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Endoplasmic reticulum stress and autophagy in cerebral ischemia/reperfusion injury:PERK as a potential target for intervention

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Neural Regeneration Research 2025年第5期20卷 1455-1466页

作者： Ju Zheng Yixin Li Ting Zhang Yanlin Fu Peiyan Long Xiao Gao Zhengwei Wang Zhizhong Guan Xiaolan Qi Wei Hong Yan Xiao Key Laboratory of Endemic and Ethnic diseases Ministry of Education&Key Laboratory of Medical Molecular Biology of Guizhou ProvinceGuizhou Medical UniversityGuiyangGuizhou ProvinceChina Guizhou center for Disease Control and Prevention GuiyangGuizhou ProvinceChina Department of Histology and Embryology Guizhou Medical UniversityGuiyangGuizhou ProvinceChina Collaborative Innovation center for Prevention and Control of Endemic and Ethnic Regional diseases Co-constructed by the Province and Ministry GuiyangGuizhou ProvinceChina

Several studies have shown that activation of unfolded protein response and endoplasmic reticulum(ER)stress plays a crucial role in severe cerebral ischemia/reperfusion *** occurs within hours after cerebral ischemia,but the relationship between ER stress and autophagy remains *** this study,we established experimental models using oxygen-glucose deprivation/reoxygenation in PC12 cells and primary neurons to simulate cerebral ischemia/reperfusion *** found that prolongation of oxygen-glucose deprivation activated the ER stress pathway protein kinase-like endoplasmic reticulum kinase(PERK)/eukaryotic translation initiation factor 2 subunit alpha(e IF2α)-activating transcription factor 4(ATF4)-C/EBP homologous protein(CHOP),increased neuronal apoptosis,and induced ***,inhibition of ER stress using inhibitors or by si RNA knockdown of the PERK gene significantly attenuated excessive autophagy and neuronal apoptosis,indicating an interaction between autophagy and ER stress and suggesting PERK as an essential target for regulating *** autophagy with chloroquine exacerbated ER stress-induced apoptosis,indicating that normal levels of autophagy play a protective role in neuronal injury following cerebral ischemia/reperfusion *** from this study indicate that cerebral ischemia/reperfusion injury can trigger neuronal ER stress and promote autophagy,and suggest that PERK is a possible target for inhibiting excessive autophagy in cerebral ischemia/reperfusion injury.

关键词： apoptosis ATF4 autophagy C/EBP homologous protein cerebral ischemia/reperfusion injury eIF2α endoplasmic reticulum stress PERK

Gastroesophageal reflux disease and morbid obesity: To sleeve or not to sleeve?

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World Journal of Gastroenterology 2017年第13期23卷 2269-2275页

作者： Fabrizio Rebecchi Marco E Allaix Marco G Patti Francisco Schlottmann Mario Morino Department of Surgical Sciences University of Torino center for esophageal diseases and Swallowing University of North Carolina

Laparoscopic sleeve gastrectomy(LSG) has reached wide popularity during the last 15 years, due to the limited morbidity and mortality rates, and the very good weight loss results and effects on comorbid conditions. However, there are concerns regarding the effects of LSG on gastroesophageal reflux disease(GERD). The interpretation of the current evidence is challenged by the fact that the LSG technique is not standardized, and most studies investigate the presence of GERD by assessing symptoms and the use of acid reducing medications only. A few studies objectively investigated gastroesophageal function and the reflux profile by esophageal manometry and 24-h p H monitoring, reporting postoperative normalization of esophageal acid exposure in up to 85% of patients with preoperative GERD, and occurrence of de novo GERD in about 5% of cases. There is increasing evidence showing the key role of the surgical technique on the incidence of postoperative GERD. Main technical issues are a relative narrowing of the mid portion of the gastric sleeve, a redundant upper part of the sleeve(both depending on the angle under which the sleeve is stapled), and the presence of a hiatal hernia. Concomitant hiatal hernia repair is recommended. To date, either medical therapy with proton pump inhibitors or conversion of LSG to laparoscopic Rouxen-Y gastric bypass are the available options for the management of GERD after LSG. Recently, new minimally invasive approaches have been proposed in patients with GERD and hypotensive LES: the LINX? Reflux Management System procedure and the Stretta? procedure. Large studies are needed to assess the safety and long-term efficacy of these new approaches. In conclusion, the recent publication of p H monitoring data and the new insights in the association between sleeve morphology and GERD control have led to a wider acceptance of LSG as bariatric procedure also in obese patients with GERD, as recently stated in the 5^(th) International Consensus Con

关键词： Sleeve gastrectomy Gastroesophageal reflux Morbid obesity Ambulatory p H monitoring esophageal manometry

Small extracellular vesicles derived from human induced pluripotent stem cell-differentiated neural progenitor cells mitigate retinal ganglion cell degeneration in a mouse model of optic nerve injury

