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
Despite intense research efforts, the specific pathogenic mechanisms that underlie the link between respiratory syncytial virus （RSV） and childhood asthma remain unclear. Recent researches suggest that changes in th...Despite intense research efforts, the specific pathogenic mechanisms that underlie the link between respiratory syncytial virus （RSV） and childhood asthma remain unclear. Recent researches suggest that changes in the structure and function of the nerves themselves in response to changing conditions, a phenomenon known as neuronal plasticity, may also contribute to the pathophysiology of airway diseases. Therefore.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
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
Summary： Viral infections are the major causes of morbidity and mortality in elderly people and young children throughout the world. The most common pathogens include coxsackie virus （CV） and respira- tory syncytia...Summary： Viral infections are the major causes of morbidity and mortality in elderly people and young children throughout the world. The most common pathogens include coxsackie virus （CV） and respira- tory syncytial virus （RSV）. However, no antiviral agents with low toxicity and drug resistance are cur- rently available in clinic therapy. The present study aimed to examine the antiviral activities of emodin （an ingredient of Rheum palmatum） against CVB5 and RSV infections, in an attempt to discover new antiviral agents for virus infection. The monomer emodin was extracted and isolated from Rheum pal- matum. The antiviral activities of emodin on HEp-2 cells were evaluated, including virus replication in- hibition, virucidal and anti-absorption effects, by 3-（4,5-dimethylthiazol-2-yl）-2,5-diphenyl-2H-tet- razolium bromide （MTT） assay and plaque reduction assay （PRA）. The kinetics of virus inhibition by emodin in a period of 14 h was further determined by plaque assay and quantitative real time PCR （qPCR）. Cytokine （IFN-γ, TNF-α） mRNA expressions after emodin treatment （7.5, 15, 30 μmol/L） were also assessed by qPCR post-infection. The results showed that emodin had potent inhibitory activities against CVB5 and RSV, with the 50% effective concentration （EC50） ranging from 13.06 to 14.27 μmol/L and selectivity index （SI） being 5.38-6.41 μmol/L. However, emodin couldn＇t directly inacti- vate the viruses or block their absorption to cells. It acted as a biological synthesis inhibitor against CVB4 and RSV in a concentration- and time-dependent manner, especially during the first 0-4 h post-infection. Moreover, emodin could decrease the mRNA expression of IFN-α but enhance TNF-γ expression significantly compared to the viral controls in vitro. Our results provide a molecular basis for development of emodin as a novel and safe antiviral agent for human enterovirus and respiratory virus infection in the clinical therapy.展开更多
Background Respiratory syncytial virus(RSV)is the leading global cause of respiratory infections and is responsible for about 3 million hospitalizations and more than 100,000 deaths annually in children younger than 5...Background Respiratory syncytial virus(RSV)is the leading global cause of respiratory infections and is responsible for about 3 million hospitalizations and more than 100,000 deaths annually in children younger than 5 years,representing a major global healthcare burden.There is a great unmet need for new agents and universal strategies to prevent RSV infections in early life.A multidisciplinary consensus development group comprising experts in epidemiology,infectious diseases,respiratory medicine,and methodology aims to develop the current consensus to address clinical issues of RSV infections in children.Data sources The evidence searches and reviews were conducted using electronic databases,including PubMed,Embase,Web of Science,and the Cochrane Library,using variations in terms for"respiratory syncytial virus","RSV","lower respiratory tract infection","bronchiolitis","acute","viral pneumonia","neonatal","infant""children",and"pediatric".Results Evidence-based recommendations regarding diagnosis,treatment,and prevention were proposed with a high degree of consensus.Although supportive care remains the cornerstone for the management of RSV infections,new monoclonal antibodies,vaccines,drug therapies,and viral surveillance techniques are being rolled out.Conclusions This consensus,based on international and national scientific evidence,reinforces the current recommendations and integrates the recent advances for optimal care and prevention of RSV infections.Further improvements in the management of RSV infections will require generating the highest quality of evidence through rigorously designed studies that possess little bias and sufficient capacity to identify clinically meaningful end points.展开更多
