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The compensatory phenomenon of the functional connectome related to pathological biomarkers in individuals with subjective cognitive decline

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Translational Neurodegeneration 2020年第2期9卷 234-247页

作者： Haifeng Chen Xiaoning Sheng Caimei Luo Ruomeng Qin Qing Ye Hui Zhao Yun Xu Feng Bai 无 Department of Neurology Drum Tower HospitalMedical School and The State Key Laboratory of Pharmaceutical BiotechnologyInstitute of Brain ScienceNanjing University321 Zhongshan RoadNanjingJiangsu210008P.R.China Jiangsu Key Laboratory of Molecular Medicine Medical School of Nanjing UniversityNanjingChina Jiangsu Province Stroke Center for Diagnosis and Therapy NanjingChina Nanjing Neuropsychiatry clinic Medical Center NanjingChina for the Alzheimer’s Disease Neuroimaging Initiative

Background Subjective cognitive decline(SCD)is a preclinical stage along the Alzheimer’s disease(AD)***,little is known about the aberrant patterns of connectivity and topological alterations of the brain functional connectome and their diagnostic value in *** Resting-state functional magnetic resonance imaging and graph theory analyses were used to investigate the alterations of the functional connectome in 66 SCD individuals and 64 healthy controls(HC).Pearson correlation analysis was computed to assess the relationships among network metrics,neuropsychological performance and pathological ***,we used the multiple kernel learning-support vector machine(MKL-SVM)to differentiate the SCD and HC *** SCD individuals showed higher nodal topological properties(including nodal strength,nodal global efficiency and nodal local efficiency)associated with amyloid-βlevels and memory function than the HC,and these regions were mainly located in the default mode network(DMN).Moreover,increased local and medium-range connectivity mainly between the bilateral parahippocampal gyrus(PHG)and other DMN-related regions was found in SCD individuals compared with HC *** aberrant functional network measures exhibited good classification performance in the differentiation of SCD individuals from HC individuals at an accuracy up to 79.23%.Conclusion The findings of this study provide insight into the compensatory mechanism of the functional connectome underlying *** proposed classification method highlights the potential of connectome-based metrics for the identification of the preclinical stage of AD.

关键词： Subjective cognitive decline rs-fMRI Machine learning Compensatory mechanism

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Failure of interferon-γ pre-treated mesenchymal stem cell treatment in a patient with crohn's disease

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World Journal of Gastroenterology 2015年第14期21卷 4379-4384页

作者： Andrea Taddio Alberto Tommasini Erica Valencic Ettore Biagi Giuliana Decorti Sara De Iudicibus Eva Cuzzoni Giuseppe Gaipa Raffaela Badolato Alberto Prandini Andrea Biondi Alessandro Ventura Institute for Maternal and Child Health-IRCCS "Burlo Garofolo" -Trieste and University of Trieste Institute for Maternal and Child Health-IRCCS "Burlo Garofolo"-Trieste "Matilde Tettamanti" Research Centre Laboratory of Cell Therapy "Stefano Verri"Paediatric ClinicUniversity of Milano-BicoccaSan Gerardo Hospital Department of Life Sciences University of Trieste clinical Department of Medical Surgical and Health SciencesUniversity of Trieste Department of clinical and Experimental Sciences Institute of Molecular Medicine "Angelo Nocivelli"University of Brescia

Mesenchymal stem cells(MSC) are cells of stromal origin which exhibit unlimited self-renewal capacity and pluripotency in *** has recently been observed that MSC may also exert a profound immunosuppressive and anti-inflammatory effect both in vitro and in vivo with consequent potential use in autoimmune *** present the case of a patient suffering from childhood-onset, multidrug resistant and steroiddependent Crohn's disease who underwent systemic infusions of MSC, which led to a temporary reduction in CCR4, CCR7 and CXCR4 expression by T-cells, and a temporary decrease in switched memory B-cells, In addition, following MSC infusion, lower doses of steroids were needed to inhibit proliferation of the patient's peripheral blood mononuclear *** these changes, no significant clinical benefit was observed, and the patient required rescue therapy with infliximab and subsequent autologous hematopoietic stem cell *** results of biological and in vitro observations after MSC use and the clinical effects of infusion are discussed, and a brief description is provided of previous data on MSC-based therapy in autoimmune disorders.

