小剂量红霉素联合孟鲁司特钠...因子及C-ACT评分的影响_李青.pdf

Hainan Med J,Feb.2023.Vol.34,No.4海南医学2023年2月第34卷第4期小剂量红霉素联合孟鲁司特钠治疗儿童难治性哮喘对血清炎症因子及C-ACT评分的影响李青，梁宽，胡梦娇，赵静利，罗婷婷宝鸡市人民医院儿科，陕西宝鸡721000【摘要】目的探讨小剂量红霉素联合孟鲁司特钠治疗儿童难治性哮喘对血清炎症因子及儿童哮喘控制测试(C-ACT)评分的影响。方法选取2018年10月至2021年10月宝鸡市人民医院收治的80例难治性哮喘患儿纳入研究，采用随机数表法将患儿分为观察组和对照组，每组40例。所有患儿均给予布地奈德吸入剂，对照组患儿在此基础上添加孟鲁司特钠片口服治疗，观察组在对照组治疗的基础上联合小剂量红霉素(35 mg/kg)口服治疗，两组患儿均持续治疗4周。比较两组患儿哮喘相关症状缓解时间，治疗前后的肺功能第一秒用力呼气量(FEV1)、最大呼气流速峰值(PEF)，用力呼气75%流速(FEF75)以及最大呼气中期流速(MMEF75/25)、血清炎症相关因子白细胞介素-8(IL-8)、白细胞介素-13(IL-13)以及肿瘤坏死因子-(TNF-)、T淋巴细胞亚群水平(CD3+、CD4+、CD8+、CD4+/CD8+)。治疗前后，采用C-ACT评分评估患儿哮喘控制情况。结果治疗后，观察组患儿的喘息、肺部湿啰音及咳嗽缓解时间分别为(6.241.32)d、(1.230.54)d、(5.490.54)d，明显短于对照组的(7.141.57)d、(1.590.47)d、(6.471.12)d，差异均有统计学意义(P0.05)；治疗后，观察组患儿的FEV1、PEF、FEF75及MMEF75/25指数分别为(1.840.37)L、(4.120.29)L/s、(1.290.32)L/s、(2.060.24)L/s，明显高于对照组的(1.670.24)L、(3.970.19)L/s、(1.120.17)L/s、(1.920.17)L/s，差异均具有统计学意义(P0.05)；治疗后，观察组患儿的IL-8、IL-13及TNF-水平分别为(74.1222.32)ng/L、(92.5712.36)g/L、(0.740.14)ng/mL，明显低于对照组的(88.5421.19)ng/L、(101.5611.25)g/L、(1.060.21)ng/mL，差异均有统计学意义(P0.05)；治疗后，观察组患儿的CD3+、CD4+、CD4+/CD8+水平分别为(68.548.97)%、(36.795.14)%、1.740.34，明显高于对照组的(63.479.12)%、(33.574.98)%、1.390.28，CD8+水平为(21.123.27)%，明显低于对照组的(24.123.32)%，差异均有统计学意义(P0.05)；治疗后，观察组患儿的C-ACT评分(22.120.97)分，明显高于对照组的(20.121.37)分，差异有统计学意义(P0.05)。结论小剂量红霉素联合孟鲁司特钠可有效降低难治性哮喘患儿的血清炎症因子，维持机体免疫平衡，提高肺功能，改善临床症状，以提高患儿哮喘控制程度。【关键词】儿童；难治性哮喘；小剂量红霉素；孟鲁司特钠；血清炎症因子；哮喘控制【中图分类号】R725.6【文献标识码】A【文章编号】10036350（2023）04052905Effects of low-dose erythromycin combined with montelukast sodium on serum inflammatory factors andC-ACT scores in children with refractory asthma.LI Qing,LIANG Kuan,HU Meng-jiao,ZHAO Jing-li,LUOTing-ting.Department of Pediatrics,Baoji Peoples Hospital,Baoji 721000,Shaanxi,CHINA【Abstract】ObjectiveTo explore the effects of low-dose erythromycin combined with montelukast sodium onserum inflammatory factors and scores of childhood asthma control test(C-ACT)in children with refractory asthma.MethodsA total of 80 children with refractory asthma admitted to Baoji Peoples Hospital between October 2018 andOctober 2021 were enrolled.According to random number table method,they were divided into an observation groupand a control group,with 40 patients in each group.Based on budesonide inhalation,patients in control group were treat-ed with montelukast sodium,while those in the observation group were treated with low-dose erythromycin(3-5 mg/kg)on basis of control