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摘要： BACKGROUND Relapsing polychondritis (RP) is a rare autoimmune disease characterized by recurrent inflammation involving the cartilaginous tissues such as ears, nose, joints, and cartilaginous small airways. The disease fluctuates in severity from mild auricular inflammation to life-threatening presentations such as cardiovascular or tracheobronchial involvement. Notably, a large number of case reports demonstrate an association between RP and inflammatory bowel disease. In these cases, ulcerative colitis (UC) is mostly seen in these patients, and very rarely Crohn's disease. CASE REPORT In our case, the patient experienced symptoms of UC in the form of abdominal pain and diarrhea after the initiation of adalimumab as treatment for RP. This raises the concern that UC might co-exist with RP as these conditions can occur concomitantly. Alternatively, the symptoms may have been related to the adalimumab treatment, as his RP symptoms improved but his UC symptoms persisted. Consequently, an alternative anti-TNF agent might be needed to induce remission of both diseases. CONCLUSIONS To conclude, both RP and inflammatory bowel disease can co-exist simultaneously in some patients. According to the literature, anti-TNF agents are emerging as a promising treatment in cases in which conventional immunosuppressive therapy has failed. In our case, treatment with adalimumab controlled the RP but it was not successful in treating the UC symptoms. This raises the question of whether infliximab should instead be the drug of choice as a TNF-alpha blocker in this situation, as the patient's UC symptoms subsided completely after the introduction of infliximab.

关键词： Visceral leishmaniasis   nanoparticle   amphotericin B   anti IL-10 dictionary peptide   in-vivo  

摘要： Aim: This study aimed to develop a novel nanotherapeutic approach by combining an interleukin-10 (IL-10) peptide antagonist with amphotericin B (AmB) to enhance antileishmanial efficacy while reducing cytotoxicity. Materials and methods: A peptide antagonist targeting IL-10, identified via in-silico analysis and showing minimal cytotoxicity (95% promastigote viability at 20 mu g/mL), was synthesized and conjugated with AmB using chemical cross-linkers. The conjugate was encapsulated in gamma-cyclodextrin to produce uniform nanoparticles (similar to 40 nm). Characterization was performed using Fourier Transform Infrared Spectroscopy (FTIR), Scanning Electron Microscopy (SEM), and Transmission Electron Microscopy (TEM). In vitro and in vivo studies were conducted to assess parasite burden, immune response, and safety parameters. Results: The nanoformulation significantly reduced parasite burden and improved amastigote clearance, as confirmed by real-time PCR. Cytokine profiling revealed elevated IL-12 and other protective cytokines, indicating enhanced immune modulation. Hematological, biochemical, and splenomegaly analyses demonstrated improved safety and therapeutic efficacy compared to AmB alone. Conclusion: The IL-10 antagonist - AmB nanoformulation represents a promising immunomodulatory therapeutic strategy for leishmaniasis. Its enhanced efficacy and safety highlight its potential for application, particularly in immunocompromised patients.

关键词： Drug-induced sarcoidosis   Etanercept   Paradoxical adverse events   Psoriasis   Secukinumab   TNF-alpha inhibitors  

摘要： BackgroundTumor necrosis factor-alpha (TNF-alpha) inhibitors are effective treatments for autoimmune diseases but may cause paradoxical adverse events (PAEs), including sarcoid-like granulomatosis. Etanercept, a soluble TNF receptor fusion protein, has been more frequently associated with this phenomenon compared to monoclonal *** presentationWe describe a 61-year-old man with chronic plaque psoriasis on long-term etanercept therapy who developed bilateral visual symptoms. Ophthalmologic evaluation revealed granulomatous panuveitis with retinal vasculitis and macular edema. Imaging and lung biopsy confirmed pulmonary sarcoidosis with non-caseating granulomas. Etanercept was discontinued, and systemic corticosteroids were started. Because of steroid dependence, secukinumab (an IL-17A inhibitor) was introduced, together with an intravitreal dexamethasone implant for refractory macular edema. Over a 4-year follow-up, the patient achieved complete and sustained resolution of ocular inflammation with stable systemic control, without the need for further *** case illustrates a rare but clinically significant presentation of etanercept-induced sarcoidosis with primary ocular involvement. Unlike typical psoriatic uveitis, the bilateral granulomatous pattern prompted further systemic work-up, which revealed otherwise silent pulmonary disease. To our knowledge, this is the first long-term report of etanercept-induced ocular sarcoidosis successfully managed with secukinumab, which allowed steroid withdrawal. While IL-17A inhibitors are not yet approved for uveitis, available data and our observation suggest a potential role in selected ***-induced ocular sarcoidosis is a rare but clinically significant PAE. Prompt recognition and multidisciplinary management are crucial to prevent vision loss. IL-17A inhibition may represent a promising steroid-sparing therapeutic option when TNF-alpha inhibitors are contraindicated

