Search

Extensive studies have shown that ERS may be implicated in the pathogenesis of DCM. We explored the therapeutic effects of lncRNAH19 on DCM and its effect on ERS-associated cardiomyocyte apoptosis.C57/BL-6j mice were randomly divided into 3 groups: non-DM group (controls), DM group (DCM), and lncRNAH19 overexpression group (DCM+H19 group). The effect of H19 on cardiac function was detected. The effect of H19 on cardiomyocyte apoptosis and cardiac fibrosis in DM was examined. Differentially expressed genes (DEGs) and activated pathways were examined by bioinformatics analysis. STRING database was applied to construct a PPI network using Cytoscape software. The expression of p-PERK, p-IRE1, ATF6, CHOP, cleaved caspase-3, -9, -12 and BAX proteins in cardiac tissue was used to determine the ERS-associated apoptotic indicators. We established the HG-stimulated inflammatory cell model. The expression of p-PERK and CHOP in HL-1 cells following HG was determined by immunofluorescence labeling. The effects of H19 on ERS and PI3K/AKT/mTOR pathway were also detected.H19 improved left ventricular dysfunction in DM. H19 could reduce cardiomyocytes apoptosis and improve fibrosisiin vivo/i. H19 could reduce the expression of p-PERK, p-IRE1α, ATF6, CHOP, cleaved caspase-3, cleaved caspase-9, cleaved caspase-12, and BAX proteins in cardiac tissues. Furthermore, H19 repressed oxidative stress, ERS and apoptosisiin vitro/i. Moreover, the effect of H19 on ERS-associated apoptosis might be rescued by LY294002 (the specific inhibitor for PI3K and AKT).H19 attenuates DCM in DM and ROS, ERS-induced cardiomyocyte apoptosis, which is associated with the activation of PI3K/AKT/mTOR signaling pathway.

Kernel adaptive filtering (KAF) algorithms derived from the second moment of error criterion perform very well in nonlinear system identification under assumption of the Gaussian observation noise; however, they inevitably suffer from severe performance degradation in the presence of non-Gaussian impulsive noise and interference. To resolve this dilemma, we propose a novel robust kernel least logarithmic absolute difference (KLLAD) algorithm based on logarithmic error cost function in reproducing kernel Hilbert spaces, taking into account of the non-Gaussian impulsive noise. The KLLAD algorithm shows considerable improvement over the existing KAF algorithms without restraining impulsive interference in terms of robustness and convergence speed. Moreover, the convergence condition of KLLAD algorithm with Gaussian kernel and fixed dictionary is presented in the mean sense. The superior performance of KLLAD algorithm is confirmed by the simulation results.

Rigosertib (RGS) is a benzyl styryl sulfone which exhibits impressive cytotoxicity in cancer cells. However, its modulating effect on tumor immune microenvironment remains elusive. In our experiments, compared with immunodeficient mouse model, increased tumor growth arrest and robust anti-tumor immunity were observed in RGS-treated colorectal cancer (CRC) xenograft tumors in immunocompetent mice.Intriguingly, RGS markedly down-regulated programmed cell death ligand 1 (PD-L1) expression in both vivo and in vitro. Meanwhile, RGS increased autophagic vacuole number in CRC cells as seen by transmission electron microscopy and immunofluorescence. Moreover, increased LC3-II level and tandem- mRFP- GFP- LC3 labeled vacuole accumulation demonstrated RGS-induced autophagic flux.Mechanistically, it is the activation of AMP-activated protein kinase-UNC-51-like kinase 1 (AMPK-ULK1) axis, rather than the canonical mTOR signaling pathway, that plays a pivotal role in RGS-induced autophagy. AMPK-ULK1 dependent autophagy inhibition, by either short interfering RNA or chemical inhibitors, blocked RGS-induced PD-L1 degradation. Finally, RGS exhibited synergistic anti-tumor activity with cytotoxic T-lymphocyte-associated protein 4 monoclonal antibody in the CRC xenograft model. Furthermore, apart from the immunomodulatory effect, we also confirmed the direct cytotoxicity of RGS in inducing mitochondria-related apoptosis. Altogether, considering its PD-L1 inhibitory and cytotoxic effects, RGS could be a promising drug for CRC therapy.

In order to explore the computerized tomography (CT) based on three-dimensional reconstruction of coronary artery model, the functional evaluation was made after percutaneous coronary intervention (PCI). In this study, 90 patients with coronary heart disease who received elective PCI were selected. The blood flow reserve fraction (FFR) and SYNTAX score were calculated by three-dimensional reconstruction of CT images, followed up for 2–4 years. According to the SYNTAX score, 0–22 points were defined as the low group (28 cases), 23–32 points as the medium group (33 cases), and 33 points as the high group (29 cases). In this paper, the accuracy, sensitivity, and specificity of CT images of three-dimensional reconstructed coronary artery model are 91%, 73%, and 62%, respectively. The follow-up results showed that the incidence of major adverse cerebrovascular events in the high group was significantly higher than that in the low group and the middle group, and the difference was statistically significant ( P < 0.05 ). Pearson correlation analysis showed that SYNTAX score was related to serum total cholesterol (r = 0.234, P = 0.003 ), triglyceride (r = 0.237, P = 0.014 ), low-density lipoprotein cholesterol (r = 0.285, P = 0.004 ), and ApoB/ApoA1 (R = 0.004). In this study, FFR is calculated by CT images based on three-dimensional reconstruction of coronary artery model, which can provide support for the diagnosis and treatment of coronary heart disease. SYNTAX score can be used as a risk predictor for PCI patients with coronary heart disease.

