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Atherosclerosis (AS) is an inflammatory disease, whose occurrence and development mechanism is related to a great number of inflammatory cytokines. β-sitosterol (BS), a natural compound extracted from numerous vegetables and plant medicines, has been suggested to improve AS, but the underlying mechanism remains vague. This work focused on investigating how BS affected the lipopolysaccharide (LPS)-treated human umbilical vein endothelial cells (HUVECs) and further exploring the potential targets and mechanisms through network pharmacology (NP) and molecular docking (MD). According to in vitro experiments, LPS resulted in an increase in the expression of inflammatory cytokines like tumor necrosis factor-α (TNF-α), cyclooxygenase-2 (Cox-2), and interleukin-6 (IL-6). Besides, secretion of IL-6, interleukin-1β (IL-1β), and TNF-α also increased in HUVECs, whereas BS decreased the expression and secretion of these cytokines. NP analysis revealed that the improvement effect of BS on AS was the result of its comprehensive actions targeting 99 targets and 42 pathways. In this network, MAPKs signaling pathway was the core pathway, whereas MAPK1, MAPK8, MAPK14, and NFKB1 were the hub targets. MD analysis also successfully validated the interactions between BS and these targets. Moreover, verification test results indicated that BS downregulated the abnormal expression and activation of MAPKs and NF-κB signaling pathways in LPS-treated cells, including p38, JNK, ERK, NF-κB, and IκB-α phosphorylation expressions. Furthermore, p65 nuclear translocation was also regulated by BS treatment. In conclusion, the BS-related mechanisms in treating AS are possibly associated with inflammatory response inhibition by regulating MAPKs and NF-κB signaling pathways.

An important indicator of cervical cancer diagnosis is to calculate the proportion of diseased cells and cancer cells, so it is necessary to segment cells and judge the cell status. The existing methods are difficult to deal with the segmentation of overlapping cells. In order to solve this problem, we put forward such a hypothesis by reading a large number of literature, that is, image segmentation and edge measurement tasks have unity in high-level features. To prove this hypothesis, in this paper, we focus on the complementary between overlapping cervical cell edge information and cell object information to get higher accuracy cell edge detection results. Specifically, we present a joint multi-task learning framework for overlapping cell edge detection by the mask guidance pyramid network. The main component of the framework is the Mask Guidance Module (MGM), which integrates two tasks and stores the shared latent semantics to interact in the two tasks. For semantic edge detection, we propose the novel Refinement Aggregated Module (RAM) fusion to promote semantic edges. Finally, to improve the edge pixel accuracy, the edge consistency constraint loss function is introduced to our model training. Our extensive experiments have proved that our method outperforms other edge detection efforts.

The in situ measurement of thick oil slick thickness (>0.5 mm) and area in real time in order to estimate the volume of an oil spill is very important for determining the oil spill response strategy and evaluating the oil spill disposal efficiency. In this article, a method is proposed to assess the volume of oil slicks by simultaneously measuring the thick oil slick thickness and area using ultrasonic inspection and image processing methods, respectively. A remotely operated vehicle (ROV), integrating two ultrasonic immersion transducers, was implemented as a platform to receive ultrasonic reflections from an oil slick. The oil slick thickness was determined by multiplying the speed of sound by the ultrasonic traveling time within the oil slick, which was calculated using the cross-correlation method. Images of the oil slick were captured by an optical camera using an airborne drone. The oil slick area was calculated by conducting image processing on images of the oil slick using the proposed image processing algorithms. Multiple measurements were performed to verify the proposed method in the laboratory experiments. The results show that the thickness, area and volume of a thick oil slick can be accurately measured with the proposed method. The method could potentially be used as an applicable tool for measuring the volume of an oil slick during an oil spill response.

Parkinson's disease (PD) is currently an ongoing challenge in daily clinical medicine. To reduce diagnosis time and arduousness and even assess PD levels, a temporal pyramid attention‐based spatiotemporal (PAST) fusion model for diagnosis of PD is produced by using gait data from ground reaction forces. This model is innovative in two aspects. First, by using the temporal pyramid attention module, multiscale temporal attention is obtained from raw sequences. Second, 1D convolutional neural network and bidirectional long short‐term memory layers are used together to learn spatial fusion features from multiple channels in the spatial domain to obtain multichannel, multiscale fusion features. Experiments are performed on the PhysioBank data set, and the results show that the proposed PAST model outperforms other state‐of‐the‐art methods on classification results. This model can assist in the diagnosis and treatment of PD by using gait data.