关键词： IL-21 variant   cancer immunotherapy   colorectal cancer   engineered cytokine   melanoma  

摘要： IL-21, as an immune agonist, has demonstrated limited therapeutic efficacy in cancer immunotherapy. To overcome this inherent limitation, we constructed a yeast surface-displayed IL-21 mutant library guided by the structure of the IL-21/IL-21 receptor (IL-21R). Following one round of magnetic bead sorting and three rounds of fluorescence-activated cell sorting, several variants were isolated and evaluated for receptor-binding affinity at the protein level. We identified an IL-21 Variant (IL-21V) featuring four critical mutations (Q19L, Y23N, V69T and K73Q) at the interaction interface with IL-21R. Compared with wild-type IL-21, IL-21V exhibited an approximately 7-fold increase in IL-21R binding affinity and a ~50-fold increase in STAT3 signalling pathway activation. In preclinical in vivo models, IL-21V exhibited broad-spectrum antitumor activity against B16F10 melanoma, MC38, and CT26 colorectal cancer. Notably, IL-21V exhibited significantly stronger antitumor effects compared to wild-type IL-21, even at a low dose of 0.15 mg/kg, highlighting its potential as a promising and effective immunotherapeutic candidate for cancer treatment.

关键词： 重症肺炎   辅助性T淋巴细胞1/辅助性T淋巴细胞2   肺炎程度评分   模型   预后  

摘要： 目的 构建重症肺炎的外周血辅助性T淋巴细胞1/辅助性T淋巴细胞2(helper T lymphocyte 1/helper T lymphocyte 2,Th1/Th2)细胞因子与肺炎程度指数(pneumonia degree index,PSI)评分的联合模型,探讨该联合模型对重症肺炎患者预后的评估价值。方法 选取2021年1月至2023年8月收治的120例重症肺炎患者,并对其进行为期1年的随访,根据随访期间患者的生存状态分为生存组(n=82)和死亡组(n=38)。比较两组患者的一般资料、实验室指标及PSI评分,采用多因素logistic回归分析重症肺炎患者预后的影响因素,根据结果构建logistic回归预测模型,并绘制受试者工作特征(receiver operating characteristic curve,ROC)曲线,采用ROC曲线下面积(area under curve,AUC)评估预测模型对重症肺炎患者预后的预测价值。结果 死亡组平均年龄[(80.62±10.41)岁]、中性粒细胞与淋巴细胞比值(neutrophil-to-lymphocyte ratio,NLR)水平(13.60±2.45)及PSI评分(127.64±22.18)均高于生存组[(70.18±18.30)岁、10.79±6.12、113.59±20.61](t=3.275、2.726、3.299,P<0.05),住院时间[(11.15±10.03)d]、外周血Th1/Th2细胞因子水平(4.02±1.02)均低于生存组[(18.45±11.26)d、5.01±1.62](t=3.146、3.458,P<0.05)。多因素logistic回归分析结果显示,年龄(OR=1.613,95%CI:1.744～3.498)、住院时间(OR=1.603,95%CI:1.729～3.525)、NLR(OR=1.793,95%CI:1.837～3.844)、Th1/Th2(OR=1.840,95%CI:1.806～4.200)、PSI评分(OR=1.817,95%CI:1.818～4.034)均为影响重症肺炎患者死亡的危险因素。基于外周血Th1/Th2细胞因子、PSI评分构建logistic回归预测模型:logistic(P)=-4.516+0.610(Th1/Th2)+0.597(PSI评分),其对重症肺炎患者死亡预测的敏感度、特异度、AUC分别为79.85%、90.65%、0.912。结论 外周血Th1/Th2细胞因子与PSI评分的联合模型对重症肺炎患者死亡预测的敏感度、特异度及AUC水平均较高,预测效能好,对临床评估重症肺炎患者预后有一定指导价值。

