Potential Association of Lead Exposure During Early Development of Mice With Alteration of Hippocampus Nitric Oxide Levels and Learning Memory

Objective Chronic lead （Pb） exposure during development is known to produce learning deficits. Nitric oxide participates in the synaptic mechanisms involved in certain forms of learning and memory. This study was designed to clarify whether Pb-induced impairment in learning and memory was associated with the changes of nitric oxide levels in mice brains. Methods Sixty Balb/c mice aged l0 days were chosen. A model of lead exposure was established by drinking 0.025%, 0.05% 0.075% lead acetate, respectively for 8 weeks. The controls were orally given distilled water. The ability to learn and memorize was examined by open field test, T-water maze test. In parallel with the behavioral data, NO level of hippocampus tissue was detected by biochemical assay. Results Compared with control groups, （1） the weight of 0.075% group was significantly reduced （P〈0.05）; （2） The number of times in mice attaining the required standards in T-water maze test was lower in 0.075% group （P〈0.01）. No significant difference was found between experimental and control groups in open field test （P〉0.05）; （3） NO level of mouse hippocampus tissue was decreased in 0.075% group （P〈0.01）. Conclusions The findings suggest that decreased hippocampus NO level may contribute to the Pb-induced deficits in learning and memory processes.

Proteomic profiling of cerebrospinal fluid in pediatric myelin oligodendrocyte glycoprotein antibody-associated disease

Background Myelin oligodendrocyte glycoprotein(MOG)antibody-associated disease(MOGAD)is an autoimmune demy-elinating disorder of the central nervous system.Methods Extracted proteins from 34 cerebrospinal fluid(CSF)samples[patients with MOGAD(MOG group,n=12);healthy controls(HC group,n=12);patients with MOG seronegative and metagenomics next-generation sequencing-negative inflammatory neurological diseases(IND group,n=10)]were processed and subjected to label-free quantitative proteomics.Supervised partial least squares-discriminant analysis(PLS-DA)and orthogonal PLS-DA(O-PLS-DA)models were also performed based on proteomics data.Functional analysis of differentially expressed proteins(DEPs)was performed using Gene Ontology,InterPro,and Kyoto Encyclopedia Genes and Genomes.An enzyme-linked immunosorbent assay was used to determine the complement levels in serum from patients with MOGAD.Results Four hundred and twenty-nine DEPs(149 upregulated and 280 downregulated proteins)were identified in the MOG group compared to the HC group according to the P value and fold change(FC).Using the O-PLS-DA model,872 differentially abundant proteins were identified with variable importance projection(VIP)scores>1.Five proteins(gamma-glutamyl hydrolase,cathepsin F,interalpha-trypsin inhibitor heavy chain 5,latent transforming growth factor beta-binding protein 4 and leukocyte-associated immunoglobulin-like receptor 1)overlapping between the top 30 DEPs with top-ranked P value and FC and top 30 proteins in PLS-DA VIP lists were acquired.Functional analysis revealed that the dysregulated proteins in the MOG group were primarily involved in complement and coagulation cascades,cell adhesion,axon guidance,and glycosphingolipid biosynthesis compared to the HC group.Conclusion The proteomic alterations in CSF samples from children with MOGAD identified in the current study might provide opportunities for developing novel biomarker candidates.

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].

A multicenter prospective study of next-generation sequencing-based newborn screening for monogenic genetic diseases in China

Background Newborn screening(NBS)is an important and successful public health program that helps improve the long-term clinical outcomes of newborns by providing early diagnosis and treatment of certain inborn diseases.The develop-ment of next-generation sequencing(NGS)technology provides new opportunities to expand current newborn screening methodologies.Methods We designed a a newborn genetic screening(NBGS)panel targeting 135 genes associated with 75 inborn disorders by multiplex PCR combined with NGS.With this panel,a large-scale,multicenter,prospective multidisease analysis was conducted on dried blood spot(DBS)profiles from 21,442 neonates nationwide.Results We presented the positive detection rate and carrier frequency of diseases and related variants in different regions;and 168(0.78%)positive cases were detected.Glucose-6-Phosphate Dehydrogenase deficiency(G6PDD)and phenylketonuria(PKU)had higher prevalence rates,which were significantly different in different regions.The positive detection of G6PD variants was quite common in south China,whereas PAH variants were most commonly identified in north China.In addi-tion,NBGS identified 3 cases with DUOX2 variants and one with SLC25A13 variants,which were normal in conventional NBS,but were confirmed later as abnormal in repeated biochemical testing after recall.Eighty percent of high-frequency gene carriers and 60%of high-frequency variant carriers had obvious regional differences.On the premise that there was no significant difference in birth weight and gestational age,the biochemical indicators of SLC22A5 c.1400C>G and ACADSB c.1165A>G carriers were significantly different from those of non-carriers.Conclusions We demonstrated that NBGS is an effective strategy to identify neonates affected with treatable diseases as a supplement to current NBS methods.Our data also showed that the prevalence of diseases has significant regional charac-teristics,which provides a theoretical basis for screening diseases in different regions.

