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Endoscopic dilation (ED) is the mainstream treatment for esophageal stricture after endoscopic submucosal dissection (ESD). However, some complex esophageal strictures do not respond well to dilation. Endoscopic radial incision (ERI) has proved to be effective in treating anastomotic strictures, but it is rarely used to treat post-ESD esophageal strictures due to technical difficulties and risks, not to mention the optimal method and timing to perform ERI. Here, we developed an integrated procedure in which ED was performed first, followed by ERI on the stiff scars that remained intact after dilation. The ED + ERI procedure resulted in complete, uniform expansion of the esophageal lumen. Between 2019 and 2022, 5 post-ESD patients who received a median number of 11 sessions of ED (range, 4–28) of ED over a period of 322 days (range, 246–584) but still had moderate to severe dysphagia were admitted. 2 or 3 sessions of ED + ERI were performed for each patient interspersed with ED. After a median number of 4 treatments (range, 2–9), all patients were symptom-free or had minimal symptoms. No serious complications occurred in any patients who underwent ED + ERI. Therefore, ED + ERI is safe, feasible, and may serve as a useful therapeutic method for refractory esophageal stricture after ESD.

Tissues consist of cells and their surrounding extracellular matrix (ECM). Cell-ECM interactions play crucial roles in embryonic development, differentiation, tissue remodeling, and diseases including fibrosis and cancer. Recent research advances in characterizing cell-matrix interactions include detailed descriptions of hundreds of ECM and associated molecules, their complex intermolecular interactions in development and disease, identification of distinctive modes of cell migration in different 3D ECMs, and new insights into mechanisms of organ formation. Exploring the roles of the physical features of different ECM microenvironments and the bidirectional regulation of cell signaling and matrix organization emphasize the dynamic nature of these interactions, which can include feedback loops that exacerbate disease. Understanding mechanisms of cell-matrix interactions can potentially lead to targeted therapeutic interventions.

Icing significantly affects the performance of wind turbines in terms of power loss and structural degradation, and an effective blade icing diagnosis is the prerequisite to achieve the optimal control of wind turbines to mitigate such icing influence. However, current icing diagnostic methods lack consideration of fundamental icing physics and have limited generalizability to large-scale applications. To address such challenges, in the present study, we aim to propose an effective and robust blade icing diagnostic method for wind turbines. Specifically, hybrid features that fully consider both short-term and long-term icing influence are extracted based on the underlying icing physics. Such features are used to build a Stacked-XGBoost model (i.e., based on a combination of stacking ensemble learning algorithm and XGBoost machine learning algorithm) to achieve blade icing diagnosis. The proposed method is evaluated at two wind farms and further compared with three single algorithm-based models (i.e., random forest, support vector machine and XGBoost algorithms). The results show that the hybrid features significantly enhance the similarity between different datasets and the Stacked-XGBoost algorithm achieves a higher diagnostic accuracy and a better generalizability compared to the single-algorithm-based models.

Inverse kinematics problems (IKP) are ubiquitous in robotics for improved robot control in widespread applications. However, the high non-linearity, complexity, and equation coupling of a general six-axis robotic manipulator pose substantial challenges in solving the IKP precisely and efficiently. To address this issue, we propose a novel approach based on neural network (NN) with numerical error minimization in this paper. Within our framework, the complexity of IKP is first simplified by a strategy called joint space segmentation, with respective training data generated by forward kinematics. Afterwards, a set of multilayer perception networks (MLP) are established to learn from the foregoing data in order to fit the goal function piecewise. To reduce the computational cost of the inference process, a set of classification models is trained to determine the appropriate forgoing MLPs for predictions given a specific input. After the initial solution is sought, being improved with a prediction error minimized, the refined solution is finally achieved. The proposed methodology is validated via simulations on Xarm6—a general 6 degrees of freedom manipulator. Results further verify the feasibility of NN for IKP in general cases, even with a high-precision requirement. The proposed algorithm has showcased enhanced efficiency and accuracy compared to NN-based approaches reported in the literature.

