Objective:Placental dysfunction is a major contributor to miscarriages in humans.We observed elevated expression of Kruppel-like factor 12(KLF12)in placental villi of women who experienced miscarriage compared to that...Objective:Placental dysfunction is a major contributor to miscarriages in humans.We observed elevated expression of Kruppel-like factor 12(KLF12)in placental villi of women who experienced miscarriage compared to that in women with healthy pregnancies.This study aimed to elucidate the role of KLF12 in maintaining a successful pregnancy.Methods:To investigate the role of KLF12 in placentation,we employed a model of forskolin-induced syncytialization in BeWo cells.Results:Our findings revealed that KLF12 expression is downregulated during normal syncytialization.Conversely,we observed that abnormally high KLF12 levels directly suppressed glial cells missing-1(GCM1)expression.This suppression of GCM1 expression subsequently impaired BeWo cell syncytialization.Furthermore,we observed placental deformities in KLF12-overexpressing mouse fetuses.Conclusion(s):This study demonstrated that elevated levels of KLF12 disrupt trophoblast syncytialization by downregulating GCM1 expression.These findings suggest that KLF12 may be a novel candidate gene contributing to unexplained miscarriages.展开更多
Respiratory syncytial virus(RSV)is a ubiquitous respiratory virus that affects individuals of all ages;however,there is a notable lack of targeted treatments.RSV infection is associated with a range of respiratory sym...Respiratory syncytial virus(RSV)is a ubiquitous respiratory virus that affects individuals of all ages;however,there is a notable lack of targeted treatments.RSV infection is associated with a range of respiratory symptoms,including bronchiolitis and pneumonia.Baicalin(BA)exhibits significant therapeutic effects against RSV infection through mechanisms of viral inhibition and anti-inflammatory action.Nonetheless,the clinical application of BA is constrained by its low solubility and bioavailability.In this study,we prepared BA nanodrugs(BA NDs)with enhanced water solubility utilizing the supramolecular self-assembled strategy,and we further conducted a comparative analysis of this pharmacological activity between free drugs and NDs of BA.Both in vitro and in vivo results demonstrated that BA NDs significantly enhanced the dual effects of viral inhibition and inflammation relief compared to free BA,attributed to prolonged lung retention,improved cellular uptake,and increased targeting affinity.Our study confirms that the nanosizing strategy,a straightforward approach to enhance drug solubility,can also increase biological activity compared to free drugs with the same content,thereby providing a potential ND for RSV treatment.This correlation analysis between the existing forms of drugs and their biological activity offers a novel perspective for research on the active ingredients of traditional Chinese medicine.展开更多
BACKGROUND Respiratory syncytial virus(RSV)is a leading cause of lower respiratory tract infections in neonates.While typically associated with bronchiolitis and pneumonia,RSV can rarely cause extrapulmonary complicat...BACKGROUND Respiratory syncytial virus(RSV)is a leading cause of lower respiratory tract infections in neonates.While typically associated with bronchiolitis and pneumonia,RSV can rarely cause extrapulmonary complications such as myocarditis,which may present with life-threatening symptoms if not promptly recognized.CASE SUMMARY We describe the case of a 26-day-old male neonate who presented with respiratory distress,poor feeding,and irritability.Initial evaluation revealed an RSV infection confirmed via nasopharyngeal swab.As the clinical course progressed,the infant developed cardiac arrhythmias,elevated cardiac enzymes,and echocardiographic findings consistent with myocarditis.Management included mechanical ventilation,corticosteroid therapy,L-carnitine,and vitamin D supplementation.The patient responded well to treatment and was successfully extubated and discharged in stable condition after nine days of hospitalization.CONCLUSION This case highlights the importance of early recognition and multidisciplinary management of RSV-associated myocarditis in neonates.展开更多
