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关键词： autoimmune disease   central nervous system demyelination   Myelin oligodendrocyte glycoprotein antibody-associated disease (MOGAD)   TNF-α inhibitors  

摘要： Background: Myelin oligodendrocyte glycoprotein antibody-associated disease (MOGAD) is a rare but emerging central nervous system demyelinating disorder that can mimic other neurological conditions. The use of TNF-α inhibitors in patients with autoimmune diseases has been linked to central nervous system demyelinating events, but the relationship remains poorly understood. Case description: We present a 64-year-old male with a history of ankylosing spondylitis previously treated with a TNF-α inhibitor who developed progressive dizziness, ataxia, visual disturbances and cognitive changes. Despite extensive workup, including imaging and cerebrospinal fluid analysis, initial evaluations were inconclusive. MRI was non-diagnostic, and cerebrospinal fluid lacked oligoclonal bands. Ultimately, a serum MOG antibody titre of 1:1,000 confirmed the diagnosis of MOGAD. The patient improved with intravenous corticosteroids and was discharged on a tapering dose of oral prednisone. This case highlights an MRI-negative presentation of MOGAD with strong serologic findings. Conclusion: This case emphasises the diagnostic challenge of MOGAD in patients with autoimmune backgrounds and neurologic symptoms without clear imaging findings. Clinicians should consider MOGAD in the differential diagnosis when evaluating such patients, particularly those with prior TNF-α inhibitor exposure. Early recognition and treatment with immunotherapy can lead to significant clinical improvement. © EFIM 2025 - European Journal of Case Reports in Internal Medicine

关键词： 丹皮酚   酒精性肝病   肠道菌群   吲哚乙酸   AhR/IL-22/STAT3   肠道屏障  

摘要： 目的 探究丹皮酚是否通过调节肠道菌群色氨酸代谢，激活环芳香烃受体（aryl hydrocarbon receptor，AhR）/白细胞介素22（Interleukin-22，IL-22）/转录激活因子3（signal transducer and activator of transcription 3，STAT3）通路，发挥对酒精性肝病（alcoholic liver disease，ALD）的改善作用。方法 将C57BL/6 J小鼠分为对照组、模型组、丹皮酚高剂量（480 mg/kg）组、丹皮酚低剂量（120 mg/kg）组、丹皮酚（480 mg/kg）+抗生素组、抗生素组，每组10只。采用Lieber-DeCarli乙醇液体饲料喂养建立ALD小鼠模型，用药组在模型复制后第2天灌胃给药，持续10 d。测定小鼠肝功能[丙氨酸氨基转移酶（alanine aminotransferase，ALT）、天门冬氨酸氨基转移酶（aspartate aminotransferase，AST）]、血脂[甘油三酯（triglyceride，TG、总胆固醇（telecine，TC）、高密度脂肪酸（high density lipoprotein cholesterol，HDL-C）、低密度脂肪酸（low density lipoprotein，LDL）]及氧化应激指标[还原型谷胱甘肽（glutathione，GSH）、过氧化氢酶（catalase，CAT）、超氧化物歧化酶（superoxide dismutase，SOD）、丙二醛（malondialdehyde，MDA）]；采用苏木素-伊红染色法、油红O染色法观察各组小鼠肝脏、回肠组织病理形态变化；采用16S rDNA基因测序技术分析对照组、模型组和丹皮酚高剂量组小鼠肠道菌群差异；采用ELISA法检测小鼠血清、回肠组织中吲哚乙酸（3-indoleacetic acid、IAA）水平；采用Western blot、免疫组化法以及免疫荧光法检测小鼠回肠组织中AhR/IL-22/STAT3通路相关蛋白及回肠组织闭锁小带蛋白1（zonula occludens-1，ZO-1）、紧密连接蛋白-1（Claudin-1）表达水平。结果 与模型组比较，丹皮酚高剂量组小鼠体质量显著升高（P＜0.05），血脂（TG、TC、HDL-C）、肝功能（ALT、AST）及氧化应激（GSH、CAT、SOD）水平显著降低（P＜0.05），MDA水平显著升高（P＜0.05）；肠道菌群发生改变，厚壁菌门（Firmicutes）、放线菌门（Actinobacteriota）丰度升高，拟杆菌门(Bacteroidetes)和变形菌门（Proteobacteria）丰度降低；乳酸杆菌属（Lactobacillus）、梭菌属（Clostridium）等有益菌属丰度升高，克雷伯氏菌属（Klebsiella）、阿德勒克罗伊茨菌属（Adlercreutzia）等有害菌属丰度降低；小鼠血清及回肠组织中IAA水平显著升高（P＜0.05）；肝脏的脂肪堆积和回肠黏膜的损伤得到显著改善；小鼠回肠组织中AhR/IL-22/STAT3信号通路蛋白、胰岛再生源蛋白Ⅲγ和ZO-1、Claudin-1等蛋白表达水平显著升高（P＜0.05）；同时，抗生素的实验结果显示其减弱了丹皮酚的治疗效果。结论 丹皮酚对小鼠的酒精性肝病具有显著改善作用，其可能是通过调节ALD小鼠肠道菌群结构，增强肠道菌群相关色氨酸代谢，激活AhR/IL-22/STAT3通路，改善肠道屏障功能实现的。

