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Pediatric and adult liver transplantation in Bahrain: The experiences in a country with no available liver transplant facilities

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World Journal of Transplantation 2024年第1期14卷 96-111页

作者： Hasan M Isa Fatema A Alkharsi Jawad K Khamis Sawsan A Hasan Zainab A Naser Zainab N Mohamed Afaf M Mohamed Shaikha A Altamimi department of pediatrics Salmaniya Medical ComplexManama 26671Bahrain department of pediatrics Arabian Gulf UniversityManama 26671Bahrain department of Medicine Salmaniya Medical ComplexManama 26671Bahrain Public Health Directorate Ministry of HealthManama 26671Bahrain The Overseas Office Supreme Committee for Treatment AbroadMinistry of HealthManama 26671Bahrain

BACKGROUND Liver transplantation(LT)is a life-saving procedure for patients with end-stage liver disease and has become the standard and most effective treatment method for these patients.There are many indications for LT that vary between countries and settings.The outcome of LT depends on the available facilities and surgical expertise,as well as the types of liver graft donors available.AIM To assess the clinical characteristics of patients from Bahrain who underwent LT overseas,and analyze factors affecting their survival.METHODS In this retrospective cohort study,we reviewed the medical records and overseas committee registry information of all pediatric and adult patients who were sent overseas to undergo LT by the Pediatric and medical departments of salmaniya medical complex and Bahrain Defence Force Hospital via the Overseas Treatment Office,Ministry of Health,Kingdom of Bahrain,between 1997 and 2023.Demographic data,LT indication,donor-recipient relationship,overseas LT center,graft type,post-LT medications,and LT complications,were collected.Outcomes measured included the overall and 5-year LT survival rate.Fisher’s exact,Pearsonχ2,and Mann-Whitney U tests were used to compare the pediatric and the adults’group in terms of clinical characteristics,donor-recipient relationship,medication,complications,and outcome.Survival analysis was estimated via the Kaplan-Meier’s method.Univariate and multivariate analyses were used to detect predictors of survival.RESULTS Of the 208 eligible patients,170(81.7%)were sent overseas to undergo LT while 38(18.3%)remained on the waiting list.Of the 170 patients,167(80.3%)underwent LT and were included in the study.The majority of the patients were Bahraini(91.0%),and most were males(57.5%).One-hundred-and-twenty(71.8%)were adults and 47(28.3%)were children.The median age at transplant was 50.0[interquartile range(IQR):14.9–58.4]years.The main indication for pediatric LT was biliary atresia(31.9%),while that of adult LT was hepatitis C-related cirrhosis(35.0%).Six(3.6%)pa

关键词： Overseas liver transplantation End-stage liver disease Liver transplant facilities Liver donor Biliary atresia Hepatitis C

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Correlations between serum kidney injury molecule-1,cystatin C and immunosuppressants:A cross-sectional study of renal transplant patients in Bahrain

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Journal of Biomedical Research 2024年第3期38卷 269-277页

作者： Kannan Sridharan Shamik Shah Mona Al Hammad Fatima Ali Mohammed Sindhan Veeramuthu Mona Abdulla Taher Mustafa Mohamed Hammad Lamees Jawad Eman Farid department of Pharmacology and Therapeutics College of Medicine and Medical SciencesArabian Gulf UniversityManamaKingdom of Bahrain department of Nephrology Salmaniya Medical ComplexManamaKingdom of Bahrain department of Internal Medicine College of Medicine and Medical SciencesArabian Gulf UniversityManamaKingdom of Bahrain salmaniya medical complex ManamaKingdom of Bahrain department of Laboratory Medicine Salmaniya Medical ComplexManamaKingdom of Bahrain department of Microbiology Immunologyand Infectious DiseasesCollege of Medicine and Medical SciencesArabian Gulf UniversityManamaKingdom of Bahrain

Renal transplant patients receive several immunosuppressive drug regimens that are potentially nephrotoxic for treatment.Serum creatinine is the standard for monitoring kidney function;however,cystatin C(Cys C)and kidney injury molecule-1(KIM-1)have been found to indicate kidney injury earlier than serum creatinine and provide a better reflection of kidney function.Here,we assessed Cys C and KIM-1 serum levels in renal transplant patients receiving mycophenolate mofetil,tacrolimus,sirolimus,everolimus,or cyclosporine to evaluate kidney function.We used both the Chronic Kidney Disease Epidemiology Collaboration(CKD-EPI)2021 equation,which is based on creatinine and combined creatinine with Cys C,and the CKD-EPI 2012 equation,which is based on Cys C alone,to estimate glomerular filtration rate(GFR).Then,we assessed the association between serum KIM-1 and GFR<90 mL per minute per 1.73 m2.We observed significantly higher serum Cys C levels in patients with the elevated serum creatinine,compared with those with normal serum creatinine.The estimated GFRs based on creatinine were significantly higher than those based on the other equations,while a significant positive correlation was observed among all equations.Serum KIM-1 levels were negatively correlated with the estimated GFRs by the CKD-EPI Cys C and the combined creatinine with Cys C equations.A serum KIM-1 level above 0.71 ng/mL is likely to indicate GFR<90 mL per minute per 1.73 m2.We observed a significant correlation between serum creatinine and Cys C in our renal transplant patients.Therefore,serum KIM-1 may be used to monitor renal function when using potentially nephrotoxic drugs in renal transplants.

