UHMK1 promotes gastric cancer progression through reprogramming nucleotide metabolism.

UHMK1 is a nuclear serine/threonine kinase recently implicated in carcinogenesis. However, the functions and action mechanisms of UHMK1 in the pathogenesis of human gastric cancer (GC) are unclear. Here, we observed that UHMK1 was markedly upregulated in GC. UHMK1 silencing strongly inhibited GC aggressiveness. Interestingly, UHMK1-induced GC progression was mediated primarily via enhancing de novo purine synthesis because inhibiting purine synthesis reversed the effects of UHMK1 overexpression. Mechanistically, UHMK1 activated ATF4, an important transcription factor in nucleotide synthesis, by phosphorylating NCOA3 at Ser (S) 1062 and Thr (T) 1067. This event significantly enhanced the binding of NCOA3 to ATF4 and the expression of purine metabolism-associated target genes. Conversely, deficient phosphorylation of NCOA3 at S1062/T1067 significantly abrogated the function of UHMK1 in GC development. Clinically, Helicobacter pylori and GC-associated UHMK1 mutation induced NCOA3-S1062/T1067 phosphorylation and enhanced the activity of ATF4 and UHMK1. Importantly, the level of UHMK1 was significantly correlated with the level of phospho-NCOA3 (S1062/T1067) in human GC specimens. Collectively, these results show that the UHMK1-activated de novo purine synthesis pathway significantly promotes GC development.

The RNA helicase Dhx15 mediates Wnt-induced antimicrobial protein expression in Paneth cells.

RNA helicases play roles in various essential biological processes such as RNA splicing and editing. Recent in vitro studies show that RNA helicases are involved in immune responses toward viruses, serving as viral RNA sensors or immune signaling adaptors. However, there is still a lack of in vivo data to support the tissue- or cell-specific function of RNA helicases owing to the lethality of mice with complete knockout of RNA helicases; further, there is a lack of evidence about the antibacterial role of helicases. Here, we investigated the in vivo role of Dhx15 in intestinal antibacterial responses by generating mice that were intestinal epithelial cell (IEC)-specific deficient for Dhx15 (Dhx15 f/f Villin1-cre, Dhx15ΔIEC). These mice are susceptible to infection with enteric bacteria Citrobacter rodentium (C. rod), owing to impaired α-defensin production by Paneth cells. Moreover, mice with Paneth cell-specific depletion of Dhx15 (Dhx15 f/f Defensinα6-cre, Dhx15ΔPaneth) are more susceptible to DSS (dextran sodium sulfate)-induced colitis, which phenocopy Dhx15ΔIEC mice, due to the dysbiosis of the intestinal microbiota. In humans, reduced protein levels of Dhx15 are found in ulcerative colitis (UC) patients. Taken together, our findings identify a key regulator of Wnt-induced α-defensins in Paneth cells and offer insights into its role in the antimicrobial response as well as intestinal inflammation.

Aurora A-mediated pyruvate kinase M2 phosphorylation promotes biosynthesis with glycolytic metabolites and tumor cell cycle progression.

Cancer cells have distinctive demands for intermediates from glucose metabolism for biosynthesis and energy in different cell cycle phases. However, how cell cycle regulators and glycolytic enzymes coordinate to orchestrate the essential metabolic processes are still poorly characterized. Here, we report a novel interaction between the mitotic kinase, Aurora A, and the glycolytic enzyme, pyruvate kinase M2 (PKM2), in the interphase of the cell cycle. We found Aurora A-mediated phosphorylation of PKM2 at threonine 45. This phosphorylation significantly attenuated PKM2 enzymatic activity by reducing its tetramerization and also promoted glycolytic flux and the branching anabolic pathways. Replacing the endogenous PKM2 with a nonphosphorylated PKM2 T45A mutant inhibited glycolysis, glycolytic branching pathways, and tumor growth in both in vitro and in vivo models. Together, our study revealed a new protumor function of Aurora A through modulating a rate-limiting glycolytic enzyme, PKM2, mainly during the S phase of the cell cycle. Our findings also showed that although both Aurora A and Aurora B kinase phosphorylate PKM2 at the same residue, the spatial and temporal regulations of the specific kinase and PKM2 interaction are context dependent, indicating intricate interconnectivity between cell cycle and glycolytic regulators.

