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MicroRNA-502-3p regulates GABAergic synapse function in hippocampal neurons

Neural Regeneration Research 2024年第12期19卷 2698-2707页

作者： Bhupender Sharma Melissa MTorres sheryl Rodriguez laxman Gangwani Subodh Kumar Center of Emphasis in Neuroscience Department of Molecular and Translational MedicinePaul L.Foster School of MedicineTexas Tech University Health Sciences CenterEl PasoTXUSA Bond life Sciences Center and Department of Veterinary Pathobiology University of MissouriColumbiaMOUSA l.Frederick Francis Graduate School of Biomedical Sciences Texas Tech University Health Sciences CenterEl PasoTXUSA

Gamma-aminobutyric acid(GABA)ergic neurons,the most abundant inhibitory neurons in the human brain,have been found to be reduced in many neurological disorders,including Alzheimer's disease and Alzheimer's disease-related dementia.Our previous study identified the upregulation of microRNA-502-3p(miR-502-3p)and downregulation of GABA type A receptor subunitα-1 in Alzheimer's disease synapses.This study investigated a new molecular relationship between miR-502-3p and GABAergic synapse function.In vitro studies were perfo rmed using the mouse hippocampal neuronal cell line HT22 and miR-502-3p agomiRs and antagomiRs.In silico analysis identified multiple binding sites of miR-502-3p at GABA type A receptor subunitα-1 mRNA.luciferase assay confirmed that miR-502-3p targets the GABA type A receptor subunitα-1 gene and suppresses the luciferase activity.Furthermore,quantitative reve rse transcription-polymerase chain reaction,miRNA in situ hybridization,immunoblotting,and immunostaining analysis confirmed that overexpression of miR-502-3p reduced the GABA type A receptor subunitα-1 level,while suppression of miR-502-3p increased the level of GABA type A receptor subunitα-1 protein.Notably,as a result of the overexpression of miR-502-3p,cell viability was found to be reduced,and the population of necrotic cells was found to be increased.The whole cell patch-clamp analysis of human-GABA receptor A-α1/β3/γ2l human embryonic kidney(HEK)recombinant cell line also showed that overexpression of miR-502-3p reduced the GABA current and overall GABA function,suggesting a negative correlation between miR-502-3p levels and GABAergic synapse function.Additionally,the levels of proteins associated with Alzheimer s disease were high with miR-502-3p overexpression and reduced with miR-502-3p suppression.The present study provides insight into the molecular mechanism of regulation of GABAergic synapses by miR-502-3p.We propose that micro-RNA,in particular miR-502-3p,could be a potential therapeutic to rget to modulate GABAergic synapse f

关键词： Alzheimer's disease GABAergic synapse gamma-aminobutyric acid type A receptor subunitα-1(GABRα1) microRNA-502-3p(miR-502-3p) miRNA in situ hybridization Patch-clamp

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Mid-term survival of the Optimys short stem: A prospective case series of 500 patients

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World Journal of Orthopedics 2024年第3期15卷 257-265页

作者： Bryan Hamans sheryl de Waard Sjoerd Kaarsemaker Esther R C Janssen Inger N Sierevelt Gino M M J Kerkhoffs Daniël Haverkamp Department of Orthopaedic Surgery Xpert ClinicAmsterdam 1101EANetherlands Department of Orthopedic Surgery Amsterdam University Medical CenterAmsterdam 1105 AZNetherlands Esther R C Janssen Department of Orthopaedic SurgeryViecuri Medisch CentrumVenlo 5912 BLNetherlands Centre for Orthopaedic Research Spaarne ZiekenhuisHoofddorp 2134 TMNetherlands Department of Orthopaedic Surgery and Sports Medicine Amsterdam UMC-Location AMCAmsterdam 1105 AZNetherlands Department of Orthopedic Surgery Xpert Orthopedic Surgery ClinicAmsterdam 1101 EANetherlands

