Characterization of CircRNA-Associated CeRNA Networks in Folate Deficiency-Induced Neural Tube Defects

Objective Circular RNAs(circRNAs)participate in several important pathological processes and have been used in the diagnosis and treatment of various diseases.This study aimed to investigate the role of circRNAs in neural tube defects(NTDs).Method We characterized circRNA-associated competitive endogenous RNA(ceRNA)networks in brain tissue of low folate-induced NTDs mouse at embryonic day 13.5 by high-throughput sequencing.The expression levels of Circzfp644,miR-20-5p and Gas7 were detected by RT-PCR.Gas7 and Circzfp644functions were determined by miRNA-mimics and inhibitors in mouse teratocarcinoma cells(F9 cells),and luciferase gene reporter assay was assessed in the F9 cells.In addition,the expression levels of Circzfp644,miR-20-5p and Gas7 were determined by Nanostring in human NTDs tissues.Results We detected 57 circRNA transcripts,16 miRNAs,and 148 mRNAs that were significantly dysregulated in NTDs brain tissues compared with their expression levels in control(normal)tissues.Circzfp644 shared miRNA response elements with the growth arrest specific 7(Gas7)gene and competitively bound with miR-20-5p to increase the expression of Gas7.Downregulation of Circzfp644and Gas7 and upregulation of miR-20-5p were found in human NTD tissue.Conclusion This study provides new perspectives on the role of circRNAs in nervous system development and the pathogenesis of NTDs.

Impact of Novel Coronavirus Vaccination on the Clinical Characteristics and Parental Care Needs of Infected Children During a High-Intensity Epidemic Period

Objective:This study aimed to investigate the impact of COVID-19 vaccination on the clinical characteristics and care needs of infected children during a high-intensity pandemic and to measure the potential effects of vaccination on children's health status and healthcare utilization.Methods:A sample of 903 children who had recently been infected with the novel coronavirus and came to our hospital's emergency department from January 11 to January 30,2023,was used as the research object in this retrospective study.The questionnaire on unknown coronavirus infection was filled out anonymously,and SPSS20.0 software was used for statistical data analysis.Results:The baseline conditions of 903 subjects were studied,including 505 males,accounting for 55.92%,and 398 females,accounting for 44.08%.The age of infection was mainly concentrated in preschool children(26.02%)and school-age children(38.76%).Regarding vaccination,561 cases were vaccinated,accounting for 62.13%.Among them,37 children received one dose of vaccine,accounting for 4.1%,463 children received two doses,accounting for 51.27%,and 61 children received three doses,accounting for 6.76%.For previous allergic diseases,180 children had a history of allergic diseases,accounting for 19.93%.Regarding sources of infection,the most common source was someone at home,accounting for 82.61%.Vaccination can effectively reduce the fever of children infected with the new coronavirus,the number of outpatient and emergency doctor visits,and the risk of hospitalization.In addition,regarding treatment,children in the vaccinated group were more likely to be treated at home,and the types of drugs used also differed from those in the non-vaccinated group.However,the vaccination group has a relatively high incidence of symptoms such as sore throat,cough,abnormal sense of smell and taste,muscle soreness,and headache.However,these are mild clinical symptoms and do not affect children's physical health and development.Parental care needs for children infected with COVID-19 are disparate,and parents of vaccinated children have lower proportions of needs for child care.Conclusion:Vaccination positively impacts the clinical outcomes of children infected with COVID-19 and their parents'well-being.

The inhibitory effect of SEMA3C/3D mutations on Neuro-2a cells migration and axonal growth in patients with Hirschsprung′s disease

