Enhanced TGF-β/SMAD signaling causes adipose dysfunction by inhibiting adipogenesis and promoting adipocyte pathological hypertrophy in obesity development. Identifying novel regulators of the TGF-β pathway could significant important for modulating adipose metabolism. While ubiquitination of SMAD attenuates TGF-β signaling, it is still unknown whether this mechanism is involved in regulating adipose function. This study revealed that SMAD proteins undergo ubiquitination and degradation during the early stages of adipogenesis. E3 ligase SMURF2 was identified as the primary regulator in this biological process. In vitro studies demonstrated that SMURF2 deficiency significantly impaired adipogenic differentiation of preadipocytes, whereas SMURF2 overexpression markedly enhanced this process. In mouse studies, SMURF2 overexpression robustly promoted de novo adipogenesis, which in turn conferred resistance to high-fat diet-induced obesity and metabolic disorders. Furthermore, increased SMURF2 expression significantly improved and therapeutically ameliorated dysregulated glucose and lipid metabolism in obese mice. Interestingly, we designed a peptide to inhibit SMAD2 phosphorylation, thereby preventing its ubiquitination by SMURF2. Administration of this polypeptide conferred substantial metabolic benefits in obese mice. Our study uncovers a novel regulatory axis controlling adipose tissue expansion via the TGF-β/SMAD pathway. We anticipate that the findings from this project will provide new targets and insights for intervening in obesity and its metabolic complications.

Minimally invasive D2 lymphadenectomy for gastric cancer is technically demanding, and its quality varies across patients, surgeons, platforms, and institutions. Conventional endpoints, including lymph node yield, margin status, operative time, blood loss, postoperative morbidity, and survival, remain essential but do not consistently capture intraoperative procedural fidelity, safety-critical deviations, or case complexity. This narrative framework review synthesized evidence from MEDLINE, Embase, and Web of Science from inception to May 10, 2026, focusing on technical difficulty, surgical quality assessment, pathology-centered oncologic adequacy, risk-adjusted outcomes, and artificial intelligence (AI)-enabled audit. Technical difficulty was conceptualized as a case- and context-dependent risk-adjustment layer shaped by anatomical complexity, vascular variation, therapy-altered tissue planes, visceral adiposity, operative platform, team workflow, and learning stage. Surgical quality was defined as a multidomain construct integrating process metrics, pathology metrics, and risk-adjusted clinical outcomes. The proposed framework provides audit-oriented guidance for identifying a simplified minimum dataset, prioritizing high-risk D2 segments for selective process review, and interpreting process, pathology, and outcome indicators together after adjustment for technical difficulty. AI may support scalable audit through video indexing, phase and step recognition, extraction of high-risk operative segments, assisted event logging, and structured feedback. However, AI outputs should be treated as candidate measurement signals requiring human confirmation, expert surgical review, pathology-based assessment, external validation, governance, and post-deployment monitoring. Future validation should proceed stepwise, from feasibility testing and inter-rater reliability assessment to prospective workflow evaluation and multicenter assessment of audit efficiency, benchmarking validity, and process- or patient-level outcomes. Quality assessment in minimally invasive D2 lymphadenectomy should shift from isolated surrogate endpoints toward an auditable, difficulty-adjusted framework that makes “D2 achieved” more measurable, reviewable, and clinically meaningful.

Preoperative assessment of lymph node dissection (LND) difficulty in gastric cancer remains challenging. Conventional clinical indicators are relatively coarse and may not adequately reflect tissue-related complexity within the surgical field. This study aimed to develop and validate a preoperative CT-based radiomics approach using suprapancreatic adipose tissue for predicting high-difficulty LND in gastric cancer. This single-center retrospective study included 192 patients with gastric cancer who underwent laparoscopic radical D2 gastrectomy between January 2022 and December 2024. Patients were randomly assigned to a training cohort (n = 134) and a validation cohort (n = 58). High-difficulty LND was defined as suprapancreatic LND time exceeding the 75th percentile (32.68 min) and/or unqualified suprapancreatic dissection according to KLASS-02-QC. A single-slice ROI was manually delineated in the suprapancreatic adipose tissue on portal venous-phase CT images. Radiomics features were extracted, followed by feature selection and model development. Four radiomics models, a clinical model, and a combined model were constructed. Sensitivity analyses were further performed using alternative time thresholds and in the subgroup without neoadjuvant chemotherapy (NCT). A total of 81 of 192 patients (42.2

