A Five-year Surveillance of Carbapenemase-producing Klebsiella pneumoniae in a Pediatric Hospital in China Reveals Increased Predominance of NDM-1

Objective To characterize carbapenem （CPM）-non-susceptible Klebsiella pneumoniae （K. pneumoniae） and carbape-nemase produced by these strains isolated from Beijing Children＇s Hospital based on a five-year surveillance. Methods The Minimal Inhibition Concentration values for 15 antibiotics were assessed using the Phonixl00 compact system. PCR amplification and DNA sequencing were used to detect genes encoding carbapenemases. WHONET 5.6 was finally used for resistance analysis. Results In total, 179 strains of CPM-non-susceptible K. pneumoniae were isolated from January, 2010 to December, 2014. The rates of non-susceptible to imipenem and meropenem were 95.0% and 95.6%, respectively. In the 179 strains, 95 （53.1%） strains carried the blalMP gene, and IMP-4 and IMP-8 were detected in 92 （96.8%） and 3 （3.2%） IMP-producing isolates, respectively. 65 （36.3%） strains carried the blaNDM_1 gene. 6 （3.4%） strains carried the blaKpc gene, and KPC-2 were detected in 6 KPC-producing isolates. In addition, New Delhi-Metallo-1 （NDM-1） producing isolates increased from 7.1% to 63.0% in five years and IMP-4 producing isolates decreased from 75.0% to 28.3%. Conclusion High frequencies of multiple resistances to antibiotics were observed in the CPM-non-susceptible K. pneumoniae strains isolated from Beijing Children＇s Hospital. The production of IMP-4 and NDM-1 metallo-13-1actamases appears to be an important mechanism for CPM-non- susceptible in K. pneumoniae.

Phylogenetic and Molecular Analysis of an H7N7 Avian Influenza Virus Isolated in East Dongting Lake in 2012

Objective In March 2012, an H7N7 subtype avian influenza virus （AIV） named A/wild goose/Dongting/PC0360/2022 （H7N7） （DT/PC0360） was recovered from a wild goose in East Dongting Lake. We performed whole-genome sequencing of the isolate, and analyzed the phylogenetic and molecular characterization. Methods RNA was extracted from environment samples （including fecal samples from wild bird or domestic ducks, and water samples） for detecting the presence of Influenza A Virus targeting Matrix gene, using realtime RT-PCR assay. The positive samples were performed virus isolation with embryonated eggs. The subtype of the isolates were identified by RT-PCR assay with the HI-HI6 and N1-N9 primer set. The whole-genome sequencing of isolates were performed. Phylogenetic and molecular characterizations of the eight genes of the isolates were analyzed. Results Our results suggested that all the eight gene segments of DT/PC0360 belonged to the Eurasian gene pool, and the HA gene were belonged to distinct sublineage with H7N9 AIV which caused outbreaks in China's Mainland in 2013. The hemagglutinin cleavage site of HA of DT/PC0360 showed characterization of low pathogenic avian influenza virus. Conclusion Strengthening the surveillance of AlVs of wild waterfowl and poultry in this region is vita for our knowledge of the ecology and mechanism of transmission to prevent an influenza pandemic.

Long-term protection against dengue viruses in mice conferred by a tetravalent DNA vaccine candidate

DEAR EDITOR,The development of an effective tetravalent vaccine against dengue viruses(DENVs)has become a world priority.We previously showed that four monovalent dengue DNA vaccines expressing premembrane(prM)and envelope(E)proteins displayed effective protection against corresponding challenges in mice.Thus,to elucidate the overall immunity and persistence of the tetravalent formulation(TetraME),we evaluated the humoral and cellular immune responses as well as the long-term protection in the current study.TetraME-immunized mice displayed increased production of Th1/Th2-typed cytokines upon stimulation with heterologous DENV antigens.Moreover,high levels of tetravalent DENV antibodies and sterilized immunity were detected long-term(30 weeks after immunization).These findings provide feasible validation for the potential utility of this vaccine formulation.

