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The compound(E)-2-(3,4-dihydroxystyryl)-3-hydroxy-4H-pyran-4-one alleviates neuroinflammation and cognitive impairment in a mouse model of Alzheimer's disease

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Neural Regeneration Research 2025年第11期20卷 3330-3344页

作者： Xueyan Liu Wei Wu Xuejuan Li Chengyan Wang Ke Chai Fanru Yuan Huijuan Zheng Yuxing Yao Chenlu Li Zu-Cheng Ye Daijun Zha department of Medicinal Chemistry School of PharmacyFujian Medical UniversityFuzhouFujian ProvinceChina Fujian Provincial Key Laboratory of Brain Aging and Neurodegenerative diseases School of Basic Medical SciencesFujian Medical UniversityFuzhouFujian ProvinceChina institute of Laboratory Animal Center Fujian Medical UniversityFuzhouFujian ProvinceChina department of Neurosurgery Neurosurgery Research InstituteThe First Affiliated HospitalFujian Medical UniversityFuzhouFujian ProvinceChina department of hyperbaric oxygen National Regional Medical CenterBinhai Campus of the First Affiliated HospitalFujian Medical UniversityFuzhouFujian ProvinceChina

Previous studies have shown that the compound(E)-2-(3,4-dihydroxystyryl)-3-hydroxy-4H-pyran-4-one(D30),a pyromeconic acid derivative,possesses antioxidant and anti-inflammatory properties,inhibits amyloid-β aggregation,and alleviates scopolamine-induced cognitive impairment,similar to the phase Ⅲ clinical drug *** this study,we established a mouse model of Alzheimer's disease via intracerebroventricular injection of fibrillar amyloid-β to investigate the effect of D30 on fibrillar amyloid-β-induced *** results showed that D30 alleviated fibrillar amyloid-β-induced cognitive impairment,promoted fibrillar amyloid-β clearance from the hippocampus and cortex,suppressed oxidative stress,and inhibited activation of microglia and astrocytes.D30 also reversed the fibrillar amyloid-β-induced loss of dendritic spines and synaptic protein ***,we demonstrated that exogenous fibrillar amyloid-βintroduced by intracerebroventricular injection greatly increased galectin-3 expression levels in the brain,and this increase was blocked by *** the role of D30 in clearing amyloid-β,inhibiting neuroinflammation,protecting synapses,and improving cognition,this study highlights the potential of galectin-3 as a promising treatment target for patients with Alzheimer's disease.

关键词： Alzheimer's disease amyloid-β astrocyte cognitive impairment D30 dendritic spines galectin-3 microglia neuroinflammation neuron

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FUBP3 mediates the amyloid-β-induced neuronal NLRP3 expression

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Neural Regeneration Research 2025年第7期20卷 2068-2083页

作者： Jing Yao Yuan Li Xi Liu Wenping Liang Yu Li Liyong Wu Zhe Wang Weihong Song The National Clinical Research Center for geriatric disease Xuanwu HospitalCapital Medical UniversityBeijingChina department of Neurology The First Affiliated Hospital of Zhengzhou UniversityZhengzhouHenan ProvinceChina department of Neurosurgery Xuanwu HospitalCapital Medical UniversityBeijingChina department of Pediatrics The Second Affiliated Hospital and Yuying Children’s HospitalKey Laboratory of Alzheimer’s Disease of Zhejiang ProvinceInstitute of AgingWenzhou Medical UniversityWenzhouZhejiang ProvinceChina Oujiang Laboratory(Zhejiang Laboratory for Regenerative Medicine Visionand Brain Health)WenzhouZhejiang ProvinceChina

Alzheimer's disease is characterized by deposition of amyloid-β,which forms extracellular neuritic plaques,and accumulation of hyperphosphorylated tau,which aggregates to form intraneuronal neurofibrillary tangles,in the *** NLRP3 inflammasome may play a role in the transition from amyloid-βdeposition to tau phosphorylation and *** NLRP3 is primarily found in brain microglia,and tau is predominantly located in neurons,it has been suggested that NLRP3 expressed by microglia indirectly triggers tau phosphorylation by upregulating the expression of pro-inflammatory ***,we found that neurons also express NLRP3 in vitro and in vivo,and that neuronal NLRP3 regulates tau *** biochemical methods,we mapped the minimal NLRP3 promoter and identified FUBP3 as a transcription factor regulating NLRP3 expression in *** primary neurons and the neuroblastoma cell line Neuro2A,FUBP3 is required for endogenous NLRP3 expression and tau phosphorylation only when amyloid-βis *** the brains of aged wild-type mice and a mouse model of Alzheimer's disease,FUBP3 expression was markedly increased in cortical *** analysis suggested that FUBP3 plays a role in neuron-mediated immune *** also found that FUBP3 trimmed the 5′end of DNA fragments that it bound,implying that FUBP3 functions in stress-induced *** findings suggest that neuronal NLRP3 may be more directly involved in the amyloid-β-to–phospho-tau transition than microglial NLRP3,and that amyloid-βfundamentally alters the regulatory mechanism of NLRP3 expression in *** that FUBP3 was only expressed at low levels in young wild-type mice and was strongly upregulated in the brains of aged mice and Alzheimer's disease mice,FUBP3 could be a safe therapeutic target for preventing Alzheimer's disease progression.

