癌因性疲劳动物模型的研究进展

癌因性疲劳(CRF)是一种与癌症本身或癌症治疗相关的常见症状,它不仅会中断患者的治疗,还会严重影响患者生存质量.目前,CRF具体的机制仍不明确,且缺乏公认的有效治疗.建立规范的相关动物模型并进一步探讨CRF的产生机制是找寻有效治疗途径的前提条件.本文综述国内外CRF的动物模型,以期找寻合适的临床前实验的造模方法,并区分...     

Automated analysis of rabbit knee calcified cartilage morphology using micro-computed tomography and deep learning

Structural dynamics of calcified cartilage (CC) are poorly understood. Conventionally, CC structure is analyzed using histological sections. Micro-computed tomography (µCT) allows for three-dimensional (3D) imaging of mineralized tissues; however, the segmentation between bone and mineralized cartilage is challenging. Here, we present state-of-the-art deep learning segmentation for µCT images to assess 3D CC morphology. The sample includes 16 knees from 12 New Zealand White rabbits dissected into osteochondral samples from six anatomical regions: lateral and medial femoral condyles, lateral and medial tibial plateaus, femoral groove, and patella (n = 96). The samples were imaged with µCT and processed for conventional histology. Manually segmented CC from the images was used to train segmentation models with different encoder–decoder architectures. The models with the greatest out-of-fold evaluation Dice score were selected. CC thickness was compared across 24 regions, co-registered between the imaging modalities using Pearson correlation and Bland–Altman analyses. Finally, the anatomical CC thickness variation was assessed via a Linear Mixed Model analysis. The best segmentation models yielded average Dice of 0.891 and 0.807 for histology and µCT segmentation, respectively. The correlation between the co-registered regions was strong (r = 0.897, bias = 21.9 µm, standard deviation = 21.5 µm). Finally, both methods could separate the CC thickness between the patella, femoral, and tibial regions (p < 0.001). As a conclusion, the proposed µCT analysis allows for ex vivo 3D assessment of CC morphology. We demonstrated the biomedical relevance of the method by quantifying CC thickness in different anatomical regions with a varying mean thickness. CC was thickest in the patella and thinnest in the tibial plateau. Our method is relatively straightforward to implement into standard µCT analysis pipelines, allowing the analysis of CC morphology. In future research, µCT imaging might be preferable to histology, especially when analyzing dynamic changes in cartilage mineralization. It could also provide further understanding of 3D morphological changes that may occur in mineralized cartilage, such as thickening of the subchondral plate in osteoarthritis and other joint diseases.     

Sleep Deprivation and Central Appetite Regulation

Research shows that reduced sleep duration is related to an increased risk of obesity. The relationship between sleep deprivation and obesity, type 2 diabetes, and other chronic diseases may be related to the imbalance of appetite regulation. To comprehensively illustrate the specific relationship between sleep deprivation and appetite regulation, this review introduces the pathophysiology of sleep deprivation, the research cutting edge of animal models, and the central regulatory mechanism of appetite under sleep deprivation. This paper summarizes the changes in appetite-related hormones orexin, ghrelin, leptin, and insulin secretion caused by long-term sleep deprivation based on the epidemiology data and animal studies that have established sleep deprivation models. Moreover, this review analyzes the potential mechanism of associations between appetite regulation and sleep deprivation, providing more clues on further studies and new strategies to access obesity and metabolic disease.     

Development and validation of a five-gene model to predict postoperative brain metastasis in operable lung adenocarcinoma

One of the most common sites of extra-thoracic distant metastasis of nonsmall-cell lung cancer is the brain. Our study was performed to discover genes associated with postoperative brain metastasis in operable lung adenocarcinoma (LUAD). RNA seq was performed in specimens of primary LUAD from seven patients with brain metastases and 45 patients without recurrence. Immunohistochemical (IHC) assays of the differentially expressed genes were conducted in 272 surgical-resected LUAD specimens. LASSO Cox regression was used to filter genes related to brain metastasis and construct brain metastasis score (BMS). GSE31210 and GSE50081 were used as validation datasets of the model. Gene Set Enrichment Analysis was performed in patients stratified by risk of brain metastasis in the TCGA database. Through the initial screening, eight genes (CDK1, KPNA2, KIF11, ASPM, CEP55, HJURP, TYMS and TTK) were selected for IHC analyses. The BMS based on protein expression levels of five genes (TYMS, CDK1, HJURP, CEP55 and KIF11) was highly predictive of brain metastasis in our cohort (12-month AUC: 0.791, 36-month AUC: 0.766, 60-month AUC: 0.812). The validation of BMS on overall survival of GSE31210 and GSE50081 also showed excellent predictive value (GSE31210, 12-month AUC: 0.682, 36-month AUC: 0.713, 60-month AUC: 0.762; GSE50081, 12-month AUC: 0.706, 36-month AUC: 0.700, 60-month AUC: 0.724). Further analyses showed high BMS was associated with pathways of cell cycle and DNA repair. A five-gene predictive model exhibits potential clinical utility for the prediction of postoperative brain metastasis and the individual management of patients with LUAD after radical resection.     

Sleep,brain development,and autism spectrum disorders: Insights from animal models

Sleep is an evolutionarily conserved and powerful drive, although its complete functions are still unknown. One possible function of sleep is that it promotes brain development. The amount of sleep is greatest during ages when the brain is rapidly developing, and sleep has been shown to influence critical period plasticity. This supports a role for sleep in brain development and suggests that abnormal sleep in early life may lead to abnormal development. Autism spectrum disorder (ASD) is the most prevalent neurodevelopmental disorder in the United States. It is estimated that insomnia affects 44%–86% of the ASD population, predicting the severity of ASD core symptoms and associated behavioral problems. Sleep problems impact the quality of life of both ASD individuals and their caregivers, thus it is important to understand why they are so prevalent. In this review, we explore the role of sleep in early life as a causal factor in ASD. First, we review fundamental steps in mammalian sleep ontogeny and regulation and how sleep influences brain development. Next, we summarize current knowledge gained from studying sleep in animal models of ASD. Ultimately, our goal is to highlight the importance of understanding the role of sleep in brain development and the use of animal models to provide mechanistic insight into the origin of sleep problems in ASD.     

Analysis of Mechanical Parameters of Asymmetrical Rolling Dealing with Three Region Percentages in Deformation Zones

A series of mathematical models were proposed to calculate the roll force, torque and power for cold strip asymmetrical rolling by means of the slab method, taking the percentages of the forward-slip, backward-slip and cross-shear zones into account. The friction power, plastic work and total energy consumption can be obtained by the models. The effects of variable rolling parameters—such as the speed ratio, entry thickness, friction coefficient and front and back tension—on the process of asymmetrical rolling are analyzed. In all cases, an increase in speed ratio leads to an increase in friction work and its proportions. The increase in entry thickness and deformation resistance causes both friction work and plastic deformation work to increase. The proportion of friction work decreases with increasing deformation resistance, entry thickness, front tension and back tension. In the circumstances of a thin strip being rolled with a large speed ratio, the proportion of friction work could exceed that of plastic deformation work. The concept of a threshold point of friction work was proposed to explain this phenomenon. As an example, threshold points T1, T2, T3 with the effect of the entry thickness and S1, S2, S3 with the effect of the friction coefficient have been obtained by computation. Finally, the experiment of the strip asymmetrical rolling was conducted, and a maximum error of 9.7% and an RMS error of 5.9% were found in the comparison of roll forces between experimental measurement values and calculated ones.