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The proteome of distal nerves: implication in delayed repair and poor functional recovery

Neural Regeneration Research 2022年第9期17卷 1998-2006页

作者： Song Guo Raymond M.Moore M.Cristine Charlesworth Kenneth L.Johnson Robert J.Spinner Anthony J.Windebank Huan Wang Department of Neurologic Surgery Mayo ClinicRochesterMNUSA Biomedical Statistics and informatics Mayo ClinicRochesterMNUSA Proteomics Core Mayo ClinicRochesterMNUSA Department of Neurology Mayo ClinicRochesterMNUSA

Chronic denervation is one of the key factors that affect nerve *** axotomy deteriorates the distal nerve stump,causes protein changes,and renders the microenvironment less permissive for *** of these factors/proteins have been individually *** better delineate the comprehensive protein expression profiles and identify proteins that contribute to or are associated with this detrimental effect,we carried out a proteomic analysis of the distal nerve using an established delayed rat sciatic nerve repair *** rats that received immediate repair after sciatic nerve transection served as control,whereas four rats in the experimental group(chronic denervation)had their sciatic nerve repaired after a 12-week *** the rats were sacrificed after 16 weeks to harvest the distal nerves for extracting ***-five micrograms of protein from each sample were fractionated in SDS-PAGE ***-MS/MS analysis was applied to the *** expression levels of nerves on the surgery side were compared to those on the contralateral *** protein with a P value of less than 0.05 and a fold change of 4 or higher was deemed differentially *** the differentially expressed proteins in both groups were further stratified according to the biological processes.A Pubmed search was also conducted to identify the differentially expressed proteins that have been reported to be either beneficial or detrimental to nerve *** Pathway Analysis(iPA)software was used for pathway *** results showed that 709 differentially expressed proteins were identified in the delayed repair group,with a bigger proportion of immune and inflammatory process-related proteins and a smaller proportion of proteins related to axon regeneration and lipid metabolism in comparison to the control group where 478 differentially expressed proteins were *** experimental group also had more beneficial proteins that were d

关键词： chronic axotomy chronic denervation delayed repair distal nerve functional recovery nerve regeneration peripheral nerve prolonged denervation proteome sciatic nerve sciatic nerve transection

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Transjugular intrahepatic portosystemic stent shunt for medically refractory hepatic hydrothorax:A systematic review and cumulative meta-analysis

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World Journal of Hepatology 2015年第13期7卷 1797-1806页

作者： ivo C Ditah Badr F Al Bawardy Behnam Saberi Chobufo Ditah Patrick S Kamath Division of Gastroenterology and Hepatology Mayo ClinicRochesterMN 55905United States Department of medicine University of Yaoundé I Faculty of Medicine

AiM:To assess the effectiveness of transjugular intrahepatic portosystemic stent shunt(TiPSS) in refractory hepatic hydrothorax(RHH) in a systematic review and cumulative ***:A comprehensive literature search was conducted on medLiNE,EMBASE,and Pub med covering the period from January 1970 to August *** authors independently selected and abstracted data from eligible *** were summarized using a random-effects *** was assessed using the i2 ***:Six studies involving a total of 198 patients were included in the *** mean(SD) age of patients was 56(1.8) *** patients(56.9%) had Child-Turcott-Pugh class C *** mean duration of follow-up was 10 mo(range,5.7-16 mo).Response to TiPSS was complete in 55.8%(95%Ci:44.7%-66.9%),partial in 17.6%(95%Ci:10.9%-24.2%),and absent in 21.2%(95%Ci:14.2%-28.3%).The mean change in hepatic venous pressure gradient post-TiPSS was 12.7 mm *** incidence of TiPSS-related encephalopathy was 11.7%(95%Ci:6.3%-17.2%),and the 45-d mortality was 17.7%(95%Ci:11.34%-24.13%).CONCLUSiON:TiPSS is associated with a clinically relevant response in *** should be considered early in these patients,given its poor prognosis.