关键词： KIM-1 cystatin C mycophenolate mofetil tacrolimus everolimus sirolimus cyclosporine

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Fever assessment in children under five: Are we following the guidelines?

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World Journal of Clinical pediatrics 2024年第1期13卷 62-72页

作者： Hasan M Isa Ahmed J Isa Murtadha A Alnasheet Mahmood M Mansoor department of pediatrics Salmaniya Medical ComplexManama 26671Bahrain department of pediatrics Arabian Gulf UniversityManama 26671Bahrain department of General Surgery Salmaniya Medical ComplexManama 26671Bahrain

BACKGROUND Fever is a common cause of medical consultation and hospital admission,particularly among children.Recently,the United Kingdom’s National Institute for Health and Care Excellence(NICE)updated its guidelines for assessing fever in children under five years of age.The efficient assessment and management of children with fever are crucial for improving patient outcomes.AIM To evaluate fever assessment in hospitalized children and to assess its adherence with the NICE Fever in under 5s guideline.METHODS We conducted a retrospective cohort review of the electronic medical records of children under five years of age at the department of pediatrics.salmaniya medical complex,Bahrain,between June and July 2023.Demographic data,vital signs during the first 48 h of admission,route of temperature measurement,and indications for admission were gathered.Fever was defined according to the NICE guideline.The children were divided into five groups according to their age(0-3 months,>3-6 months,>6-12 months,>12-36 months,and>36-60 months).Patients with and without fever were compared in terms of demography,indication for admission,route of temperature measurement,and other vital signs.Compliance with the NICE Fever in the under 5s guideline was assessed.Full compliance was defined as>95%,partial compliance as 70%-95%,and minimal compliance as≤69%.Pearson’sχ^(2),Student’s t test,the Mann-Whitney U test,and Spearman’s correlation coefficient(rs)were used for comparison.RESULTS Of the 136 patients reviewed,80(58.8%)were boys.The median age at admission was 14.2[interquartile range(IQR):1.7-44.4]months,with the most common age group being 36-60 months.Thirty-six(26.4%)patients had fever,and 100(73.6%)were afebrile.The commonest age group for febrile patients(>12-36 months)was older than the commonest age group for afebrile patients(0-3 months)(P=0.027).The median weight was 8.3(IQR:4.0-13.3)kg.Patients with fever had higher weight than those without fever[10.2(IQR:7.3-13.0)vs 7.1(IQR:3.8-13.3)kg,respectively](P=0.034).Gastro

关键词： Fever pediatrics Admission patterns Temperature measurement Guidelines Bahrain

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Fecal calprotectin in pediatric gastrointestinal diseases:Pros and cons

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World Journal of Clinical pediatrics 2024年第2期13卷 198-220页

作者： Mohammed Al-Beltagi Nermin Kamal Saeed Adel Salah Bediwy Reem Elbeltagi department of Pediatric Faculty of MedicineTanta UniversityTanta 31511AlghrabiaEgypt department of pediatrics University Medical CenterKing Abdulla Medical CityArabian Gulf UniversityManama 26671ManamaBahrain department of pediatrics University Medical CenterDr.Sulaiman Al Habib Medical GroupBahrainManama 26671ManamaBahrain medical Microbiology Section Department of PathologySalmaniya Medical ComplexMinistry of HealthKingdom of BahrainManama 12ManamaBahrain medical Microbiology Section Department of PathologyIrish Royal College of SurgeonBahrainBusaiteen 15503MuharraqBahrain department of Pulmonology Faculty of MedicineTanta UniversityTanta 31527AlghrabiaEgypt department of Pulmonology University Medical CenterKing Abdulla Medical CityArabian Gulf UniversityManama 26671ManamaBahrain department of Pulmonology University Medical CenterKing Abdulla Medical CityDr.Sulaiman Al Habib Medical GroupManama 26671ManamaBahrain department of Medicine The Royal College of Surgeons in Ireland-BahrainBusiateen 15503MuharraqBahrain

