基于泛素-蛋白酶体途径探讨远志散“益气化痰开窍”治疗阿尔茨海默病的科学内涵＊

阿尔茨海默病（Alzheimer′s disease，AD）是一种常见的神经系统退行性疾病，磷酸化Tau蛋白异常聚集所形成的神经纤维缠结（Neurofibrillary tangles，NFTs）是AD的典型病理特征，直接参与AD的发生发展。因此，AD的治疗可从调节磷酸化Tau蛋白异常聚集入手。中医学认为“痰浊”是导致AD发生的重要病理因素之一，“正气亏虚，痰浊蒙窍”是AD的核心病机。“痰浊”与磷酸化Tau蛋白异常聚集密切相关，磷酸化Tau蛋白异常聚集可归属“痰浊”的范畴。化痰开窍与减少磷酸化Tau蛋白聚集在AD的治疗中有不谋而合之处。泛素-蛋白酶体系统（Ubiquitin-proteasome system，UPS）是细胞内蛋白降解的主要途径，参与AD进程中磷酸化Tau蛋白的降解。UPS功能受损是磷酸化Tau蛋白异常聚集和AD发生的重要原因。本文试图从中医“痰”的视角认识磷酸化Tau蛋白异常聚集，探讨中医“痰浊”与现代医学磷酸化Tau蛋白异常聚集的相关性，并从UPS视角提出益气化痰开窍法治疗AD的作用机制假说，推测UPS可能是远志散益气化痰开窍干预AD的主要途径，精确调控UPS可能是未来研究防治AD的新视角，为科学阐释通过调控UPS蛋白降解途径治疗AD的作用机制提供新思路。     

Sláintecare implementation status in 2020: Limited progress with entitlement expansion

The Sláintecare report developed by political consensus sets out a ten year plan for achieving Universal Health Care (UHC) in Ireland. This paper evaluates the design and progress of the report to mid 2020, but with some reflection on the new COVID 19 era, particularly as it relates to the expansion of entitlements to achieve UHC. The authors explore how close Sláintecare is to the UHC ideal. They also review the phased strategy of implementation in Sláintecare that utilises a systems-thinking approach with interlinkages between entitlements, funding, capacity and implementation. Finally the authors review the Sláintecare milestones against the reality of implementation since the publication of the report in 2017, cognisant of government policy and practice. Some of the initial assumptions around the context of Sláintecare were not realised and there has been limited progress made toward expanding entitlements, and certainly short of the original plan. Nevertheless there have been positive developments in that there is evidence that Government’s Implementation Strategy and Action Plans are focussing on reforming a complex adaptive system rather than implementing a blueprint with such initiatives as integrated care pilots and citizen engagement. The authors find that this may help the system change but it risks losing some of the essential elements of entitlement expansion in favour of organisational change.     

A systems approach to forensic science applied in the military domain

Forensic science is undertaken in support of law enforcement investigations, criminal justice prosecutions, intelligence, and military objectives. There are different forensic operating models to meet these various objectives and no unified approach to forensic science has been described. There are common challenges in the military domain, which impacts the delivery of forensic science, including: different terminology between organizations, complex operating environments, operating siloes, inward-looking military structures, quality management, and resource constraints. One solution to these challenges is to apply modern organizational theory to military-focused forensic science. Organizational theory is the study of organizations in a structural sense, including objectives, people, structure and management. The modern organizational theory systems approach describes how organizations should be viewed as systems within larger systems. In the work presented in this paper, a systems approach has been applied, for the first time, to military forensic exploitation to address the common issues faced by military organizations. The advantages of applying a systems approach to military forensic exploitation are that it is applicable across forensic science organizations, it is flexible and scalable to meet the changing external environment, and it articulates the redundancies in the system to help address system failures.     

Circulating lectin pathway proteins do not predict short-term cardiac outcomes after myocardial infarction

Despite improvements in treatment, coronary artery disease is still responsible for one-third of all deaths globally, due predominantly to myocardial infarction (MI) and stroke. There is an important potential in developing new strategies for treatment of patients with these conditions. Inflammation, and in particular the actions of the complement system, has emerged as part of the pathogenesis in reperfusion injury in patients with MI. To further qualify this, we examined the association between the plasma levels of lectin pathway proteins and myocardial end-points, left ventricular ejection fraction (LVEF) and infarct size in a cohort of patients with ST-elevation myocardial infarction (STEMI). A blood sample was drawn the day after percutaneous coronary intervention from 73 patients with STEMI. The primary end-points, LVEF and infarct size, were measured with magnetic resonance imaging 6–9 days after the infarct. Complement pattern-recognition molecules of the lectin pathway (mannan-binding lectin, H-ficolin, L-ficolin and M-ficolin) were analysed along with soluble membrane attack complex (sMAC) and C-reactive protein (CRP) in plasma with immunofluorometric assays <50%. CRP correlated negatively with LVEF, regression coefficient = –0·17 (P = 0·01). None of the lectin pathway proteins correlated to LVEF or infarct size, nor did soluble membrane attack complex (sMAC). There were no differences in plasma levels of these complement proteins when comparing patients with ejection fraction <50% to patients with ejection fraction <50%. Pattern-recognition molecules of the lectin pathway and sMAC do not predict short-term cardiac outcomes after MI.     

