Novel beagle model of gastric local fibrotic target lesions for the evaluation and training of endoscopic techniques.

BACKGROUND: Novel endoscopic techniques used in the treatment of gastric lesions with local submucosal fibrosis need preclinical evaluation and training due to safety limitations. Therefore, the purpose of our study was to establish an animal model of gastric local fibrotic target lesions and assess its feasibility in the evaluation and training of endoscopic techniques. METHODS: In six experimental beagles, a 50% glucose solution was injected into three submucosal areas of the fundus, body, and antrum of the stomach to create gastric local fibrotic target lesions (experimental group). On post-injection day (PID) 7, the injection sites were assessed endoscopically to confirm the presence of submucosal fibrosis formation, and the dental floss clip traction assisted endoscopic submucosal dissection (DFC-ESD) procedure was performed on the gastric local fibrotic target lesions to confirm its feasibility after endoscopic observation. The normal gastric mucosa of six control beagles underwent the same procedure (control group). All the resected specimens were evaluated by histological examination. RESULTS: All 12 beagles survived without postoperative adverse events. On PID 7, 16 ulcer changes were observed at the injection sites (16/18) under the endoscope, and endoscopic ultrasonography confirmed the local submucosal fibrosis formation in all ulcer lesions. The subsequent DFC-ESD was successfully performed on the 32 gastric target lesions, and the mean submucosal dissection time in the ulcer lesions was greater than that in the normal gastric mucosa (15.3 ± 5.6 vs. 6.8 ± 0.8 min; P < 0.001). There was no difference in rates of en bloc resection, severe hemorrhage, or perforation between the two groups. Histological analysis of the ulcer lesions showed the absence of epithelial or muscularis mucosae and extensive submucosal fibrous tissue proliferations compared with normal gastric mucosa. Overall, endoscopists had high satisfaction with the realism and feasibility of the animal model. CONCLUSION: We developed a novel animal model of gastric local fibrotic target lesions to simulate difficult clinical situations, which strongly appeared to be suitable for the preclinical evaluation and learning of advanced endoscopic techniques.

Systematic Study of Heteroarene Stacking Using a Congeneric Set of Molecular Glues for Procaspase-6.

Heteroaromatic stacking interactions are important in drug binding, supramolecular chemistry, and materials science, making protein-ligand model systems of these interactions of considerable interest. Here we studied 30 congeneric ligands that each present a distinct heteroarene for stacking between tyrosine residues at the dimer interface of procaspase-6. Complex X-ray crystal structures of 10 analogs showed that stacking geometries were well conserved, while high-accuracy computations showed that heteroarene stacking energy was well correlated with predicted overall ligand binding energies. Empirically determined KD values in this system thus provide a useful measure of heteroarene stacking with tyrosine. Stacking energies are discussed in the context of torsional strain, the number and positioning of heteroatoms, tautomeric state, and coaxial orientation of heteroarene in the stack. Overall, this study provides an extensive data set of empirical and high-level computed binding energies in a versatile new protein-ligand system amenable to studies of other intermolecular interactions.

Magnetic ring-assisted endoscopic submucosal dissection for gastric lesions with submucosal fibrosis: A preliminary study in beagle model.

BACKGROUND: During endoscopic submucosal dissection (ESD) for gastric lesions with fibrosis, appropriate traction could provide clear submucosal dissection visualization to improve safety and efficiency of procedures. Therefore, the aim of this study was to evaluate the feasibility of magnetic ring-assisted ESD (MRA-ESD) for gastric fibrotic lesions. METHOD: In the eight healthy beagles, 2-3 mL of 50% glucose solution was injected into submucosal layer of the stomach to induce gastric fibrotic lesions. A week after submucosal injection, two endoscopists at different levels performed MRA-ESD or standard ESD (S-ESD) for gastric simulated lesions, respectively. The magnetic traction system consisted of external handheld magnet and internal magnetic ring. The feasibility and procedure outcomes of the magnetic traction system were mainly evaluated. RESULTS: Forty-eight gastric simulated lesions with ulceration were confirmed to have submucosal fibrosis formation by preoperative endoscopic ultrasonography. The magnetic traction system could be easily established, only took 1.57 min, and allowed excellent submucosal visualization. The total procedure time was significantly shorter in the MRA-ESD group than in the S-ESD group for both endoscopists (mean: 46.83 vs. 25.09 min, p < 0.001), and this difference was accentuated in non-skilled endoscopist. There was significant difference between two groups in bleeding and perforation rates. Histological analysis showed the depth of resected specimens was a little deeper around the fibrotic portion in the S-ESD group (p < 0.001). CONCLUSION: The magnetic ring-assisted ESD technique may be an effective and safe treatment for gastric fibrotic lesions and may shorten the endoscopic learning curve for non-skilled endoscopists.

Experimental Study on Gastric Labeling by Magnetic Detector Combined With Magnetic Bead.

