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Glucocorticoid receptor signaling in the brain and its involvement in cognitive function

Neural Regeneration Research 2025年第9期20卷 2520-2537页

作者： Chonglin Su Taiqi Huang Meiyu Zhang Yanyu Zhang Yan Zeng Xingxing Chen Brain Science and Advanced technology Institute Hubei Province Key Laboratory of Occupational Hazard Identification and ControlSchool of MedicineWuhan University of Science and TechnologyWuhanHubei ProvinceChina

The hypothalamic-pituitary-adrenal axis regulates the secretion of glucoco rticoids in response to environmental *** the brain,a nuclear receptor transcription fa ctor,the glucocorticoid recepto r,is an important component of the hypothalamicpituitary-a d renal axis's negative feedback loop and plays a key role in regulating cognitive equilibrium and *** glucoco rticoid receptor influences cognitive processes,including glutamate neurotransmission,calcium signaling,and the activation of brain-derived neurotrophic factor-mediated pathways,through a combination of genomic and non-genomic *** interactions within the central nervous system can alter the expression and activity of the glucocorticoid receptor,there by affecting the hypothalamic-pituitary-a d renal axis and stress-related cognitive *** appropriate level of glucocorticoid receptor expression can improve cognitive function,while excessive glucocorticoid receptors or long-term exposure to glucoco rticoids may lead to cognitive *** with cognitive impairment-associated diseases,such as Alzheimer's disease,aging,depression,Parkinson's disease,Huntington's disease,stroke,and addiction,often present with dysregulation of the hypothalamic-pituitary-adrenal axis and glucocorticoid receptor *** review provides a comprehensive overview of the functions of the glucoco rticoid receptor in the hypothalamic-pituitary-a d renal axis and cognitive *** emphasizes that appropriate glucocorticoid receptor signaling fa cilitates learning and memory,while its dysregulation can lead to cognitive *** provides clues about how glucocorticoid receptor signaling can be targeted to ove rcome cognitive disability-related disorders.

关键词： brain-derived neurotrophic factor calcium signaling glucocorticoid receptor glucocorticoid glutamate transmission hypothalamic-pituitary-adrenal axis long-term potentiation neurocognitive disorders neuroplasticity stress

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Neuronal regulated cell death in aging-related neurodegenerative diseases:key pathways and therapeutic potentials

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Neural Regeneration Research 2025年第8期20卷 2245-2263页

作者： Run Song Shiyi Yin Jiannan Wu Junqiang Yan Department of Neurology The First Affiliated HospitalCollege of Clinical Medicine of Henan University of Science and TechnologyLuoyangHenan ProvinceChina Neuromolecular Biology laboratory The First Affiliated HospitalCollege of Clinical Medicine of Henan University of Science and TechnologyLuoyangHenan ProvinceChina

Regulated cell death(such as apoptosis,necroptosis,pyroptosis,autophagy,cuproptosis,ferroptosis,disulfidptosis)involves complex signaling pathways and molecular effectors,and has been proven to be an important regulatory mechanism for regulating neuronal aging and ***,excessive activation of regulated cell death may lead to the progression of aging-related *** review summarizes recent advances in the understanding of seven forms of regulated cell death in age-related ***,the newly identified ferroptosis and cuproptosis have been implicated in the risk of cognitive impairment and neurodegenerative *** forms of cell death exacerbate disease progression by promoting inflammation,oxidative stress,and pathological protein *** review also provides an overview of key signaling pathways and crosstalk mechanisms among these regulated cell death forms,with a focus on ferroptosis,cuproptosis,and *** instance,FDX1 directly induces cuproptosis by regulating copper ion valency and dihydrolipoamide S-acetyltransferase aggregation,while copper mediates glutathione peroxidase 4 degradation,enhancing ferroptosis ***,inhibiting the Xc-transport system to prevent ferroptosis can increase disulfide formation and shift the NADP^(+)/NADPH ratio,transitioning ferroptosis to *** insights help to uncover the potential connections among these novel regulated cell death forms and differentiate them from traditional regulated cell death *** conclusion,identifying key targets and their crosstalk points among various regulated cell death pathways may aid in developing specific biomarkers to reverse the aging clock and treat age-related neurodegenerative conditions.

