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 co...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.展开更多
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 childr...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.展开更多
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 T...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.展开更多
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 ...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.展开更多
<strong>Objective:</strong> To explore the close relationship between respiratory syncytial virus (RSV) infection and acute attack of childhood asthma. <strong>Methods:</strong> A computer-base...<strong>Objective:</strong> To explore the close relationship between respiratory syncytial virus (RSV) infection and acute attack of childhood asthma. <strong>Methods:</strong> A computer-based search of database from Pumbed, CNKI, Wanfang, about:blank 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. <strong>Results:</strong> 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). <strong>Conclusion:</strong> 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.展开更多
Objective: Qingfei Tongluo Plaster(QFP), an improved Chinese medicine hospital preparation, is an attractive treatment option due to its well clinical efficacy, convenience, economy, and patient compliance in the trea...Objective: Qingfei Tongluo Plaster(QFP), an improved Chinese medicine hospital preparation, is an attractive treatment option due to its well clinical efficacy, convenience, economy, and patient compliance in the treatment of respiratory syncytial virus(RSV) pneumonia. The aim of this study was to investigate the efficacy mechanism of QFP on RSV rats from the perspective of alleviating lung inflammation and further explore the changes of serum metabolites and metabolic pathways in RSV rats under the influence of QFP.Methods: This study used network pharmacological methods and molecular docking combined with molecular biology and metabolomics from multi-dimensional perspectives to screen and verify the therapeutic targets. Open online databases were used to speculate the gene targets of efficient ingredients and diseases. Then, we used the String database to examine the fundamental interaction of common targets of drugs and diseases. An online enrichment analysis was performed to predict the functional pathways. Molecular docking was applied to discover the binding modes between essential ingredients and crucial gene targets. Finally, we demonstrated the anti-inflammatory ability of QFP in the RSV-evoked pneumonia rat model and explained the mechanism in combination with the metabolomics results.Results: There were 19 critical targets defined as the core targets: tumor necrosis factor(TNF), inducible nitric oxide synthase 2(NOS2), mitogen-activated protein kinase 14(MAPK14), g1/S-specific cyclin-D1(CCND1), signal transducer and activator of transcription 1-alpha/beta(STAT1), proto-oncogene tyrosine-protein kinase Src(SRC), cellular tumor antigen p53(TP53), interleukin-6(IL6), hypoxiainducible factor 1-alpha(HIF1A), RAC-alpha serine/threonine-protein kinase(AKT1), signal transducer and activator of transcription 3(STAT3), heat shock protein HSP 90-alpha(HSP90AA1), tyrosine-protein kinase JAK2(JAK2), cyclin-dependent kinase inhibitor 1(CDKN1A), mitogen-activated protein kinase 3(MAPK3), epidermal growth factor receptor(EGFR), myc proto-oncogene protein(MYC), protein c-Fos(FOS) and transcription factor p65(RELA). QFP treated RSV pneumonia mainly through the phosphatidylinositol 3-kinase(PI3K)/RAC AKT pathway, HIF-1 pathway, IL-17 pathway, TNF pathway, and MAPK pathway. Animal experiments proved that QFP could effectively ameliorate RSV-induced pulmonary inflammation. A total of 28 metabolites underwent significant changes in the QFP treatment, and there are four metabolic pathways consistent with the KEGG pathway analyzed by network pharmacology,suggesting that they may be critical processes related to treatment.Conclusion: These results provide essential perspicacity into the mechanisms of action of QFP as a promising anti-RSV drug.展开更多
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 fro...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.展开更多
Objective: The objective of this study is to explore the optimal ratio of Glycyrrhiza Radix(GR, Glycyrrhizae radix et Rhizoma) and Platycodonis Radix(PR, Platycodon grandifiorum A. DC) and its potential mechanism for ...Objective: The objective of this study is to explore the optimal ratio of Glycyrrhiza Radix(GR, Glycyrrhizae radix et Rhizoma) and Platycodonis Radix(PR, Platycodon grandifiorum A. DC) and its potential mechanism for treating respiratory syncytial virus(RSV) pneumonia in mice.Materials and Methods: Aqueous extracts of GR-PR with different ratios(1:1, 2:1, and 1:2 w/w) were prepared and analyzed using ultra-performance liquid chromatography coupled with a linear ion trap quadrupole Orbitrap mass spectrometry(UPLC/LTQ-Orbitrap-MS). The effects of various ratios of GR-PR were investigated in BALB/c mice. Changes in body weight were recorded, histopathology was evaluated, and relative mRNA levels of infiammatory mediators were measured. In addition, lipidomic analysis was performed to investigate