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Effectiveness of the A3 robot on lower extremity motor function in stroke patients:A prospective,randomized controlled trial

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World Journal of Clinical Cases 2024年第24期12卷 5523-5533页

作者： Lin-Jian Zhang Xin Wen Yang Peng Wei Hu hui Liao Zi-Cai liu hui-yu liu Department of Rehabilitation Medicine Yuebei People's HospitalShaoguan 512000Guangdong ProvinceChina Department of Rehabilitation Medicine Shaoguan First People's HospitalShaoguan 512000Guangdong ProvinceChina Department of Rehabilitation Medicine Yuebei Second People's HospitalShaoguan 512026Guangdong ProvinceChina

BACKGROUND The results of existing lower extremity robotics studies are conflicting,and few relevant clinical trials have examined short-term efficacy.In addition,most of the outcome indicators in existing studies are scales,which are not objective enough.We used the combination of objective instrument measurement and scale to explore the short-term efficacy of the lower limb A3 robot,to provide a clinical reference.AIM To investigate the improvement of lower limb walking ability and balance in stroke treated by A3 lower limb robot.METHODS Sixty stroke patients were recruited prospectively in a hospital and randomized into the A3 group and the control group.They received 30 min of A3 robotics training and 30 min of floor walking training in addition to 30 min of regular rehabilitation training.The training was performed five times a week,once a day,for 2 wk.The t-test or non-parametric test was used to compare the threedimensional gait parameters and balance between the two groups before and after treatment.RESULTS The scores of basic activities of daily living,Stroke-Specific Quality of Life Scale,FM balance meter,Fugl-Meyer Assessment scores,Rivermead Mobility Index,Stride speed,Stride length,and Time Up and Go test in the two groups were significantly better than before treatment(19.29±12.15 vs 3.52±4.34;22.57±17.99 vs 4.07±2.51;1.21±0.83 vs 0.18±0.40;3.50±3.80 vs 0.96±2.08;2.07±1.21 vs 0.41±0.57;0.89±0.63 vs 0.11±0.32;12.38±9.00 vs 2.80±3.43;18.84±11.24 vs 3.80±10.83;45.12±69.41 vs 8.41±10.20;29.45±16.62 vs 8.68±10.74;P<0.05).All outcome indicators were significantly better in the A3 group than in the control group,except the area of the balance parameter.CONCLUSION For the short-term treatment of patients with subacute stroke,the addition of A3 robotic walking training to conventional physiotherapy appears to be more effective than the addition of ground-based walking training.

关键词： Stroke Robotics Gait Robot-assisted gait training Neurological rehabilitation Walking training

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Naturally-Occurring Antibodies Against Bim are Decreased in Alzheimer’s Disease and Attenuate AD-type Pathology in a Mouse Model

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Neuroscience Bulletin 2022年第9期38卷 1025-1040页

作者： Jie-Ming Jian Dong-yu Fan Ding-yuan Tian yuan Cheng Pu-Yang Sun Cheng-Rong Tan Gui-Hua Zeng Chen-Yang He Ye-Ran Wang Jie Zhu Xiu-Qing Yao Yan-Jiang Wang yu-hui liu Department of Neurology and Centre for Clinical Neuroscience Daping HospitalThird Military Medical UniversityChongqing400000China Shigatse Branch Xinqiao HospitalThird Military Medical UniversityShigatse857000China Department of Rehabilitation the Second Affiliated Hospital of Chongqing Medical UniversityChongqing400000China Key Laboratory of Ageing and Brain Disease Chongqing400000China Center for Excellence in Brain Science and Intelligence Technology Chinese Academy of SciencesShanghai200031China