关键词： apoptosis autophagy cuproptosis disulfidptosis ferroptosis necroptosis neurodegenerative disease neurological aging diseases PANoptosis pyroptosis

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Maintaining moderate levels of hypochlorous acid promotes neural stem cell proliferation and differentiation in the recovery phase of stroke

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Neural Regeneration Research 2025年第3期20卷 845-857页

作者： Lin-Yan Huang Yi-De Zhang Jie Chen Hai-Di Fan Wan Wang Bin Wang Ju-Yun Ma Peng-Peng Li Hai-Wei Pu Xin-Yian Guo Jian-Gang Shen Su-Hua Qi School of Medical technology Xuzhou Key Laboratory of Laboratory DiagnosticsXuzhou Medical UniversityXuzhouJiangsu ProvinceChina School of Pharmacy Xuzhou Medical UniversityXuzhouJiangsu ProvinceChina Department of laboratory medicine Branch Hospital of Huai’an First People’s HospitalHuai’anJiangsu ProvinceChina Department of laboratory medicine the Affiliated Hospital of Xuzhou Medical UniversityXuzhouJiangsu ProvinceChina School of Chinese medicine The University of Hong KongHong Kong Special Administrative RegionChina

It has been shown clinically that continuous removal of ischemia/reperfusion-induced reactive oxygen species is not conducive to the recovery of late ***,previous studies have shown that excessive increases in hypochlorous acid after stroke can cause severe damage to brain *** previous studies have found that a small amount of hypochlorous acid still exists in the later stage of stroke,but its specific role and mechanism are currently *** simulate stroke in vivo,a middle cerebral artery occlusion rat model was established,with an oxygen-glucose deprivation/reoxygenation model established in vitro to mimic *** found that in the early stage(within 24 hours)of ischemic stroke,neutrophils produced a large amount of hypochlorous acid,while in the recovery phase(10 days after stroke),microglia were activated and produced a small amount of hypochlorous ***,in acute stroke in rats,hypochlorous acid production was prevented using a hypochlorous acid scavenger,taurine,or myeloperoxidase inhibitor,4-aminobenzoic acid *** results showed that high levels of hypochlorous acid(200μM)induced neuronal apoptosis after oxygen/glucose deprivation/***,in the recovery phase of the middle cerebral artery occlusion model,a moderate level of hypochlorous acid promoted the proliferation and differentiation of neural stem cells into neurons and *** suggests that hypochlorous acid plays different roles at different phases of cerebral ischemia/reperfusion *** levels of hypochlorous acid(5 and 100μM)promoted nuclear translocation ofβ-*** transfection of single-site mutation plasmids,we found that hypochlorous acid induced chlorination of theβ-catenin tyrosine 30 residue,which promoted nuclear ***,our study indicates that maintaining low levels of hypochlorous acid plays a key role in the recovery of neurological function.

关键词： cell differentiation cerebral ischemia/reperfusion injury chlorination hypochlorous acid microglia neural stem cell neurogenesis nuclear translocation stroke β-catenin

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Traditional Chinese medicine in the treatment of Helicobacter pylorirelated gastritis:The mechanisms of signalling pathway regulations

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World Journal of Gastroenterology 2025年第3期31卷 11-28页

作者： Pei-Pei Zhang Liang Li Hao-Yu Qu Guang-Yu Chen Meng-Zhou Xie Yan-Kun Chen School of Traditional Chinese medicine Hunan University of Chinese MedicineChangsha 410200Hunan ProvinceChina Hunan Engineering technology Research Center for Medicinal and Functional Food Hunan University of Chinese MedicineChangsha 410200Hunan ProvinceChina Key laboratory of Traditional Chinese medicine Heart and Lung Syndrome Differentiation and Medicated Diet and Dietotherapy Hunan University of Chinese MedicineChangsha 410200Hunan ProvinceChina School of Informatics Hunan University of Chinese MedicineChangsha 410208Hunan ProvinceChina Precision medicine Research and Development Center Zhuhai Institute of Advanced TechnologyChinese Academy of SciencesZhuhai 519000Guangdong ProvinceChina

