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Skel.tal.muscl. as a mol.cul.r and cel.ul.r biomarker of disease progression in amyotrophic l.teral.scl.rosis:a narrative review

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Neural.Regeneration Research 2024年第4期19卷 747-753页

作者： Peter H.King Department of Neurol.gy and center for Neurodegeneration and Experimental.Therapeutics The University of Alabama at BirminghamBirminghamALUSA Birmingham veterans affairs medical center BirminghamALUSA

Amyotrophic l.teral.scl.rosis is a fatal.mul.isystemic neurodegenerative disease with motor neurons being a primary *** progressive weakness is a hal.mark feature of amyotrophic l.teral.scl.rosis,there is considerabl. heterogeneity,incl.ding cl.nical.presentation,progression,and the underl.ing triggers for disease *** on l.ngitudinal.studies with famil.es harboring amyotrophic l.teral.scl.rosis-associated gene mutations,it has become apparent that overt disease is preceded by a prodromal.phase,possibl. in years,where compensatory mechanisms del.y symptom *** 85-90%of amyotrophic l.teral.scl.rosis is sporadic,there is a strong need for identifying biomarkers that can detect this prodromal.phase as motor neurons have l.mited capacity for *** Food and Drug Administration-approved therapies work by sl.wing the degenerative process and are most effective earl. in the *** muscl.,incl.ding the neuromuscul.r junction,manifests abnormal.ties at the earl.est stages of the disease,before motor neuron l.ss,making it a promising source for identifying biomarkers of the prodromal.*** accessibil.ty of muscl. through biopsy provides a l.ns into the distal.motor system at earl.er stages and in real.*** advent of“omics”technol.gy has l.d to the identification of numerous dysregul.ted mol.cul.s in amyotrophic l.teral.scl.rosis muscl.,ranging from coding and non-coding RNAs to proteins and *** technol.gy has opened the door for identifying biomarkers of disease activity and providing insight into disease mechanisms.A major chal.enge is correl.ting the myriad of dysregul.ted mol.cul.s with cl.nical.or histol.gical.progression and understanding their rel.vance to presymptomatic phases of *** are two major goal. of this *** first is to summarize some of the biomarkers identified in human amyotrophic l.teral.scl.rosis muscl. that have a cl.nicopathol.gical.correl.tion with disease activi

关键词： amyotrophic l.teral.scl.rosis biomarkers cl.nicopathol.gical.correl.tion disease progression muscl. biomarkers neurogenic atrophy neuromuscul.r junction non-coding RNAs presymptomatic stages skel.tal.muscl. SOD1G93A mouse model

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Digesting gl.ten with oral.endopeptidases to improve the management of cel.ac disease

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Worl. Journal.of Gastroenterol.gy 2024年第26期30卷 3201-3205页

作者： Katel.n Durham Mirac Nedim Ince Department of Internal.Medicine Division of Gastroenterology and HepatologyUniversity of IowaCarver College of Medicineand the Iowa City Veterans Affairs Medical CenterIowa CityIA 52242United States

In our editorial.we want to comment on the articl. by Stefanol. et al.titl.d“Effect of Aspergil.us niger prol.l.endopeptidase in patients with cel.ac disease on a l.ng-term gl.ten-free diet”.Cel.ac disease is an immune-mediated disorder triggered by dietary gl.ten in genetical.y predisposed *** avoiding gl.ten can permit patients to l.ve symptom-free,ongoing vol.ntary or invol.ntary exposure to gl.ten is common and associated with persistent vil.ous atrophy in smal. bowel.*** vil.ous atrophy predisposes patients to l.fe threatening compl.cations,such as osteoporotic fractures or mal.gnancies,therapeutic adjuncts to gl.ten-free diet become important to improve patients’qual.ty of l.fe and,if these adjuncts can be shown to improve vil.ous atrophy,avoid *** administration of enzyme preparations,such as endopeptidases that digest gl.ten and mitigate its antigenicity to trigger infl.m-mation,is one cl.nical.strategy under *** articl. is about the util.ty of one endopeptidase isol.ted from Aspergil.us *** critique findings of this cl.nical.trial.and al.o summarize endopeptidase-based as wel. as other strategies and how they can compl.ment gl.ten-free diet in the management of cel.ac disease.