This review describes how direct visualization of the dynamic interactions of cells with different extracellular matrix microenvironments can provide novel insights into complex biological processes. Recent studies have moved characterization of cell migration and invasion from classical 2D culture systems into 1D and 3D model systems, revealing multiple differences in mechanisms of cell adhesion, migration and signalling—even though cells in 3D can still display prominent focal adhesions. Myosin II restrains cell migration speed in 2D culture but is often essential for effective 3D migration. 3D cell migration modes can switch between lamellipodial, lobopodial and/or amoeboid depending on the local matrix environment. For example, “nuclear piston” migration can be switched off by local proteolysis, and proteolytic invadopodia can be induced by a high density of fibrillar matrix. Particularly, complex remodelling of both extracellular matrix and tissues occurs during morphogenesis. Extracellular matrix supports self‐assembly of embryonic tissues, but it must also be locally actively remodelled. For example, surprisingly focal remodelling of the basement membrane occurs during branching morphogenesis—numerous tiny perforations generated by proteolysis and actomyosin contractility produce a microscopically porous, flexible basement membrane meshwork for tissue expansion. Cells extend highly active blebs or protrusions towards the surrounding mesenchyme through these perforations. Concurrently, the entire basement membrane undergoes translocation in a direction opposite to bud expansion. Underlying this slowly moving 2D basement membrane translocation are highly dynamic individual cell movements. We conclude this review by describing a variety of exciting research opportunities for discovering novel insights into cell‐matrix interactions.

Bacillus amyloliquefaciens X030 (BaX030) has broad-spectrum antibacterial activity against the fish pathogens Aeromonas hydrophila and Aeromonas veronii. To improve its antibacterial effect, BaX030 was subjected to compound mutagenesis of atmospheric and room temperature plasma (ARTP) and nitrosoguanidine (NTG). The results showed that, compared with the original strain, the production of macrolactin A and oxydifficidin in mutated strain N-11 increased to 39 % and 268 %, respectively. The re-sequencing analysis suggested that there were SNPs and InDels in the gene clusters focused on the sucrose utilization pathway, glycolysis pathway and fatty acid synthesis pathway. Scanning electron microscopy revealed that strain N-11 became thin and long. The qRT-PCR results indicated that the expression of immune factors in the liver or kidney tissue of grass carp increased after feeding with N-11. H&E staining and protection experiments also showed that the mortality and surface symptoms of grass carp infected by the two pathogens were significantly reduced. The study identified a probiotic strain with potential application value in aquaculture production and provided a new strategy for the discovery of new strains with higher antibacterial biological activity.

Background: Bacillus amyloliquefaciens X030 (BaX030) was obtained by screening from peanut fields in Henan Province, China. It had broad-spectrum antibacterial activity against fish pathogens Aeromonas hydrophila and Aeromonas veronii. In order to improve its antibacterial effect, BaX030 was carried out the compound mutagenesis that atmospheric and room temperature plasma (ARTP) combined with nitrosoguanidine (NTG). Results: The result showed the yield of macrolactin A and oxydifficidin of the mutant N-11 were increased by 2.01 times and 3.68 times, respectively. Re-sequencing found that the corresponding 9th and 15th gene clusters had 4 and 6 SNP mutations, respectively, the 15th gene cluster also had 7 InDel mutations. Scanning electron microscopy observed that the N-11 became thin and long. The results of qRT-PCR indicated that feeding the N-11 can increase the expression of immune factors in the liver or kidney tissue of grass carp. It can also significantly reduce the mortality and the surface symptoms of grass carp that was infected by two pathogens through HE staining and protection experiments.Conclusion: This is the first report that after ARTP-NTG compound mutagenesis, a high-yielding strain of macrolactin A and oxydifficidin were increased by 2.01 times and 3.68 times compared with the original strain, respectively, which laid the foundation for elucidating its biological regulation, they had antibacterial effects on Aeromonas hydrophila and Aeromonas veronii. We combined re-sequencing to find the mutation sites of gene clusters and. The probiotic strain N-11 can quickly activate the immune protection mechanism of grass carp to resist pathogenic bacteria.

