Abstract Background Gastric cancer (GC) remains a major health burden because of late‐stage diagnosis and resistance to systemic therapy. Main body In GC, the Warburg effect is driven by interconnected hypoxia and oncogenic signalling, non‐coding RNA networks and transcriptional and epigenetic rewiring. These regulators converge on glucose transport and core glycolytic enzymes, including HK2, PFKFB3, PKM2 and LDHA. The resulting increase in aerobic glycolysis, pyruvate‐to‐lactate conversion and lactate export supports biosynthesis, redox homeostasis and survival under metabolic stress. Beyond its bioenergetic role, lactate acts as a signalling metabolite that acidifies and remodels the tumour microenvironment. It impairs CD8‐positive T and natural killer cells function, promotes regulatory T cells accumulation and M2 macrophages polarisation, activates stromal cells and facilitates epithelial–mesenchymal transition and immune evasion. Together, tumour‐intrinsic metabolic adaptation and lactate‐mediated microenvironmental reprogramming contribute to resistance to chemotherapy, targeted therapy and immunotherapy. Translationally, metabolic imaging, circulating LDH and lactate‐related markers, exosomal glycolytic enzymes, gene‐expression signatures and lactylation‐related features may improve prognostic assessment, treatmentresponse prediction and patient stratification. These findings support biomarker‐guided combination strategies that target tumour metabolism, lactate production or transport and stromalimmune crosstalk alongside standard therapies. This review uniquely integrates direct GC‐derived evidence with indirect evidence from non‐GC models and clinical trials and grades biomarkers and metabolic interventions according to their translational maturity. Conclusion Overall, the Warburg effect represents both a central driver of GC progression and a clinically relevant metabolic vulnerability. Key points The Warburg effect in gastric cancer is a multi‐module metabolic state, not a single glycolytic phenotype. Lactate links glycolytic reprogramming to stromal activation, immune evasion and therapy resistance. Microbiota, especially H. pylori, modulates glycolysis and creates actionable upstream vulnerabilities. Biomarker‐guided combinations, rather than isolated glycolytic inhibition, define the translational path forward.

In recent years, gastric oral contrast ultrasonography (OCUS) and double contrast-enhanced ultrasonography (DCEUS) have emerged as promising imaging techniques for evaluating gastric tumors, particularly gastric cancer (GC), by providing beneficial insights into tumor morphology, vascular characteristics and response to therapy. OCUS is capable of identifying the thickened gastric wall and lesions by utilizing oral contrast agents. DCEUS, based on OCUS, further employs intravenous contrast-enhanced ultrasound to examine regions of interest, thereby revealing both the anatomical features and perfusion characteristics of the lesions. These two methods are known for being non-irradiating, cost-effective, noninvasive and real-time. With advances in contrast agents and imaging technology, OCUS and DCEUS are expected to become increasingly reliable and contribute to improving patient prognoses. However, the clinical application of these techniques is still evolving, limited by a lack of technical standardization, operator dependence, and inadequate evaluation in certain tumor subtypes and patient populations. This review summarizes the current state in clinical practice of OCUS and DCEUS in the screening, diagnosis, staging and treatment assessment of gastric tumors. It also proposes possible orientations for clinicians to address the identified limitations and improve the clinical value of OCUS and DCEUS, including the integration of artificial intelligence and molecular imaging, alongside establishing international standardization protocols, enhancing physician training systems, and expanding accessibility to primary care settings. Through these efforts, OCUS and DCEUS may become indispensable components of future GC management strategies. By summarizing gastric contrast ultrasonography across screening, diagnosis, T staging, N staging and treatment assessment in gastric tumors, and comparing with CT, EUS and endoscopy, this review proposes protocol standardization, operator training and AI-enabled quantification to advance its clinical application.