Increased neuronal apoptosis is an important pathological feature of Alzheimer’s disease(AD).The Bcl-2-interacting mediator of cell death(Bim)mediates amyloid-beta(Aβ)-induced neuronal apoptosis.Naturally-occurring antibodies against Bim(NAbs-Bim)exist in human blood,with their levels and functions unknown in AD.In this study,we found that circulating NAbs-Bim were decreased in AD patients.Plasma levels of NAbs-Bim were negatively associated with brain amyloid burden and positively associated with cognitive functions.Furthermore,NAbs-Bim purified from intravenous immunoglobulin rescued the behavioral deficits and ameliorated Aβdeposition,tau hyperphosphorylation,microgliosis,and neuronal apoptosis in APP/PS1 mice.In vitro investigations demonstrated that NAbs-Bim were neuroprotective against AD through neutralizing Bim-directed neuronal apoptosis and the amyloidogenic processing of amyloid precursor protein.These findings indicate that the decrease of NAbs-Bim might contribute to the pathogenesis of AD and immunotherapies targeting Bim hold promise for the treatment of AD.

关键词： Alzheimer’s disease Amyloid-beta Bim Naturally-occurring antibodies Neuronal apoptosis

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Elevated Levels of Naturally-Occurring Autoantibodies Against the Extracellular Domain of p75NTR Aggravate the Pathology of Alzheimer's Disease

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Neuroscience Bulletin 2023年第2期39卷 261-272页

作者： Chen-Yang He Ding-yuan Tian Si-Han Chen Wang-Sheng Jin yuan Cheng Jia-Yan Xin Wei-Wei Li Gui-Hua Zeng Cheng-Rong Tan Jie-Ming Jian Dong-yu Fan Jun-Rong Ren yu-hui liu Yan-Jiang Wang Fan Zeng Department of Neurology and Center for Clinical Neuroscience Daping HospitalThird Military Medical UniversityChongqing 400042China The Institute of Brain and Intelligence Third Military Medical UniversityChongqing 400042China Chongqing Key Laboratory of Ageing and Brain Diseases Chongqing 400042China State Key Laboratory of Trauma Burn and Combined InjuryDaping HospitalThird Military Medical UniversityChongqing 400042China Department of Cardiology Southwest HospitalThird Military Medical UniversityChongqing 400042China Department of Neurology Nanchong Central HospitalThe Second Clinical Medical SchoolNorth Sichuan Medical CollegeNanchong 637000China Department of Clinical Medicine North Sichuan Medical CollegeNanchong 637000China Department of Neurology The General Hospital of Western Theater CommandChengdu 610000China Shigatse Branch Xinqiao HospitalThird Military Medical UniversityShigatse 857000China

The extracellular domain(p75ECD)of p75 neurotrophin receptor(p75NTR)antagonizes Aβ neurotoxicity and promotes Aβclearance in Alzheimer’s disease(AD).The impaired shedding of p75ECD is a key pathological process in AD,but its regulatory mechanism is largely unknown.This study was designed to investigate the presence and alterations of naturally-occurring autoantibodies against p75ECD(p75ECD-NAbs)in AD patients and their effects on AD pathology.We found that the cerebrospinal fluid(CSF)level of p75ECD-NAbs was increased in AD,and negatively associated with the CSF levels of p75ECD.Transgenic AD mice actively immunized with p75ECD showed a lower level of p75ECD and more severe AD pathology in the brain,as well as worse cognitive functions than the control groups,which were immunized with Re-p75ECD(the reverse sequence of p75ECD)and phosphate-buffered saline,respectively.These findings demonstrate the impact of p75ECD-NAbs on p75NTR/p75ECD imbalance,providing a novel insight into the role of autoimmunity and p75NTR in AD.

