Burden of respiratory syncytial virus infection in young children

Respiratory syncytial virus(RSV) is the most frequent and important cause of lower respiratory tract infection in infants and children. It is a seasonal virus, with peak rates of infection occurring annually in the cold season in temperate climates, and in the rainy season, as temperatures fall, in tropical climates. High risk groups for severe RSV disease include infants below six mo of age, premature infants with or without chronic lung disease, infants with hemodynamically significant congenital heart disease, infants with immunodeficiency or cystic fibrosis, and infants with neuromuscular diseases. Mortality rates associated with RSV infection are generally low in previous healthy infants(below 1%), but increase significantly in children with underlying chronic conditions and comorbidities. Following early RSV lower respiratory tract infection, some patients experience recurrent episodes of wheezing mimicking early childhood asthma with persistence of lung function abnormalities until adolescence. There is currently no RSV vaccine available, but promising candidate vaccines are in development. Palivizumab, a monoclonal RSV antibody that is the only tool for immunoprophylaxis in high-riskinfants, lowers the burden of RSV infection in certain carefully selected patient groups.

Prevalence of respiratory syncytial virus infection among children hospitalized with acute lower respiratory tract infections in Southern India

BACKGROUND Respiratory syncytial virus(RSV) is a leading cause of lower respiratory infections among children.AIM To investigate the proportion of RSV and non-RSV respiratory viral infections among hospitalized children ≤ 5 years.METHODS Hospitalized children aged < 5 years, with a diagnosis of acute lower respiratory infections(ALRI), admitted between August 2011-August 2013, were included.Cases were defined as laboratory-confirmed RSV and non-RSV respiratory viruses by direct fluorescence assay from the nasopharyngeal wash.RESULTS Of 383 1-59 mo old children hospitalized with an acute lower respiratory infection, 33.9%(130/383) had evidence of viral infection, and RSV was detected in 24.5%(94/383). Co-infections with RSV and other respiratory viruses(influenza A or B, adenovirus, para influenza 1, 2 or 3) were seen in children 5.5%(21/383). Over 90% of the RSV-positive children were under 2 years of age. RSV was detected throughout the year with peaks seen after the monsoon season.Children hospitalized with RSV infection were more likely to have been exposed to a shorter duration of breastfeeding of less than 3 mo. RSV positive children had a shorter hospital stay, although there were significant complications requiring intensive care. Use of antibiotics was high among those with RSV and non-RSV viral infections.CONCLUSION Our study provides evidence of a high proportion of RSV and other virusassociated ALRI among hospitalized children in India. RSV infection was associated with fewer days of hospital stay compared to other causes of lower respiratory infections. A high level of antibiotic use was seen among all respiratory virus-associated hospitalizations. These results suggest the need for implementing routine diagnostics for respiratory pathogens in order to minimize the use of unnecessary antibiotics and plan prevention strategies among pediatric populations.

