Application of Virtual Reality in Motor Rehabilitation of Stroke Patients

doi:10.3778/j.issn.1002-8331.2106-0364

Abstract

Abstract:

In view of the problems of the traditional rehabilitation training mode of stroke, such as long treatment cycle, boring training content, high rehabilitation cost and imbalance of doctor-patient ratio, the assisted rehabilitation treatment with virtual reality technology has realistic significance. The number of published literatures on the application of virtual reality in post-stroke rehabilitation in recent ten years has been retrieved, and the feasibility analysis of the model of virtual reality motor rehabilitation training has been carried out. Based on the application progress of virtual reality in motor rehabilitation after stroke at home and abroad, the further development of virtual reality in rehabilitation medicine is prospected.

Key words: virtual reality, rehabilitation medicine, stroke, cerebrovascular disease, motor rehabilitation

摘要：

针对传统康复医学卒中后康复训练模式治疗周期长、训练内容枯燥、康复费用过高、医患比例失衡问题，虚拟现实技术辅助康复治疗具有现实意义。进行了虚拟现实在脑卒中患者训练康复应用近十年发文量检索，对虚拟现实运动功能康复训练模式进行了可行性分析。基于虚拟现实在国内外卒中后运动功能康复中的应用进展，对其在康复医学进一步的发展方向进行了展望。

关键词: 虚拟现实, 康复医学, 脑卒中, 脑血管病, 运动功能康复

LIU Shuxuan, QIU Peng, NIE Yongqi, LIU Jing, CAO Hui. Application of Virtual Reality in Motor Rehabilitation of Stroke Patients[J]. Computer Engineering and Applications, 2021, 57(21): 68-79.

刘书轩，邱鹏，聂永琦，刘静，曹慧. 虚拟现实在脑卒中患者运动功能康复中的应用[J]. 计算机工程与应用, 2021, 57(21): 68-79.