Gastric cancer (GC) ranks among the most prevalent malignancies of the gastrointestinal system. For patients with advanced-stage disease undergoing surgical resection, postoperative 5-year survival rates remain critically low, typically below 20%. Contemporary therapeutic strategies encompass surgical intervention, cytotoxic chemotherapy, immune checkpoint blockade, and molecularly-targeted agents. Targeted therapeutics exert their effects by exploiting molecular vulnerabilities such as human epidermal growth factor receptor-2, Claudin 18.2, vascular endothelial growth factor/vascular endothelial growth factor receptor, fibroblast growth factor receptor 2, and N6-methyladenosine modification pathways, thereby suppressing tumor proliferation and offering improved clinical outcomes for advanced GC. These agents demonstrate significant potential in extending overall survival durations, underscoring their translational value and substantial research implications. This comprehensive review delineates recent advancements in GC-targeted therapies to inform precision oncology paradigms and guide future drug discovery initiatives.

Objective To explore the consistency and clinical application value of transabdominal intestinal ultrasound (IUS) and computed tomography enterography (CTE) in the diagnosis of inflammatory bowel disease (IBD) complicated with intestinal stenosis. Methods A retrospective study was conducted on 115 patients diagnosed with IBD in Beijing Friendship Hospital,Capital Medical University from 2015 to 2024 and who underwent both IUS and CTE examinations during the same period.Clinical and imaging data were collected.Endoscopy was used as the gold standard to compare the detection,localization,and diagnostic efficacy of the two methods for intestinal stenosis and evaluate their consistency. Results A total of 115 patients (70 with Crohn's disease,22 with ulcerative colitis,and 23 with unclassified IBD) were included.In the diagnosis of stenosis among all the IBD patients,the sensitivity of IUS (86.2%) was higher than that of CTE (66.7%),while the specificity of CTE (57.1%) was better than that of IUS (35.7%).The two methods exhibited poor consistency in diagnosing intestinal stenosis (κ=0.056),while they were consistent in identifying pre-stenotic dilation (κ=0.614) and localizing the affected intestinal segments (κ=0.691).The intestinal wall thickness values measured by CTE were systematically higher than those by IUS. Conclusions IUS and CTE have complementary values in the diagnosis of IBD complicated with intestinal stenosis.IUS with higher sensitivity is suitable for screening and long-term follow-up,and CTE with better specificity is suitable for comprehensive anatomical assessment.Clinically,the appropriate choice and application should be made based on specific scenarios and IBD subtypes.

Abstract Gastric cancer (GC) is often diagnosed at an advanced stage due to the absence of early symptoms and low screening rates, resulting in poor prognosis. The progression of GC is closely related to the immune response within the tumor microenvironment (TME). Tumor-associated macrophages (TAMs), particularly the M2 subtype, are the most prevalent inflammatory cells in the TME and play a crucial role in GC. Tumor cells also evade immune surveillance by upregulating CD274. OTUB2, a deubiquitinase, regulates tumor progression by deubiquitinating substrate proteins. However, the role of OTUB2 in TAMs polarization and immune evasion in GC remains unclear. Stable OTUB2 overexpression and knockdown cells were cocultured with M0 macrophages to study TAMs polarization. Flow cytometry was used to analyze M2 TAMs and CD274 expression on GC cells. Cytokine secretion was evaluated by ELISA. T cell killing assays were performed by co-culturing GC cells with CD8+ T cells. Co-immunoprecipitation and Western blotting assessed the ubiquitination levels of YAP, TAZ and CD274. In vivo studies were conducted to evaluate OTUB2’s effect on TAMs polarization, immune evasion and GC progression. Immunohistochemistry of GC tissues was performed to investigate the correlation between OTUB2 and TME components. OTUB2 overexpression activated YAP/TAZ to increase TGF-β1 and M2 TAMs polarization by inhibiting SMAD7. It also enhanced CD274 expression, promoting immune evasion. OTUB2 deubiquitinated YAP, TAZ, and CD274, preventing their degradation. In vivo, OTUB2 increased M2 TAMs polarization and CD274 expression, exacerbating GC progression. Immunohistochemistry confirmed a positive correlation between OTUB2, M2 TAMs infiltration and CD274 levels and a negative correlation with CD8+ T cell infiltration. Kaplan–Meier analysis showed reduced overall survival in GC patients with high OTUB2 expression. OTUB2 promotes M2 TAMs polarization and immune evasion in GC. Targeting OTUB2 offers a promising strategy to reshape the GC TME and improve the efficacy of immune checkpoint inhibitors.