The current recommendation to avoid non-steroidal anti-inflammatory drugs(NSAIDs)in the management of dengue virus disease(DVD)is scientifically considered of very low to low certainty,despite being widely adopted wor...The current recommendation to avoid non-steroidal anti-inflammatory drugs(NSAIDs)in the management of dengue virus disease(DVD)is scientifically considered of very low to low certainty,despite being widely adopted worldwide.The same recommendation,initially made during the coronavirus disease 2019(COVID-19)pandemic,was subsequently proven incorrect.In this clinical report,we present evidence,for the first time globally,from a real-life practice that NSAIDs may actually be lifesaving in the early management of DVD as they have proved to be in COVID-19.Moreover,we propose that the personalized immunemodulatory Kelleni’s protocol,which includes nitazoxanide as a key component,can be safely and effectively used to manage various separate or concomitant viral infections and co-infections,including DVD.Importantly,this article contributes to the current medical knowledge in the global pursuit of a safe and effective broad-spectrum antiviral protocol that can be used to early manage multiple highly infectious viruses.However,it’s crucial that sufficiently powered controlled randomized clinical trials be conducted to thoroughly assess and evaluate the safety of NSAIDs in the early management of DVD as well as the efficacy of nitazoxanide with or without NSAIDs in its management.展开更多
In this paper,we study the epidemic model of respiratory syncytial virus SIRS with age structure.Firstly,the basic reproduction number R_(0) of the model is calculated and the positivity and ultimate boundedness of th...In this paper,we study the epidemic model of respiratory syncytial virus SIRS with age structure.Firstly,the basic reproduction number R_(0) of the model is calculated and the positivity and ultimate boundedness of the solution to the model under initial conditions are proven.Secondly,it is proven that when R_(0)<1,the disease-free equilibrium is locally and globally asymptotically stable;and when R_(0)>1,the disease is uniformly persistent and there is at least a positive equilibrium.Finally,the effectiveness of the theoretical results is demonstrated by numerical simulation,and the impact of vaccination on disease transmission is predicted.展开更多
BACKGROUND Hepatic manifestations in chronic lymphocytic leukemia(CLL)are common:Elevation of liver enzymes frequently occurs,and differential diagnosis is often challenging.Liver infiltration by leukemic cells,primar...BACKGROUND Hepatic manifestations in chronic lymphocytic leukemia(CLL)are common:Elevation of liver enzymes frequently occurs,and differential diagnosis is often challenging.Liver infiltration by leukemic cells,primary and secondary hepatic malignancies,drug-induced hepatotoxicity,immunological disorders,and infections have been reported.Nevertheless,syncytial giant cell hepatitis(GCH)as a manifestation of autoimmune hepatitis in patients with CLL is an extremely rare condition,currently reported only in anecdotal cases.CASE SUMMARY Here,we report the case of a 62-year-old Caucasian woman affected by CLL,who developed GCH with peculiar histopathological features.The patient was evaluated for abnormal liver test results.Liver histology revealed significant inflammatory lymphomononuclear infiltrates with a plasma cell component,widespread syncytial changes in the hepatocytes with gigantocellular features,hepatocyte rosettes,and the typical feature of emperipolesis,consistent with a diagnosis of GCH.The patient was treated with corticosteroids and mycophenolate mofetil,resulting in a complete biochemical response.CONCLUSION Early histological diagnosis of GCH is crucial in patients with CLL,with mycophenolate mofetil representing a promising treatment option.展开更多
Respiratory syncytial virus(RSV)is one of the most common viruses leading to lower respiratory tract infections(LRTIs)in children and elderly individuals worldwide.Although significant progress in the prevention and t...Respiratory syncytial virus(RSV)is one of the most common viruses leading to lower respiratory tract infections(LRTIs)in children and elderly individuals worldwide.Although significant progress in the prevention and treatment of RSV infection was made in 2023,with two anti-RSV vaccines and one monoclonal antibody approved by the FDA,there is still a lack of postinfection therapeutic drugs in clinical practice,especially for the pediatric population.In recent years,with an increasing understanding of the pathogenic mechanisms of RSV,drugs and drug candidates,have shown great potential for clinical application.In this review,we categorize and discuss promising anti-RSV drug candidates that have been in preclinical or clinical development over the last five years.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