STUDY OF T－LYMPHOCYTE SUBSETS AND INTERLEUKIN－2 AND INTERLEUKIN－2 RECEPTOR OF RESPIRATORY SYNCYTIAL VIRUS PNEUMONIA

T-Lymphocyte subsets and humoral immune and the activity of IL-2 and IL-2R in respiratory syncytial virus (RSV) pneumonia in 26 cases were tested. The result showed in the patients with RSV pneumonia the averages of T3 and T4 were 37.56±1.46% and 27. 15±8. 02% respectively,They were significantly lower than 53.4 ±9.2% and 35.5±7.7% of averages of T3 and T4 in healthy controlled group (both. P< 0. 001 ), the average of T3 was 22. 73±7.06%, it was lower an 26. 7±6. 3 % of T8 in controlled group (P<0. 02 );the ratio of T4/T8 was 1. 245±0. 399 ,there was no significant difference from 1. 35 ±0. 17 of the ratio in controlled group (P > 0. 1). The mean value of IgG was 1. 177± 0. 3685g/L, it was significantly lower than 1. 427± 0. 498g/L of that in controlled group(P < 0. 005). The mean values of IgA and IgM were 0. 1136±0.0393g/L and 0. 768±0. 353g/L respectively, they were significantly lower than 0. 2706 ±0. 876g/L and 0. 122±0. 061g/L of IgA and IgM in controlled group. The activity of IL-2 and IL-2R were 17. 46 ±5. 79%, and 28. 32 ±5. 924% respectively, they were significantly lower than 30. 22 ±14. 55% and 39. 53±8. 61 % of those in healthy group (both P < 0. 001). The severe the pneuumonia, the greater the lowering of IL-2 and IL-2R. These about results suggested that RSV could greatly suppress the immune function of the patients, inducing secondary immunodeficiency, leading to repeated breather and asthma.

Qingfei oral liquid downregulates TRPV1 expression to reduce airway inflammation and mucus hypersecretion injury caused by respiratory syncytial virus infection and asthma in mice

Objective:Qingfei oral liquid(QF),an experimental Chinese medicine prescription developed from the ancient priscription of traditional Chinese medicines Ma Xin Shi Gan decoction and Tingli Dazao Xie Fei decoction,has been effectively used since decades to treat patients with viral pneumonia and asthma.In our previous study,we had demonstrated that QF can significantly reduce airway hyperresponsiveness,hyperemia,lung tissue edema,inflammatory lung tissue infiltration in mice,airway mucus secretion,and peripheral airway collagen hyperplasia;however,its mechanism of action is unknown.Methods:Fifty 6–8-week-old male BALB/c mice were equally and randomly divided into five groups:the control,ovalbumin(OVA),OVA+respiratory syncytial virus(RSV),QF,and dexamethasone(Dxms)groups.The QF group was administered QF at 1.17 g·kg−1·d−1,the Dxms group received dexamethasone injections at 0.2 mg·kg−1·d−1,and the remaining groups were administered PBS.Inflammation in the lung tissue was assessed by hematoxylin and eosin(HE),periodic acid–Schiff(PAS),and Van Gieson staining.ELISA was used to evaluate the IL-13,IL-25,and IL-33 in the mice.Western blotting was used to examine changes in the proteins levels of transient receptor potential vanilloid-1(TRPV1)and mucin 5AC(MUC5AC)in the lung tissues of mice.Results:Histopathological evaluation revealed that the OVA and OVA+RSV groups exhibited lung tissue edema and inflammatory lung tissue infiltration in the HE staining and airway secretions in the PAS staining;collagen hyperplasia around the airway was increased in these two groups compared with the control group.The QF group exhibited significantly reduced lung tissue edema,inflammatory lung tissue infiltration,airway secretions,and collagen hyperplasia around the airway compared with the OVA+RSV group.We analyzed the serum levels of IL-13,IL-25,and IL-33 in the mice and found that these levels were higher in the OVA and OVA+RSV groups than in the control group(P<0.05 in the OVA group,P<0.01 in the OVA+RSV group).The QF group exhibited significantly decreased serum levels of IL-13,IL-25,and IL-33 compared with the OVA+RSV group(all P<0.05).The Dxms group also exhibited significant decreases in the serum levels of IL-13 and IL-33(all P<0.05)but no significant decrease in the serum levels of IL-25 compared with the RSV+OVA group.Finally,we examined the protein levels of TRPV1 and MUC5AC in the lung tissues of mice using Western blotting.After identifying RSV infection in the mice with asthma,the protein levels of TRPV1 and MUC5AC in the lung tissues of mice were significantly higher than those in the control group(P<0.05,P<0.01).We found that compared with RSV+OVA,QF can significantly downregulate the protein level of TRPV1;further,the protein level of MUC5AC was also significantly reduced(all P<0.001).Conclusion:QF can inhibit RSV replication and reduce airway inflammation and mucus hypersecretion injury caused by RSV infection and asthma,and its mechanism of action may be associated with the downregulation of TRPV1 expression and a decrease in airway mucus hypersecretion injury.