group,continuously for 4 weeks.The remission time of asthma-related symptoms,levels of lung func-tion indexes forced expiratory volume in one second(FEV1),peak expiratory flow(PEF),forced expiratory flow after75%of vital capacity has been expelled(FEF75),maximal midexpiratory flow rate(MMEF75/25),serum inflamma-tion-related factors interleukin-8(IL-8),interleukin-13(IL-13),tumor necrosis factor-(TNF-),and T lymphocytesubsets(CD3+,CD4+,CD8+,CD4+/CD8+)before and after treatment were compared between the two groups.Before andafter treatment,asthma control of patients was evaluated by C-ACT scores.ResultsThe remission time of wheezing,lung rales,and cough in the observation group were(6.241.32)d,(1.230.54)d,and(5.490.54)d,significantly short-er than(7.141.57)d,(1.590.47)d,(6.471.12)d in the control group(P0.05).After treatment,FEV1,PEF,FEF75,and MMEF75/25 in the observation group were(1.840.37)L,(4.120.29)L/s,(1.290.32)L/s,and(2.060.24)L/s,significantly higher than(1.670.24)L,(3.970.19)L/s,(1.120.17)L/s,(1.920.17)L/s in the control group(P0.05)，具有可比性。本研究经医院伦理委员会审核通过，患儿家属知情并已签署知情同意书。1.2治疗方法两组患儿均给予布地奈德吸入粉雾剂(注册证号 H20140421，芬兰Orion CorporationOrion Pharma，Espoo Plant，200 g200吸)治疗，200400 g/次，2次/d。对照组患儿在此基础上添加孟鲁司特钠片口服治疗，即给予孟鲁司特钠咀嚼片(注册证号 H20181210/国药准字J20130054，英国Merck Sharp&Dohme Ltd，5 mg5片)5 mg/次，1次/d，睡前服用。观察组患儿在对照组治疗的基础上联合小剂量红霉素口服治疗，即给予红霉素肠溶片(国药准字H44021101，特一药业集团股份有限公司，0.125 g100片)35 mg/(kg次)，3次/d。所有患儿均持续治疗4周。1.3观察指标与评价(检测)方法(1)临床症状缓解时间：比较两组患儿的喘息、肺部湿啰音以及咳嗽缓解的时间，缓解时间越短，说明患儿恢复的越快。(2)肺功能：分别于治疗前后，检测患儿的肺功能相关指标，即第一秒用力呼气量(FEV1)、最大呼气流速峰值(PEF)，用力呼气75%流速(FEF75)以及最大呼气中期流速(MMEF75/25)。(3)T淋巴细胞亚群及血清炎症相关因子：分别于治疗前后，抽取患儿清晨空腹静脉血6 mL，平分为2份，一份用于检测血清炎症相关因子白细胞介素-8(IL-8)、白细胞介素-13(IL-13)以及肿瘤坏死因子-(TNF-)，一份用于检测T淋巴细胞亚群(CD3+、CD4+、CD8+、CD4+/CD8+)。IL-8、IL-13、TNF-均采用酶联免疫吸附法检测(试剂盒：均采自江西艾博因生物科技有限公司)，T淋巴细胞亚群检测采用流式细胞仪检测(仪器：美国贝克曼DxFLEX)。均由我院检验科资深检验师按照说明书及仪器说明进行操作。(4)哮喘控制情况：采用儿童哮喘控制测试(C-ACT)评分8评估患儿治疗前后哮喘控制情况，C-ACT 中主要包括呼吸急促，急救药物的使用，哮喘对生活和工作的影响，夜间觉醒情况，患儿对哮喘控制的标化等5各方面，共7个问题，前4个问题由儿童自行回答(每项评分03分)，后3项由家长回答(每项评分05分)，总分27分，分数越高，说明患儿哮喘控制越好。1.4统计学方法应用SPSS21.0统计学软件进行数据分析。