Diagnosis,treatment,and prevention of monkeypox in children:an experts'consensus statement

Monkeypox is a zoonotic disease.Since the first human monkeypox case was detected in 1970,it has been prevalent in some countries in central and western Africa.Since May 2022,monkeypox cases have been reported in more than 96 non-endemic countries and regions worldwide.As of September 14,2022,there have been more than 58,200 human monkeypox cases,and there is community transmission.The cessation of smallpox vaccination in 1980,which had some cross-protection with monkeypox,resulted in a general lack of immunity to monkeypox,which caused global concern and vigilance.As of Sep-tember 14,2022,there are four monkeypox cases in China,including three in Taiwan province and one in Hong Kong city.Previous foreign studies have shown that children are vulnerable to monkeypox and are also at high risk for severe disease or complications.In order to improve pediatricians'understanding of monkeypox and achieve early detection,early diagno-sis,early treatment,and early disposal,we have organized national authoritative experts in pediatric infection,respiratory,dermatology,critical care medicine,infectious diseases,and public health and others to formulate this expert consensus,on the basis of the latest"Clinical management and infection prevention and control for monkeypox"released by The World Health Organization,the"guidelines for diagnosis and treatment of monkeypox(version 2022)"issued by National Health Commission of the People's Republic of China and other relevant documents.During the development of this consensus,multidisciplinary experts have repeatedly demonstrated the etiology,epidemiology,transmission,clinical manifestations,laboratory examinations,diagnosis,differential diagnosis,treatment,discharge criteria,prevention,disposal process,and key points of prevention and control of suspected and confirmed cases.

Newborn screening for Duchenne muscular dystrophy in China: follow-up diagnosis and subsequent treatment

Background:Newborn screening for Duchenne muscular dystrophy (DMD) is currently being initiated in Zhejiang Province,China and is under consideration in other countries,including the United States.As China begins to implement DMD newborn screening (DMD-NBS),there is ongoing discussion regarding the steps forward for follow up care of positively identified patients as well as false positive and false negative results.Data sources:Relevant papers related to DMD-NBS,and NBS in China were reviewed in PubMed.Results:The current state of DMD-NBS is discussed,along with the steps needed to effectively screen infants for this disease in China,recommendations for establishment of follow up care in patients with positive and negative screens,and measurement of patient outcomes.Conclusions:Zhejiang Province,China is ready to implement DMD-NBS.Future challenges that exist for this program,and other countries,include the ability to track patients,assist with access to care,and ensure adequate follow-up care according to evidence-based guidelines.In addition,China's large rural population,lack of specialty providers,and difficulty in educating patients regarding the benefits of treatment create challenges that will need to be addressed.

Pediatrics in China: challenges and prospects

China has the largest number of children in the world. The population of children between 0 and 14 years of age was about 227 million in 2015. It is a great and arduous task to ensure the healthy growth of all children in China. Mater-nal and child health care in China has achieved significant improvements. China has achieved the Millennium Develop-ment Goal 4 [ 1 ], the mortality rate of children under 5 years of age showed an overall downward trend from 61.0 per 1000 in 1991 to 10.7 per 1000 in 2015 (2)However, China still faces many challenges, such as the serious shortage of pediatricians, shortage and uneven distribution of medical resources, imbalances among different population groups and different regions.

