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Promising use of metformin in treating neurological disorders:biomarker-guided therapies

Neural Regeneration Research 2024年第5期19卷 1045-1055页

作者： Allison Loan Charvi Syal Margarita Lui Ling He Jing Wang Regenerative Medicine Program Ottawa Hospital Research InstituteOttawaONCanada department of Biology Faculty of ScienceUniversity of OttawaOttawaONCanada department of pediatrics and Medicine Johns Hopkins Medical SchoolBaltimoreMDUSA department of Cellular and Molecular Medicine Faculty of MedicineUniversity of OttawaOttawaONCanada University of Ottawa Brain and Mind Research Institute OttawaONCanada

Neurological disorders are a diverse group of conditions that affect the nervous system and include neurodegenerative diseases(Alzheimer’s disease,multiple sclerosis,Parkinson’s disease,Huntington’s disease),cerebrovascular conditions(stroke),and neurodevelopmental disorders(autism spectrum disorder).Although they affect millions of individuals around the world,only a limited number of effective treatment options are available *** most neurological disorders express mitochondria-related metabolic perturbations,metformin,a biguanide type II antidiabetic drug,has attracted a lot of attention to be repurposed to treat neurological disorders by correcting their perturbed energy ***,controversial research emerges regarding the beneficial/detrimental effects of metformin on these neurological *** that most neurological disorders have complex etiology in their pathophysiology and are influenced by various risk factors such as aging,lifestyle,genetics,and environment,it is important to identify perturbed molecular functions that can be targeted by metformin in these neurological *** molecules can then be used as biomarkers to stratify subpopulations of patients who show distinct molecular/pathological properties and can respond to metformin treatment,ultimately developing targeted *** this review,we will discuss mitochondria-related metabolic perturbations and impaired molecular pathways in these neurological disorders and how these can be used as biomarkers to guide metformin-responsive treatment for the targeted therapy to treat neurological disorders.

关键词： Alzheimer’s disease Huntington’s disease metformin mitochondrial perturbation multiple sclerosis neural degenerative diseases Parkinson’s disease stroke targeted therapy

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Genome-wide Studies Reveal Genetic Risk Factors for Hepatic Fat Content

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Genomics, Proteomics & Bioinformatics 2024年第2期22卷 57-68页

作者： Yanni Li Eline H.van den Berg Alexander Kurilshikov Dasha V.Zhernakova Ranko Gacesa Shixian Hu Esteban A.Lopera-Maya Alexandra Zhernakova Lifelines Cohort Study Vincent E.de Meijer Serena Sanna Robin P.F.Dullaart Hans Blokzijl Eleonora A.M.Festen Jingyuan Fu Rinse K.Weersma department of Gastroenterology and Hepatology University of GroningenUniversity Medical Center GroningenGroningen 9713 GZThe Netherlands department of Genetics University of GroningenUniversity Medical Center GroningenGroningen 9713 GZThe Netherlands department of Gastroenterology and Hepatology Tianjin Medical University General HospitalTianjin Medical UniversityTianjin 300052China Laboratory of Genomic Diversity Center for Computer TechnologiesITMO UniversitySaint Petersburg 199034Russia Institute of Precision Medicine the First Affiliated HospitalSun Yat-sen UniversityGuangzhou 510080China department of Surgery Section of Hepatobiliary Surgery and Liver TransplantationUniversity of GroningenUniversity Medical Center GroningenGroningen 9713 GZThe Netherlands department of Endocrinology University of GroningenUniversity Medical Center GroningenGroningen 9713 GZThe Netherlands department of pediatrics University of GroningenUniversity Medical Center GroningenGroningen 9713 GZThe Netherlands 不详