关键词： Cel.ac disease Gl.ten-free diet Endopeptidase Vil.ous atrophy Aspergil.us niger Adjunct therapy

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Cal.ium/cal.imimetic via cal.ium-sensing receptor amel.orates chol.ra toxin-induced secretory diarrhea in mice

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Worl. Journal.of Gastroenterol.gy 2024年第3期30卷 268-279页

作者： l.e-Qi Tang Johnathan Fraebel.Shi Jin Steven P Winesett Jane Harrel. Wen-Han Chang Sam Xianjun Cheng Department of Pediatrics University of FloridaGainesvilleFL 32610United States Col.ege of Medicine University of FloridaGainesvilleFL 32610United States Appl.ed Physiol.gy and Kinesiol.gy University of FloridaGainesvilleFL 32610United States Brain Rehabil.tation Research center Malcom Randall VA Medical CenterGainesvilleFL 32610United States Department of Medicine Endocrine Research UnitVeterans Affairs Medical CenterUniversity of CaliforniaSan FranciscoSan FranciscoCA 94121United States Department of Pediatric Gastroenterol.gy Hepatologyand NutritionUniversity of Florida Shands Children’s HospitalGainesvilleFL 32608United States

BACKGROUND Enterotoxins produce diarrhea through direct epithel.al.action and indirectl. by activating the enteric nervous ***-sensing receptor(CaSR)inhibits both *** l.tter has been wel. documented in vitro but not in *** hypothesis to be tested was that activating CaSR inhibits diarrhea in *** To determine whether CaSR agonists amel.orate secretory diarrhea evoked by chol.ra toxin(CTX)in *** CTX was given oral.y to C57Bl.6 mice to induce *** and cal.i-mimetic R568 were used to activate *** maximize their l.cal.intestinal.actions,cal.ium was administered l.minal.y via oral.rehydration sol.tion(ORS),whereas R568 was appl.ed serosal.y using an intraperitoneal.*** verify that their actions resul.ed from the intestine,effects were al.o examined on Cre-l.x intestine-specific CaSR *** outcome was measured biochemical.y by monitoring changes in fecal.Cl.or cl.nical.y by assessing stool.consistency and weight *** CTX induced secretory diarrhea,as evidenced by increases in fecal.Cl.,stool.consistency,and weight l.ss fol.owing CTX exposure,but did not al.er CaSR,neither in content nor in ***,cal.ium and R568 were each abl. to amel.orate diarrhea when appl.ed to diseased *** CaSR invol.ement is suggested by gene knockout experiments where the anti-diarrheal.actions of R568 were l.st in intestinal.epithel.al.CaSR knockouts(vil.inCre/Casrfl.x/fl.x)and neuronal.CaSR knockouts(nestinCre/Casrfl.x/fl.x).CONCl.SION Treatment of acute secretory diarrheas remains a gl.bal.*** advances in diarrhea research,few have been made in the real. of diarrhea *** therapy has remained the standard of care,al.hough it does not hal. the l.sses of intestinal.fl.id and ions caused by *** is no cost-effective therapeutic for *** and other studies suggest that adding cal.ium to ORS or using cal.imimetics to activate intestinal.CaSR might

关键词： Chol.ra Enteric nervous system Secretory diarrhea Oral.rehydration sol.tion Cal.ium-sensing receptor Gene knockout

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Acute and chronic excitotoxicity in ischemic stroke and l.te-onset Al.heimer's disease

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Neural.regeneration research 2024年第7期20卷 2024 Jul 29页

作者： Shan Ping Yu Emil. Choi Michael.Q Jiang l.ng Wei Department of Anesthesiol.gy Emory University School of Medicine Atlanta GA USA. center for Visual.and Neurocognitive Rehabil.tation Atlanta Veterans Affairs Medical Center Decatur GA USA.

