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Adult-onset Still's disease (AOSD) is a rare but clinically well-known auto-inflammatory disorder. Cytokine storm, the hallmark of AOSD, is mediated by neutrophil hyperactivation and enhanced neutrophil extracellular trap (NET) formation. Type I interferons (IFNs), having a primary role in the initiation of proinflammation responses, can induce subsequent inflammatory cytokine production. However, the role of type I IFNs in AOSD is unclear. Indeed, high levels of IFN-α and IFN-ß expression are presented by AOSD patients. In this investigation, hierarchical unsupervised clustering was performed on IFN-α and IFN-ß data to identify a cluster of AOSD patients who had a serious condition. Neutrophils from treatment-naïve active AOSD patients showed very strong enrichment in their IFN-α response, as shown by RNA-seq and confirmed by the IFN score. Whether IFN-α stimulates NET formation was also tested. IFN-α had the ability to form NETs that contained oxidized mitochondrial DNA (ox-mtDNA). Moreover, the JAK inhibitor could be used to dampen type I IFN-induced NET formation and eventually control ox-mtDNA release. Our results demonstrated the important roles of type I IFNs in the pathogenesis of AOSD through their promotion of NET formation, as characterized by the enhanced level of ox-mtDNA. The findings open up new avenues of research into therapeutic approaches for AOSD.
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Armadilhas Extracelulares , Interferon Tipo I , Doença de Still de Início Tardio , Adulto , DNA Mitocondrial/genética , DNA Mitocondrial/metabolismo , Armadilhas Extracelulares/metabolismo , Humanos , Interferon Tipo I/metabolismo , Neutrófilos/metabolismo , Doença de Still de Início Tardio/tratamento farmacológicoRESUMO
OBJECTIVES: Thrombosis occurring in the central nervous system is common in APS patients, leading to neuropsychiatric symptoms. We investigated the prevalence of silent brain abnormalities on MRI in primary APS (PAPS) patients and aPL carriers and assessed the association between the vascular risk factors, aPL profile, clinical manifestations and MRI abnormalities. METHODS: We consecutively included 44 PAPS patients, 24 aPL carriers and 23 healthy controls with comparable age and gender in a single-centre, observational, cross-sectional study. None of the patients had a history of stroke, transient ischaemic attack, migraine, dementia, epilepsy or bipolar disorders. On cerebral MRI, we assessed the imaging features and location of abnormality. Multivariate analysis was performed to identify the risk factors contributing to the MRI abnormalities. RESULTS: A total of 38 (55.88%) patients had abnormal MRI findings, while only one healthy control showed some abnormalities. Lacunes were the most frequent MRI abnormality in the aPL-positive group [31/68 (45.59%)], which were followed by white matter hyperintensities [20/68 (29.41%)]. In the study population, age [odds ratio (OR) 1.086, P = 0.016] and LA positivity (OR 5.191, P = 0.002) were independent associated factors with brain MRI abnormalities. When analysed in only the aPL-positive group, age (OR 1.116, P = 0.007), female gender (OR 7.519, P = 0.025) and thrombocytopenia (OR 8.336, P = 0.047) were the significant independent risk factors with abnormal MRI. CONCLUSIONS: PAPS patients and aPL carriers showed a high prevalence of brain MRI abnormalities, indicating an increased cerebrovascular risk, which emphasized attention to silent cerebral lesions in persistently aPL-positive patients.
