Acute presentation of vomiting is a very common presenting complaint in the emergency department(ED).While majority of such complaints can be attributed to benign,self-limiting causes such as gastroenteritis,rarer alt...Acute presentation of vomiting is a very common presenting complaint in the emergency department(ED).While majority of such complaints can be attributed to benign,self-limiting causes such as gastroenteritis,rarer alternative diagnoses should be considered depending on the patient's progress after initial treatment.Here,we present a case of gastric volvulus(GV),a rare but potentially fatal condition that mimics gastroenteritis.展开更多
Background:The development of gastric cancer(GC)encompasses precancerous conditions like chronic atrophic gastritis(CAG)and premalignant lesions of gastric cancer(PLGC).In these situations,abnormal Notch signaling res...Background:The development of gastric cancer(GC)encompasses precancerous conditions like chronic atrophic gastritis(CAG)and premalignant lesions of gastric cancer(PLGC).In these situations,abnormal Notch signaling results in mucosal impairment and the initiation of cancer.Banxia Xiexin Decoction(BXD),a well-known formula in traditional Chinese medicine(TCM),shows promise in treating gastric disorders,but its mechanisms in gastric restoration remain unclear.Methods:Using MNNG-induced CAG and PLGC rat models,BXD was administered for 12 weeks.Gastric mucosal pathology was assessed via hematoxylin-eosin staining.Proliferation(Ki-67)and angiogenesis(VEGFA)markers were evaluated by immunohistochemistry.Network pharmacology identified BXD’s targets and pathways.Notch pathway components(Notch1,Jagged1,Dll4,Hes1)were analyzed via qPCR,Western blot,and immunohistochemistry.Results:BXD significantly ameliorated mucosal atrophy,glandular structural disorder,and dysplasia in CAG and PLGC rats.Network pharmacology revealed 323 overlapping targets between BXD and PLGC,with Notch signaling as a central pathway.BXD downregulated Notch1,Jagged1,Dll4,and Hes1 expression at transcriptional and protein levels,suppressed Ki-67(proliferation)and VEGFA(angiogenesis)overexpression,and restored gastric mucosal integrity.Conclusion:BXD inhibits Notch signaling,reduces aberrant proliferation and angiogenesis,and interrupts Correa’s gastric carcinogenesis cascade.This study provides mechanistic evidence supporting BXD as a TCM-based intervention for gastric precancerous lesions.展开更多
Gastric cancer(GC)has high morbidity and mortality worldwide.Due to the absence of noticeable symptoms,diagnosing GC at an early stage is very difficult,which consequently leads to advanced GC and poor prognosis.Effec...Gastric cancer(GC)has high morbidity and mortality worldwide.Due to the absence of noticeable symptoms,diagnosing GC at an early stage is very difficult,which consequently leads to advanced GC and poor prognosis.Effective biomarkers are essential for prolonging patients’survival.Helicobacter pylori(H.pylori)infection represents the most significant risk factor for GC,with nearly all cases linked to this infection.Many non-coding RNAs(ncRNAs)are dysregulated in H.pylori-infected GC,indicating that ncRNAs may serve as biomarkers of early-stage GC.In this editorial,we discuss the study by Chen et al.Although previous studies have identified roles for miR-136 in gastric cancer proliferation,apoptosis,and invasion,none have specifically explored its relationship with H.pylori-associated gastric carcinogenesis.展开更多
BACKGROUND Gastric cancer(GC)is one of the most common malignant tumors of the digestive system worldwide,the prognosis of patients with advanced GC remains poor.AIM To evaluate the combined expression characteristics...BACKGROUND Gastric cancer(GC)is one of the most common malignant tumors of the digestive system worldwide,the prognosis of patients with advanced GC remains poor.AIM To evaluate the combined expression characteristics of cancer stem cell markers CD24 and CD133 in GC pathological tissues,and to explore their association with patients’clinicopathological parameters and postoperative survival outcomes.METHODS A total of 304 GC patients who underwent surgical treatment in our hospital from January 2018 to January 2020 were retrospectively included.Immunohistochemistry was used to detect the protein expression of CD24 and CD133 in tumor tissues,adjacent tissues,and normal gastric mucosa tissues.Based on staining intensity and the proportion of positive cells,expression levels were classified into low and high expression,while clinicopathological parameters were recorded.