BACKGROUND Data regarding complex Crohn’s perianal fistulas(CPF)epidemiology are limited,and optimal treatment strategies are elusive.An improved understanding of how CPF treatment options are used in the real-world ...BACKGROUND Data regarding complex Crohn’s perianal fistulas(CPF)epidemiology are limited,and optimal treatment strategies are elusive.An improved understanding of how CPF treatment options are used in the real-world setting and factors associated with CPF development,treatment failure,and reasons for undergoing multiple surgeries may help to inform optimal patient management strategies,reduce treatment burden,and improve outcomes in patients with CPF.AIM To describe the epidemiology,treatments,outcomes,and associated risk/protective factors for complex CPF.METHODS Electronic databases(MEDLINE,EMBASE,EBM Reviews,EconLit)were searched.Two reviewers independently used populations,interventions,comparators,outcomes,study designs,and time criteria to identify relevant studies.Observational studies published in English from January 1,2015 to February 17,2022 with>50 patients were included,even if complex CPF was not defined.Items of interest included complex CPF definitions,epidemiology,treatment patterns,morbidity,mortality,and risk factors associated with complex CPF development,treatment failure,and undergoing multiple surgeries.Data were reported using descriptive statistics.RESULTS Overall,140 studies were included.Complex CPF definitions were heterogeneous and rarely reported(24 studies).Hence,data mostly related to CPF in general.CPF prevalence was variable(range:1.5%-81.0%).Incidence was wide-ranging and mostly reported cumulatively at 1-year post-Crohn’s disease diagnosis(range:3.5%-50.1%).Overall healing and failure rates after treatment were in the range of 10.5%-80.2%and 3.6%-83.0%,respectively.Abscesses were the most frequently reported morbidity(n=18).No CPF-related deaths were reported.No consistent risk or protective factors were identified.CONCLUSION Epidemiology,treatment patterns,and risk factors for CPF vary,likely due to inconsistent CPF and clinical outcome definitions.Standardization would facilitate comparability,which may inform optimal complex CPF treatment strategies.展开更多
The Mohorovicic discontinuity(Moho)boundary separating the Earth’s crust and mantle reflects the evolutionary trajectory of the Earth’s crust,yielding crucial insights into crustal formation,tectonic evolution,and p...The Mohorovicic discontinuity(Moho)boundary separating the Earth’s crust and mantle reflects the evolutionary trajectory of the Earth’s crust,yielding crucial insights into crustal formation,tectonic evolution,and profound dynamic processes.However,the prevailing Moho models for China and its adjacent areas suffer from limited accuracy,owing to the irregular and sparse distribution of seismic data collection.In this study,we employ gravimetric data to derive Moho depth,and employ Bott’s regularization method,integrating gravity and seismic data to reconstruct the Moho structure with high precision in a three-dimensional framework across China and its adjacent areas.By optimizing gravity potential field separation and interface inversion techniques,we present a detailed and accurate zoning scheme for classifying China and its adjacent areas into 35 gradient belts,6 primary tectonic units,and 35 secondary tectonic units,based on the spatial distribution characteristics of the Moho discontinuity.Notably,our tectonic pattern division results surpass previous studies in terms of resolution,providing a wealth of tectonic information.Leveraging the Moho depth model of China and its adjacent areas,we discuss orogenic belts,sedimentary basins,fault systems,plate boundaries,and land-sea coupled tectonic patterns.We meticulously summarize the Moho depth distribution characteristics of each tectonic unit,while exploring the macrostructural framework and geological significance of the study area.Our findings highlight the close relationship between China and its adjacent areas Moho depth model and deep geodynamics,elucidating the tectonic evolution both between and within tectonic plates,as well as the tectonic effects induced by mantle dynamics.These insights have crucial implications for the study of deep geodynamics in China and its adjacent areas.展开更多
Netrin-1 and its receptors play crucial roles in inducing axonal growth and neuronal migration during neuronal development.Their profound impacts then extend into adulthood to encompass the maintenance of neuronal sur...Netrin-1 and its receptors play crucial roles in inducing axonal growth and neuronal migration during neuronal development.Their profound impacts then extend into adulthood to encompass the maintenance of neuronal survival and synaptic function.Increasing amounts of evidence highlight several key points:(1)Diminished Netrin-1 levels exacerbate pathological progression in animal models of Alzheimer’s disease and Parkinson’s disease,and potentially,similar alterations occur in humans.(2)Genetic mutations of Netrin-1 receptors increase an individuals’susceptibility to neurodegenerative disorders.(3)Therapeutic approaches targeting Netrin-1 and its receptors offer the benefits of enhancing memory and motor function.(4)Netrin-1 and its receptors show genetic and epigenetic alterations in a variety of cancers.These findings provide compelling evidence that Netrin-1 and its receptors are crucial targets in neurodegenerative diseases.Through a comprehensive review of Netrin-1 signaling pathways,our objective is to uncover potential therapeutic avenues for neurodegenerative disorders.展开更多
基金Supported by Takeda Pharmaceuticals USA,Inc.Medical writing support was provided by Luke Humphreys,PhD,of Oxford PharmaGenesis,Oxford,UK and was funded by Takeda Development Center Americas,Inc.