Helicobacter pylori-associated gastritis(HPAG)is a common condition of the gastrointestinal ***,extensive and long-term antibiotic use has resulted in numerous adverse effects,including increased resistance,gastrointestinal dysfunction,and increased recurrence *** these concerns develop,traditional Chinese medicine(TCM)may have *** is based on the concept of completeness and aims to eliminate pathogens and strengthen the *** has the potential to prevent this condition while also boosting the rate of Helicobacter pylori *** review elaborates on the mechanism of TCM treatment for HPAG based on cellular signalling pathways,which reflects the flexibility of TCM in treating diseases and the advantages of multi-level,multipathway,and multi-target treatments for HPAG.

关键词： Helicobacter pylori Helicobacter pylori-associated gastritis Traditional Chinese medicine Signalling pathway Eliminate pathogens Strengthen the body

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Bidirectional regulation of the brain-gut-microbiota axis following traumatic brain injury

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Neural Regeneration Research 2025年第8期20卷 2153-2168页

作者： Xinyu You Lin Niu Jiafeng Fu Shining Ge Jiangwei Shi Yanjun Zhang Pengwei Zhuang National Key laboratory of Chinese medicine Modernization Tianjin University of Traditional Chinese MedicineTianjinChina Haihe laboratory of Modern Chinese medicine Tianjin University of Traditional Chinese MedicineTianjinChina First Teaching Hospital of Tianjin University of Traditional Chinese medicine TianjinChina National Clinical Research Center for Chinese medicine Acupuncture and Moxibustion TianjinChina

Traumatic brain injury is a prevalent disorder of the central nervous *** addition to primary brain parenchymal damage,the enduring biological consequences of traumatic brain injury pose long-term risks for patients with traumatic brain injury;however,the underlying pathogenesis remains unclear,and effective intervention methods are *** dysfunction is a significant consequence of traumatic brain *** the most densely innervated peripheral tissue in the body,the gut possesses multiple pathways for the establishment of a bidirectional“brain-gut axis”with the central nervous *** gut harbors a vast microbial community,and alterations of the gut niche contribute to the progression of traumatic brain injury and its unfavorable prognosis through neuronal,hormonal,and immune pathways.A comprehensive understanding of microbiota-mediated peripheral neuroimmunomodulation mechanisms is needed to enhance treatment strategies for traumatic brain injury and its associated *** comprehensively reviewed alterations in the gut microecological environment following traumatic brain injury,with a specific focus on the complex biological processes of peripheral nerves,immunity,and microbes triggered by traumatic brain injury,encompassing autonomic dysfunction,neuroendocrine disturbances,peripheral immunosuppression,increased intestinal barrier permeability,compromised responses of sensory nerves to microorganisms,and potential effector nuclei in the central nervous system influenced by gut ***,we reviewed the mechanisms underlying secondary biological injury and the dynamic pathological responses that occur following injury to enhance our current understanding of how peripheral pathways impact the outcome of patients with traumatic brain *** review aimed to propose a conceptual model for future risk assessment of central nervous system-related diseases while elucidating novel insights into the bidirectional effec

关键词： traumatic brain injury brain-gut-microbiome axis gut microbiota neuroimmune immunosuppression host defense vagal afferents bacterial infection dorsal root ganglia nociception neural circuitry

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BIBR1532 inhibits proliferation and metastasis of esophageal squamous cancer cells by inducing telomere dysregulation

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World Journal of Gastrointestinal Oncology 2025年第1期17卷 214-225页

作者： Qin Wang Qing-Rong Li Lei Xu Zi-Chun Yuan Xiao Liu Mao-Ju Tang Man Luo Xiao-Wu Zhong Qiang Ma Xiao-Lan Guo Department of Clinical laboratory Affiliated Hospital of North Sichuan Medical CollegeNanchong 637000Sichuan ProvinceChina School of laboratory medicine&Translational medicine Research Center North Sichuan Medical CollegeNanchong 637000Sichuan ProvinceChina