Exosomes from hepatitis B virus-infected hepatocytes activate hepatic stellate cells and aggravate liver fibrosis through the miR-506-3p/Nur77 pathway.

Cumulative evidence indicates the important role of Nur77 in organ fibrogenesis. However, the role of Nur77 in hepatitis B virus (HBV)-related liver fibrosis (LF) remains unclear. Cells were transfected with the microRNA mimic miRNA-506-3p or inhibitor, and pcDNA3.1-Nur77 or Nur77 guide RNA. Exosomes were isolated from HBV-infected HepG2-sodium taurocholate cotransporting polypeptide cells. The levels of miR-506-3p, Nur77, and LF-related genes and proteins were detected by quantitative polymerase chain reaction (qPCR) and western blot analysis, respectively. The pathology of the liver from HBV-infected patients was examined using hematoxylin-eosin and Masson's staining. The expression of Nur77 in liver tissue was determined by immunohistochemistry, and the LF score was assessed using the METAVIR system. The relationship between miR-506-3p/Nur77 and LF score was analyzed by correlation analysis. HBV infection downregulated miR-506-3p expression and upregulated Nur77 levels in hepatocytes. Exosomes from HBV-infected hepatocytes also displayed decreased gene expression of miR-506-3p and increased expressions of Nur77- and LF-related genes in stellate cells compared with exosomes from hepatocytes with mock infection. These changes were reversed by Nur77 guide RNA. Nur77 expression in liver tissue was strongly correlated with LF, whereas serum miR-506-3p was strongly negatively correlated with LF. Exosomes from HBV-infected hepatocytes activate stellate cells and aggravate LF through the miR-506-3p/Nur77 pathway. These exosomes may be the basis of a promising therapeutic strategy.

Analysis of gastric microbiome reveals three distinctive microbial communities associated with the occurrence of gastric cancer.

BACKGROUND: Gastric microbial dysbiosis were reported to be associated with gastric cancer (GC). This study aimed to explore the variation, diversity, and composition patterns of gastric bacteria in stages of gastric carcinogenesis based on the published datasets. METHODS: We conducted a gastric microbial analysis using 10 public datasets based on 16S rRNA sequencing, including 1270 gastric biopsies of 109 health control, 183 superficial gastritis (SG), 135 atrophic gastritis (AG), 124 intestinal metaplasia (IM), 94 intraepithelial neoplasia (IN), 344 GC, and 281 adjacent normal tissues. And QIIME2-pipeline, DESeq2, NetMoss2, vegan, igraph, and RandomForest were used for the data processing and analysis. RESULTS: We identified three gastric microbial communities among all the gastric tissues. The first community (designate as GT-H) was featured by the high abundance of Helicobacter. The other two microbial communities, namely GT-F, and GT-P, were featured by the enrichment of phylum Firmicutes and Proteobacteria, respectively. The distribution of GC-associated bacteria, such as Fusobacterium, Peptostreptococcus, Streptococcus, and Veillonella were enriched in tumor tissues, and mainly distributed in GT-F type microbial communities. Compared with SG, AG, and IM, the bacterial diversity in GC was significantly reduced. And the strength of microbial interaction networks was initially increased in IM but gradually decreased from IN to GC. In addition, Randomforest models constructed in in GT-H and GT-F microbial communities showed excellent performance in distinguishing GC from SG and precancerous stages, with varied donated bacteria. CONCLUSIONS: This study identified three types of gastric microbiome with different patterns of composition which helps to clarify the potential key bacteria in the development of gastric carcinogenesis.

Development of a one-plasmid system to replace the endogenous protein with point mutation for post-translational modification studies.