BACKGROUND AND OBJECTIVES:This study aimed to evaluate the safety and efficacy of a fish oil-enriched food for special medical purposes (FSMP, ProSure) compared to an oncology-specific enteral nutrition product (TPF-T). METHODS AND STUDY DESIGN:This multicenter, randomized, open-label, non-inferiority phase III trial (NCT05301556) included patients with gastrointestinal tumors scheduled for surgery and at high risk for malnutrition. Participants were randomized 1:1 to receive either FSMP or TPF-T as a sole nutritional source from 4±2 days before surgery to 9±3 days postoperatively. The primary endpoint was the change in serum pre-albumin levels from baseline to 9±3 days post-surgery (non-inferiority margin: 20.807 mg/L). RESULTS:Of the 325 patients randomized (FSMP: n = 162; TPF-T: n = 163), FSMP demonstrated non-inferiority to TPF-T in maintaining serum pre-albumin levels in the perioperative patients (least square [LS] mean differ-ence: 6.9 mg/L, 95% CI: -5.0 to 18.8). FSMP showed a greater reduction in serum triglycerides (LS mean difference: -0.133 mmol/L, 95% CI: -0.239 to -0.027, p = 0.014), while comparable changes in other lipid parameters, serum albumin, body weight, or grip strength from baseline to 9±3 days post-surgery, and the length of hospital stay were observed between groups (all p >0.05). The most common treatment-emergent adverse events were gastrointestinal disorders, including abdominal distension (FSMP: 17.3% vs. TPF-T: 18.4%), di-arrhea (21.0% vs. 11.0%), and nausea (6.8% vs. 5.5%). CONCLUSIONS:ProSure, an FSMP, when used as a sole nutritional source, is not inferior to TPF-T in maintaining perioperative nutritional status in patients with gastrointestinal tumors, demonstrating comparable efficacy and safety.

Gastric cancer (GC) remains a formidable public health challenge in China, characterized by a high incidence and mortality rate. A significant proportion of patients are diagnosed with advanced or metastatic disease, where traditional chemotherapy has historically offered limited survival benefits. However, driven by a deeper molecular understanding of GC heterogeneity, the paradigm of GC treatment is undergoing a revolutionary shift from a "one size fits all" approach toward precision medicine. The identification of predictive biomarkers, such as human epidermal growth factor receptor 2 (HER2/ERBB2; MIM: 164870) expression, microsatellite instability-high (MSI-H) status, PD-L1 (CD274; MIM: 605402) expression, and Claudin 18.2 (CLDN18; MIM: 609210) overexpression, has established biomarker-guided strategies as the unequivocal future direction for managing advanced GC. In particular, the emergence of immune checkpoint inhibitors (ICIs) and agents targeting Claudin 18.2 has revolutionized the landscape of first-line (1L) treatment for GC. China has achieved accelerated breakthroughs in gastric cancer drug research and development, leading to more innovative therapies and improved diagnostic/treatment regimens, providing patients with more abundant and effective treatment options and significantly improving the landscape of diagnosis and treatment. Nevertheless, integrating complex biomarkers and novel agents into practice poses challenges, including inconsistencies in biomarker testing and the need for nuanced treatment regimen selection. Without standardized guidelines, inconsistent application may lead to suboptimal patient outcomes and inefficient use of healthcare resources. This expert consensus has been jointly formulated with the aim of further enhancing and standardizing the biomarker testing and precision medicine of 1L therapy for advanced GC.

