社区卫生服务机构围绕重大疾病开展 单病种诊疗服务时的患者“临床判别路径”性能分析

在本文之前的研究中,我们绘制了社区围绕重大疾病开展单病种诊疗服务的ROADMAP,又对"患者纳入"环节应遵循何种原则进行了探究,提出"供方角度的覆盖能力、需方角度的可及和诊疗方案上的科学"三原则法,诊疗方案上的科学关键在于明确诊断,其中的核心技术在于,制定科学合理的"临床判别路径"。本文研究的就是"临床判别路径"性能分析与未来开发建议。依旧以"骨质疏松症社区规范化治疗项目"为例,揭示社区目前"临床判别路径"存在的问题,为今后优化改进"临床判别路径"提供依据和参考。     

Cellular and molecular mechanisms in the development of a cleft lip and/or cleft palate; insights from zebrafish (Danio rerio)

Human cleft lip and/or palate (CLP) are immediately recognizable congenital abnormalities of the face. Lip and palate develop from facial primordia through the coordinated activities of ectodermal epithelium and neural crest cells (NCCs) derived from ectomesenchyme tissue. Subtle changes in the regulatory mechanisms of NCC or ectodermal epithelial cells can result in CLP. Genetic and environmental contributions or a combination of both play a significant role in the progression of CLP. Model organisms provide us with a wealth of information in understanding the pathophysiology and genetic etiology of this complex disease. Small teleost, zebrafish (Danio rerio) is one of the popular model in craniofacial developmental biology. The short generation time and large number of optically transparent, easily manipulated embryos increase the value of zebrafish to identify novel candidate genes and gene regulatory networks underlying craniofacial development. In addition, it is widely used to identify the mechanisms of environmental teratogens and in therapeutic drug screening. Here, we discuss the value of zebrafish as a model to understand epithelial and NCC induced ectomesenchymal cell activities during early palate morphogenesis and robustness of the zebrafish in modern research on identifying the genetic and environmental etiological factors of CLP.     

Investigating the inotropic effect of pyruvic acid on the isolated rat heart and its underlying mechanism

Pyruvic acid is important organic chemical intermediates that plays a role in cardiomyocyte pathophysiology and therapy. This study sought to explore the inotropic effects of pyruvic acid on the function of the isolated rat hearts and investigate its underlying mechanism. Pyruvic acid produced a greater negative inotropic effect compared to HCl and sodium pyruvate in a concentration-dependent pattern in the hearts. The role of low dose of pyruvic acid on heart function was regulated by pyruvic acid molecules and high dose pyruvic acid may be influenced by pyruvic acid molecules and pH. K_v channels may be involved in the pyruvic acid-induced negative inotropic effect. Finally, pyruvic acid markedly increased the level of LDH and CK and reduced the level of Ca²⁺Mg²⁺-ATPase and Na⁺K⁺-ATPase. These results suggest that pyruvic acid may modulate cardiac function at physiological or low doses but can cause damage to cardiomyocytes at high doses.     

Patient assessment within the context of healthcare delivery packages: A comparative analysis

BackgroundDue to an increased focus on productivity and cost-effectiveness, many countries across the world have implemented a variety of tools for standardizing diagnostics and treatment. In Denmark, healthcare delivery packages are increasingly used for assessment of patients. A package is a tool for creating coordination, continuity and efficient pathways; each step is pre-booked, and the package has a well-defined content within a predefined category of diseases. The aim of this study was to investigate how assessment processes took place within the context of healthcare delivery packages.MethodsThe study used a constructivist Grounded Theory approach. Ethnographic fieldwork was carried out in three specialized units: a mental health unit and two multiple sclerosis clinics in Southern Denmark, which all used assessment packages. Several types of data were sampled through theoretical sampling. Participant observation was conducted for a total of 126 h. Formal and informal interviews were conducted with 12 healthcare professionals and 13 patients. Furthermore, audio recordings were made of 9 final consultations between physicians and patients; 193 min of recorded consultations all in all. Lastly, the medical records of 13 patients and written information about packages were collected. The comparative, abductive analysis focused on the process of assessment and the work made by all the actors involved. In this paper, we emphasized the work of healthcare professionals.ResultsWe constructed five interrelated categories: 1. “Standardized assessing”, 2. “Flexibility”, which has two sub-categories, 2.1. “Diagnostic options” and 2.2. “Time and organization”, and, finally, 3. “Resisting the frames”. The process of assessment required all participants to perform the predefined work in the specified way at the specified time. Multidisciplinary teamwork was essential for the success of the process. The local organization of the packages influenced the assessment process, most notably the pre-defined scope of relevant diseases targeted by the package. The inflexible frames of the assessment package could cause resistance among clinicians. Moreover, expert knowledge was an important factor for the efficiency of the process. Some types of organizational work processes resulted in many patients being assessed, but without being diagnosed with at package-relevant disease.ConclusionLimiting the grounds for using specialist knowledge in structured health care delivery may affect specialists’ sense of professional autonomy and can result in professionals employing strategies to resist the frames of the packages. Finally, when organizing healthcare delivery packages, it seems important to consider how to make the optimal use of specialist knowledge.     

