Endoscopic Submucosal Dissection Criteria for Differentiated-type Early Gastric Cancer Are Applicable to Mixed-type Differentiated Predominant.

BACKGROUND: There is a lack of sufficient evidence on whether mixed-type differentiated predominant early gastric cancer (MD-EGC) can be treated endoscopically by referring to the criteria for differentiated-type early gastric cancer (EGC). This study aims to evaluate the efficacy of endoscopic submucosal dissection (ESD) in MD-EGC. METHODS: Patients with differentiated-type EGC treated with ESD first from January 2015 to June 2021 were reviewed, including MD-EGC and pure differentiated-type EGC (PD-EGC). Clinical data, including the clinicopathological characteristics, resection outcomes of ESD, and recurrence and survival time, were collected, and the difference between MD-EGC and PD-EGC was tested. RESULTS: A total of 48 patients (48 lesions) with MD-EGC and 850 patients (890 lesions) with PD-EGC were included. Compared with PD-EGC, MD-EGC had a higher submucosal invasion rate (37.5% vs. 13.7%, P<0.001) and lymphatic invasion rate (10.4% vs. 0.4%, P<0.001). The rates of complete resection (70.8% vs. 92.5%, P<0.001) and curative resection (54.2% vs. 87.4%, P<0.001) in MD-EGC were lower than those of PD-EGC. Multivariate analysis revealed that MD-EGC (OR 4.26, 95% CI, 2.22-8.17, P<0.001) was an independent risk factor for noncurative resection. However, when curative resection was achieved, there was no significant difference in the rates of recurrence (P=0.424) between the 2 groups, whether local or metachronous recurrence. Similarly, the rates of survival(P=0.168) were no significant difference. CONCLUSIONS: Despite the greater malignancy and lower endoscopic curative resection rate of MD-EGC, patients who met curative resection had a favorable long-term prognosis.

Anti-angiogenic effect of exo-LncRNA TUG1 in myocardial infarction and modulation by remote ischemic conditioning.

The successful use of exosomes in therapy after myocardial infarction depends on an improved understanding of their role in cardiac signaling and regulation. Here, we report that exosomes circulating after myocardial infarction (MI) carry LncRNA TUG1 which downregulates angiogenesis by disablement of the HIF-1α/VEGF-α axis and that this effect can be counterbalanced by remote ischemic conditioning (RIC). Rats with MI induced through left coronary artery ligation without (MI model) and with reperfusion (ischemia/reperfusion I/R model) were randomized to RIC, or MI (I/R) or sham-operated (SO) control. Data from one cohort study and one randomized-controlled trial of humans with MI were also utilized, the former involving patients who had not received percutaneous coronary intervention (PCI) and the latter patients with PCI. Exosome concentrations did not differ between intervention groups (RIC vs. control) in rats (MI and I/R model) as well as humans (with and without PCI). However, MI and I/R exosomes attenuated HIF-1α, VEGF-α, and endothelial function. LncRNA TUG1 was increased in MI and I/R exosomes, but decreased in SO and RIC exosomes. HIF-1α expression was downregulated with MI and I/R exosomes but increased with RIC exosomes. Exosome inhibition suppressed HIF-1α upregulation through RIC exosomes. VEGF-α was identified as HIF-1α-regulated target gene. Knockdown of HIF-1α decreased VEGF-α, endothelial cell capability, and tube formation. Overexpression of HIF-1α exerted opposite effects. Transfection and co-transfection of 293 T cells with exosome-inhibitor GW4869 and HIF-1α inhibitor si-HIF-1α confirmed the exosomal-LncRNA TUG1/HIF-1α/VEGF-α pathway. LncRNA TUG1 is a potential therapeutic target after MI with or without reperfusion through PCI.

Differential diagnosis for esophageal protruded lesions using a deep convolution neural network in endoscopic images.

