Gastric tubular reconstruction (GTR) is a commonly used anti-reflux reconstruction method after proximal gastrectomy. This study compares the short-term efficacy and quality of life (QoL) between totally laparoscopic proximal gastrectomy using an endoscopic linear stapler with laparoscopic-assisted proximal gastrectomy using a circular stapler for GTR to provide a reference for the rational selection of anastomotic devices in clinical practice. A retrospective analysis of 111 upper gastric cancer patients undergoing laparoscopic proximal gastrectomy with GTR was conducted from October 2021 to April 2024. Patients were divided into CS (48 cases) and LS (63 cases) groups. Baseline characteristics, perioperative indicators, and short-term efficacy were compared. QoL was assessed using EORTC QLQ-C30 and QLQ-STO22 at three months postoperatively, and gastroscopy at six months evaluated reflux esophagitis. No significant baseline differences were found. The LS group had less intraoperative bleeding, faster recovery, and shorter hospital stay compared to CS (P < 0.05). No differences in operation time, lymph node dissection, complication rates, or nutritional status were observed (P > 0.05). QoL and reflux esophagitis incidence were similar between groups (P > 0.05). Compared with CS for GTR, the LS group had less intraoperative bleeding, faster postoperative recovery and shorter hospital stay. The QoL, nutritional status and incidence of reflux esophagitis of the two groups were comparable.

Background The optimal surgical strategy for adenocarcinoma of oesophagogastric junction (AEG) remains debated, particularly regarding lymphadenectomy extent, gastrectomy type and surgical approach, with real-world prospective evidence being scarce. Objective To map lymph node metastasis (LNM) patterns and assess surgical outcomes in a large multicentre cohort of patients with AEG undergoing radical resection. Design The Chinese League of Adenocarcinoma of Esophagogastric Junction (CLAEG) registry, initiated in 2022 across 44 high-volume Chinese centres, prospectively enrolled AEG patients. This analysis included 2044 radical resections, with LNM assessed by station, stratified by Siewert type and neoadjuvant therapy. Surgical outcomes were compared between total versus proximal gastrectomy and laparoscopic versus open resection. Results Most tumours were Siewert type II (64.6%) or III (33.4%). LNM was substantially higher in abdominal than mediastinal stations; category-1 nodes (metastasis, >10%) comprised stations 1, 2, 3, 4, 7, 8a, 9 and 11p. The LNM rates for mediastinal stations were 2.77% (No. 110), 0.71% (No. 111) and 0.68% (No. 112). Patients who received neoadjuvant therapy had lower LNM rates, indicating nodal downstaging. Among those undergoing gastrectomy, patients who underwent total gastrectomy had a lower postoperative complication rate than those who underwent proximal gastrectomy (14.8% vs 21.0%; p=0.001) and achieved more extensive lymphadenectomy. Compared with open surgery, patients who underwent laparoscopic resection experienced faster postoperative recovery without higher complication rates (16.5% vs 17.3%). No perioperative mortality occurred. Conclusion The CLAEG study shows that abdominal lymphadenectomy should be prioritised in AEG, with neoadjuvant therapy, total gastrectomy and laparoscopy associated with favourable short-term outcomes.

Purpose: To address the dual challenges of chemotherapy toxicity and poor tumor microenvironment regulation in gastric cancer, we developed a copper-molybdenum bimetallic organic framework nanozyme (CMP) that integrates chemodynamic therapy (CDT) and photothermal therapy (PTT). The system leverages synergistic reactive oxygen species (ROS) generation and localized hyperthermia to deliver efficient, low-toxicity treatment. Methods: The CMP nanodrug was synthesized by encapsulating Keggin-type phosphomolybdic acid (H3PMo12O40) into copper-based MOF pores via hydrothermal reaction. Physicochemical properties were characterized using transmission electron microscopy (TEM) and X-ray photoelectron spectroscopy (XPS). Systematic evaluation of antitumor efficacy and biosafety was conducted through in vitro assays (CCK-8, calcein-AM/PI staining, ROS detection) and in vivo xenograft models (subcutaneous implantation of NCI-N87 cells in BALB/c nude mice). Results: The CMP nanozyme demonstrated exceptional photothermal conversion efficiency (29.4% under 808 nm laser). In vitro experiments revealed significant cytotoxicity with ROS elevation. In vivo studies showed significant tumor growth inhibition without hematotoxicity (WBC, ALT levels showed no statistical significance vs. controls). Histopathology confirmed extensive tumor necrosis with preserved cytoarchitecture in vital organs (heart, liver, spleen, and kidney). Conclusion: The CMP nanozyme achieves potent antitumor efficacy through photothermal-enhanced Fenton-like reactions, depleting glutathione and amplifying ROS. It suppresses gastric cancer in vivo with minimal systemic toxicity, representing a promising nanoplatform for precision therapy.