BACKGROUND Fecal calprotectin is a valuable biomarker for assessing intestinal inflammation in pediatric gastrointestinal diseases.However,its role,pros,and cons in various conditions must be comprehensively elucidated.AIM To explore the role of fecal calprotectin in pediatric gastrointestinal diseases,including its advantages and limitations.METHODS A comprehensive search was conducted on PubMed,PubMed Central,Google Scholar,and other scientific research engines until February 24,2024.The review included 88 research articles,56 review articles,six metaanalyses,two systematic reviews,two consensus papers,and two letters to the editors.RESULTS Fecal calprotectin is a non-invasive marker for detecting intestinal inflammation and monitoring disease activity in pediatric conditions such as functional gastrointestinal disorders,inflammatory bowel disease,coeliac disease,coronavirus disease 2019-induced gastrointestinal disorders,gastroenteritis,and cystic fibrosis-associated intestinal pathology.However,its lack of specificity and susceptibility to various confounding factors pose challenges in interpretation.Despite these limitations,fecal calprotectin offers significant advantages in diagnosing,monitoring,and managing pediatric gastrointestinal diseases.CONCLUSION Fecal calprotectin holds promise as a valuable tool in pediatric gastroenterology,offering insights into disease activity,treatment response,and prognosis.Standardized protocols and guidelines are needed to optimize its clinical utility and mitigate interpretation challenges.Further research is warranted to address the identified limitations and enhance our understanding of fecal calprotectin in pediatric gastrointestinal diseases.

关键词： Fecal calprotectin Pediatric gastrointestinal diseases Functional gastrointestinal disorders Inflammatory bowel disease Coeliac disease COVID-19-induced gastrointestinal disorders Infectious gastroenteritis Cystic fibrosis

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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 individuals.This article comprehensively reviews micropenis,its etiology,epidemiology,and various treatment options.We conducted a thorough literature review to collect relevant information on micropenis and microphallus,as well as related disorders.Our primary databases were PubMed,Medline,and Google Scholar.We searched for articles published in English between 2000 and 2023.Our analysis included 67 review articles,56 research studies,11 case reports,one guideline,and one editorial.Our 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 size.Additionally,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 effectiveness.The article highlights the importance of early diagnosis and intervention in addressing the physical and psychological well-being of individuals with micropenis.Surgical procedures,such as penile lengthening and girth enhancement,and non-surgical approaches like hormonal therapy are explored.The significance of psychological support,education,and lifestyle modifications is emphasized.Early 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 recommended.Regular assessment of treatment effectiveness and the need for updated guidelines

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 behaviors.Metabolomic profiling has emerged as a valuable tool for understanding the underlying metabolic dysregulations associated with ASD.AIM 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 chapter.METHODS 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 2024.Inclusion 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 ASD.Exclusion criteria were applied to ensure the relevance and quality of included studies.RESULTS The systematic review identified specific metabolites and metabolic pathways showing consistent differences in children with ASD compared to typically developing individuals.These metabolic biomarkers may serve as objective measures to support clinical assessments,improve diagnostic accuracy,and inform personalized treatment approaches.Metabolomic profiling also offers insights into the metabolic alterations associated with comorbid conditions commonly observed in individuals with ASD.CONCLUSION Integration of metabolomic changes in children with ASD holds promise for enhancing diagnostic accuracy,guiding personalized treatment approaches,monitoring treatment response,and improving outcomes.Further research is needed to validate findings,establish standardized protocols,and overcome technical challenges in metabolomic analysis.By 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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Panoramic variation analysis of a family with neurodevelopmental disorders caused by biallelic loss-of-function variants in TMEM141,DDHD2,and LHFPL5

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Frontiers of Medicine 2024年第1期18卷 81-97页

作者： Liwei Sun Xueting Yang Amjad Khan Xue Yu Han Zhang Shirui Han Xiaerbati Habulieti Yang Sun Rongrong Wang Xue Zhang McKusick-Zhang Center for Genetic Medicine State Key Laboratory for Complex Severe and Rare DiseasesInstitute of Basic Medical Sciences Chinese Academy of Medical SciencesSchool of Basic Medicine Peking Union Medical CollegeBeijing100005China Chongqing Key Laboratory of Human Embryo Engineering Center for Reproductive MedicineNational Key Clinical Speciality Construction Project(Obstetrics and Gynecology)Chongqing Health Center for Women and ChildrenChongqing400013China Chongqing Clinical Research Center for Reproductive Medicine Women and Children’s Hospital of Chongqing Medical UniversityChongqing400013China Faculty of Biological Sciences Department of ZoologyUniversity of Lakki MarwatKhyber Pakhtunkhwa28420Pakistan Institute for medical Genetics and Applied Genomics University of TübingenTübingen72076Germany Alexander von Humboldt fellowship Foundation Berlin10117Germany department of pediatrics The First Affiliated Hospital of Guangxi Medical UniversityNanning530000China department of Laboratory Medicine State Key Laboratory for Complex Severe and Rare DiseasesPeking Union Medical College HospitalChinese Academy of Medical Science and Peking Union Medical CollegeBeijing100730China