Could the PI3K canonical pathway be a common link between chronic inflammatory conditions and oral carcinogenesis?

The association between chronic inflammatory disorders and oral carcinogenesis has been both a source of interest and contention. Based upon its central importance in oral carcinogenesis, the finding that the PI3k/Akt/mTOR pathway is activated in oral lichen planus, chronic graft‐versus‐host disease, and chronic oral candidiasis suggests that it may provide a link between benign and malignant oral conditions. Here, we discuss a possible mechanistic rationale that addresses the activation of this important signaling pathway and its downstream events, while correlating it with the carcinogenic potential of chronic oral disorders.     

慢性温和不可预知应激抑郁模型大鼠脑组织1H-NMR代谢组学研究

目的 采用高分辨核磁共振¹H谱（¹H-NMR）代谢组学技术研究慢性温和不可预知应激（CUMS）抑郁大鼠脑组织中代谢物及代谢通路的变化，探讨抑郁症的发病机制。方法 12只雄性SD大鼠随机分为模型组和对照组，采用CUMS对模型组大鼠进行为期4周的造模，进行称体质量、旷场实验和糖水偏爱实验验证模型是否成功，造模结束后收集大鼠脑组织。采用两相提取法（甲醇/氯仿/水）对脑组织进行提取，得到水溶性和脂溶性代谢物。应用¹H-NMR技术结合多元统计和代谢通路分析筛选出与抑郁相关的脑内差异代谢物，并构建其代谢通路。结果 行为学数据显示，与对照组比较，模型组大鼠的体质量、糖水偏爱率、旷场的穿格数和直立次数均显著降低（P<0.05），显示了抑郁状态。在大鼠脑组织的¹H-NMR图谱中共指认出35种内源性代谢产物。脑组织中水溶性和脂溶性代谢物主成分分析（PCA）均显示模型组与对照组分开，与行为学结果一致，表明造模成功；OPLS-DA分析找到9个水溶性差异代谢物和6个脂溶性差异代谢物。就水溶性代谢物而言，与对照组比较，模型组中肌酐、谷氨酰胺、牛磺酸和γ-氨基丁酸含量显著增加（P<0.05、0.01、0.001），丙二醇、谷氨酸、亮氨酸、缬氨酸和赖氨酸含量显著降低（P<0.05、0.01、0.001）。就脂溶性代谢物而言，与对照组比较，模型组-（CH₂） n和-N （Me₃）₃含量显著升高（P<0.05、0.001），胆固醇的C18/19甲基、R-CH₃、CH₂OPO₂-、-CH=CH-含量显著降低（P<0.05、0.01、0.001）。与对照组比较，CUMS造模后5条代谢通路发生显著变化：缬氨酸、亮氨酸和异亮氨酸生物合成，牛磺酸和亚硫磺酸代谢，丙氨酸、天冬氨酸和谷氨酸代谢，糖降解和糖异生通路和丙酮酸代谢。结论 运用¹H-NMR代谢组学技术结合多元统计分析和代谢通路分析，阐明抑郁症的发病机制与能量代谢、氨基酸代谢和神经递质合成等相关。     

Discovery of novel negletein derivatives as potent anticancer agents for acute myeloid leukemia

Baicalin and its aglycone baicalein derived from Scutellaria baicalensis exhibited potent anticancer effects in various types of cancer cell lines. However, the unfavorable pharmaceutical properties became the main obstacle for their potential clinical development. With the aim of development of novel anticancer agents based on the skeleton of baicalin, a series of novel negletein derivatives were designed and synthesized. Among them, compound 8 ( FZU ‐02,006 ) with an N,N‐dimethylamino ethoxyl moiety at the C‐6 position exhibited significant enhanced antiproliferative effect against HL‐60 cells in vitro through regulating multisignaling pathways. These results revealed that compound 8 with the improved aqueous solubility (as HCl salt, >1 mg/ml) and enhanced antileukemia potency might serve as a promising lead for further development.