Nicotinic acetylcholine receptors(nAChRs) are widely distributed ligand gated ion channels throughout the peripheral and central nervous systems of mammals.There are 16 different n AChR subunits,α1-α7,α9,α10 and ...Nicotinic acetylcholine receptors(nAChRs) are widely distributed ligand gated ion channels throughout the peripheral and central nervous systems of mammals.There are 16 different n AChR subunits,α1-α7,α9,α10 and β1-β4,as well as γ,δ,and ε,which assemble into pentamers to form different nAChR subtypes with distinct pharmacological properties in mammals.Among them α6β2*(*designates other possible subunit),α3β4 and α4β2 nAChR subtypes are potential therapeutic targets for the treatment of addiction.However,various n AChR subtypes are very difficult to pharmacologically distinguish from each other.The α6* n AChRs are expressed by dopaminergic neurons in the central nervous system,which modulate the release of dopamine and are believed to be important in mediating tobacco,morphine,cocaine and ethanol addiction.The α3β4 nAChRs present in the medial habenula with important role in influencing nicotine addiction.Blockage of α3β4 nAChRs in the medial habenula decreased the dose of nicotine that rodents would self-administer.Thus,new antagonists of α6β2* or α3β4 nA ChR subtypes are of considerable interest,which would give strategies to selectively modulate α6β2* or α3β4 nA ChR function.We characterized an α-conotoxin(α-CTx)TxIB with 16 amino acids and an α-CTx TxID with 15 amino acids from Conus textile.The sequence of TxIB is GCCSDPPCRNKHPDLCamide.The sequence of TxID is GCCSHPVCSAMSPIC with C-terminal amidation too.Both peptides with a Ⅰ-Ⅲ and Ⅱ-Ⅳ disulfide con-nectivity were chemically synthesized.The residues between Cys-Ⅱ and Cys-Ⅲ and Cys-Ⅲand Cys-Ⅳ of α-CTx are commonly referred to as loops 1 and 2,respectively.The number of residues in each of these loops is used to further classify the α-CTx.So TxIB is classified as a 4/7α-CTx,whereas the α-CTx TxIB has a 4/6 spacing.Both peptides were tested on rat nAChRs heterologously expressed in Xenopus laevis oocytes.The α-CTx TxIB blocked α6/α3β2β3 nAChR with an IC50 of 28 nmol·L^(-1),which showed little or no block of all the other tested subtypes at concentrations up to 10 μmol·L^(-1).TxIB blocking α6/α3β2β3 nAChR is rapidly reversed after toxin washout.The ability ofα-CTx TxIB to discriminate between α6/α3β2β3 and the other nAChR receptors is unique.There are no small molecules have this selectivity profile.Previously described α-CTx that potently blockα6/α3β2β3 nA ChR s also block either α6/α3β4 nAChRs,α3β2 nAChRs and(or) other nAChRs subtypes.TxID was the very potent α3β4 nAChR antagonists blocking rat α3β4 n AChRs with an IC-50 of 12.5 nmol·L1.However,TxID also blocked the closely related α6/α3β4 with an IC50 of 94 nmol·L^(-1).In fact,the expression profile ofα3β4 nAChRs and α6/α3β4 nAChRs overlap in a variety of tissues.So TxI D can′t differentiate α3β4 nA ChR from α6/α3β4 nA ChR effectively.To distinguish between these two close subtypes,positional-scanning mutagenesis of TxID was performed to identify critical residues that confer potency for α3β4 nAChRs,and hope to obtain more selective mutant to discriminate between these two close subtypes.The effects of 15 analogues and TxID were tested on both α3β4 and α6/α3β4 nAChRs.An analogue,ie [S9 A]TxID had46-fold greater potency for α3β4 versus α6/α3β4 nAChRs,which showed significantly improved selectivity for α3β4 versus α6/α3β4 nAChRs.Both TxI D and [S9 A]TxI D had little activity on other nA ChR subtypes.The three-dimensional solution structures of TxIB,TxID and [S9 A]TxID were determined using NMR spectroscopy.α-CTx TxI B,TxID and [S9 A]TxID represent uniquely selective ligand for probing the structure and function of α6β2*and α3β4 nA ChR s respectively.It is known about20% people have used drugs recreationally resulting in a substance use disorder finally.Therefore,structural insights derived from these ligands may facilitate the development of novel therapeutics for addiction involving α6β2* and α3β4 nA ChR s.展开更多