计量资料满足正态分布且方差齐，以均数标准差(x-s)表示，组间差异比较采用两样本独立tand(0.740.14)ng/mL,significantly lower than(88.5421.19)ng/L,(101.5611.25)g/L,(1.060.21)ng/mL in thecontrol group(P0.05).After treatment,levels of CD3+,CD4+,and CD4+/CD8+in the observation group were(68.548.97)%,(36.795.14)%,and 1.740.34,significantly higher than(63.479.12)%,(33.574.98)%,1.390.28 in the con-trol group(P0.05).After treatment,CD8+in the observation group was significantly lower than that in the controlgroup:(21.123.27)%vs(24.123.32)%,P0.05;C-ACT score was significantly higher than that in the control group:(22.120.97)points vs(20.121.37)points,P0.05.ConclusionLow-dose erythromycin combined with montelukastsodium can effectively reduce serum inflammatory factors in children with refractory asthma,maintain immune balance,improve lung function and clinical symptoms,so as to improve asthma control.【Key words】Children;Refractory asthma;Low-dose erythromycin;Montelukast sodium;Serum inflammatoryfactor;Asthma control530Hainan Med J,Feb.2023.Vol.34,No.4海南医学2023年2月第34卷第4期检验，同组内治疗前后比较采用配对t检验，计数资料比较采用2检验。以P0.05为差异有统计学意义。2结果2.1两组患儿的临床症状缓解时间比较所有患儿配合度较好，均顺利完成随访。观察组患儿的喘息、肺部湿啰音以及咳嗽缓解时间明显短于对照组，差异均有统计学意义(P0.05)；治疗后，两组患儿 FEV1、PEF、FEF75以及MMEF75/25指数均有上升，且观察组明显高于对照组，差异均具有统计学意义(P0.05)；治疗后，两组患儿的IL-8、IL-13以及TNF-水平均有下降，且观察组低于对照组，差异有统计学意义(P0.05)；治疗后，两组患儿CD3+、CD4+、CD4+/CD8+水平均有上升，且观察组高于对照组，差异有统计学意义(P0.05)；两组患儿CD8+水平均有下降，且观察组低于对照组，差异有统计学意义(P0.05)，治疗后，两组患儿的C-ACT评分均有上升，且观察组明显高于对照组，差异有统计学意义(P0.05)，见表5。表1两组患儿的临床症状缓解时间比较(d，x-s)Table 1Comparison on remission time of clinical symptoms betweenthe two groups(d,x-s)组别观察组对照组t值P值例数4040喘息6.241.327.141.572.7750.007肺部湿啰音1.230.541.590.473.1800.002咳嗽5.490.546.471.124.9850.001表2两组患儿治疗前后的肺功能比较(x-s)Table 2Comparison of pulmonary function between the two groups before and after treatment(x-s)组别观察组对照组t值P值例数4040治疗前1.620.241.590.310.4840.630治疗后1.840.37a1.670.24a2.4380.017治疗前3.670.313.690.260.3130.755治疗后4.120.29a3.970.19a2.7360.008治疗前0.950.260.940.340.1480.883治疗后1.290.32a1.120.17a2.9670.004治疗前1.780.241.810.280.5140.608治疗后2.060.24a1.920.17a3.0110.004注：与本组治疗前比较，aP0.05。Note：Compared with the same group before treatment,aP0.05.FEV1(L)PEF(L/s)FEF75(L/s)MMEF75/25(L/s)表3两组患儿治疗前后的血清炎症因子水平比较(x-s)Table 3Comparison on levels of serum inflammatory factors between the two groups before and after treatment(x-s)组别观察组对照组t值P值例数4040治疗前242.2147.65244.1752.120.1760.861治疗后74.1222.32a88.5421.19a2.9630.004治疗前142.6523.47143.2621.250.1220.903治疗后92.5712.36a101.5611.25a3.4020.001治疗前1.350.241.320.310.4840.630治疗后0.740.14a1.060.21a4.7610.001注：与本组治疗前比较，aP0.05。