关键词： 5′end trimming Alzheimer's disease amyloid-beta amyloid-β-dependent transcription FUBP3 inflammasome inflammation neuron NLRP3 tau transcription factor

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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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Reversible Posterior Leukoencephalopathy Syndrome in Children with Nephrotic Syndrome:a Case Report

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Chinese Medical Sciences Journal 2014年第1期29卷 55-57页

作者： Sheng-da Liu Qing-min Shen Chun-feng Lv department of hyperbaric oxygen Beijing Aerospace General Hospital

REVERSIBLE posterior leukoencephalopathy syn- drome （RPLS） is a rare neurological syndrome charac- terized by headache, altered mental status, seizures, and visual disturbance,associated with reversible white matter cnanges,- n been commonly reported in patients with severe hypertension and pre-eclampsia. Here we report a case with nephrotic syndrome complicated by RPLS.

关键词： reversible posterior leukoencephalopathy syndrome nephrotic syndrome magnetic resonance imaging

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Mechanism of delayed encephalopathy after acute carbon monoxide poisoning

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Neural Regeneration Research 2020年第12期15卷 2286-2295页

作者： Yan-Qing Huang Zheng-Rong Peng Fang-Ling Huang A-Li Yang department of hyperbaric oxygen Xiangya HospitalCentral South UniversityChangshaHunan ProvinceChina

Many hypotheses exist regarding the mechanism underlying delayed encephalopathy after acute carbon monoxide poisoning(DEACMP),including the inflammation and immune-mediated damage hypothesis and the cellular apoptosis and direct neuronal toxicity hypothesis;however,no existing hypothesis provides a satisfactory explanation for the complex clinical processes observed in ***-rich repeat and immunoglobulin-like domain-containing protein-1(LINGO-1)activates the Ras homolog gene family member A(Rho A)/Rho-associated coiled-coil containing protein kinase 2(ROCK2)signaling pathway,which negatively regulates oligodendrocyte myelination,axonal growth,and neuronal survival,causing myelin damage and participating in the pathophysiological processes associated with many central nervous system ***,whether LINGO-1 is involved in DEACMP remains unclear.A DEACMP model was established in rats by allowing them to inhale 1000 ppm carbon monoxide gas for 40 minutes,followed by 3000 ppm carbon monoxide gas for an additional 20 *** results showed that compared with control rats,DEACMP rats showed significantly increased water maze latency and increased protein and m RNA expression levels of LINGO-1,Rho A,and ROCK2 in the *** with normal rats,significant increases in injured neurons in the hippocampus and myelin sheath damage in the lateral geniculate body were observed in DEACMP *** days 1 to 21 after DEACMP,the intraperitoneal injection of retinoic acid(10 mg/kg),which can inhibit LINGO-1 expression,was able to improve the above changes observed in the DEACMP ***,the overexpression of LINGO-1 appeared to increase following carbon monoxide poisoning,activating the Rho A/ROCK2 signaling pathway,which may be an important pathophysiological mechanism underlying *** study was reviewed and approved by the Medical Ethics Committee of Xiangya Hospital of Central South Hospital(approval No.201612684)on December 26,2016.

关键词： brain injury cell death central nervous system factor injury model pathways rat

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hyperbaric oxygen Treatment Improves Hearing Level via Attenuating TLR4/NF-κB Mediated Inflammation in Sudden Sensorineural Hearing Loss Patients

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Biomedical and Environmental Sciences 2020年第5期33卷 331-337页

作者： LIU Xue Hua LIANG Fang JIA Xing Yuan ZHAO Lin ZHOU Yan YANG Jing department of hyperbaric oxygen Medicine Beijing Chaoyang HospitalCapital Medical UniversityBeijing 100020China institute of Basic Medicine Sciences Beijing Chaoyang HospitalCapital Medical UniversityBeijing 100020China department of hyperbaric oxygen Medicine Beijing Pinggu HospitalBeijing 101200China

