针刺治疗药物成瘾的研究进展

近35年来,针刺治疗物质依赖的研究引起了越来越多的国内外相关学者和临床医生的关注.该领域内的研究进展大致可以分为三个主要阶段:(一)香港的温祥来医师于1973年首次报道,采用电针(两对体针和一对耳针连接电刺激)可以减轻阿片成瘾者的戒断症状(身体依赖);(二)纽约M.Smith医师(1985)领导的美国国家针刺脱毒协会(NADA)确定,仅采用耳针,不加电刺激,治疗药物依赖(身体依赖);(三)北京大学神经科学研究所(PKU NRI)韩济生教授及其同事(1992-)用特定频率的躯体穴位电刺激缓解海洛因成瘾者的戒断症状(身体依赖),并可抑制患者脱毒后对毒品的心理渴求(精神依赖)以预防复吸.本文将综述针刺干预药物依赖的临床疗效、实验研究及初步作用机制.     

靶向神经小胶质细胞的戒毒治疗策略

鸦片用于镇痛治疗有千余年历史, 其滥用导致药物成瘾, 带来严重的社会和医学问题。关于鸦片等精神活性物质的研究主要围绕 神经元,当前的戒毒药物作用于神经元的阿片受体或离子通道受体,然而其戒毒效果非常有限。神经元不是中枢神经系统中调节神经信号 转导的唯一组分,神经小胶质细胞占中枢神经系统的 10%~15%,然而其作用和功能在很长一段时间被忽视。鸦片、可卡因、冰毒及其他 精神活性物质激活 Toll 样受体 4 (TLR4),活化小胶质细胞,产生大量炎症因子,从而调节奖赏信号通路,增加神经元的兴奋性,导致药物 依赖和成瘾,因而 TLR4 是开发新型戒毒药物的靶点。综述药物成瘾的小胶质细胞分子机制以及靶向小胶质细胞的治疗药物成瘾的药物发现。     

11例吸毒死亡法医学鉴定回顾性研究分析

目的：奉文时吸毒及体内藏毒死亡法医学尸体检验与鉴定中的相关问题进行回顾性研究。强调该类法医学鉴定中应该特别注意的问题。方法：将2003年初至2006年底昆明市及周边地区11例吸毒死亡法医学鏊定案例进行回顾性研究分析,同时对毒品作用机理、死亡原因、吸毒流行病学特征、吸毒死亡者的病理组织学特征、体内藏毒死亡特征、吸毒死亡法医学尸体检验与鉴定应注意的问题等进行论述。结果：吸毒或体内藏毒死亡的法医学尸体检验与鉴定具有一定的形态学特征,吸毒死亡法医学检验与鉴定工作具有相当的难度。结论：吸毒及体内藏毒死亡法医学尸体检验与鉴定,必须在充分进行尸体剖验的基础上并结合毒物检验、现场勘验、案情调查、临床表现和死亡经过等资料进行充分的案情研究并排除其他原因致死,才能得出正确的结论。     

Convergence and Divergence in the Etiology of Myelin Impairment in Psychiatric Disorders and Drug Addiction

Impairment of oligodendroglia (OL)-dependent myelination in the central nervous system (CNS) is a remarkable parallel recently identified in major psychiatric disorders and chronic drug abuse. Neuroimaging and neuropathological studies revealed myelin defects and microarray-profiling analysis demonstrated aberrant expression of myelin-related genes in schizophrenia (SZ), bipolar disorder (BD), major depressive disorder (MDD) and cocaine addiction. However, the etiology underlying myelin impairment in these clinically distinct subjects remains elusive. This article reviews myelin impairment in line with dopaminergic dysfunction, a prime neuropathophysiological trait shared in psychiatric disorders and drug abuse, as well as the genetic and epigenetic alterations associated with these diseases. The current findings support the hypothesis that aberrant dopamine (DA) action on OLs is a common pathologic mechanism for myelin impairment in the aforementioned mental morbidities, whereas inherited genetic variations that specifically affect OL development and myelinogenesis may further increase myelin vulnerability in psychiatric disorders. Importantly, OL defect is not only a pathological consequence but also a causative factor for dopaminergic dysfunction. Hence, myelin impairment is a key factor in the pathogenic loop of psychiatric diseases and drug addiction. Special issue article in honor of Dr. Ji-Sheng Han.     