Objective:To explore the effect and mechanism of SEMA3C/3D mutations on axonal growth of neurons and cell migration in Hirschsprung′s disease(HSCR)patients.Methods:HEK293 Tcells were transfected with wild-type and mutant SEMA3C/3D plasmids.The supernatants that contained SEMA3C/3D-AP fusion proteins were collected and added into the Neuro-2acells.The changes in the cell morphology were observed by immunofluorescence staining.The expression and phosphorylation levels of cofilin,ERM and CRMP2 were determined by western blotting.The cell migration rate was measured by transwell assay.Results:Compared with wild-type SEMA3D,SEMA3D-P615T mutant suppressed cofilin phosphorylation in Neuro-2a cells(P <0.05).The neural cells treated by five mutant SEMA3C/3D-AP fusion proteins presented different levels of axon atrophy,growth cone collapse,and sometimes,loss of normal structure.SEMA3C-S329 G,SEMA3C-V337M and SEMA3D-P615T mutants cells exhibited a significantly reduced migration rate as compared with wild-type SEMA3C/3D treated cells(P <0.01).Conclusion:SEMA3C and SEMA3 D mutations in HSCR patients could lead to the inhibition of Neuro-2a cells′migration and axonal growth.The mechanism of SEMA3 DP615T mutant might be related to down-regulation of the expression of p-cofilin,which consequently lead to cytoskeleton structure collapse and migrating ability decrease.Our study might provide important clues for the pathogenesis of HSCR.

Cost analysis and comparison of plain cotton and disposable non-woven treatment towels

Objective: To choose a reasonably priced and low-cost treatment towel suitable for clinical application of hospital so as to reduce the cost of the hospital and make a reasonable use of resources through the cost analysis and comparison of the plain cotton and disposable non-woven treatment towels. Methods: The cost of the single pack plain cotton towel and disposable non-woven towel were analyzed and at the same time, 49185 packs of plain cotton towels which were the total consumption quantity of our hospital in 2017 and the same quantity of disposable non-woven towers were analyzed in the cost for comparison. Results:A single pack of disposable non-woven towel was RMB 2.50 cheaper than the plain cotton towel and the use of disposable non-woven towel can save the cost of RMB 2.50 per pack. In 2017, 49185 packs of plain cotton towel were used in total, which cost RMB 122962.50 less than the same quantity of disposable non-woven towels and using the disposable non-woven towel could save RMB 122962.50 annually. Conclusion: Compared with the plain cotton towel, the non-woven shares the advantages of none flocculation, longer storage time and better antibacterial effect as well as the material, cleaning and labor costs-saving. The cost of the disposable non-woven treatment towel is lower than that of the reusable plain cotton towel. Therefore, it is recommended to use the disposable non-woven treatment towel.

More common RNAemia in the early stage of severe SARS-CoV-2 BF.7.14 infections in pediatric patients

The risk factors of severe infections in children during the severe acute respiratory syndrome coronavirus 2(SARS‐CoV‐2)outbreak in Beijing remain elusive.SARS‐CoV‐2‐positive children admitted to the intensive care unit(ICU)with collected plasma specimens were enrolled and screened for common pathogens using capillary electrophoresis‐based multiplex PCR from December 12,2022,to January 24,2023.The SARS‐CoV‐2 subvariants were identified using next‐generation sequencing.Plasma was positive for two(positive;P),one(suspicious;S),or no(negative;N)SARS‐CoV‐2 genes were classified as plasmatic RNA‐positive(RNAemia;P+S)or without RNAemia(N).Clinical and laboratory data of the enrolled cases were then collected and analyzed.The 34 enrolled children included 26 males and 24 younger than three years.All were negative for other respiratory pathogens.BF.7.14(18/29)was the predominant subvariant.Viral loads in respiratory specimens,hours from symptom onset to the first respiratory specimen collection(time‐variable),with comorbidities and BF.7.14 and BA.5.2 distributions were significantly different in P vs.N and RNAemia vs.without RNAemia group.Among most cases,the T lymphocyte ratios decreased,while the cytokine level and the B lymphocyte ratio increased.The time variables were 2.22±2.05 and 4.00±2.49 days in BF.7.14 and BA.5.2 infections,respectively.In conclusion,SARS‐CoV‐2 was more likely to cause severe infections among males aged≤3 years old with comorbidities during the SARS‐CoV‐2 outbreak in Beijing,while RNAemia is more common in children at the early stage of severe BF.7.14 infections,and most had high cytokine levels and B‐cell activation.

