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PCDH17 restricts dendritic spine morphogenesis by regulating ROCK2-dependent control of the actin cytoskeleton,modulating emotional behavior

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Zoological research 2024年第3期45卷 535-550页

作者： Laidong Yu Fangfang Zeng Mengshu Fan Kexuan Zhang Jingjing Duan Yalu Tan Panlin Liao Jin Wen Chenyu Wang Meilin Wang Jialong Yuan Xinxin Pang Yan Huang Yangzhou Zhang Jia-Da Li Zhuohua Zhang Zhonghua Hu Hunan Key Laboratory of Molecular Precision Medicine Department of Critical Care MedicineXiangya HospitalCentral South UniversityChangshaHunan 410008China Center for Medical Genetics and Hunan Key Laboratory of Medical Genetics School of Life SciencesCentral South UniversityChangshaHunan 410008China National Clinical research Center for Geriatric Disorders Xiangya HospitalCentral South UniversityChangshaHunan 410008China Hunan Provincial Clinical research Center for Critical Care Medicine Xiangya HospitalCentral South UniversityChangshaHunan 410008China Hunan Key Laboratory of Animal Models for Human Diseases School of Life SciencesCentral South UniversityChangshaHunan 410008China MOE Key Lab of Rare pediatric Diseases School of Life SciencesCentral South UniversityChangshaHunan 410008China Department of Neurosciences University of South China Medical SchoolHengyangHunan 421001China

Proper regulation of synapse formation and elimination is critical for establishing mature neuronal circuits and maintaining brain *** abnormalities,such as defects in the density and morphology of postsynaptic dendritic spines,underlie the pathology of various neuropsychiatric *** 17(PCDH17)is associated with major mood disorders,including bipolar disorder and ***,the molecular mechanisms by which PCDH17 regulates spine number,morphology,and behavior remain *** this study,we found that PCDH17 functions at postsynaptic sites,restricting the number and size of dendritic spines in excitatory *** overexpression of PCDH17 in the ventral hippocampal CA1 results in spine loss and anxiety-and depression-like behaviors in ***,PCDH17 interacts with actin-relevant proteins and regulates actin filament(F-actin)***,PCDH17 binds to ROCK2,increasing its expression and subsequently enhancing the activity of downstream targets such as LIMK1 and the phosphorylation of cofilin serine-3(Ser3).Inhibition of ROCK2 activity with belumosudil(KD025)ameliorates the defective F-actin organization and spine structure induced by PCDH17 overexpression,suggesting that ROCK2 mediates the effects of PCDH17 on F-actin content and spine ***,these findings reveal a novel mechanism by which PCDH17 regulates synapse development and behavior,providing pathological insights into the neurobiological basis of mood disorders.

关键词： Synapse development Dendritic spine Mood disorder Actin cytoskeleton Animal behavior

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Severe respiratory syncytial virus disease

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Journal of Intensive Medicine 2024年第04期04卷 405-416页

作者： Peña-López Y. Sabater-Riera J. Raj P. Microbiome research Laboratory (MRL) Department of Immunology University of Texas Southwestern Medical Center Dallas TX United States pediatric Critical Care Department Hospital Universitari Vall d'Hebron Barcelona Spain Global Health eCore Vall d'Hebron Institute of Research Barcelona Spain Intensive Care Department Servei de Medicina Intensiva IDIBELL-Hospital Universitari de Bellvitge L´Hospitalet de Llobregat Barcelona Spain Bellvitge Biomedical research Institute (IDIBELL) L'Hospitalet de Llobregat Barcelona Spain

The burden of respiratory syncytial virus (RSV) disease is widely recognized. Main risk factors for severe disease, such as extreme ages, chronic cardiopulmonary conditions, and immunosuppression, typically coincide with poorer outcomes. While the majority of RSV hospitalizations involve healthy children, a higher proportion of hospitalized adults with underlying conditions need intensive care. Presently, treatment primarily consists of supportive measures. RSV-induced wheezing should be distinguished from respiratory tract thickening, without response to bronchodilators. Obstructive RSV disease frequently overlaps with viral pneumonia. Non-invasive mechanical ventilation and high-flow oxygen therapy represented significant advancements in the management of severe RSV disease in children and may also hold considerable importance in specific phenotypes of RSV disease in adults. Most severe infections manifest with refractory hypoxemia necessitating more advanced ventilatory support and/or extracorporeal membrane oxygenation therapy. While bacterial co-infection rates are low, they have been associated with worse outcomes. Antibiotic prescription rates are high. Accurately diagnosing bacterial co-infections remains a challenge. Current evidence and antibiotic stewardship policies advise against indiscriminate antibiotic usage, even in severe cases. The role of currently developing antiviral therapies in severe RSV disease will be elucidated in the coming years, contingent upon the success of new vaccines and immune passive strategies involving nirsevimab. © 2024

