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Inhibition of the NLRP3 inflammasome attenuates spiral ganglion neuron degeneration in aminoglycoside-induced hearing loss

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Neural Regeneration Research 2025年第10期20卷 3025-3039页

作者： Jia Fang Zhuangzhuang li Pengjun Wang Xiaoxu Zhang Song Mao Yini li Dongzhen Yu Xiaoyan li Yazhi Xing Haibo Shi Shankai Yin Department of Otolaryngology Head and Neck Surgery Shanghai Sixth People’s Hospital Affiliated to Shanghai Jiao Tong University School of MedicineOtolaryngology Institute of Shanghai Jiao Tong UniversityShanghai Key Laboratory of Sleep Disordered BreathingShanghaiChina Department of Otorhinolaryngology-Head and Neck Surgery Shanghai Children’s HospitalSchool of MedicineShanghai Jiao Tong UniversityShanghaiChina

Aminoglycosides are a widely used class of antibacterials renowned for their effectiveness and broad antimicrobial ***,their use leads to irreversible hearing damage by causing apoptosis of hair cells as their direct *** addition,the hearing damage caused by aminoglycosides involves damage of spiral ganglion neurons upon *** investigate the mechanisms underlying spiral ganglion neuron degeneration induced by aminoglycosides,we used a C57BL/6J mouse model treated with *** found that the mice exhibited auditory deficits following the acute loss of outer hair *** ganglion neurons displayed hallmarks of pyroptosis and exhibited progressive degeneration over *** profiling of these neurons showed significant upregulation of genes associated with inflammation and immune response,particularly those related to the NLRP3 *** of the canonical pyroptotic pathway in spiral ganglion neurons was observed,accompanied by infiltration of macrophages and the release of proinflammatory *** intervention targeting NLRP3 using Mcc950 and genetic intervention using NLRP3 knockout ameliorated spiral ganglion neuron degeneration in the injury *** findings suggest that NLRP3 inflammasome-mediated pyroptosis plays a role in aminoglycoside-induced spiral ganglion neuron *** of this pathway may offer a potential therapeutic strategy for treating sensorineural hearing loss by reducing spiral ganglion neuron degeneration.

关键词： degeneration hearing loss macrophages Mcc950 neuroinflammation NLRP3 inflammasome ototoxicity pyroptosis sensorineural hearing loss spiral ganglion neuron

Targeting cholesterol trafficking to mitigate axonal degeneration in hereditary spastic paraplegia

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Neural Regeneration Research 2025年第5期20卷 1397-1398页

作者： Zhenyu Chen Xue-Jun li Department of Biomedical Sciences University of Illinois College of Medicine RockfordRockfordILUSA Department of Bioengineering University of Illinois at ChicagoChicagoILUSA

Axonal degeneration underlies many debilitating diseases including hereditary spastic paraplegia(HSP),a genetically and clinically diverse group of disorders characterized by spasticity and weakness of the lower *** is one significant cause of chronic neurodisability due to the lack of effective treatments and a wide range of onset ages from early childhood to 70 years.

关键词： degeneration diseases hereditary

Perfluoropentane-based oxygen-loaded nanodroplets reduce microglial activation through metabolic reprogramming

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Neural Regeneration Research 2025年第4期20卷 1178-1191页

作者： Wanxian Luo Chuanhui Xu linxi li Yunxiang Ji Yezhong Wang Yingjia li Yongyi Ye Department of Medicine Ultrasonics Nanfang HospitalSouthern Medical UniversityGuangzhouGuangdong ProvinceChina Institute of Neuroscience Department of NeurosurgeryThe Second Affiliated Hospital of Guangzhou Medical UniversityGuangzhouGuangdong ProvinceChina

