positive psychology, our study aimed to explore depressive symptomsand psychological well-being among Chinese nurses, as well as analyze the impacts of characterstrengths, self-efficacy and social support on the mental health of nurses. Methods: A cross-sectional and descriptive design using five self-reported questionnaires was used toinvestigate a cohort of 4238 nurses during 2018. A structural equation modeling analysis was used toverify a hypothetical model linking character strengths, self-efficacy, social support, depressive symptoms,and psychological well-being. Results: The prevalence of depression among this cohort of Chinese nurses was 58.1%. The mean scoresfor caring, inquisitiveness, and self-control were 19.93 (SD = 2.82), 15.94 (SD = 3.00), and 16.34(SD = 2.95), respectively. The hypothesized model was a good fit of the data (x2/df = 1.77, p = .183, rootmean square error of approximation = 0.04, goodness of fit index = 1.00, comparative fit index = 1.00,TuckereLewis index = 1.00). Except for the path from self-control to depression, the other hypotheticalpaths investigated were statistically significant. Conclusion Character strengths were directly and positively associated with psychological well-being.Inquisitiveness was the strongest direct protective factor for depression. In addition, characterstrengths indirectly alleviated depression and increased psychological well-being through mediatingvariables of social support and self-efficacy. This study should alert nurse managers that more attentionshould be paid to the character strengths and mental health of nurses. This study provides evidence forinterventions based on character strengths as a management strategy to support the mental health ofnurses.