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Prolonged intermittent theta burst stimulation restores the balance between A_(2A)R-and A_(1)R-mediated adenosine signaling in the 6-hydroxidopamine model of Parkinson's disease

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Neural Regeneration Research 2025年第7期20卷 2053-2067页

作者： Milica Zeljkovic Jovanovic Jelena Stanojevic Ivana Stevanovic Milica Ninkovic Tihomir V.Ilic Nadezda Nedeljkovic Milorad Dragic Laboratory for Neurobiology Department of General Physiology and BiophysicsFaculty of BiologyUniversity of BelgradeBelgradeSerbia medical Faculty of military medical academy University of DefenceBelgradeSerbia

An imbalance in adenosine-mediated signaling,particularly the increased A_(2A)R-mediated signaling,plays a role in the pathogenesis of Parkinson's *** therapeutic approaches fail to alter disease progression,demonstrating the need for novel approaches in *** transcranial magnetic stimulation is a non-invasive approach that has been shown to improve motor and non-motor symptoms of Parkinson's ***,the underlying mechanisms of the beneficial effects of repetitive transcranial magnetic stimulation remain *** purpose of this study is to investigate the extent to which the beneficial effects of prolonged intermittent theta burst stimulation in the 6-hydroxydopamine model of experimental parkinsonism are based on modulation of adenosine-mediated *** with unilateral 6-hydroxydopamine lesions underwent intermittent theta burst stimulation for 3 weeks and were tested for motor skills using the Rotarod ***,quantitative reverse transcription polymerase chain reaction,immunohistochemistry,and biochemical analysis of components of adenosine-mediated signaling were performed on the synaptosomal fraction of the lesioned caudate *** intermittent theta burst stimulation improved motor symptoms in 6-hydroxydopamine-lesioned animals.A 6-hydroxydopamine lesion resulted in progressive loss of dopaminergic neurons in the caudate *** with intermittent theta burst stimulation began 7 days after the lesion,coinciding with the onset of motor *** treatment with prolonged intermittent theta burst stimulation,complete motor recovery was *** improvement was accompanied by downregulation of the e N/CD73-A_(2A)R pathway and a return to physiological levels of A_(1)R-adenosine deaminase 1 after 3 weeks of intermittent theta burst *** results demonstrated that 6-hydroxydopamine-induced degeneration reduced the expression of A_(1)R and elevated the expression of A_(2A)***

关键词： A_(1)R A_(2A)R adenosine receptors adenosine ecto-5′-nucleotidase intermittent theta burst stimulation non-invasive brain stimulation Parkinson's disease purinergic signalling

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Investigating Müller glia reprogramming in mice: a retrospective of the last decade, and a look to the future

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Neural Regeneration Research 2025年第4期20卷 946-959页

作者： Zhiyuan Yin Jiahui Kang Xuan Cheng Hui Gao Shujia Huo Haiwei Xu Key Lab of Visual Damage and Regeneration&Restoration of Chongqing Southwest Eye HospitalSouthwest HospitalThird Military Medical University(Army Medical University)ChongqingChina

Müller glia,as prominent glial cells within the retina,plays a significant role in maintaining retinal homeostasis in both healthy and diseased *** lower vertebrates like zebrafish,these cells assume responsibility for spontaneous retinal regeneration,wherein endogenous Müller glia undergo proliferation,transform into Müller glia-derived progenitor cells,and subsequently regenerate the entire retina with restored ***,Müller glia in the mouse and human retina exhibit limited neural reprogramming.Müller glia reprogramming is thus a promising strategy for treating neurodegenerative ocular disorders.Müller glia reprogramming in mice has been accomplished with remarkable success,through various *** in molecular,genetic,epigenetic,morphological,and physiological evaluations have made it easier to document and investigate the Müller glia programming process in ***,there remain issues that hinder improving reprogramming efficiency and ***,understanding the reprogramming mechanism is crucial toward exploring factors that will improve Müller glia reprogramming efficiency,and for developing novel Müller glia reprogramming *** review describes recent progress in relatively successful Müller glia reprogramming *** also provides a basis for developing new Müller glia reprogramming strategies in mice,including epigenetic remodeling,metabolic modulation,immune regulation,chemical small-molecules regulation,extracellular matrix remodeling,and cell-cell fusion,to achieve Müller glia reprogramming in mice.