miRNAs与药物成瘾

药物成瘾是一种慢性复发性脑病,主要表现为不可控制的对药物持续渴求和戒断后的高复吸。目前观点认为,成瘾是中脑腹侧被盖（ventral tegmental area,VTA）到伏隔核（nucleus accumbens,NAc）脑区多巴胺能奖赏通路中神经可塑性发生改变而导致的一种神经精神疾病。基因表达变化在神经可塑性中发挥着重要作用,但成瘾药物导致相关脑区结构和功能改变的机制还不甚清楚。微小RNAs（microRNAs,miRNAs）是一类非编码RNA,主要通过结合靶基因mRNA 3′非翻译区（3′untranslated region,3′UTR）,在转录后水平阻断其翻译成蛋白质或触发其不稳定而降解。越来越多的研究证实,miRNAs参与调节成瘾相关神经可塑性的变化。本文较系统地阐述miRNAs在药物成瘾中的作用研究进展,将为深入阐明药物成瘾的机制以及药物成瘾临床有效干预和诊治提供新思路。     

单细胞转录组测序在药物成瘾研究中的应用

药物成瘾是复杂的中枢神经系统疾病，相关基础与临床研究均证实药物成瘾的神经机制及神经环路在成瘾行为形成的不同阶段逐渐发生改变。利用全基因组关联研究、全基因组测序、全外显子测序或高通量转录组测序等技术的组学研究对包括药物成瘾在内的精神疾病遗传的脆弱性进行了深入研究。上述单核苷酸多态性检测技术或测序技术主要预测疾病的遗传风险位点。然而，许多中枢神经系统疾病的发生与环境因素密切相关，而且在疾病发展的不同阶段，相关基因的表达存在脑区特异性的细胞异质性信息。因此，传统研究对发病机制的解释存在一定的局限性。单细胞转录组测序技术是针对单个细胞进行转录水平的测定，规避了传统测序对细胞群体平均转录水平检测的缺点，可以定量描述细胞异质性。近年来，单细胞转录测序技术在神经精神科学研究中的应用逐渐受到关注，本文总结了该技术在神经科学研究中的重要应用，并以药物成瘾为例，重点阐述说明其在中枢神经系统疾病中的应用价值。     

Recent Development in Studies of Tetrahydroprotoberberines: Mechanism in Antinociception and Drug Addiction

The tetrahydroprotoberberines (THPBs) are compounds isolated from Chinese herbs that possess a unique pharmacological profile as D2 dopamine receptor antagonists and D1 receptor agonists. l-Tetrahydropalmatine (l-THP) and l-stepholidine (SPD), members of the THPB family, were shown to have potential clinical use in the treatment of pain. However, their mechanism of action is not clear. In the past decades, Chinese scientists have made a great deal of effort to explore the mechanisms by which the THPBs and its analogues elicit antinociception and their potential utility in treating drug abuse. It is now clear that the antinociception produced by l-THP is related to inhibition of D₂ dopamine receptors. The present review focuses on the recent progress made in understanding the mechanisms of l-THP- and l-SPD-mediated antinociception and the sequel of drug addiction.     

Addiction,Heroin‐Assisted Treatment and the Idea of Abstinence: A reply to Henden

In our previous article on the question whether heroin addicts are able to give informed consent voluntarily to research on heroin‐assisted treatment, we criticized the ongoing bioethical discussion of a flawed conceptualization of heroin addicts' options. As a participant in this discussion, Edmund Henden defends the conceptualization as sufficient for determining whether heroin addicts are able to give informed consent to the research on heroin‐assisted treatment voluntarily. This discussion on research on heroin‐assisted treatment seems to go astray in several respects. In his reply to our article Henden maintains some of the biases, such as the necessity of abstinence in recovery, that seem to prevail in addiction research on a more general level as well. These biases run the danger of having implausible ethical implications on stakeholders in addiction research and treatment. In our reply to him, we will further clarify and discuss the importance of describing the relevant issues in plausible terms that do justice to the realities of the cases of informed consent in research on heroin‐assisted treatment and also raise a wider issue of the ethics of wording as well as of the narrow scope, or ‘tunnel vision’, in addiction research as currently conducted.     

