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A new anterograde trans-synaptic tracer based on Sindbis virus

Neural Regeneration Research 2022年第12期17卷 2761-2764页

作者： Xiang-Wei Shi Fan Jia Pei Lyu Fu-Qiang Xu State Key Laboratory of Magnetic Resonance and Atomic and Molecular Physics Key Laboratory of Magnetic Resonance in Biological SystemsWuhan Center for Magnetic ResonanceInnovation Academy for Precision Measurement Science and TechnologyChinese Academy of SciencesWuhanHubei ProvinceChina Guangdong Provincial Key Laboratory of Brain Connectome and Behavior CAS Key Laboratory of Brain Connectome and Manipulationthe Brain Cognition and Brain Disease Institute(BCBDI)Translational Research Center for the Nervous System(TRCNS)Shenzhen Institute of Advanced TechnologyChinese Academy of SciencesShenzhen-Hong Kong Institute of Brain Science-Shenzhen Fundamental Research InstitutionsShenzhenGuangdong ProvinceChina NMPA Key Laboratory for Research and Evaluation of Viral Vector Technology in Cell and Gene Therapy Medicinal Products Key Laboratory of Quality Control Technology for Virus-Based TherapeuticsGuangdong Provincial Medical Products AdministrationShenzhen Key Laboratory of Viral Vectors for BiomedicineShenzhen Institute of Advanced TechnologyChinese Academy of SciencesShenzhenGuangdong ProvinceChina University of Chinese Academy of Sciences BeijingChina Wuhan National Laboratory for Optoelectronics Huazhong University of Science and TechnologyWuhanHubei ProvinceChina

Mapping neural circuits is critical for understanding the structure and function of the nervous system.Engineered viruses are a valuable tool for tracing neural circuits.However,current tracers do not fully meet the needs for this approach because of various drawbacks,such as toxicity and characteristics that are difficult to modify.Therefore,there is an urgent need to develop a new tracer with low toxicity and that allows for long-term studies.In this study,we constructed an engineered Sindbis virus(SINV)expressing enhanced green fluorescent protein(EGFP)reporter gene(SINV-EGFP)and found that it had no significant difference in biological characterization compared with the wild-type Sindbis virus in BHK-21 cells and neurons in vitro.We injected the virus into the visual circuit of mouse brain and found that the virus infected neurons in the local injected site and anterogradely spread in the neural circuits.Although the efficiency of transmission was limited,the findings demonstrate that SINV can be used as a new anterograde tracer to map neural circuits in mouse brain and that it spreads exclusively in the anterograde direction.Further,use of SINV in mouse brain research will provide longer time windows for circuit tracing than is possible with herpes simplex virus and vesicular stomatitis virus tracers.

关键词： anterograde lateral geniculate nucleus mouse brains neural circuit neurons retina Sindbis virus superior colliculus synapse tracer

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Viral Tools for Neural Circuit Tracing

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Neuroscience Bulletin 2022年第12期38卷 1508-1518页

作者： Qing Liu Yang Wu Huadong Wang Fan Jia Fuqiang Xu The Brain Cognition and Brain Disease Institute(BCBDI) Shenzhen Key Laboratory of Viral Vectors for BiomedicineShenzhen Institute of Advanced TechnologyChinese Academy of SciencesShenzhen-Hong Kong Institute of Brain Science-Shenzhen Fundamental Research InstitutionsNMPA Key Laboratory for Research and Evaluation of Viral Vector Technology in Cell and Gene Therapy Medicinal ProductsShenzhen Key Laboratory of Quality Control Technology for Virus-Based TherapeuticsGuangdong Provincial Medical Products AdministrationShenzhen Institute of Advanced TechnologyChinese Academy of SciencesShenzhen 518055China State Key Laboratory of Magnetic Resonance and Atomic and Molecular Physics Key Laboratory of Magnetic Resonance in Biological SystemsWuhan Center for Magnetic ResonanceInnovation Academy for Precision Measurement Science and TechnologyChinese Academy of SciencesWuhan 430071China Center for Excellence in Brain Science and Intelligence Technology Chinese Academy of SciencesShanghai 200031China University of Chinese Academy of Sciences Beijing 100049China

Neural circuits provide an anatomical basis for functional networks.Therefore,dissecting the structure of neural circuits is essential to understanding how the brain works.Recombinant neurotropic viruses are important tools for neural circuit tracing with many advantages over non-viral tracers:they allow for anterograde,retrograde,and trans-synaptic delivery of tracers in a cell type-specific,circuit-selective manner.In this review,we summarize the recent developments in the viral tools for neural circuit tracing,discuss the key principles of using viral tools in neuroscience research,and highlight innovations for developing and optimizing viral tools for neural circuit tracing across diverse animal species,including nonhuman primates.