χ2 test was used to evaluate the correlation between expression and categorical variables,Spearman rank correlation analysis was performed to assess the correlation between the expression intensities of the two markers,and multivariate regression models were applied to identify independent risk factors influencing co-expression.Kaplan-Meier survival curves and Log-rank test were used to compare survival differences among groups with different expression patterns.RESULTS Among the 304 patients,155 cases(50.99%)were CD24 positive,including 91 low-expression and 64 highexpression;133 cases(43.75%)were CD133 positive,including 81 low-expression and 52 high-expression.There were 74 cases(24.34%)with double positivity and 81 cases(26.64%)with double negativity.Compared with tumor tissues,the positive rates of CD24 and CD133 in normal gastric tissues and adjacent tissues were significantly lower(P<0.05).Univariate analysis showed that co-expression of CD24 and CD133 in GC tissues was significantly correlated with tumor size,Lauren classification,T stage,N stage,and vascular invasion(P<0.05),but not with patient age,gender,tumor site,World Health Organization histological classification,or M stage(P>0.05).Further multivariate regression analysis suggested that tumor size,T stage,N stage,and vascular invasion were independent risk factors promoting CD24 and CD133 double positivity.Spearman rank correlation analysis indicated a moderate positive correlation between their expression intensities(r=0.420,P<0.001).During follow-up,29 of 304 patients were lost(loss rate 9.54%);146 deaths occurred.According to expression combination,there were 89 cases of CD24 single positivity(39 deaths),68 cases of CD133 single positivity(31 deaths),81 cases of double negativity(25 deaths),and 66 cases of double positivity(51 deaths).Log-rank test showed significant differences in overall survival among the four groups(χ2=20.89,P<0.001),with CD24+/CD133+group showing the worst prognosis.CONCLUSION CD24 and CD133 exhibit high positive detection rates in GC tissues,and their co-positivity is closely associated with tumor stage progression and significantly indicates unfavorable survival outcomes.The co-expression of CD24/CD133 may reflect higher aggressiveness and metastatic potential of GC,serving as a potential prognostic marker and a direction for targeted therapeutic strategies.However,as this is a single-center retrospective study with limitations such as patient loss to follow-up and sample size,further prospective,multicenter,and mechanistic studies are required to validate its clinical applicability and biological role.展开更多
BACKGROUND Chemotherapy with an immune checkpoint inhibitor is one of the standard regimens for treating advanced gastric cancer(AGC).Ascites and peritoneal dissemination are common complications and poor prognostic f...BACKGROUND Chemotherapy with an immune checkpoint inhibitor is one of the standard regimens for treating advanced gastric cancer(AGC).Ascites and peritoneal dissemination are common complications and poor prognostic factors of AGC;however,reports regarding its efficacy and safety in patients with AGC and massive ascites are limited.AIM To evaluate the safety and efficacy of nivolumab combined with chemotherapy in patients with AGC and ascites.METHODS We retrospectively collected clinical data from 124 patients with AGC who received chemotherapy plus nivolumab as first-line treatment from July 2017 to December 2024.Based on computed tomography scans,massive or moderate ascites were classified as high ascites burden(HAB),whereas mild or no ascites were classified as low ascites burden.RESULTS Ascites was detected in 47 patients(38%);26(21%)were classified into the HAB group.Patients in the HAB group exhibited a significantly poorer performance status,a higher prevalence of diffuse-type histology,and lower programmed cell death ligand 1(PD-L1)expression.Combination therapy with FOLFOX and neutropenia was significantly more common in the HAB group.Progression-free survival(PFS)(4.4 months vs 9.3 months,P=0.0012)and overall survival(OS)(7.3 months vs 21.2 months,P<0.0001)were significantly poorer in the HAB group.However,an improvement in ascites was observed in 61.5%of patients in the HAB group.PD-L1 expression did not correlate with either PFS or OS in the HAB group.CONCLUSION Nivolumab plus chemotherapy demonstrated modest efficacy and acceptable toxicity in patients with AGC and HAB.展开更多
Background: Cancer-associated fibroblasts (CAFs) play critical roles in tumor progression and immunosuppression;however, their contribution to the functional classification and personalized treatment of gastric cancer...Background: Cancer-associated fibroblasts (CAFs) play critical roles in tumor progression and immunosuppression;however, their contribution to the functional classification and personalized treatment of gastric cancerremains poorly defined. This study aimed to identify effective therapeutic targets to facilitate individualized treatmentstrategies for patients with gastric cancer. Methods: Single-cell and bulk transcriptomic analyses were integrated tocharacterize gastric cancer fibroblasts. “Seurat”, “Slingshot”, and “CellChat” were used for dimensionality reduction,trajectory inference, and cell-cell communication analyses, respectively. Key metastasis-associated fibroblast moduleswere identified using High-dimensional weighted gene co-expression network analysis (hdWGCNA) to construct aprognostic