关键词： ARDS Bronchiolitis Co-infection Pneumonia Respiratory failure RSV

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Hernandezine promotes cancer cell apoptosis and disrupts the lysosomal acidic environment and cathepsin D maturation

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Chinese Journal of Natural Medicines 2024年第5期22卷 387-401页

作者： FENG Qianwen SUN Lu Muhammad Jibran Sualeh ZHAO Qingli ZHAO Songji CUI Zhengguo INADERA Hidekuni Department of Public Health Graduate School of Medicine and Pharmaceutical SciencesUniversity of ToyamaToyama 930-8501Japan Department of pediatric Cardiology Heart CenterGuangzhou Women and Children’s Medical CenterGuangzhou Medical UniversityGuangzhou 510000China Department of Basic Medical Sciences College of MedicineUniversity of SharjahSharjah 57545United Arab Emirates Department of Radiology Graduate School of Medicine and Pharmaceutical SciencesUniversity of ToyamaToyama 930-8501Japan Advanced Clinical research Center Fukushima Global Medical Science CenterFukushima Medical UniversityFukushima CityFukushima 960-8074Japan Department of Environmental Health School of Medical SciencesUniversity of FukuiFukui 910-8580Japan

Hernandezine(Her),a bisbenzylisoquinoline alkaloid extracted from Thalictrum flavum,is recognized for its range of biological activities inherent to this herbal *** its notable properties,the anti-cancer effects of Her have remained largely *** this study,we elucidated that Her significantly induced cytotoxicity in cancer cells through the activation of apoptosis and necroptosis ***,Her triggered autophagosome formation by activating the AMPK and ATG5 conjugation systems,leading to LC3 *** findings revealed that Her caused damage to the mitochondrial membrane,with the damaged mitochondria undergoing mitophagy,as evidenced by the elevated expression of mitophagy ***,Her disrupted autophagic flux,demonstrated by the upregulation of p62 and accumulation of autolysosomes,as observed in the RFP-GFP-LC3 reporter ***,we determined that Her did not prevent the fusion of autophagosomes and ***,it inhibited the maturation of cathepsin D and increased lysosomal pH,indicating an impairment of lysosomal *** use of the early-stage autophagy inhibitor,3-methyladenine(3-MA),did not suppress LC3II,suggesting that Her also induces noncanonical autophagy in autophagosome *** application of Bafilomycin A1,an inhibitor of noncanonical autophagy,diminished the recruitment of ATG16L1 and the accumulation of LC3II by Her,thereby augmenting Her-induced cell *** observations imply that while autophagy initially plays a protective role,the disruption of the autophagic process by Her promotes programmed cell *** study provides the first evidence of Her’s dual role in inducing apoptosis and necroptosis while also initiating and subsequently impairing autophagy to promote apoptotic cell *** insights contribute to a deeper understanding of the mechanisms underlying programmed cell death,offering potential avenues for enhancing cancer prevention and therapeutic st

关键词： Hernandezine Apoptosis Mitophagy Autophagic flux Lysosome Noncanonical autophagy

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Chemical components in cultivated Cordyceps sinensis and their effects on fibrosis

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Chinese Herbal Medicines 2024年第1期16卷 162-167页

作者： Zhonghua Dong Xiao Sun Department of Clinical Pharmacy The First Affiliated Hospital of Shandong First Medical University&Shandong Provincial Qianfoshan HospitalShandong Engineering and Technology Research Center for Pediatric Drug DevelopmentShandong Medicine and Health Key Laboratory of Clinical PharmacyJinan 250014China Department of Emergency Medicine Qilu Hospital of Shandong UniversityJinan 250012China Shandong Provincial Clinical research Center for Emergency and Critical Care Medicine Institute of Emergency and Critical Care Medicine of Shandong UniversityChest Pain CenterQilu Hospital of Shandong UniversityJinan 250012China Key Laboratory of Emergency and Critical Care Medicine of Shandong Province Key Laboratory of Cardiopulmonary-Cerebral Resuscitation Research of Shandong ProvinceShandong Provincial Engineering Laboratory for Emergency and Critical Care MedicineShandong Key Laboratory:Magnetic Field-free Medicine&Functional ImagingQilu Hospital of Shandong UniversityJinan 250012China NMPA Key Laboratory for Clinical research and Evaluation of Innovative Drug Qilu Hospital of Shandong UniversityJinan 250012China