Background: Krukenberg tumors (KTs) represent a distinct form of ovarian metastasis originating from gastric cancer (GC) and are associated with dismal clinical outcomes. Despite their clinical significance, the molecular landscape and underlying mechanisms driving KTs development remain largely undefined. Our goal was to delineate the molecular landscape and metastatic evolutionary pattern of KTs, thereby informing the development of therapeutic strategies. Methods: We conducted whole-exome sequencing (WES) on paired primary gastric and metastatic ovarian tumors from 11 patients with KTs in a retrospective cohort. Results: TP53 (54.5%) and EIF1AX (45.5%) were the most frequently mutated genes in KTs. Mutational signatures analysis revealed associations with age and mismatch repair deficiency. Mutations in TP53, EIF1AX, and FBXW7, along with MYC-amplification, were highly consistent between matched primary tumors and KTs. Importantly, compared to primary GC, KTs harbored distinct mutational landscapes, including mutually exclusive receptor tyrosine kinase (RTK) gene amplifications and a significantly higher burden of copy number variations (CNVs). Furthermore, patients exhibiting high-level CNVs or TP53 mutations had worse survival outcomes. Genomic comparisons between matched tumors demonstrated low concordance (median shared mutations: 6.3%), supporting the hypothesis of early clonal divergence and a parallel progression model of metastasis. Conclusions: Frequent TP53 and EIF1AX mutations may play a critical role in the ovarian metastasis of GC. KTs demonstrate distinct mutational profiles compared with their primary counterparts, consistent with a parallel progression model, highlighting the need for tailored therapeutic approaches targeting metastasisspecific alterations.

The benefit of adjuvant chemotherapy (ACT) for patients with gastric cancer (GC) after first-line neoadjuvant chemotherapy (NACT) is debated. This study developed and validated a machine learning (ML) model to predict disease-free survival (DFS) and identify patients who benefit from ACT. A total of 1150 patients treated with NACT and radical gastrectomy across four centers in China were retrospectively analyzed. Feature selection and model development employed multiple ML learners. The optimal model was determined using the concordance index (C-index), time-dependent receiver operating characteristic curves, time-dependent calibration curves, and decision curve analysis. ACT efficacy was evaluated in different risk groups using inverse probability of treatment weighting. Eleven ML learners identified eleven feature subsets. Subsequently, eleven feature subsets and eleven machine learning learners were combined, resulting in the development of 121 models. The GAMB-AORSF model, which combines a Generalized Additive Models via Gradient Boosting-selected feature subset with an Accelerated Oblique Random Survival Forest learner, exhibited the highest prediction performance. The model demonstrated robust discrimination with C-indices of 0.864 in the training cohort, and 0.813 and 0.789 in two validation cohorts. The GAMB-AORSF model successfully stratified patients to guide decision-making. High-risk patients derived significant survival benefits from ACT, with a 3-year restricted mean survival time extension of 5–7 months and an absolute recurrence risk reduction of 14–20

M2-like macrophages and CD8+T cells are key immune components that influence tumor behavior and treatment response. Ubiquitin-specific protease 32 (USP32) is established as a key oncogenic factor in gastric cancer (GC). This study aimed to investigate the role of USP32 in regulating M2 macrophage polarization and CD8+T cell dysfunction in GC. Macrophages derived from THP1 cells (THP1-M0) or CD8+T cells were co-cultured with transfected AGS and HGC-27 GC cells. The proportion of CD206+ M2 macrophages and the apoptosis of CD8+T cells were assessed by flow cytometry. Cell invasion was analyzed by transwell assay. The interaction between USP32 and death-associated protein kinase 1 (DAPK1) was verified by GST pull down and Co-immunoprecipitation (Co-IP) experiments. The effect on tumor growth was tested by subcutaneous xenograft studies. USP32 and DAPK1 were overexpressed in GC tissues and cell lines. Mechanistically, USP32 stabilized DAPK1 protein through deubiquitination. DAPK1 downregulation reversed USP32-mediated enhancement in GC cell invasion, macrophage M2 polarization, and CD8+T cell apoptosis in vitro. USP32 depletion exhibited an in vivo anti-growth effect on AGS subcutaneous xenografts. This study identifies the USP32/DAPK1 cascade as a crucial regulator of M2 macrophage polarization and CD8+T cell apoptosis in GC, providing a novel mechanistic link between post-translational regulation and tumor immune evasion.