关键词： Neural circuit Viral tool anterograde Retrograde Trans-synaptic

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Lighting Up Neural Circuits by Viral Tracing

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Neuroscience Bulletin 2022年第11期38卷 1383-1396页

作者： Liyao Qiu Bin Zhang Zhihua Gao Department of Neurobiology and Department of Neurology of the Second Affiliated Hospital NHC and CAMS Key Laboratory of Medical NeurobiologyZhejiang University School of MedicineHangzhou 310058China The MOE Frontier Science Center for Brain Research and Brain-Machine Integration School of Brain Science and Brain MedicineZhejiang UniversityHangzhou 310058China

Neurons are highly interwoven to form intricate neural circuits that underlie the diverse functions of the brain.Dissecting the anatomical organization of neural circuits is key to deciphering how the brain processes information,produces thoughts,and instructs behaviors.Over the past decades,recombinant viral vectors have become the most commonly used tracing tools to define circuit architecture.In this review,we introduce the current categories of viral tools and their proper application in circuit tracing.We further discuss some advances in viral tracing strategy and prospective innovations of viral tools for future study.

关键词： Viral tracing Neural circuit anterograde Retrograde Transsynaptic

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Trans-synaptic Neural Circuit-Tracing with Neurotropic Viruses

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Neuroscience Bulletin 2019年第5期35卷 909-920页

作者： Jiamin Li Taian Liu Yun Dong Kunio Kondoh Zhonghua Lu Guangdong Provincial Key Laboratory of Brain Connectome and Behavior The Brain Cognition and Brain Disease Institute Shenzhen Institutes of Advanced Technology Chinese Academy of Sciences Shenzhen 518055 China University of Chinese Academy of Sciences Beijing 100049 China Division of Endocrinology and Metabolism Department of Homeostatic Regulation National Institute for Physiological Sciences National Institute of Natural Sciences Myodaiji Okazaki Aichi 444-8585 Japan Japan Science and Technology Agency PRESTO Myodaiji Okazaki Aichi 444-8585 Japan

A central objective in deciphering the nervous system in health and disease is to define the connections of neurons. The propensity of neurotropic viruses to spread among synaptically-linked neurons makes them ideal for mapping neural circuits. So far, several classes of viral neuronal tracers have become available and provide a powerful toolbox for delineating neural networks. In this paper, we review the recent developments of neurotropic viral tracers and highlight their unique properties in revealing patterns of neuronal connections.

关键词： Neurotropic virus Central nervous system Neural circuit Trans-synaptic tracer Retrograde tracing anterograde tracing

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Optimal use of fielder XT guidewire enhances the success rate of chronic total occlusion percutaneous coronary intervention

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World Journal of Clinical Cases 2019年第8期7卷 928-939页

作者： Qian-Cheng Wang Hai-Ruo Lin Yuan Han Hai Dong Kai Xu Shao-Yi Guan Zhen-Huan Chen Hui-Xin Hao Jian-Ping Bin Yu-Lin Liao Quan-Min Jing Department of Cardiology State Key Laboratory of Organ Failure Research Nanfang Hospital Southern Medical University Department of Cardiology General Hospital of Northern Theater Command

BACKGROUND Chronic total occlusion(CTO) is found in 18-31% of patients who undergo coronary angiography. Successful recanalization of CTOs is associated with reduced recurrent angina pectoris rates and increased long-term survival.Although the success rate of CTO percutaneous coronary intervention(CTO-PCI)has improved, CTO-PCI remains technically challenging. The Fielder XT guidewire was designed for CTO lesions. To validate whether the use of the guidewire increases the success rate, we compared the results of CTO-PCI with or without the guidewire. We hypothesized that the use of Fielder XT guidewire can increase the success rate of CTO-PCI.AIM To investigate whether the use of Fielder XT guidewire increases the final procedural success of CTO-PCI via the anterograde approach.METHODS Between January 2013 and December 2015, a retrospective study was conducted on 1230 consecutive patients with CTO who received PCI via the anterograde approach at the General Hospital of Northern Theater Command. The patients were divided into an XT Group(n = 686) and a no-XT Group(n = 544) depending on whether Fielder XT guidewire was used. Both groups were compared for clinical parameters, lesion-related characteristics, procedural outcomes and inhospital complications. The data were statistically analyzed using Pearson's χ~2 test for categorical variables, and Students' t test was used to compare the quantitative data. Significant independent factors and a risk ratio with 95%confidence interval(CI) were assessed by multivariate logistic regression analysis.RESULTS In total, 1230 patients were recruited; 75.4% of the patients were male, and 55.8%of the patients were in the XT group. The overall success rate was 83.9%, with87.8% in the XT group. Based on multivariate logistic regression analysis, factors positively associated with procedural success were the use of Fielder XT guidewire(P = 0.005, 95%CI: 1.172-2.380) and systolic blood pressure(P = 0.011,95%CI: 1.003-1.022), while factors negatively associated with procedural succes