关键词： cell fusion chemical small-molecules epigenetic extracellular matrix immune metabolic mice Müller glia neurodegenerative diseases reprogramming retina regeneration

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Targeting capabilities of engineered extracellular vesicles for the treatment of neurological diseases

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Neural Regeneration Research 2025年第11期20卷 3076-3094页

作者： Xinyu Yang Xiangyu Gao Xiaofan Jiang Kangyi Yue Peng Luo Department of Neurosurgery Xijing HospitalFourth Military Medical UniversityXi’anShaanxi ProvinceChina

Recent advances in research on extracellular vesicles have significantly enhanced their potential as therapeutic agents for neurological *** to their therapeutic properties and ability to cross the blood–brain barrier,extracellular vesicles are recognized as promising drug delivery vehicles for various neurological conditions,including ischemic stroke,traumatic brain injury,neurodegenerative diseases,glioma,and ***,the clinical application of natural extracellular vesicles is hindered by their limited targeting ability and short clearance from the *** address these limitations,multiple engineering strategies have been developed to enhance the targeting capabilities of extracellular vesicles,thereby enabling the delivery of therapeutic contents to specific tissues or ***,this review aims to highlight the latest advancements in natural and targeting-engineered extracellular vesicles,exploring their applications in treating traumatic brain injury,ischemic stroke,Parkinson's disease,Alzheimer's disease,amyotrophic lateral sclerosis,glioma,and ***,we summarized recent clinical trials involving extracellular vesicles and discussed the challenges and future prospects of using targeting-engineered extracellular vesicles for drug delivery in treating neurological *** review offers new insights for developing highly targeted therapies in this field.

关键词： Alzheimer's disease amyotrophic lateral sclerosis engineered extracellular vesicles glioma ischemic stroke neurological diseases Parkinson's disease psychosis targeted drug delivery traumatic brain injury

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Cerebral fat embolism following autologous fat injection in facial reconstruction:A case report

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World Journal of Clinical Cases 2025年第2期13卷 50-58页

作者： Xiu-Ying Chen Fa Shen Chang Cheng Yu-Han Wang Wen-Chao Cheng De-Zhi Yuan Wen Huang Department of Neurology Chongqing Emergency Medical CenterChongqing University Central HospitalChongqing 400000China Department of Neurology Xinqiao HospitalThe Army Medical University(Third Military Medical University)Chongqing 400000China

BACKGROUND Autologous fat injection in facial reconstruction is a common cosmetic *** cerebral fat embolism(CFE)as a complication is rare,it carries serious health *** SUMMARY We present a case of a 29-year-old female patient who developed acute CFE following facial fat filling *** the surgery,the patient experienced symptoms including headache,nausea,vomiting,and difficulty breathing,which was followed by neurological symptoms such as slurred speech and left-sided *** physical examination and auxiliary investigations,including blood tests,head and neck computed tomography angiography,and cranial magnetic resonance diffusion-weighted imaging,were performed upon *** clinical diagnosis was acute cerebral embolism following facial fat filling *** included measures to improve cerebral circulation,dehydration for intracranial pressure reduction,nutritional support,and rehabilitation therapy for left limb *** patient showed a significant improvement in symptoms after 2 weeks of *** recovered left limb muscle strength to grade 5,had clear speech,and experienced complete relief of *** Our case highlights the potential occurrence of severe complications in patients undergoing fat injection in facial *** prevent these complications,plastic surgeons should enhance their professional knowledge and skills.

关键词： Cerebral fat embolism Mechanical thrombectomy Thrombolysis Steroid therapy Symptomatic treatment Case report

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Development of Cell Lines Stably Expressing Staphylococcal Nuclease Fused to Dengue 2 Virus Capsid Protein for CTVI

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Acta Biochimica et Biophysica Sinica 2004年第8期36卷 577-582页

作者： Cheng-Feng QIN and E-De QIN Institute of Microbiology and Epidemiology, academy of military medical Sciences, Beijing 100071, China Institute of Microbiology and Epidemiology Academy of Military Medical Sciences

To explore the potential application of capsid-targeted viral inactivation (CTVI) strategy in prophylactic model against dengue virus (DV) infection, here we fused a Ca2+-dependent nuclease, staphylococcal nuclease (SN), to the capsid protein of dengue 2 virus (D2C) at the carboxyl terminal, and constructed the desired expression plasmid pc/D2C-SN and control plasmids pc/D2C-SN* and pc/D2C. A mammalian cell line BHK-21 was transfected by electroporation with those plasmids and thereafter selected by 5 μg/ml blasticidin. The resistant cell clones were then expanding cultured and screened by RT-PCR and Western Blot assays. The nuclease activity of the expressed fusion protein D2C-SN was analyzed by in vitro DNA digestion assay. It was confirmed cell lines stably expressing D2C-SN and control constructs were obtained. The intracellular expressed fusion protein D2C-SN had ideal nuclease activity and no cytotoxicity on mammalian cells. Those engineered cell lines provided the experimental system for CTVI application in prophylactic model and paved the new road for combating DV infection with CTVI.

