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Targeting harmful effects of non-excitatory amino acids as an alternative therapeutic strategy to reduce ischemic damage

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Neural Regeneration Research 2025年第9期20卷 2454-2463页

作者： Victoria Jiménez Carretero IrisÁlvarez-Merz Jorge Hernández-Campano Sergei A.Kirov Jesús M.Hernández-Guijo Department of Pharmacology and Therapeutic School of MedicineUniv.Autónoma de MadridMadridSpain Ramón y cajal Institute for Health Research(IRyCIS) Neurobiology-Research ServiceHospital Ramón y CajalMadridSpain Institute of Neurobiology Faculty of Mathematics and Natural SciencesHeinrich Heine University DüsseldorfDüsseldorfGermany Department of Neuroscience and Regenerative Medicine&Department of Neurosurgery Medical College of Georgia at Augusta UniversityAugustaGAUSA

The involvement of the excitatory amino acids glutamate and aspartate in ce rebral ischemia and excitotoxicity is ***,the role of non-excitatory amino acids in brain damage following a stroke or brain trauma remains largely *** release of amino acids by necrotic cells in the ischemic core may contribute to the expansion of the *** findings indicated that the reversible loss of field excitato ry postsynaptic potentials caused by transient hypoxia became irreversible when exposed to a mixture of just four non-excitatory amino acids(L-alanine,glycine,L-glutamine,and L-serine)at their plasma *** amino acids induce swelling in the somas of neurons and astrocytes during hypoxia,along with permanent dendritic damage mediated by N-methyl-D-aspartate *** N-methyl-D-aspartate receptors prevented neuronal damage in the presence of these amino acids during *** is likely that astroglial swelling caused by the accumulation of these amino acids via the alanine-serine-cysteine transporter 2 exchanger and system N transporters activates volume-regulated anion channels,leading to the release of excitotoxins and subsequent neuronal damage through N-methyl-D-aspartate receptor ***,previously unrecognized mechanisms involving non-excitatory amino acids may contribute to the progression and expansion of brain injury in neurological emergencies such as stroke and traumatic brain *** these pathways co uld highlight new therapeutic targets to mitigate brain injury.

关键词： cell swelling N-methyl-D-aspartate receptor non-excitatory amino acids stroke synaptic transmission

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Current and future perspectives in the management and treatment of colorectal cancer

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World Journal of Clinical Oncology 2025年第2期16卷 9-17页

作者： Sigfredo E Romero-Zoghbi Evita Krumina Fernando López-Campos Felipe Couñago Department of Radiation Oncology GenesisCare Talavera de la ReinaToledo 45600Spain Department of Radiation Oncology GenesisCare GuadalajaraGuadalajara 19004Spain Department of Radiation Oncology Hospital Universitario Ramón Y CajalMadrid 28034Spain Department of Radiation Oncology GenesisCare-Hospital Universitario Vithas Madrid La MilagrosaMadrid 28010Spain

In this editorial,we reviewed the article by Fadlallah et al that was recently published in the World Journal of Clinical *** article provided a comprehensive and in-depth view of the management and treatment of colorectal cancer(CRC),one of the leading causes of cancer-related morbidity and mortality *** article analyzed the therapeutic modalities and their sequencing,focusing on total neoadjuvant therapy for locally advanced rectal *** highlighted the role of immunotherapy in tumors with high microsatellite instability or deficient mismatch repair,addressing recent advances that have improved prognosis and therapeutic response in localized and metastatic *** in surgical techniques,advanced radiotherapy,and systemic agents targeting specific mutational profiles are also discussed,reflecting on how they revolutionized clinical *** tumor DNA has emerged as a promising tool for detecting minimal residual disease,prognosis,and therapeutic monitoring,solidifying its role in precision *** review emphasized the importance of technological and therapeutic advancements in improving clinical outcomes and personalizing CRC treatment.

