Ten-Day Vonoprazan-Amoxicillin Dual Therapy as a First-Line Treatment of Helicobacter pylori Infection Compared With Bismuth-Containing Quadruple Therapy.

INTRODUCTION: No study has investigated the efficacy and safety of vonoprazan-amoxicillin dual therapy compared with bismuth quadruple therapy (B-quadruple). This study aimed to evaluate the efficacy and safety of 10-day vonoprazan-amoxicillin dual therapy as a first-line treatment of Helicobacter pylori infection compared with B-quadruple and to explore the optimal dosage of amoxicillin in the dual therapy. METHODS: A total of 375 treatment-naive, H. pylori -infected subjects were randomly assigned in a 1:1:1 ratio into 3 regimen groups including VHA-dual (vonoprazan 20 mg twice/day + amoxicillin 750 mg 4 times/day), VA-dual (vonoprazan 20 mg + amoxicillin 1,000 mg twice/day), and B-quadruple (esomeprazole 20 mg + bismuth 200 mg + amoxicillin 1,000 mg + clarithromycin 500 mg twice/day). Eradication rates, adverse events (AEs), and compliance were compared between 3 groups. RESULTS: The eradication rates of B-quadruple, VHA-dual, and VA-dual were 90.9%, 93.4%, and 85.1%, respectively, by per-protocol analysis; 89.4%, 92.7%, and 84.4%, respectively, by modified intention-to-treat analysis; 88.0%, 91.2%, and 82.4%, respectively, by intention-to-treat analysis. The efficacy of the VHA-dual group was not inferior to the B-quadruple group ( P < 0.001), but VA-dual did not reach a noninferiority margin of -10%. The AEs rates of the B-quadruple group were significantly higher than those of the VHA-dual ( P = 0.012) and VA-dual ( P = 0.001) groups. There was no significant difference in medication compliance among 3 treatment groups ( P = 0.995). CONCLUSIONS: The 10-day VHA-dual therapy provided satisfactory eradication rates of >90%, lower AEs rates, and similar adherence compared with B-quadruple therapy as a first-line therapy for H. pylori infection. However, the efficacy of VA-dual therapy was not acceptable.

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.

Imbalance of Microbacterial Diversity Is Associated with Functional Prognosis of Stroke.

Objectives: There is mounting evidence to suggest that the pathophysiology of stroke is greatly influenced by the microbiota of the gut and its metabolites, in particular short-chain fatty acids (SCFAs). The primary purpose of the study was to evaluate whether the levels of SCFAs and the gut microbiota are altered in poststroke patients and to examine the relationship between these alterations and the physical condition, intestinal health, pain, or nutritional status of patients. Methods: Twenty stroke patients and twenty healthy controls were enrolled in the current study, and their demographics were matched. Gas chromatography was used to determine the fecal SCFAs, and 16S rRNA gene sequencing was used to evaluate their fecal microbiota. Microbial diversity and richness were examined using the diversity indices alpha and beta, and taxonomic analysis was utilized to determine group differences. The relationships between the gut microbiome and fecal SCFAs, discriminant bacteria, and poststroke clinical outcomes were analyzed. Results: Less community richness (ACE and Chao) was observed in the poststroke patients (P < 0.05), but the differences between the poststroke group and the healthy control group in terms of species diversity (Shannon and Simpson) were not statistically significant. The makeup of the poststroke gut microbiota was distinct from that of the control group, as evidenced by beta diversity. Then, the relative abundances of the taxa in the poststroke and control groups were compared in order to identify the specific microbiota changes. At the level of phylum, the poststroke subjects showed a significant increase in the relative abundances of Akkermansiaceae, Fusobacteriota, Desulfobacterota, Ruminococcaceae, and Oscillospirales and a particularly noticeable decrease in the relative abundance of Acidobacteriota compared to the control subjects (P < 0.05). In regard to SCFA concentrations, lower levels of fecal acetic acid (P = 0.001) and propionic acid (P = 0.049) were found in poststroke subjects. Agathobacter was highly correlated with acetic acid level (r = 0.473, P = 0.002), whereas Fusobacteria (r = -0.371, P = 0.018), Flavonifractor (r = -0.334, P = 0.034), Desulfovibrio (r = -0.362, P = 0.018), and Akkermansia (r = -0.321, P = 0.043) were negatively related to acetic acid levels. Additionally, the findings of the correlation analysis revealed that Akkermansia (r = -0.356, P = 0.024), Desulfovibrio (r = -0.316, P = 0.047), and Alloprevotella (r = -0.366, P = 0.020) were significantly negatively correlated with high-density lipoprotein cholesterol. In addition, the Neurogenic Bowel Dysfunction score (r = 0.495, P = 0.026), Barthel index (r = -0.531, P = 0.015), Fugl-Meyer Assessment score (r = -0.565, P = 0.009), Visual Analogue Scale score (r = 0.605, P = 0.005), and Brief Pain Inventory score (r = 0.507, P = 0.023) were significantly associated with alterations of distinctive gut microbiota. Conclusions: Stroke generates extensive and substantial alterations in the gut microbiota and SCFAs, according to our findings. The differences of intestinal flora and lower fecal SCFA levels are closely related to the physical function, intestinal function, pain, or nutritional status of poststroke patients. Treatment strategies aimed at modulating the gut microbiota and SCFAs may have the potential to enhance the clinical results of patients.