BACKGROUND: Post-translational modification (PTM) is one of the major regulatory mechanism for protein activities. To understand the function of PTMs, mutants that prevent or mimic the modification are frequently utilized. The endogenous proteins are usually depleted while the point mutations are expressed. A common strategy to accomplish these tasks includes two-steps: First, a cell line stably expressing shRNA for protein depletion is generated, then an RNAi-resistance construct is introduced to express mutant. However, these steps are time- and labor-consuming. More importantly, shRNA and mutant protein are frequently expressed in different cells at different time, which significantly disturbs the conclusions. METHODS: To overcome these technical problems, we developed a lentiviral based one-plasmid system that allowed concurrent expression of shRNA and mutant protein. The puromycin-resistant gene was inserted for the selection of stable-expression cells. RESULTS: Using this plasmid, we efficiently replaced the endogenous proteins with comparable levels of exogenous proteins for LDHB and PKM2, two glycolytic enzymes regulated by PTM in cancer cells. The system was also successfully exploited in evaluating the role of phosphorylation of LDHB serine 162 in multiple in vitro and in vivo assays. CONCLUSION: Thus, we have developed an efficient one-plasmid system to replace endogenous protein with point mutations for the functional study of PTM.

An unusual cause of ascites: Castleman disease.

BACKGROUND: Castleman disease (CD) is a group of rare lymphoproliferative diseases with common lymph node histological features that can easily be misdiagnosed as infections, multiple autoimmune diseases, and malignant tumors. CASE PRESENTATION: Here we report a rare case of a Chinese male with refractory ascites for two years and was eventually diagnosed as CD. CONCLUSIONS: The challenges in diagnosis of CD arise from the large differential, clinical heterogeneity and our limited understanding of pathology. In case of rare ascites, CD needs to be considered.

Development and validation of a prediction rule for estimating gastric cancer risk in the Chinese high-risk population: a nationwide multicentre study.

OBJECTIVE: To develop a gastric cancer (GC) risk prediction rule as an initial prescreening tool to identify individuals with a high risk prior to gastroscopy. DESIGN: This was a nationwide multicentre cross-sectional study. Individuals aged 40-80 years who went to hospitals for a GC screening gastroscopy were recruited. Serum pepsinogen (PG) I, PG II, gastrin-17 (G-17) and anti-Helicobacter pylori IgG antibody concentrations were tested prior to endoscopy. Eligible participants (n=14 929) were randomly assigned into the derivation and validation cohorts, with a ratio of 2:1. Risk factors for GC were identified by univariate and multivariate analyses and an optimal prediction rule was then settled. RESULTS: The novel GC risk prediction rule comprised seven variables (age, sex, PG I/II ratio, G-17 level, H. pylori infection, pickled food and fried food), with scores ranging from 0 to 25. The observed prevalence rates of GC in the derivation cohort at low-risk (≤11), medium-risk (12-16) or high-risk (17-25) group were 1.2%, 4.4% and 12.3%, respectively (p<0.001).When gastroscopy was used for individuals with medium risk and high risk, 70.8% of total GC cases and 70.3% of early GC cases were detected. While endoscopy requirements could be reduced by 66.7% according to the low-risk proportion. The prediction rule owns a good discrimination, with an area under curve of 0.76, or calibration (p<0.001). CONCLUSIONS: The developed and validated prediction rule showed good performance on identifying individuals at a higher risk in a Chinese high-risk population. Future studies are needed to validate its efficacy in a larger population.

Lupus enteritis masquerading as Crohn's disease.

BACKGROUND: Systemic lupus erythematosus is an autoimmune disease which can affect multiple organs, resulting in significant mortality and morbidity. Lupus enteritis is one of the rare complications of SLE, defined as vasculitis of the intestinal tract, with supportive biopsy findings and/or image. However, lupus enteritis is seldom confirmed on histology or image and the changes of intestinal mucosa are nonspecific. Crohn's disease is a chronic inflammatory disorder of the gastrointestinal tract which affects any part of the gastrointestinal tract. The diagnosis of CD is confirmed by clinical evaluation and a combination of endoscopic, histology, radiology, and/or biochemical investigations. CASE PRESENTATION: Here we report a rare case of a 71-years-old Chinese male has been diagnosed with lupus enteritis which similar to CD in the aspects of endoscopic, histology, and radiology. So far, there are no relevant cases reported. CONCLUSIONS: The endoscopic appearance of lupus enteritis is nonspecific, on the basis of our case, the features of lupus enteritis can be described as spacious, clean and no moss ulcers which discontinuous involved all gastrointestinal tract.

