Objective: The long noncoding RNA (lncRNA) nuclear paraspeckle assembly transcript 1 (NEAT1) has emerged as a novel player in hepatocellular carcinoma (HCC). Hypoxia is a common characteristic of the microenvironment of HCC. This study aimed to investigate whether lncRNA-NEAT1 is induced by hypoxia in HCC, and the mechanism that underlies LncRNA-NEAT1 function. Methods: The expression changes of lncRNA-NEAT1 in HCC cell lines under hypoxic conditions were examined by quantitative reverse transcription-polymerase chain reaction (qRT-PCR). The regulatory effect of HIF-1α on lncRNA-NEAT1 was confirmed with chromatin immunoprecipitation (ChIP) and luciferase reporter assays. The function of lncRNA-NEAT1 on HCC cell growth under hypoxic conditions was determined by CCK-8 assay and flow cytometry. lncRNA -NEAT1 was predicted to serve as a competing endogenous RNA (ceRNA) within microRNA (miRNA)/mRNA axes based on microarray data, public HCC-related datasets and integrative bioinformatics analysis, and the miR-199a-3p/UCK2 axis was selected and validated by qRT-PCR, western blotting, RNA immunoprecipitation, and luciferase reporter analyses. The role of miR-199a-3p/UCK2 in HCC and its functional association with lncRNA-NEAT1 were assessed both in vitro and in vivo. Results: LncRNA-NEAT1 expression was significantly induced by hypoxia in SNU-182 and HUH7 cells. HIF-1α was shown to regulate lncRNA-NEAT1 transcription. Under hypoxic conditions, lncRNA-NEAT1 maintained the growth of HCC cells and inhibited apoptosis and cell cycle arrest. LncRNA-NEAT1 was predicted to regulate a panel of HCC-associated miRNA-mRNA pairs consisting of 8 miRNAs and 13 mRNAs. LncRNA-NEAT1 was shown to function as a ceRNA of miR-199a-3p/UCK2 both in HCC cells under hypoxic conditions and in an animal model. Conclusion: LncRNA-NEAT1 is a hypoxia-responsive lncRNA in HCC cell lines Insilico evidence suggested that LncRNA-NEAT1 may sustainthe growth of HCC cells by regulating HCC-associated mRNAs that interact with tumor-suppressive miRNAs. The lncRNA-NEAT1/miR-199a-3p/UCK2 pathway may contribute to the progression of HCC cell lines in a hypoxic microenvironment and therefore may represent a novel therapeutic target for HCC.

Endoscopy has been routinely used to diagnose stomach diseases including intestinal metaplasia (IM) and gastritis atrophy (GA). Such routine examination usually demands highly skilled radiologists to focus on a single patient with substantial time, causing the following two key challenges: 1) the dependency on the radiologist's experience leading to inconsistent diagnosis results across different radiologists; 2) limited examination efficiency due to the demanding time and energy consumption to the radiologist. This paper proposes to address these two issues in endoscopy using novel machine learning method in three-folds. Firstly, we build a novel and relatively big endoscopy dataset of 21,420 images from the widely used White Light Imaging (WLI) endoscopy and more recent Linked Color Imaging (LCI) endoscopy, which were annotated by experienced radiologists and validated with biopsy results, presenting a benchmark dataset. Secondly, we propose a novel machine learning model inspired by the human visual system, named as local attention grouping, to effectively extract key visual features, which is further improved by learning from multiple randomly selected regional images via ensemble learning. Such a method avoids the significant problem in the deep learning methods that decrease the resolution of original images to reduce the size of input samples, which would remove smaller lesions in endoscopy images. Finally, we propose a dual transfer learning strategy to train the model with co-distributed features between WLI and LCI images to further improve the performance. The experiment results, measured by accuracy, specificity, sensitivity, positive detection rate and negative detection rate, on IM are 99.18 $\%$ , 98.90 $\%$ , 99.45 $\%$ , 99.45 $\%$ , 98.91 $\%$ , respectively, and on GA are 97.12 $\%$ , 95.34 $\%$ , 98.90 $\%$ , 98.86 $\%$ , 95.50 $\%$ , respectively, achieving state of the art performance that outperforms current mainstream deep learning models.

Background: The systematic expression characteristics and functions of collagen genes in gastric cancer (GC) have not been reported. Through public data integration, combined with bioinformatics analysis, we identified a panel of collagen genes overexpressed in GC. The functions of these genes were analyzed and validated in a GC-related cohort. microRNAs that may potentially target such genes were investigated in vitro. Methods: Four GC-related datasets retrieved from the Gene Expression Omnibus (GEO) were used to extract differentially expressed genes (DEGs) in GC. Functional annotation was performed to identify the potential roles of the identified DEGs. The association of candidate genes involved in the prognosis of GC patients (n=876) was determined using data provided by the Kaplan–Meier-plotter database, The Cancer Genome Atlas Stomach Adenocarcinoma (TCGA-STAD) repository, and a GC-related dataset (GSE15459). The expression characteristics of candidate genes and their associations with clinical parameters were validated in our in-house cohort (n=58). MicroRNAs able to target the identified candidate genes were predicted and confirmed using qRT-PCR, Western blotting, and dual-luciferase reporter assays in vitro. Results: After the integration of four GEO datasets, 76 DEGs were identified. Gene Ontology and Kyoto Encyclopedia of Genes and Genomes pathway analysis indicated that these DEGs were significantly enriched in ECM-related functions and pathways. A group of collagen genes was significantly upregulated in the GC tissues and constituted a protein–protein interaction network as important nodes. Some of these collagen genes were closely associated with poor prognosis in GC patients. Overexpression of COL1A1 and COL4A1 was confirmed in our in-house cohort, and this was related to prognosis and certain clinicopathological parameters. We found that microRNA-29c-3p could directly target COL1A1 and COL4A1 in BGC-823 cells. Conclusions: Collagen genes identified in this study were associated with patient prognosis in GC and may represent diagnostic markers or potential therapeutic targets. Aberrant expression of such candidate genes may be induced by microRNA-29c-3p.