文摘BACKGROUND Data regarding complex Crohn’s perianal fistulas(CPF)epidemiology are limited,and optimal treatment strategies are elusive.An improved understanding of how CPF treatment options are used in the real-world setting and factors associated with CPF development,treatment failure,and reasons for undergoing multiple surgeries may help to inform optimal patient management strategies,reduce treatment burden,and improve outcomes in patients with CPF.AIM To describe the epidemiology,treatments,outcomes,and associated risk/protective factors for complex CPF.METHODS Electronic databases(MEDLINE,EMBASE,EBM Reviews,EconLit)were searched.Two reviewers independently used populations,interventions,comparators,outcomes,study designs,and time criteria to identify relevant studies.Observational studies published in English from January 1,2015 to February 17,2022 with>50 patients were included,even if complex CPF was not defined.Items of interest included complex CPF definitions,epidemiology,treatment patterns,morbidity,mortality,and risk factors associated with complex CPF development,treatment failure,and undergoing multiple surgeries.Data were reported using descriptive statistics.RESULTS Overall,140 studies were included.Complex CPF definitions were heterogeneous and rarely reported(24 studies).Hence,data mostly related to CPF in general.CPF prevalence was variable(range:1.5%-81.0%).Incidence was wide-ranging and mostly reported cumulatively at 1-year post-Crohn’s disease diagnosis(range:3.5%-50.1%).Overall healing and failure rates after treatment were in the range of 10.5%-80.2%and 3.6%-83.0%,respectively.Abscesses were the most frequently reported morbidity(n=18).No CPF-related deaths were reported.No consistent risk or protective factors were identified.CONCLUSION Epidemiology,treatment patterns,and risk factors for CPF vary,likely due to inconsistent CPF and clinical outcome definitions.Standardization would facilitate comparability,which may inform optimal complex CPF treatment strategies.
基金supported by the National Natural Science Foundation of China(Grant Nos.42474121 and 42192535)the Basic Frontier Science Research Program of the Chinese Academy of Sciences(Grant No.ZDBS-LY-DQC028).
文摘The Mohorovicic discontinuity(Moho)boundary separating the Earth’s crust and mantle reflects the evolutionary trajectory of the Earth’s crust,yielding crucial insights into crustal formation,tectonic evolution,and profound dynamic processes.However,the prevailing Moho models for China and its adjacent areas suffer from limited accuracy,owing to the irregular and sparse distribution of seismic data collection.In this study,we employ gravimetric data to derive Moho depth,and employ Bott’s regularization method,integrating gravity and seismic data to reconstruct the Moho structure with high precision in a three-dimensional framework across China and its adjacent areas.By optimizing gravity potential field separation and interface inversion techniques,we present a detailed and accurate zoning scheme for classifying China and its adjacent areas into 35 gradient belts,6 primary tectonic units,and 35 secondary tectonic units,based on the spatial distribution characteristics of the Moho discontinuity.Notably,our tectonic pattern division results surpass previous studies in terms of resolution,providing a wealth of tectonic information.Leveraging the Moho depth model of China and its adjacent areas,we discuss orogenic belts,sedimentary basins,fault systems,plate boundaries,and land-sea coupled tectonic patterns.We meticulously summarize the Moho depth distribution characteristics of each tectonic unit,while exploring the macrostructural framework and geological significance of the study area.Our findings highlight the close relationship between China and its adjacent areas Moho depth model and deep geodynamics,elucidating the tectonic evolution both between and within tectonic plates,as well as the tectonic effects induced by mantle dynamics.These insights have crucial implications for the study of deep geodynamics in China and its adjacent areas.
基金supported by the National Natural Science Foundation of China(Youth Science Fund Project),No.81901292(to GC)the National Key Research and Development Program of China,No.2021YFC2502100(to GC)the National Natural Science Foundation of China,No.82071183(to ZZ).
文摘Netrin-1 and its receptors play crucial roles in inducing axonal growth and neuronal migration during neuronal development.Their profound impacts then extend into adulthood to encompass the maintenance of neuronal survival and synaptic function.Increasing amounts of evidence highlight several key points:(1)Diminished Netrin-1 levels exacerbate pathological progression in animal models of Alzheimer’s disease and Parkinson’s disease,and potentially,similar alterations occur in humans.(2)Genetic mutations of Netrin-1 receptors increase an individuals’susceptibility to neurodegenerative disorders.(3)Therapeutic approaches targeting Netrin-1 and its receptors offer the benefits of enhancing memory and motor function.(4)Netrin-1 and its receptors show genetic and epigenetic alterations in a variety of cancers.These findings provide compelling evidence that Netrin-1 and its receptors are crucial targets in neurodegenerative diseases.Through a comprehensive review of Netrin-1 signaling pathways,our objective is to uncover potential therapeutic avenues for neurodegenerative disorders.
