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T1 colorectal cancer management in the era of minimally invasive endoscopic resection

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World Journal of Gastrointestinal Oncology 2024年第6期16卷 2284-2294页

作者： shirley Xue Jiang Aein Zarrin Neal shahidi Department of Medicine University of British ColumbiaVancouver V6Z2K5British ColumbiaCanada Division of Gastroenterology St.Paul’s HospitalVancouver V6Z2K5British ColumbiaCanada

T1 colorectal cancer(CRC),defined by tumor invasion confined to the submucosa,has historically been managed by *** understanding of recurrence and lymph node metastases risk,coupled with advances in endoscopic resection techniques,have led to an increasing capacity for organ-sparing local *** invasive management of T1 CRC begins with optical evaluation of the lesion to diagnose invasive disease and quantify depth of invasion,which informs therapeutic decision *** selection between various available endoscopic resection techniques depends upon lesion characteristics,technique risk-benefit profiles,and location-specific *** endoscopic resection,established histopathology features determine the risk of recurrence and subsequent management including surveillance or adjuvant surgical *** management of non-operative candidates deviates from conventional recommendations with emerging treatment strategies in select populations.

关键词： Cancer Colonoscopy Endoscopy Polyp surgery

Role of practice standardization in outcome optimization for CDH

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World Journal of Pediatric surgery 2024年第2期7卷 110-118页

作者： Alexandra Dimmer Robert Baird Pramod Puligandla Harvey E.Beardmore Division of Pediatric surgery Department of Pediatric SurgeryMontreal Children's HospitalMontrealQuebecCanada Division of Pediatric General and Thoracic surgery British Columbia Children's HospitalVancouverBritish ColumbiaCanada Harvey E.Beardmore Department of Pediatric surgery McGill UniversityMontrealQuebecCanada

standardization of care seeks to improve patient outcomes and healthcare delivery by reducing unwanted variations in care as well as promoting the efficient and effective use of healthcare *** are many types of standardization,with clinical practice guidelines(CPGs),based on a stringent assessment of evidence and expert consensus,being the hallmark of high-quality *** article outlines the history of CPGs,their benefits and shortcomings,with a specific focus on standardization efforts as it relates to congenital diaphragmatic hernia management.

关键词： congenital clinical shortcomings

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 *** study aimed to investigate and explore the efficacy of physiological seawater nasal irrigation(PsNI)on children with mild and asymptomatic infection with *** This randomized controlled trial was conducted in shanghai,China,and 403 children with mild and asymptomatic infection with Omicron were *** children were allocated into the PsNI group and the control *** primary outcome was the duration of viral shedding(DVs),and the secondary outcome was the change in clinical *** The median age of all participants was 5.59(6.26)years *** 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 *** 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 *** 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

Comprehensive Bile Acid Profiling of ABCB4-mutated Patients and the Prognostic Role of Taurine-conjugated􀀖􀄮􀀏􀀙􀄮􀀏􀀚􀄮􀀏􀀔􀀕􀄮􀀐􀀷􀁈􀁗􀁕􀁄􀁋􀁜􀁇􀁕􀁒􀁛􀁜􀁏􀁄􀁗􀁈􀁇􀀃􀀥􀁌􀁏􀁈􀀃􀀤􀁆􀁌􀁇􀀃􀁌􀁑􀀃􀀦􀁋􀁒􀁏􀁈􀁖􀁗􀁄􀁖􀁌􀁖

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Journal of Clinical and Translational Hepatology 2024年第2期12卷 151-161页

作者： Teng Liu Ren-Xue Wang Jun Han Zhong-Die Li Jonathan Asheps Li-Juan Zheng Xiao-Xiao Xu Victor Ling Jian-she Wang Department of Pediatrics Shanghai Medical CollegeFudan UniversityThe Center for Pediatric Liver DiseasesChildren’s Hospital of Fudan UniversityShanghaiChina BC Cancer Agency VancouverBritish Columbia V5Z 1L3Canada University of Victoria-Genome BC Proteomics Center University of VictoriaVictoriaBritish Columbia V8Z 7X8Canada shanghai Key Laboratory of Birth Defect ShanghaiChina