Maternal inappropriate calcium intake aggravates dietary-induced obesity in male offspring by affecting the differentiation potential of mesenchymal stem cells

BACKGROUND The effects of inappropriate dietary calcium intake in early life on later obesity have not been fully elucidated.AIM To raise the mechanism of maternal calcium intake on the multi-differentiation potential of mesenchymal stem cells among their male offspring.METHODS Four-week-old female C57BL/6N mice were fed by deficient,low,normal and excessive calcium reproductive diets throughout pregnancy and lactation.Bone MSCs(BMSCs)were obtained from 7-day-old male offspring to measure the adipogenic differentiation potential by the Wnt/β-catenin signaling pathway.The other weaning male pups were fed a high-fat diet for 16 wk,along with normalfat diet as the control.Then the serum was collected for the measurement of biochemical indicators.Meanwhile,the adipose tissues were excised to analyze the adipocyte sizes and inflammatory infiltration.And the target gene expressions on the adipogenic differentiation and Wnt/β-catenin signaling pathway in the adipose tissues and BMSCs were determined by real-time reverse transcription polymerase chain reaction.RESULTS Compared with the control group,maternal deficient,low and excessive calcium intake during pregnancy and lactation aggravated dietary-induced obesity,with larger adipocytes,more serious inflammatory infiltration and higher serum metabolism indicators by interfering with higher expressions of adipogenic differentiation(PPARγ,C/EBPα,Fabp4,LPL,Adiponectin,Resistin and/or Leptin)among their male offspring(P<0.05).And there were significantly different expression of similar specific genes in the BMSCs to successfully polarize adipogenic differentiation and suppress osteogenic differentiation in vivo and in vitro,respectively(P<0.05).Meanwhile,it was accompanied by more significant disorders on the expressions of Wnt/β-catenin signaling pathway both in BMSCs and adulthood adipose tissues among the offspring from maternal inappropriate dietary calcium intake groups.CONCLUSION Early-life abnormal dietary calcium intake might program the adipogenic differentiation potential of BMSCs from male offspring,with significant expressions on the Wnt/β-catenin signaling pathway to aggravate high-fat-diet-induced obesity in adulthood.

The putative NAD(P)H Nitroreductase,Rv3131,is the Probable Activating Enzyme for Metronidazole in Mycobacterium Tuberculosis

Tuberculosis(TB),which is caused by the intracellular pathogen,Mycobacterium tuberculosis(Mtb),remains one of the deadliest infectious diseases worldwide,accounting for 1.45 million deaths in 2018[1].Thus,there is an increasing need to develop new antibiotics or to repurpose old drugs that have the potential to shorten the current duration of therapy.Metronidazole(MTZ)is a 5-nitroimidazole antibiotic that is mainly used in the treatment of anaerobic and protozoal infections[2].The action of mechanism for metronidazole has not been fully established.As a prodrug,MTZ is inactive until taken up and reduced by anaerobic bacteria and protozoa.It is possible that the reduction of Mtz leads to the production of toxic metabolites,which bind to deoxyribonucleic acid and electron-transport proteins of microbial pathogens,thus blocking nucleic acid synthesis[3].The impressive potency of MTZ against anaerobic bacteria indicates the potential for killing Mtb under anaerobic conditions.A previous in vitro study demonstrated that MTZ has potent activity against tubercle bacilli under anaerobic conditions[4].In a non-human primate model,MTZ has been shown to prevent reactivation of latent Mtb infection,indicating the in vivo role in targeting Mtb within an anaerobic environment[5].Although there is strong evidence for the role of MTZ in affecting anaerobic bacilli,the mechanism of action has not been elucidated in Mtb considering that MTZ must be catalyzed to a nitro-free radical form with endogenous nitroreductase.To provide insight=into how MTZ is activated in anaerobic Mtb bacilli,we first characterized the nitroreductase gene,Rv3131,and identified the key residue conferring the activation of MTZ in Mtb.

