Treatment of Chronic Migraine with OnabotulinumtoxinA: Mode of Action,Efficacy and Safety

Background: Chronic migraine is a common, highly disabling, underdiagnosed and undertreated entity of migraine. It affects 0.9%–2.2% of the general adult population. The present paper overviews the preclinical and clinical data regarding the therapeutic effect of onabotulinumtoxinA in chronic migraineurs. Methods: A literature search was conducted in the database of PubMed up to 20 May 2015 for articles related to the pathomechanism of chronic migraine, the mode of action, and the efficacy, safety and tolerability of onabotulinumtoxinA for the preventive treatment of chronic migraine. Results: The pathomechanism of chronic migraine has not been fully elucidated. The mode of action of onabotulinumtoxinA in the treatment of chronic migraine is suggested to be related to the inhibition of the release of calcitonin gene-related peptide and substance P in the trigeminovascular system. Randomized clinical trials demonstrated that long-term onabotulinumtoxinA fixed-site and fixed-dose (155–195 U) intramuscular injection therapy was effective and well tolerated for the prophylactic treatment of chronic migraine. Conclusions: Chronic migraine is a highly devastating entity of migraine. Its exact pathomechanism is unrevealed. Two-third of chronic migraineurs do not receive proper preventive medication. Recent clinical studies revealed that onabotulinumtoxinA was an efficacious and safe treatment for chronic migraine.     

刺激脉宽对脉宽阈值积的影响

目的研究脉宽阈值积与刺激脉宽之间的关系,深化对电刺激听神经反应的认识。方法首先,根据已有的单根听神经刺激脉宽与阈值之间的表达式和电诱发复合动作电位(electrically evoked compound action potential,ECAP)刺激脉宽与阈值之间的表达式,推导出脉宽阈值积与刺激脉宽之间成线性关系。其次,利用Shepherd发布的实验数据与豚鼠实验数据进行研究,发现脉宽阈值积与脉宽的关系不能用简单的线性关系进行解释,其曲线中存在极值点。结果研究结果表明,由于实验结果中脉宽阈值积与刺激脉宽之间呈现较强的非线性特性,因此由刺激脉宽与阈值之间的关系式推导出的脉宽阈值积与脉宽之间的关系式与实验结果不符。结论需进一步研究刺激脉宽对听神经反应的影响,给出符合实验结果的表达式。     

Supporting government policies to embed and expand rehabilitation in health systems in Europe: A framework for action

Investment in action is vital to confront the challenges associated with chronic diseases and disability facing European health systems. Although relevant policy responses are being increasingly developed, most of them fail to recognize the role of rehabilitation services in achieving public health and social goals. Comprehensive guidance is thus urgently needed to support rehabilitation policy development and expand access to rehabilitation care to meet population needs effectively. This paper describes a framework to guide policy action for rehabilitation in Europe. The framework was developed in collaboration with the European Academy of Rehabilitation Medicine based on a focused literature review and expert consultations. A review in PubMed and grey literature sources identified 458 references and resulted in 135 relevant documents published between 2006 and 2019. Thematic analysis of extracted information helped summarize the findings and develop the draft policy action framework. This was circulated to a wider group of experts and discussed in three workshops in 2018-2019. The framework was revised according to their feedback.The proposed framework contains 48 options for policy action organized in six domains and twelve subdomains that address several areas of health programming. The proposed framework provides a structure to understand the policy terrain related to rehabilitation in Europe and the measures required for translating aspirational political pronouncements into targeted programmatic action and tangible health and social outcomes.     