The Association of Respiratory Syncytial Virus Infection and Childhood Asthma: A Meta-Analysis

Objective: To explore the close relationship between respiratory syncytial virus (RSV) infection and acute attack of childhood asthma. Methods: A computer-based search of database from Pumbed, CNKI, Wanfang, Baidu Scholar, Chongqing VIP, GeenMedica was performed to screen the articles about respiratory syncytial virus infection and childhood asthma. Then the literatures were screened out by the selection criteria. The RevMan5.3 software was used to test the heterogeneity and effect values of each study, analyze the sensitivity and publication bias of the literature, and draw on Meta forest plot and Funnel plot. Results: 5 articles conformed to the selection criteria. There were totally 881 cases in the case group, 826 cases in the control group. The results of heterogeneity test showed no heterogeneity between each study (P > 0.05). The fixed-effects model showed the 6.68 (5.06 - 8.82), (Z = 13.38, P < 0.00001). Conclusion: The infection rate of respiratory syncytial virus in children with acute asthma attack is higher than that in remission period. Respiratory syncytial virus infection rate can be used as an indicator of the severity of asthma in children.

A multi-center study on genetic variations in the fusion protein of respiratory syncytial virus from children with Acute Lower Respiratory Tract Infections in China during 2017-2021

Respiratory syncytial virus(RSV)is a significant cause of acute lower respiratory tract infection(ALRTI)in children underfive years of age.Between 2017 and 2021,396 complete sequences of the RSV F gene were obtained from 500 RSV-positive throat swabs collected from ten hospitals across nine provinces in China.In addition,151 sequences from China were sourced from GenBank and GISAID,making a total of 549 RSV F gene sequences subjected to analysis.Phylogenetic and genetic diversity analyses revealed that the RSV F genes circulating in China from 2017 to 2021 have remained relatively conserved,although some amino acids(AAs)have undergone changes.AA mutations with frequencies10%were identified at six sites and the p27 region:V384I(site I),N276S(site II),R213S(siteØ),and K124N(p27)for RSV A;F45L(site I),M152I/L172Q/S173 L/I185V/K191R(site V),and R202Q/I206M/Q209R(siteØ)for RSV B.Comparing mutational frequencies in RSV-F before and after 2020 revealed minor changes for RSV A,while the K191R,I206M,and Q209R frequencies increased by over 10%in RSV B.Notably,the nirsevimab-resistant mutation,S211N in RSV B,increased in frequency from 0%to 1.15%.Both representative strains aligned with the predicted RSV-F structures of their respective prototypes exhibited similar conformations,with low root-mean-square deviation values.These results could provide foundational data from China for the development of RSV mAbs and vaccines.

Qingkailing Injection(清开灵注射液)for Treatment of Children Pneumonia Induced by Respiratory Syncytial Virus:A Meta-Analysis of Rando mized Controlled Trials

Objective： To evaluate the efficacy and safety of Qingkailing Injection（清开灵注射液, QKL） for treatment of children pneumonia caused by respiratory syncytial virus（RSV）. Methods： Randomized clinical trials（RCTs） comparing QKL with ribavirin injection in the treatment of children pneumonia induced by RSV were searched in Pub Med, Science Direct, Cochrane Library, Chinese VIP database, CNKI and Wanfang databases from their inception to March 2014. Meta-analyses were performed using RevMan 5.2 software. The methodological quality of the selected RCTs was evaluated by the Modified Jadad Score. The primary outcome measures were effective rate and the secondary outcomes were relief time of fever and cough. Results： Seven RCTs with 992 cases published from 2008 to 2013 were identified. The meta-analysis results indicated that QKL was more effective in cure rate [risk ratios（RR）=1.32, 95% CI（1.17, 1.50）, P〈0.01], total effective rate [RR=1.07, 95% CI（1.02, 1.13）, P=0.009] and less fever clearance time [mean difference=–0.73, 95% CI（–1.22, –0.23）, P=0.004], compared with ribavirin injection in the treatment of RSV-induced children pneumonia. No dead case was reported in all trials. There were 3 trials mentioned adverse events, 2 reported no obvious adverse event occurred while 1 reported adverse events described as skin hypersensitivity, elevation of ALT, a mild abnormal of hepatic and renal function in both QKL and ribavirin group. Conclusions： QKL was an effective and relatively safe option for the treatment of RSV-induced children pneumonia. These therapeutic effects were promising but need to be interpreted with caution due to variations in the treatment and methodological weakness in the studies.