关键词： Cirrhosis Portal hypertension Hepatichydrothorax Transjugular intrahepatic portosystemicstent shunt Meta-analysis

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Organization of future training in bariatric gastroenterology

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World Journal of Gastroenterology 2017年第35期23卷 6371-6378页

作者： Timothy R Koch Timothy R Shope Christopher J Gostout Center for Advanced Laparoscopic General and Bariatric Surgery Med Star Washington Hospital Center and Georgetown University School of Medicine Division of Gastroenterology and Hepatology Mayo Clinic

A world-wide rise in the prevalence of obesity continues. This rise increases the occurrence of, risks of, and costs of treating obesity-related medical conditions. Diet and activity programs are largely inadequate for the long-term treatment of medically-complicated obesity. Physicians who deliver gastrointestinal care after completing traditional training programs, including gastroenterologists and general surgeons, are not uniformly trained in or familiar with available bariatric care. it is certain that gastrointestinal physicians will incorporate new endoscopic methods into their practice for the treatment of individuals with medically-complicated obesity, although the longterm impact of these endoscopic techniques remains under investigation. it is presently unclear whether gastrointestinal physicians will be able to provide or coordinate important allied services in bariatric surgery, endocrinology, nutrition, psychological evaluation and support, and social work. Obtaining longitudinal results examining the effectiveness of this ad hoc approach will likely be difficult, based on prior experience with other endoscopic measures, such as the adenoma detection rates from screening colonoscopy. As a longterm approach, development of a specific curriculum incorporating one year of subspecialty training in bariatrics to the present training of gastrointestinal fellows needs to be reconsidered. This approach should be facilitated by gastrointestinal trainees' prior residency training in subspecialties that provide care for individuals with medical complications of obesity, including endocrinology, cardiology, nephrology, and neurology. Such training could incorporate additional rotations with collaborating providers in bariatric surgery, nutrition, and psychiatry. Since such training would be provided in accredited programs, longitudinal studies could be developed to examine the potential impact on accepted measures of care, such as complication rates, outcomes, and

关键词： Obesity Bariatrics Bariatric surgery intragastric balloon Endoscopic sleeve gastroplasty Nutrition Endoscopy Training

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Examining pathogenic concepts of autoimmune hepatitis for cues to future investigations and interventions

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World Journal of Gastroenterology 2019年第45期25卷 6579-6606页

作者： Albert J Czaja Division of Gastroenterology and Hepatology Mayo Clinic College of Medicine and Science

BACKGROUND Multiple pathogenic mechanisms have been implicated in autoimmune hepatitis,but they have not fully explained susceptibility,triggering events,and maintenance or escalation of the ***,they have not identified a critical defect that can be *** goals of this review are to examine the diverse pathogenic mechanisms that have been considered in autoimmune hepatitis,indicate investigational opportunities to validate their contribution,and suggest interventions that might evolve to modify their *** abstracts were identified in Pubmed by multiple search *** length articles were selected for review,and secondary and tertiary bibliographies were *** and epigenetic factors can affect susceptibility by influencing the expression of immune regulatory *** dysfunction,possibly related to deficient production of programmed cell death protein-1,can allow autoreactive T cells to escape deletion,and alterations in the intestinal microbiome may help overcome immune tolerance and affect gender *** factors may trigger the disease or induce epigenetic changes in gene *** mimicry,epitope spread,bystander activation,neo-antigen production,lymphocytic polyspecificity,and disturbances in immune inhibitory mechanisms may maintain or escalate the *** that modify epigenetic effects on gene expression,alter intestinal dysbiosis,eliminate deleterious environmental factors,and target critical pathogenic mechanisms are therapeutic possibilities that might reduce risk,individualize management,and improve *** conclusion,diverse pathogenic mechanisms have been implicated in autoimmune hepatitis,and they may identify a critical factor or sequence that can be validated and used to direct future management and preventive strategies.

关键词： Autoimmune hepatitis Pathogenesis Epigenetics Molecular mimicry Epitope spread intestinal microbiome

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Stem cell-derived exosomes-an emerging tool for myocardial regeneration

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World Journal of Stem Cells 2018年第8期10卷 106-115页

作者： Erzsebet Lazar Theodora Benedek Szilamer Korodi Nora Rat Jocelyn Lo imre Benedek Department of internal medicine Clinic of Haematology and Bone Marrow Transplantation University of Medicine and Pharmacy Tirgu Mures Department of internal medicine Clinic of Cardiology University of Medicine and Pharmacy Tirgu Mures Department of Advanced Research in Multimodality Cardiac imaging Cardio Med Medical Center Vagelos College of Physicians and Surgeons Columbia University

Cardiovascular diseases(CVDs) continue to represent the number one cause of death and disability in industrialized countries. The most severe form of CVD is acute myocardial infarction(AMi), a devastating disease associated with high mortality and disability. in a substantial proportion of patients who survive AMi, loss of functional cardiomyocytes as a result of ischaemic injury leads to ventricular failure, resulting in significant alteration to quality of life and increased mortality. Therefore, many attempts have been made in recent years to identify new tools for the regeneration of functional cardiomyocytes. Regenerative therapy currently represents the ultimate goal for restoring the function of damaged myocardium by stimulating the regeneration of the infarcted tissue or by providing cellsthat can generate new myocardial tissue to replace the damaged tissue. Stem cells(SCs) have been proposed as a viable therapy option in these cases. However, despite the great enthusiasm at the beginning of the SC era, justified by promising initial results, this therapy has failed to demonstrate a significant benefit in large clinical trials. One interesting finding of SC studies is that exosomes released by mesenchymal SCs(MSCs) are able to enhance the viability of cardiomyocytes after ischaemia/reperfusion injury, suggesting that the beneficial effects of MSCs in the recovery of functional myocardium could be related to their capacity to secrete exosomes. Ten years ago, it was discovered that exosomes have the unique property of transferring miRNA between cells, acting as miRNA nanocarriers. Therefore, exosomebased therapy has recently been proposed as an emerging tool for cardiac regeneration as an alternative to SC therapy in the post-infarction period. This review aims to discuss the emerging role of exosomes in developing innovative therapies for cardiac regeneration as well as their potential role as candidate biomarkers or for developing new diagnostic tools.

关键词： Acute myocardial infarction Exosome Stem cell Cardiac regeneration Cardiovascular diseases

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Human umbilical cord-derived mesenchymal stem cell therapy in patients with COViD-19:a phase 1 clinical trial

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Signal Transduction and Targeted Therapy 2020年第1期5卷 1010-1016页

作者： Fanping Meng Ruonan Xu Siyu Wang Zhe Xu Chao Zhang Yuanyuan Li Tao Yang Lei Shi Junliang Fu Tianjun Jiang Lei Huang Peng Zhao Xin Yuan Xing Fan Ji-Yuan Zhang Jinwen Song Dawei Zhang Yanmei Jiao Limin Liu Chunbao Zhou Markus Maeurer Alimuddin Zumla Ming Shi Fu-Sheng Wang Department of infectious Diseases Fifth Medical Center of Chinese PLA General HospitalNational Clinical Research Center for Infectious DiseasesBeijingChina immunotherapy Programme Champalimaud Centre for the UnknownLisbonPortugal i med clinic University of MainzMainzGermany Department of infection Division of Infection and ImmunityUniversity College LondonLondonUK National institute for Health Research Biomedical Research Centre University College London Hospitals NHS Foundation TrustLondonUK

No effective drug treatments are available for coronavirus disease 2019(COViD-19).Host-directed therapies targeting the underlying aberrant immune responses leading to pulmonary tissue damage,death,or long-term functional disability in survivors require clinical *** performed a parallel assigned controlled,non-randomized,phase 1 clinical trial to evaluate the safety of human umbilical cord-derived mesenchymal stem cells(UC-MSCs)infusions in the treatment of patients with moderate and severe COViD-19 pulmonary *** study enrolled 18 hospitalized patients with COViD-19(n=9 for each group).The treatment group received three cycles of intravenous infusion of UC-MSCs(3×107 cells per infusion)on days 0,3,and *** groups received standard COViD-treatment *** events,duration of clinical symptoms,laboratory parameters,length of hospitalization,serial chest computed tomography(CT)images,the PaO2/FiO2 ratio,dynamics of cytokines,and igG and igM anti-SARS-CoV-2 antibodies were *** serious UC-MSCs infusion-associated adverse events were *** patients receiving UC-MSCs developed transient facial flushing and fever,and one patient developed transient hypoxia at 12 h post UC-MSCs *** ventilation was required in one patient in the treatment group compared with four in the control *** patients recovered and were *** data show that intravenous UC-MSCs infusion in patients with moderate and severe COViD-19 is safe and well *** 2/3 randomized,controlled,double-blinded trials with long-term follow-up are needed to evaluate the therapeutic use of UC-MSCs to reduce deaths and improve long-term treatment outcomes in patients with serious COViD-19.

关键词： patients infusion clinical

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Resveratrol as an Anti-inflammatory Agent in Coronary Artery Disease:A Systematic Review,Meta-Analysis and Meta-Regression

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Chinese Journal of integrative medicine 2024年第10期30卷 927-937页

作者： Vito A.Damay ignatius ivan Department of Cardiovascular medicine Universitas Pelita HarapanTangerangBanten15811Indonesia Jakarta Varices clinic Jakarta12210Indonesia

Background:Resveratrol is a non-flavonoid polyphenol that shows promise in reducing proinflammatory factors and maintaining endothelial function,which hints at its potential role in slowing atherosclerosis and preventing acute coronary ***:To study the cardioprotective effects of resveratrol on inflammatory mediators and endothelial function in patients with coronary artery disease(CAD).Methods:A thorough search was conducted in databases(Cochrane Library,Pro Quest,Pub med,LiLACS,Science Direct,Springer,Taylor&Francis,CNKi,Wanfang,and Weipu)until September 24,*** vasopro-inflammatory mediators,endothelial function and outcomes related to cardiovascular events were *** and abstracts were assessed,and bias was evaluated with Cochrane Ro B *** of results was explored by metaregression,certainty of evidence was assessed by the GRADE system,and conclusive evidence was enhanced by trial sequence ***:Ten randomized controlled trials and 3 animal studies investigated resveratrol's impact on inflammatory mediators and endothelial *** primary prevention studies,meta-analysis showed a significant reduction(95%Ci:–0.73 to–0.20;P=0.0005)in tumor necrosis factor-α(TNF-α)expression with resveratrol,demonstrating a dose-dependent *** significant difference was observed in interleukin-6(iL-6)expression with P=0.58 for primary prevention and P=0.57 for secondary *** endothelial nitric oxide synthase(e NOS)expression was significantly increased after resveratrol pre-treatment following CAD *** prevention studies yielded no significant results;however,meta-regression identified associations between age,hypertension,and lower doses with the extent of TNF-α*** certainty of evidence supported TNF-αreduction,while evidence for iL-6 reduction and e NOS elevation was deemed ***:Resveratrol reduces TNF-αin individuals at risk for CAD,specifically 15 mg per ***

关键词： anti-inflammation coronary artery disease nitric oxide resveratrol systematic review

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FGFR3 alterations in bladder cancer:Sensitivity and resistance to targeted therapies

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Cancer Communications 2024年第10期44卷 1189-1208页

作者： Maxim Noeraparast Katarina Krajina Renate Pichler Dora Nieders-Beke Shahrokh F Shariat Viktor Grünwald Sascha Ahyai Martin Pichler Translational Oncology II.Med Clinics Hematology and OncologyAugsburgGermany Department of Urology Medical University of InnsbruckInnsbruckAustria Department of Hematology and Oncology Clinics OttakringViennaAustria Department of Urology Medical University of ViennaViennaAustria interdisciplinary Genitourinary Oncology Clinic for UrologyClinic for Medical OncologyUniversity Hospital EssenHufelandstrase 55EssenGermany Department of Urology Medical University of GrazGrazAustria

in this review,we revisit the pivotal role of fibroblast growth factor receptor 3(FGFR3)in bladder cancer(BLCA),underscoring its prevalence in both nonmuscle-invasive and muscle-invasive forms of the ***3 mutations in up to half of BLCAs play a well-established role in tumorigenesis,shaping distinct tumor initiation patterns and impacting the tumor microenvironment(TME).Emphasizing the importance of considering epithelial-mesenchymal transition profile and TME status,we revisit their relevance in predicting responses to immune checkpoint inhibitors in FGFR3-mutated *** writing highlights the initially promising yet transient efficacy of the FGFR inhibitor Erdafitinib on FGFR3-mutated BLCA,stressing the pressing need to unravel resistance mechanisms and identify co-targets for future combinatorial studies.A thorough analysis of recent preclinical and clinical evidence reveals resistance mechanisms,including secondarymutations,epigenetic alterations in pathway effectors,phenotypic heterogeneity,and population-specific variations within FGFR3 mutational ***,we discuss the potential of combinatorial treatments and concepts like synthetic lethality for discovering more effective targeted therapies against FGFR3-mutated BLCA.

关键词： Bladder Cancer Erdafitinib FGFR inhibition FGFR3 mutations Resistance to Erdafitinib Tumor Microenvironment

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Adjuvant chemotherapy in breast cancer: To use or not to use, the anthracyclines

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World Journal of clinical Oncology 2014年第3期5卷 529-538页

作者： Jennifer A Crozier Abhisek Swaika Alvaro Moreno-Aspitia Department of Hematology and Oncology Mayo Clinic JacksonvilleFL 32224 United States

Breast cancer continues to be one of the leading causes of cancer mortality in the world. The treatment generally involves multiple modalities including surgery, radiation and/or chemotherapy. Anthracyclines, one of the first chemotherapeutic agents introduced in the 1960 s, has been the backbone for the last 30 years and has been used extensively so far. However, the cardiac toxicity and the concern for secondary hematological malignancy has always been a challenge. A better understanding of the tumor biology, role of Her2 expression and the discovery of trastuzumab and other anti-Her 2 agents along with other effective novel therapeutic options, have revolutionized the treatment for breast cancer. The role of anthracyclines has come under close scrutiny, especially in the adjuvant setting for patients with early stage breast cancer and those with low or intermediate risk of disease recurrence. Recent studies have highlighted such a shift in the use of anthracyclines in both the academic and community clinical practice. However, in patients with a high risk of relapse, anthracyclines still hold promise. Ongoing clinical trials are underway to further define the role of anthracyclines in such a patient population. This review highlights the development, clinical utility, limitations and potential future use of anthracyclinesin the adjuvant setting for patients with breast cancer. We consulted Pub med, Scopus, medLiNE, ASCO annual symposium abstracts, and http://***/ for the purpose of this review.

关键词： Breast cancer Adjuvant Neoadjuvant Chemotherapy Anthracyclines

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clinical Neurophysiology 3

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丛书名： Contemporary Neurology Series

2009年

作者： Daube, Jasper R. Rubin, Devon i.

ISBN: (数字)9780199725144

ISBN: (纸本)9780195385113

clinical Neurophysiology, Third Edition will continue the tradition of the previous two volumes by providing a didactic, yet accessible, presentation of electrophysiology in three sections that is of use to both the clinician and the researcher. The first section describes the analysis of electrophysiological waveforms. Section two describes the various methods and techniques of electrophysiological testing. The third section, although short in appearance, has recommendations of symptom complexes and disease entities using electroencephalography, evoked potentials, and nerve conduction studies.

关键词： Electroencephalography Electromyography Evoked Potentials Nervous System Diseases Neurophysiology

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