Background and Aims:We asked if comprehensive bile acid profiling could provide insights into the physiopathology of ABCB4-mutated patients and evaluated the prognostic value of taurine-conjugated tetrahydroxylated bile acid(tauro-THBA)in ***:serum bile acid profiles were evaluated in 13 ABCB4-mutated patients with 65 healthy controls by ultra-high-performance liquid chromatography/multiple-reaction monitoring-mass spectrometry(UPLC/MRM-Ms).The concentration of tauro-THBA was compared between ABCB4-mutated patients with different *** areas under the curve(AUCs)of tauro-THBA were compared between ABCB11-mutated patients with native liver survival and those who died or underwent liver transplantation before 3 years of age by receiver operating characteristic curve(ROC),with another patient cohort for further ***:The overall hydrophobicity indices of bile acids in ABCB4-mutated patients(12.99±3.25 m)were significantly lower than those of healthy controls(14.02±1.74 m,ps due to markedly increased bile acid modifications including conjugation,sulfation,and *** in the tauro-THBA concentration in ABCB4-mutated patients with different prognoses were not *** analysis indicated that levels of tauro-THBA ofsensitivity of 80%and specificity of 87.5%for ABCB11-mutated patients with different prognoses(p=0.0192).Of the 15 patients with good prognosis,14 were classified correctly and four of the five patients with a poor prognosis were classified correctly(14:15 vs.1:5,p=0.005)with tauro-THBA as a ***:Tauro-THBA concentration may be a biomarker for predicting the clinical outcome in low gammaglutamyl transferase intrahepatic cholestasis patients.

关键词： Bile acids MDR3 BsEP PFIC Liquid chromatography-mass spectrometry

XBP1 splicing contributes to endoplasmic reticulum stress-induced human islet amyloid polypeptide up-regulation

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Genes & Diseases 2024年第5期11卷 350-359页

作者： Yun Zhang susan Lin Jing Yao Wantong Cai Huaqiu Chen Ailikemu Aierken Zhe Wang Weihong song National Clinical Research Center for Geriatric Disorders Xuanwu HospitalCapital Medical UniversityBeijing 100053China Townsend Family Laboratories Department of PsychiatryThe University of British Columbia2255 Wesbrook MallVancouverBC V6T 1Z3Canada Institute of Aging Key Laboratory of Alzheimer’s Disease of Zhejiang ProvinceSchool of Mental Health and the Affiliated Kangning HospitalWenzhou Medical UniversityWenzhouZhejiang 325000China Oujiang Laboratory(Zhejiang Lab for Regenerative Medicine Vision and Brain Health)WenzhouZhejiang 325001China

As a pathological hallmark of type 2 diabetes mellitus(T2DM),islet amyloid is formed by the aggregation of islet amyloid polypeptide(IAPP).Endoplasmic reticulum(ER)stress interacts with IAPP aggregates and has been implicated in the pathogenesis of *** examine the role of ER stress in T2DM,we cloned the hIAPP promoter and analyzed its promoter activity in human *** found that ER stress significantly enhanced hIAPP promoter activity and expression in human b-cells via triggering X-box binding protein 1(XBP1)*** identified a binding site of XBP1 in the hIAPP *** of this binding site by substitution or deletion mutagenesis significantly diminished the effects of ER stress on hIAPP promoter *** of XBP splicing by MKC3946 treatment inhibited ER stress-induced hIAPP up-regulation and improved human b-cell survival and *** study uncovers a link between ER stress and IAPP at the transcriptional level and may provide novel insights into the role of ER stress in IAPP cytotoxicity and the pathogenesis of T2DM.

关键词： b-cell function Endoplasmic reticulum stress Islet amyloid polypeptide Type 2 diabetes mellitus XBP1

Contactin-associated protein-like 2(CNTNAP2)mutations impair the essentialα-secretase cleavages,leading to autism-like phenotypes

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signal Transduction and Targeted Therapy 2024年第4期9卷 1625-1636页

作者： Qing Zhang Mengen Xing Zhengkai Bao Lu Xu Yang Bai Wanqi Chen Wenhao Pan Fang Cai Qunxian Wang shipeng Guo Jing Zhang Zhe Wang Yili Wu Yun Zhang Jia-Da Li Weihong song Oujiang Laboratory(Zhejiang Lab for Regenerative Medicine Vision and Brain Health)Zhejiang Key Laboratory of Alzheimer's DiseaseZhejiang Provincial Clinical Research Center for Mental DisordersSchool of Mental Health and Wenzhou Kangning HospitalThe Second Affiliated Hospital and Yuying Children's HospitalInstitute of AgingWenzhou Medical UniversityWenzhouZhejiang 325035China Townsend Family Laboratories Department of PsychiatryBrain Research CenterThe University of British Columbia2255 Wesbrook MallVancouverBC V6T 1Z3Canada Chongqing Key Laboratory of Translational Medical Research in Cognitive Development and Learning and Memory Disorders Ministry of Education Key Laboratory of Child Development and DisordersChildren's Hospital of Chongqing Medical UniversityChongqing 400014China Center for Medical Genetics Hunan Key Laboratory of Animal Models for Human DiseasesHunan Key Laboratory of Medical GeneticsHunan International Scientific and Technological Cooperation Base of Animal Models for Human DiseasesSchool of Life SciencesCentral South UniversityChangsha 410078 HunanChina The National Clinical Research Center for Geriatric Disease Xuanwu HospitalCapital Medical UniversityBeijing 100053Chin