RAS genes are the most frequently mutated oncogenes and play critical roles in the development and progression of malignancies. The mutation, isoform (KRAS, HRAS, and NRAS), position, and type of substitution vary depending on the tissue types. Despite decades of developing RAS-targeted therapies, only small subsets of these inhibitors are clinically effective, such as the allele-specific inhibitors against KRAS

Early identification of metastatic or recurrent colorectal cancer (CRC) patients who will be sensitive to FOLFOX (5‐FU, leucovorin and oxaliplatin) therapy is very important. We performed microarray meta‐analysis to identify differentially expressed genes (DEGs) between FOLFOX responders and nonresponders in metastatic or recurrent CRC patients, and found that the expression levels of WASHC4, HELZ, ERN1, RPS6KB1, and APPBP2 were downregulated, while the expression levels of IRF7, EML3, LYPLA2, DRAP1, RNH1, PKP3, TSPAN17, LSS, MLKL, PPP1R7, GCDH, C19ORF24, and CCDC124 were upregulated in FOLFOX responders compared with nonresponders. Subsequent functional annotation showed that DEGs were significantly enriched in autophagy, ErbB signaling pathway, mitophagy, endocytosis, FoxO signaling pathway, apoptosis, and antifolate resistance pathways. Based on those candidate genes, several machine learning algorithms were applied to the training set, then performances of models were assessed via the cross validation method. Candidate models with the best tuning parameters were applied to the test set and the final model showed satisfactory performance. In addition, we also reported that MLKL and CCDC124 gene expression were independent prognostic factors for metastatic CRC patients undergoing FOLFOX therapy., We performed the microarray meta‐analysis to identify common differentially expressed genes between FOLFOX responders and non‐responders in metastatic or recurrent colorectal cancer patients, and built prediction models with machine learning algorithms.

This study was to analyze the diagnostic value of coronary computed tomography angiography (CCTA) and fractional flow reserve (FFR) based on computer-aided diagnosis (CAD) system for coronary lesions and the possible impact of calcification. 80 patients who underwent CCTA and FFR examination in hospital were selected as the subjects. The FFR value of 0.8 was used as the dividing line and divided into the ischemic group ( FFR ≤ 0.8 ) and nonischemic group ( FFR > 0.8 ). The basic data and imaging characteristics of patients were analyzed. The maximum diameter stenosis rate (MDS %), maximum area stenosis rate (MAS %), and napkin ring sign (NRS) in the ischemic group were significantly lower than those in the nonischemic group ( P < 0.05 ). Remodeling index (RI) and eccentric index (EI) compared with the nonischemic group had no significant difference ( P > 0.05 ). The total plaque volume (TPV), total plaque burden (TPB), calcified plaque volume (CPV), lipid plaque volume (LPV), and lipid plaque burden (LPB) in the ischemic group were significantly different from those in the non-ischemic group ( P < 0.05 ). MAS % had the largest area under curve (AUC) for the diagnosis of coronary myocardial ischemia (0.74), followed by MDS % (0.69) and LPV (0.68). CT-FFR had high diagnostic sensitivity, specificity, accuracy, truncation value, and AUC area data for patients in the ischemic group and nonischemic group. The diagnostic sensitivity, specificity, accuracy, cutoff value, and AUC area data of CT-FFR were higher in the ischemic group (89.93%, 92.07%, 95.84%, 60.51%, 0.932) and nonischemic group (93.75%, 90.88%, 96.24%, 58.22%, 0.944), but there were no significant differences between the two groups ( P > 0.05 ). In summary, CT-FFR based on CAD system has high accuracy in evaluating myocardial ischemia caused by coronary artery stenosis, and within a certain range of calcification scores, calcification does not affect the diagnostic accuracy of CT-FFR.

The slot combination of stator and rotor plays a decisive role in the tangential force and radial force of the motor, to obtain the influence of slot combination on motor vibration and noise, taking a 55kW asynchronous motor with a maximum speed of 1500 r/min as an example, and four kinds of motors with different slot combination were designed. The order and frequency of electromagnetic force waves with different slot combinations were estimated by numerical method, and the influence of slot combination on the vibration of the motor was studied by test.

Cardiomyocyte apoptosis is a fundamental pathogenic factor leading to myocardial ischemia/reperfusion (MI/R) injury. The long non-coding RNA (IncRNA) TUG1 regulates apoptosis in various cell types. We report here that TUG1 expression is induced in mouse heart following MI/R injury as well as in cardiomyocytes subjected to simulated ischemia/reperfusion (SI/R) in vitro. Clinically, TUG1 expression is also elevated in plasma from patients with acute myocardial infarction (AMI), which implies its potential application as a disease biomarker. Functionally, TUG1 overexpression promotes, and its knockdown reduces SI/R-induced lactate dehydrogenase (LDH) release and caspase-3 activity in cardiomyocytes in vitro, illustrating that TUG1 exacerbates SI/R-induced apoptosis. Furthermore, in vivo, TUG1 aggravates MI/R injury in a mouse model, and subsequent observations show concurrent increased apoptosis of cardiomyocytes. Hence, this study unveils a clinical relevance and functional role of TUG1 in MI/R injury, and also implicates that targeting TUG1 may have therapeutic effects in treating MI/R injury.