model, which was further evaluated for immune infiltration, therapeutic response, and mutational features.The expression and function of the core gene tripeptidyl peptidase 1 (TPP1) were validated through immunoblotting, PCR, and functional assays. Results: Eight fibroblast subpopulations associated with gastric cancer metastasisexhibited distinct differentiation trajectories and transcriptional heterogeneity. Prognostic analysis indicated thatmetastasis-associated fibroblasts correlated with poor clinical outcomes. The high-risk subgroup showed markedimmunosuppression, resistance to immunotherapy, and reduced mutational burden, with tumor progression-relatedpathways significantly enriched in this group. In vitro experiments further confirmed that TPP1 knockdown suppressedgastric cancer cell metastasis, invasion, and clonogenic capacity while inducing apoptosis. Conclusion: This studycharacterized the heterogeneity of gastric cancer-associated fibroblasts using single-cell transcriptomic analysis andestablished a prognostic model based on metastasis-related fibroblast markers. The model demonstrated strongpredictive performance for patient prognosis, immune landscape, and immunotherapy response. Furthermore, thefindings highlighted the pivotal role of TPP1 in gastric cancer progression and its potential as a therapeutic target.展开更多
Accumulating evidence indicates that the neuro-immune axis is central to gastric cancer pathogenesis.Dynamic,bidirectional signaling between neural circuits and immune cells promotes tumor progression,shapes an immuno...Accumulating evidence indicates that the neuro-immune axis is central to gastric cancer pathogenesis.Dynamic,bidirectional signaling between neural circuits and immune cells promotes tumor progression,shapes an immunosuppressive microenvironment,and contributes to therapeutic resistance.We synthesize current knowledge on how autonomic(sympathetic and parasympathetic)and sensory innervation regulate gastric cancer biology.These circuits act through neurotransmitters(catecholamines,acetylcholine)and neuropeptides(substance P[SP],calcitonin gene-related peptide[CGRP])to foster tumor growth and angiogenesis,facilitate perineural invasion,and enable immune evasion by recruiting suppressive myeloid and lymphoid populations and by inducing checkpoint molecule expression.We also examine how chronic stress and the microbiota-gut-brain axis intensify immunosuppression via glucocorticoid signaling and microbially derived metabolites.In parallel,we discuss why current immunotherapies achieve only modest response rates(approximately 10%-20%)in many settings,emphasizing neurally mediated mechanisms of resistance.We evaluate therapeutic strategies that target the neuro-immune axis-including pharmacological neuromodulation,selective neural ablation,and rational combination regimens-and outline how single-cell approaches and neural-tumor-microenvironment organoid models can accelerate mechanism-driven translation.This review aims to integrate current evidence from neuroscience and immuno-oncology to construct a conceptual framework for neuro-immune regulation in gastric cancer and to identify potential therapeutic strategies to overcome treatment resistance by targeting neural-tumor-immune crosstalk.展开更多
Delayed wound healing following radical gastrectomy remains an important yet underappreciated complication that prolongs hospitalization,increases costs,and undermines patient recovery.In An et al’s recent study,the ...Delayed wound healing following radical gastrectomy remains an important yet underappreciated complication that prolongs hospitalization,increases costs,and undermines patient recovery.In An et al’s recent study,the authors present a machine learning-based risk prediction approach using routinely available clinical and laboratory parameters.Among the evaluated algorithms,a decision tree model demonstrated excellent discrimination,achieving an area under the curve of 0.951 in the validation set and notably identifying all true cases of delayed wound healing at the Youden index threshold.The inclusion of variables such as drainage duration,preoperative white blood cell and neutrophil counts,alongside age and sex,highlights the pragmatic appeal of the model for early postoperative monitoring.Nevertheless,several aspects warrant critical reflection,including the reliance on a postoperative variable(drainage duration),internal validation only,and certain reporting inconsistencies.This letter underscores both the promise and the limitations of adopting interpretable machine learning models in perioperative care.We advocate for transparent reporting,external validation,and careful consideration of clinically actionable timepoints before integration into practice.Ultimately,this work represents a valuable step toward precision risk stratification in gastric cancer surgery,and sets the stage for multicenter,prospective evaluations.展开更多
