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Nicotinamide adenine dinucleotide treatment confers resistance to neonatal ischemia and hypoxia:effects on neurobehavioral phenotypes

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Neural Regeneration Research 2024年第12期19卷 2760-2772页

作者： Xiaowen Xu Xinxin Wang Li Zhang Yiming Jin Lili Li Meifang Jin Lianyong Li Hong Ni Division of Brain science Institute of Pediatric ResearchChildren’s Hospital of Soochow UniversitySuzhouJiangsu ProvinceChina Department of Pediatric Orthopedics Shengjing Hospital of China Medical UniversityShenyangLiaoning ProvinceChina

Neonatal hypoxic-ischemic brain injury is the main cause of hypoxic-ischemic encephalopathy and cerebral palsy.Currently,there are few effective clinical treatments for neonatal hypoxic-ischemic brain injury.Here,we investigated the neuroprotective and molecular mechanisms of exogenous nicotinamide adenine dinucleotide,which can protect against hypoxic injury in adulthood,in a mouse model of neonatal hypoxic-ischemic brain injury.In this study,nicotinamide adenine dinucleotide(5 mg/kg)was intraperitoneally administered 30 minutes befo re surgery and every 24 hours thereafter.The results showed that nicotinamide adenine dinucleotide treatment improved body weight,brain structure,adenosine triphosphate levels,oxidative damage,neurobehavioral test outcomes,and seizure threshold in experimental mice.Tandem mass tag proteomics revealed that numerous proteins were altered after nicotinamide adenine dinucleotide treatment in hypoxic-ischemic brain injury mice.Parallel reaction monitoring and western blotting confirmed changes in the expression levels of proteins including serine(or cysteine)peptidase inhibitor,clade A,member 3N,fibronectin 1,5'-nucleotidase,cytosolic IA,microtubule associated protein 2,and complexin 2.Proteomics analyses showed that nicotinamide adenine dinucleotide ameliorated hypoxic-ischemic injury through inflammation-related signaling pathways(e.g.,nuclear factor-kappa B,mitogen-activated protein kinase,and phosphatidylinositol 3 kinase/protein kinase B).These findings suggest that nicotinamide adenine dinucleotide treatment can improve neurobehavioral phenotypes in hypoxic-ischemic brain injury mice through inflammation-related pathways.

关键词： brain injury cerebral palsy hypoxia hypoxic-ischemic brain injury inflammation neuroprotection nicotinamide adenine dinucleotide neonate nicotinamide adenine dinucleotide proteomics

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

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World Journal of Pediatrics 2024年第1期20卷 11-25页

作者： Xian-Li Zhang Xi Zhang Wang Hua Zheng-De Xie Han-Min Liu Hai-Lin Zhang Bi-Quan Chen Yuan Chen Xin sun Yi Xu sai-Nan shu shun-Ying Zhao Yun-Xiao shang Ling Cao Yan-Hui Jia Luo-Na Lin Jiong Li Chuang-Li Hao Xiao-Yan Dong Dao-Jiong Lin Hong-Mei Xu De-Yu Zhao Mei Zeng Zhi-Min Chen Li-su Huang Department of Infectious Disease Children's HospitalZhejiang University School of Medicine3333 Binsheng RoadBinjiang DistrictHangzhou 310052China Clinical Research Unit Xin Hua Hospital Affiliated to Shanghai Jiao Tong University School of MedicineShanghaiChina Beijing Pediatric Research Institute Beijing Children's HospitalCapital Medical UniversityBeijingChina Department of Pediatric Pulmonology West China Second University HospitalSichuan UniversityChengduChina Department of Pediatric Pulmonology the Second Affiliated Hospital&Yuying Children's HospitalWenzhou Medical UniversityWenzhouChina Department of Infectious Disease Anhui Provincial Children's HospitalHefeiChina Department of Pediatrics the Second Hospital of Hebei Medical UniversityShijiazhuangChina Department of Pediatrics Xijing Hospitalthe Fourth Military Medical UniversityXi'anChina Department of Infectious Disease Guangzhou Women and Children's Medicine CenterGuangzhou Medicine UniversityGuangzhouChina Department of Pediatrics Tongji HospitalTongji Medical CollegeHuazhong University of Science and TechnologyWuhanChina Department of Respiratory Disease Beijing Children's HospitalCapital Medical UniversityBeijingChina Department of Pediatric Respiratory Shengjing Hospital of China Medical UniversityShenyangChina Respiratory Department Children's Hospital Affiliated to Capital Institute of PediatricsBeijingChina Department of Clinical Epidemiology Aarhus UniversityAarhusDenmark Department of Respirology Children's Hospital of Soochow UniversitySuzhouChina Department of Respiratory Children's Hospital of ShanghaiChildren's Hospital Affiliated to Shanghai Jiao Tong University School of MedicineShanghaiChina Department of Infectious Disease Hainan Women and Children's Medical CenterHaikouChina Department of Infectious Disease Children's Hospital of Chongqing Medical UniversityChongqingChina Department of Respiratory Children's Hospital of Nanjing Medical UniversityNanjingChina Department of Infectious Di