Multilevel omics for the discovery of biomarkers in pediatric sepsis

Severe sepsis causes organ dysfunction and continues to be the leading reason for pediatric death worldwide.Early recognition of sepsis could substantially promote precision treatment and reduce the risk of pediatric death.The host cellular response to infection during sepsis between adults and pediatrics could be significantly different.A growing body of studies focused on finding markers in pediatric sepsis in recent years using multi-omics approaches.This narrative review summarized the progress in studying pediatric sepsis biomarkers from genome,transcript,protein,and metabolite levels according to the omics technique that has been applied for biomarker screening.It is most likely not a single biomarker could work for precision diagnosis of sepsis,but a panel of markers and probably a combination of markers detected at multi-levels.Importantly,we emphasize the importance of group distinction of infectious agents in sepsis patients for biomarker identification,because the host response to infection of bacteria,virus,or fungus could be substantially different and thus the results of biomarker screening.Further studies on the investigation of sepsis biomarkers that were caused by a specific group of infectious agents should be encouraged in the future,which will better improve the clinical execution of personalized medicine for pediatric sepsis.

Experts’Consensus on the Management of Respiratory Disease Syndemic

The global burden of respiratory diseases is a significant and increasing threat to individuals worldwide.In 2017,there were 544.9 million cases of chronic respiratory diseases,a 39.8%increase since 1990(1).These diseases were the third leading cause of global mortality in 2017,accounting for 7.0%of all deaths,an 18.0%increase compared to 1990.

Expert consensus on the diagnosis, treatment, and prevention of respiratory syncytial virus infections in children

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.

Diagnosis,treatment and prevention of severe acute respiratory syndrome coronavirus 2 infection in children:experts'consensus statement updatedforthe Omicron variant

It has been more than 3 years since the novel coronavirus(SARS-CoV-2)pandemic raged globally.The coronavirus disease 2019(COVID-19)has greatly influenced human society.According to data from the World Health Organization(WHO),there were over 656 million confirmed cases of COVID-19 in the world as of January 1,2023,including over 6.6 million deaths[1].

Pneumomediastinum Secondary to Foreign Body Aspiration： Clinical Features and Treatment Explorement in 39 Pediatric Patients

Background：Pneumomediastinum （PM） secondary to foreign body aspiration （FBA） is rare in children.Although it is mainly benign,some cases may be fatal.Due to the rare nature of this clinical entity,proper assessment and management have been poorly studied so far.Here,we characterized the presentation and management of this clinical entity and provided an evaluation system for the management.Methods：We retrospectively reviewed children with PM secondary to FBA,who were treated in Beijing Children＇s Hospital from January 2010 to December 2015.All patients were stratified according to the degree of dyspnea on admission,and interventions were given accordingly.Bronchoscopic removals of airway foreign bodies （FBs） were performed on all patients.For patients in acute respiratory distress,emergent air evacuation and/or resuscitations were performed first.Admission data,interventions,and clinical outcomes were recorded.Results：A total of 39 patients were included in this study.The clinical severity was divided into three grades （Grades Ⅰ,Ⅱ,and Ⅲ） according to the degree of dyspnea.Thirty-one patients were in Grade Ⅰ dyspnea,and they simply underwent bronchoscopic FBs removals.PM resolved spontaneously and all patients recovered uneventfully.Six patients were in Grade Ⅱ dyspnea,and emergent drainage preceded rigid bronchoscopy.They all recovered uneventfully under close observation.Two exhausted patients were in Grade Ⅲ dyspnea.They died from large PM and bilateral pneumothorax,respectively,despite of aggressive interventions in our hospital.Conclusions：PM secondary to FBA could be life-threatening in some patients.The degree of dyspnea should be evaluated immediately,and patients in different dyspnea should be treated accordingly.For patients in Grade Ⅰ dyspnea,simple bronchoscopic FBs removals could promise a good outcome.For patients in Grade Ⅱ dyspnea,emergent air evacuation and/or resuscitation should precede a bronchoscopy before the children become exhausted.

