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摘要： Inflammatory bowel diseases (IBD) affect millions of people worldwide. The use of anti-TNF-alpha for the treatment of moderate-to-severe IBD faces primary non-response, loss of response during treatment or intolerance issues. As an alternative, a strategy consisting of oral administration of TNF-alpha siRNA was evaluated in the present study for the local treatment of IBD. TNF-alpha siRNA entrapped in lipid nanoparticles (LNPs) was microencapsulated in gastroresistant alginate particles using an original process. The encapsulation yield of both siRNA and LNPs in microparticles (MPs) was at least 90%. Oral administration of MPs significantly reduced both clinical score and therapeutic index in a TNBS-induced colitis model in mice. Near complete removal of tissue damage, including edema, ulceration and necrosis, was observed in colon sections from treated mice. Reduced variation in gene sets involved in the global inflammatory response and the TNF-alpha/NF-kappa B signaling pathway was detected in the colon compared to untreated mice, demonstrating the anti-inflammatory activity of MPs. Finally, biodistribution studies showed the targeting of the inflamed colon by MPs and the colocalization of LNPs and MPs at the site of action. These MPs may represent a promising siRNA delivery platform for the oral treatment of IBD.

关键词： Mucosal immunology  

摘要： The airway epithelium plays a crucial role in maintaining lung homeostasis, and its dysregulation is often linked to various lung diseases, including asthma. Ciliated cells, abundantly present in the mammalian airway epithelium, have a critical function in clearing inhaled particles and pathogens. We show here that ciliated cells constitutively express IL-17D, which functions as an immune brake in limiting allergic inflammation in murine models of asthma. Mechanistically, IL-17D functions to prevent influx of classical monocytes into the lung and their subsequent conversion to pathogenic alveolar macrophages, through binding to CD93. Deficiency in Il17d or Cd93 increased the expression of chemokine receptors on classical monocytes, including CCR6, thereby enhancing their recruitment to the lung and type 2 inflammation. Our study thus reveals an unexpected protective role of ciliated cells and IL-17D in lung immune responses and asthma, which can be further explored for treating related diseases.

关键词： 药物超敏反应综合征   阿司匹林   吲哚布芬   药物不良反应   药源性疾病  

摘要： 本文报告了1例冠心病患者应用阿司匹林和吲哚布芬抗血小板治疗过程中发生交叉药物超敏反应（drug-induced hypersensitivity syndrome，DIHS）的病例，旨在提高临床诊疗团队对DIHS的认识及鉴别能力。通过对2024年12月心内科收治的一名DIHS患者临床资料进行回顾性分析（包括不良反应史、临床表现、病情进展、治疗及转归），明确患者交叉DIHS的发生与环氧酶-1（COX-1）通路相关。结合对同类药物DIHS的文献检索，提示既往发生过阿司匹林相关DIHS的人群，应用吲哚布芬时需谨防交叉过敏的发生。

关键词： 牛病毒性腹泻病毒   Erns蛋白   单克隆抗体   ELISA  

摘要： 为了制备牛病毒性腹泻病毒（BVDV）单克隆抗体及建立抗原捕获ELISA检测方法，采用大肠杆菌原核表达的BVDV Erns截短蛋白免疫BALB/c小鼠，三免后利用细胞融合和杂交瘤筛选，选用效价高的单克隆抗体，通过条件优化建立BVDV抗原捕获ELISA检测方法，对其特异性、敏感性和重复性进行了验证，并与IDEXX商品化试剂盒及RT-PCR进行临床样品符合。结果显示，获得2株效价较高的IgG1型单克隆抗体杂交瘤细胞2B3、2B10，轻链均为κ链。选用效价更高的2B10单克隆抗体作为检测抗体，兔源BVDV多克隆抗体作为捕获抗体，建立的BVDV抗原捕获ELISA与临床常见病原（牛轮状病毒、牛冠状病毒、牛副流感病毒3型、牛呼吸道合胞体病毒、牛支原体）无交叉反应，最低可检测102.53TCID50的BVDV病毒液，批内和批间变异系数均低于5%，与IDEXX试剂盒和RT-PCR的总体符合率分别为91.76%～93.33%和94.12%～96.67%。结果表明，基于2B10单克隆抗体建立的BVDV抗原捕获ELISA检测方法具有良好的特异性、敏感性和重复性，为BVDV的检测和防控提供借鉴技术手段。

关键词： 盖塔病毒   Cap蛋白   原核表达   多克隆抗体   免疫组织化学  

摘要： 为制备猪盖塔病毒（GETV）Cap蛋白多克隆抗体并探索其应用潜力，首先构建pCold-TF-Cap重组质粒，通过0.4 mmol/L IPTG诱导高效表达可溶性TF-Cap融合蛋白。经Ni-NTA亲和层析纯化后，利用SDS-PAGE鉴定重组蛋白纯度较高，BCA法测得蛋白浓度为22 mg/mL。以纯化的融合蛋白与佐剂乳化后免疫6～8周龄BALB/c小鼠，成功制备效价达1∶128 000的鼠源多克隆抗体。通过Western-blot分析与间接免疫荧光实验（IFA），证实该多克隆抗体能够特异性识别GETV感染的BHK-21细胞内源性Cap蛋白。此外，以制备的多克隆抗体为一抗、酶标羊抗鼠IgG为二抗，建立了检测GETV感染小鼠脾和肝组织中Cap蛋白的免疫组织化学（IHC）检测方法。结果显示，阳性信号清晰定位于细胞质中，呈现明显的棕色信号。本研究成功制备了特异性强的GETV Cap蛋白多克隆抗体，并建立了配套IHC检测方法，为GETV的基础研究和临床诊断提供了可靠的免疫学工具。