References

[1] World Health Organization.China country assessment report on ageing and health[M].Geneva：WHO，2016.
[2] ROTH G A，ABATE D，ABATE K H，et al.Global，regional，and national age-sex-specific mortality for 282 causes of death in 195 countries and territories，1980—2017：a systematic analysis for the Global Burden of Disease Study 2017[J].The Lancet，2018，392（10159）：1736-1788.
[3] BRAININ M.Stroke epidemiology in China：which are the next steps?[J].The Lancet Neurology，2019，18（4）：325-326.
[4] 江滨.现阶段我国脑卒中流行特征及防治现状对全科医疗服务的启示和建议[J].中国全科医学，2019，22（30）：3653-3661.
JIANG B.Suggestions for domestic primary stroke care arising from epidemiological characteristics，prevention and treatment of stroke in China[J].Chinese General Practice，2019，22（30）：3653-3661.
[5] WANG W，JIANG B，SUN H，et al.Prevalence，incidence，and mortality of stroke in China：results from a nationwide population-based survey of 480?687 adults[J].Circulation，2017，135（8）：759-771.
[6] 张通.中国脑卒中康复治疗指南（2011完全版）[J].中国康复理论与实践，2012，18（4）：301-318.
ZHANG T.Chinese stroke rehabilitation guide（2011 full version）[J].Chinese Journal of Rehabilitation Theory and Practice，2012，18（4）：301-318.
[7] 王陇德，刘建民，杨弋，等.我国脑卒中防治仍面临巨大挑战——《中国脑卒中防治报告2018》概要[J].中国循环杂志，2019，34（2）：105-119.
WANG L D，LIU J M，YANG Y，et al.The prevention and treatment of stroke still face huge challenges—brief report on stroke prevention and treatment in China，2018[J].Chinese Circulation Journal，2019，34（2）：105-119.
[8] 仲亮，周静芝，彭玉鑫.基于智能数据指环与虚拟现实的手功能康复系统研究[C]//第十一届全国体育科学大会，2019.
ZHONG L，ZHOU J Z，PENG Y X.Research on hand function rehabilitation system based on intelligent data ring and virtual reality[C]//Collection of Abstracts of the 11th National Sports Science Conference，2019.
[9] LANGHORNE P，O’DONNELL M J，CHIN S L，et al.Practice patterns and outcomes after stroke across countries at different economic levels（INTERSTROKE）：an international observational study[J].The Lancet，2018，391（10134）：2019-2027.
[10] 沈洪萍，张婷婷，于龙娟.脑卒中患者瘫痪的康复护理现状[J].护理实践与研究，2017，14（15）：24-27.
SHEN H P，ZHANG T T，YU L J.Rehabilitation nursing status of stroke patients with paralysis[J].Nursing Practice and Research，2017，14（15）：24-27.
[11] IACHINI T，MAFFEI L，MASULLO M，et al.The experience of virtual reality：are individual differences in mental imagery associated with sense of presence?[J].Cognitive Processing，2019，20（3）：291-298.
[12] STINEAR C M，LANG C E，ZEILER S，et al.Advances and challenges in stroke rehabilitation[J].The Lancet Neurology，2020，19（4）：348-360.
[13] WU W X，ZHOU C Y，WANG Z W，et al.Effect of early and intensive rehabilitation after ischemic stroke on functional recovery of the lower limbs：a pilot，randomized trial[J].Journal of Stroke and Cerebrovascular Diseases，2020：104649.
[14] ENGLISH C，BOWEN A，HéBERT D，et al.Rehabilitation after stroke：evidence，practice，and new directions[M]//Warlow’s stroke：practical management.[S.l.]：Wiley，2019：867-877.
[15] 陈煌，黎蔚华，罗青，等.脑卒中早期康复现状的调查与分析[J].广东医学，2018，39（2）：278-282.
CHEN H，LI W H，LUO Q，et al.Investigation and analysis of early rehabilitation of stroke[J].Guangdong Medical Journal，2018，39（2）：278-282.
[16] JAVAID M，HALEEM A.Virtual reality applications toward medical field[J].Clinical Epidemiology and Global Health，2020，8（2）：600-605.
[17] ZHANG Y，LIU H，KANG S C，et al.Virtual reality applications for the built environment：research trends and opportunities[J].Automation in Construction，2020，118：103311.
[18] 张星星，段宏为，周晨，等.虚拟现实技术应用于脑卒中康复的有效性及安全性的系统评价再评价[J].中国全科医学，2020，23（5）：566-572.
ZHANG X X，DUAN H W，ZHOU C，et al.Efficacy and safety of virtual reality for stroke rehabilitation：an overview of systematic reviews[J].Chinese General Practice，2020，23（5）：566-572.
[19] 刘守国，金娟，张霞，等.基于ICF康复组合的评定工具在老年失能评估中的验证研究：区分度及信度[J].中国康复医学杂志，2020，35（9）：1044-1048.
LIU S G，JIN J，ZHANG X，et al.The discrimination and reliability of functioning assessing tool based on ICF rehabilitation set in the assessment of aging disability[J].Chinese Journal of Rehabilitation Medicine，2020，35（9）：1044-1048.