BACKGROUND Esophageal squamous cell carcinoma(ESCC)is a malignant tumor with high morbidity and mortality,and easy to develop resistance to chemotherapeutic *** are DNA-protein complexes located at the termini of chro-mosomes in eukaryotic cells,which are unreplaceable in maintaining the stability and integrity of ***,an RNA-dependent DNA polymerase,play vital role in telomere length maintain,targeting telomerase is a promising therapeutic strategy for ***150 and KYSE410 cells were cultured and exposed to various concentrations of *** viability was assessed at 48 hours and 72 hours to determine the IC50 *** effects of BIBR1532 on ESCC cell proliferation,migration,and cellular senescence were evaluated using the cell counting kit-8 assay,plate colony formation assay,scratch assay,transwell assay,andβ-galactosidase staining,*** blotting was performed to detect the expression of RESULTS The IC50 values for KYSE150 and KYSE410 cells after 48 hours of BIBR1532 exposure were 48.53μM and 39.59μM,*** values decreased to 37.22μM and 22.71μM,respectively,following a longer exposure of 72 ***1532 exhibited dose-dependent effects on KYSE150 and KYSE410 cells,including decreased hTERT expression,inhibition of proliferation and metastasis,and induction of cellular ***,BIBR1532 upregulated the expression of the DDR protein,γ-H2AX,and activated the ataxia telangiectasia and Rad3-related protein(ATR)/check point kinase 1(CHK-1)and ataxia-telangiectasia mutated gene(ATM)/CHK2 ***1532 downregulated the expression of telomere-binding proteins,including telomeric-repeat binding factor 1(TRF1),TRF2,protection of telomeres 1,and TIN2-interacting protein *** a nude mouse xenograft model,BIBR1532 significantly suppressed tumor growth,reduced hTERT expression,and increasedγ-H2AX protein *** and eosin staining of various organs,including the heart,liver,s

关键词： Esophageal squamous cell carcinoma BIBR1532 Human telomerase reverse transcriptase DNA damage response Telomere-binding proteins

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Exploring the interaction between the gut microbiota and cyclic adenosine monophosphate-protein kinase A signaling pathway:a potential therapeutic approach for neurodegenerative diseases

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Neural Regeneration Research 2025年第11期20卷 3095-3112页

作者： Fengcheng Deng Dan Yang Lingxi Qing Yifei Chen Jilian Zou Meiling Jia Qian Wang Runda Jiang Lihua Huang College of Pharmacy Chengdu University of Traditional Chinese MedicineChengduSichuan ProvinceChina State Key laboratory of Southwestern Chinese medicine Resources Chengdu University of Traditional Chinese MedicineChengduSichuan ProvinceChina

The interaction between the gut microbiota and cyclic adenosine monophosphate(cAMP)-protein kinase A(PKA)signaling pathway in the host's central nervous system plays a crucial role in neurological diseases and enhances communication along the gut–brain *** gut microbiota influences the cAMP-PKA signaling pathway through its metabolites,which activates the vagus nerve and modulates the immune and neuroendocrine ***,alterations in the cAMP-PKA signaling pathway can affect the composition of the gut microbiota,creating a dynamic network of microbial-host *** reciprocal regulation affects neurodevelopment,neurotransmitter control,and behavioral traits,thus playing a role in the modulation of neurological *** coordinated activity of the gut microbiota and the cAMP-PKA signaling pathway regulates processes such as amyloid-β protein aggregation,mitochondrial dysfunction,abnormal energy metabolism,microglial activation,oxidative stress,and neurotransmitter release,which collectively influence the onset and progression of neurological *** study explores the complex interplay between the gut microbiota and cAMP-PKA signaling pathway,along with its implications for potential therapeutic interventions in neurological *** pharmacological research has shown that restoring the balance between gut flora and cAMP-PKA signaling pathway may improve outcomes in neurodegenerative diseases and emotional *** can be achieved through various methods such as dietary modifications,probiotic supplements,Chinese herbal extracts,combinations of Chinese herbs,and innovative dosage *** findings suggest that regulating the gut microbiota and cAMP-PKA signaling pathway may provide valuable evidence for developing novel therapeutic approaches for neurodegenerative diseases.