关键词： Alzheimer’s disease p75 neurotrophin receptor Extracellular domain Autoantibody Amyloidbeta Immunity

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Association of Polygenic Risk Score with Age at Onset and Cerebrospinal Fluid Biomarkers of Alzheimer’s Disease in a Chinese Cohort

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Neuroscience Bulletin 2020年第7期36卷 696-704页

作者： Wei-Wei Li Zhen Wang Dong-yu Fan Ying-Ying Shen Dong-Wan Chen hui-yun Li Ling Li Heng Yang yu-hui liu Xian-Le Bu Wang-Sheng Jin Fan Zeng Zhi-Qiang Xu Jin-Tai yu Li-Yong Chen Yan-Jiang Wang Department of Neurology and Centre for Clinical Neuroscience Duping HospitalThird Military Medical UniversityChongqing 400042China Department of Anaesthesiology Daping HospitalThird Military Medical UniversityChongqing 400042China Chongqing Key Laboratory of Aging and Diseases Chongqing 400042China Centre for Excellence in Brain Science and Intelligence Technology Chinese Academy of SciencesShanghai 200031China Department of Neurology Huashan HospitalFudan UniversityShanghai 200040China

To evaluate whether the polygenic profile modifies the development of sporadic Alzheimer’s disease(sAD)and pathological biomarkers in cerebrospinal fluid(CSF),462 sAD patients and 463 age-matched cognitively normal(CN)controls were genotyped for 35 singlenucleotide polymorphisms(SNPs)that are significantly associated with sAD.Then,the alleles found to be associated with sAD were used to build polygenic risk score(PRS)models to represent the genetic risk.Receiver operating characteristic(ROC)analyses and the Cox proportional hazards model were used to evaluate the predictive value of PRS for the sAD risk and age at onset.We measured the CSF levels of Aβ42,Aβ42/Aβ40,total tau(T-tau),and phosphorylated tau(P-tau)in a subgroup(60 sAD and 200 CN participants),and analyzed their relationships with the PRSs.We found that 14 SNPs,including SNPs in the APOE,BIN1,CD33,EPHA1,SORL1,and TOMM40 genes,were associated with sAD risk in our cohort.The PRS models built with these SNPs showed potential for discriminating sAD patients from CN controls,and were able to predict the incidence rate of sAD and age at onset.Furthermore,the PRSs were correlated with the CSF levels of Aβ42,Aβ42/Aβ40,T-tau,and P-tau.Our study suggests that PRS models hold promise for assessing the genetic risk and development of AD.As genetic risk profiles vary among populations,large-scale genome-wide sequencing studies are urgently needed to identify the genetic risk loci of sAD in Chinese populations to build accurate PRS models for clinical practice.

关键词： Alzheimer's disease Single nucleotide polymorphism Polygenic risk score Cerebrospinal fluid Biomarker Amyloid-beta Tau

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Bio-inspired Attachment Mechanism of Dynastes Hercules:Vertical Climbing for On-Orbit Assembly Legged Robots

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Journal of Bionic Engineering 2024年第1期21卷 137-148页

作者： yuetian Shi Xuyan Hou Zhonglai Na Jie Zhou Nan yu Song liu Linbo Xin Guowei Gao yuhui liu School of Mechatronics Engineering Harbin Institute of TechnologyHarbin 150001China

With the increasing size of space facilities,on-orbit assembly requires robots to move on different heights of trusses.This paper proposes a bio-inspired attachment mechanism for robot feet to enable climbing on different heights of trusses.Inspired by the attachment and grasping abilities of Dynastes Hercules,we utilize its foot microstructures,such as microhooks and setae,to achieve efficient contact and firm grip with the surface.The morphology and arrangement of these structures can inspire the design of robot feet to improve their grasping and stability performance.We study the biological structure of Dynastes Hercules,design and optimize the bio-inspired structure,analyze the influence of various factors from theoretical and experimental perspectives,and verify the feasibility of the scheme through simulation.We propose an ideal climbing strategy that provides useful reference for robot applications in practice.Moreover,the influence laws of various factors in this paper can be applied to robot foot design to improve their operation ability and stability performance in the space environment.This bio-inspired mechanism can improve robot working range and efficiency,which is critical for on-orbit assemblyin space.