关键词： Xiaoqinglong decoction   Yupingfeng powder   Combined allergic rhinitis and asthma   syndrome   Major histocompatibility complex II   Antigen presentation   Immune response   B lymphocytes  

摘要： Ethnopharmacological relevance: Xiaoqinglong Decoction combined with Yupingfeng Powder (XQLDwYPFP) is widely used to treat allergic rhinitis and bronchial asthma in Traditional Chinese Medicine, while its efficacy and mechanisms in combined allergic rhinitis and asthma syndrome (CARAS) remain underexplored. Aim of the study: To elucidate the mechanisms and pharmacodynamic basis of XQLDwYPFP in CARAS treatment. Materials and methods: A CARAS mouse model was established using ovalbumin (OVA). Airway allergic symptoms were assessed by recording nasal rubbing and sneezing frequencies. Serum OVA-sIgE levels were measured via ELISA. Histopathological changes were evaluated using HE, PAS, and C2R staining. Flow cytometry quantified Th cell subsets. Proteomics identified differential protein expression with GO and KEGG databases used for pathway enrichment analysis. Immunofluorescence assessed B lymphocyte activation, while Western blot and immunohistochemistry evaluated JAK1/JAK2-STAT1 pathway activation. Molecular docking validated the binding affinity of XQLDwYPFP components to JAK2 and STAT1. Results: XQLDwYPFP alleviated airway symptoms, reduced serum OVA-sIgE, and inhibited goblet cell hyperplasia and eosinophil infiltration in nasal and lung tissues. It decreased Th2 cell proportions and increased the Th1/Th2 ratio in lung and spleen tissues. Proteomics revealed that XQLDwYPFP suppresses CARAS by targeting the MHC II-mediated antigen presentation pathway. The formula reduced activated B lymphocytes and down-regulated JAK2, p-JAK2, STAT1, and p-STAT1 expression in nasal and lung tissues. XQLDwYPFP representative components exhibited strong binding affinity to JAK2 and STAT1. Conclusions: XQLDwYPFP alleviates type 2 inflammation in CARAS by regulating the JAK2-STAT1-MHC II pathway and inhibiting B lymphocyte-mediated antigen presentation. These findings provide novel pharmacological evidence supporting its clinical use for CARAS.

关键词： Intervertebral disc degeneration   Macrophage   Microangiogenesis   Nucleus pulposus  

摘要： BackgroundMacrophage infiltration accompanied by pathological microangiogenesis in the nucleus pulposus (NP) plays a critical role in the progression of intervertebral disc degeneration (IDD). However, the involvement of M2 macrophages in mediating NP pathological angiogenesis and their underlying mechanisms remain ***, the expression of M2 macrophage (CD206) and microangiogenic (CD34) markers in human degenerated NP was observed by immunohistochemical staining, subsequently, a co-culture system of M2 macrophages and NP cells was established. IL-10 expression was silenced using siRNA to assess the pro-angiogenic effects of M2 macrophages in IDD via IL-10 and its downstream janus kinase (JAK) 2/ signal transducer and activator of transcription (STAT) 3 pathway. AG490, a specific JAK2/STAT3 inhibitor, was applied to determine whether IL-10 exerts its effects through this pathway and to evaluate its impact on angiogenesis and extracellular matrix (ECM) metabolism in NP ***206 and CD34 were co-expressed in degenerated NP tissue. Degenerated NP cells secreted CCL17, CCL18, and CD206, exhibiting M2-like characteristics. Co-culture of M2 macrophages with degenerated NP cells led to IL-10 secretion to promote CD34 expression, and downregulated anabolic genes (type II collagen (COL2), aggrecan), and upregulated catabolic genes (matrix metalloproteinase (MMP)-3, MMP-7). JAK2 and STAT3 expression was significantly increased following co-culture. Activation of the JAK2/STAT3 pathway enhanced vascular endothelial growth factor (VEGF), vascular endothelial growth factor receptor (VEGFR), and CD34 expression and induced further downregulation of COL2 and aggrecan and upregulation of MMP-3 and ***2 macrophage infiltration and pathological neovascularization are prominent in degenerated NP tissue. IL-10 secreted by M2 macrophages activates the JAK2/STAT3 pathway to promote pathological microangiogenesis by up-regulate the expression o