关键词： cyclic adenosine monophosphate emotional disorders gut microbiota neurodegenerative diseases neurological diseases protein kinase A reciprocal regulation signaling pathway strategy therapies

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Targeting STAT3 with SH-4-54 suppresses stemness and chemoresistance in cancer stem-like cells derived from colorectal cancer

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World Journal of Clinical Oncology 2025年第2期16卷 63-75页

作者： Xu-Fan Zhang Qian Chen Qin Jiang Qiong-Ying Hu Department of Nuclear medicine Hospital of Chengdu University of Traditional Chinese MedicineChengdu 641000Sichuan ProvinceChina College of Medical technology Chengdu University of Traditional Chinese MedicineChengdu 610072Sichuan ProvinceChina Department of laboratory medicine Hospital of Mianyang Traditional Chinese MedicineChengdu 641000Sichuan ProvinceChina Department of laboratory medicine Hospital of Chengdu University of Traditional Chinese MedicineChengdu 610072Sichuan ProvinceChina

BACKGROUND Over the years,the numbers of treatment options for colorectal cancer(CRC)have increased,leading to notable improvements in the overall survival of CRC *** therapy may initially yield positive results,the development of drug resistance can result in treatment failure and cancer *** resistance is often attributed to the presence of cancer stem cells(CSCs).These CSCs not only contribute to therapeutic resistance but also play crucial roles in the initiation and development of tumor *** To investigate the antitumor effects of SH-4-54,which are mediated by targeting CSCs relative to treatment *** CSCs were enriched by culturing CRC cells in serum-free *** of stemness and IL-6/JAK2/STAT3 signaling were detected by Western *** of CSC malignancy,including proliferation,invasion,and tumor formation,were *** In this study,we employed SH-4-54,which exhibits anticancer activity in solid tumors through targeting the SH2 domain of both the signal transducer and activator of transcription(STAT)3 and the STAT5,and evaluated its effects on stemness and chemoresistance in colorectal *** expected,SH-4-54 treatment inhibited the phosphorylation of STAT3(p-STAT3)and decreased the percentage of ALDH1A1-positive CRC *** addition of SH-4-54 dissociated colorectal spheroids and decreased the expression of stemness markers,including ALDH1A1,CD44 and ***-4-54 treatment decreased IL-6/JAK2/STAT3 signaling by inhibiting p-STAT3 and thus inhibited spheroid formation by SW480 and LoVo ***,SH-4-54 treatment inhibited indicators of malignancy,including cell proliferation,invasion,and tumor formation,in CSCs in vitro and in ***,SH-4-54 treatment significantly increased chemosensitivity to *** Taken together,these results indicate that SH-4-54 is a promising molecule that exerts antitumor effects on colorectal CSCs by inhibiting STAT3 signaling.

关键词： SH-4-54 Colorectal cancer Cancer stem-like cells Stemness Chemosensitivity

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Integrating lipidomics and gut microbiota to study the anti-hyperlipidemia effect of Sargentodoxae Caulis extract

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Traditional medicine Research 2025年第1期10卷 1-11页

作者： Xiao-Xiao Zhang Li Jia Xiu-Jun Zhan Charity Ngina Qing-Rui Zhang Xiao-Ge Li Qi-Bao Jiang Shi Bai Miao-Miao Jiang National Key laboratory of Chinese medicine Modernization Tianjin University of Traditional Chinese MedicineTianjin 301617China Haihe laboratory of Modern Chinese medicine Tianjin 301617China School of medicine Taizhou UniversityTaizhou 318000China.