Aeromonas veronii is a widely distributed novel pathogen that can affect humans and animals, it can cause sepsis in fish with high mortality and serious economic losses to aquaculture. In the study, the gut microbiome of the infected and uninfected grass carp with Aeromonas veronii were analyzed probiotics and pathogenic bacteria by the Miseq high-throughput sequencing, the results showed that the infected fish were significantly higher in Proteobacteria, Firmicutes, Fusobacteria, and the immune factors in liver and kidney were up-regulated by qRT-PCR. In order to effectively inhibit the pathogen, we screened an actinomycete strain and had good antibacterial effect on Aeromonas veronii. The new antagonistic bacteria was named as Streptomyces flavotricini X101, the whole genome sequencing revealed that the metabolic process was most active. After grass carp was inoculated with the minimum inhibitory concentration of 900 μg/mL of the strain's fermentation supernatant, then Aeromonas veronii was injected, we found that the pathological symptoms such as body surface, anus and abdominal congestion were alleviated by H&E staining. Cellular experiments showed that it wasn't toxic to liver cells of grass carp. Overall, this is the first study of changes in intestinal flora, phenotype, and immune factors in grass crap infected with Aeromonas veronii, it had important theoretical significance and application value for immunization and prevention.

Background N-myc downstream-regulated gene 1 (NDRG1) has been shown to play a key role in tumor metastasis. Recent studies demonstrate that NDRG1 can suppress tumor growth and is related to tumor proliferation; however, the mechanisms underlying these effects remain obscure. Methods Immunohistochemistry (IHC) was used to detect NDRG1 and p21 protein expression in colorectal cancer tissue, and clinical significance of NDRG1 was also analyzed. CCK-8 assay, colony formation assay, flow cytometry, and xenograft model were used to assess the effect of NDRG1 on tumor proliferation in vivo and in vitro. The mechanisms underlying the effect of NDRG1 were investigated using western blotting, immunofluorescence, immunoprecipitation, and ubiquitylation assay. Results NDRG1 was down-regulated in CRC tissues and correlated with tumor size and patient survival. NDRG1 inhibited tumor proliferation through increasing p21 expression via suppressing p21 ubiquitylation. NDRG1 and p21 had a positive correlation both in vivo and in vitro. Mechanistically, E3 ligase NEDD4 could directly interact with and target p21 for degradation. Moreover, NDRG1 could emulatively antagonize NEDD4-mediated ubiquitylation of p21, increasing p21 expression and inhibit tumor proliferation. Conclusion Our study could fulfill potential mechanisms of the NDRG1 during tumorigenesis and metastasis, which may serve as a tumor suppressor and potential target for new therapies in human colorectal cancer.

The aberrant expression of mucin-type O-glycosylation plays important roles in cancer malignancy. The polypeptide N-acetylgalactosaminyltransferases (ppGalNAc-Ts) are a family of conserved enzymes that initiate the mucin-type O-glycosylation in cells. In human, consistent up- or down-regulation of ppGalNAc-Ts expression during cancer development has been frequently reported. Here, we provide evidence that ppGalNAc-T4 shows a stage-dependent expression at the different stages of colorectal cancer (CRC) in the 62 pair-matched tumor/normal tissues. In detail, ppGalNAc-T4 expression is significantly induced at stage I and II but not at stage III and IV. Overexpression of ppGalNAc-T4 in CRC cells enhances colony formation and sphere formation suggesting an important role of ppGalNAc-T4 in tumorigenesis. Conversely, knockdown of ppGalNAc-T4 in CRC cells increases the cell migration and invasion, and leads to an epithelial-mesenchymal transition-like transition. Further analysis suggests that loss of ppGalNAc-T4 contributes to the dedifferentiation of CRC and high expression of ppGalNAc-T4 correlates to a good prognosis of patients. Taken together, our results not only demonstrate a stage-dependent expression of ppGalNAc-T4 in CRC progression, but also suggest that such stage-dependent expression may contribute to the tumorigenesis at the early stage and promote cell migration and invasion at the advanced stage.