Genetic susceptibility to metabolic associated fatty liver disease(MAFLD)is complex and poorly *** characterization of the genetic background of hepatic fat content would provide insights into disease etiology and causality of risk *** performed genome-wide association study(GWAS)on two noninvasive definitions of hepatic fat content:magnetic resonance imaging proton density fat fraction(MRI-PDFF)in 16,050 participants and fatty liver index(FLI)in 388,701 participants from the United Kingdom(UK)Biobank(UKBB).Heritability,genetic overlap,and similarity between hepatic fat content phenotypes were analyzed,and replicated in 10,398 participants from the University Medical Center Groningen(UMCG)Genetics Lifelines Initiative(UGLI).Meta-analysis of GWASs of MRI-PDFF in UKBB revealed five statistically significant loci,including two novel genomic loci harboring CREB3L1(rs72910057-T,P=5.40E−09)and GCM1(rs1491489378-T,P=3.16E−09),respectively,as well as three previously reported loci:PNPLA3,TM6SF2,and *** of FLI in UKBB identified 196 genome-wide significant loci,of which 49 were replicated in UGLI,with top signals in ZPR1(P=3.35E−13)and FTO(P=2.11E−09).Statistically significant genetic correlation(rg)between MRI-PDFF(UKBB)and FLI(UGLI)GWAS results was found(rg=0.5276,P=1.45E−03).Novel MRI-PDFF genetic signals(CREB3L1 and GCM1)were replicated in the FLI *** identified two novel genes for MRI-PDFF and 49 replicable loci for *** a difference in hepatic fat content assessment between MRI-PDFF and FLI,a substantial similar genetic architecture was *** is identified as an easy and reliable approach to study hepatic fat content at the population level.

关键词： Hepatic fat content MAFLD Genome-wide association study Fatty liver index Magnetic resonance imaging proton density fat fraction

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Surgical Repair of Ventricular Septal Defect in Neonates: Indications and Outcomes

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Congenital Heart Disease 2024年第1期19卷 69-83页

作者： Jae Hong Lee Sungkyu Cho Jae Gun Kwak Hye Won Kwon Woong-Han Kim Mi Kyoung Song Sang-Yun Lee Gi Beom Kim Eun Jung Bae department of Thoracic and Cardiovascular Surgery Research Institute for Convergence of Biomedical Science and TechnologyPusan National University Yangsan HospitalYangsanKorea department of Thoracic and Cardiovascular Surgery Seoul National University Children’s HospitalSeoulKorea department of pediatrics Seoul National University Children’s HospitalSeoulKorea

Background:The optimal surgical timing and clinical outcomes of ventricular septal defect(VSD)closure in neo-nates remain *** aimed to evaluate the clinical outcomes of VSD closure in neonates(age≤30 days).Methods:We retrospectively reviewed 50 consecutive neonates who underwent VSD closure for isolated VSDs between August 2003 and June *** for the procedure included congestive heart failure/failure to thrive and pulmonary *** adverse events(MAEs)were deﬁned as the composite of all-cause mortality,reoperation,persistent atrioventricular block,and signiﬁcant(≥grade 2)valvular ***:The median age and body weight at operation were 26.0 days(interquartile range[IQR],18.8–28.3)and 3.7 kg(IQR,3.3–4.2),*** median follow-up duration was 110.4 months(IQR,56.8–165.0).Seven patients required preoperative respiratory support,andﬁve had signiﬁcant(≥grade 2)preoperative valvular *** early mortality occurred due to irreversible cardiogenic shock;no late mortality was *** reopera-tion was due to hemodynamically signiﬁcant residual VSD at 103.8 months *** overall survival,freedom from reoperation,and freedom from MAE at 15-years were 98.0%,96.3%,and 94.4%,***-operative mechanical ventilation was associated with a longer duration of postoperative mechanical ventilation(p<0.001)and a longer length of intensive care unit stay(p<0.001).Conclusions:VSD closure with favorable outcomes without morbidities is feasible even in ***,neonates requiring preoperative respiratory support may require careful postoperative management considering the long-term postoperative ***,surgical VSD closure might be indicated earlier in neonates with respiratory compromise.