The efficacy and long-term outcomes of endoscopic full-thickness suturing for chronic gastrointestinal fistulas with an Overstitch device: is it a durable closure?

BACKGROUND AND AIM: Endoscopic closure of chronic gastrointestinal fistulas (CGFs) is challenging due to their epithelialized surfaces. The aim of this study was to assess the efficacy and long-term closure rate of endosuturing for CGFs with an Apollo Overstitch device. PATIENTS AND METHODS: Consecutive CGF patients undergoing endosuturing for fistula closure from April 2018 to January 2020 at the First Affiliated Hospital of Nanjing Medical University were enrolled for retrospective review. Demographics, fistula characteristics, details of the suturing procedures and outcomes were collected for analysis. RESULTS: Twenty patients (mean age 59.8 ± 9.1 years; 85% males) with a total of 23 CGFs underwent sutured fistula closure. Esophagotracheal fistulas were the most common CGFs (12/23, 52.2%), and prior cancer surgery was the most common fistulization etiology (14/20, 70%). Twelve patients (12/20, 60%) had undergone failed endoscopic attempts at fistula closure before suturing. Additional endoscopic therapies used during suturing were 100% argon plasma coagulation, 50% clip fixation, and 10% stent placement. Although all patients undergoing suturing achieved immediate technical success of fistula closure, sustained fistula closure was observed in only 5 patients (5/20, 25.0%) on surveillance endoscopy 3 months after suturing with a mean follow-up of 19.5 months. Esophagotracheal fistula patients were predisposed to shorter dehiscence-free survival than those with other fistulas (HR 3.378; 95% CI 1.127-10.13). CONCLUSIONS: Endosuturing is safe and should be considered for use as the first-line or salvage therapy for CGF closure, primarily for patients with fistulas not involving the trachea. However, the long-term healing of CGFs by suturing is challenging, and CGF patients might not benefit from repeated suturing.

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.

Establishment and validation of a model to determine the progression risk of low grade intraepithelial neoplasia.