关键词： Autoimmune disease Crohn’s disease Interferon-γ pr

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老年择期关节置换术患者术后谵妄的认知和功能预测因子及其后遗症

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麻醉与镇痛 2013年第6期9卷 13-22页

作者： Christopher J. Jankowski, MD Max R. Trenerry, PhD David J. Cook, MD Shonie L. Buenvenida, m'q Susanna R. Stevens, MS Darrell R. Schroeder, MS David O. Warner, MD 张文奇(译) 刘晓(译) 郭曲练(校) Departments of Anesthesiology Psychology and Biostatistics and Department of Anesthesiology Anesthesiology Clinical Research Unit Mayo Clinic Rochester Minnesota 不详

背景术后谵妄（postoperativedelirium，POD）在老年患者中很常见，且与不良预后相关。在行择期手术的患者中，POD的认知和功能性后遗症尚且未知。我们试图研究：①在老年手术患者中，敏感性神经认知测试的较低评分能否作为POD的独立风... 详细信息

背景术后谵妄（postoperativedelirium，POD）在老年患者中很常见，且与不良预后相关。在行择期手术的患者中，POD的认知和功能性后遗症尚且未知。我们试图研究：①在老年手术患者中，敏感性神经认知测试的较低评分能否作为POD的独立风险因子；@POD能否预测手术3个月后的认知和功能下降。方法我们对年龄I〉65岁的全髋关节或全膝关节置换术患者进行了一项前瞻性队列研究。参与者接受术前的神经认知和功能测试。使用混乱评估法诊断POD。出现POD的患者组与对照组在手术后3个月接受重复的神经认知和功能测试。结果418例患者符合入选标准，有42例出现POD。各组之间在基础细微精神状态检查评分、酗酒、抑郁和语言智力等方面没有差别。POD的独立预测因子包括年龄、精神疾病史、功能状态的下降和语言记忆的下降。对于所有测试，POD患者组和匹配的对照组之／＇^-J在术前和术后3个月的变化相似。结论术前神经认知和功能状态的轻微下降可以预测POD。然而在出现POD的小群体中，没有手术后3个月出现认知和功能下降的证据。POD与术前认知功能的降低有关，但在择期手术的老年患者中，可能不存在手术后3个月有害的认知或功能后遗症。

关键词：独立预测因子全膝关节置换术老年患者神经认知择期手术术后谵妄后遗症精神状态检查

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A Twenty-Year Follow-up Case Study of an Office Worker Who Returned to Work despite Serious memory Disorder Caused by Herpes Encephalitis

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Journal of Behavioral and Brain Science 2012年第4期2卷 505-511页

作者： Mitsuko Nakano Nobuo Miyashita Kazutaka Tanabe Takeshi Yamamoto Department of Neurology Higashi-Matsudo Municipal Hospital Matsudo City Welfare and Medical Center Chiba Japan Department of Neurology Tokyo Metropolitan Matsuzawa Hospital Tokyo Japan Department of Neurosurgery Juntendo University School of Medicine Tokyo Japan Miyashita Neurological clinic Nagano Japan

This study followed a 52-year-old male patient, who had suffered from severe impairment in recent memory due to se- quelae of herpes encephalitis, for 20 years. He returned to his highly intellectual work and performed well despite his doctor’s prediction. While the patient showed consistently poor results on various neuropsychological memory tests, he demonstrated incredible performance at work. This case exemplifies an extreme case that declarative memory is formed with the support of semantic memory, procedural memory, and his strong interests. Additionally, it offers lessons that results on memory tests do not necessarily correspond to the actual level of competence. The focal sites were found on both sides of the medial temporal lobe, predominantly on the left side. The T2-weighted magnetic resonance images (MRI) obtained 9 years after the onset confirmed widespread damage to the left brain including parahippocampal gyrus, hippocampus, spindle gyrus, and amygdaloid complex, with microlesions extending from the right parahippocampal gyrus to its antero-interior rim. However, the damage to hippocampus was presumed to be minor.