Despite years of interventions in the United States, substance abuse continues to be a major national problem in our society. For individuals affected, it can constitute a major disability and a decrease in quality of...Despite years of interventions in the United States, substance abuse continues to be a major national problem in our society. For individuals affected, it can constitute a major disability and a decrease in quality of life. Current American societal expectations are that individuals who identify!they are involved in substance abuse will go to treatment, eventually recover, get off public assistance straightaway, and return to work. Most rehabilitation professionals also maintain the same expectations. The reality is that efforts of prevention do not appear to diminish the number of people with substance abuse. Traditional treatment appears to have minimal, if any, influence upon the cessation of substance abuse, and traditional vocational rehabilitation practices appear unsuited for the unique problems and types of symptoms experienced by substance abusers. Creative, yet sound, alternatives that combine effective treatment strategies and non-traditional vocational rehabilitation methods need to be exqlored and tested for effectiveness, and applied.展开更多
After abusing drugs for long,drug users will experience deteriorated self-control cognitive ability,and poor emotional regulation.This paper designs a closed-loop virtual-reality(VR),motorimagery(MI)rehabilitation tra...After abusing drugs for long,drug users will experience deteriorated self-control cognitive ability,and poor emotional regulation.This paper designs a closed-loop virtual-reality(VR),motorimagery(MI)rehabilitation training system based on brain-computer interface(BCI)(MI-BCI+VR),aiming to enhance the self-control,cognition,and emotional regulation of drug addicts via personalized rehabilitation schemes.This paper is composed of two parts.In the first part,data of 45 drug addicts(mild:15;moderate:15;and severe:15)is tested with electroencephalogram(EEG)and near-infrared spectroscopy(NIRS)equipment(EEG-NIRS)under the dual-mode,synchronous signal collection paradigm.Using these data sets,a dual-modal signal convolutional neural network(CNN)algorithm is then designed based on decision fusion to detect and classify the addiction degree.In the second part,the MIBCI+VR rehabilitation system is designed,optimizing the Filter Bank Common Spatial Pattern(FBCSP)algorithm used in MI,and realizing MI-EEG intention recognition.Eight VR rehabilitation scenes are devised,achieving the communication between MI-BCI and VR scene models.Ten subjects are selected to test the rehabilitation system offline and online,and the test accuracy verifies the feasibility of the system.In future,it is suggested to develop personalized rehabilitation programs and treatment cycles based on the addiction degree.展开更多
