Abstract Objective Type 2 diabetes mellitus (T2DM) is a common metabolic disorder with rising incidence worldwide. This study explored the anti-T2DM role of vitamin D, thereby providing novel therapeutic strategies. Methods C57BL/6 J mice and MIN6 cells were used to induce in vivo T2DM and damaged β-cell models, respectively. Body weights, fasting blood glucose, and fasting insulin were measured in mice. Oral glucose tolerance test (OGTT) and insulin tolerance test (ITT) were conducted on mice. Lipid indices (TG, TC, LDL-C, and HDL-C) were detected in mouse serum. Hematoxylin-eosin staining was used to evaluate pancreatic tissue injury. ELISA was used to assess insulin and oxidative stress (OS) markers (MDA, GSH, and SOD) in mice and MIN6 cells. Production of ROS was detected in islet β-cells and MIN6 cells. Cell viability and apoptosis were evaluated using CCK-8 and flow cytometry, respectively. QRT-PCR and western blotting were used to detect pro-inflammatory factors (TNF-α and IL-6) and endoplasmic reticulum stress (ERS) markers (CHOP and GRP78), respectively. Results Vitamin D reduced body weights, fasting blood glucose, and insulin and ameliorated glucose tolerance and insulin sensitivity in T2DM mice. Besides, vitamin D decreased serum TG, TC, LDL-C, and increased HDL-C in T2DM mice. Vitamin D inhibited pancreatic histopathological injury, cell apoptosis, OS, and β-cell decline in T2DM mice. Moreover, vitamin D alleviated cell death, insufficient insulin secretion, inflammation, OS, and ERS in damaged MIN6 cells. Notably, N-acetyl-L-cysteine (an OS inhibitor) enhanced these effects of vitamin D. Conclusions Vitamin D relieved T2DM symptoms by alleviating OS-induced β-cell impairment.
A 53-year woman and her 18-year daughter presenting with bone pain, bone fractures, bone deformities and short stature were admitted to Gansu Provincial People′s Hospital in March 2021. Laboratory tests showed low blood phosphorus, low renal phosphorus threshold, normal or low blood calcium, and normal or increased PTH. The high-throughput sequencing indicated heterozygous mutations of the PHEX gene (Phosphate-regulating gene with Homology to Endopeptidases on the X chromosome) in two patients, which was not detected in other family members; finally the diagnosis of X-linked dominant hypophosphatemic rickets/osteomalacia(XLH)was confirmed for these two patients. Treated with neutral phosphorus solution and Rocaltrol, bone pain was relieved completely in the younger patient, but not for her mother due to long disease course and severe complications. Because of the large heterogeneity of the disease there are high missed diagnosis and misdiagnosis rates for XLH. In this paper a pedigree of XLH is reported with literature review.
目的 观察瑞舒伐他汀治疗2型糖尿病(type 2 diabetes,T2DM)并发非酒精性脂肪肝(non-alcoholic fatty liver,NAFLD)患者肝功能的改善作用及其可能作用机制.方法 根据T2DM并发NAFLD患者的入院顺序将其随机均分为对照组和试验组,各54例.对照组均接受常规治疗,并于每天早中晚餐前给予二甲双胍片0.5 g口服.试验组在对照组的基础上,于晚餐前口服瑞舒伐他汀钙片,每次10 mg,每天1次.2组均持续治疗2个月.治疗前后测定肝功能指标、血脂指标、相关转录因子及其下游炎症因子.结果 治疗前后,2组患者的谷丙转氨酶(glutamic-pyruvic transaminase,GPT)、谷草转氨酶(glutamic-oxaloacetic transaminase,GOT)、总胆红素(total bilirubin,TBil)、γ-谷氨酰转肽酶(γ-glutamyl transpeptidase,γ-GT)水平比较,差异均有统计学意义(均P<0.05),且试验组和对照组治疗后的GPT、GOT、TBil、γ-GT水平比较,差异均有统计学意义(P<0.05).治疗后,试验组NOD样受体蛋白3(NOD-like receptor pro-tein 3,NLRP3)、凋亡相关斑点样蛋白(apoptosis-associated proteins,ASC)、胱天蛋白酶1(caspase-1)mRNA表达分别为1.83±0.18,1.48±0.15,1.78±0.18,对照组分别为1.99±0.19,1.60±0.16,1.97±0.21,差异有统计学意义(P<0.05);试验组白细胞介素-1β(Interleukin-1β,IL-1β)、白细胞介素-18(IL-18)水平分别为(8.40±0.83),(176.43±16.80)pg·mL-1,对照组分别为(9.65±1.03),(187.27±18.33)pg·mL-1,差异有统计学意义(P<0.05).结论 瑞舒伐他汀能够显著改善T2DM并发NAFLD患者肝功能指标,可能与调节血脂、抑制NLRP3炎症小体及下游炎症因子的过度激活有关.