BACKGROUND AND AIMS: Recent advances in deep convolutional neural networks (CNNs) have led to remarkable results in digestive endoscopy. In this study, we aimed to develop CNN-based models for the differential diagnosis of benign esophageal protruded lesions using endoscopic images acquired during real clinical settings. METHODS: We retrospectively reviewed the images from 1217 patients who underwent white-light endoscopy (WLE) and EUS between January 2015 and April 2020. Three deep CNN models were developed to accomplish the following tasks: (1) identification of esophageal benign lesions from healthy controls using WLE images; (2) differentiation of 3 subtypes of esophageal protruded lesions (including esophageal leiomyoma [EL], esophageal cyst (EC], and esophageal papilloma [EP]) using WLE images; and (3) discrimination between EL and EC using EUS images. Six endoscopists blinded to the patients' clinical status were enrolled to interpret all images independently. Their diagnostic performances were evaluated and compared with the CNN models using the area under the receiver operating characteristic curve (AUC). RESULTS: For task 1, the CNN model achieved an AUC of 0.751 (95% confidence interval [CI], 0.652-0.850) in identifying benign esophageal lesions. For task 2, the proposed model using WLE images for differentiation of esophageal protruded lesions achieved an AUC of 0.907 (95% CI, 0.835-0.979), 0.897 (95% CI, 0.841-0.953), and 0.868 (95% CI, 0.769-0.968) for EP, EL, and EC, respectively. The CNN model achieved equivalent or higher identification accuracy for EL and EC compared with skilled endoscopists. In the task of discriminating EL from EC (task 3), the proposed CNN model had AUC values of 0.739 (EL, 95% CI, 0.600-0.878) and 0.724 (EC, 95% CI, 0.567-0.881), which outperformed seniors and novices. Attempts to combine the CNN and endoscopist predictions led to significantly improved diagnostic accuracy compared with endoscopists interpretations alone. CONCLUSIONS: Our team established CNN-based methodologies to recognize benign esophageal protruded lesions using routinely obtained WLE and EUS images. Preliminary results combining the results from the models and the endoscopists underscored the potential of ensemble models for improved differentiation of lesions in real endoscopic settings.

Distribution Characteristics of Low-Molecular-Weight Organic Acids in Reclaimed Soil Filled with Fly Ash: A Study.

This study aims to assess the contents of different kinds of low-molecular-weight organic acids (LMWOAs) in reclaimed soil filled with fly ash in the Huainan mining area in China using high-performance liquid chromatography (HPLC). Using a mobile phase consisting of 0.1% phosphoric acid and acetonitrile in a volume ratio of 98:2, the detection was performed at a wavelength of 210 nm for 15 min. In addition, a cluster analysis was performed on the detected LMWOAs in the reclaimed soil. The correlations between the LMWOA and nutrient contents in the reclaimed soil were also analyzed. In total, eight and seven LMWOAs were detected in the reclaimed soil and filled fly ash, respectively. In contrast, no LMWOAs were detected in the fresh fly ash from a thermal power plant. The order of total LMWOA contents at different sampling points followed the order of farmland control soil > 1# (Triticum aestivum) > 4# (Phragmites australis) > 5# (Vigna radiata) > 2# (Sorghum bicolor) > 3# (Tamarix ramosissima) > fly ash-filled soil. The farmland control soil and fly ash-filled soil exhibited the highest and lowest LMWOA contents of 648.22 and 85.09 µg·g-1, respectively. The LMWOA contents in the reclaimed soil followed the order of oxalic acid > tartaric acid > malonic acid > lactic acid > acetic acid > citric acid > propionic acid > succinic acid. Indeed, oxalic acids exhibited the highest total amount of 1445.79 µg·g-1 and succinic acids exhibited the lowest total amount of 6.50 µg·g-1. The LMWOA contents in the reclaimed soil decreased with increasing soil depth, showing statistically significant differences between the 0-10 and 10-40 cm soil layers (p < 0.05). According to the obtained clustering results, the detected LMWOAs can be divided into two categories. The first category consisted of oxalic acid, while the second category included the remaining LMWOAs. The soil LMWOA contents of 4# (Phragmites australis) and 5# (Vigna radiata) were significantly different from those at the other sampling points. According to the Pearson correlation analysis results, the occurrence and characteristics of the soil LMWOAs can be controlled by regulating the pH values and available nutrient contents in the soil, thereby improving the eco-environmental conditions of the reclaimed rhizosphere.

Effects of folic acid supplementation on chronic atrophic gastritis based on MTHFR C677T polymorphism.

