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关键词： Worship acoustics   Acoustic simulation   Acoustic heritage   Jesuit architecture  

摘要： Following the Council of Trent, profound changes were observed in ecclesiastical architectural space as a result of the new spirit infused into the Catholic Church by the Counter-Reformation. The Jesuit mother church, Il Ges & ugrave;, contributed to the consolidation of the model of the single nave church, eliminating the aisles and reducing the size of the transept. This architectural model was disseminated in step with the expansion of the Society. The churches of Santa Catalina (Cordoba), La Anunciacion (Seville), and La Encarnacion (Marchena, Seville) provide emblematic examples of the model adopted by the Society of Jesus in the second half of the 16th century in Andalusia. The typological, geometric, and material similarities displayed by these churches enable a common analysis of the sound field, to be carried out through in-situ acoustic measurements and simulations. The study of different source positions in similar models enables the determination of the optimal source and receiver configurations. It was found that the position on the main altar, coinciding with the position of the priest in the Tridentine rite, does not facilitate the perception of the sound field, except in the positions in the high tribunes. When the source is under the dome of the transept, the sound field evaluation is more favourable. Conversely, a comparative analysis of churches considered to be 'twins', St Catalina and La Anunciacion, has shown the impact that the interior cladding of these spaces has on the perception of their sound field.

摘要： This review summarizes emerging treatment strategies in pediatric IBD. Pediatric physicians should be aware of these newer agents and familiarize themselves with their most common side effects, as they may serve as the first-line providers managing adverse effects of these therapies. Crohn’s disease (CD) and ulcerative colitis (UC), the two primary subtypes of inflammatory bowel disease (IBD), are commonly managed with immune-modulating therapies. Among the most widely used biologic agents are the tumor necrosis factor inhibitors (TNFis) infliximab and adalimumab. While these agents are effective for many patients, a subset does not respond adequately. Over the past decade, several novel therapies have been approved for adult IBD. Although none of these newer IBD medications are currently approved by the Food and Drug Administration (FDA) for pediatric use, pediatric gastroenterologists are increasingly employing them to treat children with refractory or severe disease. In parallel, specific dietary interventions aimed at reducing inflammation and inducing remission have gained popularity, particularly in pediatric and adult patients with CD. Emerging biologic and small molecule treatments offer therapeutic solutions to children with IBD in the setting of anti-TNF failure or intolerance. Dietary strategies are also increasingly employed in certain cases of CD in the perioperative period and beyond. An expanding IBD armamentarium means that providers should be aware of indications and important side effect profiles of IBD treatments.

摘要： Interleukin-17 (IL-17) has emerged as a key cytokine at the intersection of inflammation and thrombosis, potentially playing a pivotal role in thromboinflammation. This review explores the mechanistic contributions of IL-17 to endothelial dysfunction, platelet activation, monocytes activation, and neutrophil extracellular trap (NET) formation, which collectively promotes a pro-thrombotic state. We summarize findings from experimental models and clinical studies linking IL-17 to thrombosis in autoimmune diseases, atherosclerosis, and infectious diseases such sepsis and COVID-19. Additionally, we discuss the therapeutic implications of IL-17 inhibition in mitigating thromboinflammatory complications. Understanding the role of IL-17 in this process may provide new avenues for targeted interventions in thromboinflammatory disorders.

关键词： 非小细胞肺癌   颗粒酶B   白细胞介素-24   白细胞介素-2  

摘要： 目的 探讨非小细胞肺癌（NSCLC）患者颗粒酶B(GzmB)、白细胞介素-24(IL-24)、IL-2与临床病理特征及化疗敏感性的关系。方法 选取2023年1～12月中国人民解放军联勤保障部队第九八二医院和唐山市人民医院收治的89例NSCLC患者作为研究组，采用1∶1个体匹配原则将89例肺良性肿瘤患者作为对照组。统计两组及研究组不同临床病理特征患者外周血中GzmB、IL-24、IL-2水平，Spearman分析研究组临床病理特征与外周血中GzmB、IL-24、IL-2的相关性，同时给予研究组含铂两药化疗方案，化疗结束后观察敏感性并以此分组，比较二者外周血IL-24、GzmB、IL-2差异，采用受试者工作特征（ROC）曲线及曲线下面积（AUC）分析外周血GzmB、IL-24、IL-2单一及联合预测化疗敏感性的价值。结果 研究组外周血IL-2、GzmB较对照组低，IL-24较对照组高（P<0.05）。研究组外周血中IL-24表达与TNM分期、淋巴结转移、吸烟史呈正相关，与分化程度呈负相关；外周血中GzmB、IL-2表达与TNM分期、淋巴结转移、吸烟史呈负相关，与分化程度呈正相关（P<0.05）。研究组中共有3例失访，21例不敏感，65例敏感。研究组不敏感患者外周血GzmB、IL-2低于敏感患者，IL-24高于敏感患者（P<0.05）。IL-2+GzmB+IL-24预测化疗敏感性的AUC为0.936(95%CI:0.889～0.967)，灵敏度及特异度分别为83.15%、91.01%，高于单一预测价值。结论 外周血GzmB、IL-24、IL-2与NSCLC患者TNM分期、分化程度、淋巴结转移等有关，3者联合检测有助于提高化疗敏感性的预测价值，指导临床诊治。