[20] SUBRAMANIAN S K，CROSS M K K，HIRSCHHAUSER C S.Virtual reality interventions to enhance upper limb motor improvement after a stroke：commonly used types of platform and outcomes[J].Disability and Rehabilitation：Assistive Technology，2020：1-9.
[21] ERHARDSSON M，MURPHY M A，SUNNERHAGEN K S.Commercial head-mounted display virtual reality for upper extremity rehabilitation in chronic stroke：a single-case design study[J].Journal of Neuroengineering and Rehabilitation，2020，17（1）：1-14.
[22] 危昔均，韦亦茜，秦萍，等.基于沉浸式虚拟现实脑卒中偏瘫上肢功能康复系统构建及临床可行性研究[J].中西医结合心脑血管病杂志，2021，19（11）：1949-1952.
WEI X J，WEI Y X，QIN P，et al.Construction and clinical feasibility of functional rehabilitation system for hemiplegic upper limbs after stroke based on immersive virtual reality[J].Journal of Cardio Cerebrovascular Diseases of Integrated Traditional Chinese and Western Medicine，2021，19（11）：1949-1952.
[23] MEKBIB D B，ZHAO Z，WANG J，et al.Proactive motor functional recovery following immersive virtual reality-based limb mirroring therapy in patients with subacute stroke[J].Neurotherapeutics，2020，17（4）：1919-1930.
[24] MEKBIB D B，DEBELI D K，ZHANG L，et al.A novel fully immersive virtual reality environment for upper extremity rehabilitation in patients with stroke[J].Annals of the New York Academy of Sciences，2021，1493（1）：75-89.
[25] 肖湘，黄东锋，梁斌.虚拟现实训练对亚急性期脑卒中患者上肢运动功能的影响[J].中国康复医学杂志，2019，34（9）：1049-1053.
XIAO X，HUANG D F，LIANG B.Effects of virtual reality technique in rehabilitation of hemiplegic upper extremities function in stroke patients[J].Chinese Journal of Rehabilitation Medicine，2019，34（9）：1049-1053.
[26] HUNG J W，CHOU C X，CHANG Y J，et al.Comparison of Kinect-Scratch game-based training and therapist-based training for the improvement of upper extremity functions of patients with chronic stroke：a randomized controlled single-blinded trial[J].European Journal of Physical and Rehabilitation Medicine，2019，55（5）：542-550.
[27] NOROUZI-GHEIDARI N，HERNANDEZ A，ARCHAMBAULT P S，et al.Feasibility，safety and efficacy of a virtual reality exergame system to supplement upper extremity rehabilitation post-stroke：a pilot randomized clinical trial and proof of principle[J].International Journal of Environmental Research and Public Health，2020，17（1）：113.
[28] DOMíNGUEZ-TéLLEZ P，MORAL-MU?OZ J A，SALAZAR A，et al.Game-based virtual reality interventions to improve upper limb motor function and quality of life after stroke：systematic review and meta-analysis[J].Games for Health Journal，2020，9（1）：1-10.
[29] NOROUZI-GHEIDARI N，HERNANDEZ A，ARCHAMBAULT P S，et al.Feasibility，safety and efficacy of a virtual reality exergame system to supplement upper extremity rehabilitation post-stroke：a pilot randomized clinical trial and proof of principle[J].International Journal of Environmental Research and Public Health，2020，17（1）：113.
[30] MICLAUS R，ROMAN N，CALOIAN S，et al.Non-immersive virtual reality for post-stroke upper extremity rehabilitation：a small cohort randomized trial[J].Brain Sciences，2020，10（9）：655.
[31] LLORENS R，FUENTES M A，BORREGO A，et al.Effectiveness of a combined transcranial direct current stimulation and virtual reality-based intervention on upper limb function in chronic individuals post-stroke with persistent severe hemiparesis：a randomized controlled trial[J].Journal of NeuroEngineering and Rehabilitation，2021，18（1）：1-13.
[32] YAO X，CUI L，WANG J，et al.Effects of transcranial direct current stimulation with virtual reality on upper limb function in patients with ischemic stroke：a randomized controlled trial[J].Journal of Neuro Engineering and Rehabilitation，2020，17（1）：1-8.
[33] NOROUZI-GHEIDARI N，ARCHAMBAULT P S，MONTE-SILVA K，et al.Feasibility and preliminary efficacy of a combined virtual reality，robotics and electrical stimulation intervention in upper extremity stroke rehabilitation[J].Journal of Neuroengineering and Rehabilitation，2021，18（1）：1-10.