Clinical Research of Pulmonary Langerhans Cell Histiocytosis in Children

Background： Pulmonary Langerhans cell histiocytosis （PLCH） is an interstitial primary pulmonary disease, characterized by Langerhans cell proliferation. It is easily misdiagnosed in children. This study aimed to characterize the clinical manifestations and features of PLCH by retrospective analysis. Meihods： A retrospective analysis was performed in 117 PLCH patients out of 338 LCH patients who were admitted in our center from November 2006 to October 2013. Variables between two groups were compared by Mann-Whitney U-test and Chi-square test. Kaplan-Meier curves were constructed to compare the survival rates and Cox regression to evaluate the effect of risk factors. Results： The median age of PLCH group was significantly lower than that ofnon-PkCH group （ 18.63 months vs. 43.4 months, P 〈 0.001 ）. All PLCH children had other organ involvement and only 11 cases （9.4%） had respiratory symptoms. The most common radiologic finding was cystic lesions （29 cases, 24.8%）. Pulmonary thnction abnormalities were dominated by obstructive ventilatory dysfunction （63 cases, 82.9%）. The 5-year overall survival （OS） of PECH children was 93.6% ± 2.3% and the event-free survival （EFS） was 55.7% ± 5.2%. Among the 38 cases with progressed or relapsed disease, five cases （13.2%） were due to progression or recurrence of lung damage. The 5-year OS of PECH children with ＂risk organ＂ involvement was significantly lower than those without ＂risk organ＂ involvement （86.0% ± 4.9% vs. 100%,X^2 = 8.793, P= 0.003）. The difference of EFS between two groups was also significant （43.7% ± 7.7% vs. 66.3% ± 6.5%,X^2 = 5.399, P = 0.020）. The ＂＇risk organ＂ involvement had a significant impact on survival （hazard ratio = 1.9, P = 0.039）. Conclusions： PLCH mainly occurs in young children, and only a small percentage of patients have respiratory symptoms. They generally have other organ involvement. Most of PLCH children have a good prognosis and most lung lesions could have improved or stabilized. Management of＂risk organ＂ involvement is the key point to improving EFS.

Clonal and drug resistance dynamics of methicillin-resistant Staphylococcus aureus in pediatric populations in China

Importance:Regional clonal replacements of methicillin-resistant Staphylococcus aureus (MRSA) are common.It is necessary to understand the clonal and drug resistance changes in specific areas.Objective:To evaluate the clonal and drug resistance dynamics of MRSA in Chinese children from 2010 to 2017.Methods:MRSA was isolated from patients in Beijing Children's Hospital from 2010 to 2013 and from 2016 to 2017.The molecular characteristics and antibiotic resistance were determined,Results:In total,211 MRSA isolates were collected,and 104 isolates were classified as community-associated MRSA (CA-MRSA).ST59-SCCmec Ⅳ was the most prevalent type in both CA-MRSA (65.4%) and healthcare-associated-MRSA (HA-MRSA) (46.7%).ST239-SCCmec Ⅲ accounted for 21.5% of all HA-MRSA,which were not detected in 2016,and only three isolates were detected in 2017.The pvl gene carrying rate of CA-MRSA was significantly higher than that of HA-MRSA (42.3% vs.29.0%,P =0.0456).Among CA-MRSA,resistance rate to all tested antibiotics excluding chloramphenicol remained stable over the periods of 2010-2013 and 2016-2017.HA-MRSA displayed an overall trend of decreased resistance to oxacillin,gentamicin,tetracycline,ciprofloxacin,and rifampin,and increased resistance to chloramphenicol,consistent with the difference of antibiotic resistance patterns between ST59-SCCmec Ⅳ and ST239-SCCmec Ⅲ isolates.Vancomycin minimal inhibitory concentration (MIC) creep was found in the study period in all MRSA and ST59-SCCmec Ⅳ isolates.Interpretation:ST59-SCCmec Ⅳ has spread to hospitals and replaced the traditional ST239-SCCmec Ⅲ clone,accompanied by changes in drug resistance.Furthermore,vancomycin MIC creep indicated that the rational use of antibiotics should be seriously considered.