Anchor or anchor-free based Siamese trackers have achieved the astonishing advancement. However, their parallel regression and classification branches lack the tracked target information link and interaction, and the corresponding independent optimization maybe lead to task-misalignment, such as the reliable classification prediction with imprecisely localization and vice versa. To address this problem, we develop a general Siamese dense regression tracker (SDRT) with both task and feature alignments. It consists of two cooperative and mutual-guidance core branches: dense local regression with RepPoint representation, the global and local multi-classifier fusion with aligned features. They complement and boost each other to constrain the results with well-localized followed to also be well-classified. Specifically, a dense local regression with RepPoint representation, directly estimates and averages multiple dense local bounding box offsets for accurate localization. And then, the refined bounding boxes can be used to learn the global and local affine alignment features for reliable multi-classifier fusion. The classified scores in turn guide the assigned positive bounding boxes for the regression task. The mutual guidance operations can bridge the connection between classification and regression substantially, since the assigned labels of one task depend on the prediction quality of the other task. The proposed tracking module is general, and it can boost both the anchor or anchor-free based Siamese trackers to some extent. The extensive tracking comparisons on six tracking benchmarks verify its favorable and competitive performance over states-of-the-arts tracking modules.

Platinum-based cytotoxic chemotherapy is considered the standard treatment for advanced gastric cancer (GC). However, cisplatin chemoresistance often occurs with the mechanisms being not well clarified, which results in the cancer recurrence and poor survival. Ginsenoside Rg3, isolated from the Chinese Herb Panax Ginseng, is recognized as an anti-cancer agent. Herein, we aimed to reveal whether Ginsenoside Rg3 alleviates cisplatin resistance and sensitizes GC cells to cisplatin-induced apoptosis, and draw out the underlying molecular mechanism in cisplatin-resistant GC cells. The lower expression of miR-429 was found in AGSR-CDDP cells; it was also in association with cisplatin-resistance in GC cells and expression of which was restored following Ginsenoside Rg3 treatment. We also demonstrated that miR-429 made a contribution toward chemosensitivity in GC cells partly through SOX2 regulation. SOX2 was found to contribute to developing platinum resistance and was an authentic target for miR-429 in AGSR-CDDP cells. Importantly, enforced expression of SOX2 with a pcDNA3-SOX2 construct lacking the 3′-UTR miRNA binding site diminished the cytotoxic effects of miR-429 in AGSR-CDDP cells. We demonstrated that Ginsenoside Rg3 enhanced chemosensitivity in AGSR-CDDP GC cells, at least in part, through up-regulating miR-429, thereby targeting SOX2 and modulating downstream PI3K/AKT/mTOR signaling. Ginsenoside Rg3 was also found to regulate apoptosis-related genes via miR-429 in cisplatin-resistant GC cells. Ginsenoside Rg3 treatment significantly suppressed the migration rate of AGSR-CDDP GC cells, while following transfection with anti-miR-429, the anti-migratory effects of Ginsenoside Rg3 was partially abolished. This data suggested that Ginsenoside Rg3 may impede the chemoresistance and migration of GC cells mainly mediated through miR-429. We concluded that miR-429-regulated SOX2 expression was one of the main mechanisms by which Ginsenoside Rg3 dramatically promoted its anticancer effects on cisplatin-resistant GC cells. We also underscored a supporting model in which miR-429 adjusted PI3K/AKT/mTOR signaling by regulating SOX2 in cisplatin-resistant GC cells.

The 3D mesh is an important representation of geometric data. It is widely used in computer graphics and has attracted more attention in computer vision community recently. However, in the generation of mesh data, geometric deficiencies (e.g., duplicate elements, degenerate faces, isolated vertices, self-intersection, and inner faces) are unavoidable. Geometric deficiencies may violate the topology structure of an object and affect the use of 3D meshes. In this paper, we propose an end-to-end algorithm to eliminate geometric deficiencies effectively and efficiently for 3D meshes in a specific and reasonable order. Specifically, duplicate elements can be first eliminated by assessing appear times of vertices or faces. Then, degenerate faces can be removed according to the outer product of two edges. Next, since isolated vertices do not appear in any face vertices, they can be deleted directly. Afterward, self-intersecting faces are detected and remeshed by using an AABB tree. Finally, we detect and remove an inner face according to whether multiple random rays shooted from a face can reach infinity. Experiments on ModelNet40 dataset illustrate that our method can eliminate the deficiencies of 3D meshes thoroughly.