关键词： dengue 2 virus capsid protein staphylococcal nuclease CTVI stable expression

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Physiochemical and Biological Properties of Modified Collagen Sponge from Porcine Skin

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Journal of Wuhan University of Technology(Materials Science) 2009年第4期24卷 619-626页

作者：许媛媛武继民 Institute of medical Equipment Academy of Military Medical Sciences

The aim of the present study was to compare one-step method to EDC/NHS crosslinking （EDC/NHS group） and one-step simultaneous method to EDC/NHS crosslinking and heparin immobilization （EDC/NHS- Heparin group） in improving physiochemical and biological properties of native collagen sponge （Control group）. Modified collagen sponge overcome the disadvantages of native collagen sponge. IR spectra suggest the change of the functional groups. DSC data indicate that the stability of caloric transformation in EDC/NHS group is slightly higher than that of EDC/NHS-Heparin group. The crosslinking degree, stability against enzymes, stability in morphologically and biomechanical properties of EDC/NHS-Heparin group are higher than those of EDC/NHS group, whereas, the water-binding capacity in EDC/NHS-Heparin group is lower than that of EDC/NHS group. HUVECs in EDC/NHS-Heparin group scaffold proliferate fast, migrate well and distribute uniformly. One-step simultaneous method gains the better effects in above aspects, heparinized collagen matrices increase in angiogenic potential and suit for defect repairing and tissue engineering.

关键词： collagen sponge heparin one-step method to EDC/NHS crosslinking one-step simultaneous method to EDC/NHS crosslinking and heparin immobilization

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Knowledge-oriented modeling for influencing factors of battle damage in military industrial logistics:An integrated method

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Defence Technology（防务技术） 2020年第3期16卷 571-587页

作者： Xiong Li Xiao-dong Zhao Wei Pu military Exercise and Training Center Army Academy of Armored ForcesBeijing 100072China

Modeling influencing factors of battle damage is one of essential works in implementing military industrial logistics simulation to explore battle damage laws ***,one of key challenges in designing the simulation system could be how to reasonably determine simulation model input and build a bridge to link battle damage model and battle damage laws *** this paper,we propose a novel knowledge-oriented modeling method for influencing factors of battle damage in military industrial logistics,integrating conceptual analysis,conceptual modeling,quantitative modeling and simulation *** conceptualize influencing factors of battle damage by using the principle of hierarchical decomposition,thus classifying the related battle damage knowledge ***,we construct the conceptual model of influencing factors of battle damage by using Entity-Relations hip approach,thus describing their interactions ***,we extract the important influencing factors by using social network analysis,thus evaluating their importance quantitatively and further clarifying the elements of ***,we develop an agent-based military industry logistics simulation system by taking the modeling results on influencing factors of battle damage as simulation model input,and obtain simulation model output,i.e.,new battle damage laws knowledge,thus verifying feasibility and effectiveness of the proposed *** results show that this method can be used to support human decision-making and action.

关键词： Battle damage Industrial logistics Entity-relationship approach Social network analysis Agent-based simulation

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Dynamic monitoring of carcinoembryonic antigen,CA19-9 and inflammation-based indices in patients with advanced colorectal cancer undergoing chemotherapy

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World Journal of Clinical Cases 2022年第3期10卷 899-918页

作者： Nebojsa Manojlovic Goran Savic Bojan Nikolic Nemanja Rancic Clinic for Gastroenterology and Hepatology Military Medical AcademyFaculty of Medicine of the Military Medical AcademyUniversity of DefenceBelgrade 11000Serbia Faculty of Medicine of the military medical academy University of DefenceBelgradeSerbiaMilitary Medical AcademyBelgrade 11000Serbia Institute for Radiology Military Medical AcademyBelgrade 11000Serbia Center for Clinical Pharmacology Institute for RadiologyMilitary Medical AcademyFaculty of Medicine of the Military Medical AcademyUniversity of DefenceBelgrade 11000Serbia

BACKGROUND The roles of carcinoembryonic antigen(CEA)and carbohydrate antigen(CA19-9)in monitoring the patient response to chemotherapy for metastatic colorectal cancer(mCRC)are not clearly defined,and inflammatory indices,including the neutrophil-to-lymphocyte ratio(NLR),lymphocyte-to-monocyte ratio(LMR),platelet-to-lymphocyte ratio(PLR)and systemic immune-inflammation index(SII),have been sparsely investigated for this *** To aim of this study was to evaluate the relationship between the kinetics of CEA,CA19-9,NLR,LMR,PLR and SII in serum and patient response to chemotherapy estimated by computed tomography(CT)in patients with unresectable *** Patients with mCRC treated with a 1st-line and 2nd-line chemotherapy underwent at least 3 whole-body spiral CT scans during response monitoring according to the Response Evaluation Criteria in Solid Tumour 1.1(RECIST 1.1),and simultaneous determination of CEA,CA19-9,neutrophil,lymphocyte,platelet and monocyte levels was *** kinetics of changes in the tumour markers and inflammatory indices were calculated as the percentage change from baseline or nadir,while receiver operating characteristic curves were drawn to select the thresholds to define patients with progressive or responsive disease with the highest sensitivity(Se)and specificity(Sp).The correlation of tumour marker kinetics with inflammatory index changes and RECIST response was determined by univariate and multivariate logistic regression analysis and the clinical utility index(CUI).RESULTS A total of 102 patients with mCRC treated with chemotherapy were *** disease(PD),defined as a CEA increase of 25.52%,resulted in an Se of 80.3%,an Sp of 84%,a good CUI negative[CUI(Ve-)]value of 0.75 and a good fraction correct(FC)value of 81.2;at a CEA cut-off of-60.85%with an Se of 100%and an Sp of 35.7%for PD,CT could be avoided in 25.49%of *** 21.49%CA19-9 cut-off for PD had an Se of 66.5%,an Sp of 87.4%,an acceptable CUI(