Background:Gastric cancer(GC)continues to pose a significant global health challenge due to its high rates of incidence and mortality,with the majority of cases identified at advanced stages.Immunotherapy,particularly...Background:Gastric cancer(GC)continues to pose a significant global health challenge due to its high rates of incidence and mortality,with the majority of cases identified at advanced stages.Immunotherapy,particularly immune checkpoint blockades(ICBs),has demonstrated considerable therapeutic potential;however,many patients do not exhibit a favorable response.As a result,constructing a predictive model to assess ICBs'responsiveness is essential for enhancing treatment outcomes.Methods:Using consensus clustering based on anoikis-related gene expression,GC patients were stratified into two subclusters.Differences in tumor immune microenvironment,ICB resistance,genomic alterations,methylation profiles,and transcriptional networks were analyzed.A machine learning-based strategy was employed to develop a consensus anoikis-related gene signature(ARGS).Potential therapeutic targets were identified through single-cell RNA sequencing(scRNA-seq),and validation was conducted using multiplex immunofluorescence and immunohistochemistry in an in-house cohort(n=28),including 14 ICB responders and 14 nonresponders.Results:The anoikis-resistant cluster(Cluster A)was associated with poorer survival,immunosuppressive infiltration,lower tumor mutation burden,and ICB resistance.ScRNA-seq revealed high fibroblast and endothelial infiltration,with GLI3+cancer-associated fibroblasts suggesting Hedgehog pathway involvement.The ARGS model effectively stratified patients,with elevated scores associ-ated with immunotherapy resistance,enhanced AR characteristics,and poorer clinical outcomes.展开更多
BACKGROUND Inappropriate selection of patients with early gastric cancer(EGC)for endoscopic submucosal dissection(ESD)may lead to non-curative resection,necessitating additional gastrectomy.Conversely,inappropriate se...BACKGROUND Inappropriate selection of patients with early gastric cancer(EGC)for endoscopic submucosal dissection(ESD)may lead to non-curative resection,necessitating additional gastrectomy.Conversely,inappropriate selection for gastrectomy may result in overtreatment,adversely affecting patients’quality of life.Few have systematically evaluated the concordance between therapeutic indications under current Japanese guidelines and pathological criteria in EGC.To minimize noncurative resection risks while sparing unnecessary surgery for low-risk patients’,we specifically assess the suitability of Japanese guidelines in non-Japanese populations.This work aims to optimize clinical practice by refining endoscopic treatment criteria for adoption beyond Japan.AIM To evaluate EGC clinical decision accuracy by comparing therapeutic indication with postoperative pathological criteria and analyzing factors influencing discrepancies.METHODS A retrospective analysis was conducted on 796 EGC cases diagnosed at Peking University Third Hospital between January 2010 and December 2022.Cases were categorized into three groups:Same-estimated(preoperative therapeutic indication with postoperative pathological criteria matched),underestimated(preoperative ESD indication but postoperative surgical criteria),and overestimated(preoperative surgical indication but postoperative ESD criteria).The rate of discrepancy and associated risk factors were assessed.RESULTS The accuracy rates of preoperative evaluation for ESD and gastrectomy indications were 73.0%(321/430)and 76.0%(278/366),respectively.The overall discrepancy rate was 25.6%(204/796).Multivariate analysis identified tumor location in the upper-third stomach(odds ratio=2.158,95%confidence interval:1.373-3.390,P=0.001)was significantly associated with a higher likelihood of being underestimated and undifferentiated histologic type on preoperative biopsy(odds ratio=2.005,95%confidence interval:1.036-3.879,P=0.039)was more likely to be overestimated.Significant differences were observed in tumor diameter(P<0.001),depth of infiltration(P<0.001),ulcerative findings(P<0.001),and histologic type(P<0.001)between preoperative and postoperative evaluations.CONCLUSION The accuracy of preoperative EGC indications is 74.4%.Upper-third stomach and undifferentiated histology are primary discrepancy predictors.Upper-third tumors are prone to underestimation,while undifferentiated tumors are prone to overestimation.展开更多