The Neuroscience Research Institute at Peking University: A Place for the Solution of Pain and Drug Abuse

Neuroscience research in China has undergone rapid expansion since 1980. The Neuroscience Research Institute of Peking University, one of the most active neuroscience research groups in China, was founded in 1987. Currently, the institute is overseeing four research areas, i.e., (1) pain and analgesia, (2) drug abuse and acupuncture treatment for drug addiction, (3) the mechanism of neurological degenerative disorders, and (4) the role of neuroglia in central nervous system injury. The institute is simultaneously investigating both theoretical and clinical studies. Acupuncture remains the core of research, while pain and drug abuse form the two disciplines.     

改良颈静脉置管术在自身给药成瘾模型优化中的作用研究

目的:探讨技术和方法的改进,提高动物颈静脉置管以及药物成瘾自身给药模型构建的成功率,为成瘾研究提供更稳定和高效的建模方法。方法:对建立自身给药模型的传统颈静脉置管术进行改良,选取成年雄性SD大鼠60只,按照随机数字表法分为传统手术组(n=30)和改良手术组(n=30),分别完成颈静脉置管术后,按照随机数字表法,再将每组分为对照训练组(n=15)和成瘾训练组(n=15),构建大鼠自身给药模型,观察两组大鼠自身给药模型成功率。结果:大鼠的颈静脉置管手术可能出现的手术并发症主要包括堵管、漏管、感染甚至死亡等,最主要的并发症是漏管,占比最大。颈静脉置管传统手术组手术成功率为43.33%±3.333,颈静脉置管改良手术组手术成功率为90.00%±3.333,显著高于颈静脉置管传统手术组(P0.05)。两组成瘾训练组有效鼻触次数均分别明显高于其对照训练组(P0.05)。结论:大鼠改良后的颈静脉置管手术效果明显优于传统手术,颈静脉置管手术成功率明显提高。     

A Meta-Analysis of Acupuncture Combined with Opioid Receptor Agonists for Treatment of Opiate-Withdrawal Symptoms

This review extends a prior meta-analysis of acupuncture’s utility for treating opioid detoxification, addressing the efficacy of acupuncture when combined with allopathic therapies. Both English and Chinese databases were searched for randomized trials comparing acupuncture combined with opioid agonist treatment versus opioid agonists alone for treating symptoms of opioid withdrawal. The methodological quality of each study was assessed with Jadad’s scale (1–2 = low; 3–5 = high). Meta-analysis was performed with fixed- or random-effect models in RevMan software; the outcome measures assessed were withdrawal-symptoms score, relapse rate, side effects, and medication dosage. Withdrawal-symptom scores were lower in combined treatment trials than in agonist-alone trials on withdrawal days 1, 7, 9, and 10. Combined treatment also produced lower reported rates of side effects and appeared to lower the required dose of opioid agonist. There was no significant difference on relapse rate after 6 months. This meta-analysis suggests that acupuncture combined with opioid agonists can effectively be used to manage the withdrawal symptoms. One limitation of this meta-analysis is the poor quality of the methodology of some included trials. High-quality studies are needed to confirm findings regarding the side effects and medication dosage.     

肌骨超声联合剪切波弹性成像对针刺阿是穴治疗梨状肌综合征疗效的评估价值

摘要 目的：探讨肌骨超声（MSKUS）联合剪切波弹性成像技术（SWE）在评估针刺阿是穴治疗梨状肌综合征（PS）疗效中的应用价值。方法：选取临床诊断单侧急性起病的PS患者40例,以患侧为治疗组,健侧为空白对照组,患侧采用阿是穴针刺,辅以梨综五针法行针刺治疗。健侧及患侧治疗前、治疗1疗程、治疗2疗程后均运用二维MSKUS及SWE技术获取梨状肌厚度、梨状肌出口处坐骨神经厚径、梨状肌弹性模量值及弹性评分,同时于上述各个时点记录患侧视觉模拟评分（VAS）及临床症状积分,对上述超声影像学指标、VAS评分、临床症状积分进行分析比较,并计算治疗有效率。结果：针刺治疗前,患侧梨状肌厚度、梨状肌出口处坐骨神经厚径、梨状肌杨氏模量值及梨状肌弹性评分与健侧相比,差异均具有统计学意义（P＜0.05）。患侧治疗2个疗程后,梨状肌出口处坐骨神经厚径、梨状肌杨氏模量值与健侧相比,差异有统计学意义（P＜0.05）。患侧于治疗前、治疗1疗程、治疗2疗程后,上述超声影像学指标均好转,且呈逐渐下降趋势,且各时间节点两两相比较,差异均具有统计学意义（P＜0.05）。针刺治疗过程中,PS患者的疼痛症状不断改善,临床症状积分与VAS评分呈不断下降趋势,整体比较差异有统计学意义（P＜0.05）,且于任意时点两两比较,差异均具有统计学意义（P＜0.05）。治疗2个疗程后,PS患者治疗总有效率达92.50%。结论：针刺阿是穴治疗对急性期PS患者的临床疗效显著,MSKUS联合SWE技术能够为针刺阿是穴治疗的疗效评价提供科学客观的超声定量依据,具有良好的应用价值及临床意义。     