Accurate labeling is essential for supervised deep learning methods. However, it is almost impossible to accurately and manually annotate thousands of images, which results in many labeling errors for most datasets. We proposes a local label point correction (LLPC) method to improve annotation quality for edge detection and image segmentation tasks. Our algorithm contains three steps: gradient-guided point correction, point interpolation and local point smoothing. We correct the labels of object contours by moving the annotated points to the pixel gradient peaks. This can improve the edge localization accuracy, but it also causes unsmooth contours due to the interference of image noise. Therefore, we design a point smoothing method based on local linear fitting to smooth the corrected edge. To verify the effectiveness of our LLPC, we construct a largest overlapping cervical cell edge detection dataset (CCEDD) with higher precision label corrected by our label correction method. Our LLPC only needs to set three parameters, but yields 30-40$\%$ average precision improvement on multiple networks. The qualitative and quantitative experimental results show that our LLPC can improve the quality of manual labels and the accuracy of overlapping cell edge detection. We hope that our study will give a strong boost to the development of the label correction for edge detection and image segmentation. We will release the dataset and code at https://github.com/nachifur/LLPC., Published on Frontiers in Neuroinformatics. Official paper: https://www.frontiersin.org/articles/10.3389/fninf.2022.895290/full. Code and dataset: https://github.com/nachifur/LLPC

Megakaryocytic leukemia 1 (MKL1) is a key transcription factor involved in non-small cell lung cancer (NSCLC) growth and metastasis. Yet, its downstream target genes, especially long non-coding RNA (lncRNA) targets, are poorly investigated. In this study, we employed lncRNA array technology to identify differentially expressed lncRNAs in NSCLC cells with or without overexpression of MKL1. Candidate lncRNAs were further explored for their clinical significance and function in NSCLC. The results showed that MKL1 promoted the expression of lncRNA SNHG18 in NSCLC cells. SNHG18 upregulation in NSCLC specimens correlated with lymph node metastasis and reduced overall survival of NSCLC patients. SNHG18 expression served as an independent prognostic factor for NSCLC. Knockdown of SNHG18 blocked MKL1-induced growth and invasion of NSCLC cells in vitro. Animal studies validated the requirement for SNHG18 in NSCLC growth and metastasis. Moreover, overexpression of SNHG18 promoted NSCLC cell proliferation and invasion. Mechanically, SNHG18 exerted its prometastatic effects on NSCLC cells through repression of miR-211-5p and induction of BRD4. Clinical evidence indicated that SNHG18 expression was negatively correlated with miR-211-5p expression in NSCLC tissues. Altogether, SNHG18 acts as a lncRNA mediator of MKL1 in NSCLC. SNHG18 facilitates NSCLC growth and metastasis by modulating the miR-211-5p/BRD4 axis. Therefore, SNHG18 may be a potential therapeutic target for the treatment of NSCLC.

Meng Zhang,1 Xiaoli Li,1,2 Zhirui Fan,1 Jing Zhao,1 Shuzheng Liu,3 Mingzhi Zhang,1 Huixiang Li,4 Mariusz Adam Goscinski,5 Huijie Fan,1 Zhenhe Suo1,2,6 1Department of Oncology, The First Affiliated Hospital of Zhengzhou University, Zhengzhou University, Zhengzhou, Henan Province, China; 2Department of Pathology, The Norwegian Radium Hospital, Oslo University Hospital, University of Oslo, Oslo, Norway; 3Henan Office for Cancer Research and Control, Henan Cancer Hospital, Zhengzhou, Henan Province, China; 4Department of Pathology, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, Henan Province, China; 5Department of Surgery, The Norwegian Radium Hospital, Oslo University Hospital, University of Oslo, Oslo, Norway; 6Department of Pathology, Institute for Clinical Medicine, Faculty of Medicine, University of Oslo, Oslo, Norway Background: Sushi repeat-containing protein X-linked 2 (SRPX2) is overexpressed in a variety of different tumor tissues and correlated with poor prognosis in patients. Little research focuses on the role of SRPX2 expression in prostate cancer (PCa), and the clinicopathological significance of the protein expression in this tumor is relatively unknown. However, our previous transcriptome data from those cancer stem-like cells indicated the role of SRPX2 in PCa. Materials and methods: In this study, RT-PCR and Western blotting were firstly used to examine the SRPX2 expression in three PCa cell lines including LNCaP, DU145, and PC3, and then SRPX2 protein expression was immunohistochemically investigated and statistically analyzed in a series of 106 paraffin-embedded PCa tissue specimens. Results: Significantly lower levels of SRPX2 expression were verified in the LNCaP cells, compared with the expression in the aggressive DU145 and PC3 cells, in both mRNA and protein levels. Immunohistochemically, there were variable SRPX2 protein expressions in the clinical samples. Moreover, high levels of SRPX2 expression in the PCa tissues were significantly associated with Gleason score (P=0.008), lymph node metastasis (P=0.009), and distant metastasis (P=0.021). Furthermore, higher levels of SRPX2 expression in the PCa tissues were significantly associated with shorter overall survival (OS) (P

