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Chondroitinase ABC combined with Schwann cell transplantation enhances restoration of neural connection and functional recovery following acute and chronic spinal cord injury

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Neural Regeneration Research 2025年第5期20卷 1467-1482页

作者： Wenrui Qu Xiangbing Wu Wei Wu Ying Wang Yan Sun Lingxiao Deng Melissa Walker Chen Chen Heqiao Dai Qi Han Ying Ding Yongzhi Xia George Smith Rui Li Nai-Kui Liu Xiao-Ming Xu Spinal Cord and Brain Injury Research Group Stark Neurosciences Research InstituteDepartment of Neurological SurgeryIndiana University School of MedicineIndianapolisINUSA department of Hand Surgery the Second Hospital of Jilin UniversityChangchunJilin ProvinceChina Shriners Hospitals pediatric Research Center Temple University School of MedicinePhiladelphiaPAUSA department of Anatomy&Cell Biology Indiana University School of MedicineIndianapolisINUSA

Schwann cell transplantation is considered one of the most promising cell-based therapy to repair injured spinal cord due to its unique growth-promoting and myelin-forming properties.A the Food and Drug Administration-approved Phase I clinical trial has been conducted to evaluate the safety of transplanted human autologous Schwann cells to treat patients with spinal cord injury.A major challenge for Schwann cell transplantation is that grafted Schwann cells are confined within the lesion cavity,and they do not migrate into the host environment due to the inhibitory barrier formed by injury-induced glial scar,thus limiting axonal reentry into the host spinal *** we introduce a combinatorial strategy by suppressing the inhibitory extracellular environment with injection of lentivirus-mediated transfection of chondroitinase ABC gene at the rostral and caudal borders of the lesion site and simultaneously leveraging the repair capacity of transplanted Schwann cells in adult rats following a mid-thoracic contusive spinal cord *** report that when the glial scar was degraded by chondroitinase ABC at the rostral and caudal lesion borders,Schwann cells migrated for considerable distances in both rostral and caudal *** Schwann cell migration led to enhanced axonal regrowth,including the serotonergic and dopaminergic axons originating from supraspinal regions,and promoted recovery of locomotor and urinary bladder ***,the Schwann cell survival and axonal regrowth persisted up to 6 months after the injury,even when treatment was delayed for 3 months to mimic chronic spinal cord *** findings collectively show promising evidence for a combinatorial strategy with chondroitinase ABC and Schwann cells in promoting remodeling and recovery of function following spinal cord injury.

关键词： axonal regrowth bladder function chondroitinase ABC functional recovery glial scar lentivirus migration Schwann cell spinal cord injury transplantation

Inflammasome links traumatic brain injury, chronic traumatic encephalopathy, and Alzheimer's disease

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Neural Regeneration Research 2025年第6期20卷 1644-1664页

作者： Gabriela Seplovich Yazan Bouchi Juan Pablo de Rivero Vaccari Jennifer C.Munoz Pareja Andrew Reisner Laura Blackwell Yehia Mechref Kevin K.Wang J.Adrian Tyndall Binu Tharakan Firas Kobeissy department of Surgery Morehouse School of MedicineAtlantaGAUSA department of Neurobiology Center for NeurotraumaMultiomics&Biomarkers(CNMB)Neuroscience InstituteMorehouse School of MedicineAtlantaGAUSA department of Neurological Surgery and the Miami Project to Cure Paralysis University of Miami Miller School of MedicineMiamiFLUSA Division of pediatric Critical Care Department of PediatricsUniversity of Miami Miller School of MedicineMiamiFLUSA department of pediatrics Emory UniversityAtlantaGAUSA department of Neurosurgery Children’s Healthcare of AtlantaAtlantaGAUSA department of Chemistry and Biochemistry Texas Tech UniversityLubbockTXUSA Morehouse School of medicine AtlantaGAUSA

