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Comparative proteomic analysis of plasma exosomes reveals the functional contribution of N-acetyl-alpha-glucosaminidase to Parkinson’s disease

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Neural Regeneration Research 2025年第10期20卷 2998-3012页

作者： Yuan Zhao Yidan Zhang Xin Liu Jian Zhang Ya Gao Shuyue Li Cui Chang Xiang Liu Guofeng Yang Department of Geriatrics Second Hospital of Hebei Medical UniversityShijiazhuangHebei ProvinceChina Department of Neurosurgery The Second Hospital of Hebei Medical UniversityShijiazhuangHebei ProvinceChina

Parkinson’s disease is the second most common progressive neurodegenerative disorder,and few reliable biomarkers are available to track disease *** proteins,DNA,mRNA,and lipids carried by exosomes reflect intracellular changes,and thus can serve as biomarkers for a variety of *** this study,we investigated alterations in the protein content of plasma exosomes derived from patients with Parkinson’s disease and the potential therapeutic roles of these proteins in Parkinson’s *** a tandem mass tag-based quantitative proteomics approach,we characterized the proteomes of plasma exosomes derived from individual patients,identified exosomal protein signatures specific to patients with Parkinson’s disease,and identified N-acetyl-alpha-glucosaminidase as a differentially expressed protein.N-acetyl-alpha-glucosaminidase expression levels in exosomes from the plasma of patients and healthy controls were validated by enzyme-linked immunosorbent assay and western *** results demonstrated that the exosomal N-acetyl-alpha-glucosaminidase concentration was not only lower in Parkinson’s disease,but also decreased with increasing Hoehn-Yahr stage,suggesting that N-acetyl-alpha-glucosaminidase could be used to rapidly evaluate Parkinson’s disease ***,western blot and immunohistochemistry analysis showed that N-acetyl-alpha-glucosaminidase levels were markedly reduced both in cells treated with 1-methyl-4-phenylpyridinium and cells overexpressingα-synuclein compared with control ***,N-acetyl-alpha-glucosaminidase overexpression significantly increased cell viability and inhibitedα-synuclein expression in 1-methyl-4-phenylpyridinium-treated *** together,our findings demonstrate for the first time that exosomal N-acetyl-alpha-glucosaminidase may serve as a biomarker for Parkinson’s disease diagnosis,and that N-acetyl-alpha-glucosaminidase may reduceα-synuclein expression and 1-methyl-4-phenylpyridinium-induced n

关键词： biomarker diagnosis exosomes N-acetyl-alpha-glucosaminidase Parkinson’s disease proteomic α-synuclein

NOX4 exacerbates Parkinson's disease pathology by promoting neuronal ferroptosis and neuroinflammation

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Neural Regeneration Research 2025年第7期20卷 2038-2052页

作者： Zhihao Lin Changzhou Ying Xiaoli Si Naijia Xue Yi Liu Ran Zheng Ying Chen Jiali Pu Baorong Zhang Department of Neurology The Second Affiliated HospitalZhejiang University School of MedicineHangzhouZhejiang ProvinceChina

Parkinson's disease is primarily caused by the loss of dopaminergic neurons in the substantia nigra ***,a novel form of regulated cell death characterized by iron accumulation and lipid peroxidation,plays a vital role in the death of dopaminergic ***,the molecular mechanisms underlying ferroptosis in dopaminergic neurons have not yet been completely *** oxidase 4 is related to oxidative stress,however,whether it regulates dopaminergic neuronal ferroptosis remains *** aim of this study was to determine whether NADPH oxidase 4 is involved in dopaminergic neuronal ferroptosis,and if so,by what *** found that the transcriptional regulator activating transcription factor 3 increased NADPH oxidase 4 expression in dopaminergic neurons and astrocytes in an 1-methyl-4-phenyl-1,2,3,6 tetrahydropyridine-induced Parkinson's disease *** oxidase 4 inhibition improved the behavioral impairments observed in the Parkinson's disease model animals and reduced the death of dopaminergic ***,NADPH oxidase 4 inhibition reduced lipid peroxidation and iron accumulation in the substantia nigra of the Parkinson's disease model ***,we found that NADPH oxidase 4 interacted with activated protein kinase Cαto prevent ferroptosis of dopaminergic ***,by lowering the astrocytic lipocalin-2 expression,NADPH oxidase 4 inhibition reduced 1-methyl-4-phenyl-1,2,3,6 tetrahydropyridine-induced *** findings demonstrate that NADPH oxidase 4 promotes ferroptosis of dopaminergic neurons and neuroinflammation,which contribute to dopaminergic neuron death,suggesting that NADPH oxidase 4 is a possible therapeutic target for Parkinson's disease.

