目的:探讨TOLL样受体4(TLR4)、基质金属蛋白酶-9(MMP-9)在慢性阻塞性肺疾病肺血管中的表达及其与肺血管重建的关系。方法收集因肺鳞癌行肺叶切除的癌旁组织标本50例,根据肺功能分为COPD组和非COPD组各25例,镜下观察炎症程度及测定肺动脉管壁面积/管总面积( WA%)、管壁厚度/血管外径( WT%)。免疫组化法测定肺血管平滑肌细胞TLR4、MMP-9及增殖细胞核抗原( PCNA)的表达,并分析其与血管重建的相关性。结果⑴COPD组肺血管炎症程度、WA%、WT%显著高于非COPD组,差异有统计学意义( P <0.01);⑵COPD组肺血管平滑肌细胞TLR4、MMP-9的表达水平与非COPD组相比明显升高,差异有统计学意义( P <0.01);⑶TLR4、MMP-9表达水平与WA%、WT%及血管炎症程度呈正相关( r =0.67,0.74,0.47;0.59,0.71,0.61, P <0.01),与PCNA的表达呈正相关( r =0.44,0.33, P <0.01),TLR4表达水平的上调与MMP-9的表达呈正相关( r =0.55, P <0.01)。结论 COPD患者肺动脉存在明显炎症反应、血管肌化,TLR4表达的上调可能加剧炎症反应,同时促使MMP-9的表达增强,在肺血管重建过程中起到了重要作用。
目的:探究双靶治疗在晚期EGFR突变阳性的非小细胞肺癌患者中的疗效及安全性,不良反应的处理及下一步治疗方案。方法:收集并整理1例携带EGFR敏感突变的晚期肺腺癌患者在TKI耐药后接受双靶向药物联合治疗过程中出现急性间质性肺炎的临床资料,包括患者的基本信息、病史、临床表现、辅助检查、治疗经过及转归;同时,利用PubMed检索国内外相关文献对类似病例的报道及研究进展进行系统分析。结果:患者在应用伏美替尼联合克唑替尼靶向治疗3个月后发生急性间质性肺炎,及时停用靶向药物并给予全身糖皮质激素治疗1周后病情好转,后线加用全身化疗及小分子多靶点药物,取得生存获益,OS为60个月。结论:针对晚期EGFR突变阳性的NSCLC患者,在二线靶向治疗耐药后选择双靶治疗方案可能会引发严重的药物相关间质性肺疾病。因此,我们需要及时识别、调整靶向药物种类或剂量并进行积极对症支持,这对于提高患者后续生存质量至关重要。Objective: To investigate the efficacy and safety of dual-targeted therapy in patients with advanced EGFR mutation-positive non-small cell lung cancer (NSCLC), as well as the management of adverse reactions and next-step treatment strategies. Methods: We collect and organize the clinical data of a case of advanced lung adenocarcinoma harboring an EGFR-sensitive mutation who developed drug-induced interstitial lung disease (DI-ILD) during dual-targeted combination therapy following TKI resistance, including demographic characteristics, medical history, clinical manifestations, auxiliary examinations, treatment course, and outcomes;concurrently, conduct a systematic analysis of domestic and international literature on similar reported cases and research advances using PubMed. Results: The patient developed acute interstitial pneumonia three months after initiation of furmonertinib combined with crizotinib targeted therapy. Immediate disco