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关键词： Circinate balanitis   HLA B27   reactive arthritis  

摘要： Circinate balanitis is a characteristic mucocutaneous lesion commonly associated with reactive arthritis (ReA), previously described as Reiter's disease. It typically presents alongside other ReA symptoms, including urethritis, conjunctivitis, and arthritis, but can occasionally occur as an isolated finding. We report two cases of circinate balanitis occurring in patients with HLA B27-positive spondyloarthritis, without the classical triad of reactive arthritis. A 32-year-old male presented with recurrent erosions on the glans penis for 2 years, with a history of HLA B27-positive spondyloarthritis. He was on treatment with tofacitinib, deflazacort, and sulfasalazine. A skin biopsy from the scrotum confirmed the diagnosis of psoriasis. MRI spine and sacrum showed anterior syndesmophyte formation and right-sided sacroillitis. The final diagnosis was circinate balanitis in association with HLA B27-positive psoriatic spondyloarthritis. A 41-year-old male presented with recurrent erosions on the glans penis for 4 years with history of HLA B27 positivity, and ankylosing spondyloarthritis. The biopsy from the glans penis showed squamous hyperplasia. MRI spine and pelvis was suggestive of inflammatory spondyloarthropathy of the cervical, dorsal and lumbar spine with bilateral sacroilitis. The final diagnosis was circinate balanitis with primary ankylosing spondylitis. Both cases highlight the diagnostic challenge of distinguishing between different forms of spondyloarthritis in the presence of circinate balanitis.

关键词： Bariatric surgery   Metabolic surgery   Obesity   Anti-obesity drugs  

摘要： Patients suffering from chronic respiratory failure may present with obesity, which can cause respiratory failure, particularly in cases of Obesity Hypoventilation Syndrome (OHS) or certain forms of asthma. It can also aggravate symptoms such as dyspnea. In this context, patients are often asked to change their lifestyle, or even to undergo bariatric surgery, the common objective being to help them lose weight. That said, a question may be raised: is weight loss always desirable? In the present review of relevant articles, we report on: (a) the current possibilities for achieving significant and lasting weight loss, (b) the arguments in favor of a weight loss strategy for patients with respiratory failure, and (c) the arguments suggesting a need for caution. (c) 2025 SPLF. Published by Elsevier Masson SAS. All rights are reserved, including those for text and data mining, AI training, and similar technologies.

关键词： Allergic asthma   Luteolin   Type 2 inflammation   IL-33/ST pathway   M2 macrophage  

摘要： Allergic asthma is a prevalent non-infectious inflammatory disease characterized by type 2 inflammation. Although multiple treatment options are available, their efficacy is often limited due to the heterogeneous nature of asthma. Luteolin (LUT), a naturally occurring flavonoid, has demonstrated therapeutic potential in various inflammatory conditions. The aim of this research is to investigate the underlying pathogenesis mechanisms of allergic asthma and to evaluate the therapeutic effects of LUT on allergic asthma via IL-33/ST2 signaling pathway. We established a murine model of allergic asthma by sensitizing and challenging BALB/c mice with ovalbumin (OVA), followed by treatment with LUT. The effects of LUT in allergic asthma mice were evaluated via the following techniques: pathological staining, Immunohistochemical staining (IHC), enzyme-linked immunosorbent assay (ELISA), real-time quantitative polymerase chain reaction (RT-qPCR) and Western blot (WB). Additionally, we also used IL-33 to stimulate RAW264.7 cells. Assays in vitro including cell counting Kit-8 (CCK-8), RT-qPCR and WB were performed to investigate potential mechanisms of LUT on IL-33/ST2 pathway activation and M2 macrophages polarization. LUT was verified to have crucial effects on ameliorating asthmatic mice lung function as evidenced by down-regulated airway resistance by 23 % and 48 % (p < 0.05 vs. OVA/saline group);regulating airway type 2 inflammation via decrease the content of type 2 inflammatory cytokines (IL-4, IL-5, and IL-13) by 17 %-78 % (**p < 0.01;*p < 0.001 vs. OVA/saline group);decreasing airway inflammatory cells infiltration by 54 % and 65 % (*p < 0.001 vs. OVA/saline group);inhibiting mucus secretion by 75 % and 89 % (*p < 0.001 vs. OVA/saline group). Mechanistic research revealed that LUT can treat asthma via IL-33/ST2-GSK3 beta-M2 macrophages polarization pathway, thereby regulating airway inflammation, remodeling, and immune responses in allergic asthma. Collectively, these

