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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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Emerging role of regulated cell death in intestinal failure-associated liver disease

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Hepatobiliary & Pancreatic Diseases International 2024年第3期23卷 228-233页

作者： Si-Yang Cheng Lu Jiang Ying Wang Wei Cai Department of pediatric Surgery Xinhua HospitalSchool of MedicineShanghai Jiao Tong UniversityShanghai 200092China Shanghai Key Laboratory of pediatric Gastroenterology and Nutrition Shanghai 200092China Shanghai institute for pediatric research Shanghai 200092China Division of pediatric Gastroenterology and Nutrition Xinhua HospitalSchool of MedicineShanghai Jiao Tong UniversityShanghai 200092China

Intestinal failure-associated liver disease(IFALD)is a common complication of long-term parenteral nutrition that is associated with significant morbidity and mortality.It is mainly characterized by cholestasis in children and steatohepatitis in adults.Unfortunately,there is no effective approach to prevent or reverse the disease.Regulated cell death(RCD)represents a fundamental biological paradigm that determines the outcome of a variety of liver diseases.Nowadays cell death is reclassified into several types,based on the mechanisms and morphological phenotypes.Emerging evidence has linked different modes of RCD,such as apoptosis,necroptosis,ferroptosis,and pyroptosis to the pathogenesis of liver diseases.Recent studies have shown that different modes of RCD are present in animal models and patients with IFALD.Understanding the pathogenic roles of cell death may help uncover the underlying mechanisms and develop novel therapeutic strategies in IFALD.In this review,we discuss the current knowledge on how RCD may link to the pathogenesis of IFALD.We highlight examples of cell death-targeted interventions aiming to attenuate the disease,and provide perspectives for future basic and translational research in the field.

关键词： Parenteral nutrition Apoptosis Necroptosis Cholestasis Steatosis

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Therapeutic potential of urine-derived stem cells in renal regeneration following acute kidney injury:A comparative analysis with mesenchymal stem cells

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World Journal of Stem Cells 2024年第5期16卷 525-537页

作者： Fang Li Bin Zhao Lei Zhang Guo-Qing Chen Li Zhu Xiao-Ling Feng Meng-Jia Gong Cheng-Chen Hu Yuan-Yuan Zhang Ming Li Yong-Qiang Liu Department of General Surgery Chongqing General HospitalChongqing 401147China Department of pediatric research institute Children’s Hospital of Chongqing Medical UniversityChongqing 401147China

BACKGROUND Acute kidney injury(AKI)is a common clinical syndrome with high morbidity and mortality rates.The use of pluripotent stem cells holds great promise for the treatment of AKI.Urine-derived stem cells(USCs)are a novel and versatile cell source in cell-based therapy and regenerative medicine that provide advantages of a noninvasive,simple,and low-cost approach and are induced with high multidifferentiation potential.Whether these cells could serve as a potential stem cell source for the treatment of AKI has not been determined.METHODS Stem cell markers with multidifferentiation potential were isolated from human amniotic fluid.AKI severe combined immune deficiency(SCID)mice models were induced by means of an intramuscular injection with glycerol.USCs isolated from human-voided urine were administered via tail veins.The functional changes in the kidney were assessed by the levels of blood urea nitrogen and serum creatinine.The histologic changes were evaluated by hematoxylin and eosin staining and transferase dUTP nick-end labeling staining.Meanwhile,we compared the regenerative potential of USCs with bone marrow-derived mesenchymal stem cells(MSCs).RESULTS Treatment with USCs significantly alleviated histological destruction and functional decline.The renal function was rapidly restored after intravenous injection of 5×105 human USCs into SCID mice with glycerol-induced AKI compared with injection of saline.Results from secretion assays conducted in vitro demonstrated that both stem cell varieties released a wide array of cytokines and growth factors.This suggests that a mixture of various mediators closely interacts with their biochemical functions.Two types of stem cells showed enhanced tubular cell prolif-eration and decreased tubular cell apoptosis,although USC treatment was not more effective than MSC treatment.We found that USC therapy significantly improved renal function and histological damage,inhibited inflammation and apoptosis processes in the kidney,and promoted tubular epithelial proliferatio

关键词： Urine-derived stem cells Regenerative medicine Acute kidney injury Renal function recovery Cell therapy

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The current situation of semen analysis in China,based on a survey of 296 laboratories

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Asian Journal of Andrology 2024年第2期26卷 220-221页

作者： Long-Long Fu Ying Liu Xiao-Wei Wang Fang Zhou Ying Guo Wen-Hong Lu Yi-Qun Gu National Health Commission Key Laboratory of Male Reproductive Health Reproductive Health Research CenterNational Research Institute for Family PlanningBeijing 100081China institute of pediatric research Children's Hospitalof Soochow UniversitySuzhou 215025China

Dear Editor,Semen analysis is a basic test to assess male fertility and is a fundamental test in assisted reproductive technology.From the first publication of World Health Organization(WHO)Laboratory Manual of Human Semen and Sperm-Cervical Mucus Interaction in 1980,to the publication of the WHO Manual,6th edition in 2021,these 40 years have been recognized as providing a global standard that is widely used in research and clinical laboratories worldwide.The WHO Manual,6th edition in Chinese,which we have been authorized by the WHO to translate,will be published soon.