关键词： biologic   interleukin-17   interleukin-23   psoriasis   psoriatic arthritis  

摘要： OBJECTIVES:Biologic therapies for skin psoriasis (PsO) have been linked to a lower risk of developing psoriatic arthritis (PsA), but their efficacy across different mechanisms of action remains to be fully explored. This study aimed to compare PsA risk in PsO patients prescribed interleukin-23 inhibitors (IL23i) vs interleukin-17 inhibitors (IL17i). METHODS:This retrospective cohort study utilized the TriNetX database to categorize adult PsO patients into two cohorts: those newly prescribed IL23i (without IL17i exposure) and those newly prescribed IL17i (without IL23i exposure). Patients with a history of PsA or previous use of anti-tumor necrosis factor-α or anti-interleukin-12/23 agents were excluded. A total of 5,490 patients, matched 1:1 by propensity scores, were analyzed for PsA risk using hazard ratios (HR) from Cox regression. RESULTS:The 5-year cumulative incidence of PsA was significantly lower in IL23i users compared with IL17i users (11.68% vs 19.94%; p <0.001). IL23i treatment was associated with a reduced PsA risk (HR 0.475, 95% CI 0.382-0.590). This reduced risk persisted across various subgroups defined by age, sex, race, PsO subtypes, obesity, and elevated inflammatory markers. Similar results were observed in individual drug comparisons, with lower risks for guselkumab vs secukinumab (0.480, 0.358-0.645) and ixekizumab (0.698, 0.509-0.956), risankizumab vs secukinumab (0.433, 0.306-0.612) and ixekizumab (0.504, 0.347-0.732), and tildrakizumab vs secukinumab (0.339, 0.131-0.875). The comparison of tildrakizumab vs ixekizumab (0.451, 0.171-1.191) also suggested a lower risk but was not statistically significant. CONCLUSIONS:PsO patients treated with IL23i had a lower subsequent PsA risk compared with those treated with IL17i.

关键词： Natural sciences   biological sciences   Immunology   systems biology   cancer systems biology  

摘要： Interference by tumor-associated macrophages may significantly reduce the efficacy of therapeutic viruses designed to infect cancer cells and activate anti-tumor T cells. Using a computational model, we hypothesized that viruses encoding a T cell-stimulating signal, like interferon-gamma (IFN-gamma), could overcome this barrier. We engineered an alphavirus-based replicon expressing IFN-gamma and evaluated its effect in various human-derived tumor-immune coculture systems and an in vivo murine model. While alphavirus replicons do not replicate in macrophages, macrophages acted as a barrier, limiting tumor infection in afrequency-depen-dent but phenotype-independent manner. Nonetheless, T cell activation occurred even when only a fraction of infected tumor cells expressed IFN-gamma, regardless of macrophage presence, frequency, or phenotype. Additionally, viral stimulation drove macrophage repolarization toward a pro-inflammatory phenotype favoring T cell activation. These findings highlight a strategy for optimizing virotherapy in macrophage-rich tumors by designing viruses that stimulate T cell activation, ensuring therapeutic efficacy.

关键词： 抗狂犬病病毒单克隆抗体   狂犬病   暴露预防   专家共识  

摘要： 抗狂犬病病毒单克隆抗体（anti-rabies virus monoclonal antibody,RmAb）是利用现代基因工程技术开发和生产的一种新型狂犬病被动免疫制剂，其可以特异性地与狂犬病病毒表面G蛋白上的抗原位点结合，阻断病毒与细胞表面受体的结合，从而起到预防作用。与传统的狂犬病免疫球蛋白相比，RmAb具有产量可控、质量稳定、安全性高、比活性好等优势。目前，全球已有4种RmAb产品获批上市。针对临床医生对RmAb认识相对不足的现状，中华预防医学会狂犬病预防控制工作委员会、中国医学救援协会动物伤害救治分会组织中国专家，收集最新证据，参考国内外相关规范、指南和共识，结合专家临床经验等，撰写本共识，为临床工作提供科学和规范的建议。