关键词： allele variant   next generation sequencing   novel allele  

摘要： HLA-A*11:01:01:97 differs from HLA-A*11:01:01:01 by a single nucleotide position gDNA 1247 T > A within Intron 3.

关键词： Endometrial cancer   Interleukin-6   KIAA1429   Ferroptosis  

摘要： Endometrial cancer (EC) exhibits significant resistance to ferroptosis. Interleukin (IL)-6 is a pleiotropic cytokine that is a regulator of the expression of various oncogenes and tumour suppressor genes. Notably, N6methyladenosine (m6A) modification has been demonstrated to play a significant role in tumour occurrence and development. However, IL-6 regulatory role in ferroptosis during carcinogenesis and whether it affects m6A modification in EC remain unclear. The present study aimed to investigate the effect of IL-6 on m6A modification in EC. The degree of ferroptosis of EC in vitro and in vivo was evaluated using a cell proliferation assay, western blotting, total reactive oxygen species (ROS) detection, a lipid peroxidation assay, and a subcutaneous xenograft tumour model. The regulation of downstream molecules by KIAA1429 was confirmed using dot blot, RNA and methylated RNA immunoprecipitation (RIP), a RNA stability assay, and fluorescence in situ hybridisation (FISH). IL-6 upregulated overall m6A levels in EC cells, with the KIAA1429 expression upregulation being the most significant. Functionally, IL-6 inhibited EC cell ferroptosis and promoted proliferation. The downregulation of KIAA1429 triggered ferroptosis, subsequently suppressing the proliferation of EC cells in vitro and tumour growth in vivo. Mechanistically, IL-6 activated KIAA1429 expression through the JAK1/STAT3 pathway. KIAA1429 regulated DDIT3 expression and promoted its degradation through m6A modification. IL-6 is crucial in EC cell ferroptosis resistance. Overall, the IL-6/KIAA1429/DDIT3 axis is a novel pathway that promotes EC progression and provides novel directions for targeted EC therapy.

关键词： ANCA-associated vasculitis   HLA   GPA   PR3   MPO  

摘要： Objectives ANCA-associated vasculitis (AAV) is a group of systemic autoimmune diseases affecting small blood-vessels. Class-II human leukocyte antigen (HLA) genes are often reported as major genetic determinants. We conducted a systematic review and meta-analysis to evaluate the susceptibility conferred by HLA genes to AAV and five of its clinical subtypes [PR3+AAV, MPO+AAV, granulomatosis with polyangiitis (GPA), microscopic polyangiitis (MPA) and eosinophilic granulomatosis with polyangiitis (EGPA)]. Methods Relevant articles published March 2024 or previously were retrieved from electronic databases using appropriate keywords. Eligible studies were included according to inclusion/exclusion criteria. Funnel plots, the Newcastle-Ottawa Scale and GRADE tools were used to evaluate the quality of the evidence and the research findings. Statistical analyses were performed using RevMan 5.4.1. The meta-odds ratio and the Z test P-value were considered to check the HLA associations. Results This meta-analysis of associations between HLA alleles and AAV and its subtypes identified 30 significant associations, of which 17 withstood Bonferroni corrections. rs9277554-C from HLA-DPB1 [meta-analysis overall odds ratio (Meta-OR) = 3.92 (3.27-4.69)], rs1049072-A from HLA-DQB1 [Meta-OR = 1.39 (1.27-1.52)] and rs9277341-C from HLA-DPA1 [Meta-OR = 0.41 (0.03-0.57)] were found to be significantly associated (P < 0.00001) with AAV and GPA, respectively. HLA-DRB1*09:01 was found to be significantly associated with (P < 0.00001) (i.e. a predisposing allele for) AAV [Meta-OR = 1.72 (1.46-2.03)], MPO+AAV [Meta-OR = 1.65 (1.41-1.93)] and MPA [Meta-OR = 1.75 (1.41-2.19)]. Significant association (P <= 0.0005) was also observed between HLA-DPB1*01:01 and AAV [Meta-OR = 0.38 (0.24-0.62)] and between HLA-DRB1*11:01 and MPA [Meta-OR = 2.11 (1.39-3.20)]. Sensitivity analysis identified additional significant (P <= 0.001) alleles HLA-DPB1*04:01 and HLA-DPB1*02:01 predisposing patients to AAV and

