Indomethacin alters the effects of substance-P and VIP on isolated airway smooth muscle

Both substance-P and vasoactive intestinal peptide (VIP) have previously been demonstrated to contract and relax, respectively, the isolated guinea pig trachea. In addition, substance-P and VIP have been localized within the pulmonary innervation of various species. In the present studies, substance-P was found to cause a concentration-related contraction of isolated lung parenchymal strips of the guinea pig, as well as isolated tracheal strips. VIP caused a significant concentration-related relaxation of the isolated tracheal strip, but not the lung parenchymal strip. Indomethacin, a prostaglandin synthetase inhibitor, potentiated the contractile response of the trachea to substance-P and inhibited the VIP- and isoproterenol-induced relaxation. These studies are potentially important in understanding the pathogenesis of bronchospastic disorders, since alterations in prostaglandin biosynthesis may result in hyperreactivity of airways to contractile agonists such as neurotransmitters, as well as an inhibition of relaxation induced by endogenous substances such as VIP or β agonists.     

Osthole stimulates bone formation,drives vascularization and retards adipogenesis to alleviate alcohol‐induced osteonecrosis of the femoral head

Characteristic pathological changes in osteonecrosis of the femoral head (ONFH) include reduced osteogenic differentiation of bone mesenchymal stem cells (BMSCs), impaired osseous circulation and increased intramedullary adipocytes deposition. Osthole is a bioactive derivative from coumarin with a wide range of pharmacotherapeutic effects. The aim of this study was to unveil the potential protective role of osthole in alcohol‐induced ONFH. In vitro, ethanol (50 mmol/L) remarkably decreased the proliferation and osteogenic differentiation of BMSCs and impaired the proliferation and tube formation capacity of human umbilical vein endothelial cell (HUVECs), whereas it substantially promoted the adipogenic differentiation of BMSCs. However, osthole could reverse the effects of ethanol on osteogenesis via modulating Wnt/β‐catenin pathway, stimulate vasculogenesis and counteract adipogenesis. In vivo, the protective role of osthole was confirmed in the well‐constructed rat model of ethanol‐induced ONFH, demonstrated by a cascade of radiographical and pathological investigations including micro‐CT scanning, haematoxylin‐eosin staining, TdT‐mediated dUTP nick end labelling, immunohistochemical staining and fluorochrome labelling. Taken together, for the first time, osthole was demonstrated to rescue the ethanol‐induced ONFH via promoting bone formation, driving vascularization and retarding adipogenesis.     

不同病理分期肺腺癌患者血清代谢组学研究

肺癌是当今世界最常见的恶性肿瘤之一,其新发率和死亡率多年来都居于各类癌症之首,其中85%的肺癌都是非小细胞癌,而腺癌又是最常见的非小细胞癌。肺癌的高隐匿性是造成其高死亡率的最主要原因,因此为肺癌的早期诊断和病理分期寻求高效可靠的方法是十分必要的。代谢组学揭示了小分子代谢物的一系列变化,反映了生命活动的最终状态,因此也能直接反映疾病不同发展阶段的病理生理变化。本研究利用核磁共振氢谱(1H-NMR),对在我院就诊的27例不同病理分期的肺腺癌患者和13例健康志愿者进行了血清代谢物分析,运用正交偏最小二乘判别分析(OPLS-DA)对1H-NMR数据进行建模,单变量统计分析对模型进行评价。结果表明肺腺癌患者组的血清中有14种代谢物出现明显差异,其中丙酮酸、丙氨酸、NAC1、乳酸、GPC和甘氨酸比起对照组来有显著上升,而葡萄糖、谷氨酰胺、亮氨酸、异亮氨酸、缬氨酸、丙酮、乙酰乙酸和苏氨酸则显著下降。而在不同分期肺腺癌患者间进行比较后发现,异亮氨酸、乙酰乙酸、NAC1和乳酸的变化与肺腺癌的发展有相关性,可能是肺腺癌早期诊断和分期的潜在生物标志物。     