关键词： CS-PVA-IL/BaTiO   复合离子凝胶   挠曲电效应   柔性传感器   健康监测  

摘要： 传统压电器件难以有效感知关节活动引发的弯曲应变梯度，限制了其在可穿戴健康监测设备中的应用，因此亟需研发对弯曲形变响应灵敏的传感器以实现高效的人体动态信号感知。本文基于挠曲电效应，设计并制备了含有BaTiO3纳米颗粒的壳聚糖-聚乙烯醇-离子液体（CS–PVA–IL）复合离子凝胶，系统研究了BaTiO3含量对挠曲电响应特性的影响规律。当BaTiO3含量为0.25 wt%时，挠曲电响应电压高达1.8 ?V，挠曲电系数可达1.92 nC/m，展现出优异的挠曲电响应特性。所制备的传感器具有优异的线性响应特性与循环稳定性，在人体健康监测中，传感器在腕关节和食指弯曲过程中可产生清晰的响应电信号，响应电压峰值可有效反映弯曲幅度变化，验证了其在健康监测方面的实用性。本研究为柔性传感器的机电转换机制提供了新思路，为智能穿戴与生物电子领域的应用奠定了基础。

关键词： 柴胡皂苷A   柴胡皂苷D   单克隆抗体   间接竞争酶联免疫吸附分析  

摘要： 通过过碘酸盐氧化法将柴胡皂苷A、柴胡皂苷D分别与牛血清蛋白（BSA）和卵清蛋白（OVA）偶联，得到免疫抗原柴胡皂苷A/D-BSA和包被抗原柴胡皂苷A/D-OVA。使用制备得到的柴胡皂苷A/D-BSA免疫BALB/c小鼠，筛选得到抗柴胡皂苷A、柴胡皂苷D单克隆抗体细胞株共15株，其中抗柴胡皂苷单克隆抗体SD6与柴胡皂苷D、柴胡皂苷A、6''-O-乙酰基柴胡皂苷A、6''-O-乙酰基柴胡皂苷D、柴胡皂苷C、柴胡皂苷E和羟基柴胡皂苷A的交叉反应率分别为100.00%、99.94%、95.06%、94.89%、1.97%、1.89%、0.93%，与柴胡皂苷F、柴胡皂苷B1及柴胡皂苷B2等其他化合物的交叉反应率均＜0.1%。基于筛选出的抗柴胡皂苷D单克隆抗体SD6建立的间接竞争酶联免疫吸附分析（icELISA）方法的IC50为32.68 ng·mL-1，最佳检测范围为6.4～159.12 ng·mL-1，加样回收率为95.00%～104.5%，变异系数为2.7%～4.0%。利用建立的icELISA测定了19批北柴胡药材中柴胡皂苷A和柴胡皂苷D的总含量，并采用超高效液相色谱方法（UPLC）对所开发的icELISA检测结果进行验证，2种方法检测结果显示其相关性为0.994 7，表明所建立的icELISA可以用于北柴胡中柴胡皂苷A与柴胡皂苷D总含量的快速检测。

关键词： italic>DPB1*1789:01   HLA-DPB1   NGS   organ transplantation  

摘要： HLA-DPB1*1789:01 differs from HLA-DPB1*02:01:02:89 by a non-synonymous nucleotide substitution in exon 4.

摘要： At the Group for Research and Assessment of Psoriasis and Psoriatic Arthritis (GRAPPA) 2024 annual meeting, Drs. Dennis McGonagle and Wilson Liao discussed "MHC-I-opathies," a class of immune-mediated diseases genetically associated with major histocompatibility complex class I (MHC-I) and class I peptide processing. MHC-I-opathies demonstrate epistatic interactions, genetic associations, and immunopathology that are distinct from classic B cell and autoantibody-driven autoimmune diseases. Investigations into the pathomechanisms of MHC-I-opathies have revealed a blend of tissue-specific innate immunity and CD8 T cell responses. Several functional pathomechanisms by which MHC-I molecules increase psoriasis (PsO) susceptibility were presented by McGonagle and Liao, and there were multiple associations within the HLA-C locus. Antigen presentation to T cells, HLA regulation of natural killer cells and CD8 T cells through killer immunoglobulin-like receptors, and HLA regulation of dendritic cells through leukocyte immunoglobulin-like receptors were discussed. Interestingly, MHC-I associations are not only linked to excessive inflammation in MHC-I-opathies but also to the spontaneous suppression of infection (eg, HIV-1 elite controllers). This striking prominence of MHC-I in PsO and antiviral immunity provides insight into why autoimmune alleles are maintained in the human genome and how protective antiviral pathways may be linked to aberrant activation of MHC-I-opathies. Outside of spinal inflammation in HLA-B27-positive axial psoriatic arthritis (PsA), the basis for MHC-I genetics in PsA remains less clear and is at least partly linked to greater PsA heterogeneity. Understanding the contribution of MHC-I in PsO and PsA may have important implications for therapy development.