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关键词： axial spondyloarthritis   anti-TNF therapy   NSAIDs   swept-source optical coherence tomography angiography   retinal microvascular changes   choroidal thickness   vascular density  

摘要： Objectives: The aim of this study was to investigate retinal and choroidal microvascular changes in patients with axial spondyloarthritis (axSpA) treated with long-term anti-TNF therapy and NSAIDs and in healthy control subjects using optical coherence tomography angiography (SS-OCT-A). Methods: A total of 162 eyes from 81 participants were included: 52 eyes from 26 axSpA patients treated with anti-TNF therapy (>= 5 years), 44 eyes from 22 axSpA patients treated with NSAIDs, and 66 eyes from 33 healthy control subjects. SS-OCT-A imaging was used to assess retinal thickness, ganglion cell layer thickness, retinal nerve fiber layer thickness, and the vessel densities of the superficial capillary plexus (SCP), deep capillary plexus (DCP), and choriocapillaris (CC). Disease activity was assessed with ASDAS-CRP. Results: Both axSpA subgroups showed a significant expansion of the foveal avascular zone and reduced SCP and DCP densities compared to the controls. The CC vessel density was higher in axSpA patients than in healthy subjects. The anti-TNF group had a lower CC vascular density than the NSAIDs group. The disease duration correlated with a decreased central DCP density and increased paracentral SCP and CC densities. Conclusions: SS-OCT-A revealed subclinical retinal and choroidal changes in axSpA patients, highlighting the impact of chronic inflammation on the retinal vasculature. While anti-TNF therapy effectively controls systemic inflammation, it cannot completely prevent microvascular changes. Further studies are needed to assess the clinical relevance of these results.

关键词： atopic dermatitis   interleukin 33   semaphorin  

摘要： Neuroimmune interaction is crucial to inducing pruritic sensations in atopic dermatitis (AD). In this study, we examine the neuroimmune pathways involved in children with AD. HumanMethylation450 BeadChip and GeneChip Human Transcriptome Array 2.0 from 24 children with ad and 24 healthy controls were cross-referenced with gene expression data from GSE116486. SEMA7A, which encodes for semaphorin 7a and is associated with neuron development and immune response and was identified on pathway analysis as a crucial gene in children with ad. In addition, we found that SEMA7A cytosine-phosphate-guanine sites (CpG sites) cg13557411 and cg17917837 were hypomethylated, and mRNA expression of SEMA7A was higher in children with ad. Vectors containing SEMA7A were then transfected into Jurkat T cells, which increased the protein excretion of interleukin 4 (IL-4) and the mRNA expression of interleukin 1 receptor-like 1 (IL1RL1, receptor for the cytokine IL-33). Furthermore, stimulation of HaCaT keratinocytes with SEMA7A protein resulted in increased mRNA expression of the genes interleukin 33 (IL33) and IL1RL1, but suppressed mRNA expression of the tight junction protein ZO-1(TJP1). In conclusion, in this study, we found that SEMA7A is overexpressed in patients with AD and is a central gene on pathway analysis. Results of our study suggest that overexpression of SEMA7A is associated with increased expression of IL4, IL33 and its receptor IL1RL1, which are associated with pruritic sensation in AD. SEMA7A also appears to suppress the expression of TJP1 in keratinocytes, thereby possibly increasing the permeability of the skin barrier. SEMA7A may be an alternative therapeutic target in AD, especially for neuroimmune-related pruritis.