Road extraction from the remote sensing image over mountainous areas is a difficult vision problem. In this letter, we propose a multiple feature fully convolutional network (MFFCN) on the basis of FCN for mountainous road extraction. The benefits of this model are twofold: first, MFFCN is a semantic segmentation model, which has deep convolutional networks. It avoids the problem of repeated storage and computational convolutions caused by the use of pixel blocks. Second, the MFFCN model could extract the spectral and terrain features. This method ensures the integrity and continuity of the road extraction results. The dataset is composed of GF-2 data and ASTER GDEM data in the Shigatse region of Tibet. We test our network on the dataset and compare it with four road extraction methods. The result shows that the proposed MFFCN is superior to all the comparing methods.
针对半自动道路提取方法人工参与较多、提取精度不高且较为耗时的问题提出一种基于全卷积神经网络(FCN)的多源高分辨率遥感道路提取方法.首先,对高分二号和World View图像进行分割,用卷积神经网络(CNN)分类出包含道路的图像;然后,用Canny算子提取道路的边缘特征信息;最后,结合RGB、Gray和标签图放入FCN中训练,将现有的FCN模型拓展为多卫星源输入及多特征源输入的FCN模型.选取西藏日喀则地区作为研究区域,实验结果显示,所提方法在对高分辨率遥感影像进行道路提取时能够达到99.2%的提取精度,并且有效地减少了提取所需的时间.
在地质大数据背景下,为了更加精准、客观地评估泥石流易发程度,提出一种基于神经网络的区域泥石流易发性评价模型,并结合使用平均影响值算法(MIV)、遗传算法(GA)、Borderline-SMOTE算法提升模型精度.在预处理阶段使用Borderline-SMOTE算法处理非平衡数据集的分类问题,之后采用神经网络拟合主要指标与易发程度的非线性关系并结合遗传算法提升拟合速度,最后结合MIV算法定量分析指标与易发程度相关性.选取雅鲁藏布江中上游流域作为研究区域,实验结果显示,模型能够有效降低非平衡数据集的过拟合,优化原始输入维度,同时在拟合速度上有了很大提升.采用AUC指标检验评价结果,测试集的分类精度达到97.95%,说明模型能够在非平衡数据集下为评价研究区域泥石流易发程度提供参考.
Road information plays an important role in modern society. It is of great scientific significance to study the road extraction method of remote sensing image. This paper reviews the development process of road extraction method, and divides the existing road extraction methods into three categories:based on pixel, object-oriented and deep learning according to the realization form. It is used as a clue to analyze and compare the scope of application of various methods with advantages and disadvantages. Design experiments, with a number of high-resolution satellite remote sensing images as the experimental object, verify the comparison of various types of typical road extraction method of the actual perfor-mance. The experimental results show that the method of road extraction based on deep learning is the best. Finally, based on the theory of popular remote sensing data and artificial intelligence, the development trend of road extraction method of remote sensing image is prospected.
Background and aims: Toll-like receptor 4 (TLR4) has been implicated in vascular inflammation, as well as in the pathogenesis of atherosclerosis and diabetes. Vascular smooth muscle cell (VSMC) apoptosis has been shown to induce plaque vulnerability in atherosclerosis. Previous studies reported that palmitate induced apoptosis in VSMCs; however, the role of TLR4 in palmitate-induced apoptosis in VSMCs has not yet been defined. In this study, we investigated whether or not palmitate-induced apoptosis depended on the activation of the TLR4 pathway.Methods: VSMCs were treated with or without palmitate, CRISPR/Cas9z-mediated genome editing methods were used to deplete TLR4 expression, while NADPH oxidase inhibitors were used to inhibit reactive oxygen species (ROS) generation. Cell apoptosis was detected by terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL) assay, ROS was measured using the 20,7'-dichlorodihydrofluorescein diacetate (DCFH-DA) method, the mRNA and protein expression levels of caspase 3, caspase 9, BCL-2 and p53 were studied by real-time polymerase chain reaction (RT-PCR) and ELISA.Results: Palmitate significantly promotes VSMC apoptosis, ROS generation, and expression of caspase 3, caspase 9 and p53; while NADPH oxidase inhibitor pretreatment markedly attenuated these effects. Moreover, knockdown of TLR4 significantly blocked palmitate-induced ROS generation and VSMC apoptosis accompanied by inhibition of caspase 3, caspase 9, p53 expression and restoration of BCL-2 expression.Conclusions: Our results suggest that palmitate-induced apoptosis depends on the activation of the TLR4/ROS/p53 signaling pathway, and that TLR4 may be a potential therapeutic target for the prevention and treatment of atherosclerosis. (C) 2017 Elsevier B.V. All rights reserved.