Postoperative recurrence remains common in patients with Siewert type II/III gastroesophageal junction adenocarcinoma (AEG), and conventional TNM staging provides limited individualized prognostic information. This study aimed to develop and validate a composite Nutritional Risk Index and Hemoglobin-to-Platelet Ratio (NRI-HPR) score for predicting recurrence and survival. A total of 270 patients who underwent curative gastrectomy between 2011 and 2015 were included as the training cohort, and 117 patients treated between 2020 and 2023 were enrolled as an independent validation cohort. Patients were stratified into three NRI-HPR score groups according to predefined cutoffs. Survival outcomes and recurrence patterns were analyzed using Kaplan–Meier and Cox regression analyses. Prognostic nomograms incorporating NRI-HPR were constructed and validated. In the training cohort, 5-year recurrence-free survival (RFS) rates were 79.6

Bioadhesives represent promising alternatives to sutures towards gastric perforation management, however, significant challenges persist concerning instant wet adhesion and durable stability in gastric perforation sealing, particularly in direct contacting with acidic gastric fluids on large perforation injuries. Here we report an injectable acid-tolerant hydrogel composed of FDA-approved components for sutureless repair of large gastric defects. The hydrogel displays rapid in situ gelation, instant wet adhesion, and high burst pressure for efficient sealing despite excessive mechanical challenges, tissue irregularities and gastric juices. The enhanced hydrogen bonding interactions among amide-linked skeleton enable robust acid-tolerant interfaces to accommodate durable adhesion under the fluidically, chemically and mechanically dynamic in-vivo environments. A larger-scale porcine gastric perforation is applied to validate the sealing efficacy via a combined laparoscopic-endoscopic technique. The negligible postoperative adhesion, suppressed inflammation and interference-free transcriptome and microbiome verify the therapeutic outcomes. The proposed bioadhesives hold great promise for clinical treatment of digestive diseases.

BackgroundAlthough early gastric cancer (EGC) is generally limited to the mucosal and submucosal layers, lymph node metastasis can still occur, which may worsen the prognosis, particularly when the number of examined lymph nodes (ELNs) is inadequate. This study introduces log odds of positive lymph nodes (LODDS) as a prognostic factor and integrates it with machine learning to improve survival predictions in T1N+ gastric cancer (GC).MethodsThis retrospective study used data from the Surveillance, Epidemiology, and End Results (SEER) Program and an independent validation cohort from the Chinese People’s Liberation Army General Hospital First Medical Center. Predictive factors were selected using LASSO regression and multivariate Cox regression. Cox proportional-hazards (CoxPH), random survival forest (RSF), and XGBoost models were developed to predict overall survival (OS). Model interpretability and feature importance were evaluated using the SHapley Additive exPlanations (SHAP) method.ResultsA total of 419 T1N+ GC patients from the SEER database and 193 from our institution were included in the study. LODDS staging was identified as an independent prognostic factor, demonstrating superior discriminatory power compared to N staging (C-index 0.65 vs. 0.57). Based on the Brier score, area under the ROC curve (AUC), and C-index, the RSF model outperformed both the Cox model and XGBoost model. The RSF model achieved a C-index of 0.79 in the training cohort and 0.80 in the validation cohort, indicating favorable discrimination and calibration, with Brier scores below 0.25.ConclusionsIntegrating LODDS staging into the RSF model, alongside other clinical features, provides a highly accurate tool for survival prediction in T1N+ GC patients.