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Neural Regeneration Research 2025年第2期20卷 587-597页

作者： Tong Li Hui-Min Xing Hai-Dong Qian Qiao Gao Sheng-Lan Xu Hua Ma Zai-Long Chi State Key Laboratory of Ophthalmology Optometry and Visual ScienceEye HospitalWenzhou Medical UniversityWenzhouZhejiang ProvinceChina National Clinical Research center for Ocular diseases Eye HospitalWenzhou Medical UniversityWenzhouZhejiang ProvinceChina

Several studies have found that transplantation of neural progenitor cells(NPCs)promotes the survival of injured ***,a poor integration rate and high risk of tumorigenicity after cell transplantation limits their clinical *** extracellular vesicles(sEVs)contain bioactive molecules for neuronal protection and *** studies have shown that stem/progenitor cell-derived sEVs can promote neuronal survival and recovery of neurological function in neurodegenerative eye diseases and other eye *** this study,we intravitreally transplanted sEVs derived from human induced pluripotent stem cells(hiPSCs)and hiPSCs-differentiated NPCs(hiPSC-NPC)in a mouse model of optic nerve *** results show that these intravitreally injected sEVs were ingested by retinal cells,especially those localized in the ganglion cell *** with hiPSC-NPC-derived sEVs mitigated optic nerve crush-induced retinal ganglion cell degeneration,and regulated the retinal microenvironment by inhibiting excessive activation of *** analysis further revealed that hiPSC-NPC derived sEVs transported neuroprotective and anti-inflammatory miRNA cargos to target cells,which had protective effects on RGCs after optic nerve *** findings suggest that sEVs derived from hiPSC-NPC are a promising cell-free therapeutic strategy for optic neuropathy.

关键词： exosome miRNA neural progenitor cell neurodegeneration neuroinflammation neuroprotection optic nerve crush optic neuropathy retinal ganglion cell small extracellular vesicles

Storage time affects the level and diagnostic efficacy of plasma biomarkers for neurodegenerative diseases

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Neural Regeneration Research 2025年第8期20卷 2373-2381页

作者： Lifang Zhao Mingkai Zhang Qimeng Li Xuemin Wang Jie Lu Ying Han Yanning Cai Department of Clinical Biobank Xuanwu HospitalCapital Medical UniversityBeijingChina Beijing Geriatric Medical Research center BeijingChina Department of Neurology Xuanwu HospitalCapital Medical UniversityBeijingChina Department of Radiology and Nuclear Medicine Xuanwu HospitalCapital Medical UniversityBeijingChina Beijing Key Laboratory of Magnetic Resonance Imaging and Brain Informatics BeijingChina Key Laboratory of Neurodegenerative diseases Ministry of EducationBeijingChina School of Biomedical Engineering Hainan UniversityHaikouHainan ProvinceChina center of Alzheimer’s Disease Beijing Institute for Brain DisordersBeijingChina National Clinical Research center for Geriatric diseases BeijingChina Institute of Biomedical Engineering Shenzhen Bay LaboratoryGaoke Innovation CenterShenzhenGuangdong ProvinceChina Department of Neurobiology Xuanwu HospitalCapital Medical UniversityBeijingChina

Several promising plasma biomarker proteins,such as amyloid-β(Aβ),tau,neurofilament light chain,and glial fibrillary acidic protein,are widely used for the diagnosis of neurodegenerative ***,little is known about the long-term stability of these biomarker proteins in plasma samples stored at-80°*** aimed to explore how storage time would affect the diagnostic accuracy of these biomarkers using a large *** samples from 229 cognitively unimpaired individuals,encompassing healthy controls and those experiencing subjective cognitive decline,as well as 99 patients with cognitive impairment,comprising those with mild cognitive impairment and dementia,were acquired from the Sino Longitudinal study on Cognitive Decline *** samples were stored at-80°C for up to 6 years before being used in this *** results showed that plasma levels of Aβ42,Aβ40,neurofilament light chain,and glial fibrillary acidic protein were not significantly correlated with sample storage ***,the level of total tau showed a negative correlation with sample storage ***,in individuals without cognitive impairment,plasma levels of total protein and tau phosphorylated protein threonine 181(p-tau181)also showed a negative correlation with sample storage *** was not observed in individuals with cognitive ***,we speculate that the diagnostic accuracy of plasma p-tau181 and the p-tau181 to total tau ratio may be influenced by sample storage ***,caution is advised when using these plasma biomarkers for the identification of neurodegenerative diseases,such as Alzheimer's ***,in cohort studies,it is important to consider the impact of storage time on the overall results.