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.

关键词： Consensus prevention Respiratory syncytial virus Treatment

Current status of cognition and skin care behavior in adolescent patients with acne:A survey in China

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Chinese Medical Journal 2024年第4期137卷 476-477页

作者： Jing Tian Hong shu Qiufang Qian Zhong shen Chunyu Zhao Li song Ping Li Xiuping Han Hua Qian Jinping Chen Hua Wang Lin Ma Yuan Liang Department of Dermatology Beijing Children’s HospitalCapital Medical UniversityNational Center for Children’s HealthBeijing 100045China Department of Dermatology Kunming Children’s HospitalKunmingYunnan 650034China Department of Dermatology Children’s Hospital of ShanghaiChildren’s Hospital Affiliated to Shanghai Jiao Tong University School of MedicineShanghai 200127China Loreal China Co. LtdShanghai 200040China Department of Dermatology Henan Children’s HospitalChildren’s Hospital Affiliated to Zhengzhou UniversityZhengzhou Hospital Beijing Children’s HospitalZhengzhou Children’s HospitalZhengzhouHenan 450052China Department of Dermatology Shenzhen Children’s HospitalShenzhenGuangdong 518026China Department of Dermatology Shengjing Hospital of China Medical UniversityShenyangLiaoning 110004China Department of Dermatology Children’s Hospital of Soochow UniversitySuzhouJiangsu 215025China Department of Dermatology Guangzhou Women and Children's Medical CenterGuangzhouGuangdong 510623China Department of Dermatology Children’s Hospital of Chongqing Medical UniversityChongqing 400014China

To the Editor:Acne vulgaris(AV)is a common inflammatory skin condition.Population-based epidemiological studies have reported associations between dietary habits,lifestyle factors,family history,and the occurrence and development of acne.^([1–4])This study investigated the skincare behavior and cognition of patients with AV regarding predisposing factors using a designed electronic questionnaire.

关键词： patients dietary behavior

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Function and dysfunction of GEMIN5:understanding a novel neurodevelopmental disorder

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Neural Regeneration Research 2024年第11期19卷 2377-2386页

作者： Charles H.Nelson Udai B.Pandey Department of Pediatrics Division of Child NeurologyChildren’s Hospital of PittsburghUniversity of Pittsburgh Medical CenterPittsburghPAUSA children’s Neuroscience Institute Children’s Hospital of PittsburghUniversity of Pittsburgh Medical CenterPittsburghPAUSA

The recent identification of a neurodevelopmental disorder with cerebellar atrophy and motor dysfunction(NEDCAM)has resulted in an increased interest in GEMIN5,a multifunction RNA-binding protein.As the largest member of the survival motor neuron complex,GEMIN5 plays a key role in the biogenesis of small nuclear ribonucleoproteins while also exhibiting translational regulatory functions as an independent protein.Although many questions remain regarding both the pathogenesis and pathophysiology of this new disorder,considerable progress has been made in the brief time since its discovery.In this review,we examine GEMIN5 within the context of NEDCAM,focusing on the structure,function,and expression of the protein specifically in regard to the disorder itself.Additionally,we explore the current animal models of NEDCAM,as well as potential molecular pathways for treatment and future directions of study.This review provides a comprehensive overview of recent advances in our understanding of this unique member of the survival motor neuron complex.

