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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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Autophagy-targeting modulation to promote peripheral nerve regeneration

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Neural Regeneration Research 2025年第7期20卷 1864-1882页

作者： Yan Chen Hongxia Deng Nannan Zhang Department of Obstetrics and Gynecology West China Second HospitalSichuan UniversityChengduSichuan ProvinceChina Key Laboratory of Birth Defects and Women and Children’s Diseases Ministry of EducationSichuan UniversityChengduSichuan ProvinceChina Laboratory of Reproductive Endocrinology and Reproductive Regulation Sichuan UniversityChengduSichuan ProvinceChina National Center for Birth Defect Monitoring West China Second University HospitalSichuan UniversityChengduSichuan ProvinceChina

Nerve regeneration following traumatic peripheral nerve injuries and neuropathies is a complex process modulated by diverse factors and intricate molecular *** studies have focused on factors that stimulate axonal outgrowth and myelin ***,recent studies have highlighted the pivotal role of autophagy in peripheral nerve regeneration,particularly in the context of traumatic ***,autophagy-targeting modulation has emerged as a promising therapeutic approach to enhancing peripheral nerve *** current understanding suggests that activating autophagy facilitates the rapid clearance of damaged axons and myelin sheaths,thereby enhancing neuronal survival and mitigating injury-induced oxidative stress and *** actions collectively contribute to creating a favorable microenvironment for structural and functional nerve regeneration.A range of autophagyinducing drugs and interventions have demonstrated beneficial effects in alleviating peripheral neuropathy and promoting nerve regeneration in preclinical models of traumatic peripheral nerve *** review delves into the regulation of autophagy in cell types involved in peripheral nerve regeneration,summarizing the potential drugs and interventions that can be harnessed to promote this *** hope that our review will offer novel insights and perspectives on the exploitation of autophagy pathways in the treatment of peripheral nerve injuries and neuropathies.

关键词： autophagy autophagy related genes Charcot–Marie–Tooth diseases diabetic peripheral neuropathy metformin myelination peripheral nerve injury Schwann cells sciatic nerve Wallerian degeneration

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Biofabrication (3D Bioprinting) Laboratory at sichuan university

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Bio-Design and Manufacturing 2021年第2期4卷 432-439页

作者： Changchun Zhou Kefeng Wang Yong Sun Qiguang Wang Qing Jiang Jie Liang Xuan Pei Boqing Zhang Yujiang Fan Xingdong Zhang National Engineering Research Center for Biomaterials Sichuan UniversityChengdu 610064China College of Biomedical Engineering Sichuan UniversityChengdu 610064China College of Materials Science and Engineering Sichuan UniversityChengdu 610064China

Introduction and research overview Recently,increasing need for organ transplantation and lack of donated organs have led to the rapid development of new technologies for artificial organ *** the era of burgeoning breakthroughs around 3D bioprinting technologies,the personalization of organs and medicine is an ongoing nice vision[1–5].As one of the leading laboratories in the interdisciplinary field of materials,manufacturing and bioengineering,the Biofabrication(3D Bioprinting)Research Laboratory at sichuan university has been engaging in the research on customized regenerativemedicine since 2012.

关键词： printing organs Laboratory

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Quickly obtaining densely dispersed coherent particles in steel matrix and its related mechanical property

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International Journal of Minerals,Metallurgy and Materials 2025年第1期32卷 111-118页

作者： Xiaoxiao Wang Qingsong Huang School of Chemical Engineering Sichuan UniversityChengdu 610065China

Densely distributed coherent nanoparticles(DCN)in steel matrix can enhance the work-hardening ability and ductility of steel *** the routes to this end can be generally classified into the liquid-solid route and the solid-solid ***,the formation of DCN structures in steel requires long processes and complex *** far,obtaining steel with coherent particle enhancement in a short time remains a bottleneck,and some necessary steps remain ***,we show a high-efficiency liquid-phase refining process reinforced by a dynamic magnetic ***-Y-Mn-O particles had an average size of around(3.53±1.21)nm and can be obtained in just around 180 *** small nanoparticles were coherent with the matrix,implying no accumulated dislocations between the particles and the steel *** findings have a potential application for improving material machining capacity,creep resistance,and radiation resistance.