关键词： Mast cells   chronic urticaria   chronic inducible urticaria   patient reported outcome measures   pathophysiology   novel therapies   BTK   Bruton tyrosine kinase   CIndU   chronic inducible urticaria   CSU   chronic spontaneous urticaria   CU   chronic urticaria   FcεRI   high-affinity IgE receptor   FDA   Food and Drug Administration   fgAH   first-generation antihistamine   IL   interleukin   ISS7   itch severity score over 7 days   LTRA   leukotriene receptor antagonist   MRGPRX2   Mas-related G-protein-coupled receptor X2   PROMs   patient-reported outcome measures   QOL   quality of life   sgAH   second-generation antihistamines   Siglec   sialic acid-binding immunoglobulin-like lectin   TNF-α   tumor necrosis factor   TPO   IgG anti-thyroid peroxidase antibodies   TSLP   thymic stromal lymphopoietin   UAS   urticaria activity score   UAS7   urticaria activity score over 7 days   UAS7   TD   urticaria activity score twice daily over 7 days   UCT   urticaria control test   UCT7   urticaria control test over 7-day recall period  

摘要： Chronic urticaria (CU) is defined by pruritic wheals with or without angioedema, associated with severe itch, which persist for greater than 6 weeks. Lesions move from one part of the body to another and generally are evanescent, lasting less than 24 hours. The global prevalence of the disease ranges from 0.5 - 5%, and is correlated with an annual economic burden over $200 million in the United States. CU can be further divided into chronic spontaneous urticaria (CSU) and chronic inducible urticaria (CIndU). Whereas CSU has no identifiable trigger, CIndU can be provoked by both physical and non-physical stimuli. As many as 7 - 30% of CU patients can have both types. Mast cells are the major effector cells in the pathogenesis of CU. When activated, mast cells characteristically release bioactive mediators including histamine that bind to specific receptors causing vasodilation and extravasation of fluid from the blood vasculature. This causes the characteristic wheals and itch. However, the pathophysiology of CU is much more complex, involving many mast cell surface receptors, cytokines, and cell activation pathways which are targets for many of the currently available and investigational therapies. Studies have demonstrated that CU causes a significant amount of distress and disruption to patients’ daily lives that can be evaluated using validated patient-reported outcomes measures (PROMS). In this review, we will review CU epidemiology, pathophysiology, subtypes and diagnosis with discuss current and novel therapies.

关键词： cell death   IFN-gamma   mesenchymal stem/stromal cells   necroptosis   TNF-alpha  

摘要： IFN-gamma and TNF-alpha are two vital inflammatory factors elevated aberrantly in many diseases. Such an inflammatory microenvironment is detrimental to residual cells such as mesenchymal stem cells (MSCs), yet the precise mechanisms are not fully understood. IFN-gamma and TNF-alpha have distinct effects on the immunoregulatory properties of MSCs, and they have been proposed as optimal priming factors to enhance the immunosuppressive capacity of engineered MSCs. Thus, the overall effects of IFN-gamma and/or TNF-alpha exposure on MSCs needs to be elucidated. Here, it is found that IFN-gamma and TNF-alpha synergistically induce cell death of MSCs via necroptosis. When MSCs are exposed to both IFN-gamma and TNF-alpha, their morphological features and biological functions are impaired. Mechanistically revealed by RNA-Sequencing, the injured MSCs undergo a unique cell death process, namely necroptosis. Compared with controls, IFN-gamma synergized with TNF-alpha to increase the expression of RIPK1, RIPK3, MLKL, and all other genes associated with necroptosis. Rescue experiments further demonstrate that this process can be reversed by RIPK3 and MLKL inhibitors but not by the RIPK1 inhibitor, suggesting a RIPK1-independent pathway. Collectively, this study discloses an inflammatory injury mechanism of MSCs, which may shed new light on revealing the MSCs deficits in many inflammatory diseases with expectations to inspire potential targeted therapies. In addition, inflammatory impairment should be taken into consideration when delivering cell therapy based on MSCs primed with IFN-gamma and TNF-alpha.