the effects of GR-PR on lipids and related signaling pathways. Results: The aqueous extracts of GR-PR improved body weight and reduced lung infiammation compared to the RSV group, with the optimal therapeutic effect achieved with a 1:2 ratio of GR to PR. RSV infection disrupted several serum lipids, particularly sphingomyelin(SM) and ceramide(CER), which were partially restored by GR-PR administration. Overall, GR-PR significantly improved the metabolic disorder of SM-CER-induced infiammation and apoptosis, along with decreased m RNA levels of caspase-1, nucleotide-binding domain,leucine-rich repeat, and pyrin domain-containing protein 3(NLRP3), and toll-like receptor 3(TLR3), and protein expression of NLRP3, pro-caspase-1,apoptosis-associated speck-like protein containing a caspase-recruitment domain(ASC), interleukin-1β(IL-1β), IL-18, gasdermin D(GSDMD),nuclear factor kappa-B(NF-κB), Bcl2-associated X protein(BAX), caspase-3, and caspase-8. The involvement of the TLR3-NF-κB-NLRP3 signaling pathway in this process was confirmed. Conclusions: The aqueous extracts of GR-PR, particularly at a ratio of 1:2, demonstrate potential therapeutic benefits for RSV-induced pneumonia by improving lipid metabolism and inhibiting the activation of TLR3-NF-κB-NLRP3 signaling pathway.展开更多
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（RCT...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.展开更多
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 singl...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...展开更多
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 in...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.展开更多
文摘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.
文摘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.
文摘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.
基金This work was supported by Natural Science Foundation of China(81674020).
文摘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.
文摘<strong>Objective:</strong> To explore the close relationship between respiratory syncytial virus (RSV) infection and acute attack of childhood asthma. <strong>Methods:</strong> A computer-based search of database from Pumbed, CNKI, Wanfang, about:blank 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. <strong>Results:</strong> 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). <strong>Conclusion:</strong> 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.
基金supported by the National Natural Science Foundation of China (No. 81973906)。
文摘Objective: Qingfei Tongluo Plaster(QFP), an improved Chinese medicine hospital preparation, is an attractive treatment option due to its well clinical efficacy, convenience, economy, and patient compliance in the treatment of respiratory syncytial virus(RSV) pneumonia. The aim of this study was to investigate the efficacy mechanism of QFP on RSV rats from the perspective of alleviating lung inflammation and further explore the changes of serum metabolites and metabolic pathways in RSV rats under the influence of QFP.Methods: This study used network pharmacological methods and molecular docking combined with molecular biology and metabolomics from multi-dimensional perspectives to screen and verify the therapeutic targets. Open online databases were used to speculate the gene targets of efficient ingredients and diseases. Then, we used the String database to examine the fundamental interaction of common targets of drugs and diseases. An online enrichment analysis was performed to predict the functional pathways. Molecular docking was applied to discover the binding modes between essential ingredients and crucial gene targets. Finally, we demonstrated the anti-inflammatory ability of QFP in the RSV-evoked pneumonia rat model and explained the mechanism in combination with the metabolomics results.Results: There were 19 critical targets defined as the core targets: tumor necrosis factor(TNF), inducible nitric oxide synthase 2(NOS2), mitogen-activated protein kinase 14(MAPK14), g1/S-specific cyclin-D1(CCND1), signal transducer and activator of transcription 1-alpha/beta(STAT1), proto-oncogene tyrosine-protein kinase Src(SRC), cellular tumor antigen p53(TP53), interleukin-6(IL6), hypoxiainducible factor 1-alpha(HIF1A), RAC-alpha serine/threonine-protein kinase(AKT1), signal transducer and activator of transcription 3(STAT3), heat shock protein HSP 90-alpha(HSP90AA1), tyrosine-protein kinase JAK2(JAK2), cyclin-dependent kinase inhibitor 1(CDKN1A), mitogen-activated protein kinase 3(MAPK3), epidermal growth factor receptor(EGFR), myc proto-oncogene protein(MYC), protein c-Fos(FOS) and transcription factor p65(RELA). QFP treated RSV pneumonia mainly through the phosphatidylinositol 3-kinase(PI3K)/RAC AKT pathway, HIF-1 pathway, IL-17 pathway, TNF pathway, and MAPK pathway. Animal experiments proved that QFP could effectively ameliorate RSV-induced pulmonary inflammation. A total of 28 metabolites underwent significant changes in the QFP treatment, and there are four metabolic pathways consistent with the KEGG pathway analyzed by network pharmacology,suggesting that they may be critical processes related to treatment.Conclusion: These results provide essential perspicacity into the mechanisms of action of QFP as a promising anti-RSV drug.