Note:Compared with the same group before treatment,aP0.05.IL-8(ng/L)IL-13(g/L)TNF-(ng/mL)表4两组患儿治疗前后的T淋巴细胞亚群水平比较(x-s)Table 4Comparison on levels of T lymphocyte subsets between the two groups before and after treatment(x-s)组别观察组对照组t值P值例数4040治疗前58.647.1759.126.890.3050.761治疗后68.548.97a63.479.12a2.5070.014治疗前31.245.4631.174.970.0600.952治疗后36.795.14a33.574.98a2.8460.006治疗前26.575.1226.624.970.0440.965治疗后21.123.27a24.123.32a4.0720.001治疗前1.170.421.160.390.1100.913治疗后1.740.34a1.390.28a5.0260.001注：与本组治疗前比较，aP0.05。Note:Compared with the same group before treatment,aP0.05.CD3+(%)CD4+(%)CD8+(%)CD3+/CD8+531海南医学2023年2月第34卷第4期Hainan Med J,Feb.2023.Vol.34,No.43讨论目前临床无根治支气管哮喘的方案，以控制病情为主9。而难治性哮喘患儿哮喘控制率较差，常反复发作，且需长期规范性用药，随着时间的推移可能会造成气管不可逆的狭窄和气道重塑，严重影响患儿心理和生理的健康成长10。严重者可造成心肺功能不可逆性受损，有可能发展为肺源性心脏病，死亡率较高。为进一步提高难治性哮喘的临床控制率，本研究将小剂量红霉素与孟鲁司特钠片进行联合应用，结果显示，观察组患儿的临床症状缓解时间短于对照组，且治疗后观察组患儿肺功能优于对照组，提示小剂量红霉素的辅助治疗可能有效提高临床疗效。目前临床公认支气管哮喘的发展与气道慢性炎症的形成及自身免疫状态有关11。IL-8、IL-13均为白介素家族成员，IL-8由巨噬细胞和上皮细胞分泌，其主要生物学活性为吸引和激活中性粒细胞，有介导局部炎症反应的作用12，IL-13由Th2细胞生成，可激活单核巨噬细胞的活性，对炎症反应具有拮抗作用13。TNF-是一种涉及到系统性炎症的细胞因子，主要由巨噬细胞分泌，有着调节机体免疫细胞的功能，参与着机体许多生理和病理反应的过程14。本研究显示治疗后，两组患儿的IL-8、IL-13以及TNF-水平均有下降，观察组优于对照组，可能与小剂量红霉素的联合治疗有关，陈芳等15将罗红霉素应用于哮喘治疗中，具有较好的抗炎效果，本研究与其具有异曲同工之妙。本研究采用的布地奈德吸入剂具有较为高效的局部抗炎作用，孟鲁司特钠是目前临床公认效果最好的白三烯受体拮抗剂，可有效降低患儿气管敏感性，抑制气道高反应。红霉素具有广谱抗菌的作用，可通过抑制细菌蛋白的合成来达到抑制细菌生长的作用，可有效抑制炎性介质的释放，联合孟鲁司特钠及布地奈德可更好的降低患儿气道高反应性，更好的发挥激素抗炎作用，以改善患儿临床症状。免疫反应紊乱是造成炎症发生及发展的主要生理过程，CD3+、CD4+、CD8+为T淋巴细胞亚群的重要因子，在维持机体免疫平衡中具有主要作用16。CD3+水平变化可反应机体总体免疫功能状态，CD4+属于辅助性 T 细胞，具有协助细胞及体液免疫功能，CD8+与CD4+作用相反，具有杀伤或抑制T细胞免疫作用，正常情况下，两者处于平衡状态。研究结果显示，治疗后，两组患儿的CD3+、CD4+水平均有上升，CD8+水平均有下降，说明两种治疗方案均可改善患儿的机体免疫功能，但治疗后观察组患儿的CD3+、CD4+、CD8+水平优于对照组，说明观察组患儿免疫功能改善更佳，与小剂量红霉素的添加有效降低炎症反应，维持机体炎症因子动态平衡有关。C-ACT评分是反映患儿近4周的哮喘控制情况，研究显示，治疗后，观察组的C-ACT评分明显高于对照组，说明小剂量红霉素联合孟鲁司特钠可有效提高患儿的哮喘控制程度。综上所述，小剂量红霉素联合孟鲁司特钠可有效降低难治性哮喘患儿的血清炎症因子，维持机体免疫平衡，提高患儿肺功能，改善患儿临床症状，以提高患儿哮喘控制程度。参考文献1Sun Y,Wan LS,Li JX,et al.Research progress of the biomarkers ofbronchial asthma based on the metabonomics J.Anhui Med PharmJ,2018,22(3):395-398.孙益,万力生,李佳曦,等.基于代谢组学的支气管哮喘生物标志物研究进展J.安徽医药,2018,22(3):395-398.2Hao FY.Observation and nursing of sublingual desensitization treat-ment of bronchial asthma by Dusting mite J.Chinese Remedies&Clinics,2019,19(2):328-329.郝粉英.支气管哮喘粉尘螨舌下脱敏治疗的效果观察与护理J.中国药物与临床,2019,19(2):328-329.3Deng YT.Phenotypes and endotypes of difficult-to-treat asthma J.Int J Pediatr,2021,48(3):168-172.邓云天.难治性哮喘的分型研究进展J.国际儿科学杂志,2021,48(3):168-172.4Xie YM,Mo GH,Cheng GG.Effects of montelukast combined withbudesonide on airway responsiveness and asthma control in childrenwith asthma in remission stage J.Hainan Medical Journal,2019,30(7):869-861.谢逸民,莫国欢,程国冠.