Surges of hospital-based rhinovirus infection during the 2020 coronavirus disease-19(COVID-19)pandemic in Beijing,China

Background A series of public health preventive measures has been widely implemented in Beijing to control the corona-virus disease-19(COVID-19)pandemic since January 2020.An evaluation of the effects of these preventive measures on the spread of other respiratory viruses is necessary.Methods Respiratory specimens collected from children with acute respiratory infections were tested by NxTAGTN,respiratory pathogen panel assays during January 2017 and December 2020.Specimens characterized as rhinoviruses(RVs)were sequenced to identify the RV species and types.Then,the epidemiology results of respiratory pathogens in 2020 were compared with those from 2017 to 2019 using SPSS statistics 22.0.Results The positive rates of adenovirus(ADV),influenza virus(flu),RVs,and respiratory syncytial virus(RSV)dropped abruptly by 86.31%,94.679c,94.59%,and 92.17%,respectively,from February to May 2020,compared with the average level in the same period during 2017-2019.Positive rates of RVs then steeply increased from June 2020(13.77%),to an apex(37.25%)in August 2020,significantly higher than the average rates(22.51%)in August 2017-2019(7^=0.005).The increase,especially in group>3 years,was accompanied by the reopening of schools and kindergartens after the 23rd and 24th week of 2020 in Beijing.Conclusions Whereas the abrupt drop in viral pathogen positive rates from February to May 2020 revealed the remarkable effects of the COVID-19 preventive measures,the sharp increase in positive rates of RVs from the 23rd week of 2020 might be explained by the reopening of schools and kindergartens in Beijing.

A Multicenter Study of Viral Aetiology of Community-Acquired Pneumonia in Hospitalized Children in Chinese Mainland

Community-acquired pneumonia(CAP) is one of the leading causes of morbidity and mortality in children worldwide.In this study,we aimed to describe the aetiology of viral infection of pediatric CAP in Chinese mainland.During November2014 to June 2016,the prospective study was conducted in 13 hospitals.The hospitalized children under 18 years old who met the criteria for CAP were enrolled.The throat swabs or nasopharyngeal aspirates(NPAs) were collected which were then screened 18 respiratory viruses using multiplex PCR assay.Viral pathogens were present in 56.6%(1539/2721) of the enrolled cases,with the detection rate of single virus in 39.8% of the cases and multiple viruses in 16.8% of the cases.The most frequently detected virus was respiratory syncytial virus(RSV)(15.2%,414/2721).The highest detection rate of virus was in <6-month-age group(70.7%,292/413).RSV,human metapneumovirus(HMPV),human parainfluenza viruses(HPIVs) and influenza B virus(Flu B) showed the similar prevalence patterns both in north and south China,but HPIVs,Flu A,human bocavirus(HBoV),human adenovirus(HAdV) and human coronaviruses(HCoVs) showed the distinct circulating patterns in north and south China.Human enterovirus/human rhinovirus(HEV/HRV)(27.6%,27/98),HBoV(18.4%,18/98),RSV(16.3%,16/98) and HMPV(14.3%,14/98) were the most commonly detected viruses in severe pneumonia cases with single virus infection.In conclusion,viral pathogens are frequently detected in pediatric CAP cases and may therefore play a vital role in the aetiology of CAP.RSV was the most important virus in hospitalized children with CAP in Chinese mainland.

S1PR1 serves as a viable drug target against pulmonary fibrosis by increasing the integrity of the endothelial barrier of the lung

Idiopathic pulmonary fibrosis(IPF)is a progressive lung disease with unclear etiology and limited treatment options.The median survival time for IPF patients is approximately 2–3 years and there is no effective intervention to treat IPF other than lung transplantation.As important components of lung tissue,endothelial cells(ECs)are associated with pulmonary diseases.However,the role of endothelial dysfunction in pulmonary fibrosis(PF)is incompletely understood.Sphingosine-1-phosphate receptor 1(S1PR1)is a G protein-coupled receptor highly expressed in lung ECs.Its expression is markedly reduced in patients with IPF.Herein,we generated an endothelial-conditional S1pr1 knockout mouse model which exhibited inflammation and fibrosis with or without bleomycin(BLM)challenge.Selective activation of S1PR1 with an S1PR1 agonist,IMMH002,exerted a potent therapeutic effect in mice with bleomycin-induced fibrosis by protecting the integrity of the endothelial barrier.These results suggest that S1PR1 might be a promising drug target for IPF therapy.

