赵婷丽,贾兴泽,宋倩,岳学敏

• 1:华北医疗健康集团邢台总医院公共卫生科
• 2:华北医疗健康集团邢台总医院老年科
• 3:华北医疗健康集团邢台总医院医学检验科
• 4:华北医疗健康集团邢台总医院质控部

摘要(Abstract)：

目的 使用血清生物标志物对甲型流感病毒和腺病毒感染鉴别的偏最小二乘判别分析（PLS-DA）和人工神经网络多层感知器（ANN-MLP）模型评估。方法 选取2023年1月-2024年12月于华北医疗健康集团邢台总医院治疗的甲型流感病毒和腺病毒感染患者413例为研究对象。根据感染病毒情况分为甲型流感病毒组（n=349）和腺病毒感染组（n=64）。以血清C-反应蛋白（CRP）、白细胞介素-6(IL-6)、IL-8和降钙素原（PCT）为变量，建立logistic回归模型、受试者工作特征（ROC）曲线和ANN-MLP模型，并计算曲线下面积（AUC）；以血清生物标志物建立主成分分析（PCA）模型；采用SIMCA-P 12.0软件进行PLS-DA分析，采用7∶3比例划分训练集与测试集，并实施5折交叉验证。结果 CRP(OR=2.957)、IL-6(OR=1.439)、IL-8(OR=1.906)和PCT(OR=1.630)是鉴别甲型流感病毒与腺病毒感染的危险因素（P<0.05）;PCA模型中，腺病毒感染组个体间差异显著且分布较分散，而甲型流感病毒感染组则能较好地聚类，两组个体有分离的趋势；PLS-DA模型中，模型解释率R2 Y为0.873，预测率Q2为0.801，置换检验P<0.05，能有效鉴别甲型流感病毒和腺病毒感染；CRP、IL-6、IL-8和PCT鉴别两组的AUC分别为0.621、0.798、0.812和0.597；在ANN-MLP-ROC模型中，IL-6和IL-8联合检测的AUC达到0.836; CRP、 IL-6、 IL-8和PCT联合检测的AUC为0.884，经5折交叉验证，AUC均值为0.872±0.015。结论 基于血清生物标志物的PLS-DA和ANN-MLP模型在甲型流感病毒与腺病毒感染的鉴别诊断中均展现出良好的效能，其中联合四项指标的ANN-MLP模型诊断性能最优。

关键词(KeyWords)： 血清生物标志物;甲型流感病毒;腺病毒感染;偏最小二乘判别分析;人工神经网络多层感知器

Abstract:

Keywords:

基金项目(Foundation): 河北省医学科学研究课题（20201269）

作者(Author): 赵婷丽,贾兴泽,宋倩,岳学敏

参考文献(References)：

• [1]Svyatchenko VA,Ternovoi VA,Lutkovskiy RY,et al.Human adenovirus and influenza a virus exacerbate SARS-CoV-2 infection in animal models[J].Microorganisms,2023,11(1):180.
• [2]Carter T,Iqbal M.The influenza a virus replication cycle:a comprehensive review[J].Viruses,2024,16(2):316.
• [3]Al-Heeti OM,Cathro HP,Ison MG.Adenovirus infection and transplantation[J].Transplantation,2022,106(5):920-927.
• [4]张业婷，肖立，蔡冬平.单核细胞百分比联合CRP和PCT鉴别甲型流感病毒和腺病毒感染[J].中国国境卫生检疫杂志，2023,46(3):253-255.
• [5]Fan F,Lv J,Yang QY,et al.Clinical characteristics and serum inflammatory markers of community-acquired Mycoplasma pneumonia in children[J].Clin Respir J,2023,17(7):607-617.
• [6]Huang LJ,Zhang ZN,Xing HC,et al.Risk assessment based on dose-responsive and time-responsive genes to build PLS-DA models for exogenously induced lung injury[J].Ecotoxicol Environ Saf,2023,256:114891.
• [7]Luo YN,Yuan H,Pei Q,et al.Artificial neural network-based diagnostic models for lung cancer combining conventional indicators with tumor markers[J].Exp Biol Med (Maywood),2023,248(10):829-838.
• [8]人腺病毒呼吸道感染预防控制技术指南编写审定专家组.人腺病毒呼吸道感染预防控制技术指南（2019年版）[J].中华预防医学杂志，2019,53(11):1088-1093.
• [9]中国医师协会急诊医师分会，中华医学会急诊医学分会，中国人民解放军急救医学专业委员会，等.中国成人流行性感冒诊疗规范急诊专家共识[J].中国急救医学，2019,39(10):915-928.
• [10]von Lilienfeld-Toal M,Khawaja F,Compagno F,et al.Communityacquired respiratory virus infections in patients with haematological malignancies or undergoing haematopoietic cell transplantation:updated recommendations from the 10th European Conference on Infections in Leukaemia[J].Lancet Infect Dis,2026,26(3):e193-e206.
• [11]Jiang ZM,Pan WL,Chen Y,et al.ApoD mediates age-associated increase in vulnerability to influenza virus infection[J].Proc Natl Acad Sci U S A,2025,122(37):e2423973122.
• [12]Symes R,Keddie SH,Walker J,et al.Burden of respiratory syncytial virus infection in older adults hospitalised in England during 2023/24[J].J Infect,2025,91(3):106570.
• [13]Almanzar N,Yang DP,Xia JY,et al.Vagal TRPV1+sensory neurons protect against influenza virus infection by regulating lung myeloid cell dynamics[J].Sci Immunol,2025,10(110):eads6243.
• [14]Dai BW,Chen C,Shen YF,et al.Hospitalizations trends and co-infection patterns for respiratory virus infections in children in Central China 2015 to 2023:a longitudinal surveillance study[J].BMC Infect Dis,2025,25(1):1058.
• [15]Maillard A,Feghoul L,Lemiale V,et al.Clinical significance of respiratory torque teno virus in immunocompromised patients with acute respiratory failure[J].Clin Microbiol Infect,2025,31(12):2073-2081.
• [16]Liu TH,Miller LM,Dresden BP,et al.Influenza virus and Staphylococcus aureus super-infection disrupts spatially coordinated cellular immunity in the mouse lung[J].Commun Biol,2025,8:1837.
• [17]Chen LL,Ip JD,Chan WM,et al.Enhanced replication of a contemporary avian influenza A H9N2 virus in human respiratory organoids[J].Emerg Microbes Infect,2025,14(1):2576574.
• [18]Han YL,Leng DL,Zhang T,et al.A human immuno-lung organoid model to study macrophage-mediated lung cell senescence upon SARS-CoV-2 infection[J].Adv Sci,2025,12(36):e03932.
• [19]Ferreira JP,Vasques-Nóvoa F,Neves JS,et al.Comparison of interleukin-6 and high-sensitivity C-reactive protein for cardiovascular risk assessment:findings from the MESA study[J].Atherosclerosis,2024,390:117461.
• [20]Yagi K,Ethridge AD,Asai N,et al.Changes in microbiome correspond with diminished lung pathophysiology following early-life respiratory syncytial virus infection or antibiotic treatment:microbiome following RSV infection[J].Viruses,2025,17(12):1632.
• [21]Claassen-Weitz S,Xia Y,Hannan L,et al.Nasopharyngeal microbiota in South African infants with lower respiratory tract infection:a nested case-control study of the drakenstein child health study[J].Clin Infect Dis,2026,81(6):e668-e679.
• [22]Adhikari S,Carrier C,Joshi PR,et al.β2-adrenergic signaling controls neonatal respiratory syncytial virus infection by promoting viral clearance and airway protection[J].Nat Commun,2025,16:11229.
• [23]Becker AL,Borges SG,Pinheiro LGR,et al.Analysis of DNA methyltransferase 3 alpha expression during respiratory syncytial virus strain A infection[J].Sci Rep,2026,16:3996.
• [24]Chorvinsky E,Bhattacharya S,Bera BS,et al.Down syndrome alters type III IFN and proinflammatory airway epithelial responses to respiratory syncytial virus infection[J].Am J Respir Cell Mol Biol,2025,73(6):951-964.
• [25]Adam A,Wu WZ,et al.Respiratory syncytial virus infection induces heterologous protection against SARS-CoV-2 through γδ T cell-mediated trained immunity and the activation of SARS-CoV-2-reactive mucosal T cells[J].J Virol,2026,100(4):e01658-e01625.