microRNAs在儿童呼吸道合胞病毒感染中调控作用的研究进展

呼吸道合胞病毒(RSV)是儿童急性下呼吸道感染最常见的病原体,对儿童的健康构成严重威胁,但其病理机制仍不明确,目前仍然没有有效预防和治疗呼吸道合胞病毒的方法。RSV是具有包膜单负链RNA病毒,编码11种蛋白质,这些蛋白质是诱导气道高反应性(AHR)的关键因素。微小RNA(miRNAs)近来被认为是基因表达调控因子,通过调节炎症反应和免疫细胞功能以及气道上皮细胞的宿主免疫反应,在病毒感染中发挥调控作用。本文综述了miRNAs在RSV感染中调控作用的研究进展,旨在为RSV的致病机制、诊断及治疗提供新思路。

Characteristics of respiratory syncytial virus-induced bronchiolitis co-infection with Mycoplasma pneumoniae and add-on therapy with montelukast

Background:The influence of Mycoplasma pneumoniae(MP)infection on bronchiolitis remains unclear.Additionally,reports on the efficacies of leukotriene receptor antagonists in the treatment of bronchiolitis have been inconclusive.Methods:Children with respiratory syncytial virus(RSV)-induced bronchiolitis were divided into two groups:RSV+MP group and RSV group.Each group was randomly divided into two subgroups:one received routine and placebo treatment,while the other received routine and montelukast treatment for 9 months.The cumulative numbers of wheezing episodes and recurrent respiratory tract infections were recorded.Blood parameters were determined.Results:Patients in the RSV+MP group exhibited an older average age,fever,more frequent flaky and patchy shadows in chest X-rays,more frequent extrapulmonary manifestations,and longer hospital stays compared with patients in the RSV group.Additionally,higher baseline blood eosinophil counts,eosinophil cationic protein(ECP),total immunoglobulin E(IgE),interleukin(IL)-4,IL-5,IL-4/interferon-γratios,leukotriene(LT)B4,and LTC4,and lower baseline lipoxin A4(LXA4)/LTB4 ratios were observed in the RSV+MP group compared with the RSV group.Montelukast treatment decreased the cumulative numbers of recurrent wheezing episodes and recurrent respiratory tract infections at 9 and 12 months.This efficacy may be related to the montelukast-induced reductions in peripheral eosinophil counts,ECP and total IgE,as well as the montelukast-dependent recovery in T helper(Th)1/Th2 balance and LXA4/LTB4 ratios in children with bronchiolitis.Conclusions:RSV bronchiolitis with MP infection was associated with clinical and laboratory features that differed from those of RSV bronchiolitis without MP infection.Add-on therapy with montelukast for 9 months was benefi cial for children with bronchiolitis at 9 and 12 months after the initiation of treatment.