Stroke and Al.heimer's disease are common neurol.gical.disorders and often occur in the same individual.. The comorbidity of the two neurol.gical.disorders represents a grave heal.h threat to ol.er popul.tions. This review presents a brief background of the devel.pment of novel.concepts and their cl.nical.potential.. The activity of gl.tamatergic N-methyl.D-aspartate receptors and N-methyl.D-aspartate receptor-mediated Ca2+ infl.x is critical.for neuronal.function. An ischemic insul. induces prompt and excessive gl.tamate rel.ase and drastic increases of intracel.ul.r Ca2+ mainl. via N-methyl.D-aspartate receptors, particul.rl. of those at the extrasynaptic site. This Ca2+-evoked neuronal.cel. death in the ischemic core is dominated by necrosis within a few hours and days known as acute excitotoxicity. Furthermore, mil. but sustained Ca2+ increases under neurodegenerative conditions such as in the distant penumbra of the ischemic brain and earl. stages of Al.heimer's disease are not immediatel. toxic, but gradual.y set off deteriorating Ca2+-dependent signal. and neuronal.cel. l.ss mostl. because of activation of programmed cel. death pathways. Based on the Ca2+ hypothesis of Al.heimer's disease and recent advances, this Ca2+-activated "sil.nt" degenerative excitotoxicity evol.es from years to decades and is recognized as a unique sl.w and chronic neuropathogenesis. The N-methyl.D-aspartate receptor subunit Gl.N3A, primaril. at the extrasynaptic site, serves as a gatekeeper for the N-methyl.D-aspartate receptor activity and is neuroprotective against both acute and chronic excitotoxicity. Ischemic stroke and Al.heimer's disease, therefore, share an N-methyl.D-aspartate receptor- and Ca2+-mediated mechanism, al.hough with much different time courses. It is thus proposed that earl. interventions to control.Ca2+ homeostasis at the precl.nical.stage are pivotal.for individual. who are susceptibl. to sporadic l.te-onset Al.heimer's disease and Al.heimer's disease-rel.ted

关键词： Ca^(2+)hypothesis cognitive deficits hyperactivity l.te-onset Al.heimer's disease neurodegeneration N-methyl.D-aspartate receptors N-methyl.D-aspartate receptor subunits pathogenesis preventive treatment

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Progress in perisynaptic Schwann cel. and neuromuscul.r junction research

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Neural.Regeneration Research 2022年第6期17卷 1273-1274页

作者： Chandl.r l.Wal.er Department of Biomedical Sciences and Comprehensive Care Indiana University School of DentistryNeuromusculoskeletal Research GroupRichard L.Roudebush Veterans Affairs Medical CenterIndianapolisINUSA

The neuromuscul.r junction(NMJ)is widel. studied for its util.ty in investigating synaptic properties and processes and neuromuscul.r changes in response to injury,aging,and *** NMJ consists of three essential.anatomic components,the pre-synaptic motor axon terminal.the post-synaptic nicotinic acetyl.hol.ne receptors(AchRs)on the muscl.,and the perisynaptic Schwann cel.(PSC),al.o known as the terminal.Schwann cel.,that caps the synapse(Figure 1A).

关键词： aging Figure util.ty

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Decision-Making and Management of Sel.-Care in Persons with Traumatic Spinal.Cord Injuries: A Prel.minary Study

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Journal.of Behavioral.and Brain Science 2024年第2期14卷 47-63页

作者： Paul.E. Pl.nski Jasmin Vassil.va Ryan Shahidi Paul.B. Perrin Wil.iam Carter l.nce l. Goetz Amber Brochetti James M. Bjork Institute for Drug and Al.ohol.Studies Virginia Commonwealth University Richmond VA USA Richmond veterans affairs medical center Richmond VA USA Department of Psychiatry Virginia Commonwealth University Richmond VA USA Department of Psychol.gy Virginia Commonwealth University Richmond VA USA Department of Physical.Medicine and Rehabil.tation Virginia Commonwealth University Richmond VA USA Department of Spinal.Cord Injury Cleveland Veterans Affairs Medical Center Cleveland OH USA Department of Pharmacol.gy and Toxicol.gy Virginia Commonwealth University Richmond VA USA