关键词： Declarative memory Semantic memory Procedural memory Hippocampal Damage Recent memory Herpes Encephalitis

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The prevalence of cognitive dysfunction in the estonian population of the hereditary spastic paraplegia

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World Journal of Neuroscience 2012年第2期2卷 91-97页

作者： Liina Vahter Mark Braschinsky Sulev Haldre Pille Kool Tiina Talvik Katrin Gross-Paju Department of Neurology and Neurorehabilitation Children’s Clinic Tartu University Hospital Tartu Estonia Department of Paediatrics University of Tartu Tartu Estonia Institute of clinical Medicine Tallinn University of Technology Tallinn Estonia Tallinn University Tallinn Estonia Tartu University clinics Department of Neurology Tartu Estonia

The hereditary spastic paraplegias (HSPs) are neu-rodegenerative disorders of the motor system. The information about the prevalence of the cognitive dysfunction in HSP is inconsistent. The aim of the study was to describe the prevalence of cognitive dysfunction and the cognitive profiles of persons with HSP (pwHSP) compared to healthy controls. Subjects. Participating in the cognition study were 48 persons with HSP from the epidemiological study and 48 healthy controls. Of those with HSP, 81% (39/48) had pure and 19% (9/48) had complex forms. Among pwHSP, 20.8% (10/48) had pathogenic and 14.6% (7/48) had non-pathogenic mutations in the SPAST gene. There were no mutations detected in 31 persons with the SPAST gene. Methods. Neuropsychological test battery, MMSE Results. The results of the neuropsychological tests were significantly lower in persons with HSP than in the controls (Bonferroni correction, p memory and symbol digit modalities (p = 0.0015). Five persons with HSP had an MMSE score of 24 or less. Conclusions. Our results demonstrate that cognitive dysfunction is present in 16.7 to 33.3% of persons with HSP, depending on the criteria applied. There was cognitive dysfunction in 30% of persons with a known pathogenic mutation in the SPAST gene. The most frequently damaged functions in HSP are consistent long term retrieval and later recall in verbal memory and symbol digit modalities tests that discriminate between controls and pwHSP with dysfunction (1.5 SD) in three or more domains. Dementia in HSP is rare.

关键词： Hereditary Spastic Paraplegia Cognitive Dysfunction

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Neuropsychological and Social Outcome of Patients Sustaining Traumatic Brain Injury in Cotonou

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Open Journal of Modern Neurosurgery 2021年第1期11卷 49-58页

作者： Hodé Luphin Fatigba O. Holden Doningo P. S. Arsénathe Azanlin A. K. Nelly University clinic of Traumatology Orthopaedics and Restorative Surgery of the Centre National Hospitalier Universitaire Hubert Koutoukou Maga of Cotonou Cotonou Benin Neurosurgery Unit of the University Hospital Centre of Parakou Parakou Benin Department of Physical Medicine and Rehabilitation Centre Centre Hospitalier Universitaire de Yopougon Abidjan Ivory Cost

This inaugural study in Benin was aimed at assessing neuropsychological and behavioural problems of patients with traumatic brain injury managed at the Hubert Koutoukou Maga Teaching hospital in Cotonou, and the impact on their standard of leaving. This was a prospective and cross-cutting study with a descriptive and analytical aim. It was carried out from 1 July to 30 October 2018. The study population included patients over 15 years of age who had experienced TBI. A purposive sampling of 585 patients with TBI was done, of which 142 patients could not be reached by phone while. The mean age of patients was 37.16 ± 13.9 years, with extremes ranging from 16 to 87 years. The most frequent complaints were behavioural disorder (79.5%), headache (63.8%) and memory loss (50.4%). The average duration of post traumatic amnesia was 9.08 ± 38.56 days. Sixty-three patients (68.5%) had post-traumatic amnesia that lasted less than 30 minutes and 25 patients (19.2%) had post-traumatic amnesia that lasted over a month. Neuropsychological disorders were more frequent in patients with severe TBI. Attention disorders and difficulties in elaborating strategies were noticed without any statistically significant difference in mild, moderate as well as severe TBI. Nineteen patients lost their job, thus raising the unemployment rate in our sample from 6% to 21%. Among the 100 patients (75%) that recovered their job, 14% had medical follow-up and 10% returned to part-time work. Salary remained unchanged for 61.2% of TBI patients.