Background:Gastric cancer(GC)remains highly lethal,with metabolic reprogramming as a key hallmark.This study explores Centromere Protein F(CENPF)’s role in GC pathogenesis,specifically its regulation of glutamine met...Background:Gastric cancer(GC)remains highly lethal,with metabolic reprogramming as a key hallmark.This study explores Centromere Protein F(CENPF)’s role in GC pathogenesis,specifically its regulation of glutamine metabolism.Methods:The Cancer Genome Atlas-Stomach Adenocarcinoma(TCGA-STAD),GSE19826,and GSE27342 datasets were analyzed by bioinformatics to identify key candidate genes in GC.The function of CENPF was assessed by flow cytometry,colony formation assays,and Cell Counting Kit-8(CCK-8).RNA sequencing,metabolic profiling,chromatin immunoprecipitation(ChIP),western blot(WB),and luciferase reporter assay were employed to investigate the fundamental mechanisms.Results:CENPF was upregulated in GC tumor samples and had a high diagnostic potential.CENPF knockdown declined cell proliferation,caused G2 arrest,and promoted apoptosis in GC cells.RNA sequencing revealed that CENPF was involved in glutamine metabolism.CENPF overexpression enhanced glutamine consumption and glutamate production,while glutamine deficiency reversed CENPF-mediated cell survival.CENPF stabilized cellular myelocytomatosis(c-Myc)by preventing proteasomal degradation,bound to the glutaminase(GLS)promoter,promoting glutamine metabolism.Overexpression of GLS or c-Myc rescued the CENPF knockdown’s inhibitory effect on GC cell growth.Conclusion:Our findings identify a new CENPF/c-Myc/GLS axis that affects glutamine metabolism and cell survival in GC,implying that CENPF might be a novel target for the treatment of GC.展开更多
Gastric ulcer(GU)represents a clinically significant manifestation of peptic ulcer disease,driven by a complex interplay of microbial,environmental,and immuneinflammatory factors.A recent cross-sectional study by Shen...Gastric ulcer(GU)represents a clinically significant manifestation of peptic ulcer disease,driven by a complex interplay of microbial,environmental,and immuneinflammatory factors.A recent cross-sectional study by Shen et al systematically evaluated six complete blood count-derived inflammatory indices:Neutrophil-tolymphocyte ratio,monocyte-to-lymphocyte ratio,platelet-to-lymphocyte ratio,systemic immune-inflammation index,systemic inflammatory response index(SIRI),and aggregate index of systemic inflammation and demonstrated their positive associations with GU prevalence,identifying SIRI as the strongest predictor.This editorial contextualizes these findings within the broader literature,clarifies that these indices reflect systemic rather than GU-specific inflammation,highlights methodological strengths and major limitations,and proposes a conceptual clinical algorithm for integrating SIRI into GU risk assessment.Future multicenter studies incorporating Helicobacter pylori infection,non-steroidal antiinflammatory drug exposure,and prospective design are essential to validate and translate these findings into clinical practice.展开更多
Wu et al recently applied multi-region 16S rRNA sequencing to characterize the gastric cancer microbiome,demonstrating improved taxonomic resolution and detection sensitivity over conventional single-region approaches...Wu et al recently applied multi-region 16S rRNA sequencing to characterize the gastric cancer microbiome,demonstrating improved taxonomic resolution and detection sensitivity over conventional single-region approaches.While the study represents a valuable methodological step forward,it remains limited by singlecenter design,lack of quantitative calibration,and insufficient control for contamination and inter-laboratory variability.This editorial critically appraises these methodological gaps and emphasizes that future efforts must focus on harmonized,consensus-driven workflows to ensure reproducibility and clinical reliability.The translational potential of multi-region 16S lies in moving from descriptive microbial profiling to actionable clinical integration,particularly for recurrence prediction,treatment-response monitoring,and perioperative complication risk assessment.By addressing these methodological,economic,and ethical challenges,the field can advance toward evidence-based and clinically deployable microbiome-guided precision oncology.展开更多
Gastric cancer(GC)is the fifth most prevalent malignancy worldwide and remains a leading cause of cancer-related mortality.Major risk factors for GC include Helicobacter pylori infection,increasing age,high dietary sa...Gastric cancer(GC)is the fifth most prevalent malignancy worldwide and remains a leading cause of cancer-related mortality.Major risk factors for GC include Helicobacter pylori infection,increasing age,high dietary salt intake,and diets deficient in vegetables and fruits.Due to the often subtle and nonspecific early symptoms,coupled with the lack of routine screening programs,a significant proportion of GC cases are diagnosed at advanced stages.The etiology of GC is multifactorial,and diagnosis is confirmed histologically through endoscopic biopsy,followed by staging via computed tomography,positron emission tomography,staging laparoscopy,and endoscopic ultrasound.Treatment strategies typically involve a multidisciplinary approach including chemotherapy,surgical resection,radiotherapy,and emerging immunotherapeutic options.Despite advances in diagnostic and therapeutic modalities,the prognosis of advanced GC remains poor,with high rates of recurrence and metastasis.In recent years,increasing attention has been given to the role of tight junction(TJ)proteins in the