Proliferation Potential-Related Protein Promotes the Esophageal Cancer Cell Proliferation, Migration and Suppresses Apoptosis by Mediating the Expression of p53 and Interleukin-17.

OBJECTIVE: This study aims to investigate the mechanism of proliferation potential-related protein (PP-RP) in influencing the proliferation, migration, and apoptosis of esophageal cancer cells. METHODS: Quantitative real-time PCR and western blotting were performed to analyze the expression of PP-RP gene, p53, and interleukin (IL)-17 in human normal tissues and tumor tissues, as well as the expression of p53 and IL-17 in Eca109 and TE3 cells. The esophageal cancer cell proliferation was detected by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT), cell apoptosis was detected by flow cytometry, and cell migration was detected by transwell migration. RESULTS: PP-RP expressed highly in tumor tissue and Eca109 and TE3 cells, PP-RP overexpression inhibited the expression of p53 and promoted the expression of IL-17 in Eca109 and TE3 cells. PP-RP overexpression increased the expression of F-actin, promoted cell proliferation, and migration and suppressed cell apoptosis. Cell proliferation ability and cell migration ability were significantly strengthened while apoptosis was suppressed by PP-RP + pyruvate carboxylase deoxyribonucleic acid (PCDNA)-p53 group and PP-RP + IL-17 siRNA group in TE3 cells. CONCLUSION: Our data suggest that PP-RP promotes esophageal cancer cell proliferation and migration, and suppresses apoptosis by mediating the expression of p53 and IL-17.

[Molecular mechanism of cisplatin to enhance the ability of TRAIL in reversing multidrug resistance in gastric cancer cells].

OBJECTIVE: To study the molecular mechanism of cisplatin to enhance the ability of tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) in reversing multidrug resistance in vincristine-resistant human gastric cancer SGC7901/VCR cells. METHODS: MTT assay was used to measure the 50% inhibiting concentration (IC50) and cell survival in SGC7901 and SGC7901/VCR cells after different treatments. SGC7901/VCR cells were treated with different concentrations of DDP, different concentrations of TRAIL alone or in combination, and then the mRNA and protein levels of several genes were determined by RT-PCR, RT-qPCR and Western-blot analysis. After targeted silencing with specific siRNA and transfection of recombinant plasmid c-myc into the SGC7901/VCR cells, the mRNA and protein levels of DR4, DR5 and c-myc were determined by RT-PCR and Western-blot analysis. RESULTS: After combined treatment with TRAIL and DDP of the SGC7901/VCR cells, the IC50 of VCR, DDP, ADM, and 5-Fu treatment was significantly decreased compared with the control group or TRAIL-treated group (P < 0.05). After treatment with 0, 10, 50 ng/ml TRAIL in combination with 0.4 µg/ml DDP, the SGC7901/VCR cells showed significantly higher activation of caspase 3, down-regulation of DNA-PKcs/Akt/GSK-3ß signaling pathway, and higher inhibition of MDR1(P-gp) and MRP1 than those treated with TRAIL alone (P < 0.01 for all). The mRNA and protein levels of DR4, DR5, c-myc were significantly decreased after silencing c-myc with specific siRNA in the SGC7901/VCR cells (P < 0.01 for all), and were significantly increased after transfection of recombinant plasmid c-myc into the SGC7901/VCR cells (P < 0.01 foe all). After the treatment with 10 ng/ml TRAIL, 0.25 µg/ml DDP + 10 ng/ml TRAIL and 0.5 µg/ml DDP + 10 ng/ml TRAIL, the relative expression level of c-myc protein in the SGC7901/VCR cells was 0.314 ± 0.012, 0.735 ± 0.026, and 0.876 ± 0.028, respectively, and the relative expression of cytochrome C was 0.339 ± 0.036, 0.593 ± 0.020 and 0.735 ± 0.031, respectively, and the relative expression levels of DR4, DR5, active-caspase 3 and active-caspase 9 in the SGC7901/VCR cells were also increased along with increasing DDP concentrations. CONCLUSIONS: The activation of DNA-PKcs/Akt/GSK-3ß signaling pathway and high expression of MDR1 and MRP1 play an important role in the multi-drug resistance properties of SGC7901/VCR cells. After combining with TRAIL, DDP can enhance the expression of DR4 and DR5 through up-regulating c-myc and enhancing the activation of caspase 3 and caspase 9 by facilitating mitochondrial release of cytochrome C. It may be an important molecular mechanism of DDP-induced sensitization of TRAIL to reverse the multidrug resistancein SGC7901/VCR cells.