Traumatic brain injury, chronic traumatic encephalopathy, and Alzheimer's disease are three distinct neurological disorders that share common pathophysiological mechanisms involving neuroinflammation. One sequela of neuroinflammation includes the pathologic hyperphosphorylation of tau protein, an endogenous microtubule-associated protein that protects the integrity of neuronal cytoskeletons. Tau hyperphosphorylation results in protein misfolding and subsequent accumulation of tau tangles forming neurotoxic aggregates. These misfolded proteins are characteristic of traumatic brain injury, chronic traumatic encephalopathy, and Alzheimer's disease and can lead to downstream neuroinflammatory processes, including assembly and activation of the inflammasome complex. Inflammasomes refer to a family of multimeric protein units that, upon activation, release a cascade of signaling molecules resulting in caspase-induced cell death and inflammation mediated by the release of interleukin-1β cytokine. One specific inflammasome, the NOD-like receptor protein 3, has been proposed to be a key regulator of tau phosphorylation where it has been shown that prolonged NOD-like receptor protein 3 activation acts as a causal factor in pathological tau accumulation and spreading. This review begins by describing the epidemiology and pathophysiology of traumatic brain injury, chronic traumatic encephalopathy, and Alzheimer's disease. Next, we highlight neuroinflammation as an overriding theme and discuss the role of the NOD-like receptor protein 3 inflammasome in the formation of tau deposits and how such tauopathic entities spread throughout the brain. We then propose a novel framework linking traumatic brain injury, chronic traumatic encephalopathy, and Alzheimer's disease as inflammasomedependent pathologies that exist along a temporal continuum. Finally, we discuss potential therapeutic targets that may intercept this pathway and ultimately minimize long-term neurological decline.

关键词： Alzheimer's disease caspase-1 chronic traumatic encephalopathy inflammasomes neurodegeneration neuroinflammation NLRP1 NLRP3 pyroptosis tauopathy traumatic brain injury

Real-world evidence on the efficacy and safety of vonoprazanamoxicillin dual therapy for Helicobacter pylori treatment in elderly patients

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World Journal of Gastroenterology 2025年第1期31卷 68-78页

作者： Wen Gao Jing-Wen Li Hui Ye Xue-Zhi Zhang Jian-Xiang Liu Hong Cheng department of Gastroenterology Peking University First HospitalBeijing 100034China School of medicine Tsinghua MedicineTsinghua UniversityBeijing 100034China department of Traditional Chinese medicine and Integrative medicine Peking University First HospitalBeijing 100034China

BACKGROUND A dual therapy regimen containing amoxicillin is a common treatment option for the eradication of Helicobacter pylori(***).While substantial research supports the efficacy and safety of vonoprazan and amoxicillin(VA)dual therapy in the general population,there is still a lack of studies specifically focusing on its safety in elderly *** To evaluate efficacy and safety of VA dual therapy as first-line or rescue treatment for *** in elderly *** As a real-world retrospective study,data were collected from elderly patients aged 60 years and above who accepted VA dual therapy(vonoprazan 20 mg twice daily+amoxicillin 1000 mg thrice daily for 14 days)for *** eradication in the department of Gastroenterology at Peking University First Hospital between June 2020 and January *** status was evaluated by^(13)C-urease breath test 6 weeks after *** adverse events(AEs)during treatment were *** In total,401 cases were ***-one cases were excluded due to loss to follow-up,lack of re-examination,or unwillingness to take *** total of 380 included cases comprised 250 who received VA dual therapy as first-line treatment and 130 who received VA dual therapy as rescue *** was successfully eradicated in 239 cases(95.6%)in the first-line treatment group and 116 cases(89.2%)in the rescue treatment *** overall incidence of AEs was 9.5%for both ***,9.2%of patients experienced an AE in the first-line treatment group and 10.0%in the rescue treatment *** patients discontinued treatment due to AE,with a discontinuation rate of 1.3%.No serious AE *** The VA dual therapy regimen as a first-line treatment and a rescue therapy was effective and safe for elderly patients aged 60 and older.