关键词： Tofacitinib   JAK/STAT   Infectious colitis   Innate lymphoid cells   Campylobacter jejuni  

摘要： Patients with autoimmune diseases are more susceptible to foodborne infections, which can be exacerbated by immunosuppressive therapy. Tofacitinib, a JAK/STAT pathway inhibitor, was recently approved for the treatment of ulcerative colitis, yet its effects on the pathogenesis of intestinal infections remain unclear. Here, we examined the impact of oral tofacitinib treatment in a mouse model of Campylobacter jejuni (C. jejuni) infection. Our results show that early tofacitinib administration attenuates intestinal pathology without affecting bacterial colonization. Specifically, tofacitinib suppressed CXCL1, CXCL2, CCL2 chemokine expression by intestinal epithelial cells, limiting recruitment of monocytes and neutrophils to the gut. In addition, JAK/STAT inhibition reduced IFN gamma-producing innate lymphoid cells (ILCs) and T cells in the gut. Furthermore, tofacitinib suppressed IFN gamma production and ameliorated intestinal disease in humanized mice. Cell-fate mapping revealed that tofacitinib predominantly inhibited IFN gamma production by NK1.1- ILCs derived from NKp46- progenitors and reduced NK1.1- ILC proliferation without affecting ILC3 to ILC1 plasticity. Notably, tofacitinib ameliorated intestinal disease even in the absence of T cells. These findings suggest that tofacitinib alleviates C. jejuni-induced colitis by reducing proinflammatory cytokine production by monocytes/macrophages/epithelial cells and suppressing IFN gamma secretion by ILCs and T cells, while preserving antibacterial defenses.

关键词： biomarker   central nervous system   chronic disorder   generalized anxiety disorder   interleukin-6 (IL-6)   pathophysiology   transforming growth factor-beta 1 (TGF-beta 1)  

摘要： Background Generalized anxiety disorder (GAD) is a chronic psychiatric disease characterized by excessive and uncontrollable worry about common life events. Neurological, neurochemical, genomic, environmental, psychogenic, and immunological factors are thought to be involved in GAD. However, studies conducted to establish any suitable biomarkers for the assessment of anxiety disorder is limited. Hence, we aim to investigate the serum levels of interleukin-6 (IL-6) and transforming growth factor-beta 1 (TGF-beta 1) in GAD *** The present study enrolled 44 GAD patients and 44 healthy controls (HCs) from a tertiary care teaching hospital in Dhaka, Bangladesh. A qualified psychiatrist assessed the study population based on the criteria mentioned in the DSM-5. We measured the serum levels of IL-6 and TGF-beta 1 using the commercially available enzyme-linked immunosorbent assay (ELISA) *** We noted a significant reduction in serum IL-6 and TGF-beta 1 levels in GAD patients compared to HCs (IL-6: 7.72 +/- 2.14 vs. 9.39 +/- 1.22 pg/mL;p = 0.003, and TGF-beta 1: 386.77 +/- 157.91 vs. 774.51 +/- 327.73 pg/mL;p = 0.001). Moreover, a significant negative association was found between the levels of IL-6 and GAD-7 scores among the GAD patients (r = -0.395, p < 0.001). Lastly, the ROC analysis demonstrated a strong predictive accuracy with a moderately higher area under the curve (AUC) value (IL-6: 0.888 and TGF-beta 1: 0.891), relatively higher sensitivity (IL-6: 85.3% and TGF-beta 1: 85.6%), and higher specificity (IL-6: 86.7% and TGF-beta 1: 82.4%).Conclusion Our study findings underscore that lowered IL-6 and TGF-beta 1 levels might have a role in the pathophysiology and development of GAD. Therefore, the alterations of cytokines have a crucial role in evaluating the GAD patients. We suggest further interventional studies to determine the actual predictive performance of IL-6 and TGF-beta 1 in GAD.