Background Bronchiolitis is a common acute lower respiratory tract infection(ALRTI)and the most frequent cause of hospitalization of infants and young children with ALRTI.Respiratory syncytial virus is the main pathog...Background Bronchiolitis is a common acute lower respiratory tract infection(ALRTI)and the most frequent cause of hospitalization of infants and young children with ALRTI.Respiratory syncytial virus is the main pathogen that leads to severe bronchiolitis.The disease burden is relatively high.To date,few descriptions of the clinical epidemiology and disease burden of children hospitalized for bronchiolitis are available.This study reports the general clinical epidemiological characteristics and disease burden of bronchiolitis in hospitalized children in China.Methods This study included the face sheet of discharge medical records collected from 27 tertiary children’s hospitals from January 2016 to December 2020 that were aggregated into the FUTang Update medical REcords(FUTURE)database.The sociodemographic variables,length of stay(LOS)and disease burden of children with bronchiolitis were analyzed and compared using appropriate statistical tests.Results In total,42,928 children aged 0–3 years were hospitalized due to bronchiolitis from January 2016 to December 2020,accounting for 1.5%of the total number of hospitalized children of the same age in the database during the period and 5.31%of the hospitalizations for ALRTI.The male to female ratio was 2.01:1.Meanwhile,more boys than girls were observed in different regions,age groups,years,and residences.The 1–2 year age group had the greatest number of hospitalizations for bronchiolitis,while the 29 days–6 months group had the largest proportion of the total inpatients and inpatients with ALRTI in the same age group.In terms of region,the hospitalization rate of bronchiolitis was the highest in East China.Overall,the number of hospitalizations from 2017 to 2020 showed a decreasing trend from that in 2016.Seasonally,the peak hospitalizations for bronchiolitis occurred in winter.Hospitalization rates in North China in autumn and winter were higher than those in South China,while hospitalization rates in South China were higher in spring and summer.Approximately展开更多
Background Respiratory syncytial virus （RSV） is a common pathogen in the lower respiratory tract of infants and children. Recent studies have shown that in adults, especially in the eldedy population who have relati...Background Respiratory syncytial virus （RSV） is a common pathogen in the lower respiratory tract of infants and children. Recent studies have shown that in adults, especially in the eldedy population who have relatively weak immunity, lower respiratory tract infection is not uncommon. RSV was detected in 22% hospitalized patients with acute exacerbation of chronic obstructive pulmonary disease （COPD）, and the detection rate was only next to that of parvovirus and influenza virus respectively. Further studies revealed that lung infection of RSV could lead to inflammatory destruction and structural remodeling. This study was undertaken to examine the effect of infection with RSV on matrix metalloproteinase （MMPs） in mice, and to explore the role of RSV in the pathogenesis of pulmonary diseases. Methods Twenty BALB/c mice were divided randomly into an RSV infection group and a blank control group. The mice in the RSV infection group were given 100 pl liquid containing 10s PFU of RSV by intranasal instillation. Three days after the infection, the bronchoalveolar lavage fluid （BALF） was harvested and RT-PCR and Western blotting were used to detect MMP-9 and the expression of tissue inhibitors of matdx metalloproteinase （TIMP）-I mRNA in lung tissues. Gelatin zymography was employed to detect the activities of MMP-9 and MMP-2 in BALF. Immunohistochemistry was used to determine the expressions of E-cadherin （E-cd） and proliferating call nuclear antigen （PCNA） in the lung tissues. Results In the BALF of the mice infected with RSV, the activities of MMP-9 and MMP-2 were significantly increased （t=-6.08, P〈0.01 and t=5.68, P〈0.01）. The levels of mRNAand proteins of MMP-9 in the lung tissues of the mica infected with RSV were significantly elevated, and the mRNA and protein levels were significantly higher than those of the blank controls. Though the ratio of MMP-9/TIMP-1 mRNA in the lung tissues of the infected mica was not significantly different from that of the normal controls, the rat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
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