[34] XIE H，ZHANG H，LIANG H，et al.A novel glasses-free virtual reality rehabilitation system on improving upper limb motor function among patients with stroke：a feasibility pilot study[J].Medicine in Novel Technology and Devices，2021，11：100069.
[35] CHEN Y H，CHEN C L，HUANG Y Z，et al.Augmented efficacy of intermittent theta burst stimulation on the virtual reality-based cycling training for upper limb function in patients with stroke：a double-blinded，randomized controlled trial[J].Journal of Neuro Engineering and Rehabilitation，2021，18（1）：1-14.
[36] FLUET G G，PATEL J，QIU Q，et al.Motor skill changes and neurophysiologic adaptation to recovery-oriented virtual rehabilitation of hand function in a person with subacute stroke：a case study[J].Disability and Rehabilitation，2017，39（15）：1524-1531.
[37] LANSBERG M G，LEGAULT C，MACLELLAN A，et al.Home-based virtual reality therapy for hand recovery after stroke[J].PM&R，2021.
[38] KANG M G，YUN S J，LEE S Y，et al.Effects of upper-extremity rehabilitation using smart glove in patients with subacute stroke：results of a prematurely terminated multicenter randomized controlled trial[J].Frontiers in Neurology，2020，11：1488.
[39] LEE H S，LIM J H，JEON B H，et al.Non-immersive virtual reality rehabilitation applied to a task-oriented approach for stroke patients：a randomized controlled trial[J].Restorative Neurology and Neuroscience，2020，38（4）：1-8.
[40] VOURVOPOULOS A，BADIA S B.Usability and cost-effectiveness in brain-computer interaction：is it user throughput or technology related?[C]//Proceedings of the 7th Augmented Human International Conference，2016：1-8.
[41] VOURVOPOULOS A，FERREIRA A，BADIA S B.NeuRow：an immersive VR environment for motor-imagery training with the use of brain-computer interfaces and vibrotactile feedback[C]//International Conference on Physiological Computing Systems，2016：43-53.
[42] JULIANO J M，SPICER R P，VOURVOPOULOS A，et al.Embodiment is related to better performance on a brain-computer interface in immersive virtual reality：a pilot study[J].Sensors，2020，20（4）：1204.
[43] VOURVOPOULOS A，PARDO O M，LEFEBVRE S，et al.Effects of a brain-computer interface with virtual reality（VR） neurofeedback：a pilot study in chronic stroke patients[J].Frontiers in Human Neuroscience，2019，13：210.
[44] VOURVOPOULOS A，MARIN-PARDO O，NEUREITHER M，et al.Multimodal head-mounted virtual-reality brain-computer interface for stroke rehabilitation[C]//International Conference on Human-Computer Interaction.Cham：Springer，2019：165-179.
[45] 张桃，杨帮华，段凯文，等.基于运动想象脑机接口的手功能康复系统设计[J].中国康复理论与实践，2017，23（1）：4-9.
ZHANG T，YANG B H，DUAN K W，et al.Development of hand function rehabilitation system based on motor imagery brain-computer interface[J].Chinese Journal of Rehabilitation Theory and Practice，2017，23（1）：4-9.
[46] CHENG N，PHUA K S，LAI H S，et al.Brain-computer interface-based soft robotic glove rehabilitation for stroke[J].IEEE Transactions on Biomedical Engineering，2020，67（12）：3339-3351.
[47] DE CASTRO-CROS M，SEBASTIAN-ROMAGOSA M，RODRíGUEZ-SERRANO J，et al.Effects of gamification in BCI functional rehabilitation[J].Frontiers in Neuroscience，2020，14：882.
[48] WILLETT F R，AVANSINO D T，HOCHBERG L R，et al.High-performance brain-to-text communication via handwriting[J].Nature，2021，593（7858）：249-254.
[49] BORREGO A，LATORRE J，ALCA?IZ M，et al.Comparison of oculus rift and HTC vive：feasibility for virtual reality-based exploration，navigation，exergaming，and rehabilitation[J].Games for Health Journal，2018，7（3）：151-156.
[50] WINTER C，KERN F，GALL D，et al.Immersive virtual reality during gait rehabilitation increases walking speed and motivation：a usability evaluation with healthy participants and patients with multiple sclerosis and stroke[J].Journal of Neuroengineering and Rehabilitation，2021，18（1）：1-14.