Human respiratory syncytial virus(RSV) is a major pathogen of acute lower respiratory tract infection among young children. To investigate the prevalence and genetic characteristics of RSV in China, we performed a mol...Human respiratory syncytial virus(RSV) is a major pathogen of acute lower respiratory tract infection among young children. To investigate the prevalence and genetic characteristics of RSV in China, we performed a molecular epidemiological study during 2015–2019. A total of 964 RSV-positive specimens were identified from 5529 enrolled patients during a multi-center study. RSV subgroup A(RSV-A) was the predominant subgroup during this research period except in2016. Totally, 535 sequences of the second hypervariable region(HVR-2) of the G gene were obtained. Combined with182 Chinese sequences from GenBank, phylogenetic trees showed that 521 RSV-A sequences fell in genotypes ON1(512),NA1(6) and GA5(3), respectively;while 196 RSV-B sequences fell in BA9(193) and SAB4(3). ON1 and BA9 were the only genotypes after December 2015. Genotypes ON1 and BA9 can be separated into 10 and 7 lineages, respectively. The HVR-2 of genotype ON1 had six amino acid changes with a frequency more than 10%, while two substitutions H258 Q and H266 L were co-occurrences. The HVR-2 of genotype BA9 had nine amino acid substitutions with a frequency more than10%, while the sequences with T290 I and T312 I were all from 2018 to 2019. One N-glycosylation site at 237 was identified among ON1 sequences, while two N-glycosylation sites(296 and 310) were identified in the 60-nucleotide duplication region of BA9. To conclusion, ON1 and BA9 were the predominant genotypes in China during 2015–2019. For the genotypes ON1 and BA9, the G gene exhibited relatively high diversity and evolved continuously.展开更多
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
Respiratory syncytial virus(RSV) is the key underlying cause of acute lower respiratory tract infection in infants; however, no licensed vaccine against RSV infection is currently available. This study was undertaken ...Respiratory syncytial virus(RSV) is the key underlying cause of acute lower respiratory tract infection in infants; however, no licensed vaccine against RSV infection is currently available. This study was undertaken to assess the preventive effect of vaccine on RSV infection. In this metaanalysis, 1,792 published randomized clinical trials of RSV vaccines from Jan 1973 to Sep 2015 were examined. Among thirteen studies that met the inclusion criteria, eleven studies estimated the impact of RSV vaccines and four studies estimated the effect of adjuvants. The odds ratios(ORs) were 0.31(95% CI, 0.15–0.67) and 0.62(95% CI, 0.29–1.34), respectively. We found that RSV subunit vaccines can significantly reduce the incidence of RSV infection and that whether vaccination with adjuvant therapy was an effective strategy still remained to be studied. This analysis of the preventive effect of vaccines on RSV infection has direct applications for the prevention of RSV infections.展开更多
Human respiratory syncytial virus(RSV)infection is the leading cause of lower respiratory tract illness(LRTI),and no vaccine against LRTI has proven to be safe and effective in infants.Our study assessed attenuated re...Human respiratory syncytial virus(RSV)infection is the leading cause of lower respiratory tract illness(LRTI),and no vaccine against LRTI has proven to be safe and effective in infants.Our study assessed attenuated recombinant RSVs as vaccine candidates to prevent RSV infection in mice.The constructed recombinant plasmids harbored(5′to 3′)a T7 promoter,hammerhead ribozyme,RSV Long strain antigenomic cDNA with cold-passaged(cp)mutations or cp combined with temperature-sensitive attenuated mutations from the A2 strain(A2cpts)or further combined with SH gene deletion(A2cptsΔSH),HDV ribozyme(δ),and a T7 terminator.These vectors were subsequently co-transfected with four helper plasmids encoding N,P,L,and M2-1 viral proteins into BHK/T7-9 cells,and the recovered viruses were then passaged in Vero cells.The rescued recombinant RSVs(rRSVs)were named rRSV-Long/A2cp,rRSV-Long/A2cpts,and rRSV-Long/A2cptsΔSH,respectively,and stably passaged in vitro,without reversion to wild type(wt)at sites containing introduced mutations or deletion.Although rRSV-Long/A2cpts and rRSV-Long/A2cptsΔSH displayed temperature-sensitive(ts)phenotype in vitro and in vivo,all rRSVs were significantly attenuated in vivo.Furthermore,BALB/c mice immunized with rRSVs produced Th1-biased immune response,resisted wtRSV infection,and were free from enhanced respiratory disease.We showed that the combination ofΔSH with attenuation(att)mutations of cpts contributed to improving att phenotype,efficacy,and gene stability of rRSV.By successfully introducing att mutations and SH gene deletion into the RSV Long parent and producing three rRSV strains,we have laid an important foundation for the development of RSV live attenuated vaccines.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 childre...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 3831-59 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
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
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
基金supported by the National Natural Science Foundation of China(82030040,82301897,and 82171653)the Natural Science Foundation of Nanjing Drum Tower Hospital,Nanjing University Medical School(2022-JCYJ-QP-54)the Natural Science Foundation of Shandong(ZR202111300553 and ZR2022MH094).