Surveillance of Mycoplasma pneumoniae infection among children in Beijing from 2007 to 2012

Background Mycoplasma pneumonia （M.pneumoniae） is one of the key pathogens of community-acquired pneumonia.A global pandemic of M.pneumoniae has occurred since 2010.The aim of this study was to survey the prevalence of M.pneumoniae in children in Beijing from 2007-2012.Methods A total of 3 073 clinical specimens were obtained from pediatric patients with respiratory tract infections from January 2007 to December 2012,and examined by nested polymerase chain reaction.PCR products were visualized by 2％ agarose gel electrophoresis,positive products sequenced,and compared with reference sequences in GenBank.Macrolide resistance-associated mutations were also detected for some positive samples.Results Of the 3 073 specimens,588 （19.13％） were positive for M.pneumoniae,12.4％ of which were accompanied by viral infections.Positive rates for M.pneumoniae were highest in 2007 and 2012,showing a significant difference when compared with other years.Infections tended to occur in autumn and winter and positive rates were significantly higher for children aged 3-16.The rate of macrolide resistance-associated mutations was 90.7％,and the predominant mutation was an A→G transition （89.92％） at position 2063 in domain V of the 23S rRNA gene.Conclusions M.pneumoniae outbreaks occurred in 2007 and 2012 in pediatric patients in Beijing,which is consistent with the global prevalence of M.pneumoniae.M.pneumoniae can cause multi-system infections in children,and may be accompanied with viral infections.We determined that school-age children are more susceptible to this disease,particularly in autumn and winter.Gene mutations associated with macrolide resistance were very common in M.pneumoniae-positive specimens during this period in Beijing.

Characterization of human metapneumovirus from pediatric patients with acute respiratory infections in a 4-year period in Beijing, China

Background Human metapneumovirus （hMPV） was discovered by scientists in the Netherlands as a novel respiratory virus in 2001 and had been found in children with acute respiratory tract infections （ARTI） in China. The objective of this study was to determine the importance of hMPV infection in children in Beijing and the genotypes of the circulating virus by the surveillance during a four-consecutive-year period.

A single tube modified allele-specific-PCR for rapid detection of erythromycin-resistant Mycoplasma pneumoniae in Beijing

Background Mycoplasma pneumoniae （M. pneumoniae） is one of the common pathogens causing atypical pneumonia. In recent years, resistance to macrolides has become more common, especially in China. Previous studies have confirmed that the mutation at position 2063 in domain V of the 23S rRNA is the most prevalent, followed by the mutation at position 2064. Reported molecular detection methods for the identification of these mutations include direct sequencing, restriction fragment length polymorphism analysis, real-time polymerase chain reaction （PCR） with high-resolution melt analysis, and nested PCR-linked with capillary electrophoresis, etc. The most commonly used method for monitoring resistance-conferring mutations in M. pneumoniae is direct DNA sequencing of PCR or nested PCR products. However, these methods are time-consuming, labor-intensive or need expensive equipments. Therefore the development of rapid and sensitive methods is very important for monitoring the resistance globally. Methods In this study, we reported a fast and cost-effective method for detecting 2063 and/or 2064 macrolide resistant mutations from specimens using a modified allele-specific PCR analysis, and all results were compared with the sequencing data. We also analyzed the clinical courses of these samples to confirm the modified allele-specific PCR results. Results Among 97 M. pneumoniae specimens, 88 were found to possess mutations by this method, and all modified allele-specific PCR analysis results were consistent with the sequencing data. The data of the clinical courses of these 97 cases showed that they suffered from severe pneumonia. Erythromycin showed better efficacy on cases from which no macrolide resistance mutation was found on their specimens. However, in some cases from which mutations were detected, erythromycin monotherapy had poor efficacy, and on these patients severe symptoms improved only when azithromycin was added to the treatment. Conclusions The drug-resistant M. pneumoniae is very common in Beijing, China. Our modified allele-specific PCR analysis can identify erythromycin resistant mutations more rapidly from specimens than any other method currently available. Erythromycin is still effective for treating patients infected with the mutation negative M. pneumoniae, but this treatment fails to work on mutant organisms. This method can facilitate clinicians in selecting appropriate therapy within short timescales.