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Síndrome Antifosfolipídica , Epilepsia , Anticorpos Antifosfolipídeos , Síndrome Antifosfolipídica/complicações , Estudos Transversais , Feminino , Humanos , Imageamento por Ressonância Magnética , Masculino , PrevalênciaRESUMO
OBJECTIVE: Anti-ß-2 glycoprotein I (anti-ß2GPI) antibodies, defined as primary pathogenic antibody in antiphospholipid syndrome (APS). It has been reported that IgG Fc N-glycosylation affects IgG effector, we aim to investigate the association of Fc glycosylation profiles of purified anti-ß2GP1 IgG with clinical features of APS. METHODS: We purify anti-ß2GPI IgG and total IgG from 82 APS patients including nine catastrophic antiphospholipid syndrome (CAPS) patients, as well as total IgG from 103 healthy controls to quantitatively analyse all detectable Fc N-glycanforms of all IgG subclasses with Multiple Reaction Monitoring (MRM) method based on UPLC-ESI-QqQ mass spectrometry. RESULTS: Both purified anti-ß2GPI IgG and APS total IgG showed altered N-glycan profiles when compared with healthy control (HC) IgG. Anti-ß2GPI IgG presented with lower galactosylation, increased bisection and core fucosylation compared with APS total IgG and HC IgG. We found higher galactosylation of aß2GPI IgG2 in thrombotic APS compared with the obstetric APS, and lower galactosylation of aß2GPI IgG2 associated with late pregnancy morbidity. Moreover, low galactosylation of all anti-ß2GPI IgG subclasses, increased bisection and core fucosylation of anti-ß2GPI IgG1/2 were strongly associated with CAPS and triple positivity of antiphospholipid antibodies (aPLs). CONCLUSION: We comprehensively characterize the N-Glycans landscape of both anti-ß2GP1 and total IgG in APS. Altered N-glycan profiles of anti-ß2GPI IgG enables enabled the antibodies with proinflammatory properties. Furthermore, we associated levels of IgG Fc-glycosylation with clinical features antiphospholipid syndrome. These findings could increase our understanding of anti-ß2GPI antibody mediated mechanisms in APS and be used to develop diagnostics and new target treatments.
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Anticorpos Antifosfolipídeos/imunologia , Síndrome Antifosfolipídica/imunologia , Imunoglobulina G/imunologia , Complicações na Gravidez/imunologia , Trombose/imunologia , beta 2-Glicoproteína I/imunologia , Feminino , Humanos , GravidezRESUMO
In view of the possible involvement of vascular endothelial growth factor-C (VEGF-C) in pathogenesis of adult-onset Still's disease (AOSD) based on our previous genome-wide association study (GWAS) results, the primary objective of this study, therefore, was to investigate the correlations between the content of VEGF-C in serum and clinical and biochemical markers of AOSD. Blood samples were collected from 80 patients with AOSD, 26 with rheumatoid arthritis (RA), 30 with systemic lupus erythematosus (SLE) and 31 healthy control subjects. The serum VEGF-C levels were determined using an enzyme-linked immunosorbent assay (ELISA). Statistical analysis and comparisons were conducted. A significantly higher serum VEGF-C level was observed in patients with AOSD than in HC. Serum VEGF-C levels had high AUC value of 0.8145 for distinguishing AOSD group from healthy group with sensitivity of 0.7097 and specificity of 0.8250. It also showed good diagnostic value to differentiate AOSD from other autoinflammatory diseases with sensitivity of 0.7500 and specificity of 0.5500. AOSD patients with fever, arthralgia, skin rash, sore throat, lymphadenopathy, splenomegaly hepatomegaly and pleuritis, had a higher level than those who did not have these symptoms (p = 0.0012, p = 0.0092, p = 0.0056, p = 0.0123, p = 0.0068, p = 0.0030, p = 0.0020, and p = 0.0018, respectively). The serum VEGF-C levels were also positively correlated with laboratory features and several cytokines related to AOSD disease activity. In conclusion, our study unveiled a close association between serum VEGF-C levels and AOSD including disease activity and clinical hematological manifestations, suggesting the potential utility of VEGF-C as a candidate biomarker to assess disease activity in AOSD.
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Doença de Still de Início Tardio/sangue , Fator C de Crescimento do Endotélio Vascular/sangue , Adulto , Biomarcadores/sangue , Estudos de Casos e Controles , Progressão da Doença , Feminino , Estudo de Associação Genômica Ampla , Humanos , Masculino , Pessoa de Meia-IdadeRESUMO
OBJECTIVES: To describe the detailed characteristics and explore the potential risk factors of relapses in patients with adult-onset Still's disease (AOSD). METHODS: We enrolled patients with AOSD admitted to the Department of Rheumatology and Immunology, Ruijin Hospital from August 2016 to September 2019. Kaplan-Meier curves and the log rank test were used to estimate the cumulative relapse probability and persistent remission rate before the first occurrence of relapse. The multivariate Cox proportional hazard method was utilized to identify risk factors associated with relapses of AOSD. RESULTS: A total of 122 patients with AOSD were enrolled with a median follow-up of 12.6 months. Among them, 26 (21.3%) patients had at least one relapse. The cumulative relapse rates of AOSD patients were 14.42%, 21.79%, 24.81% and 28.57% at 6, 12, 18 and 36 months, respectively. According to the multivariate analysis, intensive treatment (odds ratio: 6.848; 95% CI: 2.441, 19.211) and macrophage activation syndrome (odds ratio: 4.020, 95% CI: 1.564, 10.322) were associated with increased risk of relapse. CONCLUSION: Our study indicated that relapses occurred in at least one-fifth of patients with AOSD, and patients with high disease severity at initial attack may have an increased risk of relapse, which needs more intensive therapy and close follow-up.