关键词： Space assembly robot Truss climbing Bionic structure Dynastes Hercules tarsus

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CSF Brain-Reactive Autoantibodies are Elevated in Patients with Viral Encephalitis

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Neuroscience Bulletin 2020年第8期36卷 942-946页

作者： Zhong-yuan yu Jian-Hong Wang Wei-Wei Li Ye-Ran Wang Noralyn B.Manucat-Tan Jun Wang Ju Wang Gao-yu Cui Jie-Xiang Pan Shui-Xian Zhang Zu-Juan liu Liang Tan yu-hui liu Department of Neurology and Clinical Center for Neuroscience Daping HospitalThird Military Medical University(Army Medical University)Chongqing 400042China Department of Neurology Sichuan Academy of Medical Sciences and Sichuan Provincial People's HospitalChengdu 610072China Chengdu Military General Hospital Chengdu 610083China School of Pharmacy and Medical Sciences University of South AustraliaAdelaideAustralia Department of Neurosurgery Southwest HospitalThird Military Medical University(Army Medical University)Chongqing 400038China Third Military Medical University(Army Medical University) Chongqing 400038China

Dear Editor,Brain-reactive autoantibodies are thought to play an important role in mediating disorders of the central nervous system(CNS).These antibodies direct the processes underlying several diseases,such as multiple sclerosis(MS),neuromyelitis optica(NMO),and neuropsychiatric systemic lupus erythematosus[1-3].In infectious diseases of the CNS,the pathogen itself is regarded to play a major role in the pathogenesis[4].

关键词： antibodies diseases Patients

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Clinical Research on Alzheimer's Disease: Progress and Perspectives

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Neuroscience Bulletin 2018年第6期34卷 1111-1118页

作者： Bin-Lu Sun Wei-Wei Li Chi Zhu Wang-Sheng Jin Fan Zeng yu-hui liu Xian-Le Bu Jie Zhu Xiu-Qing Yao Yan-Jiang Wang Department of Neurology Daping Hospital Third Military Medical University State Key Laboratory of Trauma Burn and Combined InjuryInstitute of Surgery Research Daping Hospital Third Military Medical University

Alzheimer’s disease(AD), the most common type of dementia, is becoming a major challenge for global health and social care. However, the current understanding of AD pathogenesis is limited, and no early diagnosis and disease-modifying therapy are currently available. During the past year, significant progress has been made in clinical research on the diagnosis, prevention, and treatment of AD.In this review, we summarize the latest achievements,including diagnostic biomarkers, polygenic hazard score,amyloid and tau PET imaging, clinical trials targeting amyloid-beta(Ab), tau, and neurotransmitters, early intervention, and primary prevention and systemic intervention approaches, and provide novel perspectives for further efforts to understand and cure the disease.

关键词： Alzheimer's disease Amyloid-beta Tau Immunotherapy BACE1 inhibitor 5-HT6 receptor antagonist Primary prevention Positron emission tomographic imaging Biomarker

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An integrative mathematical model of microwave ion thruster for mHz-frequency thrust noise analysis

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Chinese Journal of Aeronautics 2024年第4期37卷 121-136页

作者： Xiang NIU hui liu Daren yu Plasma Propulsion Laboratory Harbin Institute of TechnologyHarbin 150001China

Many high-precision space missions need thrusters to produce thrust with low noise to compensate for disturbances and ensure satellite platform stability. Microwave ion thruster is characterized with a wide thrust range and potential for these missions. A cost-effective and accurate mathematical model is crucial for mHz-frequency thrust noise analysis and feedback controller design. The Particle-In-Cell(PIC) and global models are two common simulation tools. The PIC model is characterized with high accuracy but huge computation cost, which is difficult to analyze long-time performance characteristics. Now, the global model is only used for the discharge chamber with low accuracy and cannot reflect ion extraction properties. In this paper, an integrative mathematical model is built for a 1-cm microwave ion thruster and can reflect ion beamlet divergence and impingement on the Accelerator Grid(AG). Simulation results show good agreement with experiments at 0.06 sccm. However, the model demonstrates worse consistency with experiments when the flux increases to 0.1 sccm, which may be because the influence of neutral gas on the Electron Cyclotron Resonance(ECR) is not considered in the model. A long-time(1000 s) simulation is conducted with this model under 35 μN. It takes 3 hrs, and the thrust noise reaches 1 μN/Hz^(0.5) at 1 mHz.