OBJECTIVE: To establish and validate a model to determine the progression risk of gastric low-grade intraepithelial neoplasia (LGIN). METHODS: A total of 705 patients with gastric LGIN at the endoscopy center of Jiangsu Provincial People's Hospital during January 2010 and August 2017 were retrospectively reviewed. Basic clinical and pathological information were recorded. According to the time sequence of the initial examination, the first 605 patients were enrolled in the derivation group, and the remaining 100 patients were used in the validation group. SPSS 19 software was used as statistical analysis to determine independent risk factors for progression of LGIN of the stomach and to establish a risk model. The ROC was used to verify the application value of the predictive model. RESULTS: Univariate and multivariate analysis suggested that sex, multiple location, congestion, ulceration and form were independent risk factors for prolonged or advanced progression in patients with LGIN. Based on this, a predictive model is constructed: P = ex/(1 + ex) X = - 10.399 + 0.922 × Sex + 1.934 × Multiple Location + 1.382 × Congestion + 0.797 × Ulceration + 0.525 × Form. The higher of the P value means the higher risk of progression. The AUC of the derivation group and validation group were 0.784 and 0.766, respectively. CONCLUSION: Sex, multi-site, hyperemia, ulcer and morphology are independent risk factors for the prolongation or progression of patients with gastric LGIN. These factors are objective and easy to obtain data. Based on this, a predictive model is constructed, which can be used in management of patients. The model can be used to identify high-risk groups in patients with LGIN that may progress to gastric cancer. Strengthening follow-up or endoscopic treatment to improve the detection rate of early cancer or reduce the incidence of gastric cancer can provide a reliable basis for the treatment of LGIN.

Distinctive Gut Microbiota Alteration Is Associated with Poststroke Functional Recovery: Results from a Prospective Cohort Study.

Objectives: Functional prognosis is potentially correlated with gut microbiota alterations following the dysregulation of the gut-microbiota-brain axis after stroke. This study was designed to explore the poststroke alterations of gut microbiota and potential correlations between gut microbiota and global functions. Methods: A total of thirty-eight patients with stroke and thirty-five healthy demographics-matched controls were recruited. Their fecal DNAs were extracted, and the V3-V4 regions of the conserved bacterial 16S RNA were amplified and sequenced on the Illumina MiSeq platform. Microbial composition, diversity indices, and species cooccurrence were compared between groups. Random forest and receiver operating characteristic analysis were used to identify potential diagnostic biomarkers. Relationships between discriminant bacteria and poststroke functional outcomes were estimated. Results: Higher alpha diversity of gut microbiota was observed in poststroke patients as compared to the healthy controls (p < 0.05). Beta diversity showed that microbiota composition in the poststroke group was significantly different from that in the control group. Relative abundance of nine genera increased significantly in poststroke patients, while 82 genera significantly decreased (p < 0.05). The accuracy, specificity, and susceptibility of the optimal model consisted of the top 10 discriminant species were 93%, 100%, and 86%, respectively. Subgroup analysis showed that bacterial taxa abundant between subacute and chronic stroke patients were overall different (p < 0.05). The modified Rankin scale (mRS) (r = -0.370, p < 0.05), Fugl-Meyer assessment (FMA) score (r = 0.364, p < 0.05), water swallow test (WST) (r = 0.340, p < 0.05), and Barthel index (BI) (r = 0.349, p < 0.05) were significantly associated with alterations of distinctive gut microbiota. Conclusions: The gut microbiota in patients with stroke was significantly changed in terms of richness and composition. Significant associations were detected between alterations of distinctive gut microbiota and global functional prognosis. It would facilitate novel treatment target selection in the context of stroke while the causal relationships between distinctive gut microbiota alterations and functional variations need to be further verified with well-designed studies.

circCUL2 regulates gastric cancer malignant transformation and cisplatin resistance by modulating autophagy activation via miR-142-3p/ROCK2.