BACKGROUND In recent years,there has been an increase in the number of total hip arthroplasty procedures in the younger patient population.This active group has higher expectations of their prosthesis in comparison to the older population,and there is a greater physical demand for the prosthesis.Short femoral stems were in-troduced to retain proximal bone stock and joint biomechanics and became more common to implant in this specific population.Currently,the long-term survival and functional outcomes of various short stems are still being investigated in different clinics.AIM To determine the 5-year survival of the Optimys hip stem.METHODS This was a prospective multicenter cohort study of 500 patients conducted in two hospitals in the Netherlands.All patients received the Optimys short stem(Mathys ltd,Bettlach,Switzerland).The primary outcome measure was survival of the hip stem,with revision as the endpoint.The secondary outcome measurements included patient-reported outcome measures(PROMs).Kaplan-Meier analysis was used to calculate the 5-year survival rate.log-minus-log transformation was performed to calculate the 95%confidence interval(95%CI).Mixed model analyses were performed to assess the course of the PROMs during the 1st 2 years after surgery.Analyses were modeled separately for the 1st and 2nd years to calculate the yearly change in PROMs during both follow-up periods with accompanying 95%CIs.RESUlTS The mean age of the total 500 patients was 62.3 years(standard deviation:10.6)and 202 were male(40%).At a median follow-up of 5.5 years(interquartile range:4.5-6.7),7 patients were deceased and 6 revisions were registered,for infection(n=3),subsidence(n=2)and malposition(n=1).This resulted in an overall 5-year survival of 98.8%(95%CI:97.3-99.5).If infection was left out as reason for revision,a stem survival of 99.4%(95%CI:98.1-99.8)was seen.Baseline questionnaires were completed by 471 patients(94%),317 patients(63%)completed the 1-year follow-up questionnaires and 233 patients(47%)completed the 2-year f

关键词： Total hip arthroplasty Femoral stem Short stem Optimys Survival 5-year survival Revision PROMs

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中国临床药学新方向:采用“形式遵循功能”方式,提高医疗保健效果（英文）

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Journal of Chinese Pharmaceutical Sciences 2018年第5期27卷 352-360页

作者：陈孝高翔陈杰 sheryl l chow Moses S.S.chow 中山大学附属第一医院药学部广东广州510080 College of Pharmacy Western University of Health Sciences

临床药学是现代药学实践中的重要发展。在中国,卫计委对临床药师的认可是成功改变药师职能作用的重要一步,使药师直接参与提高医疗效果。为使这种职能作用改变最优化,我们建议实行"形式遵循功能"的方式。我们认为由3个部分组成的"形式"... 详细信息

临床药学是现代药学实践中的重要发展。在中国,卫计委对临床药师的认可是成功改变药师职能作用的重要一步,使药师直接参与提高医疗效果。为使这种职能作用改变最优化,我们建议实行"形式遵循功能"的方式。我们认为由3个部分组成的"形式"是非常可取的,应精心协调建立:(1)正规教育/培训课程;(2)带领实践/研究临床改进的专业组织;(3)进行优质教育/培训和实践的认证机构。通过结合美国和其他国家的临床药学经验并采用这种"形式遵循功能"的方式,可以预见中国临床药师的光明未来,作为临床治疗团队的重要一员,对医疗保健效果产生积极的影响。

关键词：临床药学中国医疗保健

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Prevalence and risk factors for impaired renal function among Asian patients with nonalcoholic fatty liver disease

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Hepatobiliary & Pancreatic Diseases International 2024年第3期23卷 241-248页