BACKGROUND:For patients with early gastric cancer (EGC) who exceed the absolute indications for endoscopic submucosal dissection (ESD) or have undergone non-curative ESD, sentinel node navigation surgery (SNNS) represents a promising individualized surgical approach. This study aimed to conduct a systematic review and meta-analysis to evaluate the feasibility and diagnostic value of indocyanine green (ICG) guided SNNS in patients with EGC. METHODS:Eligible studies were systematically searched in PubMed, Web of Science, Ovid MEDLINE, Scopus and Cochrane Library from inception to March 2026. Identification rates and patient-level sensitivity were pooled separately with random-effects Freeman-Tukey double-arcsine models in StataNow/MP 19.5. Diagnostic analyses were restricted to studies with an adequate reference standard and reconstructable 2×2 data. Cohort overlap was handled with a conservative primary set and prespecified replacement analyses. Evidence after non-curative ESD was synthesized narratively. RESULTS:Nine non-overlapping cohorts were included in the primary identification analysis, yielding a identification rate of 98.8% (95% CI: 97.6-99.5%). The random-effects pooled identification rate was 99.9% (95% CI = 98.7-100.0%; I2 = 32.0%). Eight studies contributed valid patient-level diagnostic data (84 true positives, 4 false negatives, 0 false positives, and 577 true negatives), and the pooled sensitivity was 98.5% (95% CI 86.6-100.0%; I2 = 47.6%). Specificity was 100.0% (577/577), but estimation was structurally constrained because all studies reported zero false positives. Subgroup associations were exploratory. Evidence after non-curative ESD was heterogeneous and was not pooled. CONCLUSION:ICG-guided sentinel node navigation surgery shows high technical identification and promising patient-level sensitivity in selected EGC cohorts. These findings do not establish oncological non-inferiority of limited surgery. False-negative consequences, zero-cell constraints, overlap, heterogeneous pathology, and concentration of evidence in high-volume Asian centres require cautious interpretation and prospective validation.

Patients with functional esophageal disorders exhibit symptoms such as chest pain, heartburn, dysphagia, globus sensation, or reflux hypersensitivity in the absence of structural abnormalities. This is characterized by dysregulated gut-brain interactions and visceral hypersensitivity. A systematic search of the MEDLINE, EMBASE, Web of Science and the Cochrane central register of controlled trials databases was performed to December 31, 2025. Relevant randomized controlled trials (RCT) reporting the effects of gut–brain neuromodulator (GBN) therapy on functional chest pain (FCP), functional heartburn (FH), reflux hypersensitivity (RH), functional dysphagia (FD), and globus were analyzed. Among 2538 screened records, 29 RCTs were included. Neuromodulators provided symptom relief in 18–67

Proximal gastrectomy (PG) for proximal gastric cancer (PGC) is associated with complications such as gastroesophageal reflux. The double-flap technique (DFT) has been proposed as an effective anti-reflux reconstruction method. This systematic review aims to compare the safety and short-term outcomes of DFT versus other reconstruction methods for proximal gastrectomy. The present meta-analysis was conducted, following PRISMA guidelines. Studies comparing DFT with other reconstruction methods for proximal gastric cancer were included. Outcomes assessed included surgical parameters (operative time and intraoperative blood loss), postoperative reflux incidence (subjective reflux symptoms, objective evaluation using endoscopy and proton pump inhibitor (PPI) intake), and other short-term postoperative indicators (postoperative complications and length of postoperative hospital stay). Data were extracted from PubMed, Web of Science, EMBASE, and the Cochrane Library through June 1st, 2025. Risk of bias was assessed using the Newcastle-Ottawa Scale. We performed meta-analyses using Review Manager 5.4, presenting mean differences (MD) and odds ratios (OR) with 95