Patients with chronic dialysis dependency undergoing percutaneous coronary intervention (PCI) are at a greater risk of hemorrhagic and ischemic events. Due to their exclusion from randomized clinical trials, the optimal antithrombotic regimen for this population remains unknown. Bivalirudin has been associated with fewer hemorrhagic complications than unfractionated heparin (UFH) in patients undergoing PCI. We evaluated major adverse cardiac event (MACE) and hemorrhagic event rates for an antithrombotic regimen using bivalirudin or UFH during PCI in acute coronary syndrome (ACS) patients with chronic dialysis dependency.A retrospective study was performed, including 211 patients on dialysis undergoing PCI due to ACS from January 2014 to April 2019 at the China-Japan Friendship Hospital. Patients were divided into 2 groups based on anticoagulation regimen: the bivalirudin group (86 cases) or the UFH group (125 cases) during and after PCI. Statistical analyses were used to compare MACE and hemorrhagic events between groups at 30 days after PCI.No patients experienced stent thrombosis within 30 days after PCI regardless of anticoagulant. There was no difference in the incidence of MACE in the bivalirudin group compared with the UFH group (6.98% vs 8.80%, respectively; P.05). The rate of hemorrhagic events in the bivalirudin group was significantly lower than in the UHP group (5.81% vs 18.4%, respectively; P.05), particularly for rates of mild bleeding (4.65% vs 15.2%, respectively; P.05). There were no significant differences in rates of severe bleeding between the bivalirudin and UFH groups (1.16% vs 4.00%, respectively; P.05), although fewer severe hemorrhagic events occurred in the bivalirudin group.Bivalirudin was associated with fewer bleeding events following PCI in individuals with end-stage renal disease on dialysis.

In this paper, we propose a nonlinear recurrent kernel normalized LMS (NR-KNLMS) algorithm based on the algorithmic framework of multikernel adaptive filtering for nonlinear autoregressive systems. By introducing the time delay of the desired output as a part of augmented input, the NR-KNLMS algorithm with taking into account of the nonlinear recurrent is able to improve the filtering performance in terms of convergence rate and excess mean-square-error compared with the regular KNLMS algorithm and the existing socalled linear recurrent kernel adaptive filters. Numerical tests showcase the superiority of NR-KNLMS algorithm over state-of-the-art algorithms.

Mutant KRAS, the principal isoform of RAS, plays a pivotal role in the oncogenesis of colorectal cancer by constitutively activating the RAF/MEK/ERK and PI3K/AKT pathways. Effective targeted therapies are urgently needed. We investigated whether rigosertib, a benzyl styryl sulfone RAS signaling disruptor, could selectively killCCK-8 was used to determine the cell viability. Patient-derived tumor and cancer cell xenograft models were used to detect the inhibitory efficacy of rigosertib. Flow cytometry was used to evaluate the apoptosis and cell cycle progression. Apoptosis and cell cycle arrest markers were detected by Western blot. DCFH-DA was used to determine the reactive oxygen species. Immunohistochemistry staining and Western blot were performed to characterize RAS signaling markers in colorectal cancer tissues and cells.Rigosertib (RGS) exhibited a cytotoxic effect against colorectal cancer cells, which was greater inThese data showed that targeting RAS signaling using RGS could be a therapeutic treatment for

BACKGROUND The prognosis of percutaneous coronary intervention (PCI) for chronic total occlusion (CTO) between patients with diabetes mellitus (DM) and those without DM is unknown. This study aimed to investigate whether DM has adverse effects on CTO PCI patients. METHODS This single-center retrospective study included consecutive patients who underwent PCI for CTO at the China-Japan Friendship Hospital (Beijing, China) between January 2016 and April 2019. The clinical outcomes during follow-up were compared between patients with DM and those without DM. RESULTS The analysis included 187 patients (152 males) aged 62.6±11.5 years. A total of 99 participants (52.9%) had DM, which involved a higher body mass index (BMI) and triglyceride level than those without DM (P

This research aims to segment colonoscopic images by automatically extracting polyp features by exploiting the strengths of convolution neural networks (CNN). The proposed model employs deep learning and adaptive regularization techniques. The model is structurally composed of two cascaded encoder–decoder networks, each of which is constructed by four CNN layers and two full connection layers. The front model is built on backpropagation learning for segmenting a colonoscopic polyp image. The output images from the precedent hetero-encoder are regarded as corrupted labeled images, especially during the time period close to the end of learning, and are selectively fed into the successive auto-encoder for denoising learning to enhance its discriminative power and relieve the problem of a lack of labeled data for medical image tasks. The performance of the proposed model can be further improved by a simple fuzzy logic approach setting the regularization parameter in the loss function. The proposed method utilizes features learned from some open medical datasets and our own collected dataset. The performance of the proposed architecture is compared with a state-of-the-art network. The evaluation shows the performances of the proposed method are consistent across all the datasets and often outperform the state-of-art model.