关键词： Alzheimer’s disease amyloid-β diagnostic ability glial fibrillary acidic protein neurodegeneration neurofilament light chain plasma biomarkers single molecule array storage time tau

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World Journal of Clinical Cases 2025年第6期13卷 24-29页

作者： Wen-Jin Yuan Yi-Juan Zheng Bing-Rong Zhang Yi-Jie Lin You Li Yan-Yan Qiu Xue-Ping Yu Department of Infection Disease Clinical Medical Research Center for Bacterial and Fungal Infectious Diseases of Fujian provinceFujian Medical University Affiliated First Quanzhou HospitalQuanzhou 362000Fujian ProvinceChina

BACKGROUND Hydroxyurea,an antimetabolite,is frequently prescribed for various hemato-logical disorders,and its common side effects include gastrointestinal problems,cutaneous or mucosal lesions and pyrexia/*** SUMMARY This study reports the case of a 67-year-old woman who developed recurrent abdominal pain after 10 years of continuous hydroxyurea therapy for primary *** revealed an ileocecal *** discontinuing hydroxyurea therapy for 6 months,follow-up colonoscopy showed a significant reduction in the *** We consider cecal ulcers as a rare complication of hydroxyurea therapy which typically resolves upon stopping the drug.

关键词： Hydroxyurea Ulcer Abdominal pain Thrombocythemia Colonoscopy Case report

Altered Expression Profile of Micro RNAs in Gastric Stromal Tumor

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Journal of Huazhong University of Science and Technology(Medical Sciences) 2015年第6期35卷 842-850页

作者：肖军汪其贤朱尤庆 Department of Gastroenterology and Hubei Provincial center of Clinical study for Digestive diseases Zhongnan Hospital Wuhan University

Summary： MicroRNAs （miRNAs） play important roles in carcinogenesis, but the global miRNA ex- pression profile in gastric stromal tumor tissues remains unclear. This study was to examine the miRNA expression profile in gastric stromal tumor tissues and explore the function of dysregulated miRNAs by performing gene ontology （GO） and pathway enrichment analysis. Total RNA was extracted and puri- fied from 3 pairs of frozen gastric stromal tumor tissues and the adjacent non-tumor tissues by using mirVanaTM miRNA isolation kit. The miRNA expression was analyzed with Affymetrix microarrays （version 4.0） containing 2578 human mature microRNA probes. The dysregulated microRNAs were validated by quantitative RT-PCR in 30 pairs of gastric stromal tumor tissues. The target gene of the dysregulated microRNAs was predicted by miRanda, TargetScan and PicTar. GO and pathway enrich- ment analysis was conducted to examine the potential function of miR-3178 and miR-193a-5p. The re- suits showed that there were 12 differently expressed microRNAs in gastric stromal tumor tissues, among which 10 miRNAs were down-regulated, and 2 were up-regulated （P〈0.05）. The validation re- sults by RT-PCR were in accordance with those by microRNA microarry. GO analysis found that the target genes of miR-3178 were involved in 5 GO terms and those of miR-193a-5p in 7 GO terms in level 2. Pathway enrichment analysis suggested that miR-3178 and miR-193a-5p were related to 57 and 122 signaling pathways, respectively. It was concluded that gastric stromal tumor displays a unique miRNA signature. This specific expression may become a new diagnostic and prognostic biomarker for gastric stromal ~xnor. miR-3178 and miR-193a-5p function as suppressive microRNAs, and they may also become diagnosis and treatment targets for gastric stromal tumor.

关键词： microRNA gastric stromal tumor signal pathway gene

Difficult polypectomy-giant hypopharyngeal polyp: Case report and literature review

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World Journal of Gastroenterology 2013年第35期19卷 5936-5939页

作者： Giovanni Pallabazzer Stefano Santi Solito Biagio Simone D'Imporzano esophageal Surgery Unit Tuscany Regional Referral Center for the Diagnosis and Treatment of Esophageal Disease Medical University of Pisa

Giant esophageal and hypopharyngeal polyps are benign tumors rarely encountered in clinical *** most cases,they are completely asymptomatic;however,despite the rarity of these tumors,interest in giant esophageal polyps derives from their degree of growth(characterized by slow growth into the esophageal lumen)and their *** fact,if regurgitation occurs,they can ascend into the oral cavity and be aspirated into the airways,with potentially lethal *** removal of these giant polyps is *** adequate preoperative evaluation to identify the correct origin of the stalk is mandatory for a successful endoscopic or surgical treatment.A 60-year-old man was admitted to our hospital for *** patient underwent gastroscopy,contrast computed tomography and endoscopic *** the conclusion of the procedure,during the extraction of the echoendoscope,the patient began retching and regurgitated the polyp,without experiencing respiratory *** patient underwent a left cervicotomy and polyp dissection via a pharyngotomy.

