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Isoform-and cell-state-specific APOE homeostasis and function

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Neural Regeneration Research 2024年第11期19卷 2456-2466页

作者： Karina Lindner Anne-Claude Gavin Department of Cell Physiology and Metabolism Faculty of MedicineUniversity of GenevaGenevaSwitzerland Diabetes Center Faculty of MedicineUniversity of GenevaGenevaSwitzerland

Apolipoprotein E is the major lipid transporter in the brain and an important player in neuron-astrocyte metabolic *** ensures the survival of neurons under stressful conditions and hyperactivity by nourishing and detoxifying *** E polymorphism,combined with environmental stresses and/or age-related alterations,influences the risk of developing late-onset Alzheimer’s *** this review,we discuss our current knowledge of how apolipoprotein E homeostasis,*** synthesis,secretion,degradation,and lipidation,is affected in Alzheimer’s disease.

关键词： Alzheimer’s disease apolipoprotein E autophagy cholesterol lipid detoxification lipid transport lysosomal failure metabolic impairment triacylglycerol

Impact of Atrial Septal Defect Closure on Mortality in Older Patients

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Congenital Heart Disease 2024年第1期19卷 93-105页

作者： Sipawath Khamplod Yodying Kaolawanich Khemajira Karaketklang Nithima Ratanasit Division of Cardiology Department of MedicineFaculty of Medicine Siriraj HospitalMahidol UniversityBangkokThailand Her Majesty Cardiac Center Faculty of Medicine Siriraj HospitalMahidol UniversityBangkokThailand Department of medicine Faculty of Medicine Siriraj HospitalMahidol UniversityBangkokThailand

Background:Atrial septal defect(ASD)is a common form of adult congenital heart disease that can lead to long-term adverse outcomes if left *** closure of ASD has been associated with excellent outcomes and lower complication ***,there is limited evidence regarding the prognosis of ASD closure in older *** study aims to evaluate the mortality rates in older ASD patients with and without ***:A retrospective cohort study was conducted on patients aged 40 years or older with ASD between 2001 and *** were followed up to assess all-cause *** and multivariable analyses were performed to identify the predictors of mortality.A p-value of<0.05 was considered statistically signiﬁ***:The cohort consisted of 450 patients(mean age 56.6±10.4 years,77.3%female),with 66%aged between 40 and 60 years,and 34%over 60 *** the cohort,299 underwent ASD closure(201 with transcatheter and 98 with surgical closure).During the median follow-up duration of 7.9 years,51 patients *** unadjusted cumulative 10-year rate of mortality was 3%in patients with ASD closure,and 28%in patients without ASD closure(log-rank p<0.001).Multivariable analysis revealed that age(hazard ratio[HR]1.04,95%conﬁdence interval[CI]1.006–1.06,p=0.01),NYHA class(HR 2.75,95%CI 1.63–4.62,p<0.001),blood urea nitrogen(BUN)(HR 1.07,95%CI 1.03–1.12,p<0.001),right ventricular systolic pressure(RVSP)(HR 1.07,95%CI 1.003–1.04,p=0.01),and lack of ASD closure(HR 15.12,95%CI 5.63–40.59,p<0.001)were independently associated with ***:ASD closure demonstrated favorable outcomes in older ***,NYHA class,BUN,RVSP,and lack of ASD closure were identiﬁed as independent factors linked to mortality in this population.

关键词： Atrial septal defect congenital heart disease defect closure long-term survival mortality

Quantitative and qualitative subgenomic RNA profiles of SARS-CoV-2 in respiratory samples: A comparison between Omicron BA.2 and non-VOC-D614G

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Virologica Sinica 2024年第2期39卷 218-227页