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Índice de Gravidade de Doença , Doença de Still de Início Tardio/patologia , Adolescente , Adulto , Idoso , Feminino , Humanos , Estudos Longitudinais , Masculino , Pessoa de Meia-Idade , Análise Multivariada , Modelos de Riscos Proporcionais , Estudos Prospectivos , Recidiva , Estudos Retrospectivos , Fatores de Risco , Adulto JovemRESUMO
OBJECTIVE: Liver damage is a common manifestation and can be life-threatening in adult-onset Still's disease (AOSD), an autoinflammatory disease. The hallmark of AOSD is activation of neutrophils, whose infiltration in liver is suspected to promote tissue injury. Here we aimed to identify a candidate biomarker and to validate its association with liver damage in AOSD. METHODS: Transcriptome analysis of neutrophils from treatment-naïve active AOSD patients and healthy donors was performed. Lipocalin-2 (LCN2) expression was assessed in neutrophils, plasma and liver biopsies of AOSD. The correlations of LCN2 with different variables and its ability to identify liver damage from AOSD patients were analysed. RESULTS: LCN2, a novel biomarker in hepatic inflammation, was found to be upregulated in AOSD neutrophils by RNA sequencing and confirmed at the mRNA and protein levels. Plasma levels of LCN2 were significantly higher in AOSD patients than healthy controls, RA and SLE patients. Plasma LCN2 levels were closely correlated with inflammatory markers, systemic score, HScore and cytokines. Moreover, LCN2 levels were increased in active AOSD with liver involvement and independently associated with liver dysfunction. Enhanced expression of LCN2 was detected in liver biopsies from three patients with ongoing liver injury. Furthermore, the area under the curve value of LCN2 for identifying AOSD with liver injury from other liver diseases was 0.9694. CONCLUSION: Our results reveal that neutrophils-derived LCN2 is higher in plasma and liver tissue in AOSD patients than in healthy controls, and it could serve as a potent biomarker for identifying AOSD with systemic inflammation, especially liver damage caused by hyperinflammation.
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Lipocalina-2/metabolismo , Fígado/metabolismo , Doença de Still de Início Tardio/metabolismo , Adulto , Biomarcadores/metabolismo , Feminino , Humanos , Inflamação/metabolismo , Inflamação/patologia , Lipocalina-2/sangue , Fígado/patologia , Masculino , Pessoa de Meia-Idade , Neutrófilos/metabolismo , Índice de Gravidade de Doença , Doença de Still de Início Tardio/sangue , Doença de Still de Início Tardio/diagnóstico , Doença de Still de Início Tardio/patologiaRESUMO
OBJECTIVES: Triggering receptor expressed on myeloid cells-1 (TREM-1) is an amplifier of inflammatory signals. Recently, a soluble form of TREM-1 (sTREM-1) was described. This study aimed to investigate the role of serum sTREM-1 in patients with adult-onset Still's disease (AOSD). METHODS: Serum sTREM-1 levels were detected in 108 AOSD patients, 88 RA patients and 112 healthy controls (HC). The correlations of sTREM-1 with disease activity, clinical characteristics and laboratory parameters in AOSD patients were analysed by the Spearman correlation test. Risk factors for the chronic course of AOSD were evaluated by multivariate logistic regression analysis. RESULTS: AOSD patients had significantly higher serum sTREM-1 levels than RA patients and HC, and serum sTREM-1 levels were correlated with the systemic score, ferritin, leucocyte count, CRP, IL-1ß and IL-6. The elevation in the initial sTREM-1 level by itself could discriminate patients developing the chronic course from patients developing the nonchronic course. Moreover, an elevated sTREM-1 level (> 526.4475 pg/ml) was an independent risk factor for the chronic course in active AOSD patients. Furthermore, interfering with TREM-1 engagement led to reductions in the secretion of pro-inflammatory cytokines, such as IL-1ß, IL-6 and TNF-α, in neutrophils and monocytes from active AOSD patients. CONCLUSION: Serum sTREM-1 levels are correlated with disease activity, and an elevation in the initial serum sTREM-1 level is a potential predictor of the chronic course in AOSD patients, which currently provides the best predictive model for identifying patients prone to developing the chronic course of AOSD.
