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Dysregulation of genes involved in the long-chain fatty acid transport in pancreatic ductal adenocarcinoma

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World Journal of Gastrointestinal Oncology 2025年第1期17卷 199-206页

作者： Radu Cristian Poenaru Elena Milanesi Andrei Marian Niculae Anastasia-Maria Dobre Catalina Vladut Mihai Ciocîrlan Daniel Vasile Balaban Vlad Herlea Maria Dobre Mihail Eugen Hinescu Faculty of medicine Carol Davila University of Medicine and PharmacyBucharest 050474Romania department of Radiobiology Victor Babes National Institute of PathologyBucharest 050096Romania department of pathology Victor Babes National Institute of PathologyBucharest 050096Romania department of Gastroenterology Prof.Dr.Agrippa Ionescu Clinical Emergency HospitalBucharest 011356Romania department of pathology Fundeni Clinical InstituteBucharest 022258Romania

BACKGROUND Pancreatic ductal adenocarcinoma(PDAC)is an aggressive lethal malignancy with limited options for treatment and a 5-year survival rate of 11%in the United *** for other types of tumors,such as colorectal cancer,aberrant de novo lipid synthesis and reprogrammed lipid metabolism have been suggested to be associated with PDAC development and *** To identify the possible involvement of lipid metabolism in PDAC by analyzing in tumoral and non-tumoral tissues the expression level of the most relevant genes involved in the long-chain fatty acid(FA)import into *** A gene expression analysis of FASN,CD36,SLC2.A1,SLC2.A2.SLC2.A3,SLC2.A4,SLC2.A5,ACSL1,and ACSL3 was performed by qRT-PCR in 2. tumoral PDAC tissues and 11 samples from non-tumoral pancreatic tissues obtained via fine needle aspiration or via surgical *** genes were considered significantly dysregulated between the groups when the p value was2.A2.FC=5.66;P=0.033),SLC2.A3(FC=2.68;P=0.040),SLC2.A4(FC=3.13;P=0.033),ACSL1(FC=4.10;P2.67;P=0.012..We further investigated any possible association between the levels of the analyzed mRNAs and the specific characteristics of the tumors,including the anatomic location,the lymph node involvement,and the presence of metastasis.A significant difference in the expression of SLC2.A3(FC=3.2.;P=0.040)was found comparing patients with and without lymph nodes involvement with an overexpression of this transcript in 17 patients presenting tumoral cells in the lymph *** Despite the low number of patients analyzed,these preliminary results seem to be *** lipid metabolism through a broad strategy could be a beneficial way to treat this *** in vitro and in vivo s

关键词： Carcinoma Pancreatic ductal Fatty acid transport Gene expression Biomarkers

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 37.2.μM and 2..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-H2.X,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-H2.X 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

Transfer RNA-derived small RNA serves as potential non-invasive diagnostic marker and a novel therapeutic target for acute pancreatitis

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World Journal of Gastroenterology 2025年第1期31卷 152-156页

作者： Jing Zhang Chun-Lin Ou department of Immunology School of Basic MedicineCentral South UniversityChangsha 410000Hunan ProvinceChina department of pathology Xiangya HospitalCentral South UniversityChangsha 410008Hunan ProvinceChina

Transfer RNA(tRNA)-derived fragments,a new type of tRNA-derived small RNA(tsRNA),can be cleaved from tRNA by enzymes to regulate target gene expression at the transcriptional and translational *** are not only degradation fragments but also have biological functions,including those in immune inflammation,metabolic disorders,and cell *** dysregulation is closely associated with multiple diseases,including various cancers and acute pancreatitis(AP).AP is a common gastrointestinal disease,and its incidence increases *** development is associated with tsRNAs,which regulate cell injury and induce inflammation,especially pyroptosis and ***,serum tRF36 has the potential to serve as a non-invasive diagnostic biomarker and leads to pancreatic acinar cell ferroptosis causing inflammation to promote *** show the characteristics of tsRNAs and their diagnostic value and function in AP,and discuss the potential opportunities and challenges of using tsRNAs in clinical applications and research.