Aim Extralevator abdominoperineal resection) (ELAPR) is challenging “conventional” adbominoperineal resection (APR) yet the safety and efficacy of ELAPR is still under debate. We therefore developed a laparoscopic APR with transabdominal individualized levator transection (LAPR-TILT) approach and compared the outcome with a conventional laparoscopic APR (CLAPR). Method All eligible patients were entered a single center randomized controlled trial to compare CLAPR and LAPR-TILT. We assessed the first 185 patients, including operative findings, complications, histopathology and urogenital function. Results 93 patients in the CLAPR group and 92 patients in the APR-TILT group were included for analysis. The APR-TILT procedure took less time (137min [101-175] vs 146min [102-187], p=0.03), mainly owing to faster perineal dissection. APR-TILT resulted in reduced rate of bowel perforation (1.1% vs 8.6%, p=0.04), CRM positivity (1.1% vs 10.8%, P=0.01) and postoperative wound complications (5.4% vs 16.2%,p=0.02) as compared to the CLAPR procedure. At a median follow up of 19 months after surgery, 3 patients (3.2%) in the CLAPR group had tumor recurrence while no tumour recurrence occurred in the LAPR-TILT group. Patients underwent LAPR-TILT reported fewer urinary or sexual problems (LAPR-TILT vs CLAPR, 10.9% vs 24.7% and 17.4% vs 38.7% respectively). Conclusion Compared to CLAPR, LAPR-TILT achieved better pathological results for factors that are surrogate parameters for local recurrence. LAPR-TILT could also reduce the risk of urogenital dysfunction. This article is protected by copyright. All rights reserved.

We have discovered that basement membrane and its major components can induce rapid, strikingly robust fibronectin organization. In this new matrix assembly mechanism, α5β1 integrin-based focal adhesions slide actively on the underlying matrix towards the ventral cell center through the dynamic shortening of myosin IIA-associated actin stress fibers to drive rapid fibronectin fibrillogenesis distal to the adhesion. This mechanism contrasts with classical fibronectin assembly based on stable/fixed-position focal adhesions containing αVβ3 integrins plus α5β1 integrin translocation into proximal fibrillar adhesions. On basement membrane components, these sliding focal adhesions contain standard focal adhesion constituents but completely lack classical αVβ3 integrins. Instead, peripheral α3β1 or α2β1 adhesions mediate initial cell attachment, but over time are switched to α5β1 integrin-based sliding focal adhesions to assemble fibronectin matrix. This basement membrane-triggered mechanism produces rapid fibronectin fibrillogenesis, providing a mechanistic explanation for the well-known widespread accumulation of fibronectin at many organ basement membranes.

Metastasis is a complex process that is regulated by multiple signaling pathways, with the focal adhesion kinase (FAK)/paxillin pathway playing a major role in the formation of focal adhesions and cell motility. N-myc downstream regulated gene-1 (NDRG1) is a potent metastasis suppressor in many solid tumor types, including prostate and colon cancer. Considering the antimetastatic effect of NDRG1 and the crucial involvement of the FAK/paxillin pathway in cellular migration and cell-matrix adhesion, we assessed the effects of NDRG1 on this important oncogenic pathway. In the present study, NDRG1 overexpression and silencing models of HT29 colon cancer and DU145 prostate cancer cells were used to examine the activation of FAK/paxillin signaling and the formation of focal adhesions. The expression of NDRG1 resulted in a marked and significant decrease in the activating phosphorylation of FAK and paxillin, whereas silencing of NDRG1 resulted in an opposite effect. The expression of NDRG1 also inhibited the formation of focal adhesions as well as cell migration and cell-collagen adhesion. Incubation of cells with novel thiosemicarbazones, namely di-2-pyridylketone 4,4-dimethyl-3-thiosemicarbazone and di-2-pyridylketone 4-cyclohexyl-4-methyl-3-thiosemicarbazone, that upregulate NDRG1 also resulted in decreased phosphorylation of FAK and paxillin. The ability of these thiosemicarbazones to inhibit cell migration and metastasis could be mediated, at least in part, through the FAK/paxillin pathway.