Correlation between TERT C228T and clinic-pathological features in pediatric papillary thyroid carcinoma

The aims of the present study were to reveal the prevalence of the TERT C228 T mutation in pediatric papillary thyroid carcinoma(PPTC) and to further investigate the role of the TERT C228 T mutation in PPTC. We also tested another TERT mutation, TERT C250 T, although this was not detected in PPTC patients. In this study, 48 patients with PPTC(41 with classic PPTC) were enrolled. DNA was extracted from PPTC tissues and TERT C228 T mutation analysis was performed. Chi-squared analysis,Fisher’s exact test, and a t-test were applied to test the significance of differences. The TERT C228 T mutation presented in 13(27.1%) of the 48 PPTC patients and 10(24.4%) of the 41 classical PPTC patients. There were significant differences between PPTC patients with the TERT C228 T mutation and those without in terms of modified radical neck dissection, multifocality,capsular invasion, extrathyroidal invasion, and American Joint Committee on Cancer(AJCC) tumor stage(P<0.05). In classical PPTC, there were additional significant differences in other clinic-pathological features, such as AJCC nodal stage(P=0.009)and American Thyroid Association(ATA) PPTC stage(P=0.021) between patients with and without the TERT C228 T mutation.These findings indicate that the TERT C228 T mutation is significantly correlated with certain aggressive clinic-pathological features of PPTC.

Recombinant GII.4[P31] Was Predominant Norovirus Circulating in Beijing Area, China, 2018–2020

Dear Editor,Acute gastroenteritis(AGE)is a leading infectious cause of morbidity worldwide,particularly among children in developing countries(Mortality and Causes of Death2016).With the introduction of rotavirus vaccines,noroviruses have been identified as a leading cause of AGE outbreaks and sporadic disease worldwide(Hall et al.

Sleep Duration and Factors Related to Sleep Loss in 3-14-Year-Old Children in Beijing： A Cross-Sectional Survey

Background： It is known that short sleep duration adversely affects children＇s behavior and physical development. This study aimed to investigate the status of sleep duration in 3-14-year-old children in Beijing and explore the related factors of sleep loss with them. Methods： In this study, a cross-sectional study of random stratified cluster sampling was conducted on 3-14-year-old children and adolescents in Beijing. According to the proportion of children in each district and school, the final cohort included a total of 11 kindergartens, 7 primary schools, and 8 junior high schools from 7 districts of Beijing. Children of sampled classes were included, and their parents were invited to fill a series of questionnaires including the simplified Chinese version of Pediatric Sleep Questionnaire, Sleep Questionnaire Scale, and Hong Kong-Children Sleep Questionnaire about the performance of the last 6 months. Results： Out of the total 11,420 questionnaires, 9198 questionnaires were valid and effective with the response rate of 80.54%. The age of the investigated children was 8.8 ± 3.8 years, including 4736 males and 4462 females. The daily sleep duration of children in Beijing was 9.7 ± 0.7 h. The prevalence of sleep loss （〈9 h/day） of children in Beijing was 11.8%. The daily sleep duration of children aged 〈6, 6 ≤ age 〈11, and ≥11 years was 9.7 ± 0.6 h, 9.6 ± 0.6 h, and 9.5 ± 0.8 h, respectively. The sleep duration reduced significantly in children aged ≥11 years as compared to younger children in Beijing which was mainly contributed by the variation tendency of sleep duration on weekdays. The multivariate logistic regression analysis identified factors associated with sleep loss （P 〈 0.05）： male （odds ratio [OR] = 1.32, 95% confidence interval [CI ]： 1.15-1.51 ）, age ≥11 years （OR = 2.37, 95% CI： 1.92-2.93）, overweight （OR = 1.34, 95% CI： 1.17-1.54）, family history of snoring （OR - 1.35, 95% CI： 1.13-1.61 ） and activities before bedtime with watching TV （OR = 1.24, 95% CI： 1.08 1.43）, sports （OR = 1.22, 95% C/： 1.01-1.48）, playing cellphone （OR = 1.91,95% CI： 1.31-2.73） and surfing the Internet （OR = 1.27, 95% CI： 1.06-1.52） and among them age 〉11 years and playing cellphone betbre bedtime had greater impact on children＇s short sleep duration than that of other factors. Conclusions： Sleep loss was common among 3-14-year-old children in Beijing. Sleep duration decreased with age, especially among children over 11 years old. Factors associated with sleep loss covered sociodemographic characteristics, family sleep habits and routine activities before bedtime, and among those variables, age ≥11 years and playing with cellphones before bedtime had a greater impact on sleep duration, indicating that existing sleep loss in 3-14-year-old children could be, at least partly, improved by paying more attention to children aged of l I years or entering Grade 5 and Grade 6 and to children with a family history of snoring; by reducing the use of electronic products betbre bedtime, especially cellphones; by managing weight and keeping fit; and by improving the bedtime routine.