关键词： cerebellar atrophy GEMIN5 neurodevelopmental disorder neurological disease sMN complex

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severe pediatric COVID‑19:a review from the clinical and immunopathophysiological perspectives

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World Journal of Pediatrics 2024年第4期20卷 307-324页

作者： Yi‑Kan sun Can Wang Pei‑Quan Lin Lei Hu Jing Ye Zhi‑Gang Gao Ru Lin Hao‑Min Li Qiang shu Li‑su Huang Lin‑Hua Tan children's hospital Zhejiang University School f MedicineHangzhou 310052China The second Affiliated hospital Zhejiang University School of MedicineHangzhou 310030China surgical Intensive Care Unit Children’s HospitalZhejiang University School of MedicineHangzhou 310052China Department of General surgery Children’s HospitalZhejiang University School of MedicineHangzhou 310052China Department of Cardiopulmonary and Extracorporeal Life support Children’s HospitalZhejiang University School of MedicineHangzhou 310052China Clinical Data Center Children’s HospitalZhejiang University School of MedicineHangzhou 310052China Department of Cardiac surgery Children’s HospitalZhejiang University School of MedicineHangzhou 310052China National Clinical Research Center for Child Health Children’s HospitalZhejiang University School of MedicineHangzhou 310052China Department of Infectious Diseases Children’s HospitalZhejiang University School of MedicineHangzhou 310052China

Background Coronavirus disease 2019(COVID-19)tends to have mild presentations in children.However,severe and critical cases do arise in the pediatric population with debilitating systemic impacts and can be fatal at times,meriting further attention from clinicians.Meanwhile,the intricate interactions between the pathogen virulence factors and host defense mechanisms are believed to play indispensable roles in severe COVID-19 pathophysiology but remain incompletely understood.Data sources A comprehensive literature review was conducted for pertinent publications by reviewers independently using the PubMed,Embase,and Wanfang databases.searched keywords included“COVID-19 in children”,“severe pediatric COVID-19”,and“critical illness in children with COVID-19”.Results Risks of developing severe COVID-19 in children escalate with increasing numbers of co-morbidities and an unvaccinated status.Acute respiratory distress stress and necrotizing pneumonia are prominent pulmonary manifestations,while various forms of cardiovascular and neurological involvement may also be seen.Multiple immunological processes are implicated in the host response to COVID-19 including the type I interferon and inflammasome pathways,whose dysregulation in severe and critical diseases translates into adverse clinical manifestations.Multisystem inflammatory syndrome in children(MIs-C),a potentially life-threatening immune-mediated condition chronologically associated with COVID-19 exposure,denotes another scientific and clinical conundrum that exemplifies the complexity of pediatric immunity.Despite the considerable dissimilarities between the pediatric and adult immune systems,clinical trials dedicated to children are lacking and current management recommendations are largely adapted from adult guidelines.Conclusions severe pediatric COVID-19 can affect multiple organ systems.The dysregulated immune pathways in severe COVID-19 shape the disease course,epitomize the vast functional diversity of the pediatric immune system and highlight the immun

关键词： Immunopathophysiology MIs-C Pediatric critical care severe pediatric COVID-19

spotlight on eltrombopag concentration in pediatric immune thrombocytopenia: A single-center observational study in China

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儿科学研究(英文) 2024年第1期8卷 44-52页

作者： Dong shuyue Wang Zhifa Wang Nan Ma Jingyao Meng Jinxi sun Yixin Cheng Xiaoling Wu Runhui Hematology Oncology Center Beijing Children’s Hospital Capital Medical University National Center for Children’s Health Beijing China Department of Pharmacy Beijing Children’s Hospital Capital Medical University National Center for Children’s Health Beijing China