Enterococcus-derived tyramine hijacks α2A-adrenergic receptor in intestinal stem cells to exacerbate colitis.

Inflammatory bowel disease (IBD) is characterized by dysbiosis of the gut microbiota and dysfunction of intestinal stem cells (ISCs). However, the direct interactions between IBD microbial factors and ISCs are undescribed. Here, we identify α2A-adrenergic receptor (ADRA2A) as a highly expressed GPCR in ISCs. Through PRESTO-Tango screening, we demonstrate that tyramine, primarily produced by Enterococcus via tyrosine decarboxylase (tyrDC), serves as a microbial ligand for ADRA2A. Using an engineered tyrDC-deficient Enterococcus faecalis strain and intestinal epithelial cell-specific Adra2a knockout mice, we show that Enterococcus-derived tyramine suppresses ISC proliferation, thereby impairing epithelial regeneration and exacerbating DSS-induced colitis through ADRA2A. Importantly, blocking the axis with an ADRA2A antagonist, yohimbine, disrupts tyramine-mediated suppression on ISCs and alleviates colitis. Our findings highlight a microbial ligand-GPCR pair in ISCs, revealing a causal link between microbial regulation of ISCs and colitis exacerbation and yielding a targeted therapeutic approach to restore ISC function in colitis.

Characteristics of mass-forming autoimmune pancreatitis commonly misdiagnosed as a malignant tumor.

Objective: This study aimed to explore the clinical characteristics and differential diagnosis of patients with autoimmune pancreatitis (AIP) and pancreatic cancer to prevent misdiagnosis and mistreatment. Methods: The clinical data of patients with AIP with suspected pancreatic or bile duct malignancy and pancreatic cancer were retrospectively analyzed. The risk factors and the diagnostic value of IgG4 and Tbil levels before treatment for AIP was investigated. Moreover, the imaging features and response to hormone therapy were analyzed. Results: AIP was commonly observed in men. Compared to patients with pancreatic cancer, the incidence of poor appetite and weight loss and carbohydrate antigen 19-9 (CA19-9) level was lower in patients with AIP, while the immunoglobulin G4 (IgG4) level was higher (p < 0.05). After treatment, the IgG4 and CA19-9 levels in patients with AIP were decreased (p < 0.001). IgG4 level before treatment (OR = 2.452, 95%CI: 1.180-5.096, P = 0.016) and total bilirubin (Tbil) level before treatment (OR = 0.992, 95%CI: 0.985-0.998, P = 0.013) were independent risk factors of AIP. Furthermore, the diagnostic value of IgG4 level before treatment, Tbil level before treatment, IgG4/Tbil before treatment, and a combination of these indicators was high. Moreover, 15 (68.18%) patients with AIP had space-occupying lesions of the pancreas, and 16 (72.73%) had autoimmune cholangitis. Most patients with AIP were sensitive to hormone therapy. Conclusions: The Tbil and IgG4 levels, imaging findings, and hormone therapy reactivity could differentiate AIP from pancreatic cancer. A combination of IgG4, Tbil, and IgG4/Tbil before treatment might be a promising diagnostic biomarker for AIP.