关键词： Sepsis-associated encephalopathy   IL-1 alpha/IL-1 beta   Endothelial cell   BBB disruption  

摘要： Sepsis-Associated Encephalopathy (SAE), a disorder affecting the central nervous system (CNS), is highly prevalent, occurring in approximately 70 % of sepsis patients in intensive care units (ICU). Although numerous studies have highlighted the critical role of IL-1 beta in the pathogenesis of SAE, the specific downstream mechanisms remain poorly understood. Moreover, the Phase III clinical trial of IL-1R1 antagonists for SAE therapy ended in failure. In this study, we found that IL-1R1, the receptor for IL-1 beta, is exclusively and highly expressed on CNS endothelial cells during early sepsis. Specifically inhibiting IL-1R1 expression in endothelial cells during the early stage of sepsis can significantly suppress the onset of SAE. Mechanistically, elevated levels of LPS, IL-1 alpha, or IL-1 beta in the serum during sepsis induce IL-1R1 expression on endothelial cells, leading to the activation of IL-1 beta signaling. Activation of the IL-1 beta/IL-1R1 signaling pathway in endothelial cells triggers the expression of adhesion molecules, pro-inflammatory cytokines, and chemokines, which in turn exacerbate neuroinflammation and contribute to cognitive impairments. This research not only elucidates the pathogenic mechanisms underlying SAE but also introduces an advanced approach for targeted gene intervention in CNS endothelial cells, potentially offering a new strategy for the treatment of SAE and other neurodegenerative disease induced by systemic inflammation.

关键词： Durvalumab plus tremelimumab (DT)   Interleukin (IL)-6   Immune-related adverse events (irAE)  

摘要： Systemic therapy for advanced hepatocellular carcinoma (HCC) has progressed significantly, yet the management of immune-related adverse events (irAEs) remains a challenge, particularly with anti-CTLA-4 and anti-PD-L1 antibodies. We present two cases of severe irAEs during durvalumab plus tremelimumab (DT) therapy, demonstrating successful management and favorable outcomes. In Case 1, a 76-year-old male with metabolic-associated steatotic liver disease-related HCC experienced disease progression after lenvatinib and subsequently initiated DT therapy. He developed Grade 3 immune-related myositis at week 5, which was successfully managed with prednisolone. A partial response (PR) was achieved and maintained, with a 55% tumor reduction at 8 months. In Case 2, a 73-year-old male with alcoholic cirrhosis and a 16-cm HCC received DT therapy. On day 19, he developed Grade 3 immune-related hepatitis and thyroiditis, which were controlled with prednisolone. After steroid tapering, durvalumab was successfully rechallenged, maintaining a 38% tumor reduction at 6 months with a sustained PR. In the case series, lower baseline serum interleukin (IL)-6 levels were associated with the development of Grade >= 3 irAEs. These findings suggest that IL-6 may serve as a predictive biomarker, aiding in risk assessment and the optimization of individualized treatment strategies prior to anti-CTLA-4 therapy.