作者： Chao Sun George Boon-Bee Goh Wan-Cheng chow Wah-Kheong Chan Grace lai-Hung Wong Wai-Kay Seto Yi-Hsiang Huang Han-Chieh lin I-Cheng lee Hye Won lee Seung Up Kim Vincent Wai-Sun Wong Jian-Gao Fan Center for Fatty liver Disease Department of GastroenterologyXinhua Hospital Affiliated to Shanghai Jiao Tong University School of MedicineShanghai Key Lab of Pediatric Gastroenterology and NutritionShanghai 200092China Department of Gastroenterology&Hepatology Singapore General HospitalSingaporeSingapore Gastroenterology and Hepatology Unit Department of MedicineFaculty of MedicineUniversity of MalayaKuala LumpurMalaysia Department of Medicine and Therapeutics and State Key laboratory of Digestive Disease The Chinese University of Hong KongHong KongChina Department of Medicine The University of Hong KongHong KongChina Institute of Clinical Medicine National Yang Ming Chiao Tung University School of MedicineTaipeiTaiwanChina Division of Gastroenterology and Hepatology Taipei Veterans General HospitalTaipeiTaiwanChina Faculty of Medicine National Yang Ming Chiao Tung University School of MedicineTaipeiTaiwanChina Department of Internal Medicine Yonsei University College of MedicineSeoulKorea

Background:Nonalcoholic fatty liver disease(NAFlD)is associated with impaired renal function,and both diseases often occur alongside other metabolic disorders.However,the prevalence and risk factors for impaired renal function in patients with NAFlD remain unclear.The objective of this study was to identify the prevalence and risk factors for renal impairment in NAFlD patients.Methods:All adults aged 18-70 years with ultrasound-diagnosed NAFlD and transient elastography examination from eight Asian centers were enrolled in this prospective study.liver fibrosis and cirrhosis were assessed by FibroScan-aspartate aminotransferase(FAST),Agile 3+and Agile 4 scores.Impaired renal function and chronic kidney disease(CKD)were defined by an estimated glomerular filtration rate(eGFR)with value ofl/min/1.73 m^(2) andl/min/1.73 m^(2),respectively,as estimated by the CKD-Epidemiology Collaboration(CKD-EPI)equation.Results:Among 529 included NAFlD patients,the prevalence rates of impaired renal function and CKD were 37.4%and 4.9%,respectively.In multivariate analysis,a moderate-high risk of advanced liver fibrosis and cirrhosis according to Agile 3+and Agile 4 scores were independent risk factors for CKD(Plasma glucose(FPG)and blood pressure were significantly associated with impaired renal function after controlling for the other components of metabolic syndrome(Plycemia,those with prediabetes[FPG≥5.6 mmol/l or hemoglobin A1c(HbA1c)≥5.7%]were more likely to have impaired renal function(Plusions:Agile 3+and Agile 4 are reliable for identifying NAFlD patients with high risk of CKD.Early glycemic control in the prediabetic stage might have a potential renoprotective role in these patients.

关键词： Nonalcoholic fatty liver disease Impaired renal function Agile 3+ Agile 4 Metabolic syndrome

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Extracellular vesicles as a potential therapeutic for age-related macular degeneration

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Neural Regeneration Research 2023年第9期18卷 1876-1880页

作者： lorraine l.C.chow Ben Mead School of Optometry and Vision Sciences Cardiff UniversityCardiffUK

Age-related macular degeneration is a major global cause of central visual impairment and seve re vision loss.With an aging population,the already immense economic burden of costly anti-vascular endothelial growth fa ctor treatment is likely to increase.In addition,current conventional treatment is only available for the late neovascular stage of age-related macular degeneration,and injections can come with potentially devastating complications,introducing the need for more economical and ris kfree treatment.In recent years,exosomes,which are nano-sized extracellular vesicles of an endocytic origin,have shown immense potential as diagnostic biomarkers and in the therapeutic application,as they are bestowed with characte ristics including an expansive cargo that closely resembles their parent cell and exceptional ability of intercellular communication and targeting neighboring cells.Exosomes are currently undergoing clinical trials for various conditions such as type 1 diabetes and autoimmune diseases;however,exosomes as a potential therapy for seve ral retinal diseases have just begun to undergo scrutinizing investigation with little literature on age-related macular degeneration specifically.This article will focus on the limited literature availa ble on exosome transplantation treatment in age-related macular degeneration animal models and in vitro cell cultures,as well as briefly identify future research directions.Current literature on exosome therapy using agerelated macular degeneration rodent models includes laser retinal injury,N-methyl-N-nitrosourea,and royal college of surgeon models,which mimic inflammatory and degenerative aspects of agerelated macular degeneration.These have shown promising results in preserving retinal function and morphology,as well as protecting photoreceptors from apoptosis.Exosomes from their respective cellular origins may also act by regulating the expression of various inflammatory cyto kines,mRNAs,and proteins involved in photo receptor degeneration pathways to exert a thera