Vestibular function of pediatric patients with sudden sensorineural hearing loss:based on vertigo symptom and vestibular function testing

Background This study aimed to evaluate the relationship between vestibular and auditory functions in pediatric patients with sudden sensorineural hearing loss(SSHL).Methods A total of 30 pediatric patients experiencing unilateral SSHL between 5.9 and 13.0 years of age were enrolled in this study.Pure tone audiometry was evaluated prior to treatment initiation and again after one month of treatment.Prior to treatment initiation,vertigo symptoms were noted;then several vestibular function tests were conducted including caloric testing,ocular vestibular evoked myogenic potentials(o-VEMPs)and cervical vestibular evoked myogenic potentials(c-VEMPs).Associations between pre and post-treatment vestibular function and hearing threshold levels were analyzed.Results Initial hearing thresholds of children with vertigo were higher than thresholds of children without vertigo(92 dB vs 79 dB,F=0.033),while initial hearing thresholds of children with abnormal caloric test findings were higher than thresholds of children with normal caloric test findings(93 dB vs 67 dB.P=0.014).Cutoff values of hearing thresholds for those with vertigo symptoms and abnormal vestibular test results were 86.000-and 89.583-dB HL.respectively.Regarding prognosis,children with vertigo exhibited lower recovery rates than children without vertigo(33%vs 75%,P=0.025);recovery rates of children with abnormal caloric test results were lower than the overall recovery rate(25%vs 73%,respectively,P=0.039).Conclusion Assessments of vertigo symptoms and vestibular function are useful tools in predicting pediatric SwSHL patient disease severity and prognosis.

HIV infection among new synthetic drug abusers： a pilot study in Beijing

Background Following the increased human immunodeficiency virus （HIV） notification （infection） rates via sexual transmission and increased abuse of new synthetic drugs instead of heroin in China, a study on HIV infections and risk factors among synthetic drugs and heroin users in Beijing was conducted to provide a cue for further development of targets and strategies of HIV/AIDS control and prevention for different drug populations. Methods A total of 428 subjects including 224 heroin users and 204 new synthetic drug users was recruited from communities in Beijing by convenience sampling. A X2 test was used to compare HIV and syphilis infections between the two subpopulations. Logistic regression models were used to evaluate factors related to HIV, syphilis infections and abuse of synthetic drugs. Results Unbalanced distributions of demographics were detected between the two subpopulations. Compared with heroin users, most users of synthetic drugs were migrants, single and of younger age （age 〈30 years）. Ten HIV infections and twenty-four syphilis infections were confirmed among 428 subjects. No significant difference in HIV infection was found between the two subpopulations （crude odds ratio （OR） =0.46, 95% confidence interval （CI）： 0.07-15.80 and adjusted odds ratio （AOR） =1.26, 95% Ch 0.09-18.28） while four times as many syphilis infections were identified among users of synthetics drugs （AOR=3.92, 95% CI： 1.06-14.56）. HIV and syphilis infections appeared to work synergistically.The migrants who were of Han ethnicity, single and who had stayed in Beijing for more than six months were more likely to abuse synthetics drugs. Conclusions The new synthetic drug users and heroin users are different subpopulations. We optimistically speculate that HIV has not yet been introduced into the former in Beijing, but considering higher syphilis infections in synthetic drug users and the role of syphilis in HIV infection, synthetic drug users, as a possible and important driver of the HIV/AIDS epidemic in Beijing, should be paid more attention in HIV prevention and control strategies.

