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目的 探究呼吸道合胞病毒(Respiratory syncytial virus, RSV)感染患者血清中微小核糖核酸-140-5p(miR-140-5p)、JAK1、STAT1、磷酸化STAT1(p-STAT1)及炎症因子的表达特征,分析其与感染严重程度的相关性,评估各指标对RSV感染及病情分级的诊断价值,为RSV感染的病情评估提供潜在分子标志物。方法 选取2023年1月—2024年6月本院确诊的RSV感染患者85例(RSV感染组),其中轻症52例、重症33例,另选取同期健康体检者40例作为正常对照组。采用实时荧光定量PCR(Quantitative real-time polymerase chain reaction, qRT-PCR)检测血清miR-140-5p相对表达量,酶联免疫吸附试验(Enzyme-linked immunosorbent assay, ELISA)检测血清JAK1、STAT1、p-STAT1蛋白及炎症因子IFN-γ、IL-6、TNF-α的浓度。分析各指标与感染严重程度的关联、miR-140-5p与其他指标的相关性,通过受试者工作特征(ROC)曲线评估各指标诊断RSV感染及区分轻症与重症的价值。结果RSV感染组血清miR-140-5p相对表达量显著低于正常对照组(P<0.001),JAK1、STAT1、p-STAT1及IFN-γ、IL-6、TNF-α浓度显著高于正常对照组(P<0.001);重症组miR-140-5p表达量显著低于轻症组(P<0.05),其余指标浓度显著高于轻症组(P<0.05)。相关性分析显示,miR-140-5p与JAK1(r=-0.643)、STAT1(r=-0.601)、pSTAT1(r=-0.627)及IFN-γ(r=-0.586)、IL-6(r=-0.554)、TNF-α(r=-0.539)均呈显著负相关(P<0.001)。ROC曲线分析显示,p-STAT1诊断RSV感染的AUC最大(0.953),JAK1区分轻症与重症的AUC最大(0.928);各指标联合检测诊断RSV感染及区分病情的AUC分别为0.986和0.967,显著优于单一指标(P<0.05)。结论 RSV感染患者血清miR-140-5p表达下调,JAK1/STAT1通路相关分子及炎症因子浓度升高,且与感染严重程度密切相关;联合检测上述指标可显著提升RSV感染诊断及病情分级的准确性,为临床病情评估提供可靠参考。
Abstract:Objective To investigate the expression patterns of serum microRNA-140-5p(miR-140-5p), JAK1, STAT1, phosphorylated STAT1(p-STAT1), and inflammatory cytokines in patients with respiratory syncytial virus(RSV) infection, analyze their association with disease severity, and evaluate their diagnostic value for RSV infection and severity stratification. Methods A total of 85 patients with confirmed RSV infection admitted to our hospital between January 2023 and June 2024 were enrolled, including 52 mild cases and 33 severe cases. Forty healthy individuals undergoing routine physical examination during the same period served as the control group. Serum miR-140-5p expression levels were measured using quantitative real-time polymerase chain reaction(qRT-PCR). Serum concentrations of JAK1, STAT1, p-STAT1, and inflammatory cytokines(IFN-γ, IL-6, and TNF-α) were determined using enzyme-linked immunosorbent assay(ELISA). Associations between these indicators and disease severity were analyzed, and correlations between miR-140-5p and other indicators were evaluated. Receiver operating characteristic(ROC) curve analysis was performed to assess the diagnostic performance of each indicator and their combined detection for RSV infection and severity differentiation. Results Serum miR-140-5p expression in the RSV infection group was significantly lower than that in the control group(P < 0.001), whereas serum levels of JAK1, STAT1, p-STAT1, IFN-γ, IL-6, and TNF-α were significantly higher(P < 0.001). Compared with the mild group, the severe group showed significantly lower miR-140-5p expression(P < 0.05) and significantly higher levels of the other indicators(P < 0.05). Correlation analysis revealed significant negative correlations between miR-140-5p and JAK1(r =-0.643), STAT1(r =-0.601), p-STAT1(r =-0.627), IFN-γ(r =-0.586), IL-6(r =-0.554), and TNF-α(r =-0.539)(all P < 0.001). ROC analysis showed that p-STAT1 exhibited the highest area under the curve(AUC) for diagnosing RSV infection(AUC = 0.953), while JAK1 showed the highest AUC for distinguishing mild from severe cases(AUC = 0.928). Combined detection of all indicators yielded AUC values of 0.986 for RSV diagnosis and 0.967 for severity differentiation, significantly outperforming individual indicators(P < 0.05). Conclusion Serum miR-140-5p is significantly downregulated in patients with RSV infection, whereas components of the JAK1/STAT1 signaling pathway and inflammatory cytokines are markedly elevated and closely associated with disease severity. Combined assessment of these biomarkers markedly improves the diagnostic accuracy for RSV infection and severity stratification and may provide useful indicators for clinical disease evaluation.