ColorColorectal cancer is one of the most common cancer worldwide. Recently, tumor microenvironment (TME), especially its remoulding , is thought to control the colorectal cancer genesis and progression. In this study, we use ESTIMATEscore to make out the proportion of immune and stromal components in colorectal adenocarcinoma (CRA) samples from The Cancer Genome Atlas (TCGA) database. The differentially expressed genes (DEGs) were found by COX regression analysis and protein-protein interaction (PPI) network, among which TGFβ1 was supposed to be a prognosis factor and tumor environment indicator. Continuous analysis showed that TGFβ1 expression is positively correlated with lymph node metastasis (N stage) but negatively correlated with survival. Gene Set Enrichment Analysis (GSEA) revealed that the genes of the high-expression TGFβ1 group were mainly enriched in immune-related activities. Cluster analysis divided the samples into 2 subgroups. 24 HLA-related genes and 8 immune checkpoint genes were found upregulated in the high immunity group as well as TGFβ1, which suggests the possibility of novel therapies targeting immune checkpoints combined with TGFβ1. Tumor-infiltrating immune cell (TIC) profile of CRA patients was described by CIBERSORT analysis. Further analysis showed that the infiltration of Tregs and Neutrophils were positively correlated with TGFβ1 high expression. Then 3 TGFβ1-related genes were picked out to construct a prognostic model, which matches the survival data well.

Objectives: Allicin is an allyl 2-propenethiosulfinate or diallyl thiosulfinate acid with cardioprotective effects in myocardial ischemia/reperfusion (MI/R) injury. This study aims to examine the underlying mechanism by which Allicin protects against MI/R. Methods: C57BL6 mice were subjected to either sham or MI/R surgery, and mice in the Allicin group were injected with Allicin (5 mg/ml) before the induction of ischemia. The cardiac function and histopathology of experimental mice were evaluated by ultrasound quantification and Masson staining. We next measured the capillary angiogenesis of the peri-infarct area by Masson staining and immunohistochemical staining. The miRNA microarray was carried out to examine the expressed miRNAs in MI/R tissues and corresponding normal tissues. Real-time quantitative polymerase chain reaction (q-PCR) was performed to validate the selected miRNA-19α-3p gene expression. Besides, we evaluated the myocardial lactate dehydrogenase and COX-2 by immunofluorescence staining. The western blot analysis was used to evaluate the protein levels of p-AKT, p-PI3K, p-mTOR, COX-2, and VEGF protein in the Allicin and Model group. In vitro study, LPS stimulated Tie2 expressing macrophages were cultured in an ischemic buffer. We evaluated the accumulation of VEGF by fura-2/AM fluorescence. Besides, Western blotting was performed to examine the protein levels of p-PI3K, p-AKT, p-mTOR, VEGF, COX2, and MMP2. The PI3K inhibitor was applied to investigate whether Allicin-induced myocardial ischemia-reperfusion injury protection is mediated via the PI3K/AKT pathway. And the miR-19α-3p mimic/inhibitor were transfected to promote/inhibit the expression of miR-19a-3p for verifying the regulation of miR-19a-3p on PI3K pathway. Results: Allicin pretreatment significantly improved I/R-induced cardiac function damage. Furthermore, Allicin could repress cardiac fibrosis, as evidenced by reduced areas of cardiac fibrosis. Allicin’s effect on the MI/R was associated with increased capillary angiogenesis. Microarray analysis exposed that miR-19a-3p down-regulated PIK3CA (PI3K) expression by directly targeting the PIK3CA gene. The regulation of the angiogenesis pathway and gene miRNA-19a-3p might affect the Allicin-induced MI/R protection. Immunofluorescence staining revealed that COX-2 and myocardial lactate dehydrogenase were significantly increased after Allicin treatment. Furthermore, western blot analysis demonstrated that p-AKT, p-PI3K, p-mTOR, COX-2, and VEGF protein levels were also increased in the Allicin group. In vitro study, the protein levels of p-PI3K, p-AKT, p-mTOR, VEGF, COX2, and MMP2 were significantly increased in the Allicin-treated Tie2 expressing macrophages. These effects were partially reversed by PI3K inhibitor (Wortmannin) treatment. MiR-19α-3p plays an important role in myocardial I/R injury. It could regulate the activity of the PI3K-AKT pathway. And inhibition of miR-19a-3p promoted angiogenesis by regulating PI3K/AKT pathway. Conclusions: Allicin pretreatment protects against myocardial I/R and activating the miR-19a-3p/PI3K/AKT pathway.