We read with great interest the Commentary written by Prof. Eom and Prof. Ryu entitled:"Is sentinel node navigation surgery feasible after non-curative endoscopic resection in patients with early gastric cancer?". The authors acknowledge that the "Expert consensus on multidisciplinary management of laparoscopic-endoscopic cooperative surgery combined with sentinel lymph node navigation surgery for early gastric cancer (2026 edition)" represents a meaningful advance in clinical applicability and critically appraises consensus 4,which addresses the role of sentinel node navigation surgery (SNNS) following non-curative endoscopic submucosal dissection (ESD) (1).

Obesity is a significant global public health issue, traditionally linked to adverse health outcomes. However, the “obesity paradox” suggests that in certain populations, obesity may be associated with better prognosis. This study investigates the relationship between waist-to-hip ratio (WHR), a marker of central obesity, and cancer incidence, all-cause mortality, and cancer-specific mortality in a large prospective cohort from Northern China. Data from the Kailuan Cohort, comprising 94,139 participants, were analyzed. WHR was categorized by sex (low, normal, high), and its associations with cancer incidence, all-cause mortality, and cancer-specific mortality were evaluated using multivariate Cox proportional hazards models. Higher WHR was significantly associated with increased risks of all-cause mortality (7

Autonomic nerves comprise the sympathetic and parasympathetic systems, which act in a largely antagonistic manner to regulate diverse physiological functions. With growing interest in the roles of autonomic innervation in intestinal physiology and pathology, there is an increasing need for experimental models that enable precise manipulation of gut-directed sympathetic and parasympathetic inputs. Here, we present a surgical protocol to selectively transect the sympathetic and parasympathetic nerves innervating the intestine. Using the superior mesenteric artery (SMA) as a reproducible anatomical landmark, this approach allows reliable identification of intestinal autonomic nerve bundles and subsequent targeted transection. In contrast to broader denervation approaches such as ganglionectomy or subdiaphragmatic vagotomy, this approach is intended to achieve a more anatomically localized transection of intestine-directed autonomic bundles, which may help reduce extra-intestinal interference. The injury is controllable and is typically associated with minimal bleeding, supporting procedural consistency and postoperative recovery. Although the surgery requires appropriate microsurgical training, the protocol is adaptable, enabling users to tailor key parameters to specific experimental aims. Importantly, this model provides a practical platform to investigate the roles of sympathetic and parasympathetic nerves in regulating intestinal function under both physiological and disease conditions. This article aims to describe the procedure in detail to facilitate its adoption by new users in their research.

With the advancement of surgical techniques and enhanced management of early gastric cancer (EGC), minimally invasive function-preserving surgical approaches have emerged as a common goal for patients and clinicians. Laparoscopic-endoscopic cooperative surgery combined with sentinel lymph node navigation surgery (LECS-SNNS) has drawn increasing interest because of its dual benefits of minimal invasiveness and organ function preservation. However, robust evidence-based support for guiding clinical implementation remains limited. To address this gap, we systematically evaluated available studies on the clinical application of LECS-SNNS in EGC and integrated expert insights to formulate 20 recommendations. These included preoperative assessment, surgical techniques, intraoperative endoscopic procedures, pathological evaluation, postoperative care, and follow-up. This consensus aimed to provide comprehensive guidance for the standardized application of LECS-SNNS, thereby advancing precise, minimally invasive, and function-preserving treatment for EGC.