关键词： Chronic total occlusion Percutaneous coronary intervention anterograde wire escalation Parallel wire technique Fielder XT guidewire Success rate

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Lost in the Present: anterograde Amnesia and Medical Decision Making Capacity

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Open Journal of Medical Psychology 2014年第1期3卷 54-59页

作者： John McKelvie Christopher A. Pierce Thomas M. Dunn Philippe Weintraub Robert M. House Behavioral Health Service Denver Health Medical Center Denver USA Palm Desert VA Clinic VA Loma Linda Health Care System Palm Desert USA

Although there have been a limited number of case reports of human bilateral hippocampal injury, none of these have addressed the impact of such injuries on medical decision making capacity. The authors present a case of an elderly man with discrete bilateral hippocampal injury. As a result of his injury, the patient was hopelessly “lost in the present” and only retained the basic cognitive functions necessary to have decision making capacity for a limited period of time. He was unable to appreciate the nature of his injury, the potential risks involved in his decisions, and the recommended course of treatment longer than a few minutes. The patient’s resultant neurocognitive deficits left him lacking medical decision making capacity, a likely outcome for patients with persistent anterograde amnesia.

关键词： Bilateral Hippocampal Injury anterograde Amnesia Capacity Medical Decision Making Capacity Episodic Memory Prospective Brain

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anterograde Monosynaptic Transneuronal Tracers Derived from Herpes Simplex Virus 1 strain H129

Anterograde Monosynaptic Transneuronal Tracers Derived from ...

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中国神经科学学会第十二届全国学术会议

作者： Wen-Bo Zeng Hai-Fei Jiang Yousheng Shu Shao-Qun Zeng Fuqiang Xu Fei Zhao Min-Hua Luo State Key Laboratory of Virology CAS Center for Excellence in Brain Science and Intelligence Technology (CEBSIT) Wuhan Institute of Virology Chinese Academy of Sciences State Key Laboratory of Membrane Biology School of Life Sciences Britton Chance Center for Biomedical Photonics Wuhan National Laboratory for Optoelectronics-Huazhong University of Science and Technology State Key Laboratory of Magnetic Resonance and Atomic and Molecular Physics Brain Research Center Wuhan Institute of Physics and Mathematics Chinese Academy of Sciences

Objective Herpes simplex virus type 1 strain 129（H129） has represented a promising anterograde neuronal circuit tracing tool, which complements the existing retrograde tracers. However, the current H129 derived tracers are multisynaptic, neither bright enough to label the details of neurons nor capable of determining direct projection targets as monosynaptic tracer. The present study is to introduce an improved multisynaptic anterograde tracer H129-G4 with strong labeling intensity, and a novel mono-synaptic anterograde tracer H129-ΔTK-td T. Methods Based on the bacterial artificial chromosome of H129, we have generated a serial of recombinant viruses for neuronal circuit tracing. Among them, H129-G4 was obtained by inserting binary tandemly connected GFP cassettes into the H129 genome, and H129-ΔTK-td T was obtained by deleting the thymidine kinase（TK） gene and adding td Tomato coding gene to the H129 genome. Then the obtained viral tracers were tested in vitro and in vivo for the tracing capacity. Results H129-G4 is capable of transmitting through multiple synapses, labeling the neurons by green florescent protein, and visualizing the morphological details of the labeled neurons. H129-ΔTK-td T neither replicates nor spreads in neurons alone, but transmits to and labels the postsynaptic neurons with td Tomato in the presence of complementary expressed TK from a helper virus. H129-ΔTK-td T is also capable to map the direct projectome of the specific neuron type in the given brain regions in Cre transgenic mice. In the tested brain regions where circuits are well known, the H129-ΔTK-td T tracing patterns are consistent with the previous results. Conclusion With the assistance of the helper virus complimentarily expressing TK, H129-ΔTK-td T replicates in the initially infected neuron, transmits anterogradely through one synapse, and labeled the postsynaptic neurons with td Tomato. The H129-ΔTK-td T anterograde monosynaptic tracing system offers a useful tool for mapping the direct output in neuronal circuitry. H129

关键词： Herpes simplex virus type 1（HSV-1） H129 strain anterograde neuronal tracer H129-ΔTK-tdT monosynaptic H129-G4 multisynaptic