[51] ZAKHAROV A V，BULANOV V A，KHIVINTSEVA E V，et al.Stroke affected lower limbs rehabilitation combining virtual reality with tactile feedback[J].Frontiers in Robotics and AI，2020，7：81.
[52] KIM M J.Virtual reality community gait training using a 360° image improves gait ability in chronic stroke patients[J].The Journal of Korean Physical Therapy，2020，32（3）：185-190.
[53] LEE H C，HUANG C L，HO S H，et al.The effect of a virtual reality game intervention on balance for patients with stroke：a randomized controlled trial[J].Games for Health Journal，2017，6（5）：303-311.
[54] 张丽华，米立新，马全胜，等.虚拟现实平衡训练对脑卒中患者的临床疗效[J].中国康复，2019，34（12）：635-638.
ZHANG L H，MI L X，MA Q S，et al.Clinical effect of virtual reality balance training for stroke patients[J].Chinese Journal of Rehabilitation，2019，34（12）：635-638.
[55] 李文锋，余秋华，李雪宜，等.基于Kinect的虚拟现实康复训练对脑卒中偏瘫患者步行功能的影响[J].广州医科大学学报，2018，46（6）：11-15.
LI W F，YU Q H，LI X Y，et al.Effect of kinect based virtual reality rehabilitation training on walking function of stroke patients with hemiplegia[J].Journal of Guangzhou Medical University，2018，46（6）：11-15.
[56] BONUZZI G M G，DE FREITAS T B，PALMA G C S，et al.Effects of the brain-damaged side after stroke on the learning of a balance task in a non-immersive virtual reality environment[J].Physiotherapy Theory and Practice，2020：1-8.
[57] 付亏杰，范飞，孙丽楠，等.观察虚拟现实训练对脑卒中恢复期患者平衡功能和日常生活能力的影响[J].按摩与康复医学，2020，11（4）：18-20.
FU K J，FAN F，SUN L N，et al.Effect of virtual reality training on balance function and activities of daily living of stroke patients in convalescence[J].Massage and Rehabilitation Medicine，2020，11（4）：18-20.
[58] 钱平安，冯红静，沈凯杰，等.体感互动虚拟现实技术辅助用于脑卒中患者的康复效果[J].中国乡村医药，2020，27（7）：3-4.
QIAN P A，FENG H J，SHEN K J，et al.Rehabilitation effect of somatosensory interactive virtual reality technology for stroke patients[J].China Rural Medicine，2020，27（7）：3-4.
[59] MICLAUS R S，ROMAN N，HENTER R，et al.Lower extremity rehabilitation in patients with post-stroke sequelae through virtual reality associated with mirror therapy[J].International Journal of Environmental Research and Public Health，2021，18（5）：2654.
[60] PORRAS D C，SIEMONSMA P，INZELBERG R，et al.Advantages of virtual reality in the rehabilitation of balance and gait：systematic review[J].Neurology，2018，90（22）：1017-1025.
[61] SOLANKI D，LAHIRI U.Adaptive treadmill-assisted virtual reality-based gait rehabilitation for post-stroke physical reconditioning—a feasibility study in low-resource settings[J].IEEE Access，2020，8：88830-88843.
[62] 金庆华，林岚，冯朔，等.虚拟现实技术对脑卒中偏瘫患者下肢功能的康复效果[J].中国老年学杂志，2020，40（11）：2273-2276.
JIN Q H，LIN L，FENG S，et al.Rehabilitation effect of virtual reality technology on lower limb function of stroke patients with hemiplegia[J].Chinese Journal of Gerontology，2020，40（11）：2273-2276.
[63] SANTOS PALMA M A A S，LANGE B，EDUARDO J.Effects of the brain-damaged side after stroke on the learning of a balance task in a non-immersive virtual reality environment[J].Physiotherapy Theory and Practice，2020.
[64] KUMAR D，SINHA N，DUTTA A，et al.Virtual reality-based balance training system augmented with operant conditioning paradigm[J].Biomedical Engineering Online，2019，18（1）：90.
[65] 张尔珈，姚琼，王笑，等.虚拟现实康复锻炼对老年脑出血偏瘫患者肢体功能、神经功能、平衡功能及生活质量的影响[J].中国老年学杂志，2019，39（17）：4240-4243.
ZHANG E J，YAO Q，WANG X，et al.Effect of virtual reality rehabilitation exercise on limb function，nerve function，balance function and quality of life of elderly hemiplegic patients with cerebral hemorrhage[J].Chinese Journal of Gerontology，2019，39（17）：4240-4243.
[66] BIFFI E，BERETTA E，STORM F A，et al.The effectiveness of robot-vs.virtual reality-based gait rehabilitation：a propensity score matched cohort[J].Life，2021，11（6）：548.
[67] LANSINK I L B O，VAN KOUWENHOVE L，DIJKSTRA P U，et al.Effects of interventions on normalizing step width during self-paced dual-belt treadmill walking with virtual reality，a randomised controlled trial[J].Gait & Posture，2017，58：121-125.