BACKGROUND: Circular RNAs (circRNAs) are a class of noncoding RNAs (ncRNAs) and can modulate gene expression by binding to miRNAs; further, circRNAs have been shown to participate in several pathological processes. However, the expression and biological function of circCUL2 in gastric cancer (GC) remains largely unknown. METHODS: circRNA microarrays and quantitative real-time PCR (qRT-PCR) were used to identify differentially expressed circRNAs in GC tissues and cell lines. circCUL2 knockdown and overexpression were performed to indicate the functional role of circCUL2 in vitro and in vivo. The expression and regulation of circCUL2, miR-142-3p and ROCK2 were evaluated using fluorescence in situ hybridization (FISH), dual-luciferase assays, RNA pull-down assays, RNA immunoprecipitation (RIP) and rescue experiments. Furthermore, the regulation of cisplatin sensitivity and autophagy by circCUL2/miR-142-3p/ROCK2 was demonstrated by cellular apoptosis assays, western blot, immunofluorescence and transmission electron microscopy analyses. RESULTS: The level of circCUL2, which is stable and cytoplasmically localized, was significantly reduced in GC tissues and cells. Overexpressed circCUL2 inhibited malignant transformation in vitro and tumorigenicity in vivo. In the AGS and SGC-7901 cell lines, circCUL2 sponged miR-142-3p to regulate ROCK2, thus modulating tumor progression. Furthermore, in the AGS/DDP and SGC-7901/DDP cell lines, circCUL2 regulated cisplatin sensitivity through miR-142-3p/ROCK2-mediated autophagy activation. CONCLUSION: circCUL2 may function as a tumor suppressor and regulator of cisplatin sensitivity through miR-142-3p/ROCK2-mediated autophagy activation, which could be a key mechanism and therapeutic target for GC.

Association of MTHFR C677T polymorphism with severity and localization of chronic atrophic gastritis patients without Helicobacter pylori infection: a case control study.

BACKGROUND: Previous reports indicate that the methylenetetrahydrofolate reductase (MTHFR) 677C > T polymorphism plays a role in gastric cancer. However, whether it influences the development and progression of atrophic gastritis remains ambiguous. We aimed to determine the possible relationship between MTHFR C677T polymorphism and the severity of atrophic gastritis. METHODS: A total of 128 patients without Helicobacter pylori infection were included in the study. The severity of gastric atrophy was assessed by pathological diagnosis using OLGA and OLGIM Gastritis Staging System. MTHFR 677C > T genotyping was performed by digital fluorescence molecular hybridization. Categorical variables were analyzed by percentages using the χ2 test. RESULTS: In this study, the TT genotype was significantly more frequent among Helicobacter pylori-negative patients aged ≤44 years (age ≤ 44 years vs. > 44 years, P = 0.039). Patients with TT genotype showed a higher ratio of incisura with atrophy or intestinal metaplasia (TT vs. CC + CT, P = 0.02). Furthermore, TT genotype was associated with more severe lesions compared with the CC + CT genotypes (TT vs. CC + CT for atrophy: P = 0.07; for intestinal metaplasia: P = 0.01; for moderate-to-severe lesions: P = 0.01). OLGA and OLGIM stages III-IV were observed more frequently in patients with TT genotype compared with CC + CT genotypes (for OLGA: P = 0.003; for OLGIM: P = 0.036). CONCLUSIONS: The MTHFR 677C > T TT genotype showed an increased risk of moderate-to-severe lesions by OLGA and OLGIM stages, and these results indicate that MTHFR C677T polymorphism may act as a predictive marker for precancerous gastric lesions, especially in Helicobacter pylori-negative patients aged ≤44 years.

Lesion size and circumferential range identified as independent risk factors for esophageal stricture after endoscopic submucosal dissection.