pathogenesis and progression of GC.TJ proteins,critical components of epithelial barrier function,have been implicated in various stages of gastric carcinogenesis,from intestinal metaplasia to invasion and metastasis.Infection and inflammation,particularly due to Helicobacter pylori,disrupt TJ integrity,compromising the gastric mucosal barrier and facilitating neoplastic transformation.This review synthesizes current evidence from PubMed,EMBASE,Google Scholar,ScienceDirect,SpringerLink,and other reputable databases to provide a comprehensive overview of the involvement of TJ proteins in GC.By elucidating the molecular interplay between TJ dysregulation and gastric tumorigenesis,this work aims to highlight the potential of TJ proteins as novel diagnostic biomarkers and therapeutic targets in GC management.展开更多
BACKGROUND Early screening,preoperative staging,and diagnosis of lymph node metastasis are crucial for improving the prognosis of gastric cancer(GC).AIM To evaluate the diagnostic value of combined multidetector compu...BACKGROUND Early screening,preoperative staging,and diagnosis of lymph node metastasis are crucial for improving the prognosis of gastric cancer(GC).AIM To evaluate the diagnostic value of combined multidetector computed tomography(MDCT)and gastrointestinal endoscopy for GC screening,preoperative staging,and lymph node metastasis detection,thereby providing a reference for clinical diagnosis and treatment.METHODS In this retrospective study clinical and imaging data of 134 patients with suspected GC who were admitted between January 2023 and October 2024 were initially reviewed.According to the inclusion and exclusion criteria,102 patients were finally enrolled in the analysis.All enrolled patients had undergone both MDCT and gastrointestinal endoscopy examinations prior to surgical intervention.Preoperative clinical staging and lymph node metastasis findings were compared with pathological results.RESULTS The combined use of MDCT and gastrointestinal endoscopy demonstrated a sensitivity of 98.53%,specificity of 97.06%,accuracy of 98.04%,positive predictive value of 98.53%,and negative predictive value of 97.06%for diagnosing GC.These factors were all significantly higher than those of MDCT or endoscopy alone(P<0.05).The accuracy rates of the combined approach for detecting clinical T and N stages were 97.06%and 92.65%,respectively,outperforming MDCT alone(86.76% and 79.41%)and endoscopy alone(85.29% and 70.59%)(P<0.05).Among 68 patients with confirmed GC,50(73.53%)were pathologically diagnosed with lymph node metastasis.The accuracy for detecting lymph node metastasis was 66.00%with endoscopy,76.00%with MDCT,and 92.00% with the combined approach,all with statistically significant differences(P<0.05).CONCLUSION The combined application of MDCT and gastrointestinal endoscopy enhanced diagnostic accuracy for GC,provided greater consistency in preoperative staging,and improved the detection of lymph node metastasis,thereby demonstrating significant clinical utility.展开更多
The changes and gastric digestive properties of gel were investigated for oxidiz ed myofibrillar protein(MP)(0–1 mmol/L H_(2)O_(2))treated by 30%substitution of NaCl with KCl,MgCl_(2),and KCl/MgCl_(2).Mild oxidation ...The changes and gastric digestive properties of gel were investigated for oxidiz ed myofibrillar protein(MP)(0–1 mmol/L H_(2)O_(2))treated by 30%substitution of NaCl with KCl,MgCl_(2),and KCl/MgCl_(2).Mild oxidation level(0.3 mmol/L H_(2)O_(2))facilitated the protein unfolding,and MgCl_(2)obviously intervened the protein selfassembly by forming the salt bridge and more disulfide bonds.At the same oxidation concentration,the sodium-reduced MP substituted with KCl formed dense network structure with better gel strength(increased by 6%–18%)and water retention in comparision to the gel without sodium reduction.The KCl-substituted gel chewing work was also relatively higher among the low-sodium samples at the first chewing cycle.Reversely,the relatively soft structure and lower gel viscosity in simulated oral chewing were found in MgCl_(2)-substituted gel.These changes decreased the contact limit between pepsin and protein for better gastric disintegration or pepsin diffusivity,and increased the proportion of small molecular weight peptides(25.83%,<5 kDa).Therefore,partial substitution of NaCl with other salt replacers could influence the physicochemical properties of low-sodium MP suspension or gel under different oxidation degree and the subsequent gastric digestion characteristics.展开更多
