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Calculus bovis in hepatocellular carcinoma:Tumor molecular basis,Wnt/β-catenin pathway role,and protective mechanism

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World Journal of Gastroenterology 2024年第35期30卷 3959-3964页

作者： Khaled Mohamed Mohamed Koriem Department of Medical Physiology Medical Research and Clinical Studies InstituteNational Research CentreGiza 12622Egypt

In this editorial,we comment on the recent article by Huang et *** editorial focuses specifically on the molecular mechanisms of hepatocellular carcinoma(HCC),mechanism of Wnt/β-catenin pathway in HCC,and protective mechanism of Calculus bovis(CB)in *** cancer is the fourth most common cause of cancer-related deaths *** most prevalent kind of primary liver cancer,HCC,is typically brought on by long-term viral infections(hepatitis B and C),non-alcoholic steatohepatitis,excessive alcohol consumption,and other conditions that can cause the liver to become chronically inflamed and *** is a wellknown traditional remedy in China and Japan and has been used extensively to treat a variety of diseases,such as high fever,convulsions,and *** in lipid metabolism,cholesterol metabolism,bile acid metabolism,alcohol metabolism,and xenobiotic detoxification lead to fatty liver disease and liver ***,which is a tricarboxylic acid cycle intermediate,is vital to energy production and mitochondrial *** is also thought to be a signaling molecule in metabolism and in the development and spread of liver *** Wnt/β-catenin pathway is made up of a group of proteins that are essential for both adult tissue homeostasis and embryonic *** is frequently caused by the dysregulation of the Wnt/β-catenin signaling *** HCC liver carcinogenesis,Wnt/β-catenin signaling is activated by the expression of downstream target *** between the liver and the gut exists via the portal vein,biliary tract,and systemic ***"gutliver axis"controls intestinal *** of the main factors contributing to the development,progression,and treatment resistance of HCC is the abnormal activation of the Wnt/β-Catenin signaling ***,understanding this pathway is essential to treating *** ingredients of CB,particularly oleanolic acid,ergosterol,and ursolic acid,have anti-p

关键词： Hepatocellular carcinoma MicroRNAs Wnt/β-catenin pathway Calculus bovis Apoptosis

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Effectiveness of colorectal cancer screening integrating non-genetic and genetic risk: a prospective study based on uk Biobank data

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cancer Biology & Medicine 2024年第8期21卷 712-723页

作者： Yu Zhang Chao Sheng Zhangyan Lyu Hongji Dai Fangfang Song Fengju Song Yubei Huang Kexin Chen Department of Epidemiology and Biostatistics Key Laboratory of Molecular Cancer EpidemiologyKey Laboratory of Prevention and Control of Human Major DiseasesMinistry of EducationNational Clinical Research Center for CancerTianjin Medical University Cancer Institute and HospitalTianjin Medical UniversityTianjin 300060China

Objective: Few studies have evaluated the benefits of colorectal cancer(CRC) screening integrating both non-genetic and genetic risk factors. Here, we aimed to integrate an existing non-genetic risk model(Qcancer-10) and a 139-variant polygenic risk score to evaluate the effectiveness of screening on CRC incidence and ***: We applied the integrated model to calculate 10-year CRC risk for 430,908 participants in the uk Biobank, and divided the participants into low-, intermediate-, and high-risk groups. We calculated the screening-associated hazard ratios(HRs) and absolute risk reductions(ARRs) for CRC incidence and mortality according to risk ***: During a median follow-up of 11.03 years and 12.60 years, we observed 5,158 CRC cases and 1,487 CRC deaths, respectively. CRC incidence and mortality were significantly lower among screened than non-screened participants in both the intermediateand high-risk groups [incidence: HR: 0.87, 95% confidence interval(CI): 0.81±0.94;0.81, 0.73±0.90;mortality: 0.75, 0.64±0.87;0.70, 0.58±0.85], which composed approximately 60% of the study population. The ARRs(95% CI) were 0.17(0.11±0.24) and 0.43(0.24±0.61), respectively, for CRC incidence, and 0.08(0.05±0.11) and 0.24(0.15±0.33), respectively, for mortality. Screening did not significantly reduce the relative or absolute risk of CRC incidence and mortality in the low-risk group. Further analysis revealed that screening was most effective for men and individuals with distal CRC among the intermediate to high-risk ***: After integrating both genetic and non-genetic factors, our findings provided priority evidence of risk-stratified CRC screening and valuable insights for the rational allocation of health resources.