This study employs patient-specific computational fluid dynamics coupled with a Lagrangian discrete-phase model to quantify the influence of His angle and anastomotic caliber on intragastric hemodynamics after stomach-partitioning gastrojejunostomy (SPGJ). Three His angles (3°, 7°, 11°) and three stoma widths (narrow, intermediate, wide) were systematically analyzed. Within the physiological range, His angle altered global velocity and pressure by <5%, yet extreme values prolonged mean particle residence up to 1.9-fold, indicating a moderate angle (∼7°) minimizes stasis without elevating pressure loss. Stoma size proved decisive: very narrow or very wide orifices produced low-velocity seepage, high stagnation, and either excessive or moderate pressure drops, whereas an intermediate aperture yielded the lowest Δp and the shortest residence time. The results suggest that optimizing SPGJ requires maintaining a moderate His angle and designing an intermediate-sized anastomosis to maximize emptying efficiency while limiting tumor irritation and reflux risk. Clinically, these findings provide actionable guidance for intraoperative configuration and stoma sizing to balance functional patency with complication avoidance.

Stomach-partitioning gastrojejunostomy (SPGJ) improves gastric-outlet obstruction outcomes, yet its biomechanical basis and geometric optimization remain unclear. Patient computed tomography (CT) data were used to reconstruct realistic SPGJ models. Computational fluid dynamics combined with a discrete phase model quantified velocity, wall pressure, particle-retention time, and velocity under systematic variations of partitioning position (distal, mid, and proximal), partitioning angle (5°, 15°, and 25°; left- or right-sided), and incision angle (60°, 75°, and 90°). Distal partitioning produced the lowest pressure drop and fastest emptying, whereas proximal partitioning channeled high-speed flow toward the pylorus and prolonged retention. A ∼15° partitioning angle balanced flow restriction and clearance; extreme unilateral angles either increased particle stasis (left-side) or slowed emptying despite reduced reflux (right-side). A vertical incision (90°) further decreased pressure losses and shortened mean retention relative to oblique cuts. SPGJ biomechanics are highly geometry-sensitive. Distal placement, a 15° partitioning angle, and a near-vertical incision collectively optimize flow, reduce lesion contact, and accelerate gastric emptying, providing quantitative guidance for patient-specific SPGJ design.

PURPOSE:This study aimed to develop an artificial intelligence (AI) model for the surgical report output of laparoscopic lymph node dissection in the suprapancreatic region during gastric cancer surgery. METHODS:Patients who underwent laparoscopic radical resection for gastric cancer were included in this study, and their surgical videos were analyzed. The videos were recorded from the opening of the gastropancreatic fold as the starting point to the transection of the left gastric artery as the endpoint, with the video frame rate set to 1 frame per second. All surgical procedures were recorded following the principle of tool-tissue interaction, with annotations completed by an experienced surgeon and reviewed by a senior surgeon. The final annotated surgical videos were used as inputs for the AI model to generate the surgical report output. RESULTS:A total of 100 patients who underwent laparoscopic surgery for gastric cancer were included. A Surgical Concept Alignment Network was used as the model for surgical report output. The average number of frames in the videos was 728.71, with the grasping forceps being the most frequently used instrument. The AI model successfully generated a surgical video report output, achieving a BLEU-4 score of 0.7377, METEOR score of 0.4846, and ROUGE-L score of 0.7953. CONCLUSION:The AI model demonstrates its capability in producing surgical report output for laparoscopic lymph node dissection in the suprapancreatic region during gastric cancer surgery. This model serves as a valuable tool in clinical diagnosis, treatment, and training.

The Sentinel Lymph Node (SLN) is the primary lymph node that receives lymphatic drainage from a tumor. Sentinel lymph node biopsy (SLNB) has become an indispensable tool for surgical guidance and therapeutic decision in surgical oncology. SLNB enables targeted surgical interventions while preserving patients' postoperative quality of life and refining prognostic evaluations. This review delves into the role and current status of SLN in gastric, colorectal, breast, thyroid, pancreatic, hepatic, gallbladder diseases and other sites. Variations in anatomy and techniques specific to each organ are explained, and the current role of SLNB in diagnosis and treatment is discussed. Enhancements of technologies in imaging and pathological examination, along with supplementary tools is also included. Future research should prioritize clinical evidence to support SLN's practical use while ensuring efficacy and safety.