Objectives:Chromobox 4(CBX4),a polycomb protein family member linked to tumor pathogenesis via dysregulation,has an incompletely defined role in gastric cancer(GC).The study aimed to investigate the role and mechanism...Objectives:Chromobox 4(CBX4),a polycomb protein family member linked to tumor pathogenesis via dysregulation,has an incompletely defined role in gastric cancer(GC).The study aimed to investigate the role and mechanism of CBX4 in GC progression and evaluate its potential as a therapeutic target.Methods:CBX4 expression was assessed in GC tissues vs.adjacent non-cancerous tissues and in GC cell lines vs.normal gastric mucosal epithelial cells.Clinicopathological correlations were analyzed.Functional impacts of CBX4 were determined using knockdown and overexpression models in vitro(cell proliferation,migration,invasion)and in vivo(xenograft tumorigenesis in nude mice).Mechanistic studies evaluatedβ-catenin levels(total and nuclear)and transcriptional activity following CBX4 modulation.The functional dependency on Wnt/β-catenin signaling was tested using the pharmacological inhibitor XAV939 in CBX4-overexpressing cells.Results:CBX4 expression was significantly upregulated in GC tissues and cell lines.Elevated CBX4 levels strongly correlated with aggressive tumor characteristics,including larger tumor size,lymph node metastasis,and advanced Tumor,Node,Metastasis(TNM)stage.Functionally,CBX4 knockdown suppressed GC cell proliferation,migration,invasion in vitro,and tumorigenesis in vivo.Conversely,CBX4 overexpression enhanced these malignant traits.Mechanistically,CBX4 depletion reduced total and nuclearβ-catenin levels and inhibited its transcriptional activity,while CBX4 overexpression had the opposite effect.Critically,XAV939-mediated inhibition of Wnt/β-catenin signaling attenuated the oncogenic effects induced by CBX4 overexpression.Conclusion:CBX4 upregulation promotes GC progression viaβ-catenin signaling activation.The CBX4/β-catenin axis emerges as a promising therapeutic target,offering potential for the development of precision treatment strategies in GC management.展开更多
Objectives:Gastric cancer(GC)remains a major global health concern,and Phosphoinositide-3-Kinase Regulatory Subunit 1(PIK3R1),a regulatory subunit of the PI3K signaling pathway,may play a critical yet underexplored ro...Objectives:Gastric cancer(GC)remains a major global health concern,and Phosphoinositide-3-Kinase Regulatory Subunit 1(PIK3R1),a regulatory subunit of the PI3K signaling pathway,may play a critical yet underexplored role in GC progression.This study aimed to investigate the prognostic significance of PIK3R1 in GC and its association with the tumor immune microenvironment.Methods:PIK3R1 expression and its clinical relevance were analyzed using datasets from GC patients who underwent gastrectomy,including cohorts from The Cancer Genome Atlas(TCGA)and the Sun Yat-sen University Cancer Center(SYSUCC).Prognostic models integrating PIK3R1 expression with clinical parameters were constructed for both cohorts.The immune microenvironment associated with PIK3R1 expression was assessed through immunohistochemistry and single-cell RNA sequencing.In vitro assays were conducted to evaluate the effects of PIK3R1 on GC cell proliferation and migration.Results:PIK3R1 was significantly overexpressed in GC tissues and was closely associated with aggressive tumor characteristics and poor clinical outcomes.A nomogram combining PIK3R1 expression with clinicopathological features effectively predicted patient prognosis.Knockdown of PIK3R1 in GC cells reduced proliferation and migration in vitro.Immunological profiling revealed that high PIK3R1 expression correlated with increased infiltration of forkhead box protein P3(Foxp3^(+))and cluster of differentiation 73(CD73^(+))T cells.Patients with low PIK3R1 expression and low CD73^(+)T cell infiltration had significantly better survival.Conclusions:PIK3R1 overexpression is linked to poor prognosis in GC and influences the extent of immune cell infiltration within the tumor microenvironment.A novel prognostic model integrating PIK3R1 and CD73 expression with clinical parameters was established to stratify GC patients into distinct risk groups,offering potential value for personalized therapeutic strategies.展开更多
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.Lap...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(LECSSNNS)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.展开更多
Gastric cancer is a significant global and Chinese health issue,primarily linked to Helicobacter pylori(H.pylori)infection[1],classified as a carcinogen by the U.S.in 2022.The Correa cascade model outlines the progres...Gastric cancer is a significant global and Chinese health issue,primarily linked to Helicobacter pylori(H.pylori)infection[1],classified as a carcinogen by the U.S.in 2022.The Correa cascade model outlines the progression from H.pylori gastritis cancer via precancerous stages[2].Current antibiotic-based treatment regimens are facing increasingly severe challenges of drug resistance[3].展开更多
文摘Acute presentation of vomiting is a very common presenting complaint in the emergency department(ED).While majority of such complaints can be attributed to benign,self-limiting causes such as gastroenteritis,rarer alternative diagnoses should be considered depending on the patient's progress after initial treatment.Here,we present a case of gastric volvulus(GV),a rare but potentially fatal condition that mimics gastroenteritis.