关键词： Tumour markers Carcinoembryonic antigen Carbohydrate antigen Inflammatory-based indices Chemotherapy response Metastatic colorectal cancer

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Anti-epitope antibody, a novel site-directed antibody against human acetylcholinesterase

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Acta Pharmacologica Sinica 2004年第4期25卷 33-37页

作者： Xing-mei ZHANG, GangLIU, Man-ji SUN2 Institute of Pharmacology and Toxicology, academyof militarymedical Sciences, Beijing 100850, China Institute of Pharmacology and Toxicology Academy of Military Medical Sciences

AIM: To construct synthetic antigens using the epitope of human brain acetylcholinesterase (hbAChE) for induc- tion and detection of the specific antibody against the epitope, and to analyse the immunogenicity of the antibody. METHODS: The epitope (RTVLVSMNYR, amino acids 143-152) of hbAChEwas chemically synthesized, coupled with the carrier protein keyhole limpet hemocyanin (KLH) to construct an artificial immunogen (KLH-epitope), and injected into rabbits to raise antibody. The epitope conjugated with bovine serum albumin (BSA) was used as the detection antigen. The specificity of the antibody was tested by enzyme-linked immunosorbent assay (ELISA) and Western blotting. The immunoreaction between the anti-recombinant human butyrylcholinesterase (rhBChE) polyclonal antibody and the biotinylated-epitope was examined by indirect ELISA. RESULTS: The erythrocyte AChE, the hbAChE, rhBChE and the BSA-epitope all immunoreacted with the anti-epitope antibody against the epitope (143-152) of hbAChE, whereas the torpedo AChE did not. CONCLUSION: The hbAChE, the human erythrocyte AChE and hBChE share the conservative antigenic epitope RTVLVSMNYR, hence they can all immunoreact with the anti-epitope antibody. Since the epitope of hbAChE is less similar with the aligned amino acid sequences of AChE of Torpedo californica or Torpedo marmorata, there is not any immunoreactivity between them. The R, M, and N residues in the epitope seem to be necessary radicals for the conservation of antigenicity.

关键词： acetylcholinesterase butyrylcholinesterase epitopes antibodies enzyme-linked immunosorbent assay Western blotting

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Study on the determinants of suckling mice neurovirulence of dengue 2 virus

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Science China(Life Sciences) 2003年第1期46卷 95-103页

作者：赵卫范宝昌胡志君陈水平王鹏程苑锡同李晓萸于曼秦鄂德杨佩英 Institute of Microbiology & Epidemiology Academy of Military Medical Sciences

pDVWS501 was a genomic-length cDNA clone of dengue 2 virus, through which infec-tious virus (MON501) could be rescued. MON501 was neurovirulent in mice, whose E residues 62 and 203 were Lys and Asn, respectively. Two genomic-length cDNA clones (TB62 and TB203) were constructed by pointed mutation of pDVWS501 with OL-PCR, E62 of TB62 and E203 of TB203 were converted to Glu and Asp, respectively. RNA transcripts of pDVWS501, TB62 and TB203 were produced in vitro and electroporated into BHK-21 cells. The cultures were collected after 7 days and used as inoculum to infect C6/36 cells. The existence of rescued dengue viruses in the culture was proved by RT-PCR, and the typical cytopathic effect (CPE) of C6/36 caused by dengue virus emerged after 2—5 days?inoculation. Sequence analysis further confirmed the exis-tence of recovered and recombinant DEN2 viruses, whose 5′ termini had an additional non-virus nucleotides 揋? while the 3′ terminal sequences remained the same as natural. The neuroviru-lence of three viruses was evaluated in 1-day-old mice by the intracerebral route with 105—102 TCID50. Compared with MON501 group, the number of infected mice with the signs of encephalitis in HFT62 and HFT203 groups was less, and the surviving time was longer. The properties of these mutants demonstrated that E62 and E203 are determinants of suckling mice neurovirulence.

关键词： dengue 2 virus, virulent determinants, infectious transcripts, point mutation.

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