Objective: Mutant KRAS, the principal isoform of RAS, plays a pivotal role in the oncogenesis of colorectal cancer by constitutivelyactivating the RAF/MEK/ERK and PI3K/AKT pathways. Effective targeted therapies are urgently needed. We investigated whetherrigosertib, a benzyl styryl sulfone RAS signaling disruptor, could selectively kill KRAS-mutant colorectal cancer cells. Methods: CCK-8 was used to determine the cell viability. Patient-derived tumor and cancer cell xenograft models were used todetect the inhibitory efficacy of rigosertib. Flow cytometry was used to evaluate the apoptosis and cell cycle progression. Apoptosisand cell cycle arrest markers were detected by Western blot. DCFH-DA was used to determine the reactive oxygen species.Immunohistochemistry staining and Western blot were performed to characterize RAS signaling markers in colorectal cancer tissuesand cells. Results: Rigosertib (RGS) exhibited a cytotoxic effect against colorectal cancer cells, which was greater in KRAS-mutant cells.Furthermore, RGS induced mitotic arrest and oxidative stress-dependent apoptosis in KRAS-mutant DLD1 and HCT116 cells.Besides, RGS disrupted RAS signaling, and the inhibition of RAS/MEK/ERK was independent of cellular oxidative stress. Usingpatient-derived xenograft models, the response and tumor inhibition of RGS were significantly higher in the KRAS-mutantsubgroup, while p-MEK, p-ERK, and p-AKT levels of RGS-treated tumors were significantly decreased. Finally, in a KRAS-mutant,chemotherapy-resistant patient-derived xenograft model, RGS showed a stronger therapeutic effect than the combination standardtherapy involving fluoropyrimidine + oxaliplatin/irinotecan + bevacizumab. Conclusions: These data showed that targeting RAS signaling using RGS could be a therapeutic treatment for KRAS-mutantcolorectal cancer patients.

Background. Stage II colorectal cancer patients had heterogeneous prognosis, and patients with recurrent events had poor survival. In this study, we aimed to identify stage II colorectal cancer recurrence associated genes by microarray meta-analysis and build predictive models to stratify patients’ recurrence-free survival. Methods. We searched the GEO database to retrieve eligible microarray datasets. The microarray meta-analysis was used to identify universal recurrence associated genes. Total samples were randomly divided into the training set and the test set. Two survival models (lasso Cox model and random survival forest model) were trained in the training set, and AUC values of the time-dependent receiver operating characteristic (ROC) curves were calculated. Survival analysis was performed to determine whether there was significant difference between the predicted high and low risk groups in the test set. Results. Six datasets containing 651 stage II colorectal cancer patients were included in this study. The microarray meta-analysis identified 479 recurrence associated genes. KEGG and GO enrichment analysis showed that G protein-coupled glutamate receptor binding and Hedgehog signaling were significantly enriched. AUC values of the lasso Cox model and the random survival forest model were 0.815 and 0.993 at 60 months, respectively. In addition, the random survival forest model demonstrated that the effects of gene expression on the recurrence-free survival probability were nonlinear. According to the risk scores computed by the random survival forest model, the high risk group had significantly higher recurrence risk than the low risk group (HR = 1.824, 95% CI: 1.079–3.084, p = 0.025). Conclusions. We identified 479 stage II colorectal cancer recurrence associated genes by microarray meta-analysis. The random survival forest model which was based on the recurrence associated gene signature could strongly predict the recurrence risk of stage II colorectal cancer patients.

Additional file 4: Table S1. The stages of CRC patients and the corresponding exosomal ANGPTL1 index calculated by ImageJ from WB brands. The CRC stage was based on 7th revised edition of the AJCC Colorectal Cancer.

Background Angiopoietin-like protein 1 (ANGPTL1) has been proved to suppress tumor metastasis in several cancers. However, its extracellular effects on the pre-metastatic niches (PMNs) are still unclear. ANGPTL1 has been identified in exosomes, while its function remains unknown. This study was designed to explore the role of exosomal ANGPTL1 on liver metastasis in colorectal cancer (CRC). Methods Exosomes were isolated by ultracentrifugation. The ANGPTL1 level was detected in exosomes derived from human CRC tissues. The effects of exosomal ANGPTL1 on CRC liver metastasis were explored by the intrasplenic injection mouse model. The liver PMN was examined by vascular permeability assays. Exosomal ANGPTL1 localization was validated by exosome labeling. The regulatory mechanisms of exosomal ANGPTL1 on Kupffer cells were determined by RNA sequencing. qRT-PCR, Western Blot, and ELISA analysis were conducted to examine gene expressions at mRNA and protein levels. Results ANGPTL1 protein level was significantly downregulated in the exosomes derived from CRC tumors compared with paired normal tissues. Besides, exosomal ANGPTL1 attenuated liver metastasis and impeded vascular leakiness in the liver PMN. Moreover, exosomal ANGPTL1 was mainly taken up by KCs and regulated the KCs secretion pattern, enormously decreasing the MMP9 expression, which finally prevented the liver vascular leakiness. In mechanism, exosomal ANGPTL1 downregulated MMP9 level in KCs by inhibiting the JAK2-STAT3 signaling pathway. Conclusions Taken together, exosomal ANGPTL1 attenuated CRC liver metastasis and impeded vascular leakiness in the liver PMN by reprogramming the Kupffer cell and decreasing the MMP9 expression. This study suggests a suppression role of exosomal ANGPTL1 on CRC liver metastasis and expands the approach of ANGPTL1 functioning.

The shaft centerline orbit of the rotor is an essential characteristic in the condition monitoring system of rotating power equipment. In this paper, an intelligent method based on a convolutional neural network (CNN) used for the identification of the shaft centerline orbit. According to the features sampled data of the shaft centerline orbit, a discretization matrix is designed to characterize the feature of the orbit. The test results show that, compared with the recognition methods based on moment extraction features and the methods based on CNN with the classical network structure, the proposed method has higher accuracy and faster recognition speed in the diagnosis process of the discrete shaft centerline orbit under a small sample and fewer computer resources.