关键词： technology. analysis translate

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Longitudinal changes in body weight of breastfeeding mothers in the first year after delivery and its relationship with human milk composition:a combined longitudinal and cross-sectional cohort study

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Food Science and Human Wellness 2024年第1期13卷 254-264页

作者： Huijuan Ruan Yajie Zhang Qingya Tang Xuan Zhao Xuelin Zhao Yi Xiang Wei Geng Yi Feng Wei Cai Department of Clinical Nutrition Xinhua Hospital Affiliated to Shanghai Jiao Tong University School of MedicineShanghai 200092China Shanghai Key Laboratory of pediatric Gastroenterology and Nutrition Shanghai Institute of Pediatric ResearchShanghai 200092China Department of pediatric Surgery Xinhua Hospital Affiliated to Shanghai Jiao Tong University School of MedicineShanghai 200092China

Objective:Postpartum weight retention(PPWR)is a common problem among women after childbirth.The main objectives of this study are to understand the changes in body weight of breastfeeding mothers during long-term follow-up and preliminarily explore the relationship between maternal body weight and human milk composition,including macronutrients,leptin,and adiponectin.Methods:The study included a longitudinal cohort(122 mothers),and a cross-sectional cohort(37 mothers).The human milk,maternal weight,and dietary surveys were collected in the longitudinal cohort at different follow-up time points(1-14 days postpartum,2-4 months postpartum,5-7 months postpartum,and 12-17 months postpartum).The maternal body weight was analyzed using the responses in the survey questionnaires.A milk analyzer based on the mid-infrared spectroscopy(MIRS)was used to determine milk composition,and nutrition analysis software evaluated dietary intakes.In the cross-sectional cohort,participating mothers were asked to provide blood and human milk samples and pertinent information related to maternal body composition.Maternal body composition was measured by bioelectrical impedance analysis(BIA),while ELISA analyzed leptin and adiponectin in milk and serum.Results:At 5-7 months postpartum,the PPWR of breastfeeding mothers was(2.46±3.59)kg.At 12-17 months postpartum,the PPWR was(0.98±4.06)kg.PPWR was found to be negatively correlated with milk fat content within 14 days postpartum and positively correlated at 2-4 months postpartum.In addition,the maternal weight and body muscle mass were positively correlated with leptin and adiponectin in milk.Plasma leptin was positively correlated with the mother’s body weight,body mass index(BMI),FAT percentage,and body fat mass,while plasma adiponectin did not correlate with any parameter.The results also indicate that the PPWR did not correlate with leptin and adiponectin in plasma or milk.Conclusions:Breastfeeding mothers may retain considerable weight gain one year after delivery.Human milk composition

关键词： Human milk Milk composition Body weight Body mass index(BMI) Weight gain Postpartum weight retention

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Muscle strength deficits are associated with low bone mineral density in young pediatric cancer survivors:The iBoneFIT project

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Journal of Sport and Health Science 2024年第3期13卷 419-427页

作者： Andres Marmol-Perez Jose J.Gil-Cosano Esther Ubago-Guisado Francisco J.Llorente-Cantarero Juan Francisco Pascual-Gázquez Kirsten K.Ness Vicente Martinez-Vizcaino Jonatan R.Ruiz Luis Gracia-Marco Department of Physical Education and Sports Faculty of Sport SciencesSport and Health University Research Institute(iMUDS)University of GranadaGranada 18011Spain Department of Epidemiology and Cancer Control St.Jude Children's Research HospitalMemphisTN 38105USA Department of Communication and Education Loyola University AndalusiaSeville 41704Spain Biosanitary research institute ibs.GranadaGranada 18012Spain Maimonides Biomedical research institute of Cordoba(IMIBIC) Cordoba 14004Spain CIBEROBN Biomedical Research Networking Center for Physiopathology of Obesity and NutritionCarlos III Health InstituteMadrid 28029Spain Department of Specific Didactics Faculty of EducationUniversity of CordobaCordoba 14071Spain pediatric and adolescent hematology and oncology service Pediatrics and Pediatric Surgery Clinical Management UnitVirgen de las Nieves University HospitalGranada 18014Spain Health and Social research Center Universidad de Castilla-La ManchaCuenca 13001Spain