Background: Choline, an indispensable nutrient, plays a pivotal role in various physiological processes. The available evidence regarding the nexus between dietary choline intake and health outcomes, encompassing cardiovascular disease (CVD), cancer, and all-cause mortality, is limited and inconclusive. This study aimed to comprehensively explore the relationship between dietary choline intake and the aforementioned health outcomes in adults aged > 20 years in the U.S. Methods: This study utilized data from the National Health and Nutrition Examination Survey between 2011 and 2018. Dietary choline intake was evaluated using two 24-h dietary recall interviews. CVD and cancer status were determined through a combination of standardized medical status questionnaires and self-reported physician diagnoses. Mortality data were gathered from publicly available longitudinal Medicare and mortality records. The study utilized survey-weighted logistic and Cox regression analyses to explore the associations between choline consumption and health outcomes. Restricted cubic spline (RCS) analysis was used for dose‒response estimation and for testing for nonlinear associations. Results: In our study of 14,289 participants (mean age 48.08 years, 47.71% male), compared with those in the lowest quintile (Q1), the adjusted odds ratios (ORs) of CVD risk in the fourth (Q4) and fifth (Q5) quintiles of choline intake were 0.70 (95% CI 0.52, 0.95) and 0.65 (95% CI 0.47, 0.90), respectively (p for trend = 0.017). Each 100 mg increase in choline intake was associated with a 9% reduced risk of CVD. RCS analysis revealed a linear correlation between choline intake and CVD risk. Moderate choline intake (Q3) was associated with a reduced risk of mortality, with an HR of 0.75 (95% CI 0.60–0.94) compared with Q1. RCS analysis demonstrated a significant nonlinear association between choline intake and all-cause mortality (P for nonlinearity = 0.025). The overall cancer prevalence association was nonsignificant, except for colon cancer, where each 100 mg increase in choline intake indicated a 23% reduced risk. Conclusion: Elevated choline intake demonstrates an inverse association with CVD and colon cancer, while moderate consumption exhibits a correlated reduction in mortality. Additional comprehensive investigations are warranted to elucidate the broader health implications of choline.

Background: Wilson’s disease (WD) is a recessive genetic disorder characterized by copper metabolism dysfunction. It is difficult to obtain an accurate diagnosis due to its variable clinical presentation. This study aimed to describe the clinical characteristics and diagnostic particularities in a series of Chinese WD patients.Methods: The medical records of 371 patients with WD retrieved from January 2005 to December 2020 were retrospectively reviewed.Results: The incidence of WD has a male predominance in the adult population. However, the difference in sex distribution is not significant in the pediatric population. Females have an earlier symptom onset than males. The most common initial symptoms were neuropsychiatric manifestations both in the pediatric population (49.7%) and adult population (69.8%), and there was a male predominance (61.8%). Eighty-two percent of patients presented with more than two neurologic symptoms. Fifty-two (14%) patients presented with psychiatric symptoms. The most common WD phenotype was the neuropsychiatric form (48%). The age of onset occurred earlier in patients with the hepatic phenotype than in those with the neuropsychiatric phenotype. Moreover, there was a significant difference in sex distribution regarding phenotype. Females presented with a hepatic phenotype more often than males, and the neuropsychiatric phenotype occurred more frequently in males with an older onset age. Further study showed that the age at onset was a deciding factor for predicting the neuropsychiatric phenotype among the hepatic phenotype. However, sex did not correlate with the phenotype.Conclusion: Males seem to have a higher disease susceptibility, with symptom onset later than females. Males frequently present with a neuropsychiatric phenotype, while females present with a hepatic phenotype. Age at onset was a deciding factor for predicting the WD phenotype. Further studies focusing on the effect of estrogens on the pathology of WD are suggested.

Background and Aim: To evaluate the efficacy and safety of minocycline, vonoprazan, amoxicillin, and bismuth quadruple therapy for Helicobacter pylori (H. pylori) treatment.Methods: From August 2022 to May 2023, clinical data were collected from patients who received H. pylori eradication treatment at West China Fourth Hospital, Sichuan University. One group received the MVAB regimen (amoxicillin, minocycline, vonoprazan, and colloidal bismuth pectin), while another group received the FOAB regimen (amoxicillin, furazolidone, omeprazole, and colloidal bismuth pectin), both administered for 14 days. Follow‐up assessments of safety and compliance were conducted within 1 week after treatment completion. One and a half months after treatment, the success of eradication was evaluated using the urea breath test.Results: For the MVAB regimen as a first‐line treatment, the eradication rate was 90.1% (127/141, 95% CI: 85.1–95.1%) in the ITT analysis and 93.4% (127/136, 95% CI: 89.2–97.6%) in the PP analysis as a first‐line treatment. As a second‐line treatment, the eradication rate was 91.3% (21/23, 95% CI: 78.8–103.8%) in both analyses. For the FOAB regimen as a first‐line treatment, the eradication rate was 98.0% (50/51, 95% CI: 94.1–101.2%) in the ITT analysis and 100% (50/50, 95% CI: 100%) in the PP analysis. As a second‐line treatment, the eradication rate was 100% (6/6, 95% CI: 100%) in both analyses. Moreover, there was no significant difference in the incidence of adverse events between the two groups (MVAB regimen: 5.5% and FOAB regimen: 8.8%; P > 0.05).Conclusions: The MVAB regimen could indeed be a viable alternative treatment option to conventional therapies.