[1]Li Y, Wang X, Blau DM, et al. Global, regional, and national disease burden estimates of acute lower respiratory infections due to respiratory syncytial virus in children younger than 5 years in 2019:a systematic analysis[J]. Lancet, 2022,399(10340):2047-2064.DOI:10. 1016/S0140-6736(22)00478-0.
[2]Duan Y, Liu Z, Zang N,, et al. Landscape of respiratory syncytial virus[J]. Chin Med J(Engl),2024, 137(24):2953-2978. DOI:10. 1097/CM9. 0000000000003354.
[3]Bartel DP. microRNAs:target recognition and regulatory functions[J]. Cell, 2009, 136(2):215-233.DOI:10. 1016/j. cell. 2009. 01. 002.
[4]Zusso M, Lunardi V, Franceschini D, et al.Ciprofloxacin and levofloxacin attenuate microglia inflammatory response via TLR4/NF-kB pathway[J].J Neuroinflammation, 2019, 16(1):148. DOI:10. 1186/s12974-019-1538-9.
[5]Szabat M, Lorent D, Czapik T, et al. RNA Secondary Structure as a First Step for Rational Design of the Oligonucleotides towards Inhibition of Influenza A Virus Replication[J]. Pathogens, 2020, 9(11):925. DOI:10. 3390/pathogens9110925.
[6]Garofalo RP, Kolli D, Casola A. Respiratory syncytial virus infection:mechanisms of redox control and novel therapeutic opportunities[J]. Antioxid Redox Signal,2013,18(2):186-217. DOI:10. 1089/ars. 2011. 4307.
[7]张枫,谢正德.呼吸道合胞病毒F基因及蛋白的相关研究进展[J].病毒学报,2015, 31(2):201-206. DOI:10. 13242/j. cnki. bingduxuebao. 002648.
[8]谢智博,段晓健,郭晋源,等. 2017—2020年河南省漯河市呼吸道合胞病毒流行特征研究[J].病毒学报,2021, 37(3):554-560. DOI:10. 13242/j. cnki.bingduxuebao. 003972.
[9]Zar HJ, Cacho F, Kootbodien T, et al. Early-life respiratory syncytial virus disease and long-term respiratory health[J]. Lancet Respir Med, 2024,12(10):810-821. DOI:10. 1016/S2213-2600(24)00246-7.
[10]Samuel GH, Adelman ZN, Myles KM. Antiviral Immunity and Virus-Mediated Antagonism in Disease Vector Mosquitoes[J]. Trends Microbiol, 2018,26(5):447-461. DOI:10. 1016/j. tim. 2017. 12. 005.
[11]Wang H. COVID-19, Anti-NMDA Receptor Encephalitis and MicroRNA[J]. Front Immunol, 2022,13:825103. DOI:10. 3389/fimmu. 2022. 825103.
[12]Philips RL, Wang Y, Cheon H, et al. The JAKSTAT pathway at 30:Much learned, much more to do[J]. Cell, 185(21):3857-3876. DOI:10. 1016/j.cell. 2022. 09. 023.