BACKGROUND AND AIM: Endoscopic submucosal dissection (ESD) is used to treat early esophageal cancer and precancerous lesions. Patients undergoing ESD are prone to esophageal stenosis, which impairs therapeutic efficacy and quality of life. This retrospective study aimed to investigate the potential association between patient demographics and esophageal lesion characteristics with the risk of esophageal stenosis following ESD. METHODS: For this retrospective study 190 consecutive patients who underwent ESD between January 2013 and January 2015 were recruited. Data on patient demographics, esophageal lesion-related factors, operation details, esophageal stenosis occurrence and measures taken to prevent or treat stricture were collected, and the normality of distribution of each indicator was assessed with a Kolmogorov-Smirnov test. Stenosis risk factors were then identified using univariate and multivariate logistic regression. RESULTS: Post-ESD esophageal stenosis occurred in 51 cases. Multivariate logistic regression analysis was performed to identify independent risk factors. A history of EMR/ESD (OR = 4.185, 95% CI: 1.511-11.589), resection circumferential diameter (OR = 1.721, 95% CI: 1.135-2.610), non-en bloc resection (OR = 7.413, 95% CI: 2.398-22.921), submucosal infiltration (OR = 3.449, 95% CI: 1.014-11.734) and circumferential resection range (OR = 57.493, 95% CI: 17.236-191.782) were identified as independent risk factors for post-ESD esophageal stenosis. Spraying porcine fibrin adhesive on the resection bed reduced neither the incidence of postoperative stenosis nor the extent of postoperative dilation. CONCLUSION: Post-ESD esophageal stenosis is significantly related to size and circumferential range of lesion resection. EMR/ESD history, non-en bloc resection and submucosal infiltration may be additional risk factors.

Can inspiratory muscle training benefit patients after stroke? A systematic review and meta-analysis of randomized controlled trials.

OBJECTIVES: The aim of this study was to investigate the effects of inspiratory muscle training in post-stroke patients and to explore the effective training protocol. DATA SOURCES: PubMed/Medline, Web of Science, Scopus, Embase, Cochrane database, China National Knowledge Infrastructure, and China Science Periodical Database were searched through April 2020. REVIEW METHODS: Trials examining effects of inspiratory muscle training on pulmonary function, cardiopulmonary endurance, pulmonary infection incidence, and quality of life in post-stroke patients were included. Subgroup analysis was performed to compare different training programs. Mean differences and risk ratios with 95% confidence intervals were presented. Risk of bias was assessed with the Cochrane tool. RESULTS: Thirteen randomized controlled trials involving a total of 373 participants were identified. Meta-analysis conducted in 8 out of 13 trials revealed evidence for beneficial effects of inspiratory muscle training on forced vital capacity (MD: 0.47, 95% CI: 0.28-0.66), forced expired volume in 1 second (MD: 0.26, 95% CI: 0.18-0.35), 6-minute walk test (MD: 52.61, 95% CI: 25.22-80.01), maximum inspiratory pressure (MD: 18.18, 95% CI: 5.58-30.78), inspiratory muscle endurance (MD: 19.99, 95% CI: 13.58-26.40), and pulmonary infection incidence (RR: 0.11, 95% CI: 0.03-0.40). Omitting individual trials from the meta-analysis did not significantly change the results. The effective inspiratory muscle training protocol was suggested by subgroup analysis with three repetitions per week and more than 20 minutes per day for three weeks. CONCLUSION: Inspiratory muscle training can be considered as an effective intervention for improving pulmonary function and cardiopulmonary endurance, and reducing pulmonary infection incidence in patients after stroke.

Safety and efficacy of submucosal tunneling endoscopic septum division for epiphrenic diverticula.

BACKGROUND: Symptomatic epiphrenic diverticula are mostly treated with laparoscopic diverticulectomy. Our study aimed to demonstrate the safety and efficacy of submucosal tunneling endoscopic septum division (STESD) for treatment of symptomatic epiphrenic diverticula. METHODS: Data from patients with epiphrenic diverticula who had undergone STESD were retrospectively reviewed. The parameters analyzed were the modified Eckardt score, total procedure time, length of hospital stay (LOS), number of clips used, adverse events, and patient satisfaction. RESULTS: A total of eight patients (5 men; mean [standard deviation (SD)] age 66.25 [7.17] years) were enrolled in our study. The mean (SD) size of epiphrenic diverticula was 3.68 (1.59) cm. The mean (SD) procedure time was 52.87 (22.47) minutes, with a median number of six clips being applied. The modified Eckardt score significantly decreased post-procedure (P < 0.001). The mean (SD) LOS was 5.87 (0.83) days. No adverse events or symptom recurrences were reported. CONCLUSION: STESD is a safe and effective technique to be performed in the submucosal tunnel for the management of patients with epiphrenic diverticula.