关键词： Ventricular septal defect neonate early surgery neonatal surgery

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Prenatal and postnatal factors associated with sudden infant death syndrome:an umbrella review of meta-analyses

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World Journal of pediatrics 2024年第5期20卷 451-460页

作者： Tae Hyeon Kim Hyeri Lee Selin Woo Hayeon Lee Jaeyu Park Guillaume Fond Laurent Boyer Jong Woo Hahn Jiseung Kang Dong Keon Yon department of Medicine Kyung Hee University College of MedicineSeoulSouth Korea Center for Digital Health Medical Science Research InstituteKyung Hee University College of MedicineSeoulSouth Korea department of Regulatory Science Kyung Hee UniversitySeoulSouth Korea department of Biomedical Engineering Kyung Hee UniversityYonginSouth Korea CEReSS-Health Service Research and Quality of Life Center Assistance Publique des Hôpitaux de MarseilleAix-Marseille UniversityMarseilleFrance department of pediatrics Seoul National University College of MedicineSeoulSouth Korea department of pediatrics Seoul National University Bundang HospitalSeongnamSouth Korea department of Anesthesia Critical Care and Pain MedicineMassachusetts General Hospital14913th StreetRoom 4140CharlestownBostonMAUSA Division of Sleep Medicine Harvard Medical SchoolBostonMAUSA department of pediatrics Kyung Hee University Medical CenterKyung Hee University College of Medicine23 Kyungheedae-roDongdaemun-guSeoul02447South Korea department of Precision Medicine Kyung Hee University College of MedicineSeoulSouth Korea

Background Comprehensive quantitative evidence on the risk and protective factors for sudden infant death syndrome(SIDS)effects is *** investigated the risk and protective factors related to *** We conducted an umbrella review of meta-analyses of observational and interventional studies assessing SIDS-related ***/MEDLINE,Embase,EBSCO,and Google Scholar were searched from inception until January 18,*** extraction,quality assessment,and certainty of evidence were assessed by using A Measurement Tool Assessment Systematic Reviews 2 following PRISMA *** to observational evidence,credibility was graded and classified by class and quality of evidence(CE;convincing,highly suggestive,suggestive,weak,or not significant).Our study protocol was registered with PROSPERO(CRD42023458696).The risk and protective factors related to SIDS are presented as equivalent odds ratios(eORs).Results We identified eight original meta-analyses,including 152 original articles,covering 12 unique risk and protective factors for SIDS across 21 countries/regions and five *** risk factors,including prenatal drug exposure[eOR=7.84(95%CI=4.81–12.79),CE=highly suggestive],prenatal opioid exposure[9.55(95%CI=4.87–18.72),CE=suggestive],prenatal methadone exposure[9.52(95%CI=3.34–27.10),CE=weak],prenatal cocaine exposure[4.38(95%CI=1.95–9.86),CE=weak],prenatal maternal smoking[2.25(95%CI=1.95–2.60),CE=highly suggestive],postnatal maternal smoking[1.97(95%CI=1.75–2.22),CE=weak],bed sharing[2.89(95%CI=1.81–4.60),CE=weak],and infants found with heads covered by bedclothes after last sleep[11.01(95%CI=5.40–22.45),CE=suggestive],were *** the other hand,three protective factors,namely,breastfeeding[0.57(95%CI=0.39–0.83),CE=non-significant],supine sleeping position[0.48(95%CI=0.37–0.63),CE=suggestive],and pacifier use[0.44(95%CI=0.30–0.65),CE=weak],were also *** Based on the evidence,we propose several risk and protecti

关键词： Infant Protective factor Risk factor Sudden infant death syndrome Umbrella review

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Influence of biological treatments on intestinal microbiota of psoriasis patients

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中华医学杂志(英文版) 2024年第16期137卷 1996-1998页