Mutations in the Contactin-associated protein-like 2(CNTNAP2)gene are associated with autism spectrum disorder(AsD),and ectodomain shedding of the CNTNAP2 protein plays a role in its ***,key enzymes involved in the C-terminal cleavage of CNTNAP2 remain largely unknown,and the effect of AsD-associated mutations on this process and its role in AsD pathogenesis remain *** this report we showed that CNTNAP2 undergoes sequential cleavages by furin,ADAM10/17-dependent a-secretase and presenilindependent *** identified that the cleavage sites of ADAM10 and ADAM17 in CNTNAP2 locate at its C-terminal residue I79 and L96,and the main a-cleavage product C79 by ADAM10 is required for the subsequent y-secretase cleavage to generate CNTNAP2 intracellular domain(CICD).AsD-associated CNTNAP2 mutations impair the a-cleavage to generate C79,and the inhibition leads to AsDIlike repetitive and social behavior abnormalties in the Cntnap2l1254T knock-in ***,exogenous expression of 79 improves autism-ike phenotypes in the Cntnap2^(11254T) knock-in and Cntnap2^(-/-)knockout *** data demonstrates that the a-secretase is essential for CNTNAP2 processing and its *** study indicates that inhibition of the cleavage by pathogenic mutations underlies AsD pathogenesis,and upregulation of its C-terminal fragments could have therapeutical potentials for AsD treatment.

关键词： NAP2 cleavage subsequent

The role of inflammasomes in human diseases and their potential as therapeutic targets

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signal Transduction and Targeted Therapy 2024年第2期9卷 479-508页

作者： Jing Yao Keenan sterling Zhe Wang Yun Zhang Weihong song The National Clinical Research Center for Geriatric Disease Xuanwu HospitalCapital Medical UniversityBeijing 100053China Townsend Family Laboratories Department of PsychiatryBrain Research CenterThe University of British Columbia2255 Wesbrook MallVancouverBC V6T 1Z3Canada Key Laboratory of Neurodegenerative Diseases Ministry of EducationBeijingP.R.China Zhejiang Clinical Research Center for Mental Disorders Key Laboratory of Alzheimer’s Disease of Zhejiang ProvinceSchool of Mental Health and The Affiliated Kangning HospitalInstitute of AgingWenzhou Medical UniversityWenzhouZhejiang 325000China Oujiang Laboratory(Zhejiang Lab for Regenerative Medicine Vision and Brain Health)WenzhouZhejiang 325000China

Inflammasomes are large protein complexes that play a major role in sensing inflammatory signals and triggering the innate immune *** inflammasome complex has three major components:an upstream sensor molecule that is connected to a downstream effector protein such as caspase-1 through the adapter protein *** formation typically occurs in response to infectious agents or cellular *** active inflammasome then triggers caspase-1 activation,followed by the secretion of pro-inflammatory cytokines and pyroptotic cell *** inflammasome activation and activity contribute to the development of diabetes,cancer,and several cardiovascular and neurodegenerative *** a result,recent research has increasingly focused on investigating the mechanisms that regulate inflammasome assembly and activation,as well as the potential of targeting inflammasomes to treat various *** clinical trials are currently underway to evaluate the therapeutic potential of several distinct inflammasome-targeting ***,understanding how different inflammasomes contribute to disease pathology may have significant implications for developing novel therapeutic *** this article,we provide a summary of the biological and pathological roles of inflammasomes in health and *** also highlight key evidence that suggests targeting inflammasomes could be a novel strategy for developing new disease-modifying therapies that may be effective in several conditions.