Molecular epidemiology of coxsackievirus A16 circulating in children in Beijing, China from 2010 to 2019

Background Coxsackievirus A16(CVA16)is one of the major etiological agents of hand,foot and mouth discase(HFMD).This study aimed to investigate the molecular epidemiology and evolutionary characteristics of CVA16.Methods Throat swabs were collected from children with HFMD and suspected HFMD during 2010-2019.Enteroviruses(EVs)were detected and typed by real-ime reverse transcription-polymerase chain reaction(RT-PCR)and RT-PCR.The genotype,evolutionary rate,the most recent common ancestor,population dynamics and selection pressure of CVA16 were analyzed based on viral protein gene(VPI)by bioinformatics software.Results A total of 4709 throat swabs were screened.EVs were detected in 3180 samples and 814 were CVA16 positive.More than 81%of CVA 16-positive children were under 5 years old.The prevalence of CVA 16 showed obvious periodic fluctuations with a high level during 2010--2012 followed by an apparent decline during 2013--2017.However,the activities of CVA16 increased gradually during 2018-2019.All the Beijing CVA16 strains belonged to sub-genotype BI,and B Ib was the dominant strain.One B Ic strain was detected in Bejing for the first time in 2016.The estimated mean evolutionary rate of VPI gene was 4.49x 103 substitution/site/year.Methionine gradually fixed at site-23 of VP1 since 2012.Two sites were detected under episodic positive selection,one of which(site-223)located in neutralizing linear epitope PEP71.Conclusions The dominant strains of CVA 16 belonged to clade B lb and evolved in a fast evolutionary rate during 2010-2019 in Beiing.To provide more favorable data for HFMD prevention and control,it is necessary to keep attention on molecular epidemiological and evolutionary characteristics of CVA16.

Association of Different Human Rhinovirus Species with Asthma in Children： A Preliminary Study

Background： Human rhinoviruses （HRVs） are divided into three genetic species： HRV-A, HRV-B, and HRV-C. The association of different HRV species with asthma in children in China has not yet been evaluated. This preliminary study aimed to assess the associations between different HRV species, particularly HRV-C, and asthma in young children in China. Methods： A total of 702 nasopharyngeal aspirates were obtained from 155 children with asthma （asthma group）, 461 children with acute respiratory infection （ARI） without asthma （nonasthma ARI group）, and 86 children from the control group. Semi-nested polymerase chain reaction （PCR） was used to detect HRVs, and PCR products were sequenced for species identification. Epidemiological characteristics of HRV-positive cases were analyzed. Results： HRVs were the most common pathogen （ 15.4%; 108/702） in the patients in this study. The prevalence of HRV was significantly different （F = 20.633, P = 0.000） between tile asthma （25.8%） and nonasthma ARI groups （11.1%）. Phylogenetic analysis indicated that in the 108 cases positive for HRVs, 41 were identified as HRV-A, 8 as HRV-B, and 56 as HRV-C, Comparing the asthma with the nonasthlna ARI group, Spearman＇s rank correlation analysis revealed an association between HRV-A （P 〈 0.05） and C （P 〈 0.01） and asthma, confirmed by regression analysis, with odds ratios of 2.2 （HRV-A） and 4.2 （HRV-C）. Conclusions： Our data revealed a high prevalence of HRVs in children in China, regardless of clinical status. HRV-C was the dominant species and may be one of the key factors in the association of HRVs with asthma.

Application of Human Adenovirus Genotyping by Phylogenetic Analysis in an Outbreak to Identify Nosocomial Infection