The prediction model of operative link on gastric intestinal metaplasia stage III-IV: A multicenter study.

Purpose: Intestinal metaplasia plays a crucial role in the risk stratification of gastric cancer development. The objective of the study was to develop a prediction model for Operative Link on Gastric Intestinal Metaplasia (OLGIM) Stage III-IV. Methods: We analyzed 7945 high-risk gastric cancer individuals from 115 hospitals who underwent questionnaires and gastroscope. The participants were assigned to either the development or validation cohort randomly. Demographics and clinical characteristics were obtained. The outcome measurement was OLGIM III-IV. Univariate logistic regression was used for feature selection and multivariate logistic analysis was performed to develop the nomogram. Area under the curves, calibration plots, decision curve and clinical impact analysis were used to assess the performance of the nomogram. Results: 4600 individuals and 3345 individuals were included in the development and validation cohort, of which 124 and 86 individuals were diagnosed with OLGIM III-IV, respectively. Parameters in the training validation cohort matched well and there was no significant difference between two cohorts. A nomogram model for predicting OLGIM Stage III-IV consisted of 4 significantly associated variables, including age, gender, PG I and G-17 (AUC 0.723 and 0.700 for the 2 cohorts). The nomogram demonstrated excellent performance in the calibration curve. Decision curve and clinical impact analysis suggested clinical benefit of the prediction model. Conclusions: This reliable individualized nomogram might contribute to more accurate management for patients with OLGIM III-IV. Therefore, we suggest that this study be used as an incentive to promote the application.

A mitotic NADPH upsurge promotes chromosome segregation and tumour progression in aneuploid cancer cells.

Redox metabolites have been observed to fluctuate through the cell cycle in cancer cells, but the functional impacts of such metabolic oscillations remain unknown. Here, we uncover a mitosis-specific nicotinamide adenine dinucleotide phosphate (NADPH) upsurge that is essential for tumour progression. Specifically, NADPH is produced by glucose 6-phosphate dehydrogenase (G6PD) upon mitotic entry, which neutralizes elevated reactive oxygen species (ROS) and prevents ROS-mediated inactivation of mitotic kinases and chromosome missegregation. Mitotic activation of G6PD depends on the phosphorylation of its co-chaperone protein BAG3 at threonine 285, which results in dissociation of inhibitory BAG3. Blocking BAG3T285 phosphorylation induces tumour suppression. A mitotic NADPH upsurge is present in aneuploid cancer cells with high levels of ROS, while nearly unobservable in near-diploid cancer cells. High BAG3T285 phosphorylation is associated with worse prognosis in a cohort of patients with microsatellite-stable colorectal cancer. Our study reveals that aneuploid cancer cells with high levels of ROS depend on a G6PD-mediated NADPH upsurge in mitosis to protect them from ROS-induced chromosome missegregation.

A lncRNA from an inflammatory bowel disease risk locus maintains intestinal host-commensal homeostasis.

Inflammatory bowel diseases (IBD) are known to have complex, genetically influenced etiologies, involving dysfunctional interactions between the intestinal immune system and the microbiome. Here, we characterized how the RNA transcript from an IBD-associated long non-coding RNA locus ("CARINH-Colitis Associated IRF1 antisense Regulator of Intestinal Homeostasis") protects against IBD. We show that CARINH and its neighboring gene coding for the transcription factor IRF1 together form a feedforward loop in host myeloid cells. The loop activation is sustained by microbial factors, and functions to maintain the intestinal host-commensal homeostasis via the induction of the anti-inflammatory factor IL-18BP and anti-microbial factors called guanylate-binding proteins (GBPs). Extending these mechanistic insights back to humans, we demonstrate that the function of the CARINH/IRF1 loop is conserved between mice and humans. Genetically, the T allele of rs2188962, the most probable causal variant of IBD within the CARINH locus from the human genetics study, impairs the inducible expression of the CARINH/IRF1 loop and thus increases genetic predisposition to IBD. Our study thus illustrates how an IBD-associated lncRNA maintains intestinal homeostasis and protects the host against colitis.