关键词： ferritic steels coherent particles microstructure compression test work hardening

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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 2010 and December 2020 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 320(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

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Stiffness-tunable biomaterials provide a good extracellular matrix environment for axon growth and regeneration

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Neural Regeneration Research 2025年第5期20卷 1364-1376页

作者： Ronglin Han Lanxin Luo Caiyan Wei Yaru Qiao Jiming Xie Xianchao Pan Juan Xing Department of Pathophysiology School of Basic Medical SciencesSouthwest Medical UniversityLuzhouSichuan ProvinceChina Department of Medicinal Chemistry School of PharmacySouthwest Medical UniversityLuzhouSichuan ProvinceChina

Neuronal growth, extension, branching, and formation of neural networks are markedly influenced by the extracellular matrix—a complex network composed of proteins and carbohydrates secreted by cells. In addition to providing physical support for cells, the extracellular matrix also conveys critical mechanical stiffness cues. During the development of the nervous system, extracellular matrix stiffness plays a central role in guiding neuronal growth, particularly in the context of axonal extension, which is crucial for the formation of neural networks. In neural tissue engineering, manipulation of biomaterial stiffness is a promising strategy to provide a permissive environment for the repair and regeneration of injured nervous tissue. Recent research has fine-tuned synthetic biomaterials to fabricate scaffolds that closely replicate the stiffness profiles observed in the nervous system. In this review, we highlight the molecular mechanisms by which extracellular matrix stiffness regulates axonal growth and regeneration. We highlight the progress made in the development of stiffness-tunable biomaterials to emulate in vivo extracellular matrix environments, with an emphasis on their application in neural repair and regeneration, along with a discussion of the current limitations and future prospects. The exploration and optimization of the stiffness-tunable biomaterials has the potential to markedly advance the development of neural tissue engineering.

关键词： alginate axon growth biomaterials extracellular matrix neural repair neurons neuroregeneration polyacrylamide polydimethylsiloxane stiffness

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Induced neural stem cells regulate microglial activation through Akt-mediated upregulation of CXCR4 and Crry in a mouse model of closed head injury

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Neural Regeneration Research 2025年第5期20卷 1416-1430页

作者： Mou Gao Qin Dong Dan Zou Zhijun Yang Lili Guo Ruxiang Xu Department of Neurosurgery Sichuan Academy of Medical Sciences and Sichuan Provincial People’s HospitalSchool of MedicineUniversity of Electronic Science and Technology of ChinaChengduSichuan ProvinceChina Department of Neurosurgery Chinese PLA General HospitalBeijingChina Department of Neurology Fu Xing HospitalCapital Medical UniversityBeijingChina

Microglial activation that occurs rapidly after closed head injury may play important and complex roles in neuroinflammation-associated neuronal damage and *** previously reported that induced neural stem cells can modulate the behavior of activated microglia via CXCL12/CXCR4 signaling,influencing their activation such that they can promote neurological ***,the mechanism of CXCR4 upregulation in induced neural stem cells remains *** this study,we found that nuclear factor-κB activation induced by closed head injury mouse serum in microglia promoted CXCL12 and tumor necrosis factor-αexpression but suppressed insulin-like growth factor-1 ***,recombinant complement receptor 2-conjugated Crry(CR2-Crry)reduced the effects of closed head injury mouse serum-induced nuclear factor-κB activation in microglia and the levels of activated microglia,CXCL12,and tumor necrosis factor-α.Additionally,we observed that,in response to stimulation(including stimulation by CXCL12 secreted by activated microglia),CXCR4 and Crry levels can be upregulated in induced neural stem cells via the interplay among CXCL12/CXCR4,Crry,and Akt signaling to modulate microglial *** agreement with these in vitro experimental results,we found that Akt activation enhanced the immunoregulatory effects of induced neural stem cell grafts on microglial activation,leading to the promotion of neurological recovery via insulin-like growth factor-1 secretion and the neuroprotective effects of induced neural stem cell grafts through CXCR4 and Crry upregulation in the injured cortices of closed head injury ***,these beneficial effects of Akt activation in induced neural stem cells were positively correlated with the therapeutic effects of induced neural stem cells on neuronal injury,cerebral edema,and neurological disorders post–closed head *** conclusion,our findings reveal that Akt activation may enhance the immunoregulatory effects of induced neura

关键词： Akt signaling cerebral edema closed head injury Crry CXCR4 induced neural stem cell microglia neuroinflammation

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Kangfuxin solution alleviates esophageal stenosis after endoscopic submucosal dissection:A natural ingredient strategy

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World Journal of Gastroenterology 2025年第1期31卷 110-125页