Background:Sargentodoxae Caulis(SC)is the vine stem of Sargentodoxa Cuneata(Oliv.)Rehd.&*** in ***,and it in traditional Chinese medicine has been known for promoting blood circulation and removing blood stasis as recorded in the ancient book“Illustrated Classics of Materia Medica”.It has been used effectively to treat blood stasis too in modern clinical ***,the anti-hyperlipidemia effect of SC is not fully *** paper aims at exploring the use of SC stems to improve the balance of blood lipids in the body,and its new role in treating ***:The effects of SC extract on hyperlipidemia were explored by combining lipidomics and gut ***,we explored the potential mechanism of SC in treating hyperlipidemia by pathway ***:The results showed that the stem extract of SC could restore the physiological and biochemical indices of hyperlipidemia in mice,as well as repair the morphological and structural damage to *** to the Model group,the SC extract significantly reduced the liver index,epididymal fat index,and Lee’s *** also significantly decreased serum levels of total cholesterol,triglycerides,low-density lipoprotein cholesterol,peroxisome proliferator-activated receptor gamma(PPAR-γ),D-lactate,and free fatty acids,while significantly increasing the relative content of peroxisome proliferator-activated receptor alpha(PPAR-α).These changes were statistically ***-targeted lipidomics,based on LC-MS,were utilized to investigate the lipid metabolism characteristics in serum,liver,and epididymal fat of the *** was observed that,compared to the blank group,the Model group exhibited significant changes primarily in glycerol lipids and *** treatment group also displayed alterations in these lipids.A total of 38,81,and 27 differential lipids were identified in serum,liver,and epididymal fat samples,*** these,14 common differenti

关键词： hyperlipidemia Sargentodoxae Caulis lipidomics intestinal flora

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Prognostic model for esophagogastric variceal rebleeding after endoscopic treatment in liver cirrhosis: A Chinese multicenter study

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World Journal of Gastroenterology 2025年第2期31卷 85-101页

作者： Jun-Yi Zhan Jie Chen Jin-Zhong Yu Fei-Peng Xu Fei-Fei Xing De-Xin Wang Ming-Yan Yang Feng Xing Jian Wang Yong-Ping Mu Cell Biology laboratory Shuguang Hospital Affiliated to Shanghai University of Traditional Chinese MedicineShanghai 201203China Institute of Liver Diseases Shanghai Academy of Chinese MedicineShanghai 201203China Clinical Key laboratory of Traditional Chinese medicine of Shanghai Shuguang Hospital Affiliated to Shanghai University of Traditional Chinese MedicineShanghai 201203China Key laboratory of Liver and Kidney Disease of the Ministry of Education Shanghai University of Traditional Chinese MedicineShanghai 201203China Department of Gastroenterology and Hepatology Zhongshan Hospital Affiliated to Fudan UniversityShanghai 200032China Shanghai Institute of Liver Disease Fudan UniversityShanghai 200032China Evidence-Based medicine Center Fudan UniversityShanghai 200032China Department of Gastrointestinal Endoscopy Shuguang Hospital Affiliated to Shanghai University of Traditional Chinese MedicineShanghai 201203China Department of Hepatology Shuguang Hospital Affiliated to Shanghai University of Traditional Chinese MedicineShanghai 201203China

BACKGROUND Rebleeding after recovery from esophagogastric variceal bleeding(EGVB)is a severe complication that is associated with high rates of both incidence and *** its clinical importance,recognized prognostic models that can effectively predict esophagogastric variceal rebleeding in patients with liver cirrhosis are *** To construct and externally validate a reliable prognostic model for predicting the occurrence of esophagogastric variceal *** This study included 477 EGVB patients across 2 cohorts:The derivation cohort(n=322)and the validation cohort(n=155).The primary outcome was rebleeding events within 1 *** least absolute shrinkage and selection operator was applied for predictor selection,and multivariate Cox regression analysis was used to construct the prognostic *** validation was performed with bootstrap *** assessed the discrimination,calibration and accuracy of the model,and performed patient risk *** Six predictors,including albumin and aspartate aminotransferase concentrations,white blood cell count,and the presence of ascites,portal vein thrombosis,and bleeding signs,were selected for the rebleeding event prediction following endoscopic treatment(REPET)*** predicting rebleeding within 1 year,the REPET model ex-hibited a concordance index of 0.775 and a Brier score of 0.143 in the derivation cohort,alongside 0.862 and 0.127 in the validation ***,the REPET model revealed a significant difference in rebleeding rates(P<0.01)between low-risk patients and intermediate-to high-risk patients in both *** We constructed and validated a new prognostic model for variceal rebleeding with excellent predictive per-formance,which will improve the clinical management of rebleeding in EGVB patients.

关键词： Esophagogastric variceal bleeding Variceal rebleeding Liver cirrhosis Prognostic model Risk stratification Secondary prophylaxis

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