Background pediatric cancer survivors are at increased risk of muscle weakness and low areal bone mineral density(aBMD).However,the prevalence of muscle strength deficits is not well documented,and the associations of muscle strength with aBMD are unknown in this population.Therefore,this study aimed to investigate the prevalence of upper-and lower-body muscle strength deficits and to examine the associations of upper-and lower-body muscle strength with age-,sex,and race-specific aBMD Z-scores at the total body,total hip,femoral neck,and lumbar spine.Methods This cross-sectional study included 116 pediatric cancer survivors(12.1±3.3 years old,mean±SD;42.2%female).Upper-and lower-body muscle strength were assessed by handgrip and standing long jump test,respectively.Dual‑energy X‑ray absorptiometry was used to measure aBMD(g/cm2).Associations between muscle strength and aBMD were evaluated in multivariable linear regression models.Logistic regression was used to evaluate the contribution of muscle strength(1-decile lower)to the odds of having low aBMD(Z-score≤1.0).All analyses were adjusted for time from treatment completion,radiotherapy exposure,and body mass index.Results More than one-half of survivors were within the 2 lowest deciles for upper-(56.9%)and lower-body muscle strength(60.0%)in comparison to age-and sex-specific reference values.Muscle strength deficits were associated with lower aBMD Z-scores at all sites(B=0.133–0.258,p=0.001–0.032).Each 1-decile lower in upper-body muscle strength was associated with 30%–95%higher odds of having low aBMD Z-scores at all sites.Each 1-decile lower in lower-body muscle strength was associated with 35%–70%higher odds of having low aBMD Z-scores at total body,total hip,and femoral neck.Conclusion Muscle strength deficits are prevalent in young pediatric cancer survivors,and such deficits are associated with lower aBMD Z-scores at all sites.These results suggest that interventions designed to improve muscle strength in this vulnerable population may have the added ben

关键词： Bone health Childhood cancer DXA Lean mass Resistance training

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Complete separation of the urinary tract from proximal rectum during PSARP surgery: our experience with the novel technique

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World Journal of pediatric Surgery 2024年第1期7卷 66-69页

作者： Md Samiul Hasan Md Nazmul Islam Refoyez Mahmud Umama Huq Ashrarur Rahman pediatric Surgery Bangladesh Shishu Hospital and InstituteDhakaBangladesh

Anorectal malformation(ARM)is a frequently occurring surgical condition in neonates,with a prevalence of 1 in 4000 live births.'In boys with this anomaly,the rectum and urinary tract share a common wall for some distance,often ending up in fistulous communication.The goals of definite reconstruction are to separate the rectum from the urinary tract without injuring the urethra and mobilizing the rectum to the perineum within the muscle complex.Separating the rectum and the urinary tract is the most critical part of this operation and is associated with a significant risk of urinary tract injury.2-5 The original procedure described by Pena and Devries involves multiple stay sutures on the rectal mucosa just above the fistula,lifting the mucosa and continuing a submucosal dissection up to the prostate,where the entire thickness of the intestine can be separated from the urinary tract.

关键词： urinary rectum intestine

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COVID-19 and cardiac complications:Myocarditis and multisystem inflammatory syndrome in children

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World Journal of Cardiology 2024年第5期16卷 260-268页

作者： Muhammed Gunes Oner Ozdemir Department of pediatric Cardiology Research and Training Hospital of SakaryaAdapazarı54100SakaryaTürkiye Department of pediatric Allergy and Immunology Research and Training Hospital of SakaryaSakarya University Medical FacultyAdapazarı54100SakaryaTürkiye

Coronavirus is an important pathogen causing disease in humans and animals.At the end of 2019,an investigation into an increase in pneumonia cases in Wuhan,Hubei Province,China,found that the cause was a new coronavirus.This disease,which spread rapidly across China and caused an outbreak worldwide,resulted in a pandemic.Although this virus has previously been referred to as 2019-nCoV,which causes coronavirus disease 2019(COVID-19),later it was named severe acute respiratory syndrome coronavirus 2.Children were usually asymptomatic and rarely severely affected.In April 2020,reports from the United Kingdom indicated that children may have Kawasaki disease or a clinical condition similar to toxic shock syndrome.This clinical picture was later defined as multisystem inflammatory syndrome in children.Since then,similarly affected children as well as cases with other cardiac complications have been reported in other parts of the world.In this review,we aimed to evaluate COVID-19 in terms of cardiac involvement by reviewing the literature.