文摘Objective:Placental dysfunction is a major contributor to miscarriages in humans.We observed elevated expression of Kruppel-like factor 12(KLF12)in placental villi of women who experienced miscarriage compared to that in women with healthy pregnancies.This study aimed to elucidate the role of KLF12 in maintaining a successful pregnancy.Methods:To investigate the role of KLF12 in placentation,we employed a model of forskolin-induced syncytialization in BeWo cells.Results:Our findings revealed that KLF12 expression is downregulated during normal syncytialization.Conversely,we observed that abnormally high KLF12 levels directly suppressed glial cells missing-1(GCM1)expression.This suppression of GCM1 expression subsequently impaired BeWo cell syncytialization.Furthermore,we observed placental deformities in KLF12-overexpressing mouse fetuses.Conclusion(s):This study demonstrated that elevated levels of KLF12 disrupt trophoblast syncytialization by downregulating GCM1 expression.These findings suggest that KLF12 may be a novel candidate gene contributing to unexplained miscarriages.
基金supported by the National Natural Science Foundation of China(Grant No.:82474195)the Postgraduate Research&Practice Innovation Program of Jiangsu Province,China(Grant No.:021093002882)+2 种基金the Youth Medical Innovation Research Project of China(Grant No.:P24021887623)Taizhou Science and Technology Support Project,China(Grant No.:TS202420)grants from Nanjing Medical University,China(Grant Nos.:TZKY20230104 and 2024KF0292).
文摘Respiratory syncytial virus(RSV)is a ubiquitous respiratory virus that affects individuals of all ages;however,there is a notable lack of targeted treatments.RSV infection is associated with a range of respiratory symptoms,including bronchiolitis and pneumonia.Baicalin(BA)exhibits significant therapeutic effects against RSV infection through mechanisms of viral inhibition and anti-inflammatory action.Nonetheless,the clinical application of BA is constrained by its low solubility and bioavailability.In this study,we prepared BA nanodrugs(BA NDs)with enhanced water solubility utilizing the supramolecular self-assembled strategy,and we further conducted a comparative analysis of this pharmacological activity between free drugs and NDs of BA.Both in vitro and in vivo results demonstrated that BA NDs significantly enhanced the dual effects of viral inhibition and inflammation relief compared to free BA,attributed to prolonged lung retention,improved cellular uptake,and increased targeting affinity.Our study confirms that the nanosizing strategy,a straightforward approach to enhance drug solubility,can also increase biological activity compared to free drugs with the same content,thereby providing a potential ND for RSV treatment.This correlation analysis between the existing forms of drugs and their biological activity offers a novel perspective for research on the active ingredients of traditional Chinese medicine.
文摘BACKGROUND Respiratory syncytial virus(RSV)is a leading cause of lower respiratory tract infections in neonates.While typically associated with bronchiolitis and pneumonia,RSV can rarely cause extrapulmonary complications such as myocarditis,which may present with life-threatening symptoms if not promptly recognized.CASE SUMMARY We describe the case of a 26-day-old male neonate who presented with respiratory distress,poor feeding,and irritability.Initial evaluation revealed an RSV infection confirmed via nasopharyngeal swab.As the clinical course progressed,the infant developed cardiac arrhythmias,elevated cardiac enzymes,and echocardiographic findings consistent with myocarditis.Management included mechanical ventilation,corticosteroid therapy,L-carnitine,and vitamin D supplementation.The patient responded well to treatment and was successfully extubated and discharged in stable condition after nine days of hospitalization.CONCLUSION This case highlights the importance of early recognition and multidisciplinary management of RSV-associated myocarditis in neonates.