作者： Wen Zhuyuan Lu Xiaoling Nie Hao Xu Jing Zou Yang Huang Kun Chen Aijun Zhang Yichi Cao Min Yin Qi Wang Ping department of Dermatology The First Affiliated Hospital of Chongqing Medical University Chongqing China School of pediatrics Chongqing Medical University Pediatric College Chongqing China School of Public Health Chongqing Medical University Chongqing China department of Urology Third People’s Hospital of Chengdu Chengdu Sichuan China

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CRISPR/Cas9 system and its applications in nervous system diseases

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Genes & Diseases 2024年第2期11卷 675-686页

作者： Haibin Jiang Mengyan Tang Zidi Xu Yanan Wang Mopu Li Shuyin Zheng Jianghu Zhu Zhenlang Lin Min Zhang The Second School of Medicine Wenzhou Medical UniversityWenzhouZhejiang 325035China The first School of Medicine Wenzhou Medical UniversityWenzhouZhejiang 325035China department of pediatrics The Second School of MedicineThe Second Affiliated Hospital and Yuying Children's Hospital of Wenzhou Medical UniversityWenzhouZhejiang 325027China Key Laboratory of Perinatal Medicine of Wenzhou WenzhouZhejiang 325027China Key Laboratory of Structural Malformations in Children of Zhejiang Province WenzhouZhejiang 325000China Zhejiang Provincial Clinical Research Center for Pediatric Disease WenzhouZhejiang 325027China

The clustered regularly interspaced short palindromic repeats(CRISPR)/CRISPR-associated protein 9(Cas9)system is an acquired immune system of many bacteria and archaea,comprising CRISPR loci,Cas genes,and its associated *** system can recognize exogenous DNA and utilize the Cas9 protein's nuclease activity to break DNA double-strand and to achieve base insertion or deletion by subsequent DNA *** recent years,multiple laboratory and clinical studies have revealed the therapeutic role of the CRISPR/Cas9 system in neurological *** article reviews the CRISPR/Cas9-mediated gene editing technology and its potential for clinical application against neurological diseases.

关键词： CRISPR/Cas9 Gene editing Mutation Neurological diseases Therapeutics

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Application of artificial intelligence in the diagnosis and treatment of Kawasaki disease

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World Journal of Clinical Cases 2024年第23期12卷 5304-5307页

作者： Yan Pan Fu-Yong Jiao department of pediatrics The First Affiliated Hospital of Yangtze UniversityJingzhou 434000Hubei ProvinceChina Shaanxi Kawasaki Disease Diagnosis and Treatment Center Shaanxi Provincial People's HospitalXi’an 710000Shaanxi ProvinceChina

This editorial provides commentary on an article titled"Potential and limitationsof ChatGPT and generative artificial intelligence(AI)in medical safety education"recently published in the World Journal of Clinical *** has enormous potentialfor various applications in the field of Kawasaki disease(KD).One is machinelearning(ML)to assist in the diagnosis of KD,and clinical prediction models havebeen constructed worldwide using ML;the second is using a gene signalcalculation toolbox to identify KD,which can be used to monitor key clinicalfeatures and laboratory parameters of disease severity;and the third is using deeplearning(DL)to assist in cardiac ultrasound *** performance of the DLalgorithm is similar to that of experienced cardiac experts in detecting coronaryartery lesions to promoting the diagnosis of *** effectively utilize AI in thediagnosis and treatment process of KD,it is crucial to improve the accuracy of AIdecision-making using more medical data,while addressing issues related topatient personal information protection and AI decision-making *** is expected to provide patients with accurate and effective medicalservices that will positively impact the diagnosis and treatment of KD in thefuture.