Background: The association between serum milk fat globule-epidermal growth factor 8 (MFG-E8) concentrations and vascular complications in T2DM remains unclear.Methods: A total of 149 patients with T2DM were included. The serum concentrations of MFG-E8, glycosylated hemoglobin (HbAlc), and high-sensitivity C-reactive protein (hs-CRP) were measured.Results: There was no significant difference in serum MFG-E8 concentrations between the T2DM group and the T2DM with subclinical atherosclerosis (AS) group (615.49 +/- 143.54 vs.596.22 +/- 79.46 ng/ml, P = 0.365), while the serum concentrations of MFG-E8 in the T2DM with microvascular complications group (446.70 +/- 61.53 ng/ml) and the T2DM with subclinical AS and microvascular complications group (200.87 +/- 38.86 ng/ml) were significantly lower than those in the T2DM group (P = 0.000 for both). In addition, hs-CRP and HbAlc concentrations were independently associated with serum MFG-E8 concentrations (P = 0.024 and P = 0.01, respectively), and low serum MFG-E8 concentrations were significantly associated with an increased risk of microvascular complications in T2DM patients.Conclusions: Serum concentrations of MFG-E8 were negatively associated with the risk of microvascular complications in patients with T2DM. Thus, it might be a potential candidate biomarker for diabetic microvascular complications. (C) 2017 Elsevier B.V. All rights reserved.
BACKGROUND AND AIMS:Toll-like receptor 4 (TLR4) has been implicated in vascular inflammation, as well as in the pathogenesis of atherosclerosis and diabetes. Vascular smooth muscle cell (VSMC) apoptosis has been shown to induce plaque vulnerability in atherosclerosis. Previous studies reported that palmitate induced apoptosis in VSMCs; however, the role of TLR4 in palmitate-induced apoptosis in VSMCs has not yet been defined. In this study, we investigated whether or not palmitate-induced apoptosis depended on the activation of the TLR4 pathway. METHODS:VSMCs were treated with or without palmitate, CRISPR/Cas9z-mediated genome editing methods were used to deplete TLR4 expression, while NADPH oxidase inhibitors were used to inhibit reactive oxygen species (ROS) generation. Cell apoptosis was detected by terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL) assay, ROS was measured using the 2',7'-dichlorodihydrofluorescein diacetate (DCFH-DA) method, the mRNA and protein expression levels of caspase 3, caspase 9, BCL-2 and p53 were studied by real-time polymerase chain reaction (RT-PCR) and ELISA. RESULTS:Palmitate significantly promotes VSMC apoptosis, ROS generation, and expression of caspase 3, caspase 9 and p53; while NADPH oxidase inhibitor pretreatment markedly attenuated these effects. Moreover, knockdown of TLR4 significantly blocked palmitate-induced ROS generation and VSMC apoptosis accompanied by inhibition of caspase 3, caspase 9, p53 expression and restoration of BCL-2 expression. CONCLUSIONS:Our results suggest that palmitate-induced apoptosis depends on the activation of the TLR4/ROS/p53 signaling pathway, and that TLR4 may be a potential therapeutic target for the prevention and treatment of atherosclerosis.
On the basis of monitoring PM2.5 mass concentration data in Xuzhou city 2015, combined with MOD04_3K AOD products and meteorological data , the PM2.5 concentration multivariate regression model based on the correction of physical mechanism was established .The measured data and remote sensing retrieval data were used to analyze the spatial and temporal variation characteristics of PM 2.5 mass concentration in Xuzhou .The results show that , PM2.5 concentrations decrease during the day and rise during the night in the center of Xuzhou city .The peak concentrations of PM 2.5 appeared at 8:00~9:00 AM in spring and autumn .The peak concentrations of PM 2.5 appeared at 6:00~7:00 AM in summer.The peak concentrations of PM 2.5 appeared at 10:00~11:00 AM in win-ter.Among the seasons in which the variable characteristics of PM 2.5 concentrations increases ,winter tops the over-all ranking,and spring,autumn,summer round out the rest.The spatial distribution pattern of PM2.5 is similar to Xuzhou urbanization pattern .The center of Xuzhou city and Tongshan district , Xinyi city and the boundary of Xinyi and Pizhou are the main areas with high PM 2.5 concentrations.