文摘The current recommendation to avoid non-steroidal anti-inflammatory drugs(NSAIDs)in the management of dengue virus disease(DVD)is scientifically considered of very low to low certainty,despite being widely adopted worldwide.The same recommendation,initially made during the coronavirus disease 2019(COVID-19)pandemic,was subsequently proven incorrect.In this clinical report,we present evidence,for the first time globally,from a real-life practice that NSAIDs may actually be lifesaving in the early management of DVD as they have proved to be in COVID-19.Moreover,we propose that the personalized immunemodulatory Kelleni’s protocol,which includes nitazoxanide as a key component,can be safely and effectively used to manage various separate or concomitant viral infections and co-infections,including DVD.Importantly,this article contributes to the current medical knowledge in the global pursuit of a safe and effective broad-spectrum antiviral protocol that can be used to early manage multiple highly infectious viruses.However,it’s crucial that sufficiently powered controlled randomized clinical trials be conducted to thoroughly assess and evaluate the safety of NSAIDs in the early management of DVD as well as the efficacy of nitazoxanide with or without NSAIDs in its management.
基金supported by the Natural Science Foundation of Xinjiang(No.2022D01E41)the National Natural Science Foundation of China(No.12261087)the Open Project of Key Laboratory of Applied Mathematics of Xinjiang Autonomous Region(No.2021D04014)。
文摘In this paper,we study the epidemic model of respiratory syncytial virus SIRS with age structure.Firstly,the basic reproduction number R_(0) of the model is calculated and the positivity and ultimate boundedness of the solution to the model under initial conditions are proven.Secondly,it is proven that when R_(0)<1,the disease-free equilibrium is locally and globally asymptotically stable;and when R_(0)>1,the disease is uniformly persistent and there is at least a positive equilibrium.Finally,the effectiveness of the theoretical results is demonstrated by numerical simulation,and the impact of vaccination on disease transmission is predicted.
文摘BACKGROUND Hepatic manifestations in chronic lymphocytic leukemia(CLL)are common:Elevation of liver enzymes frequently occurs,and differential diagnosis is often challenging.Liver infiltration by leukemic cells,primary and secondary hepatic malignancies,drug-induced hepatotoxicity,immunological disorders,and infections have been reported.Nevertheless,syncytial giant cell hepatitis(GCH)as a manifestation of autoimmune hepatitis in patients with CLL is an extremely rare condition,currently reported only in anecdotal cases.CASE SUMMARY Here,we report the case of a 62-year-old Caucasian woman affected by CLL,who developed GCH with peculiar histopathological features.The patient was evaluated for abnormal liver test results.Liver histology revealed significant inflammatory lymphomononuclear infiltrates with a plasma cell component,widespread syncytial changes in the hepatocytes with gigantocellular features,hepatocyte rosettes,and the typical feature of emperipolesis,consistent with a diagnosis of GCH.The patient was treated with corticosteroids and mycophenolate mofetil,resulting in a complete biochemical response.CONCLUSION Early histological diagnosis of GCH is crucial in patients with CLL,with mycophenolate mofetil representing a promising treatment option.
基金funded by the Beijing Natural Science Foundation(5242007,L222076,L246011)the High-level Public Health Technical Talents Project by the Beijing Municipal Commission of Health(Key discipline personnel-02-05)+1 种基金the CAMS Innovation Fund for Medical Sciences(CIFMS,2019-12M-5-026,2022-I2M-CoV19-006)the Reform and Development of the Beijing Municipal Health Commission,and the Respiratory Research Project of the National Clinical Research Center for Respiratory Diseases(HXZX-202106).
文摘Respiratory syncytial virus(RSV)is one of the most common viruses leading to lower respiratory tract infections(LRTIs)in children and elderly individuals worldwide.Although significant progress in the prevention and treatment of RSV infection was made in 2023,with two anti-RSV vaccines and one monoclonal antibody approved by the FDA,there is still a lack of postinfection therapeutic drugs in clinical practice,especially for the pediatric population.In recent years,with an increasing understanding of the pathogenic mechanisms of RSV,drugs and drug candidates,have shown great potential for clinical application.In this review,we categorize and discuss promising anti-RSV drug candidates that have been in preclinical or clinical development over the last five years.
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.