Prime-boost vaccine strategy against viral infections: Mechanisms and benefits

The essential goal of vaccination is to generate potent and long-term protection against diseases. Among different vaccine modalities, prime-boost vaccine strategies could enhance cellular and also humoral immunity in several animal models. These strategies have been applied for the development of vaccines against important infectious diseases such as HIV, SIV, HCV, HSV, and HBV indicating promising results even in clinical trials. Several factors including selection of antigen, type of vector, delivery route, dose, adjuvant, boosting regimen, the order of vector injection, and the intervals between different vaccinations influence the outcome of prime-boost immunization approaches. The reported data suggest that the prime-boost strategy as a combination of vaccines (i.e., heterologous prime-boost) may be better than a single vaccine for protection against infectious diseases. Indeed, in many cases, heterologous prime-boost can be more immunogenic than homologous prime-boost strategy. This review discusses the recent advances in prime-boost immunization strategies as well as their benefits and mechanisms of action.     

Essential oils of Origanum compactum increase membrane permeability,disturb cell membrane integrity,and suppress quorum-sensing phenotype in bacteria

The aim of this study was to investigate antibacterial activity of Origanum compactum essential oils collected at three phenological stages on Escherichia coli and Bacillus subtilis. The antibacterial activity was evaluated using the agar-well diffusion assay. The MIC and MBC values were determined using the micro-dilution assay. The investigation of the antibacterial action was carried out by the evaluation of the effect of O. compactum essential oils on the antibacterial kinetic growth, the integrity of cell membrane and permeability of the cell membrane. The anti-quorum sensing activity was tested by the inhibition of the biofilm formation. The findings of this study showed that O. compactum essential oil has potent antibacterial activities against E. coli and B. subtilis. The lowest inhibition value against B. subtilis was obtained with O. compactum essential oil at the post-flowering stage (MIC = MBC = 0.0312% (v/v)). The antibacterial mechanisms of O. compactum essential oils are related to the disturbing of the cell membrane integrity and the increasing of the membrane permeability, which leads to the leakage of genetic materials (DNA and RNA). Moreover, O. compactum essential oils inhibited the formation of the biofilms, a phenotype that has been known to be quorum sensing regulated.     

基于网络药理学探讨芪苈强心胶囊治疗充血性心力衰竭的作用机制＊

目的 探讨芪苈强心胶囊（简称：QLQX）用于治疗充血性心力衰竭的活性成分和分子作用机制，为临床使用和深入开发提供依据。方法 采用超高压液相色谱-串联质谱（UPLC-MS/MS）法对QLQX中的主要化学成分进行定性分析，利用数据库查找其相关作用靶标。检索相关网络信息，筛选并确定充血性心力衰竭靶标，运用网络药理学方法，构建化学成分-靶标相互作用网络，检索DIVID数据库，进行生物过程和生物通路分析，获得QLQX的作用靶标和相关生物通路信息。结果 通过UPLC-MS/MS法在QLQX中共检测出103个化学成分，可作用于827个靶标。深入研究表明，QLQX中的98个化学成分组成的活性成分群可与91个相关靶标相互作用。网络分析表明，QLQX的主要活性成分为25个，关键靶标19个，包括STAT3、VEGFA、ADORA1、TP53、IL6、EDN1、SIRT1、ADORA3、ADRB2、HTR2A、MAPK14、MMP9、MTOR、NOS2、NOS3、TNF、PPARG、AGTR1、IL1B。QLQX可通过调节14条心血管疾病相关通路来发挥治疗DHF的作用，其中最主要的生物通路有4条，包括钙生物通路、HIF-1生物通路、TRP通道炎症介质调节和血管平滑肌收缩。结论 本研究从系统和整体的角度阐释了QLQX的作用机制，初步明确了组方的活性成分，可为QLQX物质基础和活性作用机制的深入研究提供依据。     