Background Respiratory syncytial virus(RSV)infection in infants is a global health priority.We aimed to investigate the common manifestations of RSV infection by age group and human development index(HDI)level and to ...Background Respiratory syncytial virus(RSV)infection in infants is a global health priority.We aimed to investigate the common manifestations of RSV infection by age group and human development index(HDI)level and to assess its association with the development of wheezing and recurrent wheezing illness.Methods We searched the literature published between January 1,2010 and June 2,2022 in seven databases.Outcomes included common manifestations and long-term respiratory outcomes of RSV infection in children.Random-and fixed-effect models were used to estimate the effect size and their 95%confidence intervals.Subgroup analysis was conducted by age and HDI levels.This review was registered in PROSPERO(CRD42022379401).Results The meta-analysis included 47 studies.The top five manifestations were cough(92%),nasal congestion(58%),rhinorrhea(53%),shortness of breath(50%),and dyspnea(47%).The clinical symptoms were most severe in infants.In our analysis,compared to very high and high HDI countries,fewer studies in medium HDI countries reported related manifestations,and no study in low HDI countries reported that.The RSV-infected infants were more likely to develop wheezing than the non-infected infants[odds ratio(OR),3.12;95%CI,2.59–3.76]and had a higher risk of developing wheezing illnesses after recovery(OR,2.60;95%CI,2.51–2.70).Conclusions Cough and shortness of breath are common manifestations of RSV infection.More attention should be given to infants and areas with low HDI levels.The current findings confirm an association between RSV infection and wheezing or recurrent wheezing illness.展开更多
Restrictive measures adopted worldwide against COVID19(e.g.,wearing masks,frequent hand washing,and social distancing)produced not only a decrease in SARS-CoV-2 difusion but also a drastic reduction in respiratory dis...Restrictive measures adopted worldwide against COVID19(e.g.,wearing masks,frequent hand washing,and social distancing)produced not only a decrease in SARS-CoV-2 difusion but also a drastic reduction in respiratory diseases caused by other pathogens,as reported by many authors[1,2].The spread of respiratory viruses,particularly respiratory syncytial virus(RSV),has been completely changed during the winter of 2020–2021[3,4],but an unusual resurgence of RSV infection has been recently reported in diferent countries[3-7].展开更多
Inclusion bodies(IBs)of respiratory syncytial virus(RSV)are formed by liquid-liquid phase separation(LLPS)and contain internal structures termed“IB-associated granules”(IBAGs),where anti-termination factor M2-1 and ...Inclusion bodies(IBs)of respiratory syncytial virus(RSV)are formed by liquid-liquid phase separation(LLPS)and contain internal structures termed“IB-associated granules”(IBAGs),where anti-termination factor M2-1 and viral mRNAs are concentrated.However,the mechanism of IBAG formation and the physiological function of IBAGs are unclear.Here,we found that the internal structures of RSV IBs are actual M2-1-free viral messenger ribonucleoprotein(mRNP)condensates formed by secondary LLPS.Mechanistically,the RSV nucleoprotein(N)and M2-1 interact with and recruit PABP to IBs,promoting PABP to bind viral mRNAs transcribed in IBs by RNArecognition motif and drive secondary phase separation.Furthermore,PABP-eIF4G1 interaction regulates viral mRNP condensate composition,thereby recruiting specific translation initiation factors(eIF4G1,eIF4E,eIF4A,eIF4B and eIF4H)into the secondary condensed phase to activate viral mRNAs for ribosomal recruitment.Our study proposes a novel LLPS-regulated translation mechanism during viral infection and a novel antiviral strategy via targeting on secondary condensed phase.展开更多
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 pneumoni...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.展开更多
Human milk oligosaccharides (HMO) contribute to innate immunity by enhancing growth of beneficial bacteria, epithelial cell maturation and mucosal barrier integrity. They have immunomodulatory effects and can block pa...Human milk oligosaccharides (HMO) contribute to innate immunity by enhancing growth of beneficial bacteria, epithelial cell maturation and mucosal barrier integrity. They have immunomodulatory effects and can block pathogen binding to host cell surface glycans or receptors. We investigated the effects of 2’-fucosyllactose (2’FL), 6’-sialyllactose (6’SL), 3’-sialyllactose (3’SL) and lacto-N-neoTetraose (LNnT) on human respiratory epithelial cell lines or peripheral blood mononuclear cells (PBMCs) following respiratory viral infectionin vitro. Expression of cytokines and viral load were monitored in infected cells. These biomarkers of innate immunity were selected since viral load and cytokine levels (IP-10, MIP-1α, IL-6, IL-8, TNF-α) have been correlated with disease severity in respiratory syncytial virus (RSV) and influenza (IAV) virus infectionin vivo. 2’FL significantly decreased RSV viral load and cytokines associated with disease severity (IL-6, IL-8, MIP-1α) and inflammation (TNF-α, MCP-1) in airway epithelial cells. LNnT and 6’SL significantly decreased IAV viral load in airway epithelial cells. 6’SL dose-dependently down-regulated IP-10 and TNF-α in RSV infected PBMCs. HMO at or below levels found in breast milk enhance innate immunity to respiratory viruses in vitro and may interact directly with cells to modulate biomarkers of innate immunity.展开更多