儿童清咽解热口服液体外抗呼吸道合胞病毒(RSV)作用及其抗炎活性研究

目的:研究儿童清咽解热口服液体外抗呼吸道合胞病毒(RSV)作用及其抗炎活性。方法:以利巴韦林(Ribavirin)作为阳性对照药物,在HEP-2细胞水平上,采用CellTiter-GloTM免疫荧光法测定受试样品的细胞毒性,通过间接免疫荧光法测定流感病毒蛋白表达水平,以检测细胞培养液上清中病毒复制水平,评价儿童清咽解热口服液对呼吸道合胞病毒(RSV)的作用,同时采用AlphaLISA法检测培养上清中IL-6、IL-8、MCP-1等炎症因子的表达水平。结果:儿童清咽解热口服液半数中毒浓度(CC_(50))为15.33mg·mL^(-1),对呼吸道合胞病毒(RSV)的半数有效浓度(EC_(50))为1.27mg·mL^(-1),炎性指标IL-6、IL-8、MCP-1的半数有效浓度(EC_(50))分别为0.73mg·mL^(-1)、0.83mg·mL^(-1)和0.61mg·mL^(-1)。呼吸道合胞病毒(RSV)选择指数(SI)为12.07,炎性指标IL-6、IL-8、MCP-1的SI分别为21、18.5和25.3。结论:在HEP-2细胞水平上,儿童清咽解热口服液对呼吸道合胞病毒(RSV)病毒具有明显的抗病毒作用,并显示出良好的抗炎活性。

Evaluation by Survival Analysis on Effect of Traditional Chinese Medicine in Treating Children with Respiratory Syncytial Viral Pneumonia of Phlegm-Heat Blocking Fei Syndrome

Objective:To objectively evaluate the clinical effect of traditional Chinese medicine in treating children s respiratory syncytial viral pneumonia(RSVP) of phlegm-heat blocking Fei(肺) syndrome(PHBFS). Methods:A single-blinded multi-center,blocked,randomized and parallel-controlled method was adopted.The clinical study was carried out on 206 children with RSVP-PHBFS who were assigned to two groups,108 in the test group treated through intravenous dripping of Qingkailing Injection(清开灵注射液) in combination of or...

海南省2012-2021年儿童RSV急性呼吸道感染流行病学特征分析

目的分析海南省儿童呼吸道合胞病毒(RSV)急性呼吸道感染(ARTI)的流行病学特征,为预防和诊治儿童RSV感染提供参考。方法收集2012年3月至2021年12月于海南省多家医院住院治疗的59312例ARTI患儿的临床资料,对RSV感染病例的流行病学和临床资料进行回顾性分析。采用间接免疫荧光法检测血清中RSV、肺炎支原体、嗜肺军团菌、肺炎衣原体、腺病毒、Q热立克次体、副流感病毒、甲型流感病毒、乙型流感病毒等九项呼吸道病原体IgM抗体。结果59312例ARTI患儿的RSV-IgM阳性率为2.07%(1226/59312)。2016—2018年RSV-IgM阳性率呈上升趋势,并在2017年、2018年达到高值,分别为4.46%、5.20%,随后呈下降趋势。男性ARTI患儿的RSV-IgM阳性率显著高于女性(2.21%vs 1.82%;χ^(2)=10.714,P<0.001)。夏季ARTI患儿RSV-IgM阳性率最高(2.59%),秋季最低(1.70%)。1226例RSV-IgM阳性患儿中,单纯RSV-IgM阳性485例(39.56%),混合感染741例(60.44%)。其中合并1种其他病原体感染505例(41.19%),合并2种其他病原体感染191例(15.58%),合并3种其他病原体感染45例(3.67%)。对于RSV-IgM阳性患儿,以临床诊断为肺炎的占比最高,以咳嗽为最常见的临床症状。混合感染患儿发热的发生率高于单一RSV感染者,差异有统计学意义(P<0.05)。结论海南省2012—2021年住院ARTI患儿RSV-IgM总阳性率为2.07%。RSV感染以夏季发病率最高,秋季发病率最低。各年龄段均有RSV感染发生,其中婴儿期RSV感染率最高,学龄期最低。男性RSV感染率高于女性。RSV感染常合并1种病原体感染,多为肺炎支原体。RSV感染临床症状主要为咳嗽、发热、鼻塞、流涕、喘息和气促。