Progress in treatment and newborn screening for Duchenne muscular dystrophy and spinal muscular atrophy

Background Advances in treatment for Duchenne muscular dystrophy (DMD) and spinal muscular atrophy (SMA) hold promise for children with these disorders.Accurate genetic diagnosis,early in the disease process,will allow these treatments to be most effective.Newborn screening (NBS) for SMA has been recommended in the United States,and a pilot DMD NBS program is underway in Hangzhou,China.Data sources A PubMed search,limited to the past 5 years,was conducted to identify:(1) therapeutic advancements for DMD/SMA approved by the United States Food and Drug Administration or the European Medicine Agency and (2) The status of NBS for DMD/SMA.Results We review the current state of approved treatments for DMD/SMA.We present recommendations regarding the future of NBS for these diseases,with a focus on the outcomes and challenges of SMA NBS in New York,USA,and the DMD NBS pilot program in Hangzhou,China.Conclusions Approved treatments for DMD and SMA may change the natural history of these diseases.Long-term studies of these treatments are underway.To avoid the known diagnostic delay associated with these disorders and provide optimal effectiveness of these treatments,early identification of patients through NBS will be necessary.Establishing comprehensive follow-up plans for positively identified patients will need to be in place for NBS programs to be successful.

Application of next generation sequencing in the screening of monogenic diseases in China,2021:a consensus among Chinese newborn screening experts

Newborn screening(NBS)refers to a maternal and newborn healthcare technology,in which special examinations of congenital and genetic diseases that could seriously impact the health of newborns,are implemented during the neonatal period to provide early diagnosis and treatment[1].With a history of more than 60 years,NBS has advanced greatly due to technological progress resulting in significant improvement in the number of diseases covered by NBS and in screening efficiency[2-7].

Establishment of an efficient reverse genetic system of Mumps virus S79 from cloned DNA

Background Mumps is a common type of respiratory infectious disease caused by mumps virus(MuV),and can be effectively prevented by vaccination.In this study,a reverse genetic system of MuV that can facilitate the rational design of safer,more efficient mumps vaccine candidates is established.Methods MuV-S79 cDNA clone was assembled into a full-length plasmid by means of the GeneArtTM High-Order Genetic Assembly System,and was rescued via reverse genetic technology.RT-PCR,sequencing,and immunofluorescence assays were used for rMuV-S79 authentication.Viral replication kinetics and in vivo experimental models were used to evaluate the replication,safety,and immunogenicity of rMuV-S79.Results A full-length cDNA clone of MuV-S79 in the assembly process was generated by a novel plasmid assemble strategy,and a robust reverse genetic system of MuV-S79 was successfully established.The established rMuV-S79 strain could reach a high virus titer in vitro.The average viral titer of rMuV-S79 in the lung tissues was 2.68±0.14 log10PFU/g lung tissue,and rMuV-S79 group did not induce inflammation in the lung tissues in cotton rats.Neutralizing antibody titers induced by rMuV-S79 were high,long-lasting and could provide complete protection against MuV wild strain challenge.Conclusion We have established a robust reverse genetic system of MuV-S79 which can facilitate the optimization of mumps vaccines.rMuV-S79 rescued could reach a high virus titer and the safety was proven in vivo.It could also provide complete protection against MuV wild strain challenge.

Novel ACADVL variants resulting in mitochondrial defects in long-chain acyl-CoA dehydrogenase deficiency

The pathogenesis of very-long-chain acyl-CoA dehydrogenase(VLCAD)deficiency is highly heterogeneous and still unclear.Additional novel variants have been recently detected in the population.The molecular and cellular effects of these previously unreported variants are still poorly understood and require further characterization.To address this problem,we have evaluated the various functions and biochemical consequences of six novel missense variants that lead to mild VLCAD deficiency.Marked deficiencies in fatty acid oxidation(FAO)and other mitochondrial defects were observed in cells carrying one of these six variants(c.541 C>T,c.863 T>G,c.895 A>G,c.1238 T>C,c.1276 G>A,and c.1505 T>A),including reductions in mitochondrial respiratory-chain function and adenosine teriphosphate(ATP)production,and increased levels of mitochondrial reactive oxygen species(ROS).Intriguingly,higher apoptosis levels were found in cells carrying the mutant VLCAD under glucose-limited stress.Moreover,the stability of the mutant homodimer was disturbed,and major conformational changes in each mutant VLCAD structure were predicted by molecular dynamics(MD)simulation.The data presented here may provide valuable information for improving management of diagnosis and treatment of VLCAD deficiency and for a better understanding of the general molecular bases of disease variability.