Gastrointestinal stromal tumors (GISTs) are the most common stromal tumors in the gastrointestinal tract. This study was designed to evaluate a gastrin-releasing peptide receptor antagonist PET tracer, [68Ga]Ga-NOTA-RM26, and compare it with [18F]FDG PET/CT in the assessment of patients with GISTs. Methods: With institutional review board approval and informed consent, 30 patients with suspected or proven GISTs based on abdominal CT or gastroscopy were recruited. All patients underwent [68Ga]Ga-NOTA-RM26 and [18F]FDG PET/CT scans. Pathology and other patient information were collected. Results: No radiopharmaceutical-related adverse events were observed in the patients. In total, 18 lesions in 16 patients were diagnosed as GIST, 3 patients were diagnosed with schwannoma, and 4 patients were diagnosed with leiomyoma. In 18 GISTs, the mean SUVmax of [68Ga]Ga-NOTA-RM26 PET was significantly higher than that of [18F]FDG PET (17.07 ± 19.57 vs. 2.28 ± 1.65; P < 0.01), and [68Ga]Ga-NOTA-RM26 PET/CT had a higher tumor detection rate than did [18F]FDG PET/CT (88.9% vs. 50%; P < 0.01). The uptake of [68Ga]Ga-NOTA-RM26 in GISTs was significantly higher than that in 2 other benign tumors (leiomyoma or schwannoma) (17.07 ± 19.57 vs. 4.23 ± 1.77; P = 0.014). With the SUVmax cutoff value of 6.0, the sensitivity of 68Ga-NOTA-RM26 PET/CT in diagnosing GISTs is 72% and the specificity is 85.7%. Conclusion: Compared with [18F]FDG PET/CT, [68Ga]Ga-NOTA-RM26 PET/CT is a promising and effective imaging modality for the detection of GISTs.

Background and Objectives: Perioperative enteral and parenteral nutrition have been increasingly used to treat malnutrition in patients with gastric cancer. Immunonutrients have been suggested to reduce postoperative inflammatory responses and enhance immune function compared to conventional nutritional formulas. However, the insufficiency of evidence and unclear specific mechanism limit the recommendation level of immunonutrients in clinical guidelines. This study aimed to investigate the effects of immunonutrients on intestinal barrier function and to explore potential mechanisms through gut microbiota modulation. Methods: A total of 58 patients who underwent gastric cancer surgery participated in this randomized controlled trial. The immunonutrients group (n = 29) was additionally supplemented with 282 mg of omega-3 fatty acids, 1.2 g of arginine, and 128 mg of nucleotides per 100 kilocalories compared to the standard nutrients group (n = 29). Perioperative serum immune, nutritional parameters, and intestinal barrier markers (diamine oxidase, D-lactate, endotoxin) were evaluated. Fecal microbiota structure and functional pathways were analyzed via metagenomic sequencing. Results: Postoperative immune and nutritional parameters showed no statistically significant intergroup differences, though mean value curves suggested a protective trend in the immunonutrients group. The immunonutrients group exhibited significantly lower postoperative diamine oxidase (p = 0.043) and endotoxin levels (p = 0.043), alongside a substantial increase in microbiota α-diversity (p = 0.0005). Probiotic genera such as Akkermansia (3.26%) and Bifidobacterium longum (2.31%) were enriched in the immunonutrients group. Functional pathway analysis suggested that immunonutrients enhanced intestinal barrier protection. Conclusions: Immunonutrients may attenuate surgery-induced intestinal barrier damage in gastric cancer patients by modulating gut microbiota diversity, enriching beneficial taxa, and suppressing pathogenic bacteria.