Dear Editor,Respiratory syncytial virus(RSV)is the leading cause of serious lower respiratory tract disease in children under 5 years of age worldwide,causing an estimated 3.2 million hospitalizations and 120,000 deat...Dear Editor,Respiratory syncytial virus(RSV)is the leading cause of serious lower respiratory tract disease in children under 5 years of age worldwide,causing an estimated 3.2 million hospitalizations and 120,000 deaths in children globally per year.Furthermore,nearly all children can be infected with RSV by 2 years of age,and individuals can be repeatedly re-infected with RSV throughout life,which poses great threats to infants,the elderly.展开更多
Respiratory syncytial virus （RSV） is a leading cause of .epidemic respiratory tract illness in children. Severe RSV infections involving the lower respiratory tract are primarily seen in young children with naive im...Respiratory syncytial virus （RSV） is a leading cause of .epidemic respiratory tract illness in children. Severe RSV infections involving the lower respiratory tract are primarily seen in young children with naive immune systems and/or genetic predispositions. However, RSV was not recognized as a potentially serious problem in older adults until the 1970s, when outbreaks of the virus infection occurred in long-term care facilities. Since then, additional studies in hospitalized adults have suggested that RSV may be an important cause of illness in community-dwelling elderly people, patients with suppressed T-cell immunity （such as heart transplant recipients）.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.
基金This work was supported by the National Natural Science Foundation of China (No.30470756).
文摘Despite intense research efforts, the specific pathogenic mechanisms that underlie the link between respiratory syncytial virus （RSV） and childhood asthma remain unclear. Recent researches suggest that changes in the structure and function of the nerves themselves in response to changing conditions, a phenomenon known as neuronal plasticity, may also contribute to the pathophysiology of airway diseases. Therefore.
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 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 grants from the National Mega Project on Major Drug Development(No.2009ZX09301-014-1)National Natural Science Foundation of China(No.81371865)
文摘Summary： Viral infections are the major causes of morbidity and mortality in elderly people and young children throughout the world. The most common pathogens include coxsackie virus （CV） and respira- tory syncytial virus （RSV）. However, no antiviral agents with low toxicity and drug resistance are cur- rently available in clinic therapy. The present study aimed to examine the antiviral activities of emodin （an ingredient of Rheum palmatum） against CVB5 and RSV infections, in an attempt to discover new antiviral agents for virus infection. The monomer emodin was extracted and isolated from Rheum pal- matum. The antiviral activities of emodin on HEp-2 cells were evaluated, including virus replication in- hibition, virucidal and anti-absorption effects, by 3-（4,5-dimethylthiazol-2-yl）-2,5-diphenyl-2H-tet- razolium bromide （MTT） assay and plaque reduction assay （PRA）. The kinetics of virus inhibition by emodin in a period of 14 h was further determined by plaque assay and quantitative real time PCR （qPCR）. Cytokine （IFN-γ, TNF-α） mRNA expressions after emodin treatment （7.5, 15, 30 μmol/L） were also assessed by qPCR post-infection. The results showed that emodin had potent inhibitory activities against CVB5 and RSV, with the 50% effective concentration （EC50） ranging from 13.06 to 14.27 μmol/L and selectivity index （SI） being 5.38-6.41 μmol/L. However, emodin couldn＇t directly inacti- vate the viruses or block their absorption to cells. It acted as a biological synthesis inhibitor against CVB4 and RSV in a concentration- and time-dependent manner, especially during the first 0-4 h post-infection. Moreover, emodin could decrease the mRNA expression of IFN-α but enhance TNF-γ expression significantly compared to the viral controls in vitro. Our results provide a molecular basis for development of emodin as a novel and safe antiviral agent for human enterovirus and respiratory virus infection in the clinical therapy.