Microglia,the primary immune cells within the brain,have gained recognition as a promising therapeutic target for managing neurodegenerative diseases within the central nervous system,including Parkinson’s *** perfluorocarbon droplets have been reported to not only possess a high oxygen-carrying capacity,but also exhibit remarkable anti-inflammatory ***,the role of perfluoropentane in microglia-mediated central inflammatory reactions remains poorly *** this study,we developed perfluoropentane-based oxygen-loaded nanodroplets(PFP-OLNDs)and found that pretreatment with these droplets suppressed the lipopolysaccharide-induced activation of M1-type microglia in vitro and in vivo,and suppressed microglial activation in a mouse model of Parkinson’s *** suppression led to a reduction in the inflammatory response,oxidative stress,and cell migration capacity in ***,the neurotoxic effects were mitigated,which alleviated neuronal ***,ultrahigh-performance liquid chromatography–tandem mass spectrometry showed that the anti-inflammatory effects of PFP-OLNDs mainly resulted from the modulation of microglial metabolic *** further showed that PFP-OLNDs regulated microglial metabolic reprogramming through the AKT-mTOR-HIF-1α***,our findings suggest that the novel PFP-OLNDs constructed in this study alleviate microglia-mediated central inflammatory reactions through metabolic reprogramming.

关键词： metabolic reprogramming microglia microglial migration nanotherapy neurodegenerative diseases neuroinflammation oxygen-loaded nanodroplets Parkinson’s disease perfluoropentane ultra-performance liquid chromatography–mass spectrometry

Inflammation responsive tofacitinib loaded albumin nanomedicine for targeted synergistic therapy in ulcerative colitis

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Nano Research 2023年第7期16卷 9873-9884页

作者： Bang li Xiaoyan liu Qi Long Xiaoduan Zhuang Yanfei Gao Barkat Ali haoting Chen Dongyang Zhang Xinying Wang Weisheng Guo Department of Gastroenterology Zhujiang HospitalSouthern Medical UniversityGuangzhou 510282China Department of Minimally Invasive Interventional Radiology the State Key Laboratory of Respiratory DiseaseSchool of Biomedical Engineering&The Second Affiliated HospitalGuangzhou Medical UniversityGuangzhou 510260China

Patients with ulcerative colitis(UC)often loss responses over long term usage of conventional ***,a pan-Janus kinases(JAK)inhibitor is approved for moderate to severe UC treatment,while dose-limiting systemic side effects including infections,cancers and lymphoma limit its popularity of clinical *** study sought to construct an anti-mucosal vascular addressin cell-adhesion molecule-1(anti-MAdCAM-1)antibody modified reactive oxygen species(ROS)responsive human serum albumin-based nanomedicine denoted as THM,to improve the therapeutic efficacy of tofacitinib for UC *** has the drug releasing properties in response to ROS *** vitro studies show that THM selectively adhered to the endothelial cells and had obvious anti-inflammatory effect on ***,the nanomedicine can inhibit the phenotypic switching of M1 macrophages and promote M2 polarization to produce anti-inflammatory medicators during wound *** addition,in vivo fluorescence imaging verified that THM exhibited enhanced preferential accumulation and extended retention in inflamed ***,THM significantly reduced the production of proinflammatory cytokines in the colon and suppressed the homing of T cells to the gut in dextran sodium sulfate induced experimental *** work elucidates that the inflamed colon-targeted delivery of tofacitinib by nanomedicine is promising for UC treatment and sheds light on addressing the unmet medical need.

关键词： ulcerative colitis mucosal vascular addressin cell-adhesion molecule-1(MAdCAM-1) tofacitinib reactive oxygen species(ROS)-responsive targeted delivery

Human leukocyte antigen and donor-specific antibodies in liver transplantation

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World Journal of Gastroenterology 2025年第2期31卷 157-160页

作者： Qimudesiren Sha-Na Chen li-Ren Qian School of Clinical Medicine Inner Mongolia Minzu UniversityTongliao 028000Inner Mongolia Autonomous RegionChina Department of Hematology International Mongolian Hospital of Inner MongoliaHohhot 010065Inner Mongolia Autonomous RegionChina Senior Department of Hematology The Fifth Medical Center of PLA General HospitalBeijing 100071China The Second School of Clinical Medicine Southern Medical UniversityGuangzhou 510515Guangdong ProvinceChina

In this article,we comment on an article published in a recent issue of the World Journal of *** specifically focus on the roles of human leukocyte antigen(HLA)and donor-specific antibodies(DSAs)in pediatric liver transpl-antation(LT),as well as the relationship between immune rejection after LT and ***,LT remains the standard of care for pediatric patients with end-stage liver disease or severe acute liver ***,acute and chronic re-jection continues to be a significant cause of graft dysfunction and *** mismatch significantly reduces graft survival and increases the risk of acute *** them,D→R one-way mismatch at three loci was significantly related to graft-versus-host disease incidence after *** adverse impact of HLA-DSAs on LT recipients is already ***,the evaluation of HLA and DSA is crucial in pediatric LT.