Effect of maternal lipid profile,C-peptide,insulin,and HBA1c levels during late pregnancy on large-for-gestational age newborns

Background:Large-for-gestational age(LGA)newborns can increase the risk of metabolic syndrome.Previous studies have shown that the levels of maternal blood lipids,connecting peptide(C-peptide),insulin and glycosylated hemoglobin(HbA_(1c))were significantly different between LGA and appropriate-for-gestational age(AGA)newborns.This study aimed to determine the effect of the levels of maternal lipids,C-peptide,insulin,and HbA_(1c) during late pregnancy on LGA newborns.Methods:This study comprised 2790 non-diabetic women in late pregnancy.Among their newborns,2236(80.1%)newborns were AGA,and 554(19.9%)newborns were LGA.Maternal and neonatal characteristics were obtained from questionnaires and their case records.The levels of maternal fasting serum apolipoprotein A1(ApoA1),triglyceride(TG),total cholesterol(TC),high-density lipoprotein cholesterol(HDL-C),low-density lipoprotein cholesterol(LDL-C),C-peptide,insulin and blood HbA_(1c) were measured.The chi-square and Mann-Whitney U test were used to analyze categorical variables and continuous variables between the AGA and LGA groups,respectively.Binary logistic regression analysis was made to determine the independent risk factors for LGA newborns.Results:Maternal TG,C-peptide,insulin and HbA_(1c) levels were signifi cantly higher in the LGA group than in the AGA group(P<0.05).The LGA group had signifi cantly lower levels of maternal TC,HDL-C and LDL-C than the AGA group(P<0.05).After adjustment for confounding variables,including maternal age,pre-pregnancy body mass index,education,smoking,annual household income,amniotic fluid volume,gestational hypertension,newborn gender and gestational age at blood collection,high maternal TG levels remained signifi cantly associated with LGA newborns(P<0.05).Conclusion:High maternal TG level during late pregnancy is signifi cantly associated with LGA newborns.

Secondary genomic findings in the 2020 China Neonatal Genomes Project participants

Background During next generation sequencing(NGS)data interpretation in critically ill newborns,there is a potential for recognizing and reporting secondary findings(SFs).Early awareness of SFs may provide clues for disease prevention.In this study,we assessed the frequency of SFs in the China Neonatal Genomes Project(CNGP)participants.Methods A total of 2020 clinical exome sequencing(CES)datasets were screened for variants from a list of 59 genes recommended by the American College of Medical Genetics and Genomics(ACMG)for secondary findings reporting v2.0(ACMG SF v2.0).Identified variants were classified according to the evidence-based guidelines reached by a joint consensus of the ACMG and the Association for Molecular Pathology(AMP).Results Among the 2020 CES datasets,we identified 23 ACMG-reportable genes in 61 individuals,resulting in an overall frequency of SFs at 3.02%.A total of 53 unique variants were identified,including 35 pathogenic and 18 likely pathogenic variants.The common disease categories of SFs associated were cardiovascular and cancer disease.The SF results affected the medical management and follow-up strategy in 49(80.3%)patients.Conclusions We presented the frequency of SFs and their impact on clinical management strategies in CNGP participants.Our study demonstrated that SFs have important practical value in disease prevention and intervention at an early stage.

Attenuated MuV-S79 as vector stably expressing foreign gene

Background To describe mumps virus(MuV)used as a vector to express enhanced green fluorescent protein(EGFP)or red fluorescent protein(RFP)genes.Methods Molecular cloning technique was applied to establish the cDNA clones of recombinant mumps viruses(rMuVs).rMuVs were recovered based on our reverse genetic system of MuV-S79.The properties of rMuVs were determined by growth curve,plaque assay,fluorescent microscopy and determination of fluorescent intensity.Results Three recombinant viruses replicated well in Vero cells and similarly as parental rMuV-S79,expressed heterologous genes in high levels,and were genetically stable in at least 15 passages.Conclusion rMuV-S79 is a promising platform to accommodate foreign genes like marker genes,other antigens and immunomodulators for addressing various diseases.

Management of children with COVID-19: experiences from China

The coronavirus disease 2019 (COVID-19) global pandemic caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is a major public health event.As a special population,children have special respiratory tract structure characteristics,immature immune system,and susceptibility to respiratory virus infections.Therefore,it is highly important for clinicians to treat the infected children cautiously despite most pediatric patients have milder symptoms and better prognosis compared with the adult patients.