关键词： Traumatic Brain Injury Neuropsychological Disorder Standard of Living Bénin

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N6-methyladenosine-modified circRIMS2 mediates synaptic and memory impairments by activating GluN2B ubiquitination in Alzheimer’s disease

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Translational Neurodegeneration 2023年第1期12卷 111-129页

作者： Xiong Wang Jiazhao Xie Lu Tan Yanjun Lu Na Shen Jiaoyuan Li Hui Hu Huijun Li Xiaoguang Li Liming Cheng Department of Laboratory Medicine Tongji HospitalTongji Medical CollegeHuazhong University of Science and TechnologyWuhan 430030China Departments of Pathophysiology Guangxi Medical UniversityNanning 530021China Department of Pathophysiology School of Basic MedicineKey Laboratory of Education Ministry of China/Hubei Province for Neurological DisordersTongji Medical CollegeHuazhong University of Science and TechnologyWuhan 430030China Hepatic Biliary Pancreatic Surgery Department The Central Hospital of WuhanTongji Medical CollegeHuazhong University of Science and TechnologyWuhan 430014China clinic Center of Human Gene Research Union HospitalTongji Medical CollegeHuazhong University of Science and TechnologyWuhan 430022China

Background Synaptic degeneration occurs in the early stage of Alzheimer’s disease(AD)before devastating symptoms,strongly correlated with cognitive *** RNAs(circRNAs)are abundantly enriched in neural tissues,and aberrant expression of circRNAs precedes AD symptoms,significantly correlated with clinical dementia ***,the direct relationship between circRNA dysregulation and synaptic impairment in the early stage of AD remains poorly *** Hippocampal whole-transcriptome sequencing was performed to identify dysregulated circRNAs and miRNAs in 4-month-old wild-type and APP/PS1 *** antisense purification and mass spectrometry were utilized to unveil interactions between circRIMS2 and methyltransferase 3,N6-adenosine-methyltransferase complex catalytic subunit(METTL3).The roles of circRIMS2/miR-3968 in synaptic targeting of UBE2K-mediated ubiquitination of GluN2B subunit of NMDA receptor were evaluated via numerous lentiviruses followed by morphological staining,co-immunoprecipitation and behavioral ***,a membrane-permeable peptide was used to block the ubiquitination of K1082 on GluN2B in AD *** circRIMS2 was significantly upregulated in 4-month-old APP/PS1 mice,which was mediated by METTL3-dependent N6-methyladenosine(m6A)*** of circRIMS2 led to synaptic and memory impairments in 4-month-old C57BL/6 ***-3968/UBE2K was validated as the downstream of *** UBE2K induced synaptic dysfunction of AD through ubiquitinating K1082 on *** METTL3 or blocking the ubiquitination of K1082 on GluN2B with a short membrane-permeable peptide remarkably rescued synaptic dysfunction in AD *** In conclusion,our study demonstrated that m6A-modified circRIMS2 mediates the synaptic and memory impairments in AD by activating the UBE2K-dependent ubiquitination and degradation of GluN2B via sponging miR-3968,providing novel therapeutic strategies for AD.

关键词： Alzheimer’s disease circRNA Synaptic dysfunction GluN2B Ubiquitination

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STAT3 ameliorates cognitive deficits by positively regulatingthe expression of NMDARs in a mouse model of FTDP-17

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Signal Transduction and Targeted Therapy 2021年第1期6卷 158-170页

作者： Xiao-Yue Hong Hua-Li Wan Ting Li Bing-Ge Zhang Xiao-Guang Li Xin Wang Xiao Li Qian Liu Chong-Yang Chen Ying Yang Qun Wang Shu-Peng Li Hao Yu Jian-Zhi Wang Xi-Fei Yang Gong-Ping Liu Department of Pathophysiology School of Basic Medicine and the Collaborative Innovation Center for Brain ScienceKey Laboratory of Ministry of Education of China and Hubei Province for Neurological DisordersTongji Medical CollegeHuazhong University of Science and TechnologyWuhan 430030China clinic Center of Human Gene Research Union HospitalTongji Medical CollegeHuazhong University of Science and TechnologyWuhanChina State Key Laboratory of Oncogenomics School of Chemical Biology and BiotechnologyPeking University Shenzhen Graduate SchoolShenzhenChina Bomedical Engineering Shenzhen PolytechnicShenzhen 518055China Key Laboratory of Modern Toxicology of Shenzhen Shenzhen Center for Disease Control and PreventionShenzhen 518055China Co-innovation Center of Neuroregeneration Nantong UniversityNantongJiangsu 226001China