关键词： Artificial intelligence Kawasaki disease Diagnosis Prediction Image

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Anoctamin 4 defines glucose-inhibited neurons in the ventromedial hypothalamus

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Neural Regeneration Research 2024年第6期19卷 1177-1178页

作者： Longlong Tu Yanlin He Yong Xu Children’s Nutrition Research Center Department of PediatricsBaylor College of MedicineOne Baylor PlazaHoustonTXUSA Brain Glycemic and Metabolism Control department Pennington Biomedical Research CenterLouisiana State UniversityBaton RougeLAUSA department of Molecular and Cellular Biology Section of EndocrinologyDiabetes and MetabolismDepartment of MedicineBaylor College of MedicineHoustonTXUSA

Glucose is the primary fuel source of the brain,and therefore glucose levels need to be tightly regulated and maintained within a small physiological ***,the body necessitates a stable supply of energy mainly provided by glucose for various bodily *** or low blood glucose levels would impair the physiological functions of various organs of the body.

关键词： inhibited medial organs

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Profile of Peanut Sensitization in Children Attending a Pneumo-Allergology Consultation at the Teaching Hospital Campus of Lomé, Togo

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Open Journal of pediatrics 2024年第5期14卷 889-897页

作者： Mawouto Fiawoo Manani Hemou Foli Agbéko Salimtoa Moussoma Mazama Pakoudjare Nadiedja Kokou Douti department of pediatrics Faculty of Health Sciences University of Lom Lom Togo

Introduction: Food allergies are on the constant increase worldwide. Among them is peanut allergy, which also affects children. The aim of this study was to determine the profile of peanut sensitization in children attending a pneumo-allergology consultation. Methods: This was a cross-sectional study, which ran from January 1, 2018, to December 31, 2022, on children sensitized to peanuts seen in pneumo-allergology consultations at the Teaching Hospital Campus of Lomé. Results: The sample included 137 children aged 3 months to 18 years. The frequency of peanut sensitization was 25.3%. The mean age of patients was 6.3 ± 4.3 years (minimum 6 months and maximum 18 years). The 6 months to 5 years age group was the most represented (43.1%). The sex ratio was 1.3. The main reasons for consultation were rhinorrhea (67.9%), sneezing (36.5%) and cough (35.8%). Allergic rhinitis was identified as a personal history in 75.2% of patients. Peanut allergy was manifested as rhinorrhea (62.5%), asthma (26.8%) and eczema (8.9%). The risk of onset of symptoms within 15 - 30 minutes was 1.87 times (p = 0.001, CI = [1.2 - 2.1]) for peanuts consumed in roasted form with shell. Severe clinical signs such as Quincke’s Edema and anaphylactic shock were found in 1.4% of cases. Conclusion: Peanut allergy was common in children. Severe clinical signs were rare.

关键词： Peanut Sensitization Allergy Child Togo

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The Analogy between the Immune System and Human Life

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Open Journal of Immunology 2024年第3期14卷 47-59页

作者： Gassem Gohal department of pediatrics Faculty of Medicine Jazan University Jazan Saudi Arabia

The immune system operates as a complex organization with distinct roles and functions. Excitingly we recognized the similarities between the cellular dynamics of the immune system and our lives, activities, and behaviors. Observing the immune system can guide how to respond to various daily situations, including when to react, tolerate, or ignore. Recognizing this analogy between our lives and the immune system should motivate us to adopt a wisdom-based approach when investigating the mechanisms and future discoveries related to this system and to deepen our understanding of this complex system with newfound respect. In this context, the present review examines several integral biological processes of the immune system by drawing parallels between them and human life, activities, and behaviors to learn how we must behave based on the insights offered by this complex organization. The literature search was conducted in international databases such as PubMed/MEDLINE and Google Scholar search engine using English equivalent keywords from 1998 up to April 2023. The search strategy used the following subject heading terms: Immune system, analogy, human life, cellular dynamics, memory, tolerance, and ignorance. In conclusion, the immune system is a complex organization comprising various cells interacting within specific sites and networks, communicating, drawing experiences, and learning how to tolerate certain conditions that make it share certain similarities with human life.

关键词： Immune System Analogy Memory Tolerance Ignorance

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