关键词： Helicobacter pylori Vonoprazan Amoxicillin Dual therapy Elderly

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

Fanlian Huazhuo formula:A promising therapeutic approach for metabolic associated steatotic liver disease

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World Journal of Gastroenterology 2025年第1期31卷 167-171页

作者： Chun-Han Cheng Wen-Rui Hao Tzu-Hurng Cheng department of Medical Education Linkou Chang Gung Memorial HospitalTaoyuan 33305Taiwan Division of Cardiology Department of Internal MedicineShuang Ho HospitalMinistry of Health and WelfareTaipei Medical UniversityNew Taipei 23561Taiwan Division of Cardiology Department of Internal MedicineSchool of MedicineCollege of MedicineTaipei Medical UniversityTaipei 11002Taiwan department of Biochemistry School of MedicineCollege of MedicineChina Medical UniversityTaichung 404328Taiwan

This article reviews the study,“Fanlian huazhuo formula alleviates high-fat-dietinduced nonalcoholic fatty liver disease by modulating autophagy and lipid synthesis signaling pathway”published in the World Journal of *** study explores the therapeutic potential of Fanlian Huazhuo formula(FLHZF)in treating metabolic-associated steatotic liver disease(MASLD),demonstrating that FLHZF reduces lipid accumulation,oxidative stress,and liver injury in MASLD models by modulating key signaling pathways involved in lipid metabolism and *** editorial emphasizes the potential of FLHZF as a treatment for MASLD and calls for further research to verify its clinical efficacy.

关键词： Fanlian Huazhuo formula Metabolic associated steatotic liver disease Autophagy Lipid metabolism Oxidative stress

Elafibranor:A promising therapeutic approach for liver fibrosis and gut barrier dysfunction in alcohol-associated liver disease

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World Journal of Gastroenterology 2025年第3期31卷 123-126页

作者： Chun-Han Cheng Wen-Rui Hao Tzu-Hurng Cheng department of Medical Education Linkou Chang Gung Memorial HospitalTaoyuan 33305Taiwan Division of Cardiology Department of Internal MedicineShuang Ho HospitalMinistry of Health and WelfareTaipei Medical UniversityNew Taipei City 23561Taiwan Division of Cardiology Department of Internal MedicineSchool of MedicineCollege of MedicineTaipei Medical UniversityTaipei 11002Taiwan department of Biochemistry School of MedicineCollege of MedicineChina Medical UniversityTaichung 404328Taiwan

This article discusses the recent study written by Koizumi et ***-associated liver disease(ALD)is a major cause of liver-related morbidity and mortality,which is driven by complex mechanisms,including lipid accumulation,apoptosis,and inflammatory responses exacerbated by gut barrier *** study explored the therapeutic potential of elafibranor,a dual peroxisome proliferatoractivated receptor alpha/delta *** clinical trials,elafibranor has shown promise for the treatment of other liver conditions;however,its effects on ALD remain *** authors’findings indicate that elafibranor significantly reduced liver fibrosis and enhanced gut barrier integrity in patients with *** positive effects of elafibranor are mediated through multiple *** promotes lipid metabolism,reduces oxidative stress,and inhibits inflammatory responses by restoring gut barrier ***,it improves hepatocyte function by enhancing autophagic and antioxidant capacity,and it mitigates inflammation by suppressing the lipopolysaccharide/toll-like receptor 4/nuclear factor kappa B signaling *** findings indicate that elafibranor has promising clinical *** addition,the study highlights elafibranor’s potential as a therapeutic agent for liver diseases,particularly *** article underscores the importance of understanding the mechanistic pathways underlying ALD and suggests directions for future research aimed at elucidating the benefits and limitations of elafibranor.

关键词： Elafibranor Liver fibrosis Gut barrier function Alcohol-associated liver disease Peroxisome proliferatoractivated receptor agonists

Advancing treatment strategies:Insights from network meta-analysis of hepatic arterial infusion chemotherapy for advanced hepatocellular carcinoma

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World Journal of Gastrointestinal Oncology 2025年第1期17卷 252-255页

作者： Chun-Han Cheng Wen-Rui Hao Tzu-Hurng Cheng department of Medical Education Linkou Chang Gung Memorial HospitalTaoyuan City 33305TaiwanChina Division of Cardiology Department of Internal MedicineShuang Ho HospitalMinistry of Health and WelfareTaipei Medical UniversityNew Taipei City 23561TaiwanChina Division of Cardiology Department of Internal MedicineSchool of MedicineCollege of MedicineTaipei Medical UniversityTaipei 11002TaiwanChina department of Biochemistry School of MedicineCollege of MedicineChina Medical UniversityTaichung City 404328TaiwanChina

This study examines the pivotal findings of the network meta-analysis of Zhou et al,which evaluated the efficacy of hepatic arterial infusion chemotherapy and combination therapies for advanced hepatocellular carcinoma(HCC).This meta-analysis suggests that therapeutic combinations have greater efficacy than do standard *** article highlights the key insights that have the potential to shift current clinical practice and enhance outcomes for patients with advanced ***,this article discusses further research that can be conducted to optimize these treatments and achieve personalized care for patients with HCC.