OBJECTIVE: Preoperative labeling of gastric cancer is an important means to determine the surgical margin. At present, there are many commonly used labeling methods. However, which is more accurate and has fewer complications remains to be studied. Through animal experiments, this study explored the feasibility, accuracy, and safety of a magnetic detector combined with magnetic beads for the preoperative labeling of gastric cancer. METHODS: A total of 10 beagle dogs were included in the study. Each dog was randomly labeled with magnetic beads in the gastric body and antrum. After labeling, the magnetic detector was used to explore the gastric serosa surface, and the positioning titanium clip was released at the detected magnetic bead. The main monitoring index was to measure the distance between the labeled magnetic beads and the positioning titanium clamped. The secondary indexes were detection time, magnetic induction intensity, magnetic bead shedding rate, mucosal injury rate, bleeding, and leukocyte and C-reactive protein levels before and 24 hours after the operation. RESULTS: All 10 beagle dogs completed the marking and exploration successfully. The average distance between the magnetic beads and the positioning titanium clip in 20 cases was 5.90±2.36 mm. The average detection time was 1.60±0.69 min, and the average magnetic induction intensity was 3.76±1.11 mT. No magnetic beads were found to fall off, 1 case had a mild mucosal injury, and 2 cases had a small amount of bleeding when releasing the positioning titanium clip. The white blood cells before and 24 hours after the operation were 7.43±0.94(×10 9 /L) versus 7.79±0.67(×10 9 /L) ( P =0.34). The C-reactive protein before and 24 hours after the operation were 5.24±0.97 µg/mL versus 5.95±1.02 µg/mL ( P =0.13). CONCLUSION: A magnetic detector combined with magnetic beads for gastric cancer labeling is feasible, accurate, and safe. It is expected to be further applied in the clinic.

Tembusu virus infection in laying chickens: Evidence for a distinct genetic cluster with significant antigenic variation.

Tembusu virus (TMUV) associated disease is a growing cause of egg production decrease and encephalitis in domestic waterfowl, with expanding distribution. In previous studies, TMUV isolates were phylogenetically classified into two genetic lineages and different clusters with varied pathogenicity. However, little is known about the phenotypic and virulence characteristics of cluster 3 isolates within the duck TMUV lineage. In this study, the etiological agent causing egg drop in a laying chicken farm in southern China was investigated and a TMUV was isolated from pooled tissue samples. Genome sequencing and phylogenetic analysis grouped the isolate into TMUV cluster 3 with closest relation to the mosquito-origin TMUV YN12193. Cross-neutralization testing using convalescent sera revealed significant antigenic variation between the isolate and a representative strain of cluster 2.2. The experimental infection of SPF hens confirmed the ability of the isolate to replicate in multiple tissues and led to ovary damage. Additionally, high seroconversion rates (95.83%-100%) were detected in the three flocks following retrospective investigation. Our study demonstrates the occurrence of cluster 3 TMUV infection in laying chickens and that the virus exhibits significant antigenic variation compared with cluster 2 TMUV.

Hierarchical Image Segmentation Based on Nonsymmetry and Anti-Packing Pattern Representation Model.

Image segmentation is the foundation of high-level image analysis and image understanding. How to effectively segment an image into regions that are "meaningful" to the human visual perception and ensure that the segmented regions are consistent at different resolutions is still a very challenging issue. Inspired by the idea of the Nonsymmetry and Anti-packing pattern representation Model in the Lab color space (NAMLab) and the "global-first" invariant perceptual theory, in this paper, we propose a novel framework for hierarchical image segmentation. Firstly, by defining the dissimilarity between two pixels in the Lab color space, we propose an NAMLab-based color image representation approach that is more in line with the human visual perception characteristics and can make the image pixels fast and effectively merge into the NAMLab blocks. Then, by defining the dissimilarity between two NAMLab-based regions and iteratively executing NAMLab-based merging algorithm of adjacent regions into larger ones to progressively generate a segmentation dendrogram, we propose a fast NAMLab-based algorithm for hierarchical image segmentation. Finally, the complexities of our proposed NAMLab-based algorithm for hierarchical image segmentation are analyzed in details. The experimental results presented in this paper show that our proposed algorithm when compared with the state-of-the-art algorithms not only can preserve more details of the object boundaries, but also it can better identify the foreground objects with similar color distributions. Also, our proposed algorithm can be executed much faster and takes up less memory and therefore it is a better algorithm for hierarchical image segmentation.

Clinical characteristics of non-ampullary duodenal polyps in the elderly and the outcomes of endoscopic mucosal resection.

At present, there are no reports on non-ampullary polyps of the duodenum (NAPDs) in the elderly. The aim of this study was to analyze the clinicopathological features of NAPDs in elderly and non-elderly patients to explore the efficacy and safety of endoscopic mucosal resection (EMR) of NAPDs in the elderly.A total of 110 patients underwent EMR of NAPDs between April 2016 and December 2019. The shape, location, size, postoperative complications, and histopathological types of NAPDs were compared between the elderly group (n = 44) and the non-elderly group (n = 66).Sessile type was the most common form of NAPD in both groups. In the elderly group, the average size of NAPDs was 12.6 ±â€Š3.9 mm. In the non-elderly group, NAPDs had an average size of 10.1 ±â€Š5.8 mm. Complete EMR was performed in both groups. The postoperative complications of EMR did not significantly differ between the 2 groups. Postoperative pathological examination showed that tubular villous adenomas were more common in the elderly group than in the non-elderly group (P = .005), while tubular adenomas were more common in the non-elderly group than in the elderly group (P = .007). Of the 110 patients, 99 completed postoperative follow-up (median follow-up duration, 20.93 months). There were no residual or recurrent lesions.EMR is safe and effective for the treatment of NAPDs in elderly patients.

MiR-203a-3p targets PTEN to promote hepatocyte proliferation by regulating PI3K/Akt pathway in BRL-3A cells.

This study was designed to investigate the role of miR-203a-3p in hepatocyte proliferation. Data analysis showed that up-regulation of miR-203a-3p increased the cell viability and cell proliferation, and inhibited apoptosis. Further experiments demonstrated that PTEN was a target gene of miR-203a-3p, and miR-203a-3p targeted PTEN to regulate the above functions. Overexpression of PTEN partially reversed the inhibition of PTEN and the activation of p-Akt/Akt induced by miR-203a-3p mimic. Our study revealed that miR-203a-3p might activate PI3K/Akt signaling pathway by inhibiting PTEN expression, thereby promoting cell proliferation.