关键词： Biomarker   Epithelial ovarian cancer   Interleukin-16   Prognosis   Staging  

摘要： IL-16 has been described as a chemoattractant that activates macrophages, CD4+ T cells, eosinophils, dendritic cells, and monocytes, thus activating the secretion of inflammatory cytokines, including IL-15, IL-1β, and TNF-α. The present study aimed to investigate the IL-16 expression in the serum and elucidate IL-16 significance in the clinical assessment of epithelial ovarian cancer (EOC). The study adopted an enzyme-linked immunosorbent assay (ELISA) to analyze the expressions of IL-16 in the serum derived from 80 EOC patients and 80 age-matched healthy controls. The association of IL-16 levels with EOC patients' prognosis and clinical factors were determined. The receiver operator characteristic (ROC) analysis was done to determine the accuracy of serum IL-16 in EOC diagnosis. EOC patients demonstrated significantly increased serum IL-16 levels compared to the controls (192.4 ±54.27 pg/mL versus 90.5±41.27 pg/mL, <0.001, respectively). Elevated IL-16 levels in the serum were remarkably linked with tumor size (=0.001), FIGO (International Federation of Gynecology and Obstetrics) stage (=0.001), recurrence (=0.039), and metastasis of lymph node (P=0.029). Analysis of the Kaplan-Meier survival curve confirmed elevated IL-16 levels in serum is directly associated with poor overall survival (OS) (=0.032) and progression-free survival (=0.041). Assessment of univariate and multivariate results demonstrated IL-16 serum levels (HR: 2.996, 95%CI:1.313-4.231, =0.006) were the independent EOC patients' prognostic factors. Analyses of the ROC curve confirmed AUC of 0.781, 95% CI:0.639-0.923, <0.001. Elevated IL-16 serum levels are linked with poor prognosis in EOC patients, and IL-16 might be a promising biomarker for the prognosis of EOC among patients.

关键词： dapagliflozin   IL-17   NLRP3   secukinumab   sunitinib  

摘要： Sunitinib (SUN) is a chemotherapeutic agent showing renal toxicity that limits its clinical applications. The present research aimed to clarify the potential ameliorative effects of secukinumab (SEC) and dapagliflozin (DAPA) against SUN-induced renal toxicity and the underpinning molecular mechanisms. For this purpose, adult Wistar albino rats were received SUN (25 mg/kg 3 times/week, po) and co-treated with SEC (3 mg/kg/every 2 weeks, subcutaneously) or DAPA (10 mg/kg/day, po) for 4 weeks and compared with age-matched control group (CON). Markers of kidney functions were assessed in serum samples. Kidneys were harvested for biochemical and histological examination. Compared to CON group, SUN-treated rats displayed signs of kidney dysfunction along with renal histological changes that were ameliorated by SEC or DAPA. Both drugs significantly lowered the renal levels of IL-17, but SEC exerted more inhibitory effect than DAPA. Additionally, SUN-subjected rats showed significant increases in the renal expression of NLRP3 inflammasome and the other inflammatory mediators including IL-1 beta, END-1, and MCP-1. This was associated with marked decline of the renal levels of beclin-1. Co-treatment with SEC or DAPA significantly suppressed NLRP3-induced inflammation while enhanced beclin-1-mediated autophagy. The modulatory effect of DAPA on NLRP3 and beclin-1 was superior to that of SEC. Moreover, both drugs significantly and similarly attenuated the enhanced cleaved caspase-3 expression and interstitial fibrosis in renal tissue of SUN-subjected rats. Collectively, these findings may repurpose SEC and DAPA as candidate therapies to alleviate the renal toxicity of SUN and to rescue the renal functionality in SUN-treated cancer cases.

关键词： HLA   HLA-DPA1*02:01:34   new allele   synonymous mutation  

摘要： HLA-DPA1*02:01:34 differs by a single synonymous mutation compared to HLA-DPA1*02:01:01:02 in codon 212 in Exon 4.

关键词： BK virus   Hemorrhagic Cystitis   Post-transplant   cyclophosphamide   Sirolimus   Mycophenolate mofetil  

摘要： BK hemorrhagic cystitis (BK-HC) is a common complication following hematopoietic (PTCy) is used as graft-versus-host disease (GVHD) prophylaxis. However, comparative studies of BK-HC incidence in matched sibling donors (MSD) and unrelated donors (MUD) often include small haploidentical (HAPLO) donor cohorts and usually lack detailed information on disease evolution, coinfections, management and impact on outcomes. This study aimed to evaluate the incidence, risk factors, and outcomes in patients with hematologic malignancies undergoing HSCT from MSD, MUD, HAPLO donors using PTCy as GVHD prophylaxis. Furthermore, we analyze risk factors for BK-HC and its impact on renal function and transplant outcomes. Retrospective analysis of BK-HC episodes in patients undergoing HSCT from 167 MSD, 129 MUD and 103 HAPLO from a single institution. Uniform GVHD prophylaxis with PTCy, sirolimus and mycophenolate mofetil was given, irrespective of donor type or conditioning intensity, and mesna was used