Shadow features such as colour ratio, texture, and chromaticity have proved to be quite effective in shadow detection. Many shadow detection methods have been proposed on the basis of different features. However, previous works for shadow detection mainly focus on designing an effective classifier for existing shadow features, but pay less attention on the analysis of shadow features themselves. The majority of studies simply report the final shadow detection results rather than make an evaluation on each feature. Readers often do not know which features are more effective or whether these shadow features are complementary. The following problems are still unsolved: the robustness of each feature, which feature plays the most important role in a detection method, and what is the best performance that current features can reach. The purpose of this study is to answer these questions, and the authors hope that this study can offer guidance for future shadow detection algorithms via the evaluation of frequently used shadow features. Several useful and interesting conclusions are obtained after conducting extensive comparison experiments on a large dataset.

Long non-coding RNA (lncRNA) LINC00173 has been previously shown to promote chemoresistance and progression of small-cell lung cancer. Herein, we examine the clinical significance and biological function of LINC00173 in triple-negative breast cancer (TNBC). Quantitative PCR analysis was performed to determine the expression of LINC00173 in TNBC and adjacent breast tissues (n = 84). The associations of LINC00173 expression with cancer features and survival of TNBC patients were analyzed. The function of LINC00173 in TNBC cell proliferation, colony formation, and invasion was explored. TNBCs expressed increased levels of LINC00173 relative to normal breast tissues. TNBC patients with high tumoral LINC00173 levels had a lower recurrence-free survival and overall survival rate than those with low LINC00173 expression. Silencing of LINC00173 inhibited the proliferation, colony formation, and invasion of TNBC cells, whereas overexpression of LINC00173 exerted opposite effects. In vivo studies confirmed the reduction of tumor growth by LINC00173 depletion. Mechanistic investigation revealed that LINC00173 suppressed miR-490-3p to promote aggressive phenotype in TNBC cells. There was an inverse correlation between miR-490-3p and LINC00173 in TNBC (r = -0.2647, P = 0.0149). Altogether, LINC00173 functions as an oncogene in TNBC through antagonization of miR-490-3p. Upregulation of LINC00173 is associated with poor prognosis in TNBC. Targeting LINC00173 provides a potential therapeutic strategy for TNBC.