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Artrite Reumatoide/sangue , Doença de Still de Início Tardio/sangue , Receptor Gatilho 1 Expresso em Células Mieloides/sangue , Biomarcadores/sangue , Proteína C-Reativa/análise , Estudos de Casos e Controles , Doença Crônica , Síndrome da Liberação de Citocina/complicações , Ferritinas/sangue , Humanos , Interleucina-1beta/sangue , Interleucina-6/sangue , Contagem de Leucócitos , Análise de Regressão , Fatores de Risco , Fator de Necrose Tumoral alfa/sangueAssuntos
Inibidores de Janus Quinases/uso terapêutico , Piperidinas/uso terapêutico , Pirimidinas/uso terapêutico , Pirróis/uso terapêutico , Doença de Still de Início Tardio/tratamento farmacológico , Adolescente , Adulto , Idoso , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , RetratamentoRESUMO
This study was aimed to evaluate the relationship between the changes of plasma intermedin (IMD) and atrial fibrosis in hypertensive patients with atrial fibrillation. During the period from 2010 to 2011, appropriate 150 subjects of out-patients (female 50%, male 50%) were selected in West China Hospital, Sichuan University, and were divided into three groups: the hypertension-only group, the hypertension combined with paroxysmal atrial fibrillation group and the hypertension combined with persistent atrial fibrillation group. Firstly, we collected the Physical examination results and medical history records of the patients. We then performed ultrasound cardiogram and blood biochemical tests on the patients. We also detected the plasma IMD and transforming growth factor ß1 (TGF-ß1) using ELISA. The results showed that compared with the hypertensive group, the plasma level of IMD, TGF-ß1 and left atrium director (LAD) in the hypertensive combined with atrial fibrillation group were higher significantly. Compared with the paroxymal atrial fibrillation group, the levels of IMD, TGF-ß1 and LAD were higher significantly in persistent atrial fibrillation group. Analysis of correlation and partial correlation showed that IMD was positively correlated with TGF-p1 (r=0.51, P<0. 001), IMD was positively correlated with LAD(r=0.59, P< 0.001), and TGF-ß1 was positively correlated with LAD (r = 0.57, P < 0.001). The results suggest that IMD might suppress the pathophysiological process of atrial fibrillation.
Assuntos
Fibrilação Atrial/fisiopatologia , Hipertensão/fisiopatologia , Hormônios Peptídicos/sangue , Feminino , Humanos , Masculino , Fator de Crescimento Transformador beta1/sangueRESUMO
BACKGROUND: To investigate the potential utility of quantitative parameters obtained by 18F-fibroblast activation protein inhibitor positron emission tomography/computed tomography ([18F]AlF-NOTA-FAPI-04 PET/CT) in the assessment of organ involvement and disease activity in IgG4-related disease (IgG4-RD). METHODS: This study enrolled patients who underwent [18F]AlF-NOTA-FAPI-04 PET/CT scans at the Department of Rheumatology, The First Affiliated Hospital, Zhejiang University School of Medicine from August 2021 to August 2022. The PET/CT images of the included patients were re-evaluated by PET center technicians, and the maximal standardized uptake value (SUVmax), metabolic lesion volume (MLV), and total lesion FAPI (TL-FAPI) were used to evaluate the involved organs and tissues that abnormally accumulated [18F]AlF-NOTA-FAPI-04. The clinical and laboratory data of patients are also systematically collected and analyzed. RESULTS: Among the patients included in this study, 12 patients met the IgG4-RD classification criteria established by the American College of Rheumatology in 2019. Among them, 8 were males and 4 were females, with an average age of 59.3 ± 11.5 years. 50% of IgG4-RD patients were found with more organ involvement on PET/CT than physical examination, ultrasonography, and computed tomography. IgG4 levels (Rho = 0.594, p = 0.042) and IgG4-RI (Rho = 0.647, p = 0.023) were significantly positively correlated with TL-FAPI. After linear regression analysis, only TL-FAPI showed a predictive value of RI (R2 = 0.356, B = 0.008, p = 0.041). CONCLUSIONS: [18F]AlF-NOTA-FAPI-04 PET/CT is a useful tool for identifying asymptomatic organ involvement and assessing disease activity. The TL-FAPI as an indicator was positively correlated with IgG4-RD disease activity.