孟鲁司特联合布地奈德对缓解期小儿哮喘气道反应性及哮喘控制的影响J.海南医学,2019,30(7):859-861.5 Wang XP,Yang LD,Zhou JF.Montelukast and budesonide combina-tion for children with chronic cough-variant asthma J.Medicine(Baltimore),2018,97(30):e11557-e11561.6Zhu HL,Jin M,Li RX,et al.Observation on the Therapeutic Effectof Erythromycin Combined with Aerosol Inhalation in Elderly Pa-tients with Asthma J.Chin J Med Guide,2017,19(4):402-403.朱海玲,金明,李任翔,等.红霉素联合雾化吸入对老年哮喘患者的治疗效果观察J.中国医药导刊,2017,19(4):402-403.7Wu JY,Hong JG.Highlights of bronchial asthma in children guide-line(2016 edition)for its diagnosis and treatment J.World ClinDrug,2018,39(8):512-517.吴嘉婴,洪建国.儿童支气管哮喘诊断和防治指南(2016年版)更新要点J.世界临床药物,2018,39(8):512-517.8 Gu XQ,Duan HM,Xiang L.Application of Children Asthma ControlTest in the follow-up management of asthma children J.Chin JNurs,2014,49(5):625-628.顾希茜,段红梅,向莉.儿童哮喘控制测试在门诊定期随访管理中的应用价值J.中华护理杂志,2014,49(5):625-628.9Wu JG.Effect of aminophylline combine with montelukast on the表5两组患儿治疗前后的C-ACT评分比较(x-s)Table 5Comparison of C-ACT scores between the two groups beforeand after treatment(x-s)组别观察组对照组t值P值例数4040治疗前18.571.2618.451.120.4500.654治疗后22.120.97a20.121.37a7.5350.000注：与本组治疗前比较，aP0.05。Note:Compared with the same group before treatment,aP0.05.C-ACT(分)532Hainan Med J,Feb.2023.Vol.34,No.4海南医学2023年2月第34卷第4期treatment of bronchial asthma J.Shanxi Medical Journal,2020,49(9):99-101.吴建谷.氨茶碱联合孟鲁司特钠治疗支气管哮喘的疗效观察J.山西医药杂志,2020,49(9):99-101.10 Schuh S,Sweeney J,Rumantir M,et al.Effect of Nebulized Magne-sium vs Placebo Added to Albuterol on Hospitalization Among Chil-dren With Refractory Acute Asthma Treated in the Emergency De-partment:A Randomized Clinical Trial J.JAMA,2020,324(20):2038-2047.11 Michalik M,Wjcik-Pszczoa K,Paw M,et al.Fibroblast-to-myofi-broblast transition in bronchial asthma J.Cell Mol Life Sci,2018,75(21):3943-3961.12 Zhang XH,Chang XY.The level and clinical significance of fraction-al exhaled nitric oxide and Interleukin-8 in patients with different in-flammatory phenotypes ofcough variant asthma J.Int J Respir,2020,40(20):1585-1591.张星慧,常晓悦.IL-8与FeNO在不同炎症表型的咳嗽变异性哮喘患者中的水平及临床意义J.国际呼吸杂志,2020,40(20):1585-1591.13 Cheng D,Chen HR,Wang MM,et al.Effects of interleukin-13 onSPDEF expression in human bronchial epithelial cells and role of SP-DEF in airway mucus hypersecretion of asthma J.J Clin Inter Med,2020,37(1):53-56.程丹,陈恒睿,王梦玫,等.白细胞介素-13对人支气管上皮细胞SPDEF表达的影响及SPDEF在哮喘气道黏液高分泌中的作用J.