Serotypes of human enteroviruses causing pediatric viral encephalitis and meningitis in Hebei province, China, from 2013 to 2015

Importance:Viral encephalitis and meningitis are severe infectious diseases responsible for substantial morbidity and mortality in children.Enteroviruses are typically the most common causative agents of viral encephalitis and meningitis.Objective:This study aimed to investigate the etiology of viral encephalitis and meningitis among children in Hebei province,China.Methods:Cerebrospinal fluid samples from children with viral encephalitis (n=309) and meningitis (n=133) were collected between Nov 2013 and Dec 2015 and viral pathogens were identified by real-time and multiplex PCR.Amplification and sequencing of partial VP1 genes was used to type enteroviruses.Results:The causative pathogen was successfully detected in 176 (57％) patients with viral encephalitis and 82 (61.7％) patients with viral meningitis.The most common causative agents of both viral encephalitis and meningitis were enteroviruses (55.7％ and 64.6％ of cases,respectively).The most common enterovirus serotypes identified were echovirus 18,echovirus 6 and echovirus 30.Echovirus 18 accounted for 74.4％ of all typed enteroviruses and caused a viral encephalitis and meningitis outbreak in Hebei province in 2015.By contrast,the major enterovirus serotypes circulating in 2014 were echovims 6 and echovirus 30.Interpretation:Enteroviruses were the main causative agents of viral encephalitis and meningitis in children in Hebei province from Nov 2013 to Dec 2015.Echovirus 18 became the leading cause of viral encephalitis and meningitis for the first time in Hebei province in 2015.

DCX and CRABP2 are candidate genes for differential diagnosis between pre-chemotherapy embryonic and alveolar rhabdomyosarcoma in pediatric patients

Importance Rhabdomyosarcoma(RMS)is the most common soft tissue sarcoma in children.More than 90%of cases are classified as embryonic RMS(ERMS)or alveolar RMS(ARMS).ERMS has a worse prognosis than ARMS.Early differential diagnosis is of paramount importance for optimization of treatment.Objective To identify genes that are differentially expressed between ARMS and ERMS,which can be used for accurate rhabdomyosarcoma classification.Methods Three Gene Expression Omnibus datasets composed of ARMS and ERMS samples were screened and 35 differentially expressed genes(DEGs)were identified.Receiver operating characteristic curve analysis and area under the curve analysis was performed for these 35 DEGs and seven candidate genes with the best differential expression scores between ARMS and ERMS were determined.The expression of these seven candidate genes was validated by immunohistochemical analysis of pre-chemotherapy ARMS and ERMS specimens.Results The levels of DCX and CRABP2 were confirmed to be remarkably different between paraffin-embedded ARMS and ERMS tissues,while EGFR abundance was only marginally different between these two RMS subtypes.Interpretation DCX and CRABP2 are potential biomarkers for distinguishing ARMS from ERMS in pre-chemotherapy pediatric patients.

Variant analysis of the chromodomain helicase dNA-binding protein 7 in pediatric disorders of sex development

Importance:This study investigated the role of the chromodomain helicase DNA-binding protein 7(CHD7)in disorders of sex development(DSD).Objective:We aimed to present the potential pathogenicity of CHD7 variants in pediatric patients with DSD.Methods:Choosing cases with CHD7 variants from DSD patients in Beijing Children’s Hospital to assess for the study.Prediction software tools were used to predict variant pathogenicity in these subjects.results:Among the 113 DSD patients,22 cases had CHD7 variants.Twenty-four different CHD7 variants were identified in the 22 DSD patients.Prediction software combined with ClinVar database information and their clinical manifestations revealed that,of the 18 patients with 46,XY DSD,two had CHARGE syndrome and two had Kallmann syndrome.Seven of the variants were highly categorized as“likely to be pathogenic”and seven as“suspected to be pathogenic”.Of the four patients with 46,XX DSD,three had ovotesticular DSD(c.305A>G,c.2788G>A,and c.3098G>A)and one had testicular DSD(c.2831G>A).Interpretation:A high frequency of CHD7 variants was found in the DSD patients,especially those with 46,XY DSD.Thus,the detection of a pathogenic CHD7 variant could suggest a diagnosis of hypogonadotropic hypogonadism for 46,XY DSD patients,but pre-pubescent patients should be reassessed in adolescence to confirm this diagnosis.This study also suggests that DNA sequencing could help to identify pre-pubescent DSD patients.Further data are required to determine the connection between CHD7 variants and sex-reversal in patients with 46,XX DSD,and the accumulation of these data is essential and necessary for DSD research.