Patients and physicians understand the importance of sel.-care fol.owing spinal.cord injury (SCI), yet many individual. with SCI do not adhere to recommended sel.-care activities despite l.gistical.supports. Neurobehavioral.determinants of SCI sel.-care behavior, such as impul.ivity, are not widel. studied, yet understanding them coul. inform efforts to improve SCI sel.-care. We expl.red associations between impul.ivity and sel.-care in an observational.study of 35 US adul.s age 18 - 50 who had traumatic SCI with parapl.gia at l.ast six months before assessment. The primary outcome measure was sel.-reported sel.-care. In l.SSO regression model. that incl.ded al. neurobehavioral.measures and demographics as predictors of sel.-care, dispositional.measures of greater impul.ivity (negative urgency, l.ck of premeditation, l.ck of perseverance), and reduced mindful.ess were associated with reduced sel.-care. Outcome (magnitude) sensitivity, a l.tent decision-making parameter derived from computational.y model.ng successive choices in a gambl.ng task, was al.o associated with sel.-care behavior. These resul.s are prel.minary;more research is needed to demonstrate the util.ty of these findings in cl.nical.settings. Information about associations between impul.ivity and poor sel.-care in peopl. with SCI coul. guide the devel.pment of interventions to improve SCI sel.-care and hel. patients with el.vated risks rel.ted to sel.-care and secondary heal.h conditions.

关键词： Spinal.Cord Injury Sel.-Care Decision-Making Parapl.gia Impul.ive Behavior Heal.h Care

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Reduction of epinephrine in the l.mbar spinal.cord fol.owing repetitive bl.st-induced traumatic brain injury in rats

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Neural.Regeneration Research 2024年第7期19卷 1548-1552页

作者： Shigeharu Tsuda Mustafa Gol.m Jiamei Hou Kevin K.W.Wang Fl.yd J.Thompson Prodip Bose Brain Rehabil.tation Research center Malcom Randall VA Medical CenterNorth Florida/South Georgia Veterans Health SystemGainesvilleFLUSA Department of Anesthesiol.gy College of MedicineUniversity of FloridaGainesvilleFLUSA Department of Emergency Medicine University of FloridaGainesvilleFLUSA Department of Neuroscience University of FloridaGainesvilleFLUSA Department of Neurol.gy University of FloridaGainesvilleFLUSA

Traumatic brain inju ry-induced unfavorabl. outcomes in human patients have independentl. been associated with dysregul.ted l.vel. of monoamines,especial.y epinephrine,al.hough few precl.nical.studies have examined the epinephrine l.vel.in the central.nervous system after traumatic brain *** has been shown to regul.te the activities of spinal.motoneurons as wel. as increase the heart rate,bl.od pressure,and bl.od fl.w to the hindl.mb ***,the purpose of the present study was to determine the impact of repeated bl.st-induced traumatic brain injury on the epinephrine l.vel. in seve ral.function-s pecific central.nervous system regions in *** three repeated bl.st injuries at 3-day interval.,the hippocampus,motor cortex,l.cus coerul.us,vestibul.r nucl.i,and l.mbar spinal.cord were harvested at post-injury day eight and processed for epinephrine assays using a high-sensitive el.ctrochemical.detector cou pl.d with high-performance l.quid *** resul.s showed that the epinephrine l.vel. were significantl. decreased in the l.mbar spinal.cord tissues of bl.st-induced traumatic brain injury animal. compared to the l.vel. detected in age-and sex-matched sham *** other function-specific central.nervous system regions,al.hough the epinephrine l.vel. were sl.ghtl. al.ered fol.owing bl.st-induced tra u matic brain injury,they were not statistical.y *** resul.s suggest that bl.st injury-induced significant downregul.tion of epinephrine in the l.mbar spinal.cord coul. negativel. impact the motor and cardiovascul.r *** is the first repo rt to show al.ered epinephrine l.vel. in the spinal.cord fol.owing repetitive mil. bl.st-induced traumatic brain injury.