基金This work was supported by the National Science and Technology Major Projects(Grant Number 2017ZX10104001-005-010,2017ZX10103004-004)the CAMS Innovation Fund for Medical Sciences(CIFMS)(Grant Number 2019-I2M-5-026)。
文摘Human respiratory syncytial virus(RSV) is a major pathogen of acute lower respiratory tract infection among young children. To investigate the prevalence and genetic characteristics of RSV in China, we performed a molecular epidemiological study during 2015–2019. A total of 964 RSV-positive specimens were identified from 5529 enrolled patients during a multi-center study. RSV subgroup A(RSV-A) was the predominant subgroup during this research period except in2016. Totally, 535 sequences of the second hypervariable region(HVR-2) of the G gene were obtained. Combined with182 Chinese sequences from GenBank, phylogenetic trees showed that 521 RSV-A sequences fell in genotypes ON1(512),NA1(6) and GA5(3), respectively;while 196 RSV-B sequences fell in BA9(193) and SAB4(3). ON1 and BA9 were the only genotypes after December 2015. Genotypes ON1 and BA9 can be separated into 10 and 7 lineages, respectively. The HVR-2 of genotype ON1 had six amino acid changes with a frequency more than 10%, while two substitutions H258 Q and H266 L were co-occurrences. The HVR-2 of genotype BA9 had nine amino acid substitutions with a frequency more than10%, while the sequences with T290 I and T312 I were all from 2018 to 2019. One N-glycosylation site at 237 was identified among ON1 sequences, while two N-glycosylation sites(296 and 310) were identified in the 60-nucleotide duplication region of BA9. To conclusion, ON1 and BA9 were the predominant genotypes in China during 2015–2019. For the genotypes ON1 and BA9, the G gene exhibited relatively high diversity and evolved continuously.
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supported by grants from Natural Science Foundation of China (Grant Ref.81371797)the key project of Natural Science Research Found of Education Department of Anhui Province (Grant Ref.KJ2012A152)Natural Science Foundation of Anhui Province (Grant Ref.1308085MH129)
文摘Respiratory syncytial virus(RSV) is the key underlying cause of acute lower respiratory tract infection in infants; however, no licensed vaccine against RSV infection is currently available. This study was undertaken to assess the preventive effect of vaccine on RSV infection. In this metaanalysis, 1,792 published randomized clinical trials of RSV vaccines from Jan 1973 to Sep 2015 were examined. Among thirteen studies that met the inclusion criteria, eleven studies estimated the impact of RSV vaccines and four studies estimated the effect of adjuvants. The odds ratios(ORs) were 0.31(95% CI, 0.15–0.67) and 0.62(95% CI, 0.29–1.34), respectively. We found that RSV subunit vaccines can significantly reduce the incidence of RSV infection and that whether vaccination with adjuvant therapy was an effective strategy still remained to be studied. This analysis of the preventive effect of vaccines on RSV infection has direct applications for the prevention of RSV infections.
基金This work was supported by grants from the Natural Science Foundation of China(81771777,32070922).
文摘Human respiratory syncytial virus(RSV)infection is the leading cause of lower respiratory tract illness(LRTI),and no vaccine against LRTI has proven to be safe and effective in infants.Our study assessed attenuated recombinant RSVs as vaccine candidates to prevent RSV infection in mice.The constructed recombinant plasmids harbored(5′to 3′)a T7 promoter,hammerhead ribozyme,RSV Long strain antigenomic cDNA with cold-passaged(cp)mutations or cp combined with temperature-sensitive attenuated mutations from the A2 strain(A2cpts)or further combined with SH gene deletion(A2cptsΔSH),HDV ribozyme(δ),and a T7 terminator.These vectors were subsequently co-transfected with four helper plasmids encoding N,P,L,and M2-1 viral proteins into BHK/T7-9 cells,and the recovered viruses were then passaged in Vero cells.The rescued recombinant RSVs(rRSVs)were named rRSV-Long/A2cp,rRSV-Long/A2cpts,and rRSV-Long/A2cptsΔSH,respectively,and stably passaged in vitro,without reversion to wild type(wt)at sites containing introduced mutations or deletion.Although rRSV-Long/A2cpts and rRSV-Long/A2cptsΔSH displayed temperature-sensitive(ts)phenotype in vitro and in vivo,all rRSVs were significantly attenuated in vivo.Furthermore,BALB/c mice immunized with rRSVs produced Th1-biased immune response,resisted wtRSV infection,and were free from enhanced respiratory disease.We showed that the combination ofΔSH with attenuation(att)mutations of cpts contributed to improving att phenotype,efficacy,and gene stability of rRSV.By successfully introducing att mutations and SH gene deletion into the RSV Long parent and producing three rRSV strains,we have laid an important foundation for the development of RSV live attenuated vaccines.
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 3831-59 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.