临床内科杂志,2020,37(1):53-56.14 Nasser MZ,Ezzat DA.Association of-308G/A Polymorphism andSerum Level of TNF-with Bronchial asthma in Children J.EgyptJ Immunol,2018,25(2):117-124.15 Chen F.Effect of low-dose roxithromycin on cellular immune func-tion and inflammatory factors in children with bronchial asthma J.JXinxiang Med Coll,2020,37(1):68-71.陈芳.小剂量罗红霉素对支气管哮喘患儿细胞免疫功能及炎症因子水平的影响J.新乡医学院学报,2020,37(1):68-71.16 Nguyen-Thi-Dieu T,Le-Thi-Thu H,Duong-quy S.The profile of leu-cocytes,CD3+,CD4+,and CD8+T cells,and cytokine concentrationsin peripheral blood of children with acute asthma exacerbation J.JInt Med Res,2017,45(6):1658-1669.(收稿日期：2022-03-03)双相气道正压通气治疗NRDS的疗效及对患儿脑氧代谢指标的影响王娟1，雷娜2，亢娟1，李娟丽1，梁宽3宝鸡市人民医院感染控感科1、护理站2、儿科3，陕西宝鸡721000【摘要】目的探究双相气道正压通气治疗新生儿呼吸窘迫综合征(NRDS)的疗效及对患儿脑氧代谢指标的影响。方法选取2018年11月至2021年11月宝鸡市人民医院收治的90例NRDS患儿为研究对象，采用随机数表法分为观察组和对照组各45例，两组患儿均采用常规治疗，在此基础上对照组患儿给予持续气道正压通气法治疗，观察组患儿给予双相气道正压通气法治疗，均治疗12 h。比较两组患儿治疗12 h后的疗效，治疗前后的全身氧代谢、脑氧代谢及并发症发生情况。结果观察组患儿的治疗总有效率为97.78%，明显高于对照组的84.44%，差异有统计学意义(P0.05)；治疗后，两组患者的动脉血氧分压(PaO2)、氧合指数(OI)值均升高，且观察组分别为(112.882.12)mmHg、(262.5922.31)mmHg，明显高于对照组的(100.222.23)mmHg、(223.4320.16)mmHg，二氧化碳分压(PaCO2)吸入氧浓度(FiO2)值均降低，且观察组分别为(44.141.33)mmHg、(31.237.12)%，明显低于对照组的(53.161.27)mmHg、(41.117.11)%，差异均有统计学意义(P0.05)；观察组患儿治疗12 h内、治疗后5 min、治疗后10 min的脑氧饱和度(ScO2)值分别为(80.647.02)%、(84.034.17)%、(88.876.82)%，明显高于对照组的(77.477.39)%、(81.475.27)%、(83.366.97)%，差异均有统计学意义(P0.05)。观察组患儿治疗期间的并发症总发生率为4.44%，明显低于对照组的20.00%，差异有统计学意义(P0.05)。结论较持续气道正压通气，双相气道正压通气治疗NRDS疗效更确切，对患儿全身氧代谢及脑氧代谢改善更显著，并具有更低的并发症风险。【关键词】新生儿；呼吸窘迫综合征；双相气道正压通气；持续气道正压通气；脑氧代谢；疗效【中图分类号】R722.19【文献标识码】A【文章编号】10036350（2023）04053304Effect of bi-level positive airway pressure in the treatment of neonatal respiratory distress syndrome and theinfluence on cerebral oxygen metabolism indicators.WANG Juan1,LEI Na2,KANG Juan1,LI Juan-li1,LIANG Kuan3.Department of Infection Control1,Nursing Station2,Department of Pediatrics3,Peoples Hospital of Baoji City,Baoji721000,Shaanxi,CHINA【Abstract】ObjectiveTo investigate the effect of bi-level positive airway pressure in the treatment of neonatalrespiratory distress syndrome(NRDS),and the influence on cerebral oxygen metabolism indicators.MethodsA totalof 90 neonates with NRDS admitted to Peoples Hospital of Baoji City from November 2018 to November 2021 were se-论著 doi:10.3969/j.issn.1003-6350.2023.04.016基金项目：陕西省科学技术研究发展计划项目(编号：S2018SKZ1804591)。第一作者：王娟(1973)，女，主治医师，主要研究方向为临床新生儿科和医院感染控制。通讯作者：梁宽(1981)，男，副主任医师，主要研究方向为儿内科呼吸，E-mail：。533