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Geological hazards, especially landslides and mudslides, are frequent in Caoke County, Sichuan Province, China. In September 2022, the mechanical parameters of the soil were obtained through a basic investigation of the landslide characteristics of Ni changgou. Upon that, the finite element-discrete element method was used to reconstruct the three-dimensional numerical model of the landslide on the right bank of Ni changgou, and the initiation mechanism of rainfall on landslide and the formation of debris flow impact dam process were simulated. Furthermore, the pore pressure, stability coefficient as well as displacement of the landslide body were analyzed. It turned out that with the increase of rainfall intensity, the pore water pressure value also increases, where pore water pressure rises rapidly. the slope is close to the unstable edge, Eventually, it tends to one under rainfall conditions, and due to gravity, the slide of the landslide is induced. The duration of landslide movement is about 200 s, the maximum average velocity of the landslide reaches 4.85 m/s, and the average movement distance is close to 500 m. In addition, this method is applied to the Chutougou debris flow, and the corresponding hazard analysis is added which could better show the treatment and application of debris flow in actual engineering.
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BACKGROUND: Drug-induced delirium is known risk factors associated with increased morbidity and mortality in older patients. The objective was to evaluate the risk of drug-related delirium in older patients based on the FDA Adverse Event Reporting System (FAERS). RESEARCH DESIGN AND METHODS: Delirium reports in older patients (age ≥65) extracted from the FAERS database using Open Vigil 2.1. The reported odds ratio and the proportional reported ratio were calculated to detect the adverse reaction signal of delirium. Combined with published evidence, suspected drugs were categorized as known, possible, or new potential delirium-risk-increasing drugs. RESULTS: Of the 130,885 reports (including 28,850 delirium events and 1,857 drugs) analyzed for this study, 314 positive signal drugs were detected. Positive signal drugs are mainly concentrated on the drug of nervous system, cardiovascular system , alimentary tract and metabolism and anti-infectives for systemic use. Of the positive signal drugs, 26.11% (82/314) were known delirium-risk increasing drugs, 44.90% (141/314) were possible and 28.98% (91/314) were new potential. CONCLUSION: Drug-induced delirium risk is prevalent in older patients, according to the FAERS. The risk level of drug-induced delirium should be taken into account to optimize drug therapy in clinical practice.
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OBJECTIVES: This study aimed at identifying clinical and laboratory risk factors for myocardial involvement (MI) in idiopathic inflammatory myopathies (IIMs) patients as well as constructing a risk-predicted nomogram for prediction and early identification of MI. METHODS: An IIMs cohort in southeastern China was constructed, including 504 adult IIMs patients who met the inclusion and exclusion criteria, and were hospitalized at four divisions of the First Affiliated Hospital, Zhejiang University School of Medicine from January 1st 2018 to April 30st 2022. After dividing patients into the training cohort and the validation cohort, risk factors for MI were identified through least absolute shrinkage and selection operator regression and multivariate logistic regression. A risk-predicted nomogram was established and validated internally and externally for discrimination, calibration and practicability. RESULTS: In this cohort, 17.7% of patients developed MI and the survival was significantly inferior to that of IIMs patients without MI (P < 0.001). In the training cohort, age > 55 years old (P < 0.001), disease activity > 10 points (P < 0.001), interleukin-17A (IL-17A) > 7.5 pg/ml (P < 0.001), lactic dehydrogenase (LDH) > 425 U/L (P < 0.001), anti-mitochondrial antibodies (AMAs, P = 0.017), and anti-MDA5 antibody (P = 0.037) were significantly correlated with development of MI. A nomogram was established by including the above values to predict MI and was found efficient in discrimination, calibration, and practicability through internal and external validation. CONCLUSION: This study developed and validated a nomogram model to predict the risk of MI in adult IIMs patients, which can benefit the prediction and early identification of MI as well as timely intervention in these patients.