关键词： Colorectal cancer screening polygenic risk score incidence mortality

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Targeting muscle to treat Charcot-Marie-Tooth disease

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Neural Regeneration research 2024年第8期19卷 1653-1654页

作者： David Villarroel-Campos James N.Sleigh Department of Neuromuscular Diseases and UCL Queen Square Motor Neuron Disease centre UCL Queen Square Institute of NeurologyUniversity College LondonLondonUK uk Dementia research Institute University College LondonLondonUK

Charcot-Marie-Tooth disease(CMT)is a hereditary peripheral neuropathy causing muscle weakness/wasting and sensory dysfunction predominantly in limb *** patients display gait abnormalities,foot deformities,loss of sens... 详细信息

关键词： Marie sensation neuropathy

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Prehospital transdermal glyceryl trinitrate for ultra- acute ischaemic stroke: data from the RIGHT- 2 randomised sham- controlled ambulance trial

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Stroke & Vascular Neurology 2024年第1期9卷 38-49,I0035-I0046页

作者： Jason Philip Appleton Lisa J Woodhouse Craig S Anderson Sandeep Ankolekar Lesley Cala Mark Dixon Timothy J England Kailash Krishnan Grant Mair Keith W Muir John Potter Christopher I Price Marc Randall Thompson G Robinson Christine Roffe Else C Sandset Jeffrey L Saver Angela Shone Aloysius Niroshan Siriwardena Joanna M Wardlaw Nikola Sprigg Philip M Bath Stroke University Hospitals Birmingham NHS Foundation TrustBirminghamUK Institute of Applied Healthresearch University of Birmingham College of Medical and Dental SciencesBirminghamUK Stroke Trials Unit Mental Health and Clinical NeurosciencesUniversity of NottinghamNottinghamUK Faculty of Medicine The George Institute for Global HealthSydneyNew South WalesAustralia The George Institute China at Peking University Health Science Center BeijingChina Neurology Royal Prince Alfred HospitalSydney Health PartnersSydneyNew South WalesAustralia Department of Neurology King's College Hospital NHS Foundation TrustLondonUK Faculty of Health and Medical Sciences University of Western AustraliaCrawleyWestern AustraliaAustralia East Midlands Ambulance Service NHS Trust NottinghamUK Stroke Queen's Medical CentreNottingham University Hospitals NHS TrustNottinghamUK centre for clinical Brain Sciences Dementia Research InstituteUniveristy of EdinburghEdinburghUK Institute of Neurology and Psychology University of GlasgowGlasgowUK Bob Champion research and Education Building University of East AngliaNorwichUK Institute of Neuroscience Newcastle UniversityNewcastle upon TyneUK Department of Neurology Leeds Teaching Hospitals NHS TrustLeedsUK Department of Cardiovascular Sciences and NIHR Leicester Biomedical research centre University of LeicesterLeicesterUK Stroke research in Stoke Institute for Science and Technology in MedicineKeele UniversityStoke-on TrentUK Department of Neurology Oslo University HospitalOsloNorway research and Development Norwegian Air Ambulance FoundationOsloNorway Department of Neurology and Comprehensive Stroke Center David Geffen School of MedicineUCLALos AngelesCaliforniaUSA research and Graduate Services University of NottinghamNottinghamUK Community and Health research Unit University of LincolnLincolnUK

Background The effect of transdermal glyceryl trinitrate(GTN,a nitrovasodilator)on clinical outcome when administered before hospital admission in suspected stroke patients is ***,we assess the safety and efficacy of GTN in the prespecified subgroup of patients who had an ischaemic stroke within the Rapid Intervention with Glyceryl trinitrate in Hypertensive stroke Trial-2(RIGHT-2).Methods RIGHT-2 was an ambulance-based multicentre sham-controlled blinded-endpoint study with patients randomised within 4hours of *** primary outcome was a shift in scores on the modified Rankin scale(mRS)at day *** outcomes included death;a global analysis(Wei-Lachin test)containing Barthel Index,EuroQol-5D,mRS,telephone interview for cognitive status-modified and Zung depression scale;and neuroimaging-determined‘brain frailty’*** were reported as n(%),mean(SD),median[IQR],adjusted common OR(acOR),mean difference or Mann-Whitney difference(MWD)with 95%*** 597 of 1149(52%)patients had a final diagnosis of ischaemic stroke;age 75(12)years,premorbid mRS>2107(18%),Glasgow Coma Scale 14(2)and time from onset to randomisation 67[45,108]***‘brain frailty’was common:median score 2[2,3](range 0–3).At day 90,GTN did not influence the primary outcome(acOR for increased disability 1.15,95%CI 0.85 to 1.54),death or global analysis(MWD 0.00,95%CI-0.10 to 0.09).In subgroup analyses,there were non-significant interactions suggesting GTN may be associated with more death and dependency in participants randomised within 1hour of symptom onset and in those with more severe *** In patients who had an ischaemic stroke,ultra-acute administration of transdermal GTN in the ambulance did not improve clinical outcomes in a population with more clinical and radiological frailty than seen in previous in-hospital *** IS ALREADY KNOWN ON THIS TOPIC⇒Transdermal glyceryl trinitrate(GTN)was associat-ed with less death and dependency in those w