Despite the official statistics showing that the number of drug users has been declining, the problem of drug abuse remains serious in Hong Kong. This problem is evidenced by the trend of hidden and prolonged drug abu...Despite the official statistics showing that the number of drug users has been declining, the problem of drug abuse remains serious in Hong Kong. This problem is evidenced by the trend of hidden and prolonged drug abuse. The recovery of drug abusers is an important process, because the misuse of drugs can cause many bio-psycho-social complications. Therefore, 11 Counselling Centres for Psychotropic Substance Abusers (CCPSAs) in different districts in Hong Kong play an important role on those drug abusers [<a href="#ref1">1</a>]. As a core community-based drug rehabilitation service in Hong Kong, studies about CCPSAs are limited. This study uses a descriptive qualitative approach to explore the experience of drug abusers participating in community-based drug rehabilitation services provided by CCPSAs. Five CCPSA users, who utilized the services for more than two months, participated in the semi-structured face-to-face interviews. Data collected were then analysed by thematic analysis, and five themes were generated: 1) receiving supportive counselling service in CCPSAs, 2) revealing variance towards nonmandatory services in CCPSAs, 3) encountering intrapersonal conflicts when participating in CCPSAs, 4) expanding social network through integration in group activities and 5) wishing to be a companion to other drug abusers. Findings of this study provide valuable insights towards services modification and the enhancement of drug rehabilitation and drug abusers’ wellbeing over the collaboration of healthcare workers, services providers and the media. However, this study has some limitations, and it presents suggestions for future research.展开更多
Objective:To explore the feasibility of five tones combined with electro-acupuncture for drug rehabilitation.Methods:Search and screen the literature related to drug rehabilitation with musical electrico-acupuncture i...Objective:To explore the feasibility of five tones combined with electro-acupuncture for drug rehabilitation.Methods:Search and screen the literature related to drug rehabilitation with musical electrico-acupuncture in PubMed,CNKI,CQVIP and Wanfang data to May 2019,and summarize and analyze the literature.Results:Either music therapy or acupuncture therapy has therapeutic responses respectively,and the combined use of both is more effective than the single-use.Conclusion:The combination of five tones and acupuncture is highly feasible for drug rehabilitation.展开更多
背景:眩晕与临床神经科疾病密切相关。当神经元受损或死亡时,可能导致前庭系统的异常,引发眩晕症状,因此有必要探讨并分析临床神经科常见的眩晕相关热点问题。目的:采用文献计量学方法分析临床神经科常见的眩晕相关国内外的研究热点。方...背景:眩晕与临床神经科疾病密切相关。当神经元受损或死亡时,可能导致前庭系统的异常,引发眩晕症状,因此有必要探讨并分析临床神经科常见的眩晕相关热点问题。目的:采用文献计量学方法分析临床神经科常见的眩晕相关国内外的研究热点。方法:由第一作者检索2014-2023年万方数据库和Web of Science核心集数据库,检索临床神经科常见的眩晕治疗的研究相关文献,采用VOSviewer_1.6.19软件对文献的发文量、国家/地区、机构、关键词、共被引文献及高被引文献进行计量学分析,剖析总结该研究领域的研究热点。结果与结论:(1)Web of Science核心集数据库2022年该领域文献发文量174篇最高,万方数据库2020年该领域文献发文量最高133篇;发文量最高的国家前3位分别是美国、德国、中国;国际机构中发文量最高的是德国慕尼黑大学,中国机构中发文量最高的是成都中医药大学。(2)关键词分析结果显示,中国该领域的研究热点疾病主要为梅尼埃病、颈性眩晕、老年性眩晕、良性阵发性位置性眩晕、孤立性眩晕和高血压眩晕,治疗方法包括针刺、康复、药物(天麻素、半夏白术天麻汤)和手法复位。国际上该领域的研究热点疾病主要包括良性阵发性位置性眩晕、新冠病毒病例的前庭性疾病、梅尼埃病、前庭神经鞘瘤、听神经瘤和前庭性偏头痛等,热点治疗方法为传统抗眩晕药物、抗抑郁、抗焦虑治疗和显微手术等。(3)文献共被引分析结果显示,对于以持续性眩晕为主要症状的急性前庭综合征而言,三步骤床边眼动检查(HINTS:头部-冲击-眼球震颤-斜视测试)在急性前庭综合征患者合并脑卒中的诊断方面比早期MRI更敏感,此观点是最被同行认可的前庭综合征脑卒中检测方法;对以阵发性眩晕为主要症状的前庭神经炎患者而言,使用激素治疗更有效。(4)高被引文献分析结果显示,在万方数据库中近10年热点文献中,针刺风池穴、“小醒脑开窍”针刺法改善后循环缺血性眩晕均取得了一定成效,近3年文献发现银杏叶提取物+天麻素、针刺+半夏白术汤、倍他司汀+天麻素、前庭康复训练+Epley耳石复位法,都可以不同程度地改善眩晕症状。而近10年Web of Science核心集数据中的文献并无特色性抗眩晕药物受到关注,大部分以传统抗眩晕药物和显微手术为主,但近3年国际文献中有少数病例报告发现COVID-19感染后可能导致前庭神经炎并出现眩晕症状。(5)眩晕的发生和发展可能与神经元的损伤和再生密切相关,例如,病毒感染、炎症刺激或其他病理因素可能导致神经元损伤或死亡,从而影响前庭系统的功能。目前国内外都发布了眩晕相关的诊治规范指南,国际指南较为推荐前庭康复和物理康复联合治疗眩晕症状,中国指南较为推荐中西医药物、复位及针刺联合治疗,但研究证据级别并不高,因此未来还需要大量的大样本、多中心关于抗眩晕治疗的随机对照试验来验证。展开更多
