ABSTRACT
Objective:To investigate the classification of patients with gout, and further analyze their clinical features.Methods:Outpatients with gout were enrolled from January 2018 to July 2019 in Depart-ment of Rheumatology, Zhongshan Hospital. Subjects were classified into four groups according to their 24-hour urinaryexcretion and fractional excretion of urate. Clinical features of different groups were analyzed using one-way Analysis of Variance (ANOVA), Kruskal-Wallis H test, or χ2 test. Results:Finally, 378 subjects were enrolled in this cross-sectional study. Among them, 186(49.2%) were renal underexcretion type, 100(26.5%) were combined type, 57(15.1%) were renal overload type, 35(9.3%) were the normal type. Renal underexcretion type was the main subtype in any age-stratified groups. With aging, the proportion of combined type decreased, while the normal type increased. Participants in the combined type were the youngest [(42±14) years of age] with the highest estimated glomerular filtration rate [(94±18) ml·min -1·1.73 m -2], while their serum urate levels were the highest [(554±104) μmol/L]. Subjects in the normal type were the oldest [(60±15) years of age] with the lowest estimated glomerular filtration rate [(71±19) mL·min -1·1.73 m -2], however, their serum urate concentrations were the lowest [(427±118) μmol/L], The difference was statistically significant (age, F=13.98; estimated glomerular filtration rate, F=16.11; urate, F=17.14; P<0.01). Prevalence of urolithiasis were similar among the four groups ( χ2 =2.00, P>0.05). Conclusion:The renal underexcretion type is the main type of gout. Young patients are more likely to suffer from combined type with the highest serum urate levels and the best renal function.
ABSTRACT
Background: The remarkable mechanisms of storiform fibrosis and the formation of high levels of IgG4 with a pathogenic germinal center (GC) in the inflammatory tissue of IgG4-RD remains unknown and may be responsible for the unsatisfactory therapeutic effect on IgG4-related diseases when using conventional therapy. Objectives: To investigate the mechanisms of interleukin 6 (IL-6) inducing fibroblasts to produce cytokines for pathogenic GC formation in the development of IgG4-related disease (IgG4-RD). Methods: The clinical data and laboratory examinations of 56 patients with IgG4-RD were collected. IL-6 and IL-6R expression in the serum and tissues of patients with IgG4-RD and healthy controls were detected by ELISA, immunohistochemistry, and immunofluorescence. Human aorta adventitial fibroblasts (AAFs) were cultured and stimulated with IL-6/IL-6 receptor (IL-6R). The effect of IL-6/IL-6R on AAFs was determined by Luminex assays. Results: The serum IL-6 and IL-6R levels were elevated in active IgG4-RD patients and IL-6 was positively correlated with the disease activity (e.g., erythrocyte sedimentation rate [ESR], C-reactive protein [CRP], and IgG4-RD responder index). IL-6 and IL-6R expression in the tissue lesions of IgG4-related retroperitoneal fibrosis and IgG4-related sialadenitis patients were also significantly higher than that in the normal tissues. In addition, there is a relative abundance of myofibroblasts as well as IgG4+ plasma cells in the tissues of IgG4-related retroperitoneal fibrosis. α-SMA and B cell differentiation cytokines (i.e., B cell activating factor), and α-SMA and T follicular helper (Tfh) cell differentiation cytokines (e.g., IL-7, IL-12, and IL-23) were co-expressed in the local lesions. In vitro, IL-6/IL-6R significantly promoted the production of B cell activating factor, IL-7, IL-12, and IL-23 in AAFs in a dose-dependent manner. This effect was partially blocked by JAK1, JAK2, STAT3, and Akt inhibitors, respectively. Conclusions:In vitro IL-6/IL-6R trans-signaling in fibroblasts releases Tfh and B cell differentiation factors partially via the JAK2/STAT3, JAK1/STAT3, and JAK2/Akt pathways, which may be linked to the pathogenesis of IgG4-RD. This indicated that IL-6 and fibroblasts may be responsible for GC formation and fibrosis in the development of IgG4-RD. Blocking IL-6 with JAK1/2 inhibitors or inhibiting fibroblast proliferation might be beneficial for IgG4-RD treatment.
Subject(s)
Cytokines/biosynthesis , Fibroblasts/metabolism , Immunoglobulin G4-Related Disease/immunology , Immunoglobulin G4-Related Disease/metabolism , Interleukin-6/metabolism , Receptors, Interleukin-6/metabolism , Signal Transduction , Biomarkers , Cells, Cultured , Disease Susceptibility , Female , Fluorescent Antibody Technique , Humans , Immunohistochemistry , Janus Kinase 1/metabolism , Janus Kinase 2/metabolism , Lymphocyte Activation/immunology , Male , Oncogene Protein v-akt/metabolism , Plasma Cells/immunology , Plasma Cells/metabolism , Proto-Oncogene Proteins c-akt , STAT3 Transcription Factor/metabolism , T Follicular Helper Cells/immunology , T Follicular Helper Cells/metabolismABSTRACT
Objective The aim of the present study is to measure multi-directional strain in patients with hyperuricemia through 3-dimensional speckle-tracking echocardiography (3D-STE) in order to investigate the left ventricular function early changes and clinical application value of 3D-STE. Methods 3-dimension dynamic images of left ventricular full volume in Apical 4-chamber heart view was collected and stored. 3-dimensional specke-tracking technology was applied to measure and compare the left ventricular multi-directional strain of patients with hyperuricemia and healthy controls in order to evaluate the left ventricular systolic function. Results A total of 24 healthy controls and 38 patients with hyperuricemia were included into the study. Among them,patients with hyperuricemia were divided into simple hyperuricemia group(n=12), hyperuricemia complicated with hyperlipidemia group (n=16)and hyperuricemia complicated with both hyper-tension and hyperlipidemia group (n=10). The circumferential strain [(-18.8±4.4)% vs (-25.9±6.4)%, t=-3.48, P=0.001] and area strain [(-31.2±3.9)% vs (-36.8±7.1)%, t=-2.55, P=0.018] of patients with simple hyper-uricemia significantly decreased compared with healthy controls. Besides, the circumferential strain [(-19.9 ± 5.8)% vs (-25.9 ±6.4)%, t=-3.02, P=0.002], longitudinal strain [(-12.6 ±3.3)% vs (-14.4 ±2.5)%, t=-1.95, P=0.038] and area strain [(-29.9±6.6)% vs (-25.9±6.4)%, t=-3.15, P=0.001] of patients with hyperuricemia complicated with hyperlipidemia significantly decreased compared with healthy controls. Conclusion Myo-cardial strain of patients with hyperuricemia complicated with hyperlipidemia or not is both decreased, indicating a decline in left ventricular systolic function.