A high-fat high-energy diet influences hepatic CYP3A expression and activity in low-birth-weight developing female rats

Background:The objective of this study was to investigate the effects of a high-fat,high-energy(HFHE)diet on the hepatic expression of CYP3A in low-birthweight developing female rats.Methods:Pregnant rats were divided into nourished and undernourished groups.The offspring of the nourished rats were defined as the normal-birth-weight(NBW)group,and those of undernourished rats were defined as the low-birth-weight(LBW)group.According to their birth weights and diets,the rats were subdivided into the following four groups:NBW-normal diet(NN)group;NBW-HFHE(NH)group;LBW-normal diet(LN)group;and LBW-HFHE(LH)group.Liver samples were isolated on days 3,7,14,21,28,56 and 84 after birth.Results:The CYP3A1 mRNA levels in the LH group on days 3,56 and 84 were significantly higher than those of the NN group(P<0.05).CYP3A1 expression was significantly higher in the LH group than that in the NH group on days 21,28 and 84(P<0.05).CYP3A1 mRNA expression was higher in the LH group than that in the LN group on days 3 and 21(P<0.05).No zonal CYP3A1 expression pattern was observed in the LH developmental group.The LH group had significantly higher mean activity than the LN group on days 7,14,28 and 56.Conclusion:Our results indicated that an HFHE diet can result in alterations of CYP3A expression in a developmental LBW rat model.

Expert consensus on COVID-19 vaccination in children

Coronavirus disease 2019(COVID-19)is a public health disaster that has not been encountered for a hundred years.On January 12,2020,the World Health Organization(WHO)confirmed and named the coronavirus which caused unexplained pneumonia as 2019 novel coronavirus(2019-nCoV).Since then,the disease caused by this virus had been named as coronavirus disease 2019(COVID-19).On February 11,2020,the International Committee on Taxonomy of Viruses announced that the English name of the novel coronavirus was severe acute respiratory syndrome coronavirus 2(SARS-CoV-2)[1].At present,SARS-CoV-2 infection is still rampant worldwide.As of September 10,2021,there were about 222 million confirmed cases of COVID-19 and more than 4.5 million deaths worldwide[2].According to the American Centers for Disease Control and Prevention,by July 29,2021,4.19 million pediatric COVID-19 cases had been reported in the United States。

Global Pediatric Pulmonology Alliance(GPPA)proposal for COVID-19 vaccination in children

Coronavirus disease 2019(COVID-19)remains a global epidemic.As of August 18,2021,the number of reported cases has exceeded 207 million globally,with more than 4.3 million deaths.COVID-19 has brought devastating losses to human society.The overall crude mortality rate is 1-3%.Although pediatric deaths from COVID-19 are rare,they do occur,as over 9,000 children have died from COVID-19 globally to date[1].With the gradual and broad application of COVID-19 vaccines around the world,the rising proportion of cases among children and unvaccinated young adults demands attention.According to World Health Organization surveillance data.

Journal’s responsibility in maintaining scientifc integrity

Scientifc integrity has been regarded as a priority in scientifc development in China[1].The Chinese governmental agencies have paid unprecedented attentions on promoting scientifc integrity in recent years.In May 2018,the Communist Party of China Central Committee and the State Council issued guidelines on promoting scientifc integrity[2].Ever-harsher punishments for researchers who committing scientifc misconduct were introduced by the Chinese government[3].In November,2018,43 penalties for major academic misconduct were endorsed by 41 national government agencies.Meanwhile,the Ministry of Science and Technology of China(MOST)were established a notifcation system for reporting cases involving in scientifc misconduct and the related penalties publicly.

Social responsibilities of a pediatric journal:considerations and future directions

Dr.Lundberg,the former editor of JAMA,elucidated many social responsibilities for medical journal editing as early as 1987[1].During the pandemic,a medical journal should highlight its social responsibilities in publishing high-qual-ity contents,promoting education to the health care pro-viders and providing readers with the timely and accurate information[1].At the time of this editorial published,the global cases of coronavirus disease 2019(COVID-19)had surpassed 85 million.The pandemic and its resulting eco-nomic,health,and educational disruptions have affected all aspects of the youth's lives[2].Quarantine and social isola-tion,increased risks of child abuse and neglect,financially and psychologically stressed family members have led to negative mental outcomes in children and adolescents.