Label-free quantitative proteomics reveals fibrinopeptide B and heparin cofactorⅡas potential serum biomarkers in respiratory syncytial virus-infected mice treated with Qingfei oral liquid formula

Respiratory syncytial virus(RSV) is a leading cause of acute lower respiratory tract infections. Qingfei oral liquid(QFOL), a traditional Chinese medicine, is widely used in clinical treatment for RSV-induced pneumonia. The present study was designed to reveal the potential targets and mechanism of action for QFOL by exploring its influence on the host cellular network following RSV infection. We investigated the serum proteomic changes and potential biomarkers in an RSV-infected mouse pneumonia model treated with QFOL. Eighteen BALB/c mice were randomly divided into three groups: RSV pneumonia model group(M), QFOL-treated group(Q) and the control group(C). Serum proteomes were analyzed and compared using a label-free quantitative LC-MS/MS approach. A total of 172 protein groups, 1009 proteins, and 1073 unique peptides were successfully identified. 51 differentially expressed proteins(DEPs) were identified(15 DEPs when M/C and 43 DEPs when Q/M; 7 DEPs in common). Classification and interaction network showed that these proteins participated in various biological processes including immune response, blood coagulation, complement activation, and so forth. Particularly, fibrinopeptide B(FpB) and heparin cofactor Ⅱ(HCII) were evaluated as important nodes in the interaction network, which was closely involved in coagulation and inflammation. Further, the Fp B level was increased in Group M but decreased in Group Q, while the HCII level exhibited the opposite trend. These findings not only indicated FpB and HCII as potential biomarkers and targets of QFOL in the treatment of RSV pneumonia, but also suggested a regulatory role of QFOL in the RSV-induced disturbance of coagulation and inflammation-coagulation interactions.

小儿清炎合剂(716合剂)治疗呼吸道合胞病毒所致呼吸道感染疗效观察及血清学研究

目的探究小儿清炎合剂(716合剂)治疗呼吸道合胞病毒所致呼吸道感染疗效观察及血清学研究。方法将2023年1月至2023年9月江西省儿童医院收治的呼吸道合胞病毒所致呼吸道感染的80例患儿作为研究对象,根据随机对照表法将其分为观察组40例,对照组40例。对照组采用雾化吸入联合静脉输液进行治疗,观察组在对照组的基础上口服小儿清炎合剂(716合剂)。比较两组的临床疗效,治疗前后炎性因子[白细胞介素-6(IL-6)、白细胞介素-10(IL-10)、C反应蛋白(CRP)、血清淀粉样蛋白A(SAA)、肿瘤坏死因子-α(TNF-α)],免疫功能水平(CD4^(+)、CD8^(+)、CD4^(+)/CD8^(+)),恢复情况和不良反应。结果观察组治疗有效率为95.00%,高于对照组的80.00%(P<0.05)。治疗后,两组IL-6、IL-10、CRP、SAA、TNF-α水平均下降且观察组低于对照组(P<0.05);观察组CD4^(+)、CD4^(+)/CD8^(+)水平均高于对照组,而观察组CD8^(+)水平低于对照组(P<0.05)。观察组退热、止咳、平喘以及住院时间均小于对照组(P<0.05)。两组在治疗过程中均未出现任何不良反应。结论小儿清炎合剂(716合剂)能够缓解呼吸道合胞病毒感染患儿的炎性症状,增强患儿免疫功能,促进患儿恢复,安全性良好。