// Benling Xu 1,2,* , Long Yuan 3,* , Quanli Gao 2 , Peng Yuan 2 , Peng Zhao 4 , Huijuan Yuan 5 , Huijie Fan 1 , Tiepeng Li 2 , Peng Qin 2 , Lu Han 2 , Weijia Fang 4 and Zhenhe Suo 1,6 1 Department of Oncology, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, Henan, P. R. China 2 Department of Cancer Biotherapy, The Affiliated Cancer Hospital of Zhengzhou University, Zhengzhou, Henan, P. R. China 3 Department of Surgery, The Affiliated Cancer Hospital of Zhengzhou University, Zhengzhou, Henan, P. R. China 4 Department of Oncology, The First Affiliated Hospital of Zhejiang University, Hangzhou, Zhejiang, P. R. China 5 Department of Endocrinology, Henan Provincial People’s Hospital, Zhengzhou, Henan, P. R. China 6 Department of Pathology, Oslo University Hospital and Clinical Institute, Faculty of Medicine, University of Oslo, Oslo, Norway * These authors have contributed equally to the work Correspondence to: Zhenhe Suo, email: // Keywords : colorectal cancer; T cell exhaustion; PD-1; Tim-3 Received : March 12, 2015 Accepted : April 22, 2015 Published : May 12, 2015 Abstract T-cell exhaustion represents a progressive loss of T-cell function. The inhibitory receptor PD-1 is known to negatively regulate CD8 + T cell responses directed against tumor antigen, but the blockades of PD-1 pathway didn’t show the objective responses in patients with colorectal cancer (CRC). Thus, further exploring the molecular mechanism responsible for inducing T-cell dysfunction in CRC patients may reveal effective strategies for immune therapy. This study aims to characterize co-inhibitory receptors on T cells in CRC patients to identify novel targets for immunotherapy. In this study, peripheral blood samples from 20 healthy controls and 54 consented CRC patients, and tumor and matched paraneoplastic tissues from 7 patients with advanced CRC, subjected to multicolor flow cytometric analysis of the expression of PD-1 and Tim-3 receptors on CD8 + T cells. It was found that CRC patients presented with significantly higher levels of circulating Tim-3 + PD-1 + CD8 + T cells compared to the healthy controls (medians of 3.12% and 1.99%, respectively, p = 0.0403). A similar increase of Tim-3 + PD-1 + CD8 + T cells was also observed in the tumor tissues compared to paraneoplastic tussues. Tim-3 + PD-1 + CD8 + T cells in tumor tissues produced even less cytokine than that in paraneoplastic tissues. Functional ex vivo experiments showed that Tim-3 + PD-1 + CD8 + T cells produced significantly less IFN-γ than Tim-3 - PD-1 - CD8 + T cells, followed by Tim-3 + PD-1 - CD8 + T cells, and Tim-3 - PD-1 + CD8 + T cells, indicating a stronger inhibition of IFN-γ production of Tim-3 + CD8 + T cells . It is also found in this study that Tim-3 + PD-1 + CD8 + T cell increase in circulation was correlated with clinical cancer stage but not histologic grade and serum concentrations of cancer biomarker CEA. Our results indicate that upregulation of the inhibitory receptor Tim-3 may restrict T cell responses in CRC patients, and therefore blockage of Tim-3 and thus restoring T cell responses may be a potential therapeutic approach for CRC patients.

Background: Hypercholesterolemia (HC) dominates the risk factors for atherosclerosis. Sustained oxidative stress is a central mechanism driving endothelial dysfunction (ED) in HC. But the underlying redox mechanism remains unclear. Protein S-glutathionylation, a reversible oxidative modification of cysteine residues is tightly controlled by a specific de-glutathionylation enzyme: glutaredoxin-1 (Glrx-1), which thereby plays a critical role in redox regulation of cellular function. Methods and Results: The protein levels of Glrx1 in aorta and lung tissues are inversely correlated with circulating cholesterol in WT and ApoE -/- mice. Overexpression of Glrx1 in ApoE -/- mice attenuates HC-induced ED as measured by flow-mediated dilation of femoral artery using a new vascular imaging method with optical coherence tomography technique, and impaired eNOS function as evidenced by increased eNOS monomer to dimer ratio and suppressed phosphorylation of vasodilator-stimulated phosphoprotein in the aorta. In HAECs oxidized LDL promotes downregulation of Glrx1 without altering its mRNA level. The consequent elevated PrS-SG inactivates Akt/eNOS and stimulates degradation of Rac1, a key regulator of eNOS. All of these deteriorate effects of oxLDL are prevented by adenoviral overexpression of Glrx1. Conclusions: HC-induced downregulation of Glrx1 promotes ED by redox inactivation of eNOS and its upstream regulators: Akt1 and Rac1.