Nosocomial infections are common in pediatric patients and can be fatal in infants and immunocompromised patients. In September 2018, a high positive rate of human adenovirus HAdV was occurred among hospitalized children in the Children's Hospital Affiliated to the Capital Institute of Paediatrics in Beijing. To investigate whether this outbreak of HAdV was related to nosocomial infections or the result of community infections, we collected respiratory specimens from patients with acute respiratory infections in a respiratory ward during June to December 2018, and screened for respiratory viruses. Among 1,840 cases included, 95(5.2%, 95/1840) were positive for HAdV and 81 were genotyped based on phylogenetic analysis, including seven as HAdV-1(8.6%), 30 HAdV-3(37.0%), two HAdV-6(2.5%), and 42 HAdV-7(51.9%). More HAdV-positive samples were collected in August(4.7%, 12/255), September(15.0%, 41/274) and October(6.9%, 17/247), with a peak in September 2018. By combining the results of HAdV phylogenetic analysis with clinical data of patients, there were 77 cases(4.2%, 77/1840;81.1%, 77/95) excluded from nosocomial infections, eight cases representing possible infections transmitted by visitors or attending parents, three cases without sequences that might have been due to infection transmitted by roommates positive for HAdV, one case of a roommate without an HAdV sequence, and six cases that shared highly homologous sequences with those of their roommates, for which nosocomial infections might be considered. In conclusion, genotyping of HAdVs based on phylogenetic analysis combined with clinical information provides a powerful method to distinguish nosocomial infections from community acquired infection, especially when tracing the origins of nosocomial infections.

Delivery room resuscitation and short-term outcomes of extremely preterm and extremely low birth weight infants: a multicenter survey in North China

Background:Delivery room resuscitation assists preterm infants,especially extremely preterm infants(EPI)and extremely low birth weight infants(ELBWI),in breathing support,while it potentially exerts a negative impact on the lungs and outcomes of preterm infants.This study aimed to assess delivery room resuscitation and discharge outcomes of EPI and ELBWI in China.Methods:The clinical data of EPI(gestational age[GA]<28 weeks)and ELBWI(birth weight[BW]<1000 g),admitted within 72 h of birth in 33 neonatal intensive care units from five provinces and cities in North China between 2017 and 2018,were analyzed.The primary outcomes were delivery room resuscitation and risk factors for delivery room intubation(DRI).The secondary outcomes were survival rates,incidence of bronchopulmonary dysplasia(BPD),and risk factors for BPD.Results:A cohort of 952 preterm infants were enrolled.The incidence of DRI,chest compressions,and administration of epinephrine was 55.9%(532/952),12.5%(119/952),and 7.0%(67/952),respectively.Multivariate analysis revealed that the risk factors for DRI were GA<28 weeks(odds ratio[OR],3.147;95%confidence interval[CI],2.082–4.755),BW<1000 g(OR,2.240;95%CI,1.606–3.125),and antepartum infection(OR,1.429;95%CI,1.044–1.956).The survival rate was 65.9%(627/952)and was dependent on GA.The rate of BPD was 29.3%(181/627).Multivariate analysis showed that the risk factors for BPD were male(OR,1.603;95% CI,1.061–2.424),DRI(OR,2.094;95% CI,1.328–3.303),respiratory distress syndrome exposed to≥2 doses of pulmonary surfactants(PS;OR,2.700;95%CI,1.679–4.343),and mechanical ventilation≥7 days(OR,4.358;95% CI,2.777–6.837).However,a larger BW(OR,0.998;95% CI,0.996–0.999),antenatal steroid(OR,0.577;95%CI,0.379–0.880),and PS use in the delivery room(OR,0.273;95%CI,0.160–0.467)were preventive factors for BPD(all P<0.05).Conclusion:Improving delivery room resuscitation and management of respiratory complications are imperative during early management of the health of EPI and ELBWI.

Inductively Coupled Plasma Mass Spectrometry as a Reference Method to Evaluate Serum Calcium Measurement Bias and the Commutability of Processed Materials during Routine Measurements