Assuntos
Miosite , Nomogramas , Humanos , Pessoa de Meia-Idade , Masculino , Feminino , Adulto , Miosite/diagnóstico , China , Fatores de Risco , Infarto do Miocárdio/diagnóstico , L-Lactato Desidrogenase/sangue , Modelos Logísticos , Idoso , Interleucina-17RESUMO
AIMS: The aim of this study was to evaluate the prevalence of PBK/TOPK (PDZ-binding kinase/T-LAK cell-originated protein kinase) expression, and explore the prognostic significance of PBK/TOPK expression alone and in combination with Ki67 and p53 expression in non-small-cell lung cancer (NSCLC). METHODS AND RESULTS: We detected PBK/TOPK expression in 30 samples of normal lung tissue, 32 lymph node metastases and 279 primary non-small-cell lung cancers by immunohistochemistry, and analysed the correlation of PBK/TOPK expression with Ki67 and p53 expression in primary tumour tissues. The results showed that PBK/TOPK expression was higher in lymph node metastases (75%) than in primary tumours (44.8%) and normal lung tissues (0%). PBK/TOPK expression was associated with histological type, lymph node metastasis, and TNM stage, and was positively correlated with Ki67 and p53 expression in NSCLC. Univariate and multivariate survival analyses showed that PBK/TOPK expression was significantly associated with an unfavourable prognosis in NSCLC. The prognosis of patients with tumours positive for both PBK/TOPK expression and Ki67 or p53 expression was also significantly unfavourable. CONCLUSIONS: PBK/TOPK expression is positively correlated with Ki67 and p53 expression, and can be used as an independent prognostic factor in NSCLC.
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Carcinoma Pulmonar de Células não Pequenas/metabolismo , Neoplasias Pulmonares/metabolismo , Pulmão/metabolismo , Quinases de Proteína Quinase Ativadas por Mitógeno/metabolismo , Adulto , Idoso , Biomarcadores Tumorais/metabolismo , Carcinoma Pulmonar de Células não Pequenas/patologia , Feminino , Humanos , Antígeno Ki-67/metabolismo , Pulmão/patologia , Neoplasias Pulmonares/patologia , Masculino , Pessoa de Meia-Idade , Estadiamento de Neoplasias , Prognóstico , Proteína Supressora de Tumor p53/metabolismoRESUMO
OBJECTIVE: To determine the mRNA expressions of PPARalpha and PPARbeta in peripheral blood mononuclear cells of non-vavular hypertensive atrial fibrillation (AF) patients and elucidate its possible role in the pathogenesis of AF. METHODS: Peripheral blood samples were collected from 103 patients with hypertensive AF (persistent AF: 55, paroxysmal AF: 48) and 50 age-adjusted hypertension patients without AF. The mRNA expressions of PPARalpha, PPARbeta, interleukin-6 (IL-6), and tumor necrosis factor-alpha (TNF-alpha) in monocytes were detected by using a Real time polymerase chain reaction. The concentrations of high sensitive C-reactive protein (CRP) and interleukin-1 (IL-1) were measured by immunoenzymetric method. RESULTS: The PPARalpha mRNA expression level was persistently decreased in hypertensive non-AF group, paroxysmal AF group, and persistent AF group (1.34 +/- 0.17, 1.09 +/- 0.23, 0.85 +/- 0.22), while the difference was statistically significant (P < 0.001; respectively). TNF-alpha mRNA, IL-6 mRNA,CRP and IL-1 persistently increased in hypertensive non-AF group, paroxysmal AF group, persistent AF group, also the difference was statistically significant (P < 0. 001; respectively). The difference of PPARbeta mRNA was not statistically significant between non-AF group, paroxysmal AF group and persistent AF group. Left atrial diameter (LAD) was in positive correlation with CRP, IL-1, IL-6 mRNA and TNF-alpha mRNA (P < 0.05). PPARalpha mRNA level was in negative correlation with CRP, IL-1, IL-6 mRNA and TNF-alpha mRNA, the correlation coefficient was -0.519, -0.532, -0.491 and -0.528, respectively (P < 0.05). CONCLUSION: In hypertensive patients with AF, increased inflammatory cytokines were associated with atrial remodeling and lead to the development of atrial fibrillation; PPARalpha was negatively correlated with these inflammatory cytokines and may play a vital role in the process of atrial fibrillation development.