Neoadjuvant chemotherapy (NAC) combined with gastrectomy has been a standard therapeutic strategy for resectable gastric cancer (GC). However, it remains unclear whether postoperative adjuvant chemotherapy (AC) brings better survival in ypTNM stage I GC patients. Data on ypTNM stage I GC patients with or without AC following systemic NAC and radical gastrectomy were retrospectively retrieved from the Surveillance, Epidemiology, and End Results (SEER) database between 2010 and 2021. Inverse probability of treatment weighting (IPTW) was used to balance covariates. Overall survival (OS) and cancer-specific survival (CSS) were assessed through Kaplan-Meier and Cox proportional hazards models. Two nomograms were developed to predict OS and CSS of patients with ypTNM stage I GC who received AC. 661 patients met the inclusion criteria, 230 received AC and 431 were AC nonuser. AC was significantly associated with improved OS (weighted HR = 0.63, 95

Endoscopic procedures often subject endoscopists to heavy workloads and significant radiation exposure, while inappropriate maneuvers can potentially cause patient discomfort or clinical complications. This work presents a novel robotic endoscope system that integrates shape perception and depth estimation for autonomous navigation in complex gastrointestinal (GI) environments. The system features a custom-designed endoscope integrated with the fiber Bragg gratings (FBGs) sensor for shape tracking and a monocular camera for visual input. The FBGs enable real-time endoscopic shape perception through precisely reconstructing the endoscopic pose during dynamic interventions. A unified control framework is proposed to enhance the system's generality by integrating depth estimation and shape perception. The direction and velocity of endoscopic intervention are adaptively synchronized. Highly realistic GI phantoms and in vivo animal experiments demonstrate that the system successfully performs autonomous interventions in complex GI environments, with a bending angle error of 2.75 degrees and a mean pixel tracking error of 74.2 pixels. This work advances robotic endoscopes by enhancing perceptual accuracy and autonomy, demonstrating significant potential for clinical applications in endoscopic examinations and procedures.

Oral squamous cell carcinoma (OSCC) exhibits poor prognosis due to aggression, metastasis, and chemoresistance. Protein Arginine Methyltransferase 1 (PRMT1) and Signal Transducer and Activator of Transcription 3 (STAT3) are implicated in oncogenesis, but their interplay and downstream effects, particularly concerning ferroptosis and immune evasion in OSCC remain unclear. PRMT1 was significantly upregulated in OSCC tissues and cell lines, correlating with advanced grade, metastasis, and poor patient survival. PRMT1 knockdown inhibited OSCC proliferation, invasion, metastasis, and chemoresistance in vitro and in vivo. Mechanistically, PRMT1 directly interacted with, methylated, and activated STAT3 (increased p-STAT3 and target genes VEGFA, IL-6, c-myc). The PRMT1/STAT3 axis suppressed ferroptosis; PRMT1 knockdown decreased GPX4 expression, increased Fe2 + , ROS, and MDA, and decreased GSH, effects rescued by STAT3 overexpression. STAT3 directly bound and activated the GPX4 promoter. Crucially, inhibiting ferroptosis with liproxstatin-1 reversed the anti-tumor effects (chemosensitization, reduced proliferation/invasion) of PRMT1 knockdown. PRMT1 KO also enhanced anti-PD-1 therapy efficacy in vivo. PRMT1 drives OSCC aggressiveness by methylating and activating STAT3. This axis promotes chemoresistance and oncogenic phenotypes primarily by suppressing ferroptosis through STAT3-mediated transcriptional upregulation of GPX4. Targeting PRMT1 represents a promising strategy to overcome chemoresistance and inhibit progression in OSCC.