BACKGROUND:Gastrointestinal stromal tumors (GISTs) exhibit significant heterogeneity, posing substantial challenges for personalized treatment strategies. Patients often display varied responses to different therapeutic agents and dosages. Currently, the absence of robust and physiologically relevant in vitro models for GISTs impedes accurate prediction of therapeutic efficacy, thereby constraining the advancement of effective treatment strategies. Traditional 2D cell cultures fail to replicate the tumor microenvironment (TME) and lack patient-specific characteristics, limiting their predictive value. In contrast, three-dimensional bioprinting (3DP) technology faithfully recapitulates key histological architecture and molecular features of their parental tumors, enhancing the physiological relevance of in vitro models. METHODS:We employed patient-derived 3DP-GIST models via 3D bioprinting technology, followed by comprehensive histopathological, genomic, and transcriptomic analyses. Subsequently, we applied clinically approved targeted therapeutic agents to perform drug screening and response prediction on the 3DP-GIST models. The drug sensitivity profiles obtained from these models were then correlated with retrospective clinical data and patient follow-up records to assess the models' potential in guiding the selection and prediction of effective GIST therapies. RESULTS:In our study, we successfully constructed 12 patient-derived 3DP-GIST models. Histopathological assessments, whole-exome sequencing (WES), and transcriptomic analyses confirmed that these models accurately recapitulate the histological architecture, biomarker expression, and molecular features of their corresponding parental tumors. Transcriptomic profiling further revealed gene expression signatures associated with GIST recurrence risk and imatinib resistance. Importantly, the 3DP-GIST models demonstrated the capacity to provide precise, individualized treatment recommendations within 10 days post-surgery, potentially reducing treatment delays and improving patient outcomes. CONCLUSIONS:Overall, the 3DP-GIST model represents a robust and efficient platform for evaluating patient-specific drug sensitivities in vitro, thereby guiding personalized therapeutic strategies for GIST patients.

Objective To compare the diagnostic value of transabdominal intestinal ultrasound (IUS) and magnetic resonance enterography (MRE) for intestinal stenosis in inflammatory bowel disease (IBD). Methods A retrospective analysis was conducted on the imaging features of 51 IBD patients who underwent both IUS and MRE at Beijing Friendship Hospital,Capital Medical University,between January 2021 and February 2025.With endoscopy as the gold standard,the diagnostic performance of the two methods was compared. Results The sensitivity (84.2% vs. 52.6%,P=0.008) and accuracy (66.7% vs. 45.1%,P=0.035) of IUS for stenosis were higher than those of MRE.In the localization of stenosis,IUS demonstrated higher sensitivity than MRE for detecting stenosis in the terminal ileum (78.6% vs. 35.7%,P=0.070) and colorectum (86.7% vs. 53.3%,P=0.060).Furthermore,IUS showed higher diagnostic accuracy than MRE for terminal ileum stenosis (70.6% vs. 29.4%,P=0.039).The intestinal wall thickness[(8.2±2.7) mm vs. (10.3±3.8) mm;t=3.20,P=0.002)] and stenosis inner diameter[(3.0±1.6) mm vs. (4.3±1.8) mm;t=2.15,P=0.035] measured by IUS were lower than those measured by MRE,with a moderate level of consistency (ICC:0.19-0.53).In addition,IUS demonstrated a higher detection rate for mesenteric fat hypertrophy (70.6% vs. 27.5%,Kappa=0.27,P=0.005),whereas MRE was more sensitive in detecting lymphadenopathy (90.2% vs. 56.9%,Kappa=0.16,P=0.080). Conclusions IUS is superior to MRE in the diagnosis and localization sensitivity for intestinal stenosis in IBD.However,the two methods showcase poor consistency in detecting and quantitating some inflammatory signs.IUS can be used as a first-line screening method for diagnosing intestinal stenosis in IBD patients,while its clinical application should be combined with specific needs to optimize diagnosis.