Purpose: This study aims at sharing our experience as how to obtain and identify axial view image of the acetabular anterior column in patients. Methods: Pelvic computed tomography data of six normal adults were used to reconstruct three-dimensional (3D) models. The transparency of each 3D model was downgraded at the view perpendicular to the cross section of the anterior column axis to simulate the anterior column axial view image. Fluoroscopy was performed in all patients to obtain the anterior column axial view image in the operating room. Each fluoroscopic image was compared with the corresponding simulation image to analyze potential anatomic landmarks that were helpful to identify the translucent area (projection of the screw path) in the patients. Results and Conclusions: To obtain ideal anterior column axial fluoroscopic image, the patient should be positioned supine with the leg of “abnormal side” straight and contralateral side flexion, abduction, and external rotation; the C-arm machine should be placed at the caudal end of the operation table with the C-arm fluoroscopic intensifier first positioned at the pelvic lateral view and then tilted approximately 30° toward the “abnormal side” and rotated approximately 45° toward the caudal end of the operation table. To identify the translucent area on the anterior column axial view fluoroscopic image obtained from the patient, the greater sciatic notch, the true pelvis edge, and the acetabulum should be identified first and the translucent area is located in the area surrounded by these three anatomic landmarks.

Aims To investigate the aberrant expression of CD117 in oesophageal squamous cell carcinoma (SCC) and its prognostic significance. Methods and results Immunohistochemical staining for CD117 was performed on tissue microarray and routine tissue sections from 157 oesophageal SCC patients and 10 normal oesophageal epithelia adjacent to tumour. The positive rate of CD117 expression was 29.9% in oesophageal SCC tissues, whereas no CD117 expression was detected in the 10 normal oesophageal epithelia. CD117 expression was significantly associated with T stage (P

Automatic diagnosis of gastropathy disease plays an important role in supporting the clinician and speeding up the examination process. In this paper, we propose a general algorithm for stomach disease detection using sparse representation, which can get robust result even using a small size of high-dimensional training dataset. First, a noval large scale dictionary selection model based on the low rank property is designed to initialize the meaningful dictionary with minimal size. Then in comparison with the state-of-the-arts, we consider disease diagnosing as both supervised classification issue and one-class classification issue, where a new criterion, weighted sparsity concentration index (WSCI) is designed for outlier detection. Experiments on our dataset and comparisons with state-of-the-arts demonstrate the effectiveness and effciency of our algorithm.

Goal: Most state-of-the-art computer-aided endoscopic diagnosis methods require pixelwise labeled data to train various supervised machine learning models. However, it is a tedious and time-consuming work to collect sufficient precisely labeled image data. Fortunately, we can easily obtain huge endoscopic medical reports including the diagnostic text and images, which can be considered as weakly labeled data. Methods: In this paper, our motivation is to design a new computer-aided endoscopic diagnosis system without human specific labeling; in comparison with most state of the arts, ours only depends on the endoscopic images with weak labels mined from the diagnostic text. To achieve this, we first cast the endoscopic image folder and included images as bag and instances and represent each instance based on the global bag-of-words model. We then adopt a feature mapping scheme to represent each bag by mining the most suspicious lesion instance from each positive bag automatically. In order to achieve self-online updating from sequential new coming data, an online metric learning method is used to optimize the bag-level classification. Results: Our computer-aided endoscopic diagnosis system achieves an AUC of 0.93 on a new endoscopic image dataset captured from 424 volunteers with more than 12k images. Conclusion: The system performance outperforms other state of the arts when we mine the most positive instances from positive bags and adopt the online phase to mine more information from the unseen bags. Significance: We present the first weakly labeled endoscopic image dataset for computer-aided endoscopic diagnosis and a novel system that is suitable for use in clinical settings.

Yong-Xu Jia,1,2,* Teng-Fei Li,3,* Dan-Dan Zhang,4 Zong-Min Fan,5 Hui-Jie Fan,1,2 Jie Yan,1,2 Li-Juan Chen,6 Hong Tang,6 Yan-Ru Qin,1,2 Xing-Ya Li1 1Department of Oncology, The First Affiliated Hospital of Zhengzhou University, 2Esophageal and Gastric Cancer Center of Henan Province, 3Department of Interventional Radiology, 4Department of Pathology, 5Henan Key Laboratory for Esophageal Cancer Research, The First Affiliated Hospital of Zhengzhou University, 6Department of Oncology, Tumor Hospital of Henan Province, Zhengzhou, Henan, People’s Republic of China *These authors contributed equally to this work Abstract: Molecular-targeted therapy against tyrosine kinase receptors (RTKs) plays an important role in gastric cancer (GC) treatment. Understanding the correlation between RTK coexpression could better guide clinical drug use. In the present study, the coexpression status of c-MET, fibroblast growth factor receptor 2 (FGFR2), and human epidermal growth factor receptor 2 (HER2) in human GC and their clinical significance in clinical therapy were explored. Immunohistochemical (IHC) staining, quantitative real-time polymerase chain reaction and fluorescent in situ hybridization were performed in 143 cases of GC who had undergone gastrectomy without preoperative chemoradiotherapy. Their association with clinicopathological features and clinical prognosis was analyzed. The frequencies of c-MET, FGFR2, and HER2 overexpression were 47.6% (68/143), 34.3% (49/143), and 10.5% (15/143), respectively. In the RTK coexpression study, 30.1% of patients (43/143) were positive for only one RTK, 25.8% (37/143) were positive for two RTKs, 3.5% (5/143) had triple-positive status, and 40.6% (58/143) had triple-negative status. In survival analysis, the overexpression of c-MET, FGFR2, and HER2 were significantly associated with overall survival (OS) (P=0.018, 0.004, and 0.049, respectively). In coexpression analysis, patients with triple-positive GC had the poorest OS (P=0.013). In conclusion, RTK coexpression is significantly associated with poor clinical outcome in GC. Keywords: c-MET, FGFR2, HER2, gastric cancer, coexpression, survival, target therapy