BACKGROUND: It has been shown the methylenetetrahydrofolate reductase (MTHFR) 677TT (rs 1801133) genotype predicts histopathological alterations in the incisura of patients with chronic atrophic gastritis (CAG). MTHFR is a crucial enzyme in fatty acid (FA) metabolism. This study aimed to evaluate the influence of FA supplementation in CAG patients without Helicobacter pylori infection and the MTHFR C677T (rs 1801133) genotype as a potential CAG predictor. METHODS: A total of 96 CAG patients, aged 21 to 72 years old, were enrolled in this study. After 6 months of treatment, histopathological outcomes were compared among patients treated with weifuchun (WFC) (1.44 g 3 times per os per day), those treated with WFC and FA (5 mg once daily), and those treated with WFC, FA, and vitamin B12 (VB12) (0.5 mg 3 times per day) based on the Operative Link on Gastritis/Intestinal Metaplasia assessment staging systems. RESULTS: Atrophic lesions in patients treated with WFC and FA improved more than in patients treated only with WFC therapy (78.1% vs 53.3%, P = .04). Atrophic or intestinal metaplasia (IM) lesions in the incisura of patients with the TT genotype were better than those in patients with the CC/CT genotype (P = .02). CONCLUSION: The treatment of CAG patients with 5 mg of FA supplements daily for 6 months improved their gastric atrophy status, especially for the Operative Link on Gastritis/Intestinal Metaplasia assessment stages I/II. Moreover, our study is the first to reveal that patients with the MTHFR 677TT genotype require more timely and effective FA treatment than those with the CC/CT genotype.

A Multimodal Multipath Artificial Intelligence System for Diagnosing Gastric Protruded Lesions on Endoscopy and Endoscopic Ultrasonography Images.

INTRODUCTION: The aim of this study was to develop a novel artificial intelligence (AI) system that can automatically detect and classify protruded gastric lesions and help address the challenges of diagnostic accuracy and inter-reader variability encountered in routine diagnostic workflow. METHODS: We analyzed data from 1,366 participants who underwent gastroscopy at Jiangsu Provincial People's Hospital and Yangzhou First People's Hospital between December 2010 and December 2020. These patients were diagnosed with submucosal tumors (SMTs) including gastric stromal tumors (GISTs), gastric leiomyomas (GILs), and gastric ectopic pancreas (GEP). We trained and validated a multimodal, multipath AI system (MMP-AI) using the data set. We assessed the diagnostic performance of the proposed AI system using the area under the receiver-operating characteristic curve (AUC) and compared its performance with that of endoscopists with more than 5 years of experience in endoscopic diagnosis. RESULTS: In the ternary classification task among subtypes of SMTs using modality images, MMP-AI achieved the highest AUCs of 0.896, 0.890, and 0.999 for classifying GIST, GIL, and GEP, respectively. The performance of the model was verified using both external and internal longitudinal data sets. Compared with endoscopists, MMP-AI achieved higher recognition accuracy for SMTs. DISCUSSION: We developed a system called MMP-AI to identify protruding benign gastric lesions. This system can be used not only for white-light endoscope image recognition but also for endoscopic ultrasonography image analysis.

Enhancement of photodynamic bactericidal activity of curcumin against Pseudomonas Aeruginosa using polymyxin B.

BACKGROUND: Pseudomonas aeruginosa (P. aeruginosa) is an emerging opportunistic pathogen, which can cause bacterial skin diseases such as green nail syndrome, interdigital infections and folliculitis. Curcumin-mediated antimicrobial photodynamic therapy (aPDT) has been demonstrated as a promising therapeutic option for the treatment of skin infection though its inactivation of gram-negative bacteria such as P. aeruginosa. MATERIALS AND METHODS: In the present study, we examined the adjuvant effect of polymyxin B on the antibacterial activity of curcumin-mediated aPDT against P. aeruginosa. P. aeruginosa was treated with curcumin in the presence of 0.1-0.5 mg/L polymyxin B and irradiated by blue LED light (10 J/cm2). Bacterial cultures treated with curcumin alone served as controls. Colony forming units (CFU) were counted and the viability of P. aeruginosa was calculated after aPDT treatment. The possible underlying mechanisms for the enhanced killing effects were also explored. RESULTS: The killing effects of curcumin-mediated aPDT against P. aeruginosa was significantly enhanced by polymyxin B (over 2-log reductions). Moreover, it was also observed that addition of polymyxin B in the curcumin-mediated aPDT led to the apparent bacterial membrane damage with increased leakage of cytoplasmic contents and extensive DNA and protein degradation. DISCUSSION: The photodynamic action of curcumin against P. aeruginosa could be significantly enhanced by the FDA-approved drug polymyxin B. Our results highlight the potential of introducing polymyxin B to enhance the effects of aPDT treatment against gram-negative skin infections, in particular, P. aeruginosa.