作者： Zigui Chen Rita Way Yin Ng Grace Lui Lowell Ling Agnes S.Y.Leung Chit Chow Siaw Shi Boon Wendy C.S.Ho Maggie Haitian Wang Renee Wan Yi Chan Albert Martin Li David Shu Cheong Hui Paul Kay Sheung Chan Department of Microbiology Faculty of MedicineThe Chinese University of Hong KongHong KongChina Department of medicine and Therapeutics Faculty of MedicineThe Chinese University of Hong KongHong KongChina Department of Anaesthesia and Intensive Care Faculty of MedicineThe Chinese University of Hong KongHong KongChina Department of Paediatrics Faculty of MedicineThe Chinese University of Hong KongHong KongChina Department of Anatomical and Cellular Pathology Faculty of MedicineThe Chinese University of Hong KongHong KongChina Jockey Club School of Public Health and Primary Care Faculty of MedicineThe Chinese University of Hong KongHong KongChina Stanley Ho Centre for Emerging Infectious Diseases Faculty of MedicineThe Chinese University of Hong KongHong KongChina

The SARS-CoV-2 Omicron variants are notorious for their transmissibility,but little is known about their subgenomic RNA(sgRNA)*** study applied RNA-seq to delineate the quantitative and qualitative profiles of canonical sgRNA of 118 respiratory samples collected from patients infected with Omicron BA.2 and compared with 338 patients infected with non-variant of concern(non-VOC)-D614G.A unique characteristic profile depicted by the relative abundance of 9 canonical sgRNAs was reproduced by both BA.2 and non-VOCD614G regardless of host gender,age and presence of ***,such profile was lost in samples with low viral load,suggesting a potential application of sgRNA pattern to indicate viral activity of individual patient at a specific time point.A characteristic qualitative profile of canonical sgRNAs was also reproduced by both BA.2 and *** presence of a full set of canonical sgRNAs carried a coherent correlation with crude viral load(AUC¼0.91,95%CI 0.88–0.94),and sgRNA ORF7b was identified to be the best surrogate marker allowing feasible routine application in characterizing the infection status of individual *** potentials in using sgRNA as a target for vaccine and antiviral development are worth pursuing.

关键词： Coronavirus SARS-CoV-2 Omicron BA.2 Non-VOC-D614G RNA-seq Subgenomic RNA(sgRNA)

On the functions of astrocyte-mediated neuronal slow inward currents

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Neural Regeneration Research 2024年第12期19卷 2602-2612页

作者： Balázs Pál Department of Physiology Faculty of MedicineUniversity of DebrecenDebrecenHungary

Slow inward currents are known as neuronal excitatory currents mediated by glutamate release and activation of neuronal extra synaptic N-met hyl-D-aspartate receptors with the contribution of *** events are significantly slower than the excitatory postsynaptic *** of slow inward currents are determined by seve ral factors including the mechanisms of astrocytic activation and glutamate release,as well as the diffusion pathways from the release site towards the extra synaptic recepto *** are stimulated by neuronal network activity,which in turn excite neurons,forming an astrocyte-neuron feedback *** as a consequence of brain edema,astrocytic swelling can also induce slow inward currents under pathological *** is a growing body of evidence on the roles of slow inward currents on a single neuron or local network *** events often occur in synchro ny on neurons located in the same astrocytic *** synchronization of neuronal excitability,slow inward currents also set synaptic strength via eliciting timing-dependent synaptic *** addition,slow inward currents are also subject to non-synaptic plasticity triggered by long-la sting stimulation of the excitatory *** note,there might be important regionspecific differences in the roles and actions triggering slow inward *** greater networks,the pathophysiological roles of slow inward currents can be better understood than physiological *** inward currents are identified in the pathophysiological background of autism,as slow inward currents drive early hypersynchrony of the neural *** inward currents are significant contributors to paroxysmal depolarizational shifts/interictal *** events are related to epilepsy,but also found in Alzheimer's disease,Parkinson's disease,and stroke,leading to the decline of cognitive *** with features overlapping with slow inward currents(excitatory,N-methyl-Dasp

关键词： astrocyte cortical spreading depolarization gliotransmission glutamate neural synchronization NMDA receptor paroxysmal depolarizational shift slow inward current

Suppression of mature TAU isoforms prevents Alzheimer's disease-like amyloid-beta oligomer-induced spine loss in rodent neurons

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Neural Regeneration Research 2024年第8期19卷 1655-1657页

作者： Sarah Buchholz Hans Zempel Institute of Human Genetics Faculty of Medicine and University Hospital CologneUniversity of CologneCologneGermany Center for Molecular medicine Cologne(CMMC) Faculty of Medicine and University Hospital CologneUniversity of CologneCologneGermany

Introduction:TAU isoforms as disease mediators:The microtubule-associated protein TAU is predominantly present in the axons of neurons under physiological *** Alzheimer’s disease(AD)and related tauopathies,TAU also mislocalizes("TAU missorting")to the soma and the dendrites,where it eventually forms aggregates,the so-called neurofibrillary tangles(for review see Zimmer-Bensch and Zempel,2021;Zempel,2023).