Highly clinical and genetic heterogeneity of neurodevelopmental disorders presents a major challenge in clinical genetics and medicine.Panoramic variation analysis is imperative to analyze the disease phenotypes resulting from multilocus genomic variation.Here,a Pakistani family with parental consanguinity was presented,characterized with severe intellectual disability(ID),spastic paraplegia,and deafness.Homozygosity mapping,integrated single nucleotide polymorphism(SNP)array,whole-exome sequencing,and whole-genome sequencing were performed,and homozygous variants in TMEM141(c.270G>A,p.Trp90^(*)),DDHD2(c.411+767_c.1249-327del),and LHFPL5(c.250delC,p.Leu84^(*))were identified.A Tmem141^(p.Trp90^(*)/p.Trp90^(*))mouse model was generated.Behavioral studies showed impairments in learning ability and motor coordination.Brain slice electrophysiology and Golgi staining demonstrated deficient synaptic plasticity in hippocampal neurons and abnormal dendritic branching in cerebellar Purkinje cells.Transmission electron microscopy showed abnormal mitochondrial morphology.Furthermore,studies on a human in vitro neuronal model(SH-SY5Y cells)with stable shRNA-mediated knockdown of TMEM141 showed deleterious effect on bioenergetic function,possibly explaining the pathogenesis of replicated phenotypes in the cross-species mouse model.Conclusively,panoramic variation analysis revealed that multilocus genomic variations of TMEM141,DDHD2,and LHFPL5 together caused variable phenotypes in patient.Notably,the biallelic loss-of-function variants of TMEM141 were responsible for syndromic ID.

关键词： neurodevelopmental disorder autosomal recessive intellectual disability consanguinity spastic paraplegia hearing loss TMEM141

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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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Efficacy of physiological seawater nasal irrigation for the treatment of children with SARS-CoV-2 Omicron BA.2 variant infection:a randomized controlled trial

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World Journal of pediatrics 2024年第5期20卷 461-469页

作者： Ji-Lei Lin Fen Zhang Yan-Bo Li Shu-Hua Yuan Jin-Hong Wu Jing Zhang Lei Zhang Yi He Jie Chen Yong Yin department of Respiratory Medicine Shanghai Children’s Medical CenterSchool of MedicineShanghai Jiao Tong University1678 Dongfang RoadPudong DistrictShanghaiChina University of British Columbia VancouverCanada Information Technology department Shanghai Children’s Medical Center National Children’s Medical CenterSchool of MedicineShanghai Jiao Tong University1678 Dongfang RoadPudong DistrictShanghaiChina department of Otorhinolaryngology Shanghai Children’s Medical CenterSchool of MedicineShanghai Jiao Tong University1678 Dongfang RoadPudong DistrictShanghaiChina department of Respiratory Medicine Sanya Women and Children’s Hospital Affiliated to Hainan Medical CollegeHainan Branch of Shanghai Children’s Medical CenterSanyaChina department of Respiratory Medicine Linyi Maternal and Child Healthcare HospitalLinyiChina Shanghai Children’s medical Center Pediatric medical complex(Pudong) ShanghaiChina Pediatric AI Clinical Application and Research Center Shanghai Children’s Medical CenterShanghaiChina

Background Saline nasal irrigation is an effective therapy for relieving common cold symptoms.This study aimed to investigate and explore the efficacy of physiological seawater nasal irrigation(PSNI)on children with mild and asymptomatic infection with Omicron.Methods This randomized controlled trial was conducted in Shanghai,China,and 403 children with mild and asymptomatic infection with Omicron were included.These children were allocated into the PSNI group and the control group.The primary outcome was the duration of viral shedding(DVS),and the secondary outcome was the change in clinical symptoms.Results The median age of all participants was 5.59(6.26)years old.The DVS was significantly shorter in the PSNI group[2.40(1.13)]than in the control group[3.09(2.14)](P=0.014).The multivariable Cox regression model also showed that patients in the PSNI group had an increased probability of shorter DVS compared with patients in the control group[hazard ratio(HR),1.27;95%confidence interval(CI),1.04–1.55;P=0.017].Subgroup analysis suggested that the DVS of patients without full vaccination was significantly reduced in the PSNI group.The proportions of runny nose and stuffy nose were apparently reduced in the first three days in the PSNI group or the control group,but there was no evidence showing that PSNI contributes to the benefit compared with the control group.Conclusion PSNI can reduce the DVS of patients with mild and asymptomatic infection with SARS-CoV-2 Omicron BA.2 variant.

关键词： Children Duration of viral shedding Omicron Physiological seawater nasal irrigation

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

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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 today.Since 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 metabolism.However,controversial research emerges regarding the beneficial/detrimental effects of metformin on these neurological disorders.Given 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 disorders.These 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 therapy.In 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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