关键词： Glasgow nitrate random

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LKB1 depletion-mediated epithelial-mesenchymal transition induces fibroblast activation in lung fibrosis

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Genes & Diseases 2024年第3期11卷 417-426页

作者： Zijian Xu Elizabeth R.Davies Liudi Yao Yilu Zhou Juanjuan Li Aiman Alzetani Ben G.Marshall David Hancock Tim Wallis Julian Downward Rob M.Ewing Donna E.Davies Mark G.Jones Yihua Wang Biological Sciences Faculty of Environmental and Life SciencesUniversity of SouthamptonSouthampton SO171BJUK clinical and Experimental Sciences Faculty of MedicineUniversity of SouthamptonSouthampton SO166YDUK Institute for Life Sciences University of SouthamptonSouthampton SO171BJUK NIHR Southampton Biomedical research centre University Hospital SouthamptonSouthampton SO166YDUK University Hospital Southampton Southampton SO166YDUK Oncogene Biology The Francis Crick InstituteLondon NW11ATUK

The factors that determine fibrosis progression or normal tissue repair are largely *** previously demonstrated that autophagy inhibition-mediated epithelial-mesenchymal transition(EMT)in human alveolar epithelial type Il(ATIl)cells augments local myofibroblast differentiation in pulmonary fibrosis by paracrine ***,we report that liver kinase B1(LKB1)inactivation in ATIl cells inhibits autophagy and induces EMT as a *** IPF lungs,this is caused by the down-regulation of CAB39L,a key subunit within the LKB1 complex.3D co-cultures of ATIl cells and MRC5 lung fibroblasts coupled with RNA sequencing(RNA-seq)confirmed that paracrine signaling between LKB1-depleted ATIl cells and fibroblasts augmented myofibroblast ***,these data suggest that reduced autophagy caused by LKB1 inhibition can induce EMT in ATIl cells and contribute to fibrosis via aberrant epithelial-fibroblast crosstalk.

关键词： CAB39L Crosstalk EMT LKB1 Pulmonary fibrosis

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Enhancing the clinical relevance of haemorrhage prediction models in trauma

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Military Medical research 2024年第3期11卷 467-468页

作者： Sankalp Tandle Jared M.Wohlgemut Max E.R.Marsden Erhan Pisirir Evangelia Kyrimi Rebecca S.Stoner William Marsh Zane B.Perkins Nigel R.M.Tai centre for Trauma Sciences Blizard InstituteQueen Mary University of LondonLondon E12ATUK The Royal London Hospital Barts Health NHS TrustLondon E11FRUK Academic Department of Military Surgery and Trauma Research and Clinical InnovationThe Royal Centre for Defence MedicineBirmingham B152WBUK Department of Electronic Engineering and Computer Science Queen Mary University of LondonLondon E14NSUK

We read with interest the recent systematic reviewaArtificial intelligence and machine learning for hemorrhagic trauma careoby Peng et al.[1],which evaluated literature on machine learning(ML)in the management of trau... 详细信息

关键词： Trauma Injury Blood transfusion Massive transfusion Prediction Artificial intelligence Machine learning

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Comparative analysis of real-world data of frequent treatment sequences in metastatic prostate cancer

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Current Urology 2024年第2期18卷 104-109页