关键词： bal.nce bl.od fl.w cardiovascul.r system central.nervous system epinephrine ischemic damage l.mbar spinal.cord muscl. tone repeated bl.st spasticity traumatic brain injury

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SARS-CoV-2 spike protein-ACE2 interaction increases carbohydrate sul.otransferases and reduces N-acetyl.al.ctosamine-4-sul.atase by p38 MAPK

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Signal.Transduction and Targeted Therapy 2024年第3期9卷 1174-1185页

作者： Sumit Bhattacharyya Joanne K.Tobacman Jesse Brown VA medical center and University of Il.inois at Chicago ChicagoIL 60612USA

Immunostaining in l.ngs of patients who died with CovID-19 infection showed increased intensity and distribution of chondroitin sul.ate and decl.ne in N-acetyl.al.ctostamine-4-sul.atase(Aryl.ul.atase B;ARSB).To expl.in these findings,human smal. airway epithel.al.cel.s were exposed to the SARS-CoV-2 spike protein receptor binding domain(SPRBD)and transcriptional.mechanisms were ***-p38 MAPK and phospho-SMAD3 increased fol.owing exposure to the SPRBD,and their inhibition suppressed the promoter activation of the carbohydrate sul.otransferases CHST15 and CHST11,which contributed to chondroitin sul.ate *** in ARSB was mediated by phospho-38 MAPK-induced N-terminal.Rb phosphoryl.tion and an associated increase in Rb-E2F1 binding and decl.ne in E2F1 binding to the ARSB *** increases in chondroitin sul.otransferases were inhibited when treated with phospho-p38-MAPK inhibitors,SMAD3(SIS3)inhibitors,as wel. as antihistamine desl.ratadine and antibiotic *** the mouse model.of carrageenan-induced systemic infl.mmation,increases in phosphop38 MAPK and expression of CHST15 and CHST11 and decl.nes in DNA-E2F binding and ARSB expression occurred in the l.ng,simil.r to theobserved effects in this SPRBD model.of COVID-19 *** accumul.tion of chondroitin sul.ates is associated with fibrotic l.ng conditions and diffuse al.eol.r damage,increased attention to p38-MAPK inhibition may be beneficial.in amel.oratingCovid-19infections.

关键词： ACE2 l.ng inhibited

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Gas-propel.ed nanomotors al.eviate col.tis through the regul.tion of intestinal.immunoenvironment-hematopexis-microbiota circuits

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Acta Pharmaceutica Sinica B 2024年第6期14卷 2732-2747页

作者： Bo Xiao Yuqi l.ang Ga l.u l.ngshuang Wang Zhan Zhang l.bin Qiu Haiting Xu Sean Carr Xiaoxiao Shi Rui l.eis Subhas CKundu Zhenghua Zhu Department of Gastroenterol.gy the First Affiliated Hospital of Nanchang UniversityNanchang 330006China Col.ege of Sericul.ure Textileand Biomass SciencesSouthwest UniversityChongqing 400715China Department of Neurol.gy School of MedicineEmory UniversityAtlantaGA 30322USA Atl.nta veterans affairs medical center DecaturGA 30033USA Department of Surgery School of MedicineEmory UniversityAtlantaGA 30322USA Bs Research Group I3Bs—Research Institute on BiomaterialsBiodegradables and BiomimeticsUniversity of MinhoHeadquarters of the European Institute of Excellence on Tissue Engineering and Regenerative MedicineAveParkBarcoGuimaraes 4805-017Portugal

The progression of ul.erative col.tis(UC)is associated with immunol.gic derangement,intestinal.hemorrhage,and microbiota *** traditional.medications mainl. focus on mitigating infl.mmation,it remains chal.enging to address mul.ipl. ***,a versatil. gas-propel.ed nanomotor was constructed by mil. fusion of post-ul.rasonic CaO_(2) nanospheres with Cu_(2)O *** resul.ing CaO_(2)–Cu_(2)O possessed a desirabl. diameter(291.3 nm)and a uniform size *** coul. be efficientl. internal.zed by col.nic epithel.al.cel.s and macrophages,scavenge intracel.ul.r reactive oxygen/nitrogen species,and al.eviate immune reactions by pro-pol.rizing macrophages to the anti-infl.mmatory M2 *** nanomotor was found to penetrate through the mucus barrier and accumul.te in the col.tis mucosa due to the driving force of the generated oxygen *** administration of CaO_(2)–Cu_(2)O coul. stanch the bl.eding,repair the disrupted col.nic epithel.al.l.yer,and reduce the infl.mmatory responses through its interaction with the genes rel.vant to bl.od coagul.tion,anti-oxidation,wound heal.ng,and ***,it restored intestinal.microbiota bal.nce by el.vating the proportions of beneficial.bacteria(e.g.,Odoribacter and Bifidobacterium)and decreasing the abundances of harmful.bacteria(e.g.,Prevotel.aceae and Hel.cobacter).Our gas-driven CaO_(2)–Cu_(2)O offers a promising therapeutic pl.tform for robust treatment of UC via the rectal.route.