Flow-mediated vasodilation (FMD) is used for assessment of vascular endothelial function in humans as a predictor of cardiovascular events. It has been challenging to carry it on preclinical murine models due to the diminutive size of the femoral artery. Here, we present a new approach to accurately measure the blood velocity and femoral artery diameters of mice by acquiring Doppler optical coherence tomography and optical coherence tomography angiography continuously within 1 single experimental scanning protocol. Using the 3-dimensional imaging and new velocity algorithm, the measurement precision of diameter, blood flow, velocity and wall shear stress are improved to 0.91%, 11.0%, 10.7% and 14.0%, respectively. FMD of healthy mouse femoral artery measured by this method was 11.96% ± 0.98%, which was blunted to 5.69% ± 0.4% by intravenous administration of endothelial nitric oxide synthase inhibitor (L-NG -Nitroarginine methyl ester), in agreement with that reported in the literature.

The digitalization processes of documents produce frequently images with small rotation angles. The skew angles in document images degrade the performance of optical character recognition (OCR) tools. Therefore, skew detection of document images plays an important role in automatic document analysis systems. In this paper, we propose a Rectangular Active Contour Model (RAC Model) for content region detection and skew angle calculation by imposing a rectangular shape constraint on the zero-level set in Chan–Vese Model (C-V Model) according to the rectangular feature of content regions in document images. Our algorithm differs from other skew detection methods in that it does not rely on local image features. Instead, it uses global image features and shape constraint to obtain a strong robustness in detecting skew angles of document images. We experimented on different types of document images. Comparing the results with other skew detection algorithms, our algorithm is more accurate in detecting the skews of the complex document images with different fonts, tables, illustrations, and layouts. We do not need to pre-process the original image, even if it is noisy, and at the same time the rectangular content region of a document image is also detected.

Aerobic glycolysis is an important hallmark of cancer cells. Deficiency of pyruvate dehydrogenase component α subunit (PDHE1α) leads to mitochondrial dysfunction and promotes glycolysis. Therefore, studies on the expression of PDHE1α in cancer are warranted.The PDHE1α protein was immunohistochemically investigated and analyzed in 157 samples of surgically dissected esophageal squamous cell carcinoma (ESCC) and 21 'normal' esophageal epithelia tissues.PDHE1α protein expression was lower in ESCC. Absence of PDHE1α protein expression in tumor cells was found in 77.1% of cases. Negativity for PDHE1α protein in tumor cells was correlated with poor tumor differentiation (p0.05) and shorter overall survival (p0.05).Lack of PDHE1α protein expression in ESCC is associated with poor prognosis. Our findings also verify the existence of aerobic glycolysis switch in ESCC, and strongly advocate novel therapeutic strategies in reversing the Warburg effect in tumors.