儿童急性淋巴细胞白血病直接医疗成本分析

目的分析急性淋巴细胞白血病(ALL)患儿直接医疗成本及构成比,为医疗制度的改革提供参考依据,为白血病患儿的规范治疗提供保障。方法收集2015年1月至2018年4月重庆医科大学附属儿童医院血液肿瘤科收治的ALL患儿110例,描述性分析ALL患儿的直接医疗成本,探讨其主要构成比。结果ALL患儿规范治疗期间,直接医疗成本主要由门诊费用(平均23597元)、一日化疗病房治疗费用(平均23216元)及普通病房住院费用(平均158152元)三部分构成,在这些费用中,其中药品费、治疗费及化验费所占比例较大。平均报销比例为59.1%(93415/158152),从住院时长上看,ALL患儿平均住院时间为131 d,日均住院费用为1207元(158152/131)。结论降低药品费用,规范的治疗和检查能降低医疗成本。全方位、多角度为白血病患儿家庭提供支持,为患儿的治疗提供有力保障。

更昔洛韦联合雾化重组人干扰素α1b治疗对呼吸道合胞病毒感染肺炎患儿炎症因子及免疫功能的影响

目的:分析更昔洛韦联合雾化重组人干扰素α1b治疗对呼吸道合胞病毒感染肺炎患儿炎症因子及免疫功能的影响。方法:选取本院收治的呼吸道合胞病毒感染肺炎患儿100例作为研究对象。根据随机数表法分为对照和观察两组,各50例;比较两组治疗前、后的炎性因子降钙素原(PCT)、白介素-6(IL-6)、C反应蛋白(CRP)与免疫球蛋白IgA、IgG、IgM水平,详细记录症状体征消失时间并分析治疗期间发生的不良症状。结果:治疗后两组比较,观察组持续发热、咳嗽、憋喘以及肺啰音消失时间短(P<0.05),血清PCT、IL-6与CRP水平低(P<0.05),血清IgG、IgA、IgM水平明显升高(P<0.05);治疗期间,两组恶心呕吐、白细胞降低、皮疹的总发生率比较无统计学意义(P>0.05)。结论:对呼吸道合胞病毒感染肺炎患儿实施更昔洛韦联合雾化重组人干扰素α1b联合用药可缩短症状体征消失时间,减轻机体炎症反应,提高机体免疫力,安全性相对较好。

化湿败毒颗粒治疗呼吸道合胞病毒肺炎模型小鼠的脂质组学研究

目的探究化湿败毒颗粒对呼吸道合胞病毒(Respiratory syncytial virus,RSV)肺炎模型小鼠的治疗作用以及对肺组织脂质代谢的影响。方法将BALB/c小鼠随机分为空白组、模型组、利巴韦林组、地塞米松组、化湿败毒颗粒低剂量组和化湿败毒颗粒高剂量组。分别采集各组小鼠肺组织样本,观察其病理改变,检测肺组织中RSV-F、RSV-G、IL-1β、IL-6、TNF-αmRNA表达水平。采用超高效液相色谱-四极杆-静电场轨道阱高分辨质谱联用(UPLC-Q Exactive Orbitrap MS)技术对肺组织进行脂质组学分析,寻找脂质代谢变化。结果与空白组相比,模型组小鼠肺组织出现肺间质增厚,可见明显炎症浸润。肺组织病毒载量及肺部炎症因子如IL-1β、TNF-αmRNA水平显著升高(P<0.001)。同时,与空白组相比,模型组呈现脂质代谢的明显异常,具体表现为磷脂酰丝氨酸(PS)、磷脂酰甘油(PG)、鞘磷脂(SM)、神经酰胺(Cer)、甘油三酯(TG)、甘油二酯(DG)、脂肪酸(FA)、醚磷脂酰胆碱(PC O)、醚溶血磷脂酰胆碱(LPC O)等脂质代谢紊乱。经化湿败毒颗粒(25.12 g·kg^(-1)·d^(-1))干预可以调节上述脂质紊乱。结论化湿败毒颗粒可以通过调控脂质代谢,降低RSV感染小鼠肺组织中的病毒载量,减轻炎症反应等途径治疗RSV肺炎。