关键词： Transfer RNA derived small RNAs Acute pancreatitis Liquid biopsy Biomarker Cell pyroptosis Ferroptosis

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 {2. Branch Hospital of Huai’an First People’s HospitalHuai’anJiangsu ProvinceChina department of laboratory {2. 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 2. 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(2.0μM)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

Retrospective analysis of pathological types and imaging features in pancreatic cancer: A comprehensive study

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World Journal of Gastrointestinal Oncology 2025年第1期17卷 121-129页

作者： Yang-Gang Luo Mei Wu Hong-Guang Chen pathology department Xuanhan County People’s HospitalDazhou 636150Sichuan ProvinceChina

BACKGROUND Pancreatic cancer remains one of the most lethal malignancies worldwide,with a poor prognosis often attributed to late *** the correlation between pathological type and imaging features is crucial for early detection and appropriate treatment *** To retrospectively analyze the relationship between different pathological types of pancreatic cancer and their corresponding imaging *** We retrospectively analyzed the data of 500 patients diagnosed with pancreatic cancer between January 2.10 and December 2.2. at our *** types were determined by histopathological examination of the surgical spe-cimens or biopsy *** imaging features were assessed using computed tomography,magnetic resonance imaging,and endoscopic *** analyses were performed to identify significant associations between pathological types and specific imaging *** There were 32.(64%)cases of pancreatic ductal adenocarcinoma,75(15%)of intraductal papillary mucinous neoplasms,50(10%)of neuroendocrine tumors,and 55(11%)of other rare *** imaging features were identified in each pathological *** ductal adenocarcinoma typically presents as a hypodense mass with poorly defined borders on computed tomography,whereas intraductal papillary mucinous neoplasms present as characteristic cystic lesions with mural *** tumors often appear as hypervascular lesions in contrast-enhanced *** analysis revealed significant correlations between specific imaging features and pathological types(P<0.001).CONCLUSION This study demonstrated a strong association between the pathological types of pancreatic cancer and imaging *** findings can enhance the accuracy of noninvasive diagnosis and guide personalized treatment approaches.

关键词： Pancreatic cancer Pathological types Imaging features Retrospective analysis Diagnostic accuracy

The emerging role of nitric oxide in the synaptic dysfunction of vascular dementia

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Neural Regeneration Research 2025年第2期20卷 402-415页

作者： Xiaorong Zhang Zhiying Chen Yinyi Xiong Qin Zhou Ling-Qiang Zhu Dan Liu department of pathology Affiliated Hospital of Jiujiang UniversityJiujiangJiangxi ProvinceChina Jiujiang Clinical Precision medicine Research Center JiujiangJiangxi ProvinceChina Center for Cognitive Science and Transdisciplinary Studies Jiujiang UniversityJiangxi ProvinceChina department of Neurology Affiliated Hospital of Jiujiang UniversityJiujiangJiangxi ProvinceChina department of Rehabilitation Affiliated Hospital of Jiujiang UniversityJiujiangJiangxi ProvinceChina department of Pathophysiology School of Basic MedicineTongji Medical CollegeHuazhong University of Science and TechnologyWuhanHubei ProvinceChina

With an increase in global aging,the number of people affected by cerebrovascular diseases is also increasing,and the incidence of vascular dementia-closely related to cerebrovascular risk-is increasing at an epidemic ***,few therapeutic options exist that can markedly improve the cognitive impairment and prognosis of vascular dementia *** in Alzheimer’s disease and other neurological disorders,synaptic dysfunction is recognized as the main reason for cognitive *** oxide is one of the ubiquitous gaseous cellular messengers involved in multiple physiological and pathological processes of the central nervous ***,nitric oxide has been implicated in regulating synaptic plasticity and plays an important role in the pathogenesis of vascular *** review introduces in detail the emerging role of nitric oxide in physiological and pathological states of vascular dementia and summarizes the diverse effects of nitric oxide on different aspects of synaptic dysfunction,neuroinflammation,oxidative stress,and blood-brain barrier dysfunction that underlie the progress of vascular ***,we propose that targeting the nitric oxide-sGC-cGMP pathway using certain specific approaches may provide a novel therapeutic strategy for vascular dementia.

