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摘要： Highlights•We experienced Surfer's myelopathy (SM) occurred during exercise unrelated to surfing. •Spine MRI showed T2 hyperintensity with “pencil-like” long-axis lesion, typical for SM. •Significant elevation of IL-6 levels were seen in the CSF. •The nerve conduction tests indicated motor dominant neuropathy in the lower limbs. •The flaccid paralysis and sensory loss only slightly improved after steroid pulse therapies.

关键词： Subarachnoid hemorrhage   IL-33   ST2   AKT   Microglia  

摘要： Background and purpose: ST2, a member of the interleukin-1 (IL-1) receptor family, along with its ligand IL-33, plays critical roles in immune regulation and inflammatory responses. This study investigates the roles of endogenous IL-33/ST2 signaling in subarachnoid hemorrhage (SAH) and elucidates the underlying mechanisms. Methods: Dynamic changes in endogenous IL-33 levels were examined following SAH induction in vivo. Rats underwent the endovascular perforation model of SAH and were randomly assigned to receive either recombinant IL-33 (rIL-33) or a vehicle, administered intranasally 1 h post-SAH. ST2 siRNA or an AKT selective inhibitor was administered intraperitoneally (i.p.) 48 h prior to SAH induction to explore the potential mechanisms of IL33-mediated neuroprotection. Results: Endogenous IL-33 and ST2 levels were elevated in in vitro models of SAH. Exogenous IL-33 significantly alleviated neuronal apoptosis, reduced brain edema, and enhanced short-term neurofunction in a dosedependent manner following SAH in rats. Conclusion: Exogenous rIL-33 alleviates SAH-induced neurological deficits by promoting M2-like polarization of microglia post-SAH. These findings suggest a potential role of the microglial ST2/AKT axis in IL-33-related neuroprotection, which warrants further investigation.

关键词： TNF-alpha   Anti-TNF-alpha therapy   Sepsis   Treatment failure  

摘要： Sepsis, a condition of significant clinical concern, is characterized by life-threatening organ dysfunction that arises from an infection and is exacerbated by a dysregulated host response. Targeting immune modulation, particularly against tumor necrosis factor-alpha (TNF-alpha), has emerged as a promising anti-inflammatory therapeutic strategy. However, approaches such as blood purification to eliminate inflammatory mediators or the use of anti-TNF-alpha therapies have shown limited efficacy in clinical practice. This literature review aims to elucidate the pathogenesis of sepsis and dissect the factors contributing to unfavorable outcomes in TNF-alpha-targeted treatments. Our analysis highlights several potential reasons for therapeutic failure. Complete blockade of TNF-alpha may adversely affect both TNFR1 and TNFR2 signaling, thereby reducing the efficacy of TNF-alpha inhibitors. Additionally, the complex heterogeneity of sepsis, including the etiology of infection, patient-specific factors (e. g., immune responsiveness, body mass index, and obesity), the development of anti-drug antibodies, and treatment duration, significantly influences therapeutic outcomes. Based on these insights, we emphasize the need for precision medicine in sepsis management. This includes stratifying patients into subgroups, using TNFR2 agonists or TNFR1-specific antagonists, refining drug design, implementing multi-target combination therapies, and considering the patient's physiological state at the time of treatment. Collectively, these strategies could enhance the efficacy of sepsis management. This review underscores the multifaceted nature of sepsis treatment and highlights the imperative for personalized, multimodal therapeutic approaches to improve clinical outcomes.