BACKGROUND In recent years, the global prevalence of gastric cancer (GC) has witnessed a progressive decrease, accompanied by a step-growth in the incidence of gastric signet ring cell carcinoma (GSRCC). As precision medicine concepts progress, GSRCC, a distinct sub-type of GC, has drawn considerable attention from researchers. However, there still persist some controversies regarding the associated research findings. AIM To summarize the current obstacles and potential future directions for research on GSRCC. METHODS To begin with, all literature related to GSRCC published from January 1, 2004 to December 31, 2023 was subjected to bibliometric analysis in this article. Additionally, this paper analyzed the research data using CiteSpace, GraphPad Prism v8.0.2, and VOSviewer, which was obtained from the Web of Science Core Collection database. The analysis results were visually represented. RESULTS This study provided a comprehensive overview of the statistical characteristics of the 995 English articles related to GSRCC, including cited references, authors, journals, countries, institutions, and keywords. The popular keywords and clusters contain "prognosis", "survival", "expression", "histology", and "chemotherapy". CONCLUSION The prognosis, precise definition and classification, as well as chemoresistance of GSRCC, continue to be crucial areas of ongoing research, whose directions are closely tied to advancements in molecular biology research on GSRCC.

Despite recent advances in surgical adhesives as promising alternatives to sutures or staplers for colonic defects and gastrointestinal management, significant challenges persist regarding to excellent biocompatibility, injectability operation, robust tissue adhesion and durable stability in colon environments due to the growing popularity of minimally invasive laparoscopy. In this work, we reported an in situ injectable hydrogel bioadhesive (OSG) consisting of FDA-approved Octa-armed poly (ethylene glycol) succinimidyl glutarate (Octa-PEGSG) and Octa-armed poly (ethylene glycol) amine (Octa-PEG-NH2) polymers for sutureless repair of large colonic defects. The OSG hydrogel was advantageous to rapid injection to cover the whole irregular surfaces via the formation of uniform networks and chemical interface binding, and capable of instant adhesion, high burst pressure, secure sutureless closure and durable compliance in the ex vivo porcine colonic injury models, thus enabling robust wet adhesion interfaces even in direct contact with intestinal fluids and constant colonic peristalsis. In terms of excellent biocompatibility and suitable degradability after a comprehensive evaluation from in vivo and in vitro studies, OSG hydrogel was validated with efficient sutureless colonic repair in a rat-injured model without causing postoperative adhesion, long-term inflammatory response and colonic transcriptome and microbiome interference. Innovatively, we further established large-size (3 cm) of porcine colonic defect models by minimally invasive technique, and verified its therapeutic effect under laparoscopic technology. Overall, the proposed OSG bioadhesive offers a promising clinical alternative to sutures for the treatment of colonic defects.

BACKGROUND:Textbook outcome (TO) is an increasingly utilized metric for evaluating perioperative treatment quality. However, a standardized and universally accepted definition of TO in gastrectomy has not yet been established. This multicenter study aimed to evaluate the incidence of a modified definition of TO (mTO) and its association with long-term oncologic survival following gastrectomy. METHODS:Data from all consecutive patients undergoing curative-intent resection for gastric cancer were analyzed from institutional databases of seven high-volume centers in China between 7 January 2010, and 30 September 2019. The achievement rates of TO and mTO were measured. mTO was defined as achieving all of the following: pR0 resection, retrieval of at least 15 lymph nodes, absence of severe postoperative complications (Clavien-Dindo grade ≥IIIa) within 90 days, length of hospital stay below the 75th percentile, no 90-day mortality, and no 90-day readmission. The primary outcomes were the associations between mTO and 5-year overall survival (OS) and disease-free survival (DFS). The secondary outcome was to determine the rate of mTO and identify independent factors associated with its achievement. RESULTS:Among 2608 eligible patients, the rates of mTO and TO were 62.4% (1628 patients) and 72.0% (1877 patients), respectively. Achieving mTO was independently associated with reduced hazards of death in Cox regression analysis for 5-year OS and DFS (HR 0.565 [95% CI: 0.504-0.633] and HR 0.561 [95% CI: 0.502-0.628], respectively). Similarly, achieving TO was independently associated with reduced hazards of death for 5-year OS and DFS (HR 0.737 [95% CI: 0.653-0.831] and HR 0.735 [95% CI: 0.65-0.827], respectively). Subgroup analyses demonstrated that mTO was consistently associated with a greater reduction in death hazards compared to TO for both OS and DFS. CONCLUSION:mTO serves as a more comprehensive and beneficial indicator for assessing perioperative quality, providing superior survival benefits compared to TO.