3种治法对RSV诱导的肺炎小鼠炎性细胞因子的表达及TLR-4/NF-кB信号通路调控研究

目的:探讨3种治法代表方剂对呼吸道合胞病毒(RSV)诱导引起肺炎的小鼠血清IL-6、IL-8及肺组织Toll样受体4(TLR4)、细胞核转录因子(NF-кB)的影响,揭示其治疗机制。方法:将Wister小鼠随机分为正常组、模型组、利巴韦林组、银翘散组、玉屏风散组、银屏散组。于感染前3 d,玉屏风散组、银屏散组连续给予玉屏风散(7.5 g·kg·d-1)3 d;除正常组以外,50μL 10 LD50病毒液滴鼻建立呼吸道合胞病毒感染的小鼠RSV肺炎模型。感染2 h后,银翘散组、银屏散组继续给予银翘散治疗(10 g·kg·d-1),连续给药3 d;采用ELISA法检测各组小鼠血清中IL-6、IL-8含量,免疫组化法检测分析肺组织TLR4、NF-кB P65蛋白的表达。结果:与正常组比较,RSV感染诱导小鼠肺组织中TLR4蛋白表达上调,增加NF-кB的活化(P<0.05),使血清中IL-6、IL-8水平升高(P<0.05)。银翘散组、玉屏风散组、双表法组测得IL-6、IL-8含量以及TLR4、NF-κB P65表达相较于模型组显著减弱(P<0.05)。与利巴韦林组比较,双表法组减弱尤为突出(P<0.05)。结论:3种治法对于治疗RSV肺炎均有显著疗效,尤其以双表法疗效更佳。其作用机制可能与抑制炎症因子IL-6、IL-8分泌及阻断TLR4/NF-κB信号通路有关。

清开灵注射液治疗小儿RSV肺炎痰热闭肺证主症不同时点的疗效

目的从主症不同时点的疗效变化评价清开灵注射液治疗小儿RSV肺炎痰热闭肺证的临床疗效。方法对206例患儿进行中西药对照观察,试验组给予清开灵注射液静脉滴注,儿童清肺口服液口服;对照组给予利巴韦林注射液静脉滴注,复方愈创木酚磺酸钾口服液口服,疗程均为10天。对治疗过程中主症(发热、咳嗽、痰壅、气促)不同时点的疗效分别进行评价。结果试验组各主症的优势均表现在早期起效上,起效时间均为第4天,且咳嗽、痰壅症状的优势疗效贯穿于整个疗程。结论中医药在治疗小儿RSV肺炎痰热闭肺证中显示出多靶点的治疗效应。

RSV感染毛细支气管炎患儿血清Clara细胞分泌蛋白、总IgE及ECP的临床研究

目的探讨血清Clara细胞分泌蛋白(Clara cell secretory protein,CCSP)、总IgE和嗜酸性粒细胞阳离子蛋白(eosinophil cationic protein,ECP)在呼吸道合胞病毒(respiratory syncytial virus,RSV)感染所致毛细支气管炎发病中的临床意义。方法采用酶联免疫吸附法测定32例RSV感染引起的毛细支气管炎患儿血清的CCSP含量,同时应用uniCAP100变态反应检测仪检测血清总IgE、ECP;另设25例正常婴幼儿作对照。结果与正常对照组比较,RSV组患儿血清的CCSP含量显著降低(t=10.52,P<0.001)、血清总IgE显著增高(t=5.96,P<0.01)、血清ECP水平差异无统计学意义(t=1.97,P>0.05)。RSV组患儿血清CCSP与总IgE之间呈显著负相关(r=-0.654,P<0.05)、血清CCSP与ECP(r=-0.166,P>0.05)以及总IgE与ECP(r=0.137,P>0.05)之间无统计学相关关系。结论血清CCSP的降低与总IgE水平的增高在呼吸道合胞病毒感染所致毛细支气管炎发病中发挥着重要作用,呼吸道合胞病毒感染毛细支气管炎患儿血清ECP无异常改变。