关键词： age-related macular degeneration exosomes extracellular vesicles miRNA neuroprotection photoreceptors retina retinal pigment epithelium

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Femoroacetabular offset restoration in total hip arthroplasty;Digital templating a short stem vs a conventional stem

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World Journal of Orthopedics 2022年第2期13卷 139-149页

作者： sheryl de Waard Tom Verboom Niels Hendrik Bech Inger N Sierevelt Gino M Kerkhoffs Daniël Haverkamp Orthopedic Surgery Xpert Orthopedie AmsterdamAmsterdam 1101 EANetherlands Orthopaedic Surgery Academic Medical CentreAmsterdam 1105 AZNetherlands

BACKGROUND Failure in restoring individual anatomy could be a reason for persistent functional limitations post total hip arthroplasty.Femoroacetabular offset(FAO)plays an important role in anatomic restoration,as loss of offset≥5 mm is associated with altered gait and decreased functional outcome.Preoperative assessment by use of digital templating has shown to be a reliable method for sizing the components in total hip arthroplasty,and can show if anatomic restoration is achieved.In recent years,short stems are growing in popularity as it could allow better restoration due to more variety in placement.AIM To assess whether restoration of the FAO differs between a short or a conventional stem by use of digital templating.Additionally,association of the preoperative offset and caput-colllum-diaphyseal angle(CCD-angle)within restoration of both stems was investigated,and the reliability of measurements was assessed.METHODS A total of 100 standardized hip radiographs were used for digital templating.Restoration of FAO was classified into“restored”or“not restored”,when aline value presented,respectively.Differences between the two stems concerning proportions of correct restoration of the FAO were analyzed by use of McNemar tests.To assess association between CCDangle and preoperative FAO with absolute FAO restoration,multi-level analysis was performed by use of a linear mixed model to account for paired measurements.Through determination of the optimal point under the curve in operating curve-analysis,bootstrapping of thousand sets was performed to determine the optimal cutoff point of the preoperative FAO for restoration within the limits of 5 mm.Three observers participated for inter-observer reliability,with two observers measuring the radiographs twice for intra-observer reliability.RESUlTS The mean preoperative FAO was 79.7 mm(range 62.5-113 mm),with a mean CCD-angle of 128.6°(range 114.5°-145°).The conventional stem could only restore the FAO in 72 of the cases,whereas the sh

关键词： Offset Anatomic offset restoration Total hip arthroplasty Short hip stem Conventional hip stem

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Integrity of the hip capsule measured with magnetic resonance imaging after capsular repair or unrepaired capsulotomy in hip arthroscopy

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World Journal of Orthopedics 2022年第4期13卷 400-407页