Objective:Cultivated Cordyceps sinensis powder has been used as clinical drug and healthy food to nourish the lung and kidney,which solves the problem of serious shortage of wild *** study aims to explore the chemical components and compared their anti-fibrotic effects in cultivated ***:Nucleosides,sterols and polysaccharides were separated and purified from cultivated ***,and analyzed by high performance liquid chromatography,gas chromatography-mass spectrometry and chemical chromogenic methods,*** high glucose-induced rat mesangial cell models,fibronectin and type 1 collagen were used as evaluation ***:There were 10 kinds of nucleosides and one sterol in cultivated *** contents of nucleosides,sterols and polysaccharides in the cultivated *** were close to 2%,0.55%and 4.4%,***,nucleoside,sterol and polysaccharide components exhibited varying degrees of antifibrotic *** nucleoside components and sterol components inhibited the expression of extracellular matrix more effectively in the three main ***:Cultivated *** remains the similar compounds with the wild ***,and nucleosides and sterols may be the main active substances that contribute to its anti-fibrotic *** project of this study may provide valuable information on further optimization of more effective remedies with few side effects based on cultivated ***.

关键词： anti-fibrotic effects cultivated Cordyceps sinensis ergosterol nucleosides polysaccharides

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Genetics on early onset inflammatory bowel disease:An update

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Genes & Diseases 2020年第1期7卷 93-106页

作者： Johnson Nameirakpam Rashmi Rikhi Sanjay Singh Rawat Jyoti Sharma Deepti Suri pediatric Allergy and Immunology Unit Department of PediatricsAdvanced Pediatrics CentrePostgraduate Institute of Medical Education and ResearchChandigarhIndia

Inflammatory bowel disease(IBD)is more common in adults than in *** of IBD before 17 years of age is referred as pediatric onset IBD and is further categorized as very early onset IBD(VEO-IBD)for children who are diagnosed before 6 years of age,infantile IBD who had the disease before 2 years of age and neonatal onset IBD for children less than 28 days of *** presenting with early onset disease may have a monogenic *** and awareness of the clinical manifestations facilitates early evaluation and *** generation sequencing is helpful in making the genetic *** of childhood IBD is difficult;targeted therapies and hematopoietic stem cell transplantation form the *** this review we aim to summarize the genetic defects associated with IBD *** describe genetic location and functions of various genetic defect associated with VEO-IBD with their key clinical *** also provide clinical clues to suspect these conditions and approaches to the diagnosis of these disorders and suitable treatment options.

关键词： Il-10 signalling defect IPEX Next generation sequencing Targeted therapy Very early onset inflammatory bowel disease

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Microphallus early management in infancy saves adulthood sensual life:A comprehensive review

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World Journal of Clinical pediatrics 2024年第2期13卷 16-37页

作者： Mohammed Al-Beltagi Nermin Kamal Saeed Adel Salah Bediwy Majed A Shaikh Reem Elbeltagi Department of pediatric Faculty of MedicineTanta UniversityTanta 31511Egypt Department of pediatric University Medical CenterKing Abdulla Medical CityArabian Gulf UniversityManama 26671Bahrain Department of pediatric University Medical CenterSulaiman Al Habib Medical GroupManama 26671Bahrain Department of Medical Microbiology Section and Pathology Salmaniya Medical ComplexMinistry of HealthKingdom of BahrainManama 12Bahrain Department of Medical Microbiology Section and Pathology Irish Royal College of SurgeonBusaiteen 15503Bahrain Department of Pulmonology Faculty of MedicineTanta UniversityTanta 31527Egypt Department of Pulmonology University Medical CenterKing Abdulla Medical CityArabian Gulf UniversityManama 26671Bahrain Department of Pulmonology University Medical CenterSulaiman Al Habib Medical GroupManama 26671Bahrain Department of pediatrics Ibn Al Nafees HospitalManama 54533Bahrain Department of Medicine The Royal College of Surgeons in Ireland-BahrainBusiateen 15503Bahrain