关键词： Alzheimer Zimmer tau

Lacidipine,thiamine pyrophosphate and their combination on the ocular ischemic syndrome induced by bilateral common carotid artery ligation

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International Journal of Ophthalmology(English edition) 2024年第5期17卷 815-821页

作者： Ibrahim Cicek Ahmet Mehmet Somuncu Durdu Altuner Bahadir Suleyman Renad Mammadov Seval Bulut Taha Abdulkadir Coban Tugba Bal Tastan Halis Suleyman Department of Ophthalmology Faculty of MedicineErzincan Binali Yildirim UniversityErzincan 24100Turkey Department of Pharmacology Faculty of MedicineErzincan Binali Yildirim UniversityErzincan 24100Turkey Department of Clinical Biochemistry Faculty of MedicineErzincan Binali Yildirim UniversityErzincan 24100Turkey Department of Histology and Embryology Faculty of MedicineErzincan Binali Yildirim University ErzincanErzincan 24100Turkey

AIM:To investigate the effect of lacidipine,thiamine pyrophosphate(TPP)and the combination of lacidipine and TPP against oxidative and inflammatory eye damage induced by bilateral common carotid artery ligation in ***:Male albino Wistar rats were categorized as those who underwent sham surgery(SG),right and left common carotid cross-clamping and unclamping procedure(CCU),lacidipine+CCU(LCCU),TPP+CCU(TCCU),and combination of lacidipine and TPP(LTC)+CCU(LTCCU).One hour before anesthesia,the LCCU(n=6)received lacidipine(4 mg/kg,orally)and the TCCU(n=6)received TPP(20 mg/kg,intraperitoneally).The SG(n=6)and CCU(n=6)received the same volume of distilled water from the same *** anesthesia(60 mg/kg ketamine,intraperitoneally),the necks of the rats were opened in the *** was created for 10min by placing clips on the right and left common carotid *** in the SG only underwent subcutaneous *** 10min,the clips were removed and reperfusion was achieved for six ***,the animals were euthanized(120 mg/kg ketamine,intraperitoneally)and the levels of oxidant,antioxidant and proinflammatory cytokines in the eye tissues were *** retinal tissue of the eye was also examined ***:Lacidipine,TPP,and LTC significantly prevent the increase in malondialdehyde,tumor necrosis factoralpha,interleukin-1β(IL-1β),and IL-6 levels,decrease in total glutathione levels,superoxide dismutase and catalase activities and histopathological retinal damage in eye tissue induced by bilateral common carotid artery ligation in *** impact of these drugs on protection is determined to be LTC>lacidipine>***:As a result of the study,it is concluded that LTC may be more effective than lacidipine and TPP alone in treating ocular ischemic syndrome.

关键词： ocular ischemic syndrome lacidipine thiamine pyrophosphate oxidative stress

Inflammatory bowel disease(ulcerative colitis type)severity shows inverse correlation with semen parameters and testosterone levels

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Asian Journal of Andrology 2024年第2期26卷 155-159页

作者： Darmadi Darmadi Cennikon Pakpahan Rajender Singh Ankur Saharan Wanly Syahrizal Pasaribu Hermansyah Hermansyah Andri Rezano Department of Internal medicine Faculty of MedicineUniversitas Sumatera UtaraMedan 20155Indonesia Andrology Study Program Faculty of MedicineUniversitas AirlanggaSurabaya 60132Indonesia Department of Biomedical Sciences Faculty of MedicineUniversitas AirlanggaSurabaya 60132Indonesia Division of Endocrinology Central Drug Research InstituteLucknowUtar Pradesh 226031India Amity University LucknowUttar Pradesh 226010India Department of Biomedical Sciences Faculty of MedicineUniversitas PadjadjaranSumedang 45363Indonesia