In addition to forming spores, Bacillus thuringiensis (Bt) 4.0718 can produce toxins, insecticidal crystal protein (ICP) and vegetative insecticidal protein (Vip). The Bt spoIVA was successfully knocked out by gene recombination and was shown to inhibit sporulation. The mutant strain also exhibited significantly decreased growth and crystal formation, which inhibited spore formation and partially reduced the rate of crystal synthesis. The 50 % lethal concentrations (LC50) values of Bt 4.0718, replacement, complementation and multi-copy mutant strains against the fourth larval stage of H. armigera was determined as 5.422, 6.776, 6.223 and 5.018 μg/mL, respectively. A total of 1814 proteins were identified through isobaric tags for relative and absolute protein (iTRAQ), with 41 and 54 up and downregulated proteins observed. Gene ontology enrichment analysis showed that differentially expressed proteins were primarily involved in the biological process and molecular function. Quantitative real-time PCR analysis confirmed that 9 differential expressed genes exhibited a positive correlation between changes at transcriptional and translational levels. The results of this study provide a basis for further studies of the metabolic regulatory network of spores and crystal protein formation. Moreover, they can be used to ecologically safe insecticide of farmland production because the constructed Bt spoIVA mutants did not produce spores.Provides new ideas for the targeted improvement and application of environmentally friendly spore-free strains.

The small heat shock protein plays an important role in response to stresses. We wanted to investigate how Hsp20 affects sporulation and production of insecticidal crystal proteins (ICPs) in Bacillus thuringiensis (Bt) at the stationary growth phase when cells are starved. The hsp20 gene was knocked out in Bt4.0718 (wide type), which is a B. thuringiensis strain screened in our laboratory, using endonuclease I-SceI mediated unmarked gene replacement method. Deletion of Hsp20 resulted in a decrease in both sporulation and ICPs production. Bt4-Δhsp20 cells and its ICP did not have a significant difference in shape and size but entered the decline phase 2 h earlier than the Bt4.0718. In order to find the mechanism that underlies these phenotypes, we completed a proteomic study of differentially expressed proteins (DEPs). In Bt4-Δhsp20 cells, 11 DEPs were upregulated and 184 DEPs downregulated. These affected DEPs are involved in multiple metabolic pathways: (1) six DEPs (two upregulated and four downregulated) are directly related to the sporulation and ICPs synthesis; (2) supply of amino acids including amino acid synthesis and protein recycling; (3) the energy supplementation (the tricarboxylic acid cycle and glycolysis); (4) purine metabolism and mRNA stability. These results suggest that hsp20 may be critical in maintaining the homeostasis of B. thuringiensis during the production of spores and ICPs, and could provide new sight into the sporulation and ICPs formation in B. thuringiensis.

Supplemental Material, Supplementary_tables_and_figures for Prediction of Target Genes and Pathways Associated With Cetuximab Insensitivity in Colorectal Cancer by Chaoran Yu, Hiju Hong, Jiaoyang Lu, Xuan Zhao, Wenjun Hu, Sen Zhang, Yaping Zong, Zhihai Mao, Jianwen Li, Mingliang Wang, Bo Feng, Jing Sun, and Minhua Zheng in Technology in Cancer Research & Treatment

Elevated expression of β-galactoside α2,6-sialyltranferase 1 (ST6GAL1) has been observed in colorectal cancer (CRC) and demonstrated to be important for its tumorigenesis. Here, we found that ST6GAL1 expression was significantly higher in non-metastatic tumors (stage I and II) than that in metastatic tumors (stage III and IV) using 62 pair-matched tumor/normal tissues. To elucidate the molecular mechanisms of how ST6GAL1 affected the CRC progression, we performed a global identification of the substrates of ST6GAL1 in the colon adenocarcinoma cell line SW480. A total of 318 membrane proteins were identified differentially affected by ST6GAL1 overexpression using metabolic labeling and proteomic analysis. Subsequent bioinformatic analysis revealed a list of potential substrates that might mediate the different functions of ST6GAL1 in CRC including cell movement, cell death and survival. Taken together, these results indicate a dynamic change in the expression of ST6GAL1 during the CRC progression and provide a list of sialylated proteins potentially relevant to the different functions of ST6GAL1 in CRC.