Validated Impacts of N6-Methyladenosine Methylated mRNAs on Apoptosis and Angiogenesis in Myocardial Infarction Based on MeRIP-Seq Analysis.

Objectives: N6-methyladenosine (m6A) is hypothesized to play a role in the regulation of pathogenesis of myocardial infarction (MI). This study was designed to compare m6A-tagged transcript profiles to identify mRNA-specific changes on pathophysiological variations after MI. Methods: N6-methyladenosine methylated RNA immunoprecipitation sequencing (MeRIP-seq) and RNA sequencing (RNA-seq) were interacted to select m6A-modified mRNAs with samples collected from sham operated and MI rat models. m6A methylation regulated mRNAs were interacted with apoptosis/angiogenesis related genes in GeneCards. Afterwards, MeRIP-quantitative real-time PCR (MeRIP-qRT-PCR) was performed to measure m6A methylation level of hub mRNAs. m6A methylation variation was tested under different oxygen concentration or hypoxic duration in H9c2 cells and HUVECs. In addition, Western blot and qRT-PCR were employed to detect expression of hub mRNAs and relevant protein level. Flow cytometry and Tunel assay were conducted to assess apoptotic level. CCK-8, EdU, and tube formation assay were performed to measure cell proliferation and tube formation ability. Results: Upregulation of Mettl3 was firstly observed in vivo and in vitro, followed by upregulation of m6A methylation level. A total of 567 significantly changed m6A methylation peaks were identified, including 276 upregulated and 291 downregulated peaks. A total of 576 mRNAs were upregulated and 78 were downregulated. According to combined analysis of MeRIP-seq and RNA-seq, we identified 26 significantly hypermethylated and downregulated mRNAs. Based on qRT-PCR and interactive analysis, Hadh, Kcnn1, and Tet1 were preliminarily identified as hub mRNAs associated with apoptosis/angiogenesis. MeRIP-qRT-PCR assay confirmed the results from MeRIP-seq. With the inhibition of Mettl3 in H9c2 cells and HUVECs, downregulated m6A methylation level of total RNA and upregulated expression of hub mRNAs were observed. Increased m6A level was verified in the gradient context in terms of prolonged hypoxic duration and decreased oxygen concentration. Under simulated hypoxia, roles of Kcnn1 and Tet1 in angiogenesis and Hadh, Tet1, and Kcnn1 in apoptosis were further confirmed with our validation experiments. Conclusion: Roles of m6A-modified mRNA transcripts in the context of MI were preliminarily verified. In the context of m6A methylation, three hub mRNAs were validated to impact the process of apoptosis/angiogenesis. Our study provided theoretical basis and innovative targets for treatment of MI and paved the way for future investigations aiming at exploring upstream epigenetic mechanisms of pathogenesis after MI.

Photodynamic inactivation of Burkholderia cepacia by curcumin in combination with EDTA.

Burkholderia cepacia (B. cepacia) is an aerobic Gram-negative bacillus found in various aquatic environments and can cause food contamination. We investigated the photodynamic antibacterial effects of food additive curcumin combined with EDTA on B. cepacia. We found a ~4-log reduction in B. cepacia viability when photo-irradiated with curcumin at 50 µM by blue LED light (16 mW/cm2) for 30 min with 0.4% (w/v) EDTA. Moreover, the bacterial morphological alterations and the leakage of intracellular contents were observed after photodynamic treatment. There were also obvious genomic DNA cleavage and a general loss of bacterial proteins assigned to large-scale protein degradation after photodynamic inactivation treatment. Collectively, curcumin in combination with EDTA illuminated by blue LED is a potential candidate for photodynamic inactivation of B. cepacia.