蒜氨酸抗菌机制研究

目的 检测蒜氨酸最低抑菌浓度（MIC）与最低杀菌浓度（MBC），探讨蒜氨酸体内外抗菌机制。方法 体外微量稀释法检测蒜氨酸MIC和MBC，荧光显微镜观察菌体表面蒜氨酸，探讨蒜氨酸抗菌机制。体内蒜氨酸和青霉素分别治疗金葡菌感染家兔脓肿，检测脓汁标本中细菌存活情况，探讨体内蒜氨酸抗菌作用。结果 蒜氨酸对大肠杆菌、伤寒杆菌、金黄色葡萄球菌、白色葡萄球菌的MIC分别为3.047 μg·mL^-1、6.094 μg·mL^-1、0.386 μg·mL^-1、0.386 μg·mL^-1，蒜氨酸体外无杀菌活性。浓汁标本：死菌率蒜氨酸治疗组显著高于阴性对照组（P < 0.01），与青霉素治疗组无明显差异（P > 0.05）；活菌率蒜氨酸治疗组显著低于阴性对照组（P < 0.01），与青霉素治疗组无明显差异（P > 0.05）。结论 蒜氨酸与菌体蛋白、细菌酶蛋白结合阻断细菌与环境物质交换，抑制细菌生命活动，具有较强的抑菌作用，无杀菌活性；蒜氨酸体内代谢成大蒜素，具有较强杀菌作用。     

基于数据挖掘和网络药理学的血脂异常用药规律和作用机制研究＊

目的 从文献研究的角度出发，运用数据挖掘和网络药理学研究方法，探讨中医药在血脂异常治疗中的组成规律和作用机制研究，为该病的防治提供参考。方法 以1979-2019年“中国知网（CNKI）”、“万方数据”、“维普中文期刊”等数据库中检索到的中药复方治疗血脂异常文献为数据来源，采用中医传承辅助平台对其进行频次分析、关联规则分析和熵聚类方法分析，研究防治血脂异常方药组成规律，并在此基础上采用网络药理学方法，通过KEGG通路和基因本体富集分析，研究高频核心药物的生物信号通路，阐明其作用机制。结果 共计786篇文献符合检索条件，包含314味中药，发现48味高频中药，按照药物使用频次从高到低排序为：活血化瘀药、补虚药（健脾补肾为主）、利水渗湿药、消食化积药；药物性味以温、苦为主，归肝经和脾经最多；进一步关联分析得到高频药对（药组）17个；经过熵聚类分析发现潜在药物组合22个和新方组合11个。应用网络药理学研究方法，对核心药组“山楂、泽泻和决明子”的作用机制进行探索，发现其主要通过作用于包括雌激素受体1（ESR1）、大麻素受体1型（CNR1）、糖皮质激素受体基因（NR3C1）、环氧合酶2（PTGS2/COX2）等潜在靶点，干预三羧酸（TCA）循环、脂质代谢、脂肪酸降解等调节血脂相关的关键信号通路而发挥调节血脂作用。结论 中药治疗血脂异常以健脾补肾治其本，活血化瘀、消痰化积治其标的方法为主，核心药组的作用机制可能是通过干预脂质代谢和基础代谢相关通路发挥治疗作用。     

虎杖苷药理作用及机制研究进展

虎杖苷是从传统中药虎杖中分离出的一种多酚类单体化合物，是虎杖的主要有效成分，具有多种药理活性。近年来，有关虎杖苷药理作用及机制的研究日益增多。现代药理学研究表明，虎杖苷对神经系统，心脑血管系统，呼吸系统等均有保护作用，对肝、肾、肺等器官亦作用明显，其调节血糖血脂的作用对抗动脉粥样硬化效果显著；其抗纤维化的作用对肝、肾保护效果明显。虎杖苷对多种肿瘤细胞均有抑制作用，可抑制肿瘤细胞增殖并诱导肿瘤细胞凋亡。虎杖苷还具有抗炎，保护骨髓，促进创面愈合，抗辐射等药理活性。笔者查阅有关虎杖苷的药理作用文献发现其单个药理作用机制往往受多靶点蛋白、多条通路调控，但大多还未明确其作用靶点，有待深入研究。该文就近5年来有关虎杖苷的药理作用及机制研究进展进行归纳总结，并对其研究现状及未来研究方向提出相关建议，以期拓宽科研者的研究思路，加快明确其发挥药效作用的靶点，为虎杖苷的进一步开发利用提供科学的理论依据。