Jingsun Wei,1,2,* Yucheng Qian,1,2,* Yang Tang,1,2 Xiaoxu Ge,1,2 Kai Jiang,1,2 Yimin Fang,1,2 Dongliang Fu,1,2 Xiangxing Kong,1 Qian Xiao,1 Kefeng Ding1,2 1Department of Colorectal Surgery and Oncology, Key Laboratory of Cancer Prevention and Intervention, Ministry of Education, The Second Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, Zhejiang, People’s Republic of China; 2Cancer Institute, The Second Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, Zhejiang, People’s Republic of China*These authors contributed equally to this workCorrespondence: Kefeng DingDepartment of Colorectal Surgery and Oncology, Key Laboratory of Cancer Prevention and Intervention, Ministry of Education, The Second Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou 310009, Zhejiang, People’s Republic of ChinaTel/Fax +86-571-87784820Email dingkefeng@zju.edu.cnPurpose: N6-methyladenosine (m6A) modifications represent one of the most common methylation modifications, and they are mediated by m6A RNA methylation regulators. However, their functions in renal cell carcinoma (RCC) are not completely understood. The aim of this study was to investigate the effects of the regulators in RCC.Materials and Methods: The expression levels of the 13 main m6A RNA methylation regulators in RCC were detected and consensus clustering was performed to explore their relationships with RCC. Thereafter, a risk signature based on the regulators was established. This risk model was fully verified by conducting prognostic analyses using two datasets (The Cancer Genome Atlas [TCGA] and Gene Expression Omnibus [GEO] datasets) and a ROC curve analysis.Results: Of the 13 main m6A regulators, six were significantly upregulated and four were significantly downregulated in 893 RCC cases compared to 128 normal controls in the TCGA database. Consensus clustering based on the regulators identified two clusters of RCC cases, which were significantly associated with a pathological characteristic (T status). Thus, these results indicated that m6A RNA methylation regulators were associated with RCC. Thereafter, a risk model involving two of the regulators (METTL14 and WTAP) was established. The alterations in the mRNA and protein expression levels of these two regulators were further confirmed based on Human Protein Atlas data and real-time PCR in RCC and normal cell lines. The results indicated that the risk model may serve as an independent prognostic marker of overall survival, and it was also associated with clinicopathological characteristics (T status, M status, pathological stage, and gender) in RCC.Conclusion: Collectively, the results of this study indicated that the risk model (based on two m6A RNA methylation regulators) may serve as an independent prognostic indicator of RCC, which may aid further investigation into m6A RNA modification in RCC.Keywords: renal cell carcinoma, m6A methylation, TCGA, prognostic signature

Background: Angiopoietin-like protein 1 (ANGPTL1) has been proved to suppress tumor metastasis in several cancers. However, its extracellular effects on the pre-metastatic niches (PMNs) are still unclear. ANGPTL1 has been identified in exosomes, while its function remains unknown. This study was designed to explore the role of exosomal ANGPTL1 on liver metastasis in colorectal cancer (CRC).Methods: Exosomes were isolated by ultracentrifugation. The ANGPTL1 level was detected in exosomes derived from human CRC tissues. The effects of exosomal ANGPTL1 on CRC liver metastasis were explored by the intrasplenic injection mouse model. The liver PMN was examined by vascular permeability assays. Exosomal ANGPTL1 localization was validated by exosome labeling. The regulatory mechanisms of exosomal ANGPTL1 on Kupffer cells were determined by RNA sequencing. qRT-PCR, Western Blot, and ELISA analysis were conducted to examine gene expressions at mRNA and protein levels.Results: ANGPTL1 protein level was significantly downregulated in the exosomes derived from CRC tumors compared with paired normal tissues. Besides, exosomal ANGPTL1 attenuated liver metastasis and impeded vascular leakiness in the liver PMN. Moreover, exosomal ANGPTL1 were mainly taken up by KCs and regulated the KCs secretion pattern, especially decreasing the MMP9 expression, which finally prevented the liver vascular leakiness. In mechanism, exosomal ANGPTL1 downregulated MMP9 level in KCs by inhibiting the JAK2-STAT3 signaling pathway.Conclusions: Taken together, exosomal ANGPTL1 attenuated CRC liver metastasis and impeded vascular leakiness in the liver PMN by reprogramming the Kupffer cell and decreasing the MMP9 expression. This study suggests a suppression role of exosomal ANGPTL1 on CRC liver metastasis and expands the approach of ANGPTL1 functioning.