关键词： Colorectal cancer Metastatic colorectal cancer Total neoadjuvant therapy Chemoradiotherapy Colon surgery Rectal surgery Chemotherapy Immunotherapy

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Nanomaterials-mediated lysosomal regulation:a robust protein-clearance approach for the treatment of Alzheimer’s disease

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Neural Regeneration Research 2025年第2期20卷 424-439页

作者： Mengqi Hao Jianjian Chu Tinglin Zhang Tong yin yuankai Gu Wendanqi Liang Wenbo Ji Jianhua Zhuang yan Liu Jie Gao you yin Department of Neurology Second Affiliated Hospital of Naval Medical University(Shanghai Changzheng Hospital)ShanghaiChina School of Health Science and Engineering University of Shanghai for Science and TechnologyShanghaiChina Changhai Clinical Research Unit Shanghai Changhai HospitalNaval Medical UniversityShanghaiChina Department of Clinical Pharmacy Xinhua HospitalShanghai Jiao Tong University School of MedicineShanghaiChina Department of Neurology Shanghai East HospitalSchool of MedicineTongji UniversityShanghaiChina

Alzheimer’s disease is a debilitating,progressive neurodegenerative disorder characterized by the progressive accumulation of abnormal proteins,including amyloid plaques and intracellular tau tangles,primarily within the ***,crucial intracellular organelles responsible for protein degradation,play a key role in maintaining cellular *** studies have suggested a link between the dysregulation of the lysosomal system and pathogenesis of neurodegenerative diseases,including Alzheimer’s *** the normal physiological function of lysosomes hold the potential to reduce the pathological burden and improve the symptoms of Alzheimer’s ***,the efficacy of drugs in treating Alzheimer’s disease is limited,with major challenges in drug delivery efficiency and ***,nanomaterials have gained widespread use in Alzheimer’s disease drug research owing to their favorable physical and chemical *** review aims to provide a comprehensive overview of recent advances in using nanomaterials(polymeric nanomaterials,nanoemulsions,and carbon-based nanomaterials)to enhance lysosomal function in treating Alzheimer’s *** review also explores new concepts and potential therapeutic strategies for Alzheimer’s disease through the integration of nanomaterials and modulation of lysosomal *** conclusion,this review emphasizes the potential of nanomaterials in modulating lysosomal function to improve the pathological features of Alzheimer’s *** application of nanotechnology to the development of Alzheimer’s disease drugs brings new ideas and approaches for future treatment of this disease.

关键词： Alzheimer’s disease autophagy dysfunction lysosomal acidification lysosomal system nanomaterials neurodegenerative diseases

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Endoscopic ultrasound guided vascular access and therapy:A promising indication

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World Journal of Gastrointestinal Endoscopy 2010年第6期2卷 198-202页

作者： Enrique Vazquez-Sequeiros Jose ramon Foruny Olcina university hospital ramon y cajal

Endoscopic ultrasound(EUS)is an imaging technique that has consolidated its role as an important tool for diagnosis and *** recent years we have seen a dramatic increase in the number of EUS-guided therapeutic indications(celiac plexus neurolysis/block, pseudocyst drainage,etc).Preliminary reports have suggested EUS may also be used to guide vascular access for both imaging and treating different vascular *** review aims to objectively describe the existing evidence in the field.

关键词： Endosonography Fine needle aspiration Endoscopic ultrasound-FNA Bleeding Vascular therapy

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Lipid levels and insulin resistance markers in patients with colorectal cancer:Propensity score matching analysis

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World Journal of Gastrointestinal Oncology 2025年第1期17卷 130-142页

作者： Ren-Hao Hu Dong-yi yan Ke-Hui Zhang Di Zhang Xi-Mao Cui Xiao-Hua Jiang Shun Zhang Department of Gastrointestinal Surgery Shanghai East HospitalSchool of MedicineTongji UniversityShanghai 200120China School of Medicine Tongji UniversityShanghai 200092China Department of Emergency Medicine Shanghai East HospitalSchool of MedicineTongji UniversityShanghai 200120China

BACKGROUND Colorectal cancer(CRC)is a prevalent malignant neoplasm characterized by subtle early *** To investigate the correlation among serum lipid profiles,the triglyceride-glucose(TyG)index,and the atherosclerotic index(AI)in patients with ***,it explored the clinical diagnostic utility of combining serum lipids with cancer antigens in the context of *** A retrospective analysis encompassed 277 patients with CRC and 1034 healthy *** Following propensity score matching,patients with CRC exhibited significantly reduced levels of serum triglyceride(TG),total cholesterol(TC),high-density lipoprotein cholesterol,and low-density lipoprotein cholesterol(LDL-C),as well as a diminished TyG ***,they displayed elevated AI levels compared to their healthy *** in advanced stages exhibited lower serum levels of TG,TC,and LDL-C compared to those in early *** with positive lymph node metastasis demonstrated reduced levels of TG,LDL-C,and the TyG *** operating characteristic analysis revealed that the combination of the TyG index,carcinoembryonic antigen,and carbohydrate antigen 19-9 yielded the highest positive prediction rate for CRC at 75.3%.CONCLUSION Preoperative serum lipid profiles exhibit a robust association with patients with *** concurrent assessment of multiple serum lipids and cancer antigens effectively enhances the diagnostic accuracy for CRC.