文摘Background Respiratory syncytial virus(RSV)is the leading global cause of respiratory infections and is responsible for about 3 million hospitalizations and more than 100,000 deaths annually in children younger than 5 years,representing a major global healthcare burden.There is a great unmet need for new agents and universal strategies to prevent RSV infections in early life.A multidisciplinary consensus development group comprising experts in epidemiology,infectious diseases,respiratory medicine,and methodology aims to develop the current consensus to address clinical issues of RSV infections in children.Data sources The evidence searches and reviews were conducted using electronic databases,including PubMed,Embase,Web of Science,and the Cochrane Library,using variations in terms for"respiratory syncytial virus","RSV","lower respiratory tract infection","bronchiolitis","acute","viral pneumonia","neonatal","infant""children",and"pediatric".Results Evidence-based recommendations regarding diagnosis,treatment,and prevention were proposed with a high degree of consensus.Although supportive care remains the cornerstone for the management of RSV infections,new monoclonal antibodies,vaccines,drug therapies,and viral surveillance techniques are being rolled out.Conclusions This consensus,based on international and national scientific evidence,reinforces the current recommendations and integrates the recent advances for optimal care and prevention of RSV infections.Further improvements in the management of RSV infections will require generating the highest quality of evidence through rigorously designed studies that possess little bias and sufficient capacity to identify clinically meaningful end points.
基金XZD was supported by the CAMS Innovation Fund for Med‑ical Sciences(2019-I2M-5-026)the National Major Science&Technology Project(2017ZX10103004-004).
文摘Background Bronchiolitis is a common acute lower respiratory tract infection(ALRTI)and the most frequent cause of hospitalization of infants and young children with ALRTI.Respiratory syncytial virus is the main pathogen that leads to severe bronchiolitis.The disease burden is relatively high.To date,few descriptions of the clinical epidemiology and disease burden of children hospitalized for bronchiolitis are available.This study reports the general clinical epidemiological characteristics and disease burden of bronchiolitis in hospitalized children in China.Methods This study included the face sheet of discharge medical records collected from 27 tertiary children’s hospitals from January 2016 to December 2020 that were aggregated into the FUTang Update medical REcords(FUTURE)database.The sociodemographic variables,length of stay(LOS)and disease burden of children with bronchiolitis were analyzed and compared using appropriate statistical tests.Results In total,42,928 children aged 0–3 years were hospitalized due to bronchiolitis from January 2016 to December 2020,accounting for 1.5%of the total number of hospitalized children of the same age in the database during the period and 5.31%of the hospitalizations for ALRTI.The male to female ratio was 2.01:1.Meanwhile,more boys than girls were observed in different regions,age groups,years,and residences.The 1–2 year age group had the greatest number of hospitalizations for bronchiolitis,while the 29 days–6 months group had the largest proportion of the total inpatients and inpatients with ALRTI in the same age group.In terms of region,the hospitalization rate of bronchiolitis was the highest in East China.Overall,the number of hospitalizations from 2017 to 2020 showed a decreasing trend from that in 2016.Seasonally,the peak hospitalizations for bronchiolitis occurred in winter.Hospitalization rates in North China in autumn and winter were higher than those in South China,while hospitalization rates in South China were higher in spring and summer.Approximately
