基于系统药理学分析野生真菌硬皮马勃治疗肿瘤多层次作用机制＊

目的 鉴定当地民间应用普遍的野生药用真菌，并探讨其治疗肿瘤的作用机制。方法 采用形态学和分子生物学方法对一株采自定陶仿山野生药用真菌进行鉴定，确定为硬皮马勃。通过文献检索收集硬皮马勃化学成分，利用PubChem软件和TCMSP、GCS数据库得到化学成分结构信息及其药用动力学参数和相关靶点分析，通过SysDT和WES系统鉴定潜在化学成分靶点，利用CTD数据库获得靶点功能，将潜在化合物和肿瘤相关靶点导入Cytoscape3.8.0软件构建分子-靶标网络。应用DAVID数据库对肿瘤相关靶点进行GO和KEGG富集分析，揭示有关活性成分靶点所涉及的生物学过程和通路，将肿瘤相关靶点和通路导入Cytoscape3.8.0软件构建靶点-通路网络。结果 从文献中获得硬皮马勃的化学成分59个，通过ADME计算系统筛选出5个潜在活性的化合物即活性成分，预测到38个靶点，其中与肿瘤相关靶点16个。这些活性成分主要通过Toll-like receptor、PI3K-AKT、MAPK和NF-kappa B等通路参与免疫应答，抑制肿瘤细胞生长、增殖，促进其凋亡。结论 表明硬皮马勃治疗肿瘤具有多靶点、多途径协同作用的特点，并通过多层次效应达到治疗肿瘤的效果。本研究为更好理解硬皮马勃作用肿瘤的机制和肿瘤药物开发提供理论依据。     

The usefulness of measuring n-butyric acid concentration as a new indicator of blood decomposition in forensic autopsy

In forensic medicine, although various alcohols have been reported as indicators of decomposition in collected blood, no studies have examined short-chain fatty acids as indicators. In this study, the blood n-butyric acid concentration was quantified, and the association between n-butyric acid and decomposition was investigated to determine whether the detection of n-butyric acid could be a new indicator of decomposition. Among the forensic autopsies performed from 2016 to 2018 in our laboratory, the cases were divided into decomposed (n = 20) and non-decomposed (n = 20) groups based on macroscopic findings. Blood samples collected at the time of autopsy were derivatized with 3-nitrophenylhydrazine hydrochloride after solid-phase extraction. The n-butyric acid concentration was measured using liquid chromatography–tandem mass spectrometry. In addition, ethanol and n-propanol were measured using a gas chromatography-flame ionization detector. There was a significant difference (p < 0.01) in the concentrations of n-butyric acid between the decomposed and non-decomposed groups (0.343 ± 0.259 [0.030–0.973] and 0.003 ± 0.002 [0.001–0.007] mg/mL, respectively). In the decomposed group, n-butyric acid was detected at high concentrations, even in cases where n-propanol was low. These results suggest that n-butyric acid is more likely to be an indicator of blood decomposition than n-propanol.     

Climate Change: Effects on the Older Adult

The effects of climate change include floods, hurricanes, heat waves, and fires; these natural disasters can result in respiratory, cardiovascular, and psychological harm in older adults, who experience the highest morbidity and mortality during heat waves. Advanced practice registered nurses (APRNs) need education on preparing, assessing, and treating older adults for climate-change disasters, especially heat waves. This article will help APRNs understand the effects of climate-change events on the vulnerable older adults and advocates for the need to integrate health effects of climate change into curricula, practicums, policy, and research agendas.     

Pan-cancer proteomic map of 949 human cell lines

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Demarcation of arteriopulmonary segments: a novel and effective method for the identification of pulmonary segments

ObjectiveEach pulmonary segment is an anatomical and functional unit. However, it is fundamentally difficult to precisely distinguish every pulmonary segment using the conventional pulmonary intersegmental planes from computed tomography images. Building arteriopulmonary segments is likely to be an effective way to identify pulmonary segments.MethodsThe thoracic computed tomography images of 40 patients were collected. The anatomic structures of interest were extracted in the transverse, sagittal, and coronal planes using the semi-automated segmentation tools provided by Amira software. The intrapulmonary vessels were subsequently segmented and reconstructed. The distributions of the pulmonary arteries, veins, and bronchi were observed. In patients with pulmonary masses, the mass was also reconstructed.ResultsThe three-dimensional reconstructed images showed the branches of the pulmonary artery ramified up to their eighth order covering the entire lung as well as evident intersegmental gaps without pulmonary arteries. The segmental artery was closely accompanied by the segmental bronchi in 486 pulmonary segments (90% of total number of segments). The size and spatial location of the pulmonary mass within a pulmonary segment were also clearly visible.ConclusionsDemarcation of arteriopulmonary segments can be used to precisely distinguish every pulmonary segment and provide its detailed anatomical structure before pulmonary segmentectomy.     

Protection against corneal hyperosmolarity with soft-contact-lens wear

Hyperosmotic tear stimulates human corneal nerve endings, activates ocular immune response, and elicits dry-eye symptoms. A soft contact lens (SCL) covers the cornea preventing it from experiencing direct tear evaporation and the resulting blink-periodic salinity increases. For the cornea to experience hyperosmolarity due to tear evaporation, salt must transport across the SCL to the post-lens tear film (PoLTF) bathing the cornea. Consequently, limited salt transport across a SCL potentially protects the ocular surface from hyperosmotic tear. In addition, despite lens-wear discomfort sharing common sensations to dry eye, no correlation is available between measured tear hyperosmolarity and SCL-wear discomfort. Lack of documentation is likely because clinical measurements of tear osmolarity during lens wear do not interrogate the tear osmolarity of the PoLTF that actually overlays the cornea. Rather, tear osmolarity is clinically measured in the tear meniscus. For the first time, we mathematically quantify tear osmolarity in the PoLTF and show that it differs significantly from the clinically measured tear-meniscus osmolarity. We show further that aqueous-deficient dry eye and evaporative dry eye both exacerbate the hyperosmolarity of the PoLTF. Nevertheless, depending on lens salt-transport properties (i.e., diffusivity, partition coefficient, and thickness), a SCL can indeed protect against corneal hyperosmolarity by reducing PoLTF salinity to below that of the ocular surface during no-lens wear. Importantly, PoLTF osmolarity for dry-eye patients can be reduced to that of normal eyes with no-lens wear provided that the lens exhibits a low lens-salt diffusivity. Infrequent blinking increases PoLTF osmolarity consistent with lens-wear discomfort. Judicious design of SCL material salt-transport properties can ameliorate corneal hyperosmolarity. Our results confirm the importance of PoLTF osmolarity during SCL wear and indicate a possible relation between PoLTF osmolarity and contact-lens discomfort.