实验性急性肺损伤部分液体通气效应与剂量的关系

目的:对肺灌洗诱导的急性肺损伤家兔实施不同剂量氟碳(perfluorocarbon,PFC)的部分液体通气(partialliquidventilation,PLV),观察其疗效及剂量-效应关系。方法:14只成年健康家兔,麻醉后经气管导管用生理盐水反复肺内灌洗,直至动脉氧分压(PaO2)<13 33kPa(100mmHg)达1h,记录肺气体交换、血液动力学及呼吸动力各参数作为肺损伤(acutelunginjury,ALI)基础值。随机分为PLV组及对照组,对照组以呼吸机行常规机械通气,不给予任何治疗措施;PLV组动物于ALI后每30min气管内灌入PFC(FC3280,3M,德国)6mL·kg-1共3次,总量为18mL·kg-1。以上述呼吸参数行机械通气。最后一次灌注后继续行机械通气3h,每小时记录各参数次。结果:PLV组PaO2及动脉血氧饱和度(HbO2)在灌注第一个剂量的PFC后即显著改善,并与剂量呈相关性;PaCO2在灌注第一个PFC剂量后较ALI时显著降低,但并不随剂量的增加而继续降低。结论:以氟碳为媒介的部分液体通气可明显改善肺灌洗诱导的急性肺损伤家兔的肺氧合,并呈剂量相关性,同时呼吸动力的改善与剂量无关。     

Mechanical model of lung parenchyma as a two-phase porous medium

The anatomy and geometry of the lung at the micro- and macroscopic level have been described briefly. A notion of lung parenchyma — a macroscopically continuous medium whose mechanical properties result from those of microstructural components — has been adapted. Simplifying assumptions propounded in the constitutive model have been discussed. Two phases have been distinguished in the medium: the solid phase — a highly deformable, nonlinearly elastic skeleton in the form of a thin-walled tissue structure on the micro-scale — and the fluid phase — perfect gas (air) filterating through the structure. General constitutive relations for both phases and their mechanical interactions have ben formulated. Further, the fundamental set of differential equations of the quasi-static coupled problem has been developed. Large deformations, material nonlinearities, and dependence of permeability on skeleton deformation have been included. Matrix formulation of the problem has been presented from the point of view of the finite element method. An implicit iterative time integration scheme has been proposed. The algorithm has been illustrated with results of simple numerical tests.     

Molecular dynamics and pharmacophore modelling studies of different subtype (ALK and EGFR (T790M)) inhibitors in NSCLC

Extensively validated 3D pharmacophore models for ALK (anaplastic lymphoma kinase) and EGFR (T790M) (epithelial growth factor receptor with acquired secondary mutation) were developed. The pharmacophore model for ALK (r² = 0.96, q² = 0.692) suggested that two hydrogen bond acceptors and three hydrophobic groups arranged in 3-D space are essential for the binding affinity of ALK inhibitors. Similarly, the pharmacophore model for EGFR (T790M) (r² = 0.92, q² = 0.72) suggested that the presence of a hydrogen bond acceptor, two hydrogen bond donors and a hydrophobic group plays vital role in binding of an inhibitor of EGFR (T790M). These pharmacophore models allowed searches for novel ALK and EGFR (T790M) dual inhibitors from multiconformer 3D databases (Asinex, Chembridge and Maybridge). Finally, the eight best hits were selected for molecular dynamics simulation, to study the stability of their complexes with both proteins and final binding orientations of these molecules. After molecular dynamics simulations, one hit has been predicted to possess good binding affinity for both ALK and EGFR (T790M), which can be further investigated for its experimental in-vitro/in-vivo activities.     

基于全局注意力引导的肺结节分割方法

肺结节的精确分割能有效地辅助医生的治疗诊断工作,但由于不同患者所呈现的肺结节病灶形式多种多样,基于传统专家系统和统计学习的方法难以获得准确的肺结节分割结果。针对这种情况,提出一种由全局注意力引导的注意力机制,达到了从一张完整的胸部影像切片中自动定位并分割出肺结节的效果。该方法首先对目标区域进行肺实质分割,再利用区域建议网络（region proposal network,RPN）进一步缩小感兴趣区域,并生成注意力权重图,最后使用融合了残差网络（residual network,ResNet）与卷积长短期记忆网络（convolutional long short-term memory,ConvLSTM）的结构结合注意力权重进行肺结节分割。将所提方法在肺图像数据库联盟（lung image database consortium,LIDC-IDRI）数据集上进行了全面的评估,结果表明,本文方法分割结果的平均dice得分（标准差）为89.97%（8.9%）,具有出色的分割性能,精度相较其他方法取得一定提升。进一步在相同数据集上将所提方法的肺结节分割结果与4位放射科医生的手工标注结果进行了比较,结果表明本文方法的分割结果与医生们的标注结果的一致性达到了85.81%,相较于医生们手工标注之间的一致性高出了3.39%。     