关键词： Esophagus Giant fibrovascular polyp esophageal polyp Fibroepithelial polyps

Longitudinal assessment of peripheral organ metabolism and the gut microbiota in an APP/PS1 transgenic mouse model of Alzheimer’s disease

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Neural Regeneration Research 2025年第10期20卷 2982-2997页

作者： Hongli Li Jianhua Huang Di Zhao Lemei Zhu Zheyu Zhang Min Yi Weijun Peng Department of Integrated Traditional Chinese&Western Medicine The Second Xiangya HospitalCentral South UniversityChangshaHunan ProvinceChina National Clinical Research center for Metabolic diseases ChangshaHunan ProvinceChina Hunan Academy of Chinese Medicine ChangshaHunan ProvinceChina Academician Workstation Changsha Medical UniversityChangshaHunan ProvinceChina

Alzheimer’s disease not only affects the brain,but also induces metabolic dysfunction in peripheral organs and alters the gut *** aim of this study was to investigate systemic changes that occur in Alzheimer’s disease,in particular the association between changes in peripheral organ metabolism,changes in gut microbial composition,and Alzheimer’s disease *** do this,we analyzed peripheral organ metabolism and the gut microbiota in amyloid precursor protein-presenilin 1(APP/PS1)transgenic and control mice at 3,6,9,and 12 months of ***-month-old APP/PS1 mice exhibited cognitive impairment,Alzheimer’s disease-related brain changes,distinctive metabolic disturbances in peripheral organs and fecal samples(as detected by untargeted metabolomics sequencing),and substantial changes in gut microbial composition compared with younger APP/PS1 ***,a strong correlation emerged between the gut microbiota and kidney metabolism in APP/PS1 *** findings suggest that alterations in peripheral organ metabolism and the gut microbiota are closely related to Alzheimer’s disease development,indicating potential new directions for therapeutic strategies.

关键词： Alzheimer’s disease APP/PS1 mice brain-kidney axis gut microbiota heart-brain axis liver-brain axis lung-brain axis microbiota-gut-brain axis peripheral organ metabolism spleen-brain axis

High-dose dexamethasone regulates microglial polarization via the GR/JAK1/STAT3 signaling pathway after traumatic brain injury

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Neural Regeneration Research 2025年第9期20卷 2611-2623页

作者： Mengshi Yang Miao Bai Yuan Zhuang Shenghua Lu Qianqian Ge Hao Li Yu Deng Hongbin Wu Xiaojian Xu Fei Niu Xinlong Dong Bin Zhang Baiyun Liu Beijing Tiantan Hospital Capital Medical UniversityBeijingChina Department of Neurology The First Hospital of Tsinghua UniversityBeijingChina Department of Neurotrauma and Beijing Key Laboratory of Central Nervous System Injury Beijing Neurosurgical InstituteCapital Medical UniversityBeijingChina Department of Critical Care Medicine Beijing Tiantan HospitalCapital Medical UniversityBeijingChina center for Nerve Injury and Repair Beijing Institute of Brain DisordersChina National Clinical Research Center for Neurological DiseasesBeijingChina

Although microglial polarization and neuroinflammation are crucial cellular responses after traumatic brain injury,the fundamental regulatory and functional mechanisms remain insufficiently *** potent anti-inflammato ry agents,the use of glucoco rticoids in traumatic brain injury is still controversial,and their regulatory effects on microglial polarization are not yet *** the present study,we sought to determine whether exacerbation of traumatic brain injury caused by high-dose dexamethasone is related to its regulatory effects on microglial polarization and its mechanisms of *** vitro cultured BV2 cells and primary microglia and a controlled cortical impact mouse model were used to investigate the effects of dexamethasone on microglial ***,dexamethasone,RU486(a glucocorticoid receptor antagonist),and ruxolitinib(a Janus kinase 1 antagonist)were ***-sequencing data obtained from a C57BL/6 mouse model of traumatic brain injury were used to identify potential targets of *** Morris water maze,quantitative reverse transcription-polymerase chain reaction,western blotting,immunofluorescence and confocal microscopy analysis,and TUNEL,Nissl,and Golgi staining were performed to investigate our ***-throughput sequencing results showed that arginase 1,a marker of M2 microglia,was significantly downregulated in the dexamethasone group compared with the traumatic brain injury group at3 days post-traumatic brain *** dexamethasone inhibited M1 and M2 microglia,with a more pronounced inhibitory effect on M2microglia in vitro and in *** receptor plays an indispensable role in microglial polarization after dexamethasone treatment following traumatic brain ***,glucocorticoid receptor activation increased the number of apoptotic cells and neuronal death,and also decreased the density of dendritic spines.A possible downstream receptor signaling mechanism is th

关键词： apoptosis BV2 microglia dexamethasone glucocorticoid receptor glucocorticoids innate immune system microglial polarization neuroinflammation primary microglia traumatic brain injury