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Myla Lôbo de Souza Lucas Amadeu Gonzaga da Costa Emerson de Oliveira Silva André Luiz Moreira Domingues de Sousa Widson Michael dos Santos Pedro José Rolim Neto 《Drug development research》2020,81(7):803-814
Considered prevalent in many countries on five continents, especially in low-income regions, leishmaniasis is a neglected tropical disease classified by World Health Organization as one of the diseases for which the development of new treatments is a priority. It is an infectious disease caused by protozoa of the genus Leishmania, whose species may cause different clinical manifestations, such as cutaneous and visceral leishmaniasis (VL). Treatment is exclusively by drug therapy, as it has not been possible to develop vaccines yet. Currently available drugs are not fully effective in all cases; they have parenteral administration and exhibit a number of serious and very common adverse effects. The only oral drug available is expensive and it is not available in many endemic countries. Injectable administration is the main problem of treatments, since it requires patients to go to health centers, hospitalization and professional administration, which are conditions that are not adapted to the reality of the poverty conditions of patients with the disease. In this context, the development of an oral medicine has become a focus as it may solve many of these issues. Based on this scenario, this review aimed to investigate which therapeutic alternatives have been studied for the development of oral drugs directed to the treatment of human VL. 相似文献
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Acetylcholinesterase is a potent enzyme that regulates neurotransmission by rapidly hydrolyzing the neurotransmitter acetylcholine in synapses of the nervous system. As drug target of anti‐AD, it has catalytic and peripheral anionic sites. However, the regulation relation between these two sites is unclear. Therefore, we constructed dynamics fluctuation network based on all‐atom molecular dynamics simulations to reveal the regulation mechanism. The results suggest that the correlation network in double‐site system (hAChE/TZ5) is distinctly different from that in the free state and single‐site systems (hAChE/huprine and hAChE/1YL). The community network analysis indicates that the information freely transfers from the peripheral anionic site to the catalytic active site in hAChE/TZ5. Furthermore, the binding free energy between the inhibitor and hAChE for hAChE/TZ5 is significantly lower than of either hAChE/huprine or hAChE/1YL. Thus, a hypothesis of ‘positive cooperative regulation’ is proposed for the regulation of double binding sites and further confirmed by the weakening and mutation community analyses. Finally, one possible cooperative regulation pathway of W86‐TZ5‐W286 was identified based on the shortest path algorithm and was confirmed by the network perturbation analysis. Interestingly, the regulation pathway for single‐site systems is significantly different from that of dual‐site system. The process targeting on the shortest pathway can better regulate the hydrolyzing the neurotransmitter acetylcholine and significantly inhibit the aggregation of Aβ amyloid. 相似文献
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粤港澳大湾区(大湾区)同时具有三种不同体制下的公共卫生体系,在我国公共卫生体系建设中具有重要地位。进一步加强大湾区公共卫生体系建设对我国未来公共卫生体系优化和升级具有重要借鉴作用。本文基于中国工程院重大战略研究与咨询项目“我国现代公共卫生体系及能力建设战略研究”,深入分析大湾区公共卫生体系建设的现状和存在的问题,提出要健全和创新大湾区公共卫生风险协同防控、资源协同和共研共享、信息共享和交流、人才培养和队伍建设等机制,全面提升大湾区公共卫生体系的能力,助推健康中国建设。 相似文献
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王红莲 《贵阳中医学院学报》2016,(5):83-85
本文针对中医汉英翻译的困境,分析其原因主要为翻译人才匮乏、翻译质量良莠不齐、翻译速度缓慢,提出中医汉英合作翻译可以通过整合现有资源解决上述问题,并就中医著作汉英合作翻译团队的构建模式提出一些建议。 相似文献
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在医学史课程教学改革中应用问题引导式数学(Problem-Based Learning,PBL),以专题重新组织教材内容,以问题引导教学,开展师生互换型教学和学生参与体验型教学,教考分离,旨在提高课程教学水平,使其从知识性课程提升为知识与思辨相结合的课程,使学生通过医学史课程知史、思史、明史。 相似文献
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目的 比较某三甲医院参加城镇居民医保(简称居民医保)和参加新型农村合作医疗(简称新农合)住院患者疾病构成及住院医疗费用,分析其现状和影响因素。方法 选择该医院2013年所有住院的城乡居民患者的病例资料,比较居民医保和新农合住院患者的疾病构成、科室分布、住院费用构成、医疗费用。结果 居民医保和新农合住院患者的疾病类型和科室分布各有特点;新农合患者平均住院总医疗费13855.25元、平均统筹支付费用6086.17元及平均个人支付费用7769.08元均较居民医保的11676.42元、5394.95元及6216.06元要高,差异均有统计学意义(P<0.05);药费、材料及其他费用均占两类患者总住院费用的70%。结论 居民医保患者住院费用较新农合患者低。降低住院费用要控制药费、材料和其他费用尤其高值耗材使用,完善城乡统一医疗保障、实施分级诊疗等综合措施。 相似文献