The promising endoscopic resection techniques for upper gastrointestinal submucosal tumors (SMTs) are challenged when performed in the gastric fundus. Here, we report on the development of a transcardiac endoscopic tunneling technique (TCTT) for the resection of tumors in this area. A total of 18 patients with gastric fundus SMTs arising from the muscularis propria on endoscopic ultrasound underwent TCTT. The procedure involved the excavation of a submucosal tunnel from the esophagus, through the cardia, to the gastric SMT for resection. The tunnel was closed by clips after retrieval of the tumor. The mean tumor size was 2.1 cm (range 0.8 - 5.0 cm). The mean procedure time was 75.1 minutes (range 40 - 100 minutes). Complete resection was achieved in all cases. Iatrogenic perforation occurred in one case. This and one other patient developed mild pneumoperitoneum on the day after the procedure; symptoms resolved under conservative management. No patient developed gastrointestinal leakage, delayed bleeding, or secondary infection. Therefore, in this pilot study, TCTT provided a definitive histological diagnosis as well as a feasible, safe, and easy therapeutic approach for gastric fundus SMTs arising from muscularis propria in the circular area within 8 cm below the cardia.

Endoscopic submucosal excavation (ESE) and submucosal tunneling endoscopic resection (STER) are nowadays both adopted by endoscopists to resect upper gastrointestinal submucosal tumors (SMTs) arising from muscularis propria. This study aimed to compare the efficacy and safety of these two techniques.Seventy-seven patients were included in this retrospective study, among them, 35 received ESE and 42 received STER. Main outcome measurements included complete resection rate, perforation rate, adverse events, and tumor recurrence. Subgroup analysis based on tumor size was also performed.In general, ESE and STER had similar complete resection rate (94.7 vs. 97.7%), perforation rate (10.5 vs. 13.3%), and incidence of postoperative air leakage symptoms (13.2 vs. 2.2%). No tumor recurrence occurred in any group. Subgroup analysis revealed that for tumors10 mm, both techniques achieved satisfactory therapeutic effects (100 % complete resection, no adverse events); for tumors10 mm, perforation rate increased in both ESE and STER (16 vs. 18.2%), yet incidence of air leakage symptoms was significantly low in STER (3%) compared to it in ESE (20%).For SMTs10 mm, both ESE and STER have satisfactory therapeutic results, it is not necessary to pursue a difficult procedure when a simple method is available. For SMTs10 mm, STER is a preferable choice in terms of preventing air leakage symptoms, especially, when perforation is likely to happen.