关键词： liver transplantation Human leukocyte antigen Donor-specific antibodies De novo donor-specific antibody Antibody-mediated rejection

Multi-Stage-Based Siamese Neural Network for Seal Image Recognition

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Computer Modeling in Engineering & Sciences 2025年第1期142卷 405-423页

作者： Jianfeng Lu Xiangye Huang Caijin li Renlin Xin Shanqing Zhang Mahmoud Emam School of Computer Science and Technology Hangzhou Dianzi UniversityHangzhou310018China Shangyu Institute of Science and Engineering Hangzhou Dianzi UniversityShaoxing312300China Faculty of Artificial Intelligence Menoufia UniversityShebin El-Koom32511Egypt

Seal authentication is an important task for verifying the authenticity of stamped seals used in various domains to protect legal documents from tampering and *** seal inspection is commonly audited manually to ensure document ***,manual assessment of seal images is tedious and laborintensive due to human errors,inconsistent placement,and completeness of the *** image recognition systems are inadequate enough to identify seal types accurately,necessitating a neural network-based method for seal image ***,neural network-based classification algorithms,such as Residual Networks(ResNet)andVisualGeometryGroup with 16 layers(VGG16)yield suboptimal recognition rates on stamp ***,the fixed training data categories make handling new categories to be a challenging *** paper proposes amulti-stage seal recognition algorithmbased on Siamese network to overcome these ***,the seal image is pre-processed by applying an image rotation correction module based on Histogram of Oriented Gradients(HOG).Secondly,the similarity between input seal image pairs is measured by utilizing a similarity comparison module based on the Siamese ***,we compare the results with the pre-stored standard seal template images in the database to obtain the seal *** evaluate the performance of the proposed method,we further create a new seal image dataset that contains two subsets with 210,000 valid labeled pairs in *** proposed work has a practical significance in industries where automatic seal authentication is essential as in legal,financial,and governmental sectors,where automatic seal recognition can enhance document security and streamline validation ***,the experimental results show that the proposed multi-stage method for seal image recognition outperforms state-of-the-art methods on the two established datasets.

关键词： Seal recognition seal authentication document tampering siamese network spatial transformer network similarity comparison network

Current status of drug therapy for chronic hepatitis B

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World Journal of Gastroenterology 2025年第2期31卷 1-12页

作者： Chuang Jiang Zhi-Hong Zhang Jia-Xin li Division of liver Surgery Department of General Surgery and Laboratory of Liver Surgeryand State Key Laboratory of Biotherapy and Collaborative Innovation Center of BiotherapyWest China HospitalSichuan UniversityChengdu 610041Sichuan ProvinceChina Department of General Surgery Dafang County People's HospitalBijie 551600Guizhou ProvinceChina

In this editorial,we comment on the article by Meng et *** hepatitis B(CHB)is a significant global health problem,particularly in developing *** B virus(HBV)infection is one of the most important risk factors for cirrhosis and hepatocellular *** and treatment of HBV are key measures to reduce *** present,drug therapy can effectively control virus replication and slow disease progression,but completely eliminating the virus remains a ***-HBV treatment is a long-term process,and there are many kinds of antiviral drugs with different mechanisms of action,it is essential to evaluate the safety and efficacy of these drugs to reduce side effects and improve patients’*** will summarize the current status of CHB drug treatment,hoping to provide a reference for the selection of clinical antiviral drugs.