关键词： HLA   HLA-A*11:481   NGS novel allele  

摘要： The HLA-A*11:481 allele differs from HLA-A*11:01:01:01 by one nucleotide substitution in codon -8 in exon 1.

关键词： anakinra   normothermic machine perfusion   renal transplantation  

摘要： BackgroundThe interleukin 1 (IL-1) cytokine group plays a key role in sterile inflammation and may be an important target for transplant-related renal injury. This study examined the effects of anakinra, a non-specific IL-1 receptor antagonist, administered during normothermic machine perfusion (NMP) of porcine *** porcine kidneys (n = 5 pairs) underwent 15 min of warm ischemia plus 2 h of static cold storage in ice. Kidneys were then perfused with autologous whole blood using an ex vivo NMP platform. Kidneys were randomly allocated to receive anakinra or vehicle administered at the start of NMP. Cortical biopsies were collected at baseline before ischemic injury and at the end of NMP. Functional parameters were recorded and calculated, and inflammatory markers were measured by qPCR and ELISA *** NMP, there were no statistically significant differences in renal blood flow, urine output, creatinine clearance or fractional excretion of sodium in the anakinra and control groups. The administration of anakinra significantly downregulated transcriptional expression of IL-6, Fas ligand and intercellular adhesion molecule 1 (p = 0.029, 0.029, 0.028, respectively).ConclusionAnakinra, an IL-1 receptor blocker, successfully attenuated the downstream inflammatory and immune-mediated response within the kidney during NMP.

关键词： B10 cells   CD40/CD40L   low IgG   primary nephrotic syndrome   Th17/Treg  

摘要： Aim: This study aimed to investigate the contribution of interleukin (IL)-10-producing regulatory B cells (B10 cells) to the pathogenesis of PNS. Methods: The percentages of B10 cells, CD19(+)CD24(hi)CD27(+) B cells, CD19(+)CD24(hi)CD38(hi) B cells, CD19(+)CD24(hi)CD27(+)IL-10(+) B cells, CD19(+)CD24(hi)CD38(hi)IL-10(+) B cells, Th17 cells, and regulatory T (Treg) cells within the peripheral blood mononuclear cells (PBMCs) from healthy subjects and PNS patients with active disease or in remission were analysed by flow cytometry. Results: The percentages and IL-10 production of circulating B10 cells and the two subsets were decreased in children with active PNS and returned to normal levels in PNS patients in remission. B10 cells and their subsets were negatively correlated with the Th17/Treg ratio. The percentages of B10pro+B10 cells, CD19(+)CD24(hi)CD27(+)IL-10(+) B cells, CD19(+)CD24(hi)CD38(hi)IL-10(+) B cells, Th17 cells, Treg cells, and the Th17/Treg ratio did not significantly differ between groups after CpG and CD40L stimulation. However, in the presence of CpG and anti-CD40L mAb, the percentages of B10pro+B10 cells, CD19(+)CD24(hi)CD27(+)IL-10(+) B cells, CD19(+)CD24(hi)CD38(hi)IL-10(+) B cells, and Treg cells were significantly reduced, whereas the Th17 cell percentage and the Th17/Treg ratio were significantly increased. Furthermore, the Th17/Treg ratio correlated negatively, whereas the percentages of B10 cells and their subsets correlated positively with serum immunoglobulin G (IgG) concentration. Conclusion: Our study demonstrates that the numbers of B10 cells and their ability to produce IL-10 are decreased, leading to an imbalance in the Th17/Treg ratio and low IgG levels, which may then contribute to the pathogenesis of PNS.