Software simulation of tumour motion dose effects during flattened and unflattened ITV-based VMAT lung SBRT

PurposeRestricted studies comparing different dose rate parameters are available while ITV-based VMAT lung SBRT planning leads to perform the analysis of the most suitable parameters of the external beams used. The special emphasis was placed on the impact of dose rate on dose distribution variations in target volumes due to interplay effects.MethodsFour VMAT plans were calculated for 15 lung tumours using 6 MV photon beam quality (flattening filter FF vs. flattening filter free FFF beams) and maximum dose rate of 600 MU/min, 1000 MU/min and 1400 MU/min. Three kinds of motion simulations were performed finally giving 180 plans with perturbed dose distributions.Results6FFF-1400 MUs/min plans were characterized by the shortest beam on time (1.8 ± 0.2 min). Analysing the performed motion simulation results, the mean dose (Dmean) is not a sensitive parameter to related interplay effects. Looking for local maximum and local minimum doses, some discrepancies were found, but their significance was presented for individual patients, not for the whole cohort. The same was observed for other verified dose metrics.ConclusionsGenerally, the evaluation of VMAT robustness between FF and FFF concepts against interplay effect showed a negligible effect of simulated motion influence on tumour coverage among different photon beam quality parameters. Due to the lack of FFF beams, smaller radiotherapy centres are able to perform ITV-based VMAT lung SBRT treatment in a safe way. Radiotherapy department having FFF beams could perform safe, fast and efficient ITV-based VMAT lung SBRT without a concern about significance of interplay effects.     

Impact of lung density on isolated lung tumor dose in VMAT using inline MR-Linac

PurposeThis study investigated the impact of lung density on the isolated lung tumor dose for volumetric modulated arc therapy (VMAT) in an inline magnetic resonance linear accelerator (MR-Linac) using the Monte Carlo (MC) simulation.MethodsCT images of the thorax phantoms with lung tumors of 1, 2, and 3 cm diameters were converted into voxel-base phantoms with lung densities of 0.1, 0.2, and 0.3 g/cm³, respectively. The dose distributions were calculated for partial-arc VMAT. The dose distributions were compared using dose differences, dose volume histograms, and dose volume indices.ResultsIn all cases, the inline magnetic field significantly enhanced the lung tumor dose compared to that at 0 T. For the 1 cm lung tumor, the inline magnetic field of 1 T increased the minimum dose of 95% of the Planning target volume (PTV D₉₅) by 14.0% in 0.1 g/cm³ lung density as compared to that in 0.3 g/cm³ at 0 T. In contrast, at 0 and 0.5 T, the PTV D₉₅ in 0.3 g/cm³ lung density was larger than that in lung density of 0.1 g/cm³. For the 2 cm lung tumor, a similar tendency to 1 cm was observed, whereas the dose impact of lung density was smaller than that for 1 cm. For the 3 cm lung tumor, the lung tumor dose was independent of lung density at 0.5 T and 1.0 T.ConclusionThe inline MR-Linac with the magnetic field over 1 T can enhance the PTV D₉₅ for VMAT regardless of the lung density.     

T-UCRs with digestive and respiratory diseases

From the perspective of histoembryology, the lung, gaster, and intestines that derived from the endoderm of the gastrula are structurally homologous. The interplay of intestines and lung in many pathologic changes is called the gut-lung axis. RNAs transcribed from ultraconserved regions (T-UCRs) are highly evolutionarily conserved in many mammalian genomes and have been found to be important in the pathogenesis and diagnosis of many diseases. More and more studies in recent years have shown that T-UCRs play important roles both in digestive and respiratory diseases. Taking the gut-lung axis as the entry point, this review summarizes the T-UCRs related to digestive and respiratory diseases in recent years. Meanwhile, these T-UCRs and their targets can lay a foundation for future drug research.     