关键词： Chronic hepatitis B Hepatitis B virus Anti virus Drug treatment Therapy

Development of a nomogram for overall survival in patients with esophageal carcinoma:A prospective cohort study in China

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World Journal of Gastrointestinal Oncology 2025年第1期17卷 158-168页

作者： Shi-Shi Yu Xi Zheng Xiao-Sheng li Qian-Jie Xu Wei Zhang Zhong-li liao Hai-Ke Lei Department of Gastroenterology Chongqing University Cancer HospitalChongqing 400030China Chongqing Cancer Multi-omics Big Data Application Engineering Research Center Chongqing University Cancer HospitalChongqing 400030China Department of Health Statistics School of Public HealthChongqing Medical UniversityChongqing 400016China

BACKGROUND Esophageal carcinoma(EC)presents a significant public health issue in China,with its prognosis impacted by myriad *** creation of a reliable prog-nostic model for the overall survival(OS)of EC patients promises to greatly advance the customization of treatment *** To create a more systematic and practical model that incorporates clinically significant indicators to support decision-making in clinical *** This study utilized data from a prospective longitudinal cohort of 3127 EC patients treated at Chongqing University Cancer Hospital between January 1,2018,and December 12,*** the least absolute shrinkage and selection operator regression alongside multivariate Cox regression analyses helped pinpoint pertinent variables for constructing the *** efficacy was assessed by concordance index(C-index),area under the receiver operating characteristic curve(AUC),calibration curves,and decision curve analysis(DCA).RESULTS Nine variables were determined to be significant predictors of OS in EC patients:Body mass index(BMI),Karnofsky performance status,TNM stage,surgery,radiotherapy,chemotherapy,immunotherapy,platelet-to-lymphocyte ratio,and albumin-to-globulin ratio(ALB/GLB).The model demonstrated a C-index of 0.715(95%CI:0.701-0.729)in the training cohort and 0.711(95%CI:0.689-0.732)in the validation *** the training cohort,AUCs for 1-year,3-year,and 5-year OS predictions were 0.773,0.787,and 0.750,respectively;in the validation cohort,they were 0.772,0.768,and 0.723,respectively,illustrating the model's *** curves and DCA verified the model's predictive accuracy and net *** A novel prognostic model for determining the OS of EC patients was successfully developed and validated to help clinicians in devising individualized treatment schemes for EC patients.

关键词： Esophageal carcinoma High-risk factors Prognosis Overall survival Prediction model

Transforming growth factor-beta 1 enhances discharge activity of cortical neurons

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Neural Regeneration Research 2025年第2期20卷 548-556页

作者： Zhihui Ren Tian li Xueer liu Zelin Zhang Xiaoxuan Chen Weiqiang Chen Kangsheng li Jiangtao Sheng Department of Microbiology and Immunology Guangdong Provincial Key Laboratory of Infectious Diseases and Molecular ImmunopathologyShantou University Medical CollegeShantouGuangdong ProvinceChina Department of Neurosurgery First Affiliated Hospital of Shantou University Medical CollegeShantouGuangdong ProvinceChina

Transforming growth factor-beta 1(TGF-β1)has been extensively studied for its pleiotropic effects on central nervous system *** neuroprotective or neurotoxic effects of TGF-β1 in specific brain areas may depend on the pathological process and cell types ***-gated sodium channels(VGSCs)are essential ion channels for the generation of action potentials in neurons,and are involved in various neuroexcitation-related ***,the effects of TGF-β1 on the functional properties of VGSCs and firing properties in cortical neurons remain *** this study,we investigated the effects of TGF-β1 on VGSC function and firing properties in primary cortical neurons from *** found that TGF-β1 increased VGSC current density in a dose-and time-dependent manner,which was attributable to the upregulation of Nav1.3 *** VGSC current density and Nav1.3 expression were significantly abolished by preincubation with inhibitors of mitogen-activated protein kinase kinase(PD98059),p38 mitogen-activated protein kinase(SB203580),and Jun NH2-terminal kinase 1/2 inhibitor(SP600125).Interestingly,TGF-β1 significantly increased the firing threshold of action potentials but did not change their firing rate in cortical *** findings suggest that TGF-β1 can increase Nav1.3 expression through activation of the ERK1/2-JNK-MAPK pathway,which leads to a decrease in the firing threshold of action potentials in cortical neurons under pathological ***,this contributes to the occurrence and progression of neuroexcitatory-related diseases of the central nervous system.

关键词： central nervous system cortical neurons ERK firing properties JNK Nav1.3 p38 transforming growth factor-beta 1 traumatic brain injury voltage-gated sodium currents