Importance: Eltrombopag has been recommended for pediatric immune thrombocytopenia (ITP). Response and adverse drug reactions (ADRs) varied widely between individuals, even at the same dose of eltrombopag. The appropriate eltrombopag concentration in ITP has not been reported.Objective: This study aims to explore the appropriate eltrombopag concentration in pediatric ITP.Methods: This was a single-center, prospective cohort study. children diagnosed with refractory persistent/chronic ITP and platelet count st 2 months. Concentration was detected by high-performance liquid chromatography-mass spectrometry at least 2 weeks after eltrombopag. The clinical characteristics-concentration, concentration-response, and concentration-ADRs were analyzed.Results: A total of 30 patients were enrolled, comprising 13 males and 17 females, with a median age of 72 (45-94) months. The median dose and concentration were 1.39 (1.09-1.56) mg/kg and 2.70 (2.25-4.13) mg/L, respectively. Of the enrolled patients, 14 responded to treatment, whereas 16 did not. Additionally, five experienced adverse drug reactions. No linear correlation was observed between eltrombopag concentration and clinical characteristics. The concentration was lower in the response group than in the nonresponse group, but there was no significant difference (t = 0.755,P = 0.457). Patients who experienced ADRs had a higher concentration than those without ADRs (t = 2.538,P = 0.017). The area under the receiver operating characteristic curve of ADRs was 0.78 (95% confidence interval: 0.56-1.00). Youden’s index identified the cutoff point as 4.33 mg/L, with a sensitivity of 88% and a specificity of 60%. Logistic regression analysis demonstrated that a higher platelet count before eltrombopag predicted a favorable response.Interpretation: Eltrombopag proves efficacious and well-tolerated for treating pediatric ITP. However, prolonged and high-dose administration may increase the likelihood of ADRs. Thus

关键词： Concentration Efficacy Eltrombopag Immune thrombocytopenia Pediatrics safety

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

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World Journal of Pediatrics 2024年第3期20卷 259-271页

作者： Yi-Long Wang Meng-Ying Zhu Zhe-Feng Yuan Xiao-Yan Ren Xiao-Tong Guo Yi Hua Lu Xu Cong-Ying Zhao Li-Hua Jiang Xin Zhang Guo-Xia sheng Pei-Fang Jiang Zheng-Yan Zhao Feng Gao Department of Neurology Children's HospitalZhejiang University School of MedicineHangzhou 310052China children's hospital Zhejiang University School of MedicineHangzhou 310052China children's hospital National Clinical Research Center for Child HealthZhejiang University School of MedicineHangzhou 310052China

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.

关键词： Acute disseminated encephalomyelitis Cerebrospinal fluid Complement cascades Myelin oligodendrocyte glycoprotein-associated disease Proteomics

X-box binding protein 1 caused an imbalance in pyroptosis and mitophagy in immature rats with di-(2-ethylhexyl)phthalate-induced testis toxicity

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Genes & Diseases 2024年第2期11卷 935-951页

作者： Yifan Hong Xiazhu Zhou Qi Li Jing Chen Yuexin Wei Chunlan Long Lianju shen Xiangqin Zheng Dinggang Li Xia Wang Chenjun Yu shengde Wu Guanghui Wei Department of Urology Children's Hospital of Chongqing Medical UniversityChongqing 400014China Pediatric Research Institute Children's Hospital of Chongqing Medical UniversityChongqing 400014China Chongqing Key Laboratory of children Urogenital Development and Tissue Engineering Children's Hospital of Chongqing Medical UniversityChongqing 400014China Chongqing Key Laboratory of Pediatrics Children's Hospital of Chongqing Medical UniversityChongqing 400014China Ministry of Education Key Laboratory of Child Development and Disorders Children's Hospital of Chongqing Medical UniversityChongqing 400014China National Clinical Research Center for Child Health and Disorders Children's Hospital of Chongqing Medical UniversityChongqing 400014China China International science and Technology Cooperation Base of Child Development and Critical Disorders Children's Hospital of Chongqing Medical UniversityChongqing 400014China