Lentinus edodes Polysaccharides Alleviate Acute Lung Injury by Inhibiting Oxidative Stress and Inflammation

Acute lung injury (ALI) is a kind of lung disease with acute dyspnea, pulmonary inflammation, respiratory distress, and non-cardiogenic pulmonary edema, accompanied by the mid- and end-stage characteristics of COVID-19, clinically. It is imperative to find non-toxic natural substances on preventing ALI and its complications. The animal experiments demonstrated that Lentinus edodes polysaccharides (PLE) had a potential role in alleviating ALI by inhibiting oxidative stress and inflammation, which was manifested by reducing the levels of serum lung injury indicators (C3, hs-CRP, and GGT), reducing the levels of inflammatory factors (TNF-α, IL-1β, and IL-6), and increasing the activities of antioxidant enzymes (SOD and CAT) in the lung. Furthermore, PLE had the typical characteristics of pyran-type linked by β-type glycosidic linkages. The conclusions indicated that PLE could be used as functional foods and natural drugs in preventing ALI.     

基于胸部CT图像的肺部自动分割

肺区自动分割是肺部肿瘤计算机辅助诊断系统的关键之一。文章采用多阈值和区域生长方法,先去掉背景,再去掉气管／支气管,最后对提取出来的肺区使用滚球的方法进行修补。该方法速度快、人工干预少、准确。     

Structure-Based Discovery and Biological Assays of a Novel PRMT5 Inhibitor for Non-Small Cell Lung Cancer

Protein arginine methyltransferase 5 (PRMT5) is a popular anticancer target that regulates histone or nonhistone methylation and is linked to the development and poor prognosis of non-small cell lung cancer. PRMT5 inhibitors have shown great promise in clinical trials as a cancer therapy. However, most inhibitors reported recently act in a SAM-competitive mode and lack structural diversity. In this paper, a novel non-SAM inhibitor, 3039-0164, was discovered by the structure-based virtual screening method. The binding mechanism of 3039-0164 to PRMT5 was revealed via molecular docking and molecular dynamics simulations. 3039-0164 inhibited PRMT5 enzymatic activity, downregulated the expression of PRMT5 downstream target genes (FGFR3 and eIF4E), and blocked the activation of the PI3K/AKT/mTOR and ERK signaling pathways. The discovery of 3039-0164 provides precise and creative hit compounds for the design optimization of PRMT5 lead compounds in non-small cell lung cancer.     

Evidence of the Beneficial Effects of Ursolic Acid against Lung Cancer

Lung cancer is the leading cause of cancer-related deaths globally. Despite current treatment approaches that include surgery, chemotherapy, radiation and immunotherapies, lung cancer accounted for 1.79 million deaths worldwide in 2020, emphasizing the urgent need to find novel agents and approaches for more effective treatment. Traditionally, chemicals derived from plants, such as paclitaxel and docetaxel, have been used in cancer treatment, and in recent years, research has focused on finding other plant-derived chemicals that can be used in the fight against lung cancer. Ursolic acid is a polyphenol found in high concentrations in cranberries and other fruits and has been demonstrated to have anti-inflammatory, antioxidant and anticancer properties. In this review, we summarize recent research examining the effects of ursolic acid and its derivatives on lung cancer. Data from in vitro cell culture and in vivo animal studies show potent anticancer effects of ursolic acid and indicate the need for clinical studies.     

58例肺结核患者肺功能分析

目的：探讨肺结核对肺功能的影响。方法：回顾分析58例肺结核患者的肺功能。结果：浸润型肺结核肺功能大致正常，慢性纤维空洞型肺结核肺功能普遍异常。结论：肺结核的肺功能障碍呈混合性。