作者： Xin Zhou Dan Ma Yi-Xiang He Jing Jin Hong-Lian Wang Yun-Feng Wang Fan Yang Jian-Qin Liu Jie Chen Zhi Li Department of Spleen and Stomach Diseases the Affiliated Traditional Chinese Medicine HospitalSouthwest Medical UniversityLuzhou 646000Sichuan ProvinceChina The Key Laboratory of Integrated Traditional Chinese and Western Medicine for Prevention and Treatment of Digestive System Diseases of Luzhou City The Affiliated Traditional Medicine HospitalSouthwest Medical UniversityLuzhou 646000Sichuan ProvinceChina Department of Gastroenterology Changhai HospitalNaval Medical UniversityShanghai 20082China Research Center of Integrated Chinese and Western Medicine The Affiliated Traditional Chinese Medicine HospitalSouthwest Medical UniversityLuzhou 646000Sichuan ProvinceChina School of Integrated Traditional Chinese and Western Clinical Medicine North Sichuan Medical CollegeNanchong637100Sichuan ProvinceChina

BACKGROUND Esophageal stricture ranks among the most significant complications following endoscopic submucosal dissection(ESD).Excessive fibrotic repair is a typical pathological feature leading to stenosis after *** To examine the effectiveness and underlying mechanism of Kangfuxin solution(KFX)in mitigating excessive fibrotic repair of the esophagus *** Pigs received KFX at 0.74 mL/kg/d for 21 days after esophageal full circumferential *** examinations occurred on days 7 and 21 *** vitro,recombinant transforming growth factor(TGF)-β1(5 ng/mL)induced a fibrotic microenvironment in primary esophageal fibroblasts(pEsF).After 24 hours of KFX treatment(at 1.5%,1%,and 0.5%),expression ofα-smooth muscle actin-2(ACTA2),fibronectin(FN),and type collagen I was *** signaling was analyzed,including TGF-β1,Smad2/3,and phosphor-smad2/3(p-Smad2/3).RESULTS Compared to the Control group,the groups treated with KFX and prednisolone exhibited reduced esophageal stenosis,lower weight loss rates,and improved food tolerance 21 d after *** treatment,Masson staining revealed thinner and less dense collagen fibers in the submucosal ***,the expression of fibrotic effector molecules was notably ***,KFX downregulated the transduction levels of fibrotic functional molecules such as TGF-β1,Smad2/3,and p-Smad2/*** vitro,pEsF exposed to TGF-β1-induced fibrotic microenvironment displayed increased fibrotic activity,which was reversed by KFX treatment,leading to reduced activation of ACTA2,FN,and collagen *** 1.5%KFX treatment group showed decreased expression of p-Smad 2/3 in TGF-β1-activated *** KFX showed promise as a therapeutic option for post-full circumferential esophageal ESD strictures,potentially by suppressing fibroblast fibrotic activity through modulation of the TGF-β1/Smads signaling pathway.

关键词： Kangfuxin solution Natural component Endoscopic submucosal dissection Esophagus stricture Fibrosis

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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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Physical rehabilitation for sensorineural hearing loss in childhood:Progress and challenges

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World Journal of Clinical Cases 2025年第7期13卷 57-62页

作者： Lu Zhang Pu-Jue Huang Xue Deng Jiao Tang Yang Zhai Tao Wang Department of Pediatrics Luzhou Maternal and Child Health HospitalLuzhou 646600Sichuan ProvinceChina Department of Pediatrics West China Second University HospitalSichuan UniversityChengdu 610041Sichuan ProvinceChina Department of Pediatrics The First People's Hospital of Longquanyi DistrictChengdu 610100Sichuan ProvinceChina Ministry of Education Key Laboratory of Birth Defects and Related Diseases of Women and Children(Sichuan University)Chengdu 610041Sichuan ProvinceChina Department of Pediatrics Chengdu Women’s and Children’s Central HospitalChengdu 610000Sichuan ProvinceChina

Early intervention for sensorineural hearing loss(SNHL)in childhood is crucial for auditory and language *** recent years,innovative auditory stimulation techniques and speech therapy strategies,such as middle ear implants,cochlear implants,auditory brainstem implants,and midbrain implants,have provided new avenues for improving patient ***,basic research advancements in cell reprogramming and regeneration,stem cell therapy,and targeted drug delivery offer promising approaches to meet the individualized needs of children with ***,many challenges and unresolved issues remain in the treatment of *** article comments on the case report,which describes a female pediatric patient with SNHL who underwent foot reflexology which led to the normalization of hearing *** is considered to have potential benefits in physical rehabilitation,but its efficacy in hearing restoration requires further scientific validation through rigorous clinical trials and large-scale prospective studies.

关键词： Sensorineural hearing loss Childhood Physical rehabilitation therapy Recent advances in rehabilitation techniques Reflexology

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