针刺测力仪及脉象仪在针灸治疗中的应用

目的设计一套在体实时监测针刺针体受力情况和同步观察针刺前后脉象的系统。方法利用设计的针刺测力仪及脉象仪采集针刺时针体受力的力学信号及人体脉象的信号并将这些信号传换成计算机能识别的信号,把脉象的信号与针刺信号相对应运用软件进行分析整理。结果针刺前后脉象有比较明显的变化。结论利用脉象仪和针刺测力仪能够观察针刺前后脉象的变化,将为针刺选穴,配穴及疗效监测提供有效的手段。     

Focus: Addiction: Video Game Use in the Treatment of Amblyopia: Weighing the Risks of Addiction

Video games have surged in popularity due to their entertainment factor and, with recent innovation, their use in health care. This review explores the dual facets of video games in treating vision impairment in amblyopia as well as their potential for overuse and addiction. Specifically, this review examines video game addiction from a biopsychosocial perspective and relates the addictive qualities of video games with their use as a therapeutic treatment for amblyopia. Current literature supports both the identification of video game addiction as a disease, as well as the therapeutic potential of video games in clinical trials. We show the need for clinicians to be aware of the dangers associated with video game overuse and the need for future studies to examine the risks associated with their health care benefits.     

胃炎的针灸治疗近况及作用机理探讨

本文阐述了关于针灸治疗胃炎的研究概况,从治疗方法和机制两方面进行归纳总结,为今后的进一步研究提供参考依据。针灸治疗胃炎的方法比较多,如毫针刺法、艾灸、温针法、穴位注射等;研究认为针灸治疗胃炎是通过调节神经通路,提高免疫功能,调节胃肠激素和胃分泌功能,调节运动功能和保护胃黏膜等方面来实现的。目前针灸治疗胃炎的疗效确切,值得推广。     

针刺加艾灸结合疗法对类风湿性关节炎的近远期疗效

目的:探讨针刺加艾灸配合治疗类风湿关节炎的近远期疗效。方法:选择我院2013年4月~2014年1月门诊病房治疗的74例类风湿关节炎患者为研究对象,以随机数字表法分组,观察组37例,对照组37例,对照组实施西医疗法治疗,观察组在对照组基础上采取针刺配合艾灸治疗,对两组患者治疗后效果进行分析。结果:观察组治疗后1个月有效率为89.19%,对照组为70.27%,差异显著(P0.05);治疗后1年疗效显示,对照组有效率为59.46%,观察组94.59%,两组差异存在统计学意义(P0.05);治疗前两组患者晨僵时间、关节压痛指数、关节肿胀指数、关节功能评分、握力等指标水平无明显差异,治疗后两组患者均有变化,观察组治疗后以上指标水平明显优于对照组,两组差异有统计学意义(P0.05);治疗前血沉(ESR)、C-反应蛋白(CRP)与类风湿因子(RF)指标无明显差异,治疗后均有改善,但是观察组治疗后各项指标水平明显低于对照组,差异有统计学意义(P0.05);对照组治疗后不良反应发生率为16.22%,观察组为2.70%,两组差异有统计学意义(P0.05)。结论:艾灸配合针刺治疗类风湿关节炎可取得较好近远期疗效,提高了患者关节功能及握力,有效缓解晨僵、关节疼痛、肿胀等症状。     

内感受对成瘾行为的诱导及其岛叶的调控机制

内感受是机体对自身生理状态的感觉.近年来,越来越多的研究证据表明,内感受可以调控成瘾行为,岛叶是其发挥作用的重要神经基础之一.目前,对岛叶作用机制的研究正受到高度重视.本文从岛叶的基本结构和功能出发,结合近几年来岛叶调控成瘾行为、行为抑制以及情感决策的重要发现,讨论岛叶在成瘾发生及发展过程中的可能作用及其机制,并根据已有的实验证据,试图提出较为合理的研究展望,以推动相关神经环路和神经化学机制研究的深入.