作者： Niels H Bech lode A van Dijk sheryl de Waard Gwendolyn Vuurberg Inger N Sierevelt Gino MMJ Kerkhoffs Daniël Haverkamp Department of Orthopedic Surgery Amsterdam University Medical CenterAmsterdam 1105 AZNetherlands Department of Orthopedic Surgery Xpert Orthopedic Surgery ClinicAmsterdam 1101 EANetherlands Department of Orthopedic Surgery Tergooi ZiekenhuisHilversum 1213 XZNetherlands Department of Radiology and Nuclear Medicine Rijnstate HospitalArnhem 6815 ADNetherlands Department of Radiology and Nuclear Medicine Amsterdam University Medical CenterAmsterdam 1105 AZNetherlands Centre for Orthopaedic Research Spaarne ZiekenhuisHoofddorp 2134 TMNetherlands Academic Center for Evidence-Based Sports Medicine Amsterdam University Medical CenterAmsterdam 1105 AZNetherlands Amsterdam Collaboration on Health and Safety in Sports Amsterdam UMC/IOC Research CenterAmsterdam 1105 AZNetherlands

BACKGROUND Current literature shows no clear answer on the question how to manage the capsule after hip arthroscopy.Regarding patient reported outcome measures there seems to be no difference between capsular repair or unrepaired capsulotomy.AIM To evaluate and compare the integrity of the hip capsule measured on a magnetic resonance imaging(MRI)scan after capsular repair or unrepaired capsulotomy.METHODS A case series study was performed;a random sample of patients included in a trial comparing capsular repair vs unrepaired capsulotomy had a postoperative MRI scan.The presence of a capsular defect and gap size were independently evaluated on MRI.RESUlTS A total of 28 patients(29 hips)were included.Patient demographics were comparable between treatment groups.There were 2 capsular defects in the capsular repair group and 7 capsular defects in the unrepaired capsulotomy group(P=0.13).In the group of patients with a defect,median gap sizes at the acetabular side were 5.9 mm(range:2.7-9.0)in the repaired and 8.0 mm(range:4.5-18.0)in the unrepaired group(P=0.462).At the muscular side gap sizes were 6.6 mm(range:4.1-9.0)in the repaired group and 11.5 mm(range:3.0-18.0)in the unrepaired group(P=0.857).The calculated Odds ratio(OR)for having a capsular defect with an increasing lateral center-edge(CE)angle was 1.12(P=0.06).The OR for having a capsular defect is lower in the group of patients that underwent a labral repair with an OR of 0.1(P=0.05).CONClUSION There is no significant difference in capsular defects between capsular repair or unrepaired capsulotomy.Regarding clinical characteristics our case series shows that a larger CE angle increases the likelihood of a capsular defect and the presence of a labral repair decreases the likelihood of a capsular defect.

关键词： Hip Arthroscopy Magnetic resonance imaging Capsule Thickness

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linewidth narrowing in self-injection-locked on-chip lasers

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light(Science & Applications) 2023年第10期12卷 2074-2083页

作者： Emad Alkhazraji Weng W.chow Frédéric Grillot John E.Bowers Yating Wan Integrated Photonics lab King Abdullah University of Science and TechnologyThuwal 23955Saudi Arabia Sandia National laboratories AlbuquerqueNM 87185-1086USA lTCI Télécom ParisInstitut Polytechnique de Paris91120 PalaiseauFrance Department of Electronic and Computer Engineering University of California-Santa BarbaraSanta BarbaraCA 93106USA

Stable laser emission with narrow linewidth is of critical importance in many applications,including coherent communications,lIDAR,and remote sensing.In this work,the physics underlying spectral narrowing of self-injection-locked on-chip lasers to Hz-level lasing linewidth is investigated using a composite-cavity structure.Heterogeneously integrated III–V/SiN lasers operating with quantum-dot and quantum-well active regions are analyzed with a focus on the effects of carrier quantum confinement.The intrinsic differences are associated with gain saturation and carrier-induced refractive index,which are directly connected with 0-and 2-dimensional carrier densities of states.Results from parametric studies are presented for tradeoffs involved with tailoring the linewidth,output power,and injection current for different device configurations.Though both quantum-well and quantum-dot devices show similar linewidth-narrowing capabilities,the former emits at a higher optical power in the self-injection-locked state,while the latter is more energy-efficient.lastly,a multi-objective optimization analysis is provided to optimize the operation and design parameters.For the quantum-well laser,minimizing the number of quantum-well layers is found to decrease the threshold current without significantly reducing the output power.For the quantum-dot laser,increasing the quantum-dot layers or density in each layer increases the output power without significantly increasing the threshold current.These findings serve to guide more detailed parametric studies to produce timely results for engineering design.