2612 Background: This study evaluated the efficacy and safety of neoadjuvant Serplulimab combined with concurrent chemoradiotherapy for locally advanced resectable esophagogastric junction (EGJ) adenocarcinoma. Methods: Eligible patients with resectable EGJ（cT3-4 or N+M0）adenocarcinoma received neoadjuvant Serplulimab (300 mg) plus SOX (oxaliplatin 130 mg/㎡; TS1 40-60 mg) for the first cycle, followed by Serplulimab with concurrent chemoradiotherapy (oxaliplatin 100 mg/㎡, TS1 40-60 mg; radiotherapy dose 45 Gy/ 25 fractions) during the second and third cycles. Surgery was performed 6-8 weeks after chemoradiotherapy. Tissue and blood samples were collected for genetic analysis. Primary endpoints included pathological complete response (pCR) and major pathological response (MPR). Results: From March 2023 to November 2024, 24 patients were enrolled and 19 patients underwent radical resection. The R0 rate was 100%. pCR rate was 26.3%, MPR rate was 36.8%. T downstaging rate 78.9%, ypN0 89.5%. The median DFS was not reached. Microsatellite stable status was 100%. PD-L1 CPS expression: < 1 (5.3%), 1-5 (42%), > 5 (52.6%), > 10 (31.6%). PD-L1 expression was associated with pathological response, with MPR rates of 57.1% for CPS ≥5 and 14.3% for CPS < 5. Minimal residual disease positivity (MDR+) before enrollment was 68.7%, and 6 MRD+ patients converted to MRD- after neoadjuvant therapy. Grade ≥3 adverse events occurred in 33.3% of patients, with manageable treatment-related adverse events. Conclusions: Neoadjuvant Serplulimab with concurrent chemoradiotherapy showed promising efficacy for locally advanced resectable EGJ adenocarcinoma. Improved R0 and ypN0 rate may change the surgical procedure in the future. Follow-up will assess correlations between biomarkers and outcomes. Clinical trial information: NCT05918419 .

Gastric contrast-enhanced ultrasound includes oral contrast-enhanced ultrasound (OCUS) and double contrast-enhanced ultrasound (DCEUS),which can provide valuable clinical information about tumor morphology,vascular characteristics,and treatment responses.OCUS can clearly identify the gastric wall structure and the extent and depth of lesions by applying oral contrast agents.DCEUS,based on OCUS combined with venography,can display the anatomical and perfusion characteristics of lesions.In recent years,gastric contrast agents and imaging techniques have developed rapidly.However,the clinical application of gastric contrast-enhanced ultrasound is still in the developmental stage.This article reviews the clinical status of OCUS and DCEUS in the screening,diagnosis,staging,pathological typing,and treatment evaluation of gastric cancer.Studies have shown that gastric contrast-enhanced ultrasound has high sensitivity and specificity in the assessment of diagnosis and T-staging of gastric cancer.Furthermore,gastric contrast-enhanced ultrasound has the advantages of being cost-effective,convenient,non-invasive,free from radiation exposure,real-time,and easy to repeat.In the diagnosis and treatment of gastric cancer,it is expected to become one of the important imaging assessment tools.

Antigen-presenting and processing fibroblasts (APPFs) have emerged as pivotal regulators of antitumor immunity. However, the predictive value of APPF-related genes (APPFRGs) in the prognosis and tumor immune status of gastric cancer (GC) remains largely unexplored. Bioinformatics analysis was conducted using single-cell and bulk RNA sequencing datasets of GC retrieved from the Gene Expression Omnibus (GEO) and The Cancer Genome Atlas (TCGA) databases. The APPFs were identified using AUCell algorithm based on APP-associated genes obtained from the InnateDB database. CellChat algorithm was utilized to evaluate interactions between cells. The non-negative matrix factorization (NMF) clustering analysis was performed to identify APPF-related subgroups based on TCGA‑stomach adenocarcinoma cohort. LASSO and multivariate Cox regression analysis were conducted to establish the predictive model. Immunohistochemistry of GC tissue microarrays was performed to validate the model. Compared to non-APPFs, APPFs exhibited more interactions with myeloid cells, endothelial cells, and lymphocytes via MHC-II signaling network. The two APPF-related subgroups clustered by NMF demonstrated significant differences in prognosis and immune cell infiltration. Five APPFRGs (CPVL, ZNF331, TPP1, LGALS9, TNFAIP2) were identified to establish the predictive model and stratify GC patients based on risk score. The prognosis was significantly different between the two risk groups and was validated using GEO datasets. A nomogram that efficiently predicted the overall survival of GC patients was established by integrating the risk score with age, T stage, N stage, and M stage. Furthermore, the high-risk group exhibited reduced infiltration of activated CD4+ T cell and increased infiltration of Treg cells, higher resistance to chemotherapy and immunotherapy, and lower tumor mutation burden. Finally, the immunohistochemical results of GC tissue microarrays revealed higher expression of CPVL, ZNF331, and TPP1, and lower expression of LGALS9 and TNFAIP2 in GC compared to adjacent normal tissues. Additionally, higher risk score in GC samples was relevant with poor differentiation, positive nerve invasion, advanced T and TNM stages, and higher expression of FOXP3. APPFs may play an important role in the regulation of tumor immune microenvironment in GC and warrant further exploration. The predictive model based on APPFRGs effectively predicts the prognosis and tumor immune status of GC.