文摘Nicotinic acetylcholine receptors(nAChRs) are widely distributed ligand gated ion channels throughout the peripheral and central nervous systems of mammals.There are 16 different n AChR subunits,α1-α7,α9,α10 and β1-β4,as well as γ,δ,and ε,which assemble into pentamers to form different nAChR subtypes with distinct pharmacological properties in mammals.Among them α6β2*(*designates other possible subunit),α3β4 and α4β2 nAChR subtypes are potential therapeutic targets for the treatment of addiction.However,various n AChR subtypes are very difficult to pharmacologically distinguish from each other.The α6* n AChRs are expressed by dopaminergic neurons in the central nervous system,which modulate the release of dopamine and are believed to be important in mediating tobacco,morphine,cocaine and ethanol addiction.The α3β4 nAChRs present in the medial habenula with important role in influencing nicotine addiction.Blockage of α3β4 nAChRs in the medial habenula decreased the dose of nicotine that rodents would self-administer.Thus,new antagonists of α6β2* or α3β4 nA ChR subtypes are of considerable interest,which would give strategies to selectively modulate α6β2* or α3β4 nA ChR function.We characterized an α-conotoxin(α-CTx)TxIB with 16 amino acids and an α-CTx TxID with 15 amino acids from Conus textile.The sequence of TxIB is GCCSDPPCRNKHPDLCamide.The sequence of TxID is GCCSHPVCSAMSPIC with C-terminal amidation too.Both peptides with a Ⅰ-Ⅲ and Ⅱ-Ⅳ disulfide con-nectivity were chemically synthesized.The residues between Cys-Ⅱ and Cys-Ⅲ and Cys-Ⅲand Cys-Ⅳ of α-CTx are commonly referred to as loops 1 and 2,respectively.The number of residues in each of these loops is used to further classify the α-CTx.So TxIB is classified as a 4/7α-CTx,whereas the α-CTx TxIB has a 4/6 spacing.Both peptides were tested on rat nAChRs heterologously expressed in Xenopus laevis oocytes.The α-CTx TxIB blocked α6/α3β2β3 nAChR with an IC50 of 28 nmol·L^(-1),which showed little or no block of all the other tested subtypes at concentrations up to 10 μmol·L^(-1).TxIB blocking α6/α3β2β3 nAChR is rapidly reversed after toxin washout.The ability ofα-CTx TxIB to discriminate between α6/α3β2β3 and the other nAChR receptors is unique.There are no small molecules have this selectivity profile.Previously described α-CTx that potently blockα6/α3β2β3 nA ChR s also block either α6/α3β4 nAChRs,α3β2 nAChRs and(or) other nAChRs subtypes.TxID was the very potent α3β4 nAChR antagonists blocking rat α3β4 n AChRs with an IC-50 of 12.5 nmol·L1.However,TxID also blocked the closely related α6/α3β4 with an IC50 of 94 nmol·L^(-1).In fact,the expression profile ofα3β4 nAChRs and α6/α3β4 nAChRs overlap in a variety of tissues.So TxI D can′t differentiate α3β4 nA ChR from α6/α3β4 nA ChR effectively.To distinguish between these two close subtypes,positional-scanning mutagenesis of TxID was performed to identify critical residues that confer potency for α3β4 nAChRs,and hope to obtain more selective mutant to discriminate between these two close subtypes.The effects of 15 analogues and TxID were tested on both α3β4 and α6/α3β4 nAChRs.An analogue,ie [S9 A]TxID had46-fold greater potency for α3β4 versus α6/α3β4 nAChRs,which showed significantly improved selectivity for α3β4 versus α6/α3β4 nAChRs.Both TxI D and [S9 A]TxI D had little activity on other nA ChR subtypes.The three-dimensional solution structures of TxIB,TxID and [S9 A]TxID were determined using NMR spectroscopy.α-CTx TxI B,TxID and [S9 A]TxID represent uniquely selective ligand for probing the structure and function of α6β2*and α3β4 nA ChR s respectively.It is known about20% people have used drugs recreationally resulting in a substance use disorder finally.Therefore,structural insights derived from these ligands may facilitate the development of novel therapeutics for addiction involving α6β2* and α3β4 nA ChR s.