Glucocorticoid Treatment Strategies in Liver Failure.

Liver failure is characterized by serious liver decompensation and high mortality. The activation of systemic immune responses and systemic inflammation are widely accepted as the core pathogenesis of liver failure. Glucocorticoids (GCs) are most regularly utilized to suppress excessive inflammatory reactions and immunological responses. GCs have been used in the clinical treatment of liver failure for nearly 60 years. While there has been no unanimity on the feasibility and application of GC treatment in liver failure until recently. The most recent trials have produced conflicting results when it comes to the dose and time for GC therapy of different etiology of liver failure. Our review outlines the issues and options in managing GC treatment in liver failure based on an investigation of the molecular mechanism that GC may give in the treatment.

Comparison between Endoscopic Submucosal Dissection and Surgery in Patients with Early Gastric Cancer.

Background: Endoscopic submucosal dissection (ESD) has become a preferred treatment option for early gastric cancer (EGC). This study aimed to compare the clinical outcomes of ESD and surgical resection for EGC. Methods: This was a retrospective case-control study. Patients with a diagnosis of EGC who underwent ESD or surgery in our hospital from 2011 to 2020 were enrolled. We compared the clinical characteristics and treatment outcomes of these two groups according to propensity score-matching. The primary outcome comparison was overall survival (OS). Secondary outcomes were disease-specific survival (DSS), recurrence-free survival (RFS), and treatment-related events. Results: In the matched cohort, the ESD group showed comparable OS, RFS, and DSS with the surgery group. Statistical differences were shown in blood loss and adverse events. Furthermore, the ESD group showed lower hospital cost, as well as a shorter operative time and hospital duration than the surgery group. The R0 resection and recurrence rates were similar between the two groups. In Cox regression analysis, age, tumor size, poor differentiation, and lymphovascular invasion were regarded as independent factors of OS. Conclusions: With sufficient safety and advantages, ESD can be a first-line treatment of EGC. Preoperative evaluation is vital to the appropriate treatment and prognosis.

Helicobacter pylori Infection Combined with OLGA and OLGIM Staging Systems for Risk Assessment of Gastric Cancer: A Retrospective Study in Eastern China.

Purpose: Helicobacter pylori (H. pylori) infection is a high-risk factor for gastric cancer (GC). The main aim of this study was to evaluate the effect of H. pylori on gastritis staging systems and the value of H. pylori combined with gastritis staging systems in predicting GC risk. Patients and Methods: This study enrolled 609 patients with gastric atrophy (GA) and 527 patients with gastric intestinal metaplasia (GIM), who were graded by the OLGA and OLGIM staging systems, respectively. Each individual underwent serum pepsinogen (PG) test, H. pylori detection and questionnaire investigation. We did a real-world retrospective follow-up survey for them in April 2022. Results: Compared with H. pylori-negative patients, H. pylori-positive patients had higher serum PGs/gastrin-17 (G-17) levels and lower PGR levels, regardless of OLGA/OLGIM stages I-II or III-IV. Furthermore, eight patients with atrophic gastritis who progressed to GC were previously in OLGA stages III-IV and OLGIM stages II-IV. The average duration of this process was 2.19±1.03 years. Logistic regression analysis indicated that PGI and H. pylori infection were independent risk factors of individuals with OLGA stages III-IV. Age and PGR were independent risk factors of patients with OLGIM stages III-IV. PGI and PGR had good clinical diagnostic values for OLGA stages III-IV and OLGIM stages III-IV, respectively. Conclusion: Patients with OLGA/OLGIM stages III-IV should undergo endoscopic surveillance regardless of H. pylori infection. H. pylori-positive patients with OLGIM stage II also have a high risk of GC. H. pylori combined with PGI and PGR is helpful to evaluate the severity of chronic gastritis.