Interactions between the microbiota and host have been proven to be critical regulators of homeostasis, and pain perception is no exception. Emerging evidence has identified the mechanisms by which microbiota dysbiosis contributes to hyperalgesia and revealed the potential value of microbiota-associated therapies in pain management. Herein, the authors introduce the basic knowledge of pain and microbiota for readers who are not simultaneously majoring in these two fields. The clarified mechanisms underlying the regulation of pain by the microbiota are outlined in terms of three ways. This review summarizes the current advancements in pain management and microbiology research for clinicians who wish to focus on this area. Probiotics, fecal microbiota transplantation, and other methods of microbiota modulation for pain management have entered clinical translation. The authors further propose the present limitations and prospects for high-quality development of preclinical and clinical investigations. Importantly, despite the large amount of attention given to gut bacteria, this review also puts forward great expectations on the role of nongut and nonbacterial microbiota in pain sensation. Efforts to decipher the mechanisms of microbiota functions will help to promote achievements in pain management from bench to bedside.

A fasting mimic diet (FMD) has been proven to be a potential therapeutic regimen for gastric cancer (GC) patients. However, the intolerance of energy restriction and limited efficacies hinder wide application of FMD. To identify critical targets mediating resistance against glucose starvation and explore novel approaches to GC therapy, proteomics profiling was performed to depict the landscape of protein expression changes in cells under glucose deprivation. MZT1 was found to be greatly upregulated. We next investigated potential clinical value and regulatory functions of MZT1. Compared to adjacent normal tissues, MZT1 was upregulated in GC specimens and associated with unfavorable patient prognosis. Both in vitro and in vivo experiments indicated that downregulation of the MZT1 level inhibited GC proliferation, migration, invasion, glycolysis and sensitized cells to glucose starvation. Mechanistically, MZT1 functioned as an oncogenic factor by inhibiting NEDD1 ubiquitination and increasing its expression. In conclusion, during glucose starvation, MZT1 is upregulated in GC cells, which promotes resistance by directly suppression of NEDD1 ubiquitination. Our findings unveil the novel mechanisms by which MZT1 can promote GC malignancy. The potential clinical value of MZT1 as GC biomarkers has been first revealed. Suppression of MZT1 may become a promising approach to improve FMD efficacy, which require further validation by future investigations.

BACKGROUND:Chronic psychological stress is a critical oncogenic factor of gastric cancer (GC). However, the mechanisms underlying stress-induced malignant progression remain largely unknown. Gut microbiota dysregulation is tightly associated with cancer development and metabolism. MATERIALS AND METHODS:Chronic unpredictable mild stress (CUMS) modeling was used to prepare mice suffering from chronic psychological stress. 16s rRNA sequencing and Q300 targeted metabolite quantification were jointly conducted to depict landscapes of gut microbiome and metabolomics of CUMS mice. Fecal microbiota transplantation was employed to investigate the functions of gut microbial communities in regulating CUMS-mediated GC growth. Drug affinity responsive target stability, surface plasmon resonance and molecular docking assays were performed to screen direct target proteins of 5Z-dodecenoic acid. The interactions between RIOK2 and BYSL were verified with co-immunoprecipitation and GST pull-down and fluorescent co-localization analysis. A series of experiments for malignant behaviors and glycolysis and subcutaneous tumor transplantation were employed to detect alterations of GC cell phenotypes ex vivo and in vivo, respectively. RESULTS:Microbiome and metabolomics collectively demonstrated disrupted gut microbial communities and metabolic patterns. Particularly, Blautia coccoides-derived 5Z-dodecenoic acid was predominately declined by CUMS. Supplementation with Blautia coccoides or 5Z-dodecenoic acid effectively mitigated the negative effects of CUMS on glycolysis and malignancy. Mechanistically, 5Z-dodecenoic acid directly inhibits the functions of RIOK2, which maintained ectopic glycolysis and malignant behaviors. RIOK2 further interacted with BYSL and maintained its properties of potentiation of GC progression and metabolism. CONCLUSION:Our findings advance the insights of Blautia coccoides-derived 5Z-dodecenoic acid implicated in chronic psychological stress-induced GC progression and provide novel strategies for dampening GC progression.