文摘Despite years of interventions in the United States, substance abuse continues to be a major national problem in our society. For individuals affected, it can constitute a major disability and a decrease in quality of life. Current American societal expectations are that individuals who identify!they are involved in substance abuse will go to treatment, eventually recover, get off public assistance straightaway, and return to work. Most rehabilitation professionals also maintain the same expectations. The reality is that efforts of prevention do not appear to diminish the number of people with substance abuse. Traditional treatment appears to have minimal, if any, influence upon the cessation of substance abuse, and traditional vocational rehabilitation practices appear unsuited for the unique problems and types of symptoms experienced by substance abusers. Creative, yet sound, alternatives that combine effective treatment strategies and non-traditional vocational rehabilitation methods need to be exqlored and tested for effectiveness, and applied.
基金supported by Key Research&Development Project of National Science and Technique Ministry of China(No.2018YFC0807405,No.2018YFC1312903)Defense Industrial Technology Development Program(JCKY2019413D002)National Natural Science Foundation of China(No.61976133).
文摘After abusing drugs for long,drug users will experience deteriorated self-control cognitive ability,and poor emotional regulation.This paper designs a closed-loop virtual-reality(VR),motorimagery(MI)rehabilitation training system based on brain-computer interface(BCI)(MI-BCI+VR),aiming to enhance the self-control,cognition,and emotional regulation of drug addicts via personalized rehabilitation schemes.This paper is composed of two parts.In the first part,data of 45 drug addicts(mild:15;moderate:15;and severe:15)is tested with electroencephalogram(EEG)and near-infrared spectroscopy(NIRS)equipment(EEG-NIRS)under the dual-mode,synchronous signal collection paradigm.Using these data sets,a dual-modal signal convolutional neural network(CNN)algorithm is then designed based on decision fusion to detect and classify the addiction degree.In the second part,the MIBCI+VR rehabilitation system is designed,optimizing the Filter Bank Common Spatial Pattern(FBCSP)algorithm used in MI,and realizing MI-EEG intention recognition.Eight VR rehabilitation scenes are devised,achieving the communication between MI-BCI and VR scene models.Ten subjects are selected to test the rehabilitation system offline and online,and the test accuracy verifies the feasibility of the system.In future,it is suggested to develop personalized rehabilitation programs and treatment cycles based on the addiction degree.
文摘Despite the official statistics showing that the number of drug users has been declining, the problem of drug abuse remains serious in Hong Kong. This problem is evidenced by the trend of hidden and prolonged drug abuse. The recovery of drug abusers is an important process, because the misuse of drugs can cause many bio-psycho-social complications. Therefore, 11 Counselling Centres for Psychotropic Substance Abusers (CCPSAs) in different districts in Hong Kong play an important role on those drug abusers [<a href="#ref1">1</a>]. As a core community-based drug rehabilitation service in Hong Kong, studies about CCPSAs are limited. This study uses a descriptive qualitative approach to explore the experience of drug abusers participating in community-based drug rehabilitation services provided by CCPSAs. Five CCPSA users, who utilized the services for more than two months, participated in the semi-structured face-to-face interviews. Data collected were then analysed by thematic analysis, and five themes were generated: 1) receiving supportive counselling service in CCPSAs, 2) revealing variance towards nonmandatory services in CCPSAs, 3) encountering intrapersonal conflicts when participating in CCPSAs, 4) expanding social network through integration in group activities and 5) wishing to be a companion to other drug abusers. Findings of this study provide valuable insights towards services modification and the enhancement of drug rehabilitation and drug abusers’ wellbeing over the collaboration of healthcare workers, services providers and the media. However, this study has some limitations, and it presents suggestions for future research.