文摘Background Respiratory syncytial virus （RSV） is a common pathogen in the lower respiratory tract of infants and children. Recent studies have shown that in adults, especially in the eldedy population who have relatively weak immunity, lower respiratory tract infection is not uncommon. RSV was detected in 22% hospitalized patients with acute exacerbation of chronic obstructive pulmonary disease （COPD）, and the detection rate was only next to that of parvovirus and influenza virus respectively. Further studies revealed that lung infection of RSV could lead to inflammatory destruction and structural remodeling. This study was undertaken to examine the effect of infection with RSV on matrix metalloproteinase （MMPs） in mice, and to explore the role of RSV in the pathogenesis of pulmonary diseases. Methods Twenty BALB/c mice were divided randomly into an RSV infection group and a blank control group. The mice in the RSV infection group were given 100 pl liquid containing 10s PFU of RSV by intranasal instillation. Three days after the infection, the bronchoalveolar lavage fluid （BALF） was harvested and RT-PCR and Western blotting were used to detect MMP-9 and the expression of tissue inhibitors of matdx metalloproteinase （TIMP）-I mRNA in lung tissues. Gelatin zymography was employed to detect the activities of MMP-9 and MMP-2 in BALF. Immunohistochemistry was used to determine the expressions of E-cadherin （E-cd） and proliferating call nuclear antigen （PCNA） in the lung tissues. Results In the BALF of the mice infected with RSV, the activities of MMP-9 and MMP-2 were significantly increased （t=-6.08, P〈0.01 and t=5.68, P〈0.01）. The levels of mRNAand proteins of MMP-9 in the lung tissues of the mica infected with RSV were significantly elevated, and the mRNA and protein levels were significantly higher than those of the blank controls. Though the ratio of MMP-9/TIMP-1 mRNA in the lung tissues of the infected mica was not significantly different from that of the normal controls, the rat
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.
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.
基金supported by the Non-profit Central Research Institute Fund of the Chinese Academy of Medical Sciences(CAMS)(grant number 2021-RC330-002)the Disease Burden of Respiratory Syncytial Virus and Policy Recommendations Project(grant number 202108180001).
文摘Background Respiratory syncytial virus(RSV)infection in infants is a global health priority.We aimed to investigate the common manifestations of RSV infection by age group and human development index(HDI)level and to assess its association with the development of wheezing and recurrent wheezing illness.Methods We searched the literature published between January 1,2010 and June 2,2022 in seven databases.Outcomes included common manifestations and long-term respiratory outcomes of RSV infection in children.Random-and fixed-effect models were used to estimate the effect size and their 95%confidence intervals.Subgroup analysis was conducted by age and HDI levels.This review was registered in PROSPERO(CRD42022379401).Results The meta-analysis included 47 studies.The top five manifestations were cough(92%),nasal congestion(58%),rhinorrhea(53%),shortness of breath(50%),and dyspnea(47%).The clinical symptoms were most severe in infants.In our analysis,compared to very high and high HDI countries,fewer studies in medium HDI countries reported related manifestations,and no study in low HDI countries reported that.The RSV-infected infants were more likely to develop wheezing than the non-infected infants[odds ratio(OR),3.12;95%CI,2.59–3.76]and had a higher risk of developing wheezing illnesses after recovery(OR,2.60;95%CI,2.51–2.70).Conclusions Cough and shortness of breath are common manifestations of RSV infection.More attention should be given to infants and areas with low HDI levels.The current findings confirm an association between RSV infection and wheezing or recurrent wheezing illness.
文摘Restrictive measures adopted worldwide against COVID19(e.g.,wearing masks,frequent hand washing,and social distancing)produced not only a decrease in SARS-CoV-2 difusion but also a drastic reduction in respiratory diseases caused by other pathogens,as reported by many authors[1,2].The spread of respiratory viruses,particularly respiratory syncytial virus(RSV),has been completely changed during the winter of 2020–2021[3,4],but an unusual resurgence of RSV infection has been recently reported in diferent countries[3-7].
基金supported by the grants from National Key R&D Program of China(2021YFC2300702 and 2021YFC2300200)the Hubei Provincial Natural Science Foundation of China(2021CFB364)+1 种基金the National Natural Science Foundation of China(82130064,81825015,U22A20337 and 32000119)the Key Biosafety Science and Technology Program of Hubei Jiangxia Laboratory(JXBS001).