BACKGROUND:The extensive utilization of immune checkpoint inhibitors (ICIs) targeting programmed cell death protein 1 (PD-1) has achieved significant advancements in the treatment of diverse solid tumors. The present meta-analysis aims to evaluate the safety and efficacy of neoadjuvant chemotherapy (NCT) plus PD-1 inhibitors for patients with locally advanced gastric cancer (LAGC). METHODS:An electronic search of PubMed, EmBase, and the Cochrane Library was performed to identify the clinical trials of NCT + PD-1 inhibitor vs. NCT in patients with LAGC. The retrieval period extended from the establishment of the corresponding database until April 2024, and meta-analysis was conducted using Stata (version 15) software. Subsequently, direct comparative analysis was used to compare pooled results of neoadjuvant immunochemotherapy (NICT) with NCT. RESULTS:After screening, six phase II/III randomized controlled trials (RCTs) and nine retrospective studies with 2953 patients were included. In meta-analysis, the NICT group demonstrated a significantly higher rate of pathological complete response (pCR) ( P <0.001) and R0 resection ( P =0.001), and a lower 2-year recurrence rate ( P =0.001) compared to the NCT group. The NICT group, however, exhibited a higher incidence of severe treatment-related adverse events (TRAEs) ( P =0.044). Additionally, the NICT and NCT groups exhibited no statistical differences in terms of the number of harvested lymph nodes, the occurrence of total TRAEs and postoperative complications, as well as the duration of postoperative hospitalization. CONCLUSIONS:The combination of PD-1 inhibitor + NCT in LAGC patients enhances the likelihood of achieving radical surgery and improves prognosis, albeit to some extent increasing the risk of severe TRAEs. NICT is anticipated to emerge as the preferred neoadjuvant therapy option for patients diagnosed with LAGC.

CircRNAs, a class of covalently closed noncoding RNAs, have emerged as pivotal regulators of the NF-κB signaling pathway in carcinogenesis. Accumulating evidence demonstrates that the circRNA/NF-κB axis regulates key cancer-related processes, such as proliferation, invasion, apoptosis, and immune escape. These regulatory effects are mediated by circRNAs' functional mechanisms-including miRNA sponging, direct protein interactions, and translation into functional peptides-which converge on modulating NF-κB pathway activity. Expression levels of NF-κB-associated circRNAs correlate with clinicopathological features such as tumor stage, metastasis, and patient survival. Furthermore, these circRNAs hold promise as diagnostic and prognostic biomarkers and as novel targets for therapeutic intervention. In this review, we summarize recent advances in elucidating the mechanisms and clinical relevance of NF-κB-linked circRNAs across diverse cancer types.

Neoadjuvant therapy (NAT) effectively downstages locally advanced gastric cancer (LAGC), increasing the proportion of patients achieving ypTNM stage 0–I. However, it is still controversial whether the LAGC patients with better tumor regression (ypTNM stage 0–I) had similar prognosis compared with pTNM I early gastric cancer (EGC) patients or not. This study compared short- and long-term outcomes between ypTNM 0-I LAGC and EGC patients. A retrospective analysis of 1,193 patients with pTNM I EGC or ypTNM 0-I LAGC treated between January 2020 and November 2024 from three medical centers was conducted. Propensity score matching (PSM) at a 1:1 ratio balanced baseline characteristic. Short- and long-term outcomes were compared between groups. After PSM, baseline characteristics were comparable with no significant difference (P > 0.05). The ypTNM 0-I group had longer operative times, greater estimated blood loss, and extended postoperative hospital days compared with pTNM I group (P < 0.05), but no differences in complication rates, recurrence rates, 3-year overall survival (OS: 93.3