关键词： dopaminergic neuron ferroptosis NADPH oxidase 4(NOX4) neuroinflammation Parkinson's disease

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

Gut-brain axis as a bridge in obesity and depression:Mechanistic exploration and therapeutic prospects

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World Journal of Psychiatry 2025年第1期15卷 12-20页

作者： Rui-Ying Fang Xiao-Rui Pan Xin-Xing Zeng Zheng-Zheng Li Bo-Fan Chen Hai-Min Zeng Jie Peng The second Clinical Medical College The Second Affiliated HospitalJiangxi Medical CollegeNanchang UniversityNanchang 330006Jiangxi ProvinceChina

A recent study by Wang et al,published in the World Journal of Psychiatry,provided preventative and therapeutic strategies for the comorbidity of obesity and *** gut-brain axis,which acts as a two-way communication system between the gastrointestinal tract and the central nervous system,plays a pivotal role in the pathogenesis of these *** suggests that metabolic byproducts,such as short-chain fatty acids,lipopolysaccharide and bile acids,which are generated by the gut microbiota,along with neurotransmitters and inflammatory mediators within the gut-brain axis,modulate the host's metabolic processes,neuronal regulation,and immune responses through diverse *** interaction between obesity and depression via the gut-brain axis involves disruptions in the gut microbiota balance,inflammatory immune responses,and alterations in the neuroendocrine *** the gut-brain axis,for example,through a ketogenic diet,the use of probiotics,and the supplementation of antioxidants,offers new remedial approaches for obesity and *** research that explores the mechanisms of the gut-brain axis is needed to provide more evidence for clinical treatment.

关键词： Gut-brain axis Obesity Depression Gut microbiota Mechanism

Expression of sIL-2R before and after Chemotherapy in Patients with breast Cancer

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Chinese Journal of Cancer Research 2008年第2期20卷 150-154页

作者：范原铭孙治君 Department of breast and Pancreas surgery Second Affiliated HospitalChongqing Medical UniversityChongqing 400000

Objective： To investigate the difference of peripheral blood sIL-2R before and after chemotherapy in breast cancer patients, and evaluate the clinical value of the sIL-2R in breast cancer＇s diagnosis and therapy. Methods： The peripheral blood sIL-2R levels of the breast cancer patients with or without chemotherapy were detected by ELISA. The healthy persons were made as the control group. Results： The sIL-2R levels of the breast cancer patients were higher than that of the control group（P（0.05）; the sIL-2R＇s levels in I^II stage breast cancer were lower than that in Ill^IV stage breast cancer （P（0.05）; the sIL-2R levels of the patients before chemotherapy were higher than that of the patients undergone chemotherapy（P（0.05）; The level of the patient with chemotherapy was still higher than that of the control group （P（0.05）; the sIL-2R levels of the patients whose chemotherapies were noneffective were higher than that of the patients received effective chemotherapies （P（0.05）. There was no significant difference between the group with ER（＋） or PR（＋） and the group with ER（-） or PR（-）（P〉0.05）. Conclusion： The breast cancer patients have the high sIL-2R levels. There is a close relationship between the cancer incidence and the patients, immune situation. The level of sIL-2R could be a clinical index which can be used for evaluating the cancer degree, because the higher levels of sIL-2R can indicate that the immune ability of patient is worse. There is a significant difference between the sIL-2R levels of the patients before chemotherapy and that of the patients undergone chemotherapy.

关键词： Soluble interleukin-2 receptor (sIL-2R) breast cancer Chemotherapy

breast-conserving surgery and sentinel lymph node biopsy for breast cancer and their correlation with the expression of polyligand proteoglycan-1

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World Journal of Clinical Cases 2022年第10期10卷 3113-3120页

作者： Fu-Ming Li Dan-Ying Xu Qi Xu Yan Yuan Department of breast surgery The Second Hospital of JiaxingJiaxing 314000Zhejiang ProvinceChina

BACKGROUND breast cancer is a malignant tumor with an unclear etiology and is the most common malignant tumor in *** is the main clinical treatment for breast *** traditional total mastectomy combined with axillary lymph node dissection is effective,it can result in shoulder dysfunction,especially in middle-aged and elderly patients with breast cancer with weak constitution and other underlying ***,the postoperative quality of life is *** To assess breast-conserving surgery and sentinel lymph node biopsy for breast cancer treatment and their correlation with polyligand *** Overall,80 patients with breast cancer treated in our hospital from January 2021 to July 2021 were retrospectively selected and divided into an observation group(n=44)and control group(n=36)according to the treatment *** observation group was treated with breast-conserving surgery and sentinel lymph node biopsy,and the control group was treated with total breast ***,immunohistochemical staining was used to detect the expression of syndecan-1(SDC-1)in the lesions,and its relationship with clinicopathological findings was *** Intraoperative blood loss,operation time,and hospital stay in the observation group were 65.51±9.94 m L,65.59±9.40 min,and 14.80±3.03 d,respectively,which were significantly lower than those in the control group(P0.05).The positive expression rate of SDC-1 in patients with American Joint Committee on Cancer(AJCC)stageⅡwas 14.29%,which was significantly lower than that in patients with AJCC stageⅠ(P<0.05).The positive expression of SDC-1 had no significant relationship with age,course of dise