文摘Inclusion bodies(IBs)of respiratory syncytial virus(RSV)are formed by liquid-liquid phase separation(LLPS)and contain internal structures termed“IB-associated granules”(IBAGs),where anti-termination factor M2-1 and viral mRNAs are concentrated.However,the mechanism of IBAG formation and the physiological function of IBAGs are unclear.Here,we found that the internal structures of RSV IBs are actual M2-1-free viral messenger ribonucleoprotein(mRNP)condensates formed by secondary LLPS.Mechanistically,the RSV nucleoprotein(N)and M2-1 interact with and recruit PABP to IBs,promoting PABP to bind viral mRNAs transcribed in IBs by RNArecognition motif and drive secondary phase separation.Furthermore,PABP-eIF4G1 interaction regulates viral mRNP condensate composition,thereby recruiting specific translation initiation factors(eIF4G1,eIF4E,eIF4A,eIF4B and eIF4H)into the secondary condensed phase to activate viral mRNAs for ribosomal recruitment.Our study proposes a novel LLPS-regulated translation mechanism during viral infection and a novel antiviral strategy via targeting on secondary condensed phase.
基金supported by the National Natural Science Foundation of China(No.81574025)the Open Project Program of Jiangsu Key Laboratory of Pediatric Respiratory Disease,Nanjing University of Chinese Medicine(No.JKLPRD201410)
文摘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.
文摘Human milk oligosaccharides (HMO) contribute to innate immunity by enhancing growth of beneficial bacteria, epithelial cell maturation and mucosal barrier integrity. They have immunomodulatory effects and can block pathogen binding to host cell surface glycans or receptors. We investigated the effects of 2’-fucosyllactose (2’FL), 6’-sialyllactose (6’SL), 3’-sialyllactose (3’SL) and lacto-N-neoTetraose (LNnT) on human respiratory epithelial cell lines or peripheral blood mononuclear cells (PBMCs) following respiratory viral infectionin vitro. Expression of cytokines and viral load were monitored in infected cells. These biomarkers of innate immunity were selected since viral load and cytokine levels (IP-10, MIP-1α, IL-6, IL-8, TNF-α) have been correlated with disease severity in respiratory syncytial virus (RSV) and influenza (IAV) virus infectionin vivo. 2’FL significantly decreased RSV viral load and cytokines associated with disease severity (IL-6, IL-8, MIP-1α) and inflammation (TNF-α, MCP-1) in airway epithelial cells. LNnT and 6’SL significantly decreased IAV viral load in airway epithelial cells. 6’SL dose-dependently down-regulated IP-10 and TNF-α in RSV infected PBMCs. HMO at or below levels found in breast milk enhance innate immunity to respiratory viruses in vitro and may interact directly with cells to modulate biomarkers of innate immunity.
基金We thank Xuefang An,Fan Zhang in the Core Facility and Technical Support Facility of the Wuhan Institute of Virology for their technical assistance.This work was partially supported by the National Natural Science Foundation of China(31970165 to L.Z.)the National Key Research and Development Program of China(2021YFC2300700)the Shanghai Municipal Science and Technology Major Project,and the Youth Innovation Promotion Association CAS(2018367 to L.Z.).
文摘Dear Editor,Respiratory syncytial virus(RSV)is the leading cause of serious lower respiratory tract disease in children under 5 years of age worldwide,causing an estimated 3.2 million hospitalizations and 120,000 deaths in children globally per year.Furthermore,nearly all children can be infected with RSV by 2 years of age,and individuals can be repeatedly re-infected with RSV throughout life,which poses great threats to infants,the elderly.
文摘Respiratory syncytial virus （RSV） is a leading cause of .epidemic respiratory tract illness in children. Severe RSV infections involving the lower respiratory tract are primarily seen in young children with naive immune systems and/or genetic predispositions. However, RSV was not recognized as a potentially serious problem in older adults until the 1970s, when outbreaks of the virus infection occurred in long-term care facilities. Since then, additional studies in hospitalized adults have suggested that RSV may be an important cause of illness in community-dwelling elderly people, patients with suppressed T-cell immunity （such as heart transplant recipients）.