关键词： inflam therapeutic potential

miR-429-3p mediates memory decline by targeting MKP-1 to reduce surface GluA1- containing AMPA receptors in a mouse model of Alzheimer’s disease

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Acta Pharmaceutica sinica B 2024年第2期14卷 635-652页

作者： Man Luo Yayan Pang Junjie Li Lilin Yi Bin Wu Qiuyun Tian Yan He Maoju Wang Lei Xia Guiqiong He Weihong song Yehong Du Zhifang Dong Pediatric Research Institute Ministry of Education Key Laboratory of Child Development and DisordersNational Clinical Research Center for Child Health and DisordersChina International Science and Technology Cooperation Base of Child Development and Critical DisordersChongqing Key Laboratory of Translational Medical Research in Cognitive Development and Learning and Memory DisordersChildren’s Hospital of Chongqing Medical UniversityChongqing 400014China Department of Anatomy Basic Medical CollegeChongqing Medical UniversityChongqing 400016China Townsend Family Laboratories Department of PsychiatryThe University of British ColumbiaVancouver BC V6T 1Z3Canada Oujiang Laboratory(Zhejiang Lab for Regenerative Medicine Vision and Brain Health)Institute of AgingKey Laboratory of Alzheimer’s Disease of Zhejiang ProvinceZhejiang Clinical Research Center for Mental DisordersSchool of Mental Health and the Affiliated Kangning HospitalWenzhou Medical UniversityWenzhou 325000China Institute for Brain science and Disease of Chongqing Medical University Chongqing 400016China

Alzheimer ’s disease(AD) is a leading cause of dementia in the ***-activated protein kinase phosphatase 1(MKP-1) plays a neuroprotective role in ***,the molecular mechanisms underlying the effects of MKP-1 on AD have not been extensively ***(miRNAs) regulate gene expression at the post-transcriptional level,thereby repressing mRNA ***,we reported that the microRNA-429-3p(miR-429-3p) was significantly increased in the brain of APP23/Ps45 AD model mice and N2AAPPAD model *** further found that miR-429-3p could downregulate MKP-1 expression by directly binding to its 3’-untranslated region(3’ UTR).Inhibition of miR-429-3p by its antagomir(A-miR-429) restored the expression of MKP-1 to a control level and consequently reduced the amyloidogenic processing of APP and Aβ *** importantly,intranasal administration of A-miR-429 successfully ameliorated the deficits of hippocampal CA1 long-term potentiation and spatial learning and memory in AD model mice by suppressing extracellular signal-regulated kinase(ERK1/2)-mediated GluAl hyperphosphorylation at ser831 site,thereby increasing the surface expression of GluAl-containing α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptors(AMPARs).Together,these results demonstrate that inhibiting miR-429-3p to upregulate MKP-1 effectively improves cognitive and synaptic functions in AD model mice,suggesting that miR-429/MKP-1 pathway may be a novel therapeutic target for AD treatment.

关键词： Alzheimer's disease MKP-1 miR-429-3p AMPAreceptor Learning and memory Long-term potentiation

Biliary brush cytology:Factors associated with positive yields on biliary brush cytology

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World Journal of Gastroenterology 2008年第4期14卷 569-573页

作者： Nasim Mahmoudi Robert Enns Jack Amar Jaber AlAli Eric Lam Jennifer Telford st Paul's hospital University of British ColumbiaVancouver British ColumbiaCanada

AIM: To evaluate the yield of brushing biliary strictures and the factors associated with a positive result in biliary strictures. METHODs: Data on all consecutive patients (01/02 -10/05) who were identified to have a biliary stricture and who underwent biliary brush cytology were collected. The yield of positive biliary brush cytology was evaluated and compared to results with the gold standard for diagnosis (defi ned as either defi nitive surgical histology or clinical course). Additionally,associated factors of positive results including stricture location,gender,age,mass size,length of stricture,and dilatation prior to brushing cytology were assessed. REsULTs: From 199 patients who had brushing cytology samples (10 patients were excluded due to lack of gold standard diagnosis),77 patients had positive brushing cytology (yield 41%). Variables associated with positive cytology brushing on initial endoscopic retrograde cholangiography were age 1.02 (1.00-1.05),mass size > 1 cm 2.22 (1.01-4.89) and length of stricture > 1 cm 3.49 (1.18-10.2). The sensitivity of biliary brushing was 61%,its specifi city 98%,the positive predictive value reached 99%,and the negative predictive value was 57%. CONCLUsION: Our results revealed a 41% positive yield from brushing cytology. The sensitivity of biliary brushing cytology in our center was 61% and the specif icity was 98%. Predictors of positive yield include older age,mass size > 1 cm,and stricture length of > 1 cm.

关键词： Biliary Endoscopic retrograde cholangiopanc reatography Pancreas Gallbladder Ampulla