关键词： endoplasmic reticulum stress endothelial nitric oxide synthase gene therapy nitric oxide NO-sGC-cGMP pathway synaptic dysfunction vascular dementia

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=32.)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 0.12. 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

Calcium channels caught in peripheral glia’s tug-of-war on axon regeneration in Drosophila

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Neural Regeneration Research 2025年第2期20卷 475-476页

作者： Jackson Powell Tobias Steinschaden Rose Horowitz Yuanquan Song Raymond G.Perelman Center for Cellular and Molecular Therapeutics The Children’s Hospital of PhiladelphiaPhiladelphiaPAUSA The Neuroscience Graduate Group University of PennsylvaniaPhiladelphiaPAUSA department of pathology and {2. medicine University of PennsylvaniaPhiladelphiaPAUSA Medical University of Vienna Center for Brain ResearchDepartment of NeuroimmunologyViennaAustria

Neural damage or degeneration is at the crux of many diseases,and treatment of these diseases will require the development of therapeutics to enhance and guide neural *** intrinsic and extrinsic factors dictate a neuron’s ability to regenerate,and the combination of these factors results in the great regenerative capacity of the peripheral nervous system(PNS)and the poor regenerative capacity of the central nervous system(CNS)following *** the core of a neuron’s function is its ability to relay electrochemical signals,and a neuron’s excitability is a key factor in its ability to *** works have focused on the changes in neuronal electrophysiological properties,firing patterns,and ion flux after injury,which differentially activate signaling pathways at the core of *** role of glia in neuron regeneration has long been studied.

关键词： degeneration firing system

Pan-TRK positive uterine sarcoma in immunohistochemistry without neurotrophic tyrosine receptor kinase gene fusions:A case report

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World Journal of Clinical Cases 2025年第2期13卷 39-49页

作者： Seungmee Lee Yu-Ra Jeon Changmin Shin Sun-Young Kwon Sojin Shin department of Obstetrics and Gynecology Keimyung University School of MedicineDaegu 42601South Korea department of pathology and Institute for Cancer Research Keimyung University School of MedicineDaegu 42601South Korea

BACKGROUND The classification of uterine sarcomas is based on distinctive morphological and immunophenotypic characteristics,increasingly supported by molecular genetic *** on neurotrophic tyrosine receptor kinase(NTRK)gene fusionpositive uterine sarcoma,potentially aggressive and morphologically similar to fibrosarcoma,are limited due to its recent ***-TRK immunohistochemistry(IHC)analysis serves as an effective screening tool with high sensitivity and specificity for NTRK-fusion *** SUMMARY We report a case of a malignant mesenchymal tumor originating from the uterine cervix,which was pan-TRK IHC-positive but lacked NTRK gene fusions,accompanied by a brief literature review.A 55-year-old woman presented to the emergency department with abdominal pain and distension,exhibiting significant ascites and multiple solid pelvic *** examination revealed a tumor encompassing the uterine cervix,extending to the vagina and uterine corpus.A punch biopsy of the cervix indicated NTRK sarcoma with positive immunochemical pan-TRK ***,subsequent next generation sequencing revealed no NTRK gene fusion,leading to a diagnosis of poorly differentiated,advanced-stage *** The clinical significance of NTRK gene fusion lies in potential treatment with TRK inhibitors for positive *** such rare tumors is crucial due to the potential applicability of tropomyosin receptor kinase inhibitor treatment.

关键词： Uterine sarcoma Cervical sarcoma Neurotrophic tyrosine receptor kinase gene fusion Next generation sequencing Case report