关键词： Hepatic arterial infusion chemotherapy Advanced hepatocellular carcinoma Combination therapy Network meta-analysis Treatment efficacy

Unveiling the intricacies:Insight into gastroesophageal reflux disease

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World Journal of Gastroenterology 2025年第1期31卷 24-41页

作者： Nilanka Wickramasinghe Niranga Manjuri Devanarayana department of Physiology Faculty of MedicineUniversity of ColomboColombo 00800Western ProvinceSri Lanka department of Physiology Faculty of MedicineUniversity of KelaniyaRagama 11010Western ProvinceSri Lanka

Gastroesophageal reflux disease(GERD)poses a substantial global health challenge,with prevalence rates exhibiting geographical *** its widespread recognition,the exact prevalence and associated risk factors remain *** article comprehensively analyzed the global burden of GERD,shedding light on its risk factors,underlying pathophysiological mechanisms,current diagnostic modalities,evolving management strategies tailored to diverse patient profiles,and complex determinants contributing to treatment failures.A deeper comprehension of GERD is achieved by dissecting these intricate facets,paving the way for enhanced clinical management and improved patient outcomes.

关键词： Gastroesophageal reflux disease Risk factors Pathophysiological mechanisms Diagnosis Management

The complex effects of miR-146a in the pathogenesis of Alzheimer's disease

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Neural Regeneration Research 2025年第5期20卷 1309-1323页

作者： Yunfan Long Jiajia Liu Yu Wang Haidong Guo Guohong Cui department of Neurology Shanghai No.9 People’s HospitalShanghai Jiaotong University School of MedicineShanghaiChina Academy of Integrative medicine Shanghai University of Traditional Chinese MedicineShanghaiChina School of Integrative medicine Shanghai University of Traditional Chinese MedicineShanghaiChina department of Neurology Shuguang Hospital Affiliated to Shanghai University of Traditional Chinese MedicineShanghaiChina

Alzheimer's disease is a neurodegenerative disorder characterized by cognitive dysfunction and behavioral *** plaques formed through the extracellular deposition of amyloid-βproteins,as well as neurofibrillary tangles formed by the intracellular deposition of hyperphosphorylated tau proteins,comprise two typical pathological features of Alzheimer's *** symptomatic treatment,there are no effective therapies for delaying Alzheimer's disease ***(miR)are small,non-coding RNAs that negatively regulate gene expression at the transcriptional and translational levels and play important roles in multiple physiological and pathological ***,miR-146a,a NF-κB-regulated gene,has been extensively implicated in the development of Alzheimer's disease through several *** has demonstrated substantial dysregulation of miR-146a both during the initial phases and throughout the progression of this *** R-146a is believed to reduce amyloid-βdeposition and tau protein hyperphosphorylation through the TLR/IRAK1/TRAF6 pathway;however,there is also evidence supporting that it can promote these processes through many other pathways,thus exacerbating the pathological manifestations of Alzheimer's *** has been widely reported that miR-146a mediates synaptic dysfunction,mitochondrial dysfunction,and neuronal death by targeting m RNAs encoding synapticrelated proteins,mitochondrial-related proteins,and membrane proteins,as well as other *** the impact on glial cells,miR-146a also exhibits differential *** one hand,it causes widespread and sustained inflammation through certain pathways,while on the other hand,it can reverse the polarization of astrocytes and microglia,alleviate neuroinflammation,and promote oligodendrocyte progenitor cell differentiation,thus maintaining the normal function of the myelin sheath and exerting a protective effect on *** this review,we provide a

关键词： Alzheimer's disease amyloid-β glial cells microRNAs miR-146a neuroinflammatory