基金supported by the National Natural Science Foundation of China(Grant No.82274442)the Key Research Project in Traditional Chinese Medicine of Tianjin Municipal Health Commission(Grant No.202007)the Integrated Traditional Chinese and Western Medicine Research Project of Tianjin Municipal Health Commission(Grant No.2023134).
文摘Background:The development of gastric cancer(GC)encompasses precancerous conditions like chronic atrophic gastritis(CAG)and premalignant lesions of gastric cancer(PLGC).In these situations,abnormal Notch signaling results in mucosal impairment and the initiation of cancer.Banxia Xiexin Decoction(BXD),a well-known formula in traditional Chinese medicine(TCM),shows promise in treating gastric disorders,but its mechanisms in gastric restoration remain unclear.Methods:Using MNNG-induced CAG and PLGC rat models,BXD was administered for 12 weeks.Gastric mucosal pathology was assessed via hematoxylin-eosin staining.Proliferation(Ki-67)and angiogenesis(VEGFA)markers were evaluated by immunohistochemistry.Network pharmacology identified BXD’s targets and pathways.Notch pathway components(Notch1,Jagged1,Dll4,Hes1)were analyzed via qPCR,Western blot,and immunohistochemistry.Results:BXD significantly ameliorated mucosal atrophy,glandular structural disorder,and dysplasia in CAG and PLGC rats.Network pharmacology revealed 323 overlapping targets between BXD and PLGC,with Notch signaling as a central pathway.BXD downregulated Notch1,Jagged1,Dll4,and Hes1 expression at transcriptional and protein levels,suppressed Ki-67(proliferation)and VEGFA(angiogenesis)overexpression,and restored gastric mucosal integrity.Conclusion:BXD inhibits Notch signaling,reduces aberrant proliferation and angiogenesis,and interrupts Correa’s gastric carcinogenesis cascade.This study provides mechanistic evidence supporting BXD as a TCM-based intervention for gastric precancerous lesions.
基金Supported by The Joint Fund of Zhejiang Provincial Natural Science Foundation of China,No.LKLY25H160002.
文摘Gastric cancer(GC)has high morbidity and mortality worldwide.Due to the absence of noticeable symptoms,diagnosing GC at an early stage is very difficult,which consequently leads to advanced GC and poor prognosis.Effective biomarkers are essential for prolonging patients’survival.Helicobacter pylori(H.pylori)infection represents the most significant risk factor for GC,with nearly all cases linked to this infection.Many non-coding RNAs(ncRNAs)are dysregulated in H.pylori-infected GC,indicating that ncRNAs may serve as biomarkers of early-stage GC.In this editorial,we discuss the study by Chen et al.Although previous studies have identified roles for miR-136 in gastric cancer proliferation,apoptosis,and invasion,none have specifically explored its relationship with H.pylori-associated gastric carcinogenesis.
基金National Natural Science Foundation of China,No.82003223and China Postdoctoral Science Foundation,No.2020M671398.
文摘BACKGROUND Gastric cancer(GC)is one of the most common malignant tumors of the digestive system worldwide,the prognosis of patients with advanced GC remains poor.AIM To evaluate the combined expression characteristics of cancer stem cell markers CD24 and CD133 in GC pathological tissues,and to explore their association with patients’clinicopathological parameters and postoperative survival outcomes.METHODS A total of 304 GC patients who underwent surgical treatment in our hospital from January 2018 to January 2020 were retrospectively included.Immunohistochemistry was used to detect the protein expression of CD24 and CD133 in tumor tissues,adjacent tissues,and normal gastric mucosa tissues.Based on staining intensity and the proportion of positive cells,expression levels were classified into low and high expression,while clinicopathological parameters were recorded.χ2 test was used to evaluate the correlation between expression and categorical variables,Spearman rank correlation analysis was performed to assess the correlation between the expression intensities of the two markers,and multivariate regression models were applied to identify independent risk factors influencing co-expression.Kaplan-Meier survival curves and Log-rank test were used to compare survival differences