作者： Jiten Jaipuria Ishleen Kaur Mohammad Najmud Doja Tanvir Ahmad Amitabh Singh Sudhir Kumar Rawal Vineet Talwar Girish Sharma Uro-oncology division Rajiv Gandhi Cancer Institute and Research CentreNew DelhiIndia Amity centre for cancer Epidemiology and cancer research Amity Institute of BiotechnologyAmity UniversityNoidaIndia School of Engineering and Technology Vivekananda Institute of Professional Studies–Technical CampusNew DelhiIndia Department of Computer Engineering Jamia Millia IslamiaNew DelhiIndia Indian Institute of Information Technology SonepatIndia Department of MedicalOncology Rajiv Gandhi Cancer Institute and Research CentreNew DelhiIndia

Background:The incidence of prostate cancer is increasing worldwide.A significant proportion of patients developmetastatic disease and are initially prescribed androgen deprivation therapy(ADT).However,subsequent sequences of treatments in real-world settings that may improve overall survival remain an area of active *** and methods:Data were collected from 384 patients presenting with de novo metastatic prostate cancer from 2011 to 2015 at a tertiary cancer *** were categorized into surviving(n=232)and deceased(n=152)groups at the end of 3 *** sequence pattern mining techniques(Generalized Sequential Pattern Mining and Sequential Pattern Discovery using Equivalence Classes)were applied to determine the exact order of the most frequent sets of treatments in each ***:Degarelix,as the initial form of ADT,was uniquely in the surviving *** sequence of ADT followed by abiraterone and docetaxel was uniquely associated with a higher 3-year overall *** followed by fosfestrol was found to have a unique niche among surviving patients with a long duration of response to the initial *** who received chemotherapy followed by radiotherapy and those who received radiotherapy followed by chemotherapy were found more frequently in the deceased ***:We identified unique treatment sequences among surviving and deceased patients at the end of 3 *** should be the preferred formof *** who received ADT followed by abiraterone and chemotherapy showed better *** requiring palliative radiation and chemotherapy in any sequence were significantlymore frequent in the deceased group,identifying the need to offer such patients the most efficacious agents and to target them in clinical trial design.

关键词： Hormone therapy Metastatic prostate cancer Sequence mining Survival

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Fluidization and Transport of Vibrated Granular Matter:A Review of Landmark and Recent Contributions

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Fluid Dynamics & Materials Processing 2024年第1期20卷 1-29页

作者： Peter Watson Sebastien Vincent Bonnieu Marcello Lappa Department of Mechanical and Aerospace Engineering University of StrathclydeGlasgowUK European Space Agency European Space Research and Technology CentreNoordwijkNetherland

We present a short retrospective review of the existing literature about the dynamics of(dry)granular matter under the effect of *** main objective is the development of an integrated resource where vital information about past findings and recent discoveries is provided in a single *** attention is paid to those works where successful synthetic routes to as-yet unknown phenomena were *** landmark results are analyzed,while smoothly blending them with a history of the field and introducing possible categorizations of the prevalent *** no classification is perfect,and it is hard to distillate general properties out of specific observations or realizations,two possible ways to interpret the existing results are defined according to the type of forcing or the emerging(ensuing)regime of *** particular,first results concerning the case where vibrations and gravity are concurrent(vertical shaking)are examined,then the companion situation with vibrations perpendicular to gravity(horizontal shaking)is *** classes are introduced as follows:(1)Regimes where sand self-organizes leading to highly regular geometrical“pulsating”patterns(thin layer case);(2)Regimes where the material undergoes“fluidization”and develops an internal multicellular convective state(tick layers case);(3)Regimes where the free interface separating the sand from the overlying gas changes inclination or develops a kind a patterned configuration consisting of stable valleys and mountains or travelling waves;(4)Regimes where segregation is produced,i.e.,particles of a given size tend to be separated from the other grains(deep containers).Where possible,an analogy or parallelism is drawn with respect to the companion field of fluid-dynamics for which the assumption of“continuum”can be applied.

关键词： Granular materials vibrations fluidization flowability symmetry breaking

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Reconstruction of Postinfarcted Cardiac Functions Through Injection of Tanshinone ⅡA@Reactive Oxygen Species-Sensitive Microspheres Encapsulated in a Thermoreversible Hydrogel

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Energy & Environmental Materials 2024年第2期7卷 187-199页