Objective hyperbaric oxygen treatment(HBOT)has demonstrated efficacy in improving hearing levels of patients with idiopathic sudden sensorineural hearing loss(ISSHL);however,the underlying mechanisms are not well *** alleviates the inflammatory response,which is mediated by Toll-like receptor(TLR)4 and nuclear factor(NF)-κ*** this study we investigated whether HBOT attenuates inflammation in ISHHL patients via alteration of TLR4 and NF-κB *** ISHHL patients(n=120)and healthy control subjects(n=20)were enrolled in this *** were randomly divided into medicine group treated with medicine only(n=60)and HBO group receiving both HBOT and medicine(n=60).Audiometric testing was performed pre-and ***4,NF-кB,and TNF-αexpression in peripheral blood of ISSHL patients and healthy control subjects was assessed by ELISA before and after *** TLR4,NF-κB,and TNF-αlevels were upregulated in ISSHL patients relative to healthy control subjects;the levels were decreased following treatment and were lower in the HBO group than that in the medicine group post-treatment(P<0.05 and P<0.01).Conclusion HBOT alleviates hearing loss in ISSHL patients by suppressing the inflammatory response induced by TLR4 and NF-κB signaling.

关键词： hyperbaric oxygen treatment Sudden sensorineural hearing loss Toll-like receptor 4 Nuclear factor-kB

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Acute flaccid paralysis and neurogenic respiratory failure associated with enterovirus D68 infection in children: Report of two cases

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World Journal of Clinical Cases 2021年第14期9卷 3327-3333页

作者： Yv Zhang Sheng-Yuan Wang Da-Zhi Guo Shu-Yi Pan Yan Lv department of hyperbaric oxygen The Sixth Medical Center of PLA General HospitalBeijing 100048China

BACKGROUND Acute flaccid paralysis(AFP)and neurogenic respiratory failure rarely occur in *** the end of 2018,some children with such symptoms were admitted to our *** this study,we aimed to assess two children with AFP and neurogenic respiratory failure associated with enterovirus D68(EV-D68).CASE SUMMARY Two children admitted to our hospital presented with symptoms and imaging results different from those of acute disseminated encephalomyelitis and hand,foot,and mouth *** main symptoms were AFP and neurogenic respiratory *** resonance imaging showed severe inflammatory injury mainly to the anterior horn cells of the spinal *** and cerebrospinal fluid samples were collected to assess for pathogens,including bacteria,tuberculosis,cryptococcus,herpes virus,and coxsackie virus,and the results were *** the beginning,the two cases were not assessed for EV-D68 in the nasopharyngeal,blood,and cerebrospinal fluid *** 2 mo later,EVD68 was detected in the stool sample of one of the *** symptom of AFP was caused by injury to the anterior horn cells at levels C5-L5 of the spinal cord,while neurogenic respiratory failure was at levels *** We should pay attention to the detection and diagnosis of EV-D68 and make efforts to develop antivirus drugs and vaccines.

关键词： Infection Enterovirus D68 Flaccid Paralysis Neurogenic Respiratory failure Case report

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Single-cell transcriptomic profiling reveals ZEB1-mediated regulation in microglial subtypes and the impact of exercise on neuroinflammatory responses

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Traditional Medicine Research 2025年第2期10卷 55-64页

作者： Jin-Fang Wu Yi-Sheng Chen Yu-Chun Xie department of Rehabilitation Medicine Jiangsu Province Geriatric HospitalNanjing 210024China Fujian Key Laboratory of Toxicant and Drug Toxicology Medical CollegeNingde Normal UniversityNingde 352100China Central Laboratory Jiangsu Province Geriatric HospitalNanjing 210024China

Background:This study aims to identify distinct cellular subtypes within brain tissue using single-cell transcriptomic analysis,focusing on specific biomarkers that differentiate cell types and the effects of traditional and exercise ***:Four samples were analyzed:older control(OC),older exercise(OE),younger control(YC),and younger exercise(YE).Single-cell RNA sequencing was used to distinguish cellular subtypes through their biomarker *** visualization included violin and t-SNE plots to illustrate biomarker expression across cell clusters such as oligodendrocytes,microglia,and ***,BV2 cells were exposed to amyloid-beta fragments to simulate Alzheimer’s disease,assessing the impact of exercise-induced cellular ***:Distinct cellular subtypes were identified:oligodendrocytes(MBP,St18),microglia(Dock8),and astrocytes(Aqp4,Gpc5).Sample OE was predominantly oligodendrocytes,while YE had more astrocytes,inhibitory neurons,and Canal-Retzius *** showed a significant presence of Olfm3+ganglion ***1 gene knockout revealed changes in SMAD family gene expression,which regulate *** stress levels were also ***:This profiling enhances our understanding of brain cellular functions and interactions,potentially informing targeted therapies in neurological *** may influence brain cell immune responses and cell death pathways by regulating specific gene expressions,offering new insights for treating neuroinflammation and degeneration.