As a widely used plasticizer,di-(2-ethylhexyl)phthalate(DEHP)is known to induce significant testicular injury.However,the potential mechanism and effects of pubertal exposure to DEHP on testis development remain unclear.In vivo,postnatal day(PND)21 male rats were gavaged with 0,250,and 500 mg/kg DEHP for ten days.Damage to the seminiferous epithelium and disturbed spermatogenesis were observed after DEHP exposure.Meanwhile,oxidative stress-induced injury and pyroptosis were activated.Both endoplasmic reticulum(ER)stress and mitophagy were involved in this process.Monoethylhexyl phthalate(MEHP)was used as the biometabolite of DEHP in vitro.The GC-1 and GC-2 cell lines were exposed to 0,100μM,200μM,and 400μM MEHP for 24 h.Reactive oxygen species(ROs)generation,oxidative stress damage,ER stress,mitophagy,and pyroptosis were significantly increased after MEHP exposure.The ultrastructure of the ER and mitochondria was destroyed.X-box binding protein 1(XBP1)was observed to be activated and translocated into the nucleus.ROs generation was inhibited by acetylcysteine.The levels of antioxidative stress,ER stress,mitophagy,and pyroptosis were decreased as well.After the administration of the ER stress inhibitor 4-phenyl-butyric acid,both mitophagy and pyroptosis were inhibited.Toyocamycin-induced XBP1 down-regulation decreased the levels of mitophagy and pyroptosis.The equilibrium between pyroptosis and mitophagy was disturbed by XBP1 accumulation.In summary,our findings confirmed that DEHP induced a ROs-mediated imbalance in pyroptosis and mitophagy in immature rat testes via XBP1.Moreover,XBP1 might be the key target in DEHP-related testis dysfunction.

关键词： DEHP Mitophagy Pyroptosis Testicular development XBP1

Irisin-loaded electrospun core-shell nanofibers as calvarial periosteum accelerate vascularized bone regeneration by activating the mitochondrial sIRT3 pathway

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Regenerative Biomaterials 2024年第1期3卷 44-57页

作者： Xi Hua Mingzhuang Hou Lei Deng Nanning Lv Yong Xu Xuesong Zhu Huilin Yang Qin shi Hao Liu Fan He Department of Orthopaedics The First Affiliated Hospital of Soochow UniversitySoochow UniversitySuzhou 215006China Orthopaedic Institute Suzhou Medical CollegeSoochow UniversitySuzhou 215000China Department of Orthopedics Suzhou Wuzhong People’s HospitalSuzhouJiangsu Province 215128China Department of Orthopedic surgery Lianyungang Clinical College of Xuzhou Medical UniversityLianyungang 222003China

The scarcity of native periosteum poses a significant clinical barrier in the repair of critical-sized bone defects.The challenge of enhancing regenerative potential in bone healing is further compounded by oxidative stress at the fracture site.However,the introduction of artificial periosteum has demonstrated its ability to promote bone regeneration through the provision of appropriate mechanical support and controlled release of proosteogenic factors.In this study,a poly(L-lactic acid)(PLLA)/hyaluronic acid(HA)-based nanofibrous membrane was fabricated using the coaxial electrospinning technique.The incorporation of irisin into the core-shell structure of PLLA/HA nanofibers(PLLA/HA@Irisin)achieved its sustained release.In vitro experiments demonstrated that the PLLA/HA@Irisin membranes exhibited favorable biocompatibility.The osteogenic differentiation of bone marrow mesenchymal stem cells(BMMsCs)was improved by PLLA/HA@Irisin,as evidenced by a significant increase in alkaline phosphatase activity and matrix mineralization.Mechanistically,PLLA/HA@Irisin significantly enhanced the mitochondrial function of BMMsCs via the activation of the sirtuin 3 antioxidant pathway.To assess the therapeutic effectiveness,PLLA/HA@Irisin membranes were implanted in situ into critical-sized calvarial defects in rats.The results at 4 and 8 weeks post-surgery indicated that the implantation of PLLA/HA@Irisin exhibited superior efficacy in promoting vascularized bone formation,as demonstrated by the enhancement of bone matrix synthesis and the development of new blood vessels.The results of our study indicate that the electrospun PLLA/HA@Irisin nanofibers possess characteristics of a biomimetic periosteum,showing potential for effectively treating critical-sized bone defects by improving the mitochondrial function and maintaining redox homeostasis of BMMsCs.

关键词： periosteum irisin mitochondrial function critical-sized bone defect redox homeostasis