作者： Ling Yu Yubin Liang Lei Gao Peipei Chen Zhiqiang Yu Minzhou Zhang Aleksander Hinek Shuai Mao Second clinical College Guangzhou University of Chinese MedicineGuangzhou 510120China Department of Critical Care Medicine Guangdong Provincial Hospital of Chinese MedicineGuangzhou 510120China Guangdong Provincial Branch of National clinical research centre for Chinese Medicine Cardiology Guangzhou 510120China Department of Radiation Medicine and Applied Sciences University of California San DiegoLa JollaCalifornia 92093USA Department of Laboratory Medicine Dongguan Institute of Clinical Cancer ResearchAffiliated Dongguan HospitalSouthern Medical UniversityDongguan 523018China Translational Medicine Hospital for Sick ChildrenToronto M5G 0A4Canada

Myocardial damage resulting from acute myocardial infarction often leads to progressive heart failure and sudden death,highlighting the urgent clinical need for effective ***,tanshinoneⅡA has been identified as a promising therapeutic agent for myocardial ***,efficient delivery remains a major issue that limits clinical *** address this problem,an injectable thermosensitive poly(lactic acid-co-glycolic acid)-block-poly(ethylene glycol)-block-poly(lactic acid-co-glycolic acid)gel(PLGA-PEG-PLGA)system encapsulating tanshinoneⅡA-loaded reactive oxygen species-sensitive microspheres(Gel-MS/tanshinoneⅡA)has been designed and synthesized in this *** thermosensitive hydrogel exhibits good mechanical properties after reaching body *** initially immobilized by the gel exhibit excellent reactive oxygen species-triggered release properties in a high-reactive oxygen species environment after myocardial infarction *** a result,encapsulated tanshinoneⅡA is effectively released into the infarcted myocardium,where it exerts local anti-pyroptotic and anti-inflammatory ***,the combined advantages of this technique contribute to the mitigation of left ventricular remodeling and the restoration of cardiac function following tanshinoneⅡ***,this novel,precision-guided intra-tissue therapeutic system allows for customized local release of tanshinoneⅡA,presenting a promising alternative treatment strategy aimed at inducing beneficial ventricular remodeling in the post-infarct heart.

关键词： myocardial infarction ROS-sensitive polymer tanshinoneⅡA thermoreversible hydrogel ventricular remodeling

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Remote-controlled dexamethasone-duration on eye-surface with a micelle-magnetic nanoparticulate co-delivery system for dry eye disease

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Acta Pharmaceutica Sinica B 2024年第8期14卷 3730-3745页

作者： Qinxiang Zheng Chaoxiang Ge Kexin Li Longxin Wang Xiaoyu Xia Xiao Liu Rashid Mehmood Jianliang Shen Kaihui Nan Wei Chen Sen Lin National Engineering research Center of Ophthalmology and Optometry Eye HospitalWenzhou Medical UniversityWenzhou 325027China National clinical research Center for Ocular Diseases Eye HospitalWenzhou Medical UniversityWenzhou 325027China Zhejiang Engineering research Center for Tissue Repair Materials Wenzhou InstituteUniversity of Chinese Academy of SciencesWenzhou 325000China School of Chemical Engineering UNSW SydneyHigh StreetBuilding E10KensingtonNSW 2052Australia Adult cancer Program Lowy Cancer Research CentreUNSW SydneyCorner Botany&High StreetsKensingtonNSW 2052Australia

Dexamethasone(DEX)is used to treat ocular surface ***,regulating DEX duration in tears while preventing its absorption into the anterior chamber is critical for balancing its therapy effects and the side *** this study,a novel magnetic nanoparticle(MNP)-micelle(MC)codelivery system(MMDS)was *** MC moiety in the MMDS served as the carrier for DEX and the MNP part endowed the MMDS with magnetic-responsive *** extend its residency,the MMDS was magnetically attracted by an external magnet after instilling,which acted as a precorneal drug-depot enabling a sustainable release of DEX in *** combination of magnet treatment,the topical instillation of MMDS@DEX significantly prolonged the DEX-retention in tears and increased the DEX-concentration in the cornea and conjunctiva,as well as concurrently reduced the DEX-level in the aqueous humor,when compared with the commercial DEX eye drop *** combination of MMDS@DEX and magnet treatment exerted significantly better therapeutic effects against DED with smaller side effects than conventional treatments including DEX suspension,commercial DEX eye drops,as well as the MMDS@DEX treatment *** present work provided a new method for the effective delivery of DEX to ocular surface tissues while reducing its side effects,which will be beneficial to the treatments of a wide range of ocular surface diseases.

关键词： Magnetic nanoparticle Micelle Dexamethasone Eye drop Bioavailability Dry eye disease Cornea Conjunctiva

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