关键词： single-cell transcriptomics brain tissue cellular subtypes biomarker expression neuronal diversity

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Effects of Loading-Dose Statins Combined with PCSK9 Inhibitor Pre-Treatment before Primary Percutaneous Coronary Intervention on the Short-Term Prognosis in Patients with ST-Segment Elevation Myocardial Infarction

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cardiovascular Innovations and Applications 2022年第3期7卷 8-15页

作者： Zhe Wang Qingbo Bao Xiaojian Song Hengjie Song Shoudong Wei Junwei Lv Fei Wang Jian An department of Cardiology Shanxi Cardiovascular Disease HospitalTaiyuanChina Emergency department Shanxi Cardiovascular Disease HospitalTaiyuanChina Cardiac Catheterization Laboratory Shanxi Cardiovascular Disease HospitalTaiyuanChina department of geriatric Medicine Shanxi Cardiovascular Disease HospitalTaiyuanChina

Objective:This study was aimed at investigating the effects of preoperative treatment with a loading dose of statins combined with a PCSK9 inhibitor on coronary blood perfusion and short-term cardiovascular adverse events in patients with ST-segment elevation myocardial infarction(STEMI).Method:Sixty-five patients with STEMI who had visited the Shanxi cardiovascular disease Hospital between May 2018 and May 2021 were enrolled in the *** enrolled patients had no history of oral statins or antiplatelet *** patients were divided into a combined treatment group(loading dose of statins combined with PCSK9 inhibitors,35 patients)and a routine treatment group(loading dose of statins only,30 patients).The primary endpoints were thrombolysis in myocardial infarction(TIMI)blood flow grading,corrected TIMI frame count(CTFC),and TIMI myocardial perfusion grading(TMPG),immediately after and 30 days after the *** secondary endpoint was a composite endpoint of cardiovascular death,nonfatal myocardial infarction,and target vessel revascularization 30 days after the ***:The combined treatment group had significantly lower CTFC(14.09±8.42 vs 26±12.42,P=0.04)and better TMPG(2.74±0.61 vs 2.5±0.73,P=0.04)than the routine treatment group immediately after the ***,the combined treatment group had a significantly lower CTFC(16.29±7.39 vs 26.23±11.53,P=0.04)and significantly better TMPG(2.94±0.24 vs 2.76±0.43,P=0.01)than the routine treatment group 1 month after the ***:Preoperative treatment with a loading dose of high-intensity statins combined with PCSK9 inhibitors increased coronary blood flow and myocardial perfusion after emergency thrombus aspiration in patients with ***,the treatment did not significantly decrease the incidence of cardiovascular death,nonfatal myocardial infarction,or target vessel revascularization.

关键词： PCSK9 inhibitor ST-segment elevation myocardial infarction thrombus aspiration

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Sex modification of the association of the radial augmentation index and incident hypertension in a Chinese community-based population

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Journal of geriatric Cardiology 2021年第1期18卷 39-46页

作者： Qiao QIN Fang-Fang FAN Meng-Yuan LIU Bo LIU Jia JIA Long ZHANG Yu-Xi LI Yi-Meng JIANG Peng-Fei SUN Dan-Mei HE Jian-Ping LI Ming CHEN Bo ZHENG Yan ZHANG department of Cardiology Institute of Cardiovascular DiseasePeking University First HospitalBeijingChina

BACKGROUND Arterial stiffness,as assessed by aortic ultrasound and pulse wave velocity,is associated with incident ***,there is still no consensus on whether the augmentation index(AI)affects new onset of *** study investigated the relationship of radial AI(r AI)and incident hypertension in a Chinese community-based population without hypertension at *** A total of 1,615 Chinese non-hypertensive participants from an atherosclerosis cohort in Beijing,China were included in our *** r AI normalized to heart rate of 75 beats/min(r AIp75)was obtained using HEM-9000 ***-onset hypertension was defined as blood pressure≥140/90 mm Hg or self-reported hypertension or taking anti-hypertensive medications at the follow up *** regression models were used to evaluate the impact of r AIp75 on the risk of new-onset *** After a mean 2.35-year follow-up,213(13.19%)participants developed incident *** significant relation between r AIp75 and incident hypertension was observed in the whole population after adjustment for possible confounders(adjusted odds ratio(OR)and 95%confidence interval(CI):1.09[0.95-1.27];P=0.2260).However,r AIp75 was significantly associated with incident hypertension in women,but not in men(adjusted OR and 95%CI:1.29[1.06-1.56],P=0.0113 for women;0.91[0.72-1.15],P=0.4244 for men;P for interaction=0.0133).CONCLUSIONS Sex modified the effect of the r AI on incident hypertension in a Chinese,community-based,non-hypertensive *** of the r AI could be considered in women with a high risk of hypertension for the purpose of primary intervention.

关键词： Sex modification of the association of the radial augmentation index and incident hypertension in a Chinese community-based population

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