Introduction:The GINS complex subunit 2 (GINS2) is crucial for DNA replication, but its specific roles in oral squamous cell carcinoma (OSCC) pathogenesis and tumor microenvironment (TME) modulation are poorly defined. Methods:GINS2 expression was analyzed using TCGA data and validated in OSCC patient tissues and cell lines via qPCR, Western blot (WB), and immunohistochemistry (IHC). Functional assays (CCK-8, colony formation, wound healing, Transwell invasion) and in vivo xenograft models assessed the impact of GINS2 knockdown (sh-GINS2) or overexpression (OE-GINS2) on OSCC cell behavior and tumorigenesis. Mechanistic links involving PTP4A1 and PKM2 were explored using Co-immunoprecipitation (Co-IP) and immunofluorescence (IF). Immune correlations were assessed in TCGA/TIMER2.0 (PDCD1, LAG3, CTLA4, HAVCR2), and PD-1/TIM-3 on CD8+ T cells were quantified by flow cytometry in co-culture. Neutrophil features (PD-L1 expression) and interventions (neutrophil depletion, anti-PD-L1) were evaluated in vitro and immune-reconstituted in vivo settings. Results:GINS2 was significantly upregulated in OSCC tissues and cell lines, correlating with advanced clinical stage and higher pathological grade. GINS2 knockdown suppressed proliferation, colony formation, migration, and invasion in vitro, and inhibited tumor growth in vivo. At the protein level, GINS2 physically associated with PTP4A1 and monotonically modulated its steady-state abundance; PTP4A1 interacted and co-localized with PKM2. In TCGA, GINS2 expression positively correlated with T-cell exhaustion markers, and altering GINS2 in OSCC cells changed PD-1 and TIM-3 on co-cultured CD8+ T cells. GINS2 expression also correlated with neutrophil infiltration; GINS2 overexpression increased tumor-associated neutrophils (TANs) in vivo, and Ly6G neutrophil depletion attenuated GINS2-driven tumor enhancement. OSCC-associated neutrophils exhibited elevated PD-L1 expression, correlating positively with GINS2 levels. GINS2 knockdown sensitized OSCC models to anti-PD-L1 therapy, reducing tumor growth and Ki67 expression, particularly when combined with T cells and neutrophils. Discussion:GINS2 acts as a key oncogenic driver in OSCC, promoting tumor progression and facilitating immune evasion. Its effects appear to involve a proximal GINS2-PTP4A1-PKM2 module and the recruitment/polarization of PD-L1+ neutrophils linked to T-cell dysfunction. Targeting the GINS2 axis-potentially in combination with PD-L1 blockade-warrants further investigation in OSCC, with downstream signaling mechanisms to be clarified in future work.

BACKGROUND:Immunotherapy has surfaced as a promising therapeutic modality for gastric cancer (GC). A comprehensive review of advancements, current status, and research trends in GC immunotherapy is essential to inform future investigative efforts. AIM:To delineate the trends, advancements, and focal points in immunotherapy for GC. METHODS:We performed a bibliometric analysis of 2906 articles in English concerning GC immunotherapy published from 2000 to December 20, 2023, indexed in the Web of Science Core Collection. Data analysis and visualization were facilitated by CiteSpace (6.1.6R), VOSviewer v.1.6.17, and GraphPad Prism v8.0.2. RESULTS:There has been an increase in the annual publication rate of GC immunotherapy research. China leads in publication volume, while the United States demonstrates the highest citation impact. Fudan University is notable for its citation frequency and publication output. Co-citation analysis and keyword frequency revealed and highlighted a focus on GC prognosis, the tumor microenvironment (TME), and integrative immunotherapy with targeted therapy. Emerging research areas include gastroesophageal junction cancer, adoptive immunotherapy, and the role of Treg cell in immunotherapy. CONCLUSION:GC immunotherapy research is an expanding field attracting considerable scientific interest. With the clinical adoption of immunotherapy in GC, the primary goals are to enhance treatment efficacy and patient outcomes. Unlike hematological malignancies, GC's solid TME presents distinct immunological challenges that may attenuate the cytotoxic effects of immune cells on cancer cells. For instance, although CAR-T therapy is effective in hematological malignancies, it has underperformed in GC settings. Current research is centered on overcoming immunosuppression within the TME, with a focus on combinations of targeted therapy, adoptive immunotherapy, Treg cell dynamics, and precise prognosis prediction in immunotherapy. Additionally, immunotherapy's role in treating gastroesophageal junction cancer has become a novel research focus.