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Fibrilação Atrial/sangue , Hipertensão/complicações , Leucócitos Mononucleares/metabolismo , PPAR alfa/sangue , PPAR beta/sangue , Idoso , Fibrilação Atrial/etiologia , Proteína C-Reativa/genética , Proteína C-Reativa/metabolismo , Feminino , Humanos , Hipertensão/sangue , Interleucina-6/genética , Interleucina-6/metabolismo , Masculino , Pessoa de Meia-Idade , PPAR alfa/genética , PPAR beta/genética , RNA Mensageiro/sangue , RNA Mensageiro/genética , Fator de Necrose Tumoral alfa/genética , Fator de Necrose Tumoral alfa/metabolismoRESUMO
Background: Adult-onset still's disease (AOSD) and lymphoma are the common causes of fever of unknown origin (FUO) and show some similar clinical symptoms. This study aimed to establish a reliable and easy-to-used scoring model based on clinical information, laboratory characteristics and 18F-fluorodeoxyglucose positron emission tomography/computer tomography (18F-FDG PET/CT) images for the differential diagnosis of these two diseases. Methods: A development cohort including 70 AOSD and 37 lymphoma patients was used to establish a scoring model based on the features of PET/CT images. The scoring model was then validated in a validation cohort of 15 AOSD and 12 lymphoma patients. The features of involved bone marrow, spleen, lymph nodes, and other organs or tissues displayed on PET/CT images were compared. Multiple logistics regression and decision tree analysis were used to establish the scoring model. Results: Four features that could significantly differentiate these two diseases were selected to establish a scoring model discriminating AOSD from lymphoma, including (I) white blood cell (WBC) count ≤10×109/L (1 point); (II) ferritin ≤ upper limit of normal (ULN) (1 point); (III) no abnormal bone marrow metabolism (1 point); (IV) total lesion glycolysistotal (TLGtotal) >9.0 (1 point). After decision tree analysis, it showed that a score ≤1 indicates AOSD. A score ≥3 strongly suggested lymphoma, with a sensitivity of 81.1% and specificity of 90.0% in the development cohort, and a sensitivity of 58.3% and specificity of 100% in the validation cohort. Conclusions: Our scoring model showed good diagnosis performance in distinguishing AOSD from lymphoma.
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OBJECTIVES: To compare the ability of the modified Systemic Manifestation Score (mSMS) and the mPouchot score to distinguish adult-onset Still's disease (AOSD) with high disease severity in a large cohort. METHODS: We scored the disease severity of 174 patients and categorized them into high and low disease severity states. The correlation of mSMS and mPouchot score with ESR, CRP, ferritin, liver function tests, and serum cytokines was investigated. Receiver operator characteristic (ROC) curve and logistic regression analysis were performed to compare the ability of mSMS and mPouchot to distinguish patients with severe AOSD. RESULTS: Both mSMS and mPouchot score were positively correlated with ESR (both P < 0.001), CRP (both P < 0.0001), and serum ferritin (both P < 0.0001). Moreover, both mSMS and mPouchot score are significantly associated with liver dysfunction and high IL-18 (both P < 0.0001) and IL-6 (both P < 0.01) levels in AOSD patients. Furthermore, the area under curve (AUC) value of mSMS was significantly less than of mPouchot score (0.71 for mSMS, 0.81 for mPouchot score, P < 0.0001). Compared with mPouchot score, mSMS had higher sensitivity (75.64% vs 74.36%) and lower specificity (55.06% vs 76.40%). And mSMS had a worse performance in assessing high disease severity than mPouchot score in logistic analysis. CONCLUSION: Both scores are proven as effective to assess disease severity of AOSD. By contrast, mSMS perform worse in assessing high disease severity of AOSD patients than mPouchot score. Key Points ⢠Both modified Systemic Manifestation Score (mSMS) and modified Pouchot score (mPouchot score) positively correlated with ESR, CRP, and serum ferritin of AOSD patients. ⢠Both scores are significantly associated with impaired liver function and high serum cytokine levels. ⢠mSMS had lower discriminative ability than mPouchot score to distinguish high disease severity of AOSD patients.
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Artrite Juvenil , Doença de Still de Início Tardio , Adulto , Humanos , Doença de Still de Início Tardio/complicações , Doença de Still de Início Tardio/diagnóstico , Citocinas , Ferritinas , BiomarcadoresRESUMO
Hyperferritinemic syndrome, an overwhelming inflammatory condition, is characterized by high ferritin levels, systemic inflammation and multi-organ dysfunction, but the pathogenic role of ferritin remains largely unknown. Here we show in an animal model that ferritin administration leads to systemic and hepatic inflammation characterized by excessive neutrophil leukocyte infiltration and neutrophil extracellular trap (NET) formation in the liver tissue. Ferritin-induced NET formation depends on the expression of peptidylarginine deiminase 4 and neutrophil elastase and on reactive oxygen species production. Mechanistically, ferritin exposure increases both overall and cell surface expression of Msr1 on neutrophil leukocytes, and also acts as ligand to Msr1 to trigger the NET formation pathway. Depletion of neutrophil leukocytes or ablation of Msr1 protect mice from tissue damage and the hyperinflammatory response, which further confirms the role of Msr1 as ferritin receptor. The relevance of the animal model is underscored by the observation that enhanced NET formation, increased Msr1 expression and signalling on neutrophil leukocytes are also characteristic to adult-onset Still's disease (AOSD), a typical hyperferritinemic syndrome. Collectively, our findings demonstrate an essential role of ferritin in NET-mediated cytokine storm, and suggest that targeting NETs or Msr1 may benefit AOSD patients.