Purpose. Colorectal cancer is one of the most common malignant primary tumors, prone to metastasis, and associated with a poor prognosis. As autophagy is closely related to the development and treatment of colorectal cancer, we investigated the potential prognostic value of long noncoding RNA (lncRNA) associated with autophagy in colorectal cancer. Methods. In this study, we acquired information on the expression of lncRNAs in colorectal cancer from the Cancer Genome Atlas (TCGA) database and found that 860 lncRNAs were associated with autophagy-related genes. Subsequently, univariate Cox regression analysis was used to investigate 32 autophagy-related lncRNAs linked to colon cancer prognosis. Subsequently, eight of the 32 autophagy-related lncRNAs (i.e., long intergenic nonprotein coding RNA 1503 [LINC01503], ZEB1 antisense RNA 1 [ZEB1-AS1], AC087481.3, AC008760.1, AC073896.3, AL138756.1, AL022323.1, and TNFRSF10A-AS1) were selected through multivariate Cox regression analysis. Based on these autophagy-related lncRNAs, a risk signature was constructed, and the patients were divided into high- and low-risk groups. Results. The high-risk group’s overall survival time was significantly shorter than that of the low-risk group p < 0.0001 . Receiver operating characteristic curve analysis was performed to further confirm the validity of the model (area under the curve: 0.689). Moreover, multivariate regression suggested that the risk score was a significant prognostic risk factor in colorectal cancer. Gene set enrichment analysis showed that these gene sets are significantly enriched in cancer-related pathways, such as Kirsten rat sarcoma viral oncogene homolog (KRAS) signaling. Conclusion. The risk signature of eight autophagy-related lncRNAs has prognostic potential for colorectal cancer. These autophagy-related lncRNAs may play a vital role in the biology of colorectal cancer.

Summary: Lumbar laminectomy often results in failed back surgery syndrome. Most scholars support the three-dimensional theory of adhesion: Fibrosis surrounding the epidural tissues is based on the injured sacrospinalis behind, fibrous rings and posterior longitudinal ligaments. Approaches including using the minimally invasive technique, drugs, biomaterial and nonbiomaterial barriers to prevent the postoperative epidural adhesion were intensively investigated. Nevertheless, the results are far from satisfactory. Our review is based on various implant biomaterials that are used in clinical applications or are under study. We show the advantages and disadvantages of each method. The summary will help us to figure out ideas towards new techniques.The translational potential of this article: This review summarises recent biomaterials-related clinical and basic research that focuses on prevention of epidural adhesion after lumbar laminectomy. We also propose a novel possible translational method where a soft scaffold acts as a physical barrier in the early stage, engineered adipose tissue acts as a biobarrier in the later stage in the application of biomaterials and adipose-derived mesenchymal stem cells are used for prevention of epidural adhesion. Keywords: Adhesion, Biomaterials, Fibrosis, Implant, Laminectomy

We present a polymer-coated silicon microring resonator to detect volatile organic compounds (VOC) gases. Absorption of VOC gases into the polymer alters the refractive index around the microring, which enables quantification of absorbed gases as a resonance wavelength shift in the resonator. Two different polymers, hyperbranched polyesteramid and poly(2-vinyl pyridine), are tested as the absorption layers on the highly sensitive (80 nm/RIU and 10,000 Q-factor) silicon microring resonator. The sensing responses to VOC gases are characterized by flowing four different gases: styrene, acetone, toluene, and isoprene, in a wide range of concentration (sub-ppm to 100 ppm range). The hyperbranched polyesteramid coated sensor shows the highest sensitivity to styrene. Similarly, Poly(2-vinyl pyridine) coated device exhibits sensitive responses to styrene and acetone. From experiments with a wide range of gas concentrations, we observe that the sensors have two distinguished characteristics; linear and non-linear response with respect to gas concentration. To account for it, a dual mode sensing mechanism is proposed; Langmuir mode (doping effect) in the low concentration (

Background: Coronary intervention therapy is the main treatment for uremic patients with coronary heart disease. The studies on whether dialysis reduces the efficacy of dual antiplatelet drugs are limited. The aim of this study was to examine the effect of dialysis on antiplatelet drugs in uremic patients with coronary heart disease. Methods: This study included 26 uremic patients who had undergone percutaneous coronary intervention in China-Japan Friendship Hospital from November 2015 to May 2017. We examined their thromboelastography results before and after hemodialysis. Self-paired t-tests were employed to analyze changes in the inhibition rate of platelet aggregation. Results: The mean inhibition rates of arachidonic acid-induced platelet aggregation before and after hemodialysis were 82.56 ± 2.79% and 86.42 ± 3.32%, respectively (t = −1.278, P = 0.213). The mean inhibition rates of adenosine diphosphate-induced platelet aggregation before and after hemodialysis were 67.87 ± 5.10% and 61.94 ± 5.90%, respectively (t = 1.425, P = 0.167). There was no significant difference in the inhibition rates of platelet aggregation before or after hemodialysis. These results also applied to patients with different sensitivity to aspirin and clopidogrel. Conclusion: Dialysis did not affect the antiplatelet effects of aspirin and clopidogrel in uremic patients with coronary heart disease. Key words: Antiplatelet Drug; Coronary Intervention; Dialysis; Thromboelastography