In tauopathies,memory impairment positively strongly correlates with the amount of abnormal tau aggregates;however,how tau accumulation induces synapse impairment is ***,we found that human tau accumulation activated Signal Transduction and Activator of Transcription-1(STAT1)to inhibit the transcription of synaptic N-methyl-D-aspartate receptors(NMDARs).Here,overexpressing human P301L mutant tau(P301L-hTau)increased the phosphorylated level of Signal Transduction and Activator of Transcription-3(STAT3)at Tyr705 by JAK2,which would promote STAT3 translocate into the nucleus and activate ***,STAT3 was found mainly located in the *** study found that P301L-htau acetylated STAT1 to bind with STAT3 in the cytoplasm,and thus inhibited the nuclear translocation and inactivation of *** of STAT3 in STAT3^(flox/flox) mice mimicked P301L-hTau-induced suppression of NMDARs expression,synaptic and memory *** STAT3 rescued P301L-hTau-induced synaptic and cognitive deficits by increasing NMDARs *** study proved that STAT3 positively regulated NMDARs transcription through direct binding to the specific GAS element of NMDARs *** findings indicate that accumulated P301L-hTau inactivating STAT3 to suppress NMDARs expression,revealed a novel mechanism for tau-associated synapse and cognition deficits,and STAT3 will hopefully serve as a potential pharmacological target for tauopathies treatment.

关键词： STAT3 inhibited expressing

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Effect of Dimethoate on Object Recognition memory in Wistar Rats and Essay of Treatment with Nettle

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Journal of Behavioral and Brain Science 2017年第9期7卷 425-445页

作者： Majda Samih Pacome Kouadio N’Go Sabah Belaaouja Amina Ouazzani Touhami Ahmed Omar Touhami Ahami Unit of clinic and Cognitive Neuroscience Laboratory of Biology and HealthDepartment of BiologyFaculty of SciencesIbn Tofail UniversityKenitraMorocco Training and Research Unit of Biology Sciences Peleforo Gon Coulibaly UniversityKorhogoIvory Coast Botanical and Plant Protection Unit Laboratory of Biology and HealthDepartment of BiologyFaculty of SciencesIbn Tofail UniversityKenitraMorocco

Pesticides were economically important chemicals in agriculture. Their use has permitted agricultural progress, through the eradication of harmful insect and the fight against vectors of disease. However, several studies question the beneficial effects of organophosphorus compounds, showing that their deregulated use causes various problems of environmental pollution and human health. The present study shows that chronic exposure to a subtoxic dose of dimethoate is likely to affect cognitive and behavioral functions of rats (both males and females). Our results show that exposure to dimethoate affects both short and long-term memory capacities. The short-term memory results are more pronounced. Treatment with nettle extract allowed a significant improvement in cognitive and behavioral performance of the rats after their exposure to dimethoate.

关键词： Dimethoate Dioic Nettle Acetylcholinesterase Chelation memory

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Long-term Helicobacter pylori infection does not induce tauopathy and memory impairment in SD rats

Long-term Helicobacter pylori infection does not induce tauo...

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中国神经科学学会第十二届全国学术会议

作者： Huan Zhou Yin Guo Xing Li Zheng-yu Liuyang Yang-ping Shengtu Xiao-peng Jing Jia-wei Liang Xin-wen Zhou Xiao-chuan Wang Jian-zhi Wang Ji Zeng Rong Liu Department of Pathophysiology Key Laboratory of Ministry of Education for Neurological Disorders School of Basic Medicine Tongji Medical College Huazhong University of Science and Technology The Institute for Brain Research Collaborative Innovation Center for Brain Science Huazhong University of Science and Technology Department of clinic Laboratory Pu Ai Hospital Tongji Medical College Huazhong University of Science and Technology

Object Helicobacter pylori（***） infection is a recognized risk factor of dementia, while its role and mechanism in Alzheimer Disease（AD） remained unclarified. Our previous study has identified that soluble *** filtrate injection could induce ADlike pathologic changes and cognitive impairment in SD rats. In the present study, we further explored the effect of long-term stomach colonization of *** bacteria on the brains of SD rats. Methods The SD rats were infected by oral gavage with ***（*** strain TN2 GF4）. The successful infection was confirmed by polymerase chain reaction（PCR） and Gram *** tau hyperphosphorylation was measured by western bloting. The spatial learning and memory ability was identified by open field and morris water maze. Results（1） There was an efficient colonization of *** in the stomach after *** bacteria gavage.（2） *** infection does not induce AD-like tau hyperphosphorylation and cognitive impairment in rats. Conclusion Long-term *** colonization in the stomach of SD rats is not a suitable animal model to mimic the effects of *** infection on brain function in human beings.

关键词： Alzherimer disease Tauopathy memory impairment Helicobacter pylori

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