Background： Measuring total serum calcium is important for the diagnosis of diseases. Currently, results from commercial kits for calcium measurement are variable. Generally, the performance of serum calcium measurements is monitored by external quality assessment （EQA） or proficiency testing schemes. However, the commutability of the EQA samples and calibrators is often unknown, which limits the effectiveness of EQA schemes. The aim of this study was to evaluate the bias of serum calcium measurements and the commutability of processed materials. Methods： Inductively coupled plasma mass spectrometry was applied as a comparative method, and 14 routine methods were chosen as test methods. Forty-eight serum samples from individual patients and 25 processed materials were quantified. A scatter plot was generated from patient samples, and 95% prediction intervals were calculated to evaluate the commutability of the processed materials and measurement bias at three concentration levels was used to determine the accuracy of routine assays. Results： All assays showed high precision （total coefficient of variation [CV] 〈2.26%） and correlation coefficients （r 〉 0.99）. For all assays, the mean bias for the 48 patient samples ranged from 0.13 mmol/L to 0.00 mmol/L （-5.61 0.01%）, and the ranges for the three concentrations were 0.10-0.04 mmoUL （-5.71-2.35%）, -0.14-0.01 mmol/L （-5.80-0.30%）, and -0.19-0.04 mmol/L （-6.24-1.22%）. The EQA samples, calibrators, and animal sera exhibited matrix effects in some assays; human serum pools were commutable in all assays; certificate reference materials were commutable in most assays, and only GBW09152 exhibited a matrix effect in one assay： and aqueous reference materials exhibited matrix effects in most assays. Conclusions： Biases for most assays were within the acceptable range, although the accuracy of some assays needs improvement. Human serum pools prepared from patient samples were commutable, and the other tested materials exhibited a matrix effect.

Development patterns of adenoids in Chinese children without sleep-disordered breathing: a retrospective magnetic resonance imaging study with consecutive age groups

To the Editor:Sleep-disordered breathing(SDB)is a health problem affecting approximately 12%of children in China,[1]characterized by habitual loud snoring and increased respiratory effort.Increased upper airway resistance related to enlarged adenoids has been identified as the most common cause in children with obstructive SDB,and adenoidectomy is the standard treatment for the disorder.Similar to lymphoid tissues,adenoids show a unique natural growth pattern,which incorporates both overgrowth and involution.However,the development patterns of adenoids have not been clearly elucidated.Since the adenoids are located in the nasopharynx roof,direct evaluation of their size and proportion to the upper airway area is difficult.Thus,radiological methods have been employed widely for such purposes,including traditional plain cranial radiographs,computed tomography(CT),cone-beam CT,and magnetic resonance imaging(MRI).MRI can reveal the accurate size of adenoids by differentiating them from other soft tissue structures without any ionizing radiation;therefore,it can effectively study the adenoids’developmental pattern in normal children.Previous studies have evaluated age-associated changes in adenoid size by MRI.Arens et al[2]indicated that adenoids grow proportionally to the skeletal structures in children aged 1 to 11 years.Papaioannou et al[3]reported that head MRI examinations demonstrated increased adenoid size during the first 7–8 years of life and then decreased gradually in children without snoring signs.Variabilities of the above-reported adenoids’development pattern exist due to the limitations associated with the small sample size.Furthermore,none of the above-mentioned studies on normal children used a strict method to exclude SDB.Additionally,for adenoid hypertrophy,the adenoid/nasopharyngeal(A/N)ratio was found to be a useful,tolerable,and confident diagnostic method in pediatric patients,with emphasis on the correlation of the adenoid size and upper airway lumen to variable degrees.Therefore,the A/N ratio can be considered a useful objective tool in evaluating adenoid development in children.We aimed to investigate the growth and involution patterns of adenoids in consecutive age groups from birth to 16 years in Chinese children without SDB using MRI data,which may benefit the study of diseases associated with the development of adenoids.

Effect of human rhinovirus infection in pediatric patients with influenza-like illness on the 2009 pandemic influenza A（H1N1） virus

