简介：AbstractObjective:Subjective tinnitus is characterized by the perception of sound in the absence of any external auditory stimuli. This perceived sound may be related to altered intrinsic neural activity generated along the central auditory pathway. This retrospective study was designed to investigate regional homogeneity and functional connectivity in the resting-state brain activity of patients with tinnitus.Methods:We recruited tinnitus patients with normal hearing or mild hearing loss (n = 17) and age-matched healthy controls (n = 20), and examined regional homogeneity and functional connectivity in resting-state brain activity using resting-state functional magnetic resonance imaging data. The present study protocol was approved by the Institutional Review Board on Experimental Ethics at Sun Yat-sen University, China (approval No. SYSEC-KY-KS-2019-083).Results:Compared with normal controls, patients with tinnitus had significantly decreased regional homogeneity in the anterior lobe of the cerebellum and increased homogeneity in the inferior frontal gyrus (P < 0.05 corrected at a cluster-level). In addition, tinnitus patients showed enhanced functional connectivity between the inferior frontal gyrus and the ventral striatum and midbrain, as well as increased connectivity between the cerebellum and ventromedial prefrontal cortex (P < 0.05 corrected at a cluster-level). We also found decreased connectivity between the cerebellum and the anterior insula compared with controls (P < 0.05 corrected at a cluster-level).Conclusion:Abnormal connectivity in non-auditory brain structures, particularly those related to emotion processing, may be associated with tinnitus persistence.

简介：AbstractBackground:Fibroblast-like synoviocytes (FLSs), resident mesenchymal cells of synovial joints, play an important role in the pathogenesis of rheumatoid arthritis (RA). Dickkopf-1 (DKK-1) has been proposed to be a master regulator of bone remodeling in inflammatory arthritis. Here, potential impairation on the activity of FLSs derived from RA to small interfering RNAs (siRNAs) targeting DKK-1 was investigated.Methods:siRNAs targeting DKK-1 were transfected into FLSs of patients with RA. Interleukin (IL)-1β, IL-6, IL-8, matrix metalloproteinase (MMP) 2, MMP3, MMP9, transforming growth factor (TGF)-β1, TGF-β2 and monocyte chemoattractant protein (MCP)-1 levels in the cell culture supernatant were detected by enzyme-linked immunosorbent assay (ELISA). Invasion assay and 3H incorporation assay were utilized to investigate the effects of siRNAs targeting DKK-1 on FLSs invasion and cell proliferation, respectively. Western blotting was performed to analyze the expression of nuclear factor (NF)-κB, interleukin-1 receptor-associated kinase (IRAK)1, extracellular regulated protein kinases (ERK)1, Jun N-terminal kinase (JNK) and β-catenin in FLSs.Results:DKK-1 targeting siRNAs inhibited the expression of DKK-1 in FLSs (P < 0.01). siRNAs induced a significant reduction of the levels of IL-6, IL-8, MMP2, MMP3 and MMP9 in FLSs compared to the control group (P < 0.05). DKK-1 targeting siRNAs inhibited the proliferation and invasion of FLSs (P < 0.05). Important molecules of pro-inflammatory signaling in FLSs, including IRAK1 and ERK1, were decreased by the inhibition of DKK-1 in FLSs. In contrast, β-catenin, a pivotal downstream molecule of the Wnt signaling pathway was increased.Conclusions:By inhibiting DKK-1, we were able to inhibit the proliferation, invasion and pro-inflammatory cytokine secretion of FLSs derived from RA, which was mediated by the ERK or the IRAK-1 signaling pathway. These data indicate the application of DKK-1 silencing could be a potential therapeutic approach to RA.

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简介：AbstractBackground:Rheumatoid arthritis (RA), a systemic autoimmune disease characterized by synovial inflammation, can cause cartilage and bone damage as well as disability. The aim of this study was to explore whether serum glucose-6-phosphate isomerase (GPI) is correlated with disease activity and the value of GPI in the evaluation of infliximab treatment in patients with RA.Methods:Sixty-two patients with RA who had an inadequate response to methotrexate (MTX) were enrolled in Peking University People’s Hospital from July 1, 2016 to July 31, 2018. Infliximab (3 mg/kg, intravenous at weeks 0, 2, and 6 and then every 8 weeks) was administered to patients with stable background MTX therapy. Serum samples were obtained at baseline and week 18. Serum GPI levels were determined using enzyme-linked immunosorbent assay. The associations between serum GPI levels and clinical features were analyzed.Results:Serum GPI was positively correlated with Disease Activity Score in 28 joints (DAS28), swollen joint count, tender joint count and C-reactive protein level (P < 0.001, P < 0.001, P < 0.001, and P = 0.033, respectively). The change of DAS28 in GPI-positive patients was greater than that in GPI-negative patients (P < 0.001). Compared with those for patients receiving MTX monotherapy at baseline, the GPI levels were significantly declined when MTX was combined with infliximab (P < 0.001).Conclusion:Serum GPI is related to disease activity and clinical response to infliximab treatment.

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