Neoadjuvant therapy targeting genotype-specific gastrointestinal stromal tumors (GISTs) may be indicated in select cases. While the majority of patients respond to Imatinib with a reduction in tumor size, some exhibit either poor response or resistance, necessitating the exploration of alternative therapeutic strategies. This report describes a high-risk patient facing potential multiorgan resections whose tumor responded poorly after 14 months of Imatinib therapy. After 8 months of transitioning to Ripretinib treatment, there was a 26% reduction in the largest tumor diameter. This improvement allowed better delineation of the tumor from the surrounding tissues, which in turn made it possible to perform an R0 resection while preserving the possibly involved organs. To our knowledge, this is the first case report of Ripretinib as a neoadjuvant therapy for GIST with peripheral organ invasion to achieve complete resection. This case report may present the effectiveness of Ripretinib and introduce a relatively novel approach to clinical treatment.

ARID1A mutations are a common occurrence in colorectal cancer (CRC) cells, but clinical therapeutic options targeting this anomaly remain unavailable. The loss of ARID1A functionality compromises DNA damage repair processes, potentially causing cancer cells to rely more heavily on PARP-dependent DNA repair pathways to preserve genomic integrity, thereby making them susceptible to PARP inhibitor (PARPi) therapy. To evaluate the suitability of PARPi treatment for CRC patients with ARID1A sufficiency (ARID1A+) and ARID1A deficiency (ARID1A-), our study enrolled 80 patients who had undergone surgical treatment for primary CRC. Surgical specimens underwent immunohistochemical examination to assess ARID1A protein expression. The study explored correlations between ARID1A expression loss and clinicopathological characteristics. Moreover, primary CRC cells were isolated through enzymatic digestion and validated using the colorectal carcinoma marker CK20. Subsequently, PARPi sensitivity was investigated in untreated ARID1A+ and ARID1A- CRC patients using an ATP-tumor chemosensitivity assay (ATP-TCA). Additionally, we confirmed the efficacy of PARPi in these primary CRC cells through clone formation and assessed its impact on cell cycle dynamics, apoptosis, and DNA damage repair signaling pathways using immunofluorescence and flow cytometry. The results demonstrated that the ARID1A- group displayed greater sensitivity to PARPi compared to the ARID1A+ group. PARPi treatment led to increased tumor cell death in the ARID1A- group. Mechanistically, ARID1A deficiency resulted in cell cycle abnormalities, particularly G2/M phase arrest, which was further exacerbated by PARPi treatment. Furthermore, PARPi treatment significantly increased the number of RAD51 foci in ARID1A- cell lines. In conclusion, our study highlights the potential of PARPi as an effective therapeutic option for ARID1A- CRC patients.