Individuals with inflammatory bowel disease(IBD)have been reported to be at an increased risk of infertility and sexual *** the relationship between them remains unclear,IBD severity is suspected to affect hormone levels and *** analyze the impact of IBD severity on semen parameters and sex hormone levels in ulcerative colitis-type IBD(UC-IBD),we conducted a cross-sectional study involving 120 patients with UC-IBD in Adam Malik General Hospital,Medan,*** patients were classified into three groups based on the Mayo score for Uc,followed by a comparison of various semen and hormone parameters among these *** addition to the cross-sectional analysis,a simple correlation test was conducted irrespective of the patient *** concentration,motility,and morphology were found to decline significantly with an increase in IBD *** classifying patients with IBD into subgroups,the Mayo score showed negative correlations with sperm concentration(r=-0.375,P<0.0001),rapid progressive motility(r=-0.660,P<0.0001),free testosterone(r=-0.732,P<0.0001),and total testosterone(r=-0.721,P<0.0001),and positivecorrelations with immotile sperm(r=0.660,P<0.0001),abnormal morphology(r=0.657,P<0.0001),and sex hormone-binding globulin(SHBG;r=0.278,P=0.002).Sperm concentration,motility,and morphology declined significantly with the severity of *** study suggests a significant negative impact of IBD severityonsemenqualityand sexhormones.

关键词： inflammatory bowel disease reproductive health sexual health sperm parameter testosterone

Genomic medicine and cancer clinical trial in Thailand

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Cancer Biology & medicine 2024年第1期21卷 10-15页

作者： Lucksamon Thamlikitkul Napa Parinyanitikul Virote Sriuranpong Division of Medical Oncology Department of MedicineFaculty of Medicine Siriraj HospitalMahidol UniversityBangkok 10700Thailand Division of Medical Oncology Department of MedicineFaculty of MedicineChulalongkorn University&The King Chulalongkorn Memorial HospitalBangkok 10330Thailand

Introduction Cancer treatment has been revolutionized with the advent of targeted therapy and *** the past,when cancer treatment modalities were restricted,conventional chemotherapy was the only option for systemic *** chemotherapy empirically affects all dividing cells,the targets are virtually *** this regard,toxic effects on normal tissue are essentially inevitable.

关键词： chemotherapy cancer Cancer

Early endotracheal intubation is not associated with the rate of return of spontaneous circulation following cardiac arrest at the emergency department:an exploratory analysis

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World Journal of Emergency medicine 2024年第4期15卷 297-300页

作者： Siwat Neamjun Phichayut Phinyo Borwon Wittayachamnankul Wachira Wongtanasarasin Department of Emergency medicine Faculty of MedicineChiang Mai UniversityChiang Mai 50200Thailand Department of Family medicine Faculty of MedicineChiang Mai UniversityChiang Mai 50200Thailand Center for Clinical Epidemiology and Clinical Statistics Faculty of MedicineChiang Mai UniversityChiang Mai 50200Thailand Department of Emergency medicine University of California Davis School of MedicineSacramento 95817USA

Cardiac arrest poses a significant global public health challenge,manifesting in approximately 550,000 cases annually within the United States.[1]In-hospital cardiac arrest(IHCA)is commonly attributed to airways and respiratory issues.[2]Recommendations emphasize the expertise of responders in airway management.[3]Various options exist,such as chest compression-only cardiopulmonary resuscitation(CPR),bag-mask ventilation(BMV),and advanced *** BMV and advanced airways are not deemed equivalent or superior based on previous evidence.[4]Achieving consistency in choosing and timing the optimal airway approach during IHCA is *** current American Heart Association guidelines suggest an advanced airway strategy when endotracheal intubation(ETI)success rates are high,but the optimal time for advanced airway management remains unclear.[5]Wong et al[6]revealed that survival improved by less than 5 min with advanced airway *** to a subgroup analysis of IHCA patients in emergency departments(EDs),early intubation was associated with a 1.5-fold greater rate of return of spontaneous circulation(ROSC)than in other locations.[7]ED patients’constant monitoring and immediate management,with readily available intubation equipment,enhance early intubation and survival rates.[6]Nonetheless,IHCA patients intubated within the first 15 min had a lower ROSC rate.

关键词： intubation return annually