关键词： narrowing injection quantum

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Effects of music and video on perceived exertion during high-intensity exercise

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Journal of Sport and Health Science 2017年第1期6卷 81-88页

作者： Enoch C.chow Jennifer l.Etnier Department of Kinesiology University of North Carolina at GreensboroGreensboroNC 27412USA

Background: Dissociative attentional stimuli(e.g., music, video) are effective in decreasing ratings of perceived exertion(RPE) during low-tomoderate intensity exercise, but have inconsistent results during exercise at higher intensity. The purpose of this study was to assess attentional focus and RPE during high-intensity exercise as a function of being exposed to music, video, both(music and video), or a no-treatment control condition.Methods: During the first session, healthy men(n = 15) completed a maximal fitness test to determine the workload necessary for high-intensity exercise(operationalized as 125% ventilatory threshold) to be performed during subsequent sessions. On 4 subsequent days, they completed 20 min of high-intensity exercise in a no-treatment control condition or while listening to music, watching a video, or both. Attentional focus, RPE,heart rate, and distance covered were measured every 4 min during the exercise.Results: Music and video in combination resulted in significantly lower RPE across time(partial η~2= 0.36) and the size of the effect increased over time(partial η~2= 0.14). Additionally, music and video in combination resulted in a significantly more dissociative focus than the other conditions(partial η~2= 0.29).Conclusion: Music and video in combination may result in lower perceived exertion during high-intensity exercise when compared to music or video in isolation. Future research will be necessary to test if reductions in perceived exertion in response to dissociative attentional stimuli have implications for exercise adherence.

关键词： Acute exercise Attentional focus Effort Perceived exertion

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Amygdala neural ensemble mediates mouse social investigation behaviors

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National Science Review 2023年第1期10卷 108-126页

作者： Ji-an Wei Qing Han Zhihua luo linglin liu Jing Cui Jiahui Tan Billy K.C.chow Kwok-Fai So li Zhang Key laboratory of CNS Regeneration(Ministry of Education) Guangdong-Hong Kong-Macau Institute of CNS RegenerationJinan University School of Biological Sciences The University of Hong Kong State Key laboratory of Brain and Cognitive Science Li Ka Shing Faculty of Medicine The University of Hong Kong Center for Brain Science and Brain-Inspired Intelligence Guangdong-Hong Kong-Macao Greater Bay Area Bioland laboratory(Guangzhou Regenerative Medicine and Health Guangdong laboratory) Co-Innovation Center of Neuroregeneration Nantong University Neuroscience and Neurorehabilitation Institute University of Health and Rehabilitation Sciences Institute of Clinical Research for Mental Health Jinan University

Innate social investigation behaviors are critical for animal survival and are regulated by both neural circuits and neuroendocrine factors.Our understanding of how neuropeptides regulate social interest,however,is incomplete at the current stage.In this study,we identified the expression of secretin(SCT) in a subpopulation of excitatory neurons in the basolateral amygdala.With distinct mole cular and physiological features,BlASCT+cells projected to the medial prefrontal cortex and were necessary and sufficient for promoting social investigation behaviors,whilst other basolateral amygdala neurons were anxiogenic and antagonized social behaviors.Moreover,the exogenous application of secretin effectively promoted social interest in both healthy and autism spectrum disorder model mice.These results collectively demonstrate a previously unrecognized group of amygdala neurons for mediating social behaviors and suggest promising strategies for social deficits.

关键词： social interaction basolateral amygdala secretin

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