关键词： 低强度超声   微泡   结直肠癌   免疫逃逸   JNK/c-Jun信号通路  

摘要： 目的 探究低强度超声（LIUS）联合微泡（MBs）对结直肠癌恶性进展和免疫逃逸的影响及机制。方法 将SW480细胞随机分为Control组、LIUS+MBs 60s组、LIUS+MBs 120s组和LIUS+MBs 240s组。CCK-8检测各组细胞增殖活性以及各组细胞共培养的CD8+T细胞的细胞活力；流式细胞术检测各组细胞以及共培养的CD8+T细胞的凋亡率；Transwell实验检测各组细胞迁移和侵袭能力；Western blot检测各组细胞中PD-L1、p-JNK和p-c-Jun蛋白表达。结果 低强度超声联合微泡降低结直肠癌细胞的增殖活性、迁移和侵袭细胞数，增加细胞凋亡率，降低细胞中PD-L1、p-JNK和p-c-Jun蛋白表达，增加与结直肠癌细胞共培养的CD8+T细胞的细胞活力，并降低细胞的凋亡率。结论 低强度超声联合微泡抑制结直肠癌细胞增殖、迁移、侵袭和免疫逃逸并诱导细胞凋亡，其机制与抑制JNK/c-Jun信号通路激活介导的PD-L1表达下调有关。

关键词： alloreactivity   T cell receptor   human leucocyte antigen   protein interface   receptor cross-reactivity  

摘要： Peptides presented by major histocompatibility complex class I (MHC-I) proteins provide biomarkers for therapeutic targeting using T cell receptors (TCRs), TCR-mimicking antibodies (TMAs), or other engineered protein binders. Despite the extreme sequence diversity of the human leukocyte antigen (HLA, the human MHC), a given TCR or TMA is restricted to recognize epitopic peptides in the context of a limited set of different HLA alleles. Here, guided by our analysis of 98 TCR:pHLA complex structures, we identify TCR contact residues and classify 148 common HLA alleles into T cell cross-reactivity groups (T-CREGs) on the basis of their presented surface features. Insights from our work have actionable value for predicting MHC-I restriction of TCRs, guiding therapeutic expansion of existing TCR-based approaches and informing the selection of peptide targets for the development of new therapeutics.

关键词： 抗原修复   免疫组织化学   FFPE   Tris   EDTA  

摘要： 目的 探究一种新型抗原修复液增强石蜡切片免疫组织化学染色效果。方法 分别用三种不同的抗原修复液（即常规使用的柠檬酸修复液、EDTA修复液，及新配方修复液）对30例不同组织的石蜡组织切片进行加热高压抗原修复，然后选择30个在细胞不同表达部位（细胞膜、浆及核）的抗体完成免疫组织化学染色，观察和统计比较用不同抗原修复液的染色效果（阳性染色染色深浅及阳性细胞数量）。结果 使用柠檬酸修复液组染色+为30.0%(9/30)、++为66.6%(20/30)、+++为3.3%(1/30)，EDTA修复液组+为10.0%(3/30)、++为83.3%(25/30)、+++为6.66%(2/30)，新型修复液组+为3.3%(1/30)、++为60.0%(18/30)、+++为36.6%(11/30)。结论 新型抗原修复液在多种石蜡组织样本中表现出较好的修复效果，可以缩短抗原修复时间，为组织抗原修复提供了一种新的选择，具有实用价值。