Microphallus/Micropenis is a rare condition with significant physical and psychological implications for affected *** article comprehensively reviews micropenis,its etiology,epidemiology,and various treatment *** conducted a thorough literature review to collect relevant information on micropenis and microphallus,as well as related *** primary databases were PubMed,Medline,and Google *** searched for articles published in English between 2000 and *** analysis included 67 review articles,56 research studies,11 case reports,one guideline,and one *** search terms included"microphallus","micropenis","congenital hypogonadotropic hypogonadism","androgen insensitivity syndrome","pediatric management of micropenis","testosterone therapy",and"psychosocial implications of micropenis".We focused on diagnosing micropenis and related conditions,including hormonal assessments,medical and surgical treatment options,psychosocial and psychological well-being,sexual development of adolescents,and sociocultural influences on men's perceptions of penile ***,we explored parenting and family dynamics in cases of micropenis and disorders of sex development,implications of hormonal treatment in neonates,and studies related to penile augmentation procedures and their *** article highlights the importance of early diagnosis and intervention in addressing the physical and psychological well-being of individuals with *** procedures,such as penile lengthening and girth enhancement,and non-surgical approaches like hormonal therapy are *** significance of psychological support,education,and lifestyle modifications is *** management and comprehensive care are crucial for individuals with micropenis,from infancy to adolescence and beyond.A multidisciplinary approach involving urologists,endocrinologists,and mental health professionals is *** assessment of treatment e

关键词： Microphallus Micropenis Hypogonadism Children Adults Sensual life Testosterone therapy

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Metabolomic changes in children with autism

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World Journal of Clinical pediatrics 2024年第2期13卷 171-197页

作者： Mohammed Al-Beltagi Nermin Kamal Saeed Adel Salah Bediwy Reem Elbeltagi Department of pediatric Faculty of MedicineTanta UniversityTanta 31511AlghrabiaEgypt Department of pediatric University Medical CenterKing Abdulla Medical CityArabian Gulf UniversityManama 26671Bahrain Department of pediatric University Medical CenterDr.Sulaiman Al Habib Medical GroupManamaBahrainManama 26671Bahrain Medical Microbiology Section Department of PathologySalmaniya Medical ComplexMinistry of HealthKingdom of BahrainManama 12Bahrain Medical Microbiology Section Department of PathologyIrish Royal College of SurgeonBahrainBusaiteen 15503MuharraqBahrain Department of Pulmonology Faculty of MedicineTanta UniversityTanta 31527AlghrabiaEgypt Department of Chest Disease University Medical CenterKing Abdulla Medical CityArabian Gulf UniversityManama 26671Bahrain Department of Chest Disease University Medical CenterDr.Sulaiman Al Habib Medical GroupManamaManama 26671Bahrain Department of Medicine The Royal College of Surgeons in Ireland-BahrainBusiateen 15503MuharraqBahrain

BACKGROUND Autism spectrum disorder(ASD)is a neurodevelopmental condition characterized by deficits in social communication and repetitive *** profiling has emerged as a valuable tool for understanding the underlying metabolic dysregulations associated with *** To comprehensively explore metabolomic changes in children with ASD,integrating findings from various research articles,reviews,systematic reviews,meta-analyses,case reports,editorials,and a book *** A systematic search was conducted in electronic databases,including PubMed,PubMed Central,Cochrane Library,Embase,Web of Science,CINAHL,Scopus,LISA,and NLM catalog up until January *** criteria encompassed research articles(83),review articles(145),meta-analyses(6),systematic reviews(6),case reports(2),editorials(2),and a book chapter(1)related to metabolomic changes in children with *** criteria were applied to ensure the relevance and quality of included *** The systematic review identified specific metabolites and metabolic pathways showing consistent differences in children with ASD compared to typically developing *** metabolic biomarkers may serve as objective measures to support clinical assessments,improve diagnostic accuracy,and inform personalized treatment *** profiling also offers insights into the metabolic alterations associated with comorbid conditions commonly observed in individuals with *** Integration of metabolomic changes in children with ASD holds promise for enhancing diagnostic accuracy,guiding personalized treatment approaches,monitoring treatment response,and improving *** research is needed to validate findings,establish standardized protocols,and overcome technical challenges in metabolomic *** advancing our understanding of metabolic dysregulations in ASD,clinicians can improve the lives of affected individuals and their families.

关键词： Autism spectrum disorder Metabolic dysregulations Metabolomic changes Children Mitochondrial dysfunction Oxidative stress Amino acids

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Acute symptomatic seizures in newborns:a narrative review

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Acta Epileptologica 2024年第1期7卷 1-13页

作者： Carlotta Spagnoli Francesco Pisani Child Neurology Unit Pediatric DepartmentAzienda USL-IRCCS Di Reggio EmiliaReggio Emilia42123Italy Child Neurology and Psychiatry Unit Department of Human NeurosciencesSapienza University of RomeRome00185Italy Azienda Ospedaliero Universitaria Policlinico Umberto I Rome00185Italy