关键词： COVID-19 Cardiac complication Myocarditis Multisystem inflammatory syndrome in children SARS-CoV-2

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The roles of RACK1 in the pathogenesis of Alzheimer's disease

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Journal of Biomedical research 2024年第2期38卷 137-148页

作者： Wenting He Xiuyu Shi Zhifang Dong pediatric research institute Ministry of Education Key Laboratory of Child Development and DisordersNational Clinical Research Center for Child Health and DisordersChongqing Key Laboratory of Child Neurodevelopment and Cognitive DisordersChildren's Hospital of Chongqing Medical UniversityChongqing 400014China

The receptor for activated C kinase 1(RACK1)is a protein that plays a crucial role in various signaling pathways and is involved in the pathogenesis of Alzheimer's disease(AD),a prevalent neurodegenerative disease.RACK1 is highly expressed in neuronal cells of the central nervous system and regulates the pathogenesis of AD.Specifically,RACK1 is involved in regulation of the amyloid-β precursor protein processing through α-or β-secretase by binding to different protein kinase C isoforms.Additionally,RACK1 promotes synaptogenesis and synaptic plasticity by inhibiting N-methyl-D-aspartate receptors and activating gamma-aminobutyric acid A receptors,thereby preventing neuronal excitotoxicity.RACK1 also assembles inflammasomes that are involved in various neuroinflammatory pathways,such as nuclear factor-kappa B,tumor necrosis factor-alpha,and NOD-like receptor family pyrin domain-containing 3 pathways.The potential to design therapeutics that block amyloid-β accumulation and inflammation or precisely regulate synaptic plasticity represents an attractive therapeutic strategy,in which RACK1 is a potential target.In this review,we summarize the contribution of RACK1 to the pathogenesis of AD and its potential as a therapeutic target.

关键词： RACK1 Alzheimer's disease PKC amyloid-β synaptic plasticity neuroinflammation

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Mitophagy in neurodegenerative disease pathogenesis

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Neural Regeneration research 2024年第5期19卷 998-1005页

作者： Kan Yang Yuqing Yan Anni Yu Ru Zhang Yuefang Zhang Zilong Qiu Zhengyi Li Qianlong Zhang Shihao Wu Fei Li Department of Developmental and Behavioural pediatric&Child Primary Care Brain and Behavioural Research Unit of Shanghai Institute for Pediatric Research and MOE-Shanghai Key Laboratory for Children’s Environmental HealthXinhua HospitalShanghai Jiao Tong University School of MedicineShanghaiChina Center for Excellence in Brain Science and Intelligence Technology Institute of NeuroscienceState Key Laboratory of NeuroscienceCAS Key Laboratory of Primate NeurobiologyChinese Academy of SciencesShanghaiChina College of Materials and Chemical Engineering Hunan Institute of EngineeringXiangtanHunan ProvinceChina School of Medicine Yunnan UniversityKunmingYunnan ProvinceChina Songjiang research institute Shanghai Jiao Tong University School of MedicineShanghaiChina Neurosurgery Department Kunming Yenan HospitalKunmingYunnan ProvinceChina

Mitochondria are critical cellular energy resources and are central to the life of the neuron.Mitophagy selectively clears damaged or dysfunctional mitochondria through autophagic machinery to maintain mitochondrial quality control and homeostasis.Mature neurons are postmitotic and consume substantial energy,thus require highly efficient mitophagy pathways to turn over damaged or dysfunctional mitochondria.Recent evidence indicates that mitophagy is pivotal to the pathogenesis of neurological diseases.However,more work is needed to study mitophagy pathway components as potential therapeutic targets.In this review,we briefly discuss the characteristics of nonselective autophagy and selective autophagy,including ERphagy,aggrephagy,and mitophagy.We then introduce the mechanisms of Parkin-dependent and Parkin-independent mitophagy pathways under physiological conditions.Next,we summarize the diverse repertoire of mitochondrial membrane receptors and phospholipids that mediate mitophagy.Importantly,we review the critical role of mitophagy in the pathogenesis of neurodegenerative diseases including Alzheimer’s disease,Parkinson’s disease,and amyotrophic lateral sclerosis.Last,we discuss recent studies considering mitophagy as a potential therapeutic target for treating neurodegenerative diseases.Together,our review may provide novel views to better understand the roles of mitophagy in neurodegenerative disease pathogenesis.

关键词： Alzheimer’s disease amyotrophic lateral sclerosis autophagy mitochondria mitophagy mitophagy receptor Parkin Parkinson’s disease PINK1

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