关键词： 沙丁胺醇   羧甲司坦   慢性支气管炎   急性发作  

摘要： 目的:探讨沙丁胺醇联合羧甲司坦对慢性支气管炎急性发作患者的疗效及对血清PCT、CRP、IL-6的影响。方法:选取无为市中医医院2020年7月～2024年2月收治的120例慢性支气管炎急性发作患者,随机分为观察组和对照组各60例。对照组予以沙丁胺醇雾化吸入治疗,观察组在对照组治疗基础上予以羧甲司坦口服溶液,疗程1周。比较两组患者呼吸系统症状的缓解时间、肺功能指标、临床有效率及血清炎性因子水平,并记录研究期间不良事件发生率。结果:观察组和对照组各有59例纳入研究。与对照组相比,观察组患者治疗后咳嗽、咳痰及喘息症状的缓解时间缩短(P<0.05),FEV1、FVC及FEV1/FVC升高(P<0.05),而血清CRP、PCT及IL-6水平降低(P<0.05)。观察组患者临床有效率高于对照组(P<0.05),而不良事件发生率差异无统计学意义(P>0.05)。结论:沙丁胺醇联合羧甲司坦对慢性支气管炎急性发作具有较好的临床疗效,可缩短呼吸道症状的缓解时间,改善肺功能,其主要机制可能与抑制机体炎症反应程度有关。

关键词： Endothelial dysfunction   Hypoxia inducible factor 1 subunit alpha   Preeclampsia   Pregnancy complications   Vascular regeneration  

摘要： Pre-eclampsia (PE) is a common pregnancy complication, closely associated with endothelial dysfunction and inhibition of angiogenesis. This study aims to explore the pathological mechanisms causing endothelial dysfunction and suppressed angiogenesis in PE, with the aim of identifying potential drug targets. Human umbilical vein endothelial cells (HUVECs) were exposed to angiotensin II (Ang-II) to mimic PE-related endothelial dysfunction. Angiogenic capacity was evaluated using tube formation assay, scratch assay, flow cytometry, and CCK-8 assay. A Reduced Uterine Perfusion Pressure (RUPP) mouse model was established to recapitulate PE. Expression profiles of hypoxia-inducible factor-1α (HIF-1α), intercellular adhesion molecule-1 (ICAM-1), vascular cell adhesion molecule-1 (VCAM-1), vascular endothelial growth factor (VEGF), placental growth factor (PlGF), soluble fms-like tyrosine kinase-1 (sFlt-1), soluble endoglin (sENG), and tumor necrosis factor-α (TNF-α) were quantified via Western blot and RT-qPCR. Biochemical assessments included levels of malondialdehyde, superoxide dismutase, glutathione, and the urine protein/creatinine (UP/cr) ratio. Systolic blood pressure was measured while placental histopathology was examined using hematoxylin and eosin (HE) staining. In HUVECs exhibiting endothelial dysfunction, ICAM-1 and VCAM-1 were markedly upregulated, whereas HIF-1α expression was significantly reduced. Overexpression of HIF-1α boosted HUVEC proliferation and migration, attenuated apoptosis and oxidative stress, enhanced expression of VEGF and PlGF, and suppressed expression of sFlt-1, sENG, and TNF-α, thereby promoting angiogenesis. In the RUPP-modeled PE mouse model, diminished HIF-1α expression coincided with elevated ICAM-1 and VCAM-1, leading to endothelial dysfunction, elevated systolic blood pressure, and increased UP/cr ratio. Conversely, HIF-1α overexpression ameliorated placental tissue damage and oxidative stress, upregulated VEGF and PlGF, downregula

关键词： 呼吸道合胞病毒   单克隆抗体   被动免疫   临床试验   F蛋白   呼吸道感染   抗病毒药   预防  

摘要： 呼吸道合胞病毒（respiratory syncytial virus， RSV）作为全球公共卫生的重要威胁，其引发的下呼吸道感染（如毛细支气管炎、肺炎）是导致婴幼儿和老年人住院的首要原因。?值得注意的是，尽管该病毒造成的疾病负担持续加重，当前防治手段的迭代速度却未能匹配其临床需求的迫切性。究其根本，现行防治体系仍面临双重瓶颈：一方面，传统疫苗因中和抗体效价不足导致免疫应答滞后；另一方面，抗病毒药物（如利巴韦林）则受限于耐药性，难以形成持续保护。在此背景下，基于RSV F蛋白融合前构象状态（prefusion fusion protein， preF）的高分辨结构解析及抗体工程技术的突破性发展，靶向preF抗原表位的高效中和性单克隆抗体（monoclonal antibody， mAb）应运而生。特别值得关注的是，这类抗体凭借高特异性和长效保护成为研究热点。现基于RSV结构生物学的深入解析，系统综述RSV单克隆抗体的研发进展与临床转化潜力。首先，通过对比分析已上市药物与在研抗体的作用机制差异，揭示其相较于传统疗法的被动免疫优势；其次，结合临床试验数据，探讨其面临的挑战；最后，从联合疗法、新型给药途径等维度提出未来研究方向。