Aurora-A激酶对急性胰腺炎大鼠肺脏损伤的修复作用研究

摘要 目的：探讨与研究Aurora-A激酶对急性胰腺炎大鼠肺脏损伤的修复作用。方法：36只雄性SD大鼠均分为三组：对照组、模型组与Aurora-A组。对照组进行假手术操作,模型组建立急性胰腺炎模型后给予注射等量生理盐水治疗,Aurora-A组建立急性胰腺炎模型后给予阴茎背静脉注射鼠Aurora-A类因子-MLN8054 10 mg/kg治疗,记录大鼠肺脏损伤的修复情况。结果：造模过程中无大鼠死亡情况发生,模型组与Aurora-A组造模后2 w与4 w的肺组织病理评分、血清中性粒细胞弹性蛋白酶(neutrophil elastase,NE)与髓过氧化物酶(myeloperoxidase,MPO)含量、肺组织W/D、肺组织蛋白激酶B(AKT)、细胞外信号调节激酶1(ERK1)蛋白相对表达水平都高于对照组(P<0.05),Aurora-A组少于模型组(P<0.05)。结论：Aurora-A激酶在急性胰腺炎大鼠的应用能抑制Akt/ERK信号通路激活,减少血清NE与MPO的表达,从而促进肺脏损伤修复。     

Automatic lung segmentation in COVID-19 patients: Impact on quantitative computed tomography analysis

PurposeTo assess the impact of lung segmentation accuracy in an automatic pipeline for quantitative analysis of CT images.MethodsFour different platforms for automatic lung segmentation based on convolutional neural network (CNN), region-growing technique and atlas-based algorithm were considered. The platforms were tested using CT images of 55 COVID-19 patients with severe lung impairment. Four radiologists assessed the segmentations using a 5-point qualitative score (QS). For each CT series, a manually revised reference segmentation (RS) was obtained. Histogram-based quantitative metrics (QM) were calculated from CT histogram using lung segmentationsfrom all platforms and RS. Dice index (DI) and differences of QMs (ΔQMs) were calculated between RS and other segmentations.ResultsHighest QS and lower ΔQMs values were associated to the CNN algorithm. However, only 45% CNN segmentations were judged to need no or only minimal corrections, and in only 17 cases (31%), automatic segmentations provided RS without manual corrections. Median values of the DI for the four algorithms ranged from 0.993 to 0.904. Significant differences for all QMs calculated between automatic segmentations and RS were found both when data were pooled together and stratified according to QS, indicating a relationship between qualitative and quantitative measurements. The most unstable QM was the histogram 90th percentile, with median ΔQMs values ranging from 10HU and 158HU between different algorithms.ConclusionsNone of tested algorithms provided fully reliable segmentation. Segmentation accuracy impacts differently on different quantitative metrics, and each of them should be individually evaluated according to the purpose of subsequent analyses.     

Antiproliferative and antioxidant properties of nematocysts crude venom from jellyfish Acromitus flagellatus against human cancer cell lines

This study aimed to investigate the antiproliferative and antioxidant properties of crude venom from the nematocyst of Jellyfish Acromitus flagellates on human lung cancer (A549) and liver cancer (HepG2) cell lines. The prepared crude venom was subjected to analyses of the biochemical constituents, protein profiles, antioxidant and anticancer activities by standard methods. The extracted venom was pale-yellow in color and viscous/sticky. The biochemical composition such as, protein (1.547 mg/ml), lipid (0.039 mg/ml) and carbohydrate (0.028 mg/ml) was estimated. Protein profiles were determined by SDS PAGE, the result revealed that the molecular weight range from 205 ? 3.5 kDa. The free radical scavenging activity was analyzed by the reducing potential (56.36%), DPPH (72.47%), hydroxyl (68.50%), superoxide anion (65.75%), and nitric oxide (33.04%). The cell viability was observed by using different concentrations (20 to 100 µg/ml) of crude venom on A549 and HepG2 cancer cell lines and the IC₅₀ values were recorded in (60 μg/ml and 40 μg/ml) respectively, while it had none cytotoxic effects on Vero cell line up to the concentration of 90 μg/ml. These results suggest that crude venom from nematocyst of A. flagellatus possesses anti-cancer activity and able to develop novel drugs on marine-derived compounds.