Disseminated histoplasmosis in an immunocompetent individual diagnosed with gastrointestinal endoscopy: a case report.

BACKGROUND: Histoplasmosis is one of the invasive fungal infections and presents with symptoms mainly in the lungs. Disseminated histoplasmosis (DH) is rare and its lesions in the gastrointestinal tract are even uncommon. The concomitant involvement of the upper and lower gastrointestinal tract has never been described in the immunocompetent individuals. CASE PRESENTATION: A 44-year-old immunocompetent Chinese man presented with fever, hepatosplenomegaly, fungal esophagitis and protuberant lesions with central depression and erosion along the mucous membrane of the colon. The patient was diagnosed as disseminated histoplasmosis by gastrointestinal endoscopy. CONCLUSIONS: Histoplasmosis should be taken caution in patients with fever and hepatosplenomegaly. Actions should be taken to avoid its disseminated infection associated high mortality.

MicroRNA-150 as a Potential Biomarker in Diagnosis of Cancer: a Meta-Analysis.

BACKGROUND: Altered expression of microRNAs contributes to human carcinogenesis. Previous studies assessed the association of aberrant circulating microRNA (miR)-150 level with the risk in developing various human cancers, but the data were inconsistent. METHODS: This meta-analysis further assessed the potential diagnostic value of miR-150 in cancer. PubMed, Embase, and Web of Science for publications were searched using the keywords of miR-150 and human cancer. Summary odds ratios (ORs) and 95% confidence intervals (CIs) were obtained to assess the diagnostic value. RESULTS: The summary estimates revealed that the pooled sensitivity was 80% (95% CI: 74% - 85%), the specificity was 81% (95% CI: 71% - 87%), the DOR was 16.47 (95% CI: 10.41 - 26.06), and the AUC was 0.86 (95% CI: 0.82 - 0.89) for miR-150 as a tumor marker. CONCLUSIONS: miR-150 may be a potential noninvasive tumor marker for various human cancers and further studies with a large sample size are needed to confirm.

LncRNA HOTAIR promotes cisplatin resistance in gastric cancer by targeting miR-126 to activate the PI3K/AKT/MRP1 genes.

Altered expression of long noncoding RNAs (lncRNAs) has shown to associate with human cancer development and progression and drug resistance. LncRNA HOX antisense intergenic RNA (HOTAIR) regulates chromatin state and highly expressed in various human cancers. This study analyzed HOTAIR expression in gastric cancer cells and tissues and then assessed the effects of HOTAIR on modulation of gastric cancer cell sensitivity to cisplatin and the underlying molecular events. The data showed that HOTAIR was significantly upregulated in cisplatin-resistant gastric cancer cells and tissues compared with control cells and noncancerous gastric tissues. Overexpression of HOTAIR enhanced gastric cancer cell proliferation, promoted cell cycle G1/S transition, but decreased tumor cell apoptosis. Furthermore, HOTAIR was shown to directly bind to and inhibit miR-126 expression and then to promote VEGFA and PIK3R2 expression and activate the PI3K/AKT/MRP1 pathway. In conclusion, the data demonstrated that high HOTAIR expression acted as a competitive endogenous RNA to promote cisplatin resistance in gastric cancer. Further study will evaluate HOTAIR expression as a biomarker to predict treatment response of cisplatin and explore inhibition of HOTAIR expression as a novel strategy for anti-cisplatin resistance in human gastric cancer.

A MDM2-dependent positive-feedback loop is involved in inhibition of miR-375 and miR-106b induced by Helicobacter pylori lipopolysaccharide.