基金supported by the National Key Research and Development Program of China(grant number 2023YFC2306002)National Science and Technology Major Projects(grant number 2017ZX10104001-005-010)+1 种基金CAMS Innovation Fund for Medical Sciences(CIFMS)(Grant Number 2019-I2M-5-026)Funding for Reform and Development of Beijing Municipal Health Commission.
文摘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.
基金the support of the National Natural Science Foundation of China (grant numbers 82174098,81774156)Jiangsu Provincial Six Talent Peaks Project (grant number YY-022)+1 种基金Jiangsu Qing Lan ProjectNatural Science Foundation of Jiangsu Provincial Department of Education (20KJB320018)
文摘Objective: The objective of this study is to explore the optimal ratio of Glycyrrhiza Radix(GR, Glycyrrhizae radix et Rhizoma) and Platycodonis Radix(PR, Platycodon grandifiorum A. DC) and its potential mechanism for treating respiratory syncytial virus(RSV) pneumonia in mice.Materials and Methods: Aqueous extracts of GR-PR with different ratios(1:1, 2:1, and 1:2 w/w) were prepared and analyzed using ultra-performance liquid chromatography coupled with a linear ion trap quadrupole Orbitrap mass spectrometry(UPLC/LTQ-Orbitrap-MS). The effects of various ratios of GR-PR were investigated in BALB/c mice. Changes in body weight were recorded, histopathology was evaluated, and relative mRNA levels of infiammatory mediators were measured. In addition, lipidomic analysis was performed to investigate the effects of GR-PR on lipids and related signaling pathways. Results: The aqueous extracts of GR-PR improved body weight and reduced lung infiammation compared to the RSV group, with the optimal therapeutic effect achieved with a 1:2 ratio of GR to PR. RSV infection disrupted several serum lipids, particularly sphingomyelin(SM) and ceramide(CER), which were partially restored by GR-PR administration. Overall, GR-PR significantly improved the metabolic disorder of SM-CER-induced infiammation and apoptosis, along with decreased m RNA levels of caspase-1, nucleotide-binding domain,leucine-rich repeat, and pyrin domain-containing protein 3(NLRP3), and toll-like receptor 3(TLR3), and protein expression of NLRP3, pro-caspase-1,apoptosis-associated speck-like protein containing a caspase-recruitment domain(ASC), interleukin-1β(IL-1β), IL-18, gasdermin D(GSDMD),nuclear factor kappa-B(NF-κB), Bcl2-associated X protein(BAX), caspase-3, and caspase-8. The involvement of the TLR3-NF-κB-NLRP3 signaling pathway in this process was confirmed. Conclusions: The aqueous extracts of GR-PR, particularly at a ratio of 1:2, demonstrate potential therapeutic benefits for RSV-induced pneumonia by improving lipid metabolism and inhibiting the activation of TLR3-NF-κB-NLRP3 signaling pathway.
基金Supported by Medical Research Foundation of Guangdong Province(No.B2014262)
文摘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.
基金Supported by the National Key Technologies Research and Development Program of China during the 10th Five-Year PlanPeriod(No.2004BA716B03)
文摘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...
基金supported by a grant from the Priority Academic Program Development of Jiangsu Higher Education Institution(JX10231801).
文摘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.