Cavum velum interpositum cysts in normal and anomalous fetuses in second trimester of pregnancy: Comparison of its size and prevalence

ObjectiveCavum veli interpositi (CVI) is a potential space below the splenium of corpus callosum and sometimes presents as a cyst.Materials and methodsIn this prospective cross-sectional study, 360 fetuses with normal second trimester scan and 152 s trimester fetuses with structural abnormalities were included.ResultsThe CVI cysts were more common in fetuses with brain anomaly compared to normal fetuses and fetuses with extra-central nervous system (CNS) anomalies (23% vs 18.3% and 18% respectively; p value < 0.01). The mean size of cysts in normal fetuses, fetuses with extra-CNS anomalies and fetuses with brain abnormalities was 4.6 mm, 5.8 mm and 9.2 mm respectively. There was a significant difference between cysts size in normal fetuses and fetuses with brain anomalies (p value < 0.01) and the cut-point was 7.1 mm.ConclusionThe prevalence of CVI cysts is more in fetuses with brain anomaly. Fetuses with a cyst size >7.1 mm need a more detailed brain examination.     

知信行评价体系对初产妇产褥期母婴照护能力的影响

目的 构建初产妇知信行评价体系并探讨其对初产妇产褥期母婴照护能力的影响。 方法 选取2017年2月-2018年2月在我院产科分娩的120例初产妇为研究对象,采用随机数字表法将其分成研究组和对照组,每组各60例;对照组采取常规护理和健康宣教,研究组应用知信行评价体系,比较2组产褥期健康知识水平及母婴照护能力。 结果 干预4周后,研究组产褥期一般知识、新生儿护理知识及母乳喂养知识水平均高于对照组(t=8.373,P<0.001; t=9.495,P<0.001; t=13.946,P<0.001);产褥期母婴照护行为能力高于对照组。 结论 应用知信行评价体系对初产妇开展针对性干预,有助于提升产妇的康复知识水平及新生儿照护知识和技能,保障母婴安全,具有重要社会价值和临床意义。     

载三氧化二砷脑胶质瘤靶向纳米递药系统i RGD/TGN-PEG-PAMAM/ATO的构建及体外研究

目的以树状大分子为载体材料并修饰血脑屏障(blood brain barrier,BBB)靶向短肽TGN和肿瘤靶向短肽i RGD构建脑胶质瘤靶向递药系统(i RGD/TGN-PEG-PAMAM/ATO),旨在解决三氧化二砷(arsenictrioxide,As2O3,ATO)在治疗脑胶质瘤过程中分布缺乏特异性、透BBB难等问题,使其具有更好抗脑胶质瘤作用。方法核磁共振图谱(1H-NMR)、透射电子显微镜(TEM)等考察载体的理化性质;电感耦合等离子发射光谱(ICP)、透析袋法分析其包封率及体外释放情况;通过激光共聚焦及流式细胞仪分析i RGD、TGN对细胞摄取的影响;MTT法考察纳米载体对脑微血管内皮细胞(HBMEC)和脑胶质瘤U87细胞的毒性及BBB模型中递药系统抑制U87细胞生长的情况。结果成功合成了i RGD/TGN-PEG-PAMAM载体,其形态规整,大小均匀,测得其粒径(24.87±0.84)nm,电位(17.26±1.64)m V;该载体对HBMEC和U87细胞均具有较小的毒性;递药系统i RGD/TGN-PEG-PAMAM/ATO的包封率为(71.92±1.17)%,体外释放表明ATO经载体包载后呈现一种缓慢释放趋势,且在酸性条件下更有利于ATO的释放;细胞摄取结果提示iRGD/TGN的修饰有利于U87细胞对递药系统的摄取;体外跨BBB抑制U87细胞生长实验结果表明,i RGD/TGN-PEG-PAMAM/ATO组具有更好的跨BBB抑制U87细胞生长效果。结论 i RGD/TGN-PEG-PAMAM/ATO脑胶质瘤靶向递药系统具有较好的体外跨BBB抑制U87细胞生长的效果,为脑胶质瘤治疗提供了新的策略。