Background:Accurate preoperative staging of gastric cancer (GC) is essential for guiding treatment strategies. However, reliable noninvasive tools for distinguishing early-stage from advanced-stage GC remain limited. Methods:This retrospective study enrolled 434 patients with GC. Eleven supervised machine learning algorithms were developed using preoperative laboratory parameters and engineered ratio features capturing inflammatory, metabolic, and tumor-related profiles. CatBoost showed superior performance and was selected for SHapley Additive exPlanations (SHAP)-based interpretation. A forward feature selection strategy identified an optimal nine-feature panel. Model performance was evaluated by area under the receiver operating characteristic curve (AUC), accuracy, precision, recall, and F1-score, with robustness validated through repeated 10-fold cross-validation and 1000 bootstrap iterations. Results:Among 434 patients, 251 (57.8%) had stage I and 183 (42.2%) had stages II-III disease. Incorporating biologically informed ratio features significantly enhanced model performance; CatBoost's AUC improved from 0.802 to 0.981. SHAP-based selection yielded a compact, interpretable nine-feature model. The final CatBoost model achieved a mean AUC of 0.9499 (95% confidence interval (CI): 0.9421-0.9570), with high consistency across cross-validation folds. SHAP analysis identified uric acid (UA) and APTT as key predictors, and interaction analysis revealed stable multivariate relationships, supporting the model's biological plausibility. Conclusions:We developed a robust, interpretable machine learning model for GC staging using routine blood tests and derived ratio features. The model demonstrated excellent discrimination, interpretability, and clinical utility, offering a practical tool for personalized risk stratification and treatment planning.

BACKGROUND AND OBJECTIVES:Patients with gastrointestinal (GI) malignancies are at high risk for malnutrition because of reduced food intake, poor digestion, and altered absorption. METHODS AND STUDY DESIGN:In a ret-rospective review of medical records for patients admitted to urban hospitals in an Asian nation for GI tumor surgery (gastric, colon, or anorectal cancers), we found that malnutrition was common yet often overlooked. Our review identified records for 349 adult GI-tumor surgery patients. The Nutrition Risk Screening-2002 (NRS-2002) was the most frequently used screening instrument. In further review, we compared outcomes for malnourished GI tumor surgery patients given daily oral nutritional supplements (ONS) to outcomes for patients who were not given ONS. RESULTS:Review of results revealed that only 20% of patients in our sample underwent nutritional screening or assessment on admission. Of those who did, nearly 60% were malnourished. Although due to small sample sizes, no statistically significant differences were observed, mal-nourished patients who received ONS had fewer complications and shorter lengths of stay by 1-day. Such findings reveal many missed opportunities to improve patient outcomes and to avert excess healthcare costs for treatment of complications, slowed recovery, longer hospital stays, and readmissions. CONCLUSIONS:Based on our findings, nutritional training for professionals is necessary to address the serious problems of under-recognition and inadequate treatment of malnutrition in hospitalized patients.

BACKGROUND: The pronounced chemotherapeutic heterogeneity observed in gastric cancer (GC) poses significant challenges to personalized treatment strategies, with current approaches lacking reliable predictive modalities for chemotherapy efficacy and postoperative prognosis. While patient-derived organoid (PDO) and xenograft (PDX) models serve as established three-dimensional platforms, their prohibitive costs and inherent batch effect limit faithful replication of native tumor extracellular matrix (ECM) complexity. METHODS: We utilized patient-derived GC tissues to construct individualized 3D bioprinting (3DP)-GC models. After screening bioinks for optimal mechanical properties and biocompatibility, we successfully and efficiently constructed 3DP-GC models of 33 patients, and performed histopathological and genomic analyses to determine that the 3DP-GC model effectively preserved the histological architecture, biomarker expression abundance and genetic mutation profiles of the parental tumors. Drug screening on the 3DP-GC models was conducted using clinical gastric cancer therapies. Retrospective analysis of patients’ post-neoadjuvant therapy and follow-up of those post-adjuvant therapies were performed to evaluate the model’s potential in predicting and selecting chemotherapeutic agents for gastric cancer patients. RESULTS: In this study, we successfully and efficiently constructed 3D in vitro models of 33 GC patients using 3D bioprinting technology, and performed histopathological and genomic validation to find that the 3DP-GC model well preserved the expression abundance and mutation profiles of markers in the parental tumors. A significant correlation was observed in drug sensitivity between the 3DP-GC platform and the actual clinical efficacy observed in patients. CONCLUSION: Our study establishes a robust and stable 3DP-GC model. Crucially, drug testing of 3DP-GC model can accurately predict the clinical chemotherapy of patients in a shorter time and at a lower cost, offering a promising tool for high-throughput drug screening and personalized treatment decision-making.