关键词： Electric propulsion Microwave ion thruster Integrative model Sheath property Ion beamlet divergence Thrust noise Plasma

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Generic Existence of Infinitely Many Non-contractible Closed Geodesics on Compact Space Forms

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Acta Mathematica Sinica,English Series 2024年第7期40卷 1674-1684页

作者： hui liu yu Chen Wang School of Mathematics and Statistics Wuhan UniversityWuhan430072P.R.China School of Mathematics Tianjin Normal UniversityTianjin300384P.R.China

Let M=S^(n)/Γand h be a nontrivial element of finite order p inπ_(1)(Μ),where the integers n,p≥2,Γis a finite abelian group which acts freely and isometrically on the n-sphere and therefore M is diffeomorphic to a compact space form.In this paper,we prove that there are infinitely many non-contractible closed geodesics of class[h]on the compact space form with C^(r)-generic Finsler metrics,where 4≤r≤∞.The conclusion also holds for Cr-generic Riemannian metrics for 2≤r≤∞.The proof is based on the resonance identity of non-contractible closed geodesics on compact space forms.

关键词： Compact space forms non-contractible closed geodesics generic Finsler metrics resonance identity

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Prenatal amoxicillin exposure induces developmental toxicity in fetal mice and its characteristics

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Journal of Environmental Sciences 2024年第3期137卷 287-301页

作者： Yongguo Dai yu Peng Wen Hu Yi liu hui Wang Department of Pharmacology Wuhan University School of Basic Medical SciencesWuhan 430071China Department of Pharmacy Zhongnan Hospital of Wuhan UniversityWuhan 430071China Hubei Provincial Key Laboratory of Developmentally Originated Disease Wuhan 430071China

Amoxicillin,a widely used antibiotic in human and veterinary pharmaceuticals,is now considered as an“emerging contaminant”because it exists widespreadly in the environment and brings a series of adverse outcomes.Currently,systematic studies about the developmental toxicity of amoxicillin are still lacking.We explored the potential effects of amoxicillin exposure on pregnancy outcomes,maternal/fetal serum phenotypes,and fetal multiple organ development in mice,at different doses(75,150,300 mg/(kg·day))during late-pregnancy,or at a dose of 300 mg/(kg·day)during different stages(mid-/latepregnancy)and courses(single-/multi-course).Results showed that prenatal amoxicillin exposure(PAmE)had no significant infuence on the body weights of dams,but it could inhibit the physical development and reduce the survival rate of fetuses,especially during the midpregnancy.Meanwhile,PAmE altered multiple maternal/fetal serum phenotypes,especially in fetuses.Fetal multi-organ function results showed that PAmE inhibited testicular/adrenal steroid synthesis,long bone/cartilage and hippocampal development,and enhanced ovarian steroid synthesis and hepatic glycogenesis/lipogenesis,and the order of severity might be gonad(testis,ovary)>liver>others.Further analysis found that PAmE-induced multiorgan developmental and functional alterations had differences in stages,courses and fetal gender,and the most obvious changes might be in high-dose,late-pregnancy and multicourse,but there was no typical rule of a dose-response relationship.In conclusion,this study confirmed that PAmE could cause abnormal development and multi-organ function alterations,which deepens our understanding of the risk of PAmE and provides an experimental basis for further exploration of the long-term harm.

关键词： Amoxicillin Prenatal exposure Fetal development Organ function Developmental toxicity

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