关键词： IL-1 beta   Rheumatoid arthritis   Epilepsy  

摘要： Aims: Numerous clinical studies have revealed a positive correlation between rheumatoid arthritis (RA) and an elevated risk of epilepsy. This study aimed to investigate the seizure susceptibility in the collagen-induced arthritis (CIA) mice model. Main methods: The classic CIA model was used to mimic RA pathogenesis in mice. The pentylenetetrazole (PTZ)induced seizure model and audiogenic seizure model were used to evaluate seizure susceptibility. Neuroinflammation was assessed through ELISA, Western blot, and immunofluorescence staining. Additionally, electrophysiological techniques were applied to investigate the excitation/inhibition (E/I) balance. Key findings: CIA modeling raised the level of IL-1(3, induced E/I imbalance in the dentate gyrus (DG) region, and enhanced seizure susceptibility to PTZ in C57BL/6 mice. However, knockout (KO) of IL-1(3 attenuated peripheral inflammatory symptoms and blocked the increase in seizure susceptibility in CIA-modeled mice. Additionally, conditional IL-1R1 KO in CaMKII alpha-positive neurons did not affect the peripheral inflammatory symptoms but rescued both the increased seizure susceptibility and E/I imbalance in CIA-modeled mice. Furthermore, increased susceptibility to audiogenic seizure susceptibility was also observed in CIA-modeled BDA/1 mice, accompanied by the elevated IL-1(3 levels and neuronal IL-1R1-related Akt phosphorylation in the hippocampus. Significance: Increased seizure susceptibility in the CIA mouse model depends on IL-1(3 and neuronal IL-1R1. These data indicated that IL-1(3 and neuronal IL-1R1 may be the key targets for its intervention.

关键词： Crohn's disease   Entyvio   Humira   Omvoh   Otulfi   Pyzchiva   Remicade   Rinvoq   Selarsdi   Skyrizi   Stelara   Steqeyma   TNF inhibitors   Tremfya   Wezlana   Yesintek   adalimumab   adverse effects   dosage   drug interactions   efficacy   guselkumab   infliximab   lactation   mirikizumab   pregnancy   risankizumab   safety   upadacitinib   ustekinumab   vedolizumab  

摘要： 特发性肺纤维化（IPF）是一种严重的间质性肺疾病，发病机制至今尚未完全阐明。近年来研究表明补体系统激活在IPF病变过程中扮演重要角色。抑制补体系统激活为IPF治疗策略提供新思路。现就有关补体系统激活参与IPF病变的分子机制与以补体系统为潜在治疗靶点进行IPF药物研发进展进行综述，以期为IPF防治提供新观点。

摘要： 抗细胞因子自身抗体（AAb）是由浆细胞产生的，可干扰相应细胞因子信号的传导，阻断靶细胞因子的生物学功能，导致患者对病原菌的易感性增加，患者可出现反复复杂感染。目前已被认识的AAb包括抗干扰素、抗粒细胞-巨噬细胞集落刺激因子、抗IL-6、抗IL-17、抗IL-12/23自身抗体，这些抗体均可引起免疫缺陷相关感染。现对其临床表现和已发现的相关机制进行综述。

关键词： IL-21   Radiotherapy   Melanoma   Anti-tumor  

摘要： Melanoma, known for its aggressive behavior and tendency to metastasize to the brain and lungs, is a formidable challenge in oncology. Radiotherapy is a potent treatment for localized solid tumors, effective against both intracranial and extracranial metastases. Yet, some melanoma patients exhibit substantial resistance to radiotherapy, with the underlying mechanisms of this resistance remaining elusive. While radiotherapy can stimulate the infiltration of immune cells, thereby triggering a range of immunostimulatory effects, it can also suppress the tumor microenvironment (TME), limiting its effectiveness. In physiological conditions, cytokines inhibit the activity of immunosuppressive cells through paracrine and autocrine signaling, while also activating immune cells to boost antitumor responses. Here, we found that Interleukin (IL)-21 expression was higher in the mice with good radiotherapy response to melanoma than in the mice with poor radiotherapy response. Interestingly, we also observed the higher infiltration of M2 TAMs and lower CD8+ T cells in the group with poor radiotherapy response. To tackle this issue, we explored the therapeutic potential of a plasmid encoding IL-21, delivered via attenuated Salmonella, in mice bearing melanomas. Our findings revealed that IL-21 administration significantly reduced M2 TAMs infiltration and enhanced CD8+ T cells infiltration and granzyme B (GZMB) expression within melanoma tumors. Most importantly, the combination of IL-21 with radiotherapy led to markedly tumor reduction compared to either treatment alone. This research highlights the potential of IL-21 as a valuable adjunct to radiotherapy in the treatment of melanoma, presenting a promising strategy for enhancing antitumor immune responses and optimizing patient outcomes.