[13]Schroder K, Hertzog PJ, Ravasi T, et al. Interferongamma:an overview of signals, mechanisms and functions[J]. J Leukoc Biol, 2004, 75(2):163-189.DOI:10. 1189/jlb. 0603252.
[14]Russell CD, Unger SA, Walton M,, et al. The Human Immune Response to Respiratory Syncytial Virus Infection[J]. Clin Microbiol Rev, 2017,30(2):481-502. DOI:10. 1128/CMR. 00090-16.
[15]Bahmani M, Chegini R, Ghanbari E, et al. Severe acute respiratory syndrome coronavirus 2 infection:Role of interleukin-6 and the inflammatory cascade[J].World J Virol, 2022,11(3):113-128. DOI:10. 5501/wjv. v11. i3. 113.
[16]Rossi GA, Silvestri M, Colin AA. Respiratory syncytial virus infection of airway cells:Role of microRNAs[J]. Pediatr Pulmonol, 2015,50(7):727-32. DOI:10. 1002/ppul. 23193.
[17]de Lima JD, de Paula AGP, Yuasa BS, et al. Genetic and Epigenetic Regulation of the Innate Immune Response to Gout[J]. Immunol Invest, 2023,52(3):364-397. DOI:10. 1080/08820139. 2023.
[18]Wrotek A, Badyda A, Jackowska T. Molecular Mechanisms of N-Acetylcysteine in RSV Infections and Air Pollution-Induced Alterations:A Scoping Review[J]. Int J Mol Sci, 2024,25(11):6051. DOI:10. 3390/ijms25116051.
[19]宋金华,王慧玲,石晶,等. 2008-2014年中国6省市流行的人呼吸道合胞病毒B亚型G蛋白编码基因特征分析[J].病毒学报,2019,35(2):211-219. DOI:10. 13242/j. cnki. bingduxuebao. 003520.
[20]Min JY, Jang YJ. Macrolide therapy in respiratory viral infections[J]. Mediators Inflamm, 2012,2012:649570.DOI:10. 1155/2012/649570.
[21]李丰辰,蒋豪然,夏百成,等.急性呼吸道感染病例中人冠状病毒229E感染情况及病毒基因特征分析[J].病毒学报,2024, 40(1):13-26. DOI:10. 13242/j.cnki. bingduxuebao. 004458.
[22]Dong L, Hou R, Xu Y, et al. Analyzing the Correlation between the Level of Serum Markers and Ischemic Cerebral Vascular Disease by Multiple Parameters[J]. Comput Math Methods Med, 2015,2015:972851. DOI:10. 1155/2015/972851.
[23]詹炉停,赵敏,依含,等.呼吸道合胞病毒在不同龄期BALB/c小鼠上的感染差异[J].病毒学报,2016,32(4):411-416. DOI:10. 13242/j. cnki.bingduxuebao. 002979.
[24]Plays M, Müller S, Rodriguez R. Chemistry and biology of ferritin[J]. Metallomics, 2021,13(5):mfab021. DOI:10. 1093/mtomcs/mfab021.
[25]中华医学会儿科学分会呼吸学组,中华医学会《中华儿科杂志》编辑委员会.儿童严重急性呼吸综合征诊断标准和诊疗方案(试行)(案语)[J].中华儿科杂志,2003, 41(6):413-414. DOI:10. 3760/j. issn:0578-1310. 2003. 06. 005.
基本信息:
DOI:10.13242/j.cnki.bingduxuebao.260018
中图分类号:R511
引用信息:
[1]王亚军,李佳佳,王云龙.呼吸道合胞病毒感染患者外周血miR‑140‑5p及JAK1/STAT1信号通路相关分子血清含量分析[J].病毒学报,2026,42(02):557-563.DOI:10.13242/j.cnki.bingduxuebao.260018.
基金信息:
河南省2024医院医学高质量发展项目(项目号:NI-HAZX202437),题目:基于真实世界数据的硫培非格司亭用于预防乳腺癌新辅助化疗患者中重度中性粒细胞减少症的临床综合性评价研究
2026-03-11
2026-03-11
2026-03-11