Background Some research groups have hypothesized that human rhinoviruses （HRVs） delayed the circulation of the 2009 pandemic influenza A（H1N1） virus （A（H1N1）pdm09） at the beginning of Autumn 2009 in France.This study aimed to evaluate the relationship between HRV and A（H1N1）pdm09 in pediatric patients with influenza-like illness in Beijing,China.Methods A systematic analysis to detect A（H1N1）pdm09 and seasonal influenza A virus （FLU A） was performed on 4 349 clinical samples from pediatric patients with influenza-like illness during the period June 1,2009 to February 28,2010,while a one-step real-time RT-PCR （rRT-PCR） assay was used to detect HRV in 1 146 clinical specimens selected from those 4 349 specimens.Results During the survey period,only one wave of A（H1N1）pdm09 was observed.The percentage of positive cases for A（H1N1）pdm09 increased sharply in September with a peak in November 2009 and then declined in February 2010.Data on the monthly distribution of HRVs indicated that more HRV-positive samples were detected in September （2.2％） and October （3.3％）,revealing that the peak of HRV infection in 2009 was similar to that of other years.Among the 1 146 specimens examined for HRVs,21 （1.8％） were HRV-positive,which was significantly lower than that reported previously in Beijing （15.4％ to 19.2％） （P ＜0.01）.Overall,6 samples were positive for both A（H1N1）pdm09 and HRV,which represented a positive relative frequency of 1.60％ and 2.08％ HRV,considering the A（H1N1）pdm09-positive and-negative specimens,respectively.The odds ratio was 0.87 （95％ CI 0.32; 2.44,P=0.80）.Conclusions HRVs and A （H1N1）pdm09 co-circulated in this Chinese population during September and October 2009,and the HRV epidemic in 2009 did not affect A（H1N1）pdm09 infection rates in Beijing,China as suggested by other studies.However,the presence of A（H1N1）pdm09 might explain the unexpected reduction in the percentage of HRV positive cases during the period studied.

TRIB3 promotes pulmonary fibrosis through inhibiting SLUG degradation by physically interacting with MDM2

Pulmonary fibrosis(PF)is the pathological structure of incurable fibroproliferative lung diseases that are attributed to the repeated lung injury-caused failure of lung alveolar regeneration(LAR).Here,we report that repetitive lung damage results in a progressive accumulation of the transcriptional repressor SLUG in alveolar epithelial type II cells(AEC2s).The abnormal increased SLUG inhibits AEC2s from self-renewal and differentiation into alveolar epithelial type I cells(AEC1s).We found that the elevated SLUG represses the expression of the phosphate transporter SLC34A2 in AEC2s,which reduces intracellular phosphate and represses the phosphorylation of JNK and P38 MAPK,two critical kinases supporting LAR,leading to LAR failure.TRIB3,a stress sensor,interacts with the E3 ligase MDM2 to suppress SLUG degradation in AEC2s by impeding MDM2-catalyzed SLUG ubiquitination.Targeting SLUG degradation by disturbing the TRIB3/MDM2 interaction using a new synthetic staple peptide restores LAR capacity and exhibits potent therapeutic efficacy against experimental PF.Our study reveals a mechanism of the TRIB3—MDM2—SLUG—SLC34A2 axis causing the LAR failure in PF,which confers a potential strategy for treating patients with fibroproliferative lung diseases.

Upper airway cough syndrome in 103 children

Background: In China, upper airway cough syndrome (UACS) is only less frequent than cough-variant asthma and accounts for 24.71% of chronic cough. This study aimed to determine the pathogenetic constituents and factors affecting UACS in children of different age groups, and to identify clinical clues for diagnosing UACS and a method for curative effect evaluation. Methods: A total of 103 children with UACS whose chief complaint was chronic cough were studied from January to November 2013 at Children's Hospital, Capital Institute of Pediatrics. According to their age, children with UACS were divided into 3 groups: nursing children, pre-school children, and school-age children. We analyzed the differences in pathogenetic constituents and factors affecting UACS in children. The effect of UACS treatment was evaluated by the visual analog scale (VAS) and an objective examination. Chi-squared test and analysis of variance were performed with the SPSS 19.0 statistical software. Results: There was a high incidence of UACS in school-age children. Rhinitis with adenoid hypertrophy was the main cause of 103 suspected UACS cases. Adenoidal hypertrophy was the major cause of UACS in the pre-school children group, while rhinitis was the major reason in the nursing children and school-age children groups. Among the 103 children, there were 45 allergenpositive children, with no significant difference among different age groups. VAS scores in the different disease groups after treatment were lower than those before treatment (all P<O.Ol). VAS scores in different disease groups showed significant differences, except for 12 vs. 24 weeks after treatment (P = 0.023). Different age groups had different secondary complaints. Conclusions: There are different pathogeneses in different UACS age groups. Clinical treatment efficacy of children with UACS can be evaluated by the VAS combined with an objective examination. We recommend that the course of treatment should be 12 weeks.