关键词： breast preservation Sentinel lymph node biopsy breast cancer Clinical effectiveness Polyligand proteoglycan-1

Blood diagnostic and prognostic biomarkers in amyotrophic lateral sclerosis

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Neural Regeneration Research 2025年第9期20卷 2556-2570页

作者： Yongting Lv Hongfu Li Department of Neurology Second Affiliated HospitalZhejiang University School of MedicineHangzhouZhejiang ProvinceChina Department of Medical Genetics and Center for Rare disease Second Affiliated HospitalZhejiang University School of MedicineHangzhouZhejiang ProvinceChina Nanhu Brain-Computer Interface Institute HangzhouZhejiang Province

Amyotrophic lateral sclerosis is a devastating neurodegenerative disease for which the current treatment approaches remain severely *** principal pathological alterations of the disease include the selective degeneration of motor neurons in the brain,brainstem,and spinal cord,as well as abnormal protein deposition in the cytoplasm of neurons and glial *** biological markers under extensive scrutiny are predominantly located in the cerebrospinal fluid,blood,and even *** these biomarke rs,neurofilament proteins and glial fibrillary acidic protein most accurately reflect the pathologic changes in the central nervous system,while creatinine and creatine kinase mainly indicate pathological alterations in the peripheral nerves and *** light chain levels serve as an indicator of neuronal axonal injury that remain stable throughout disease progression and are a promising diagnostic and prognostic biomarker with high specificity and ***,there are challenges in using neurofilament light chain to diffe rentiate amyotrophic lateral sclerosis from other central nervous system diseases with axonal *** fibrillary acidic protein predominantly reflects the degree of neuronal demyelination and is linked to non-motor symptoms of amyotrophic lateral sclerosis such as cognitive impairment,oxygen saturation,and the glomerular filtration *** DNA-binding protein 43,a pathological protein associated with amyotrophic lateral sclerosis,is emerging as a promising biomarker,particularly with advancements in exosome-related *** is currently lacking for the value of creatinine and creatine kinase as diagnostic markers;however,they show potential in predicting disease *** the vigorous progress made in the identification of amyotrophic lateral sclerosis biomarkers in recent years,the quest for definitive diagnostic and prognostic biomarke rs remains a formidable *** review summarizes the lat

关键词： amyotrophic lateral sclerosis biomarker blood biomarkers diagnosis glial fibrillary acidic protein neurofilament light chain prognosis TAR DNA-binding protein 43

Hepatoid adenocarcinoma of the rectal

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Hepatobiliary surgery and Nutrition 2023年第6期12卷 987-990页

作者： Sitong Zhou Ziqi Wang Hao Sun Shuo Han Pengda Sun Department of Gastrointestinal Nutrition and Hernia surgery The Second Hospital of Jilin UniversityChangchunChina Department of breast surgery The Second Hospital of Jilin UniversityChangchunChina

We would here like to present a treatment experience of an interesting case of hepatoid adenocarcinoma(HAC),which is a very rare clinical malignancy of the gastrointestinal tract.A 58-year-old male was admitted to our hospital with intermittent hematochezia for 1 month.A computed tomography(CT)of the abdomen revealed the thickened anterior wall and nodules of the middle rectum,the lumen of which was narrowed.

关键词： admitted adenocarcinoma clinical

secondary pouchitis in a post-operative patient with ulcerative colitis,successfully treated by salvage surgery

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World Journal of Gastroenterology 2005年第43期11卷 6888-6890页

作者： Yuji Toiyama Toshimitsu Araki Shigeyuki Yoshiyama Chikao Miki Masato Kusunoki The second Department of surgery

We report a case of secondary pouchitis, defined as a mucosal inflammatory lesion in the ileal reservoir provoked by pouch-related complication following total colectomy and pouch anal anastomosis, which was successfully treated by salvage surgery. A 20-year-old woman with ulcerative colitis developed acute severe bloody diarrhea following proctocolectomy, ileal pouchanal anastomosis and diverting ileostomy. She was diagnosed as having a secondary pouchitis mainly caused by a peripouch abscess and partly concerned with the abnormal pouch formation. The remnantrectum and ileal pouch were excised and ileal pouch-anal anastomosis and diverting ileostomy were *** postoperative course was uneventful with no sign of pouchitis. Salvage surgery may be indicated to treat secondary pouchitis when caused by surgery-related complications.

关键词： Ulcerative colitis Ileal pouch-anal anastomosis secondary pouchitis Salvage operation