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Surgical treatment of a rare complication after endoscopic stent placement for anastomotic leakage after esophageal resection

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World Journal of Surgical Procedures 2017年第1期7卷 1-5页

作者： Marjan Klinkert Mechteld C de Jong Meindert N Sosef Annick B van Nunen Henricus J Belgers Department of Surgery Zuyderland Medical Centre Department of Gastroenterology Zuy-derland Medical Centre

The best approach to achieve cure in esophageal cancer is a combination of chemo-radiation and surgery. However, complications occur in half of patients. The current report, reports a rare but severe complication: Complete obstruction of the esophagus, induced by preoperative chemo-radiation therapy. Normally, strictures are treated by repeated dilatations, however, in case of complete obstruction, the perforation rate of standard blind anterograde wire access and dilation is severely increased. In order to minimize the risk of perforations, the rendezvous technique was introduced. This technique involves an anterograde approach in combination with a retrograde approach in order to open and dilatate the esophagus. While technical success rates between 83% and 100% have been reported in literature, data on clinical outcomes are scarcer. The limited amount of studies available claim that success was achieved in almost half of patients. The patient in our case currently has an oral diet without restrictions and rates his quality of life with a VAS-score ten out of ten.

关键词： Esophageal cancer Esophageal obstruction Rendezvous procedure anterograde dilatation Combined anterograde-retrograde endoscopic dilatation

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Compression Test and Finite Element Analysis for Failure Criterion of the Tibial Post of a Posterior-Stabilized Knee Prosthesis

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Journal of Biomedical Science and Engineering 2019年第5期12卷 285-292页

作者： Rina Sakai Urabe Ken Kazuhiro Yoshida Kiyoshi Mabuchi Masanobu Ujihira Department of Biomedical Engineering and Technology School of Allied Health Sciences Kitasato University Sagamihara Japan Department of Orthopedic Surgery Kitasato University Medical Center Kitamoto Japan

Post cam mechanism of Posterior Stabilized (PS) knee prostheses is useful to realize intrinsic stability for cases with severe degeneration. However, some retrieval studies report severe failure of the polyethylene tibial post. We thought that severe failures were caused by high loads during daily activities. In the current study, we performed a compression test and a finite element analysis of the mechanical forces produced in the tibial post in posterior-stabilized knee prostheses in order to develop a specification for the tibial posts found in the polyethylene inserts of PS knee prostheses. Anterior tibial post impingement and posterior tibial post impingement were simulated. The surface pressure values detected in the compression test were consistent with those obtained in the FE analysis. Of the three designs, the lowest von Mises stress values were generated inside the round tibial post;therefore, tibial posts should be round. The risk of tibial post failure was low when 500 or 1000 N was loaded onto the knee joint. It was suggested that tibial post failure occurs when the shear strain at the base of the tibial post exceeds 0.1.

关键词： Proximal Humeral Fracture Retrograde Intramedullary Nailing anterograde Intramedullary Nailing Locking Plate Internal Fixation

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Risk Assessment of Retrograde Intramedullary Nailing for Proximal Humeral Fracture

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Journal of Biomedical Science and Engineering 2019年第5期12卷 277-284页

作者： Rina Sakai Uchino Masataka Kazuhiro Yoshida Masanobu Ujihira Department of Biomedical Engineering and Technology School of Allied Health Sciences Kitasato University Sagamihara Japan Department of Orthopedic Surgery Hakujikai Memorial General Hospital Tokyo Japan

In proximal humeral fracture except AO classification 11A1, fixations with a locking plate and nails are recommended. We performed mechanical tests to investigate whether retrograde intramedullary nailing has fixation stability comparable to those of anterograde intramedullary nailing and locking plate which achieve clinically favorable outcomes. In retrograde intramedullary nailing, a nail entry point is made in the diaphysis, for which reduction of stiffness of the humerus is of concern. Thus, we investigated the influence of a nail entry point made in the diaphysis on humeral strength. Retrograde intramedullary nailing had fixation stability against bending and a force loaded in the rotation direction comparable to those of anterograde intramedullary nail and locking plate. Displacement by the main external force loaded on the humerus, compressive load, was less than half in the bone fixed by retrograde intramedullary nailing compared with that in the bone fixed with a locking plate, showing favorable fixation stability. It was clarified that stiffness of the humerus against rotation and a load in the compression direction is not reduced by a nail entry point made by retrograde intramedullary nailing.

关键词： Proximal Humeral Fracture Retrograde Intramedullary Nailing anterograde Intramedullary Nailing Locking Plate Internal Fixation

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