Notch signaling involves the processes that govern cell proliferation, cell fate decision, cell differentiation and stem cell maintenance. Due to its fundamental role in stem cells, it has been speculated during the recent years that Notch family may have critical functions in cancer stem cells or cancer cells with a stem cell phenotype, therefore playing an important role in the process of oncogenesis. In this study, expression of Notch family in KYSE70, KYSE140 and KYSE450 squamous esophageal cancer cell lines and virus transformed squamous esophageal epithelial cell line Het-1A was examined by quantitative RT-PCR. Compared to the Het-1A cells, higher levels of Nocth1 and Notch3 expression in the cancer cell lines were identified. Due to the finding that NOTCH3 mainly mediates squamous cell differentiation, NOTCH1 expression was further studied in these cell lines. By Western blot analyses, the KYSE70 cell line which derived from a poorly differentiated tumor highly expressed Notch1, and the Notch1 expression in this cell line was hypoxia inducible, while the KYSE450 cell line which derived from a well differentiated tumor was always negative for Notch1, even in hypoxia. Additional studies demonstrated that the KYSE70 cell line was more 5-FU resistant than the KYSE450 cell line and such 5-FU resistance is correlated to Notch1 expression verified by Notch1 knockdown experiments. In clinical samples, Notch1 protein expression was detected in the basal cells of human esophagus epithelia, and its expression in squamous cell carcinomas was significantly associated with higher pathological grade and shorter overall survival. We conclude that Notch1 expression is associated with cell aggressiveness and 5-FU drug resistance in human esophageal squamous cell carcinoma cell lines in vitro and is significantly associated with a poor survival in human esophageal squamous cell carcinomas.

Xinjun Zhao,1,2,* Yue Hua,1,2,* Hongmei Chen,1,2,* Haiyu Yang,3,* Tao Zhang,1,2,* Guiqiong Huang,4,* Huijie Fan,1,2 Zhangbin Tan,1,2 Xiaofang Huang,1,2 Bin Liu,5 Yingchun Zhou1,21The Key Laboratory of Molecular Biology, State Administration of Traditional Chinese Medicine, School of Traditional Chinese Medicine, Southern Medical University, Guangdong, Guangzhou, People’s Republic of China; 2Nanfang Hospital, Southern Medical University, Guangdong, Guangzhou, People’s Republic of China; 3Jiangmen Wuyi Traditional Chinese Medicine Hospital, Guangdong, Jiangmen, People’s Republic of China; 4Huizhou Hospital of Traditional Chinese Medicine, Huizhou, People’s Republic of China; 5The Second Affiliated Hospital of Guangzhou Medical University, Guangdong, Guangzhou, People’s Republic of China*These authors contributed equally tothis workBackground: Aldehyde dehydrogenase-2 (ALDH2) has a protective effect on ischemic heart disease. Here, we examined the protective effects of ALDH2 on cardiac fibrosis through modulation of the Wnt/ß-catenin signaling pathway in a rat model of myocardial infarction (MI).Methods: Wistar rats were divided into the sham (control), MI (model), and ALDH2 activator (Alda-1) groups. After 10 days of treatment, the left ventricular (LV) remodeling parameters of each animal were evaluated by echocardiography. Myocardial fibrosis was evaluated by Masson’s trichrome staining and Sirius Red staining. Expression levels of collagen types I and III and β-smooth muscle actin (α-SMA) were examined. Finally, the expression and activity of ALDH2 and the levels of several Wnt-related proteins and genes, such as phospho-glycogen synthase kinase (GSK)-3β, GSK-3β, β-catenin, Wnt-1, WNT1-inducible signaling-pathway protein 1, and tumor necrosis factor (TNF)-α, were also analyzed.Results: After MI, the heart weight/body weight ratio, LV dimension at end diastole, and LV dimension at end systole were decreased, while the LV ejection fraction and LV fractional shortening were increased in the Alda-1 group. Myocardial fibrosis was also reduced in the Alda-1 group, accompanied by decreased expression collagen types I and III and α-SMA. β-Catenin, phosphorylated GSK-3β, and Wnt-1 levels were significantly increased in the model group. Interestingly, this alteration was partly reversed by Alda-1 treatment. Immunohistochemical staining showed that numerous WNT1-inducible signaling-pathway protein 1 (WISP-1)- and TNF-α-positive cells were found in the model group. However, few WISP-1- and TNF-α-positive cells were detected in the Alda-1 group.Conclusion: The reduction of cardiac fibrosis and the down-regulation of β-catenin, phosphorylated GSK-3β, Wnt-1, and WISP-1 may be mediated by increased ALDH2 activity, leading to reduction of MI-related cardiac fibrosis.Keywords: myocardial infarction, aldehyde dehydrogenase, cardiac fibrosis, Wnt signaling