Acute symptomatic seizures are the main sign of neurological dysfunction in *** is linked to the unique characteristics of the neonatal brain,making it hyperexcitable compared to older ages,and to the common occurrence of some forms of acquired brain injury,namely hypoxic-ischemic *** this narrative review we will provide an overview of neonatal seizures definition,their main underlying etiologies,diagnostic work-up and differential diagnoses,and will discuss about therapeutic options and prognostic *** latest publications from the ILAE Task Force on Neonatal Seizures will be presented and *** note,they highlight the current lack of robust evidence in this field of clinical *** will also report on specificities pertaining to low-and-middle income countries in terms of incidence,main etiologies and *** possibilities offered by telemedicine and automated seizures detection will also be summarized in order to provide a framework for future directions in seizures diagnosis and management with a global *** challenges and opportunities for improving identification,monitoring and treatment of acute symptomatic seizures in newborns *** current caveats potentially represent different lines of research with the aim to provide better care and reach a deeper understanding of this important topic of neonatal neurology.

关键词： Acute symptomatic Neonatal seizures EEG Newborn Outcome Diagnosis Etiologies

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Esophageal inserted subclavian catheter:a rare complication

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World Journal of Emergency Medicine 2024年第3期15卷 243-245页

作者： DilberÜçöz Kocaşaban SertaçGüler Emergency Medicine Clinic Health Sciences University Ankara Training and Research HospitalAnkara 06930Turkey

Central venous catheterization(CVC) is an invasive procedure for administering fluids,nutrients,and drugs;monitoring central venous pressure;performing pulmonary artery catheterization;and placing transvenous pacemakers in intensive care units and all specialties,from anesthesia to emergency medicine,for the treatment of trauma and hemodynamically unstable pediatric and adult patients.[1,2]Complications have been observed in more than 15% of patients who underwent ***,infectious,and thrombotic complications have been reported in 5%–19%,5%–26%,and 2%–26% of patients,respectively.[3] Malposition,on the other hand,is common in subclavian catheter insertion and is usually associated with an initially misplaced guidewire.[4]

关键词： unstable insertion initially

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Carbocysteine as Adjuvant Therapy in Acute Respiratory Tract Infections in Patients without Underlying Chronic Conditions: Systematic Review and Meta-Analysis

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Open Journal of Respiratory Diseases 2024年第2期14卷 39-50页

作者： Myriam Calle Rubio Olga de la Serna Blazquez José Luis R. Martin Manuel Ruiz Cuetos Pulmonology Department Hospital Clínico San Carlos Madrid Spain Department of Medicine School of Medicine Universidad Complutense de Madrid Madrid Spain Instituto de Investigacion Sanitaria del Hospital Clínico San Carlos (IdISSC) Madrid Spain pediatric Pulmonology Unit Pediatrics Department Hospital Universitario La Paz Madrid Spain Simplifying research Institute Layos Spain Medical department in ITF research Pharma S.L.U. Alcobendas Spain

Objective: This study aims to systematically examine the existing evidence regarding the clinical benefits of carbocysteine as an adjunctive treatment in acute bronchopulmonary and otorhinological processes. Design: Systematic review and meta-analysis. Data sources: An electronic search was conducted across PubMed, Cochrane Library, ***, and the European Clinical Trial Register, with the search dated to May 2023. Bibliographic references from other literature reviews and meta-analyses were also reviewed. The search was limited to randomized clinical trials published in any language and year. It was completed by cross-checking the references of the located articles. Methods: Inclusion criteria covered studies assessing systemic or inhaled carbocysteine, regardless of dosing regimen. Concomitant medication use was acceptable if balanced between intervention and control groups. Authors independently extracted data, resolving disagreements through consensus. Methodological quality assessment relied on critical reading of each study. Dichotomous variables were analyzed using odds ratio (OR), and a final effect size was calculated. Statistical significance was established when confidence intervals did not cross the neutral value. Heterogeneity was assessed via the X2 test and I2 index. Results: Out of 318 initially identified studies, 4 met inclusion criteria. The meta-analysis for poor general condition yielded an OR of 0.45 in favor of intervention, p = 0.013, with non-significant heterogeneity. Cough events showed a percentage of 15.8% for carbocysteine vs. 27.2% for placebo. On the seventh day, expectoration rates were 18.37% for carbocysteinevs 33.3% for placebo. Conclusions: The observed clinical benefits align with carbocysteine’s mucoactive and muco-regulatory properties, complemented by anti-inflammatory and antioxidant actions. Carbocysteine stands out among mucolytic agents. In the context of persistent infectious diseases,

关键词： Acute Respiratory Infections Carbocystenine Systematic Review Meta-Analysis

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