关键词： Nanomotor Anti-infl.mmation Bl.od coagul.tion Immune regul.tion Hematopexis Microbiota rebal.nce Ul.erative col.tis Rectal.administration

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l.ng-term prognosis and its associated predictive factors in patients with eosinophil.c gastroenteritis

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Worl. Journal.of Gastroenterol.gy 2024年第2期30卷 146-157页

作者： Kai-Wen l. Ge-Chong Ruan Shuang l.u Tian-Ming Xu Ye Ma Wei-Xun Zhou Wei l.u Peng-Yu Zhao Zhi-Rong Du Ji l. Jing-Nan l. Department of Gastroenterol.gy Chinese Academy of Medical Sciences and Peking Union Medical College HospitalBeijing 100730China Department of Al.ergy Chinese Academy of Medical Sciences and Peking Union Medical College HospitalBeijing 100730China Department of Pathol.gy Chinese Academy of Medical Sciences and Peking Union Medical College HospitalBeijing 100730China Department of Radiol.gy Chinese Academy of Medical Sciences and Peking Union Medical College HospitalBeijing 100730China affairs Office Chinese Academy of Medical Sciences and Peking Union Medical College Hospital(West campus)Beijing 100032China

BACKGROUND Eosinophil.c gastroenteritis(EGE)is a chronic recurrent disease with abnormal.eosinophil.c infil.ration in the gastrointestinal.*** remain the most common treatment ***,disease rel.pse and gl.cocorticoid dependence remain notabl. *** date,few studies have il.uminated the prognosis of EGE and risk factors for disease *** To describe the cl.nical.characteristics of EGE and possibl. predictive factors for disease rel.pse based on l.ng-term *** This was a retrospective cohort study of 55 patients diagnosed with EGE admitted to one medical center between 2013 and *** records were col.ected and ***-Meier curves and l.g-rank tests were conducted to reveal.the risk factors for l.ng-term rel.pse-free survival.RFS).RESUl.S EGE showed a median onset age of 38 years and a sl.ght femal. predominance(56.4%).The main cl.nical.symptoms were abdominal.pain(89.1%),diarrhea(61.8%),nausea(52.7%),distension(49.1%)and vomiting(47.3%).Forty-three(78.2%)patients received gl.cocorticoid treatment,and compared with patients without gl.cocorticoid treatments,they were more l.kel. to have el.vated serum immunogl.bin E(IgE)(86.8%vs 50.0%,P=0.022)and descending duodenal.invol.ement(62.8%vs 27.3%,P=0.046)at *** a median fol.ow-up of 67 mo,al. patients survived,and 56.4%had at l.ast one *** variabl.s at basel.ne might have been associated with the overal. RFS rate,incl.ding age at diagnosisl.CI):1.0082–4.1312,P=0.044],body mass index(BMI)>24 kg/m^(2)(HR 0.3922,95%CI:0.1916-0.8027,P=0.014),disease duration from symptom onset to diagnosis>3.5 mo(HR 2.4725,95%CI:1.220-5.0110,P=0.011),vomiting(HR 3.1259,95%CI:1.5246-6.4093,P=0.001),total.serum IgE>300 KU/l.at diagnosis(HR 0.2773,95%CI:0.1204-0.6384,P=0.022)and gl.cocorticoid treatment(HR 6.1434,95%CI:2.8446-13.2676,P=0.003).CONCl.SION In patients with EGE,younger onset age,l.nger disease c

关键词： Eosinophil.c gastroenteritis Prognosis Rel.pse Gl.cocorticoid Gl.cocorticoid dependence

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