Background Laparoscopic surgery, fast-track perioperative treatment and XELOX chemotherapy are effective strategies for shortening the duration of hospital stay for cancer patients. This trial aimed to clarify the safety and efficacy of the fast-track multidisciplinary treatment (FTMDT) model compared to conventional surgery combined with chemotherapy in Chinese colorectal cancer patients. Methods This trial was a prospective randomized controlled study with a 2 × 2 balanced factorial design and was conducted at six hospitals. Patients in group 1 (FTMDT) received fast-track perioperative treatment and XELOX adjuvant chemotherapy. Patients in group 2 (conventional treatment) received conventional perioperative treatment and mFOLFOX6 adjuvant chemotherapy. Subgroups 1a and 2a had laparoscopic surgery and subgroups 1b and 2b had open surgery. The primary endpoint was total length of hospital stay during treatment. Results A total of 374 patients were randomly assigned to the four subgroups, and 342 patients were finally analyzed, including 87 patients in subgroup 1a, 85 in subgroup 1b, 86 in subgroup 2a, and 84 in subgroup 2b. The total hospital stay of group 1 was shorter than that of group 2 [13 days, (IQR, 11–17 days) vs. 23.5 days (IQR, 15–42 days), P = 0.0001]. Compared to group 2, group 1 had lower surgical costs, fewer in-hospital complications and faster recovery (all P P P = 0.7420]. Conclusions The FTMDT model, which integrates laparoscopic surgery, fast-track treatment, and XELOX chemotherapy, was the superior model for enhancing the recovery of Chinese patients with colorectal cancer. Trial registration ClinicalTrials.gov: NCT01080547, registered on March 4, 2010.

IntroductionPatients with chronic heart failure (CHF) can benefit from exercise rehabilitation (ER) with significant improvements in exercise capacity, quality of life and reduction in hospitalisations. Despite its reported benefits, only a small number of patients with CHF attend ER due to poor adherence, and improper exercise may even lead to adverse events. Remote ECG monitoring system (REMS) has the potential to overcome these obstacles. We hypothesise that home-based cardiac ER using REMS in CHF patients is effective compared with conventional ER without monitoring.Methods and analysisThis study is a prospective, randomised, parallel controlled clinical trial designed to evaluate the effectiveness of home-based phase-II ER with REMS in the treatment of CHF with a target enrolment of 120 patients (left ventricular ejection fraction 2 peak) (baseline vs 3 m). Secondary outcomes include 6-min walk test, NYHA classes, echocardiographic parameters, cardiac biomarkers, major adverse cardiovascular events, quality of life, psychological well-being and patients’ adherence to the rehabilitation programme.Ethics and disseminationThis study was approved by Ethics Committee of China-Japan Friendship Hospital for Clinical Research (No. 2018–55 K39). The results of this study will be disseminated via peer-reviewed publications and presentations at conferences.Trial registration numberChiCTR-RNR-17012446; Pre-results.

Based on double screw pump as the research object, the vibration of twin screw pump under different outlet conditions and different technological parameters were tested. The vibration characters of the pump under various technological parameters were analyzed from the experimental point of view. The key parameters influencing the vibration characteristic of twin screw pump were found out and corresponding optimization measures were taken. By using the numerical method of fluid mechanics, the three-dimensional flow field inside the pump chamber was analyzed, and the internal working mechanistic and influencing factors were discussed. Local optimization was carried out to reduce the influence of fluid excitation force on structure vibration. The research results of this paper can provide necessary practical basis for the optimization of vibration and noise reduction of twin screw pump.

In General, the frequency feature of cavitation was obtained by comparing it with normal signal. However, when there were a large number of samples, it was difficult to analyse the sensitive features of cavitation fault effectively. So, a neural network based method for sensitive frequency component analysis of cavitation fault was proposed, and Empirical Mode Decomposition(EMD) method, Fourier Transform and neural network were used. Firstly, the raw vibration signal was decomposed to 5 Intrinsic Mode Function(IMF) components and the frequency spectrum of each component were computed. So, the dataset of raw signal was divided into 5 datasets which contained different frequency components. And a neural network was built, trained and tested by the different datasets. By comparing the diagnosis accuracy of the neural network, the sensitivity of different IMF was analysed. And it is verified that the method can effectively analyse the sensitive frequency components of cavitation faults, reduce the size of the neural network.

Hepatocyte nuclear factor 6 (HNF6), as a transcription factor, has been reported to be involved in cell proliferation, carcinogenesis, and tumor metastasis. Here, we demonstrated the role of HNF6 in tumor growth and liver metastasis in colorectal cancer (CRC). Through bioinformatics and clinical samples analysis, we found HNF6 messenger RNA was upregulated both in CRC primary sites and liver metastases, and its high expression indicated poor survival in CRC patients. In vitro studies confirmed that HNF6 promoted cell proliferation and colony formation. What is more, in mouse models, the xenografts grew significantly faster and liver metastasis rate was nearly 45% higher in mice injected with HNF6-overexpressing cells. Further mechanism exploration showed that HNF6 expression affected cell adhesion and conferred resistance to anoikis in CRC cells. Taken together, HNF6 expression was upregulated in CRC and closely correlated with poor survival. HNF6 promoted CRC cell proliferation and tumor growth, and may contribute to liver metastasis via conferring cell resistance to anoikis.

Detection of volatile organic compounds (VOCs) at parts-per-billion (ppb) level is one of the most challenging tasks for miniature gas sensors because of the high requirement on sensitivity and the possible interference from moisture. Herein, for the first time, we present a novel platform based on a hybrid photonic cavity with metal-organic framework (MOF) coatings for VOCs detection. We have fabricated a compact gas sensor with detection limitation ranging from 29 to 99 ppb for various VOCs including styrene, toluene, benzene, propylene and methanol. Compared to the photonic cavity without coating, the MOF-coated solution exhibits a sensitivity enhancement factor up to 1000. The present results have demonstrated great potential of MOF-coated photonic resonators in miniaturized gas sensing applications.