Dysregulation of microRNAs (miRNAs) has been linked to virulence factors of Helicobacter pylori and shown to contribute to the progression of gastric cancer. However, the mechanisms of these processes remain poorly understood. The aim of this study was to investigate the mechanisms by which lipopolysaccharide (LPS), a virulence factor of H. pylori, regulates miR-375 and miR-106b expression in gastric epithelial cells. The results show that LPS from H. pylori 26695 downregulated the expression of miR-375 and miR-106b in gastric epithelial cells, and low levels of Dicer were also observed. Downregulation of miR-375 was found to increase expression of MDM2 with SP1 activation. Overexpression of MDM2 inhibited Dicer by repressing p63 to create a positive-feedback loop involving SP1/MDM2/p63/Dicer that leads to inhibition of miR-375 and miR-106b expression. In addition, we demonstrated that JAK1 and STAT3 were downstream target genes of miR-106b. H. pylori LPS also enhanced the tyrosine phosphorylation of JAK1, JAK2 and STAT3. Together, these results provide insight into the regulatory mechanisms of MDM2 on H. pylori LPS-induced specific miRNAs, and furthermore, suggest that gastric epithelial cells treated with H. pylori LPS may be susceptible to JAK/STAT3 signal pathway activation via inhibition of miR-375 and miR-106b.

Machine learning algorithms assisted identification of post-stroke depression associated biological features.

Objectives: Post-stroke depression (PSD) is a common and serious psychiatric complication which hinders functional recovery and social participation of stroke patients. Stroke is characterized by dynamic changes in metabolism and hemodynamics, however, there is still a lack of metabolism-associated effective and reliable diagnostic markers and therapeutic targets for PSD. Our study was dedicated to the discovery of metabolism related diagnostic and therapeutic biomarkers for PSD. Methods: Expression profiles of GSE140275, GSE122709, and GSE180470 were obtained from GEO database. Differentially expressed genes (DEGs) were detected in GSE140275 and GSE122709. Functional enrichment analysis was performed for DEGs in GSE140275. Weighted gene co-expression network analysis (WGCNA) was constructed in GSE122709 to identify key module genes. Moreover, correlation analysis was performed to obtain metabolism related genes. Interaction analysis of key module genes, metabolism related genes, and DEGs in GSE122709 was performed to obtain candidate hub genes. Two machine learning algorithms, least absolute shrinkage and selection operator (LASSO) and random forest, were used to identify signature genes. Expression of signature genes was validated in GSE140275, GSE122709, and GSE180470. Gene set enrichment analysis (GSEA) was applied on signature genes. Based on signature genes, a nomogram model was constructed in our PSD cohort (27 PSD patients vs. 54 controls). ROC curves were performed for the estimation of its diagnostic value. Finally, correlation analysis between expression of signature genes and several clinical traits was performed. Results: Functional enrichment analysis indicated that DEGs in GSE140275 enriched in metabolism pathway. A total of 8,188 metabolism associated genes were identified by correlation analysis. WGCNA analysis was constructed to obtain 3,471 key module genes. A total of 557 candidate hub genes were identified by interaction analysis. Furthermore, two signature genes (SDHD and FERMT3) were selected using LASSO and random forest analysis. GSEA analysis found that two signature genes had major roles in depression. Subsequently, PSD cohort was collected for constructing a PSD diagnosis. Nomogram model showed good reliability and validity. AUC values of receiver operating characteristic (ROC) curve of SDHD and FERMT3 were 0.896 and 0.964. ROC curves showed that two signature genes played a significant role in diagnosis of PSD. Correlation analysis found that SDHD (r = 0.653, P < 0.001) and FERM3 (r = 0.728, P < 0.001) were positively related to the Hamilton Depression Rating Scale 17-item (HAMD) score. Conclusion: A total of 557 metabolism associated candidate hub genes were obtained by interaction with DEGs in GSE122709, key modules genes, and metabolism related genes. Based on machine learning algorithms, two signature genes (SDHD and FERMT3) were identified, they were proved to be valuable therapeutic and diagnostic biomarkers for PSD. Early diagnosis and prevention of PSD were made possible by our findings.

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.

Exosomal circRELL1 serves as a miR-637 sponge to modulate gastric cancer progression via regulating autophagy activation.