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Armadilhas Extracelulares , Doença de Still de Início Tardio , Camundongos , Animais , Doença de Still de Início Tardio/metabolismo , Armadilhas Extracelulares/metabolismo , Síndrome da Liberação de Citocina , Ferritinas/metabolismo , Inflamação/metabolismo , Receptores Depuradores Classe A/metabolismoRESUMO
Gout is a common form of inflammatory arthritis where urate crystals deposit in joints and surrounding tissues. With the high prevalence of gout, the standardized and effective treatment of gout is very important, but the long-term treatment effect of gout is not satisfied because of the poor adherence in patients to the medicines. Recently, advanced imaging modalities, including ultrasonography (US), dual-energy computed tomography (DECT), and magnetic resonance imaging (MRI), attracted more and more attention for their role on gout as intuitive and non-invasive tools for early gout diagnosis and evaluation of therapeutic effect. This review summarized the role of US, DECT, and MRI in the management of gout from four perspectives: hyperuricemia, gout attacks, chronic gout, and gout complications described the scoring systems currently used to quantify disease severity and discussed the challenges and limitations of using these imaging tools to assess response to the gout treatment.
Assuntos
Diagnóstico por Imagem/métodos , Gota/diagnóstico por imagem , Biomarcadores , Diagnóstico por Imagem/normas , Gerenciamento Clínico , Suscetibilidade a Doenças , Gota/etiologia , Gota/metabolismo , Gota/terapia , Humanos , Hiperuricemia/complicações , Hiperuricemia/metabolismo , Imageamento por Ressonância Magnética , Imagem Multimodal/métodos , Imagem Multimodal/normas , Prognóstico , Tomografia Computadorizada por Raios X , Ultrassonografia , Ácido Úrico/sangue , Ácido Úrico/metabolismoRESUMO
BACKGROUND: To investigate the potential utility of quantitative parameters obtained by 18F-fluorodeoxyglucose positron emission tomography/computed tomography (18F-FDG PET/CT) in the assessment of disease severity and the occurrence of macrophage activation syndrome (MAS) in adult-onset Still's disease (AOSD). METHODS: Fifty-seven patients with AOSD who underwent pre-treatment 18F-FDG PET/CT were recruited in this study and compared with 60 age- and sex-matched healthy controls. Clinical features and laboratory data were recorded. The systemic score was assessed to determine the disease severity. The maximal standardized uptake value (SUVmax), metabolic lesion volume (MLV), and total lesion glycolysis (TLG) were used to evaluate the involved organs and tissues that abnormally accumulated 18F-FDG. Multivariate analysis was performed to identify the PET/CT-derived risk factors contributing to the AOSD-related MAS, and their diagnostic efficiency was evaluated. RESULTS: High 18F-FDG accumulation was observed in the bone marrow (SUVmax median, 5.10), spleen (SUVmax median, 3.70), and lymph nodes (LNs, SUVmax median, 5.55). The SUVmax of the bone marrow (rho = 0.376, p = 0.004), SUVmax of the spleen (rho = 0.450, p < 0.001), TLGtotal of LNs (rho = 0.386, p = 0.017), and MLVtotal of LNs (rho = 0.391, p = 0.015) were correlated with the systemic score. The SUVmax of the spleen (p = 0.017), TLGtotal of LNs (p = 0.045), and MLVtotal of LNs (p = 0.012) were higher in patients with MAS than in those without MAS. A MLVtotal of LNs > 62.2 (OR 27.375, p = 0.042) was an independent predictive factor for MAS with a sensitivity of 80.0% and a specificity of 93.9%. CONCLUSIONS: The glucose metabolic level of the spleen could be an effective and easy-to-use imaging indicator of disease severity, and MLVtotal of LNs > 62.2 was a strong predictor of MAS occurrence in patients with AOSD.