基金This study is supported by Shandong University of Traditional Chinese Medicine Research and Training(SRT)Program(No.2019074).
文摘Objective:To explore the feasibility of five tones combined with electro-acupuncture for drug rehabilitation.Methods:Search and screen the literature related to drug rehabilitation with musical electrico-acupuncture in PubMed,CNKI,CQVIP and Wanfang data to May 2019,and summarize and analyze the literature.Results:Either music therapy or acupuncture therapy has therapeutic responses respectively,and the combined use of both is more effective than the single-use.Conclusion:The combination of five tones and acupuncture is highly feasible for drug rehabilitation.
文摘背景:眩晕与临床神经科疾病密切相关。当神经元受损或死亡时,可能导致前庭系统的异常,引发眩晕症状,因此有必要探讨并分析临床神经科常见的眩晕相关热点问题。目的:采用文献计量学方法分析临床神经科常见的眩晕相关国内外的研究热点。方法:由第一作者检索2014-2023年万方数据库和Web of Science核心集数据库,检索临床神经科常见的眩晕治疗的研究相关文献,采用VOSviewer_1.6.19软件对文献的发文量、国家/地区、机构、关键词、共被引文献及高被引文献进行计量学分析,剖析总结该研究领域的研究热点。结果与结论:(1)Web of Science核心集数据库2022年该领域文献发文量174篇最高,万方数据库2020年该领域文献发文量最高133篇;发文量最高的国家前3位分别是美国、德国、中国;国际机构中发文量最高的是德国慕尼黑大学,中国机构中发文量最高的是成都中医药大学。(2)关键词分析结果显示,中国该领域的研究热点疾病主要为梅尼埃病、颈性眩晕、老年性眩晕、良性阵发性位置性眩晕、孤立性眩晕和高血压眩晕,治疗方法包括针刺、康复、药物(天麻素、半夏白术天麻汤)和手法复位。国际上该领域的研究热点疾病主要包括良性阵发性位置性眩晕、新冠病毒病例的前庭性疾病、梅尼埃病、前庭神经鞘瘤、听神经瘤和前庭性偏头痛等,热点治疗方法为传统抗眩晕药物、抗抑郁、抗焦虑治疗和显微手术等。(3)文献共被引分析结果显示,对于以持续性眩晕为主要症状的急性前庭综合征而言,三步骤床边眼动检查(HINTS:头部-冲击-眼球震颤-斜视测试)在急性前庭综合征患者合并脑卒中的诊断方面比早期MRI更敏感,此观点是最被同行认可的前庭综合征脑卒中检测方法;对以阵发性眩晕为主要症状的前庭神经炎患者而言,使用激素治疗更有效。(4)高被引文献分析结果显示,在万方数据库中近10年热点文献中,针刺风池穴、“小醒脑开窍”针刺法改善后循环缺血性眩晕均取得了一定成效,近3年文献发现银杏叶提取物+天麻素、针刺+半夏白术汤、倍他司汀+天麻素、前庭康复训练+Epley耳石复位法,都可以不同程度地改善眩晕症状。而近10年Web of Science核心集数据中的文献并无特色性抗眩晕药物受到关注,大部分以传统抗眩晕药物和显微手术为主,但近3年国际文献中有少数病例报告发现COVID-19感染后可能导致前庭神经炎并出现眩晕症状。(5)眩晕的发生和发展可能与神经元的损伤和再生密切相关,例如,病毒感染、炎症刺激或其他病理因素可能导致神经元损伤或死亡,从而影响前庭系统的功能。目前国内外都发布了眩晕相关的诊治规范指南,国际指南较为推荐前庭康复和物理康复联合治疗眩晕症状,中国指南较为推荐中西医药物、复位及针刺联合治疗,但研究证据级别并不高,因此未来还需要大量的大样本、多中心关于抗眩晕治疗的随机对照试验来验证。