关键词： Astilbin   Flavonoid   Endometritis   PPAR-gamma   NF-kappa B   STAT3  

摘要： Ethnopharmacological relevance: Astilbin (ATB), a natural flavonoid compound with anti-inflammatory bioactivities, can be isolated from Smilax china L., which has been used in traditional Chinese medicine to treat pelvic inflammatory disease (PID) (including endometritis). Our previous studies reported that flavonoids from Smilax china rhizome (FSCR) have therapeutic effects in rats with PID. However, the effects of ATB, the main active component of FSCR, against endometritis remain unknown. Aim of the study: We aim to investigate the role of ATB on endometritis induced by lipopolysaccharide (LPS) in rats and elucidate the mechanisms underlying anti-inflammatory action of ATB on LPS-stimulated endometrial epithelial cells (EECs). Methods: The effects and action mechanisms of ATB on LPS-induced endometritis in rats and LPS-induced EECs were systematically assessed using H&E staining, immunohistochemistry, ELISA, RT-PCR, western blotting, immunofluorescence, molecular docking and siRNA knockdown technology. Results: ATB significantly alleviated typical uterine pathological damages in endometritis, decreased inflammatory cytokine levels in both serum and uterus, and also inhibited the excessive release of inflammatory cytokines in EECs induced by LPS. Mechanistically, ATB markedly upregulated PPAR-gamma levels and suppressed the overexpression of TLR4 and IL-6R proteins and their downstream signals, MyD88, and phosphorylation of NF-kappa B P65, JAK2, and STAT3, in vivo. Further, the effects of ATB on PPAR-gamma protein expression, and NF-kappa B and STAT3 signalling activation in LPS-induced EECs were consistent with the results of in vivo experiments. Furthermore, both PPAR-gamma-specific siRNA transfection and a selective PPAR-gamma antagonist abolished ATB-induced inhibition of NF-kappa B and STAT3 signalling activation and production of inflammatory cytokines. Molecular docking and in vitro experiments further proved that ATB can target PPAR-gamma binding. Conclusi

关键词： 妥昔单克隆抗体   环磷酰胺   长春地辛   表柔比星   泼尼松   弥漫大B细胞淋巴瘤  

摘要： 评价利妥昔单抗与CHOP化疗方案相结合在治疗弥漫性大B细胞淋巴瘤(DLBCL)过程中的临床治疗反应。方法 在本院选取2023年1月至2024年6月间确诊患有DLBCL的104例患者作为研究样本并将其随机划分为两个治疗组别。观察组接受利妥昔单抗与CHOP方案联合治疗而对照组则仅接受CHOP方案单一治疗。本研究旨在比较两种治疗方案在临床应用中的疗效差异。结果 观察组的总有效率显著高于对照组(P<0.05)。较于对照组,观察组在接受治疗后的血清中的CD3+与CD4+水平呈现上升趋势而CD8+水平则相对较低(P<0.05)。观察组的患者出现不良事件的比率明显低于对照组,但差异不具有统计学意义(P>0.05)。相较于对照组,观察组的生存率显著升高而复发率显著降低(P<0.05)。相较于对照组,观察组在接受治疗后所得到的预后指数评分呈现出降低的趋势(P<0.05)。结论 合并利妥昔单抗与CHOP方案对弥漫性大B细胞淋巴瘤进行治疗展现出显著的治疗效果,不仅提升了总体有效率而且并未导致不良反应的增加,因此该治疗方案具有较高的临床应用价值。

摘要： T cells rely on short peptides presented by highly polymorphic major histocompatibility complexes (MHCs) to selectively initiate adaptive immune responses. Despite its importance, few techniques can systemically evaluate stable peptide presentation across diverse MHC alleles. Here, we describe a yeast display pipeline that can be deployed to rapidly screen proteomic space to identify class I pMHC binders across many alleles. Through this, we capture unique biological phenomena such as interference with peptide presentation via type IV drug-induced hypersensitivity. We apply this approach to multiple pathogen proteomes (Mtb Type 7S substrates, SARS-CoV-2, Dengue, and Zika) to create a high-resolution catalog of potential T cell antigens. Altogether, this platform acts as a flexible tool to generate large unbiased datasets for class I peptide presentation at a speed and scale competitive with the biological systems they represent.

关键词： 中性粒细胞与淋巴细胞比值(NLR)   PD-1抑制剂   晚期胃癌   免疫治疗   临床价值  

摘要： 探讨外周血中性粒细胞与淋巴细胞比值(NLR)在PD-1抑制剂治疗HER2阴性晚期胃癌患者中的临床应用价值。方法 分析2022年1月至2023年6月期间40例接受PD-1抑制剂治疗的HER2阴性晚期胃癌患者的病历。所有患者进行了血常规检测,并通过NLR值(中性粒细胞计数/淋巴细胞计数)评估炎症状况,分为高NLR组(NLR>2.43)和低NLR组(NLR≤2.43),比较两组的临床病理特征和治疗效果。结果 肿瘤分化类型、分期、远处转移和浸润度在两组间有显著差异(P<0.05)。高NLR组和低NLR组的治疗有效率分别为38.89%和80.82%,差异显著(P<0.05)。NLR是影响进展期胃癌免疫治疗效果的独立危险因素。结论 NLR作为反映全身免疫与炎症状况的血液学指标,在HER2阴性晚期胃癌患者免疫治疗中具有重要的临床价值。低NLR组的治疗有效率显著高于高NLR组,提示NLR可作为预测免疫治疗效果的潜在生物标志物。