// Xiao Yang 1, 2, * , Fan Zhu 1, 2, * , Chaoran Yu 1, 2, * , Jiaoyang Lu 1, 2 , Luyang Zhang 1, 2 , Yanfeng Lv 3 , Jing Sun 1, 2 and Minhua Zheng 1, 2 1 Department of General Surgery, Ruijin Hospital, Shanghai Jiao Tong University, School of Medicine, Shanghai 200025, P.R.China 2 Shanghai Minimally Invasive Surgery Center, Ruijin Hospital, Shanghai Jiao Tong University, School of Medicine, Shanghai 200025, P.R.China 3 Department of Colorectal Surgery, Second Hospital of Shandong University, Shandong University, Jinan 250000, P.R.China * These authors have contributed equally to this work Correspondence to: Minhua Zheng, email: ZhengMHrjhospital@163.com Jing Sun, email: jingsun1982@sina.cn Yanfeng Lv, email: yanfenglv1979@sina.com Keywords: apoptosis, colorectal cancer, neoadjuvant chemotherapy, NDRG1, Bcl-2 Received: November 15, 2016 Accepted: April 14, 2017 Published: May 09, 2017 ABSTRACT N-myc downstream-regulated gene1 ( NDRG1 ) has been identified as a potent tumor suppressor gene. The molecular mechanisms of anti-tumor activity of NDRG1 involve its suppressive effects on a variety of tumorigenic signaling pathways. The purpose of this study was to investigate the role of NDRG1 in the apoptosis of colorectal cancer (CRC) cells. We first collected the clinical data of locally advanced rectal cancer (LARC) patients receiving oxaliplatin-based neoadjuvant chemotherapy in our medical center. Correlation analysis revealed that NDRG1 positively associated with the downstaging rates and prognosis of patients. Then, the effects of over-expression and depletion of NDRG1 gene on apoptosis of colorectal cancer were tested in vitro and in vivo . NDRG1 over-expression promoted apoptosis in colorectal cancer cells whereas depletion of NDRG1 resulted in resistance to oxaliplatin treatment. Furthermore, we observed that Bcl-2, a major anti-apoptotic protein, was regulated by NDRG1 at post-transcriptional level. By binding Protein kinase Cα (PKCα), a classical regulating factor of Bcl-2, NDRG1 enhanced the ubiquitination and degradation of Bcl-2, thus promoting apoptosis in CRC cells. In addition, NDRG1 inhibited tumor growth and promoted apoptosis in mouse xenograft model. In conclusion,NDRG1 promotes oxaliplatin-triggered apoptosis in colorectal cancer. Therefore, colorectal cancer patients can be stratified by the expression level of NDRG1. NDRG1-positive patients may benefit from oxaliplatin-containing chemotherapy regimens whereas those with negative NDRG1 expression should avoid the usage of this cytotoxic drug.

N-myc downstream-regulated gene 1 (NDRG1) has been reported to act as a key regulatory molecule in tumor progression-related signaling pathways, especially in tumor metastasis. However, the related mechanism has not been fully discovered yet. Herein we demonstrated that the novel molecule of cell migration and invasion, caveolin-1, has direct interaction with NDRG1 in human colorectal cancer (CRC) cells. Moreover, we discovered that NDRG1 reduces caveolin-1 protein expression through promoting its ubiquitylation and subsequent degradation via the proteasome in CRC cells. In addition, caveolin-1 mediates the suppressive function of NDRG1 in epithelial–mesenchymal transition, migration and invasion in vitro and metastasis in vivo. These results help to fulfill the potential mechanisms of NDRG1 in anti-metastatic treatment for human colorectal cancer.

Background: Cetuximab has been regularly added to the treatments for metastatic colorectal cancer worldwide. However, due to its therapeutic insensitivity and underlying mechanisms being largely unknown, the clinical implementation of cetuximab in colorectal cancer remains limited. Methods: The gene expression profile GSE56386 was retrieved from the Gene Expression Omnibus database. Differentially expressed genes were identified between cetuximab-responsive patients and nonresponders, annotated by gene ontology, Kyoto Encyclopedia of Genes and Genomes pathway analysis, and further analyzed by protein–protein interaction networks. The integrative prognostic analysis was based on The Cancer Genome Atlas and PrognoScan. Results: 1350 differentially expressed genes were identified with 298 upregulated and 1052 downregulated. Epidermis development, the cornified envelope, calcium ion binding, and amoebiasis were enriched in upregulated genes while digestion, the apical part of the cell, the 3′,5′-cyclic-adenosine monophosphate phosphodiesterase activity and pancreatic secretion were found enriched in downregulated genes. The top 10 hub genes were identified, including epithermal growth factor, G-protein subunit β 5, G-protein subunit γ 4, fibroblast growth factor 2, B-cell lymphoma protein 2, acetyl-coenzyme A carboxylase β, KIT proto-oncogene receptor tyrosine kinase, adenylate cyclase 4, neuropeptide Y, and neurotensin. The hub genes exhibited distinct correlations in cetuximab-treated and untreated genomic profiles (GSE56386, GSE5851 and GSE82236). The highest correlation was found between B-cell lymphoma protein 2 and acetyl-coenzyme A carboxylase β in GSE56386. The mRNA expression of hub genes was further validated in the genomic profile GSE65021. Furthermore, B-cell lymphoma protein 2 and acetyl-coenzyme A carboxylase β also exhibited highest degrees among the hub genes correlation networks based on The Cancer Genome Atlas. Both B-cell lymphoma and acetyl-coenzyme A carboxylase β were not independent prognostic factors for colorectal cancer in univariate and multivariate Cox analysis. However, integrative survival analysis indicated that B-cell lymphoma protein 2 was associated with favorable prognosis (hazard ratio = 0.62, 95% confidence interval, 0.30-0.95, P = .024). Discussion: This in silico analysis provided a feasible and reliable strategy for systematic exploration of insightful target genes, pathways and mechanisms underlying the cetuximab insensitivity in colorectal cancer. B-cell lymphoma protein 2 was associated with favorable prognosis.