[68] ENAM N，VEERUBHOTLA A，EHRENBERG N，et al.Augmented-reality guided treadmill training as a modality to improve functional mobility post-stroke：a proof-of-concept case series[J].Topics in Stroke Rehabilitation，2020：1-7.
[69] WALKER M L，RINGLEB S I，MAIHAFER G C，et al.Virtual reality-enhanced partial body weight-supported treadmill training poststroke：feasibility and effectiveness in 6 subjects[J].Archives of Physical Medicine and Rehabilitation，2010，91（1）：115-122.
[70] 周秀新，吴爱萍.虚拟现实结合减重平板训练对高血压性脑出血患者下肢运动功能恢复的效果观察[J].护理实践与研究，2019，16（14）：63-64.
ZHOU X X，WU A P.Effect of virtual reality combined with weight-loss treadmill training on the recovery of lower limb motor function in patients with hypertensive cerebral hemorrhage[J].Nursing Practice and Research，2019，16（14）：63-64.
[71] CALABRò R S，NARO A，RUSSO M，et al.The role of virtual reality in improving motor performance as revealed by EEG：a randomized clinical trial[J].Journal of Neuroengineering and Rehabilitation，2017，14（1）：1-16.
[72] SOLANKI D，KUMAR S，RAJ P，et al.Body weight support assisted virtual reality based treadmill walk with gait characterization[C]//2019 10th International Conference on Computing，Communication and Networking Technologies（ICCCNT），2019：1-7.
[73] 黄飞，沈爱明，卫燕，等.虚拟现实技术联合减重步行训练对脑卒中偏瘫患者步行功能恢复的影响[J].按摩与康复医学，2020，11（21）：17-19.
HUANG F，SHEN A M，WEI Y，et al.Effect of virtual reality technology combined with weight-loss walking training on walking function recovery of stroke patients with hemiplegia[J].Massage and Rehabilitation Medicine，2020，11（21）：17-19
[74] Qualcomm developer network.Reducing cybersickness in virtual reality[M/OL].https：//developer.qualcomm.com/ebook/reducing-cybersickness-virtual-reality.
[75] 王新悦，聂光宇，刘越.探讨影响虚拟现实博物馆系统的视觉不舒适度因素及减缓方法[J].中国传媒大学学报（自然科学版），2018，25（5）：66-72.
WANG X Y，NIE G Y，LIU Y.Discussion on visual discomfort factors and mitigation methods of virtual reality museum system[J].Journal of Communication University of China（Natural Science Edition），2018，25（5）：66-72.
[76] FARMANI Y，TEATHER R J.Evaluating discrete viewpoint control to reduce cybersickness in virtual reality[J].Virtual Reality，2020：1-20.
[77] WIENRICH C，WEIDNER C K，SCHATTO C，et al.A virtual nose as a rest-frame-the impact on simulator sickness and game experience[C]//2018 10th International Conference on Virtual Worlds and Games for Serious Applications（VS-Games），2018：1-8.
[78] SOMRAK A，POGA?NIK M，GUNA J.Impact of different types of head-centric rest-frames on VRISE and user experience in virtual environments[J].Applied Sciences，2021，11（4）：1593.
[79] SHI R，LIANG H N，WU Y，et al.Virtual reality sickness mitigation methods：a comparative study in a racing game[J].Proceedings of the ACM on Computer Graphics and Interactive Techniques，2021，4（1）：1-16.
[80] 张晓婷，陆菁，刘渊，等.VR交互体验中沉浸感与舒适度的平衡设计[J].包装工程，2021，42（12）：91-97.
ZHANG X T，LU J，LIU Y，et al.Balance design of immersion and comfort in VR interactive experience[J].Packaging Engineering，2021，42（12）：91-97.
[81] WEECH S，WALL T，BARNETT-COWAN M.Reduction of cybersickness during and immediately following noisy galvanic vestibular stimulation[J].Experimental Brain Research，2020，238（2）：427-437.
[82] QI R R，XIAO S F，PAN L L，et al.Profiling of cybersickness and balance disturbance induced by virtual ship motion immersion combined with galvanic vestibular stimulation[J].Applied Ergonomics，2021，92：103312.
[83] MITTELSTAEDT J，WACKER J，STELLING D.Effects of display type and motion control on cybersickness in a virtual bike simulator[J].Displays，2018，51：43-50.
[84] RIZZO-SIERRA C V，GONZALEZ-CASTA?O A，LEON-SARMIENTO F E.Galvanic vestibular stimulation：a novel modulatory countermeasure for vestibular-associated movement disorders[J].Arquivos de Neuro-Psiquiatria，2014，72：72-77.
[85] CHEN Y，ZHANG C，ZHANG M，et al.Three statistical experimental designs for enhancing yield of active compounds from herbal medicines and anti-motion sickness bioactivity[J].Pharmacognosy Magazine，2015，11（43）：435.