Circular RNAs (circRNAs) play a vital role in the occurrence and development of tumors, including gastric cancer (GC). However, there are still many circRNAs related to GC whose functions and molecular mechanisms remain undetermined. Herein, we discover circRNA RELL1, which has not been investigated in GC, and it is markedly downregulated in GC tissues, which is related with poor prognosis, more pronounced lymph node metastasis and poor TNM stage. After confirming the circular structure of circRELL1, we found that circRELL1 could block cell proliferation, invasion, migration, and anti-apoptosis in patients with GC by a series of in vivo and in vitro function-related studies. Further mechanism investigation demonstrated that circRELL1 could sponge miR-637 and indirectly unregulated the expression of EPHB3 via modulating autophagy activation in GC. Additionally, circRELL1 can be transmitted by exosomal communication, and exosomal circRELL1 suppressed the malignant behavior of GC in vivo and in vitro. Taken together, this study elucidates the suppressive roles of circRELL1/miR-637/EPHB3 axis through autophagy activation in GC progression, inspiring for further understanding of the underlying molecular mechanisms of GC and providing a promising novel diagnostic circulating biomarker and therapeutic target in GC.

FTH1- and SAT1-Induced Astrocytic Ferroptosis Is Involved in Alzheimer's Disease: Evidence from Single-Cell Transcriptomic Analysis.

OBJECTIVES: Despite significant advances in neuroscience, the mechanisms of AD are not fully understood. Single-cell RNA sequencing (scRNA-seq) techniques provide potential solutions to analyze cellular composition of complex brain tissue and explore cellular and molecular biological mechanisms of AD. METHODS: We investigated cellular heterogeneity in AD via utilization of bioinformatic analysis of scRNA-seq in AD patients and healthy controls from the Gene Expression Omnibus (GEO) database. The "GOplot" package was applied to explore possible biological processes in oligodendrocytes, astrocytes, and oligodendrocyte progenitor cells (OPCs). Expression patterns and biological functions of differentially expressed genes (DEGs) from scRNA-seq data were validated in RNA sequencing data. DEGs in astrocytes interacted with ferroptosis-related genes in FerrDb. CCK-8 and EdU assays were performed to measure cell proliferation ability. ROS, Fe2+ level, mitochondrial membrane potentials, iron concentrations, and total iron binding capacity (TIBC) in serum were evaluated. Y-maze and elevated maze were used to measure anxiety-like behavior. Autonomous and exploration behaviors or learning and memory ability in mice were analyzed using open field test and novel object recognition test. RESULTS: Multiple clusters were identified, including oligodendrocytes, astrocytes, OPCs, neurons, microglia, doublets, and endothelial cells. Astrocytes were significantly decreased in AD, while oligodendrocytes and OPCs increased. Cell-to-cell ligand-receptor interaction analysis revealed that astrocytes, neurons, and OPCs mainly established contacts with other cells via the NRG3-ERBB4 ligand-receptor pair. GO and KEGG analyses found that astrocytes were enriched in the ferroptosis pathway. FTH1 and SAT1 in astrocytes were identified as hub mRNAs associated with ferroptosis. Serum iron concentration of 5xFAD mice was higher than that of WT, and emotional and cognitive function were significantly impaired as compared to WT. Serum iron concentration was negatively correlated with number of astrocytes and percentage of time spent entering the novelty arm in the Y-maze test, while it was positively correlated with percentage of time spent in the central area. Meanwhile, number of astrocytes was negatively correlated with percentage of time spent in the central area, while it was positively correlated with percentage of time spent entering the novelty arm. CONCLUSIONS: Through scRNA-seq analysis, we found that ferroptosis was activated in astrocytes and may contribute to the pathophysiological process in the entorhinal cortex. FTH1 and SAT1 were identified to impact astrocyte ferroptosis. Emotional and cognitive impairment in AD was associated with astrocyte ferroptosis. Our findings provide clues to reveal the pathophysiological processes following AD at the cellular level and highlight potential drug targets for the treatment of AD.