Background and Aims Endoscopic full-thickness resection (EFTR) is difficult to perform in a retroflexed fashion in the gastric fundus and lesser curvature. Here we describe two simple methods to provide countertraction and thereby facilitate dissection. Methods In this retrospective cohort study, 62 patients diagnosed as having gastric submucosal tumors in the fundus or in the lesser curvature received EFTR with or without countertraction methods. For the clip-with-thread method, a clip tied with surgical suture was anchored on the distal edge of the tumor to provide countertraction; for the loop-assisted method, a snare placed on the transparent cap beforehand was adopted to grasp the tumor to provide countertraction. Results Mean operative time was significantly reduced in the thread-with-clip group and loop-assisted group (45 minutes, 40 minutes, respectively) compared with the time needed in the traditional EFTR group (85 minutes). Intraoperative pneumoperitoneum occurred regularly among the 3 groups because of iatrogenic perforation, but fewer patients in the thread-with-clip group and loop-assisted group (23%, 18%, respectively) needed abdominal puncture to relieve free air and stabilize life signs compared with patients in the traditional EFTR group (63%). A reduced occurrence of high fever after surgery may contribute as another advantage from accelerated dissection. Both techniques did not jeopardize oncologic safety during short-term follow-up. Conclusions Both the thread-with-clip method and loop-assisted method provide effective countertraction and offer faster and safer gastric EFTR in difficult anatomic locations.

Background The emerging submucosal tunneling and endoscopic resection (STER) technique provides definitive histological diagnosis as well as a therapeutic method for the gastric submucosal tumors (SMTs). We aim to present our experience and discuss key technical issues of STER. Methods 45 patients with gastric SMTs arising from MP received STER. First, a mucosal incision was made 3cm proximal to the tumour, a submucosal tunnel was subsequently built from the incision to the tumor. The tumor was gradually exposed and dissected from surrounding tissue and retrieved from the tunnel. The initial mucosal incision was closed by metal clips. For SMTs in the gastric fundus near cardia, the submucosal tunnel was built from lower esophagus, through the angle of His, to the tumor for resection. Results STER was successfully performed in 43 patients; the other two were converted to surgery. Mean operating time was 79.3min (range 45–150min). Mean tumor size was 1.4cm (range 0.5–5cm). Of the total 47 resected SMTs, 36 were GISTs, 10 were leiomyomas and 1 was schwannoma. Complete resection was achieved in all patients. Intra-procedural peumoperitoneum occurred in 3 cases because of iatrogenic perforation, no special treatment was given. 7 patients presented with mild abdominal pain/distention and fever were given antibotics. No severe post-operative complication happened. No tumor recurrence occurred in the median 11 month follow-up period. Conclusion Based on short-term follow-up observation, STER is a feasible, safe and minimally invasive method for the diagnosis and treatment of small (

Small (