关键词： Colorectal cancer Serum lipids Triglyceride-glucose index Atherosclerotic index Diagnostic marker

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Radiomics in pancreatic cancer for oncologist:Present and future

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Hepatobiliary & Pancreatic Diseases International 2022年第4期21卷 356-361页

作者： Carolina de la Pinta Radiation Oncology Department Ramón y Cajal University HospitalIRYCISAlcaláUniversity28034 MadridSpain

Radiomics is changing the world of medicine and more specifically the world of *** diagnosis and treatment improve the prognosis of patients with *** treatment,the evaluation of the response will determine future *** oncology,every change in treatment means a loss of therapeutic options and this is key in pancreatic *** has been developed in oncology in the early diagnosis and differential diagnosis of benign and malignant lesions,in the evaluation of response,in the prediction of possible side effects,marking the risk of recurrence,survival and prognosis of the *** studies have validated its use to differentiate normal tissues from tumor tissues with high sensitivity and specificity,and to differentiate cystic lesions and pancreatic neuroendocrine tumor grades with texture *** addition,these parameters have been related to survival in patients with pancreatic cancer and to response to radiotherapy and *** review aimed to establish the current status of the use of radiomics in pancreatic cancer and future perspectives.

关键词： Pancreatic cancer Radiomics Radiogenomics

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Stereotactic body radiotherapy in pancreatic adenocarcinoma

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Hepatobiliary & Pancreatic Diseases International 2024年第1期23卷 14-19页

作者： Carolina de la Pinta Radiation Oncology Department Ramón y Cajal University HospitalIRYCISAlcaláUniversity28034 MadridSpain

Background:Stereotactic body radiotherapy(SBRT)in pancreatic cancer allows high delivery of radiation doses on tumors without affecting surrounding *** review aimed at the SBRT application in the treatment of pancreatic *** sources:We retrieved articles published in MEDLINE/PubMed from January 2017 to December *** used in the search included:“pancreatic adenocarcinoma”OR“pancreatic cancer”AND“stereotactic ablative radiotherapy(SABR)”OR“stereotactic body radiotherapy(SBRT)”OR“chemoradiotherapy(CRT)”.English language articles with information on technical characteristics,doses and fractionation,indications,recurrence patterns,local control and toxicities of SBRT in pancreatic tumors were *** articles were assessed for validity and relevant ***:Optimal doses and fractionation have not yet been ***,SBRT could be the standard treatment in patients with pancreatic adenocarcinoma in addition to ***,the combination of SBRT with chemotherapy may have additive or synergic effect on pancreatic ***:SBRT is an effective modality for patients with pancreatic cancer,supported by clinical practice guidelines as it has demonstrated good tolerance and good disease *** opens a possibility of improving outcomes for these patients,both in neoadjuvant treatment and with radical intent.

关键词： Chemoradiotherapy Pancreatic adenocarcinoma Radiotherapy Stereotactic body radiotherapy Stereotactic ablative radiotherapy

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DNA-guided hepatitis B treatment,viral load is essential,but not sufficient

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World Journal of Gastroenterology 2009年第4期15卷 423-430页

作者： Rafael Bárcena Marugán Silvia García Garzón Services of Liver-Gastroenterology Hospital Ramón y CajalUniversity of Alcalá Department of Gastroenterology Hospital Universitario de GuadalajaraUniversity of Alcalá

Hepatitis B virus （HBV） infection is a global public health problem that concerns 350 million people worldwide. Individuals with chronic hepatitis B （CriB） are at increased risk of developing liver cirrhosis, hepatic de-compensation and hepatocellular carcinoma. To maintain undetectable viral load reduces chronic infection complications. There is no treatment that eradicates HBV infection. Current drugs are expensive, are associated with adverse events, and are of limited efficacy. Current guidelines try to standardize the clinical practice. Nevertheless, controversy remains about management of asymptomatic patients with CriB who are hepatitis B e antigen （HBeAg）-positive with normal alanine aminotransferase, and what is the cut-off value of viral load to distinguish HBeAg- negative CriB patients and inactive carriers. We discuss in detail why DNA level alone is not sufficient to begin treatment of CriB.

关键词： Hepatitis B virus Viral DNA Alaninetransaminase Antiviral drug Hepatitis B e antigen Antiviral drug resistance

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Prediction and stratification for the surgical adverse events after minimally invasive esophagectomy:A two-center retrospective study

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World Journal of Gastroenterology 2025年第3期31卷 50-61页

作者： Qi-Hong Zhong Jiang-Shan Huang Fei-Long Guo Jing-yu Wu Mao-Xiu yuan Jia-Fu Zhu Wen-Wei Lin Sui Chen Zhen-yang Zhang Jiang-Bo Lin Department of Thoracic Surgery Fujian Medical University Union HospitalFuzhou 350001Fujian ProvinceChina The Graduate School Fujian Medical UniversityFuzhou 350001Fujian ProvinceChina Department of Thoracic Surgery Affiliated Hospital of Jinggangshan UniversityJi’an 343000Jiangxi ProvinceChina

BACKGROUND Minimally invasive esophagectomy(MIE)is a widely accepted treatment for esophageal cancer,yet it is associated with a significant risk of surgical adverse events(SAEs),which can compromise patient recovery and long-term *** preoperative identification of high-risk patients is critical for improving *** To establish and validate a risk prediction and stratification model for the risk of SAEs in patients with *** This retrospective study included 747 patients who underwent MIE at two centers from January 2019 to February *** were separated into a train set(n=549)and a validation set(n=198).After screening by least absolute shrinkage and selection operator regression,multivariate logistic regression analyzed clinical and intraoperative variables to identify independent risk factors for SAEs.A risk stratification model was constructed and validated to predict the probability of *** SAEs occurred in 10.2%of patients in train set and 13.6%in the validation *** with SAE had significantly higher complication rate and a longer hospital stay after *** key independent risk factors identified included chronic obstructive pulmonary disease,a history of alcohol consumption,low forced expiratory volume in the first second,and low albumin *** stratification model has excellent prediction accuracy,with an area under the curve of 0.889 for the training set and an area under the curve of 0.793 for the validation *** The developed risk stratification model effectively predicts the risk of SAEs in patients undergoing MIE,facilitating targeted preoperative interventions and improving perioperative management.

关键词： Surgical adverse events Minimally invasive esophagectomy Esophageal cancer Stratification model Perioperative management

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Cirrhotic cardiomyopathy

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World Journal of Gastroenterology 2015年第41期21卷 11502-11521页

作者： Luís Ruíz-del-árbol Regina Serradilla Hepatic Hemodynamic Unit Gastroenterology Department Hospital Ramón y Cajal University of Alcalá

During the course of cirrhosis, there is a progressive deterioration of cardiac function manifested by the disappearance of the hyperdynamic circulation due to afailure in heart function with decreased cardiac output. This is due to a deterioration in inotropic and chronotropic function which takes place in parallel with a diastolic dysfunction and cardiac hypertrophy in the absence of other known cardiac disease. Other findings of this specific cardiomyopathy include impaired contractile responsiveness to stress stimuli and electrophysiological abnormalities with prolonged QT interval. The pathogenic mechanisms of cirrhotic cardiomyopathy include impairment of the b-adrenergic receptor signalling, abnormal cardiomyocyte membrane lipid composition and biophysical properties, ion channel defects and overactivity of humoral cardiodepressant factors. Cirrhotic cardiomyopathy may be difficult to determine due to the lack of a specific diagnosis test. However, an echocardiogram allows the detection of the diastolic dysfunction and the E/e′ ratio may be used in the followup progression of the illness. Cirrhotic cardiomyopathy plays an important role in the pathogenesis of the impairment of effective arterial blood volume and correlates with the degree of liver failure. A clinical consequence of cardiac dysfunction is an inadequate cardiac response in the setting of vascular stress that may result in renal hypoperfusion leading to renal failure. The prognosis is difficult to establish but the severity of diastolic dysfunction may be a marker of mortality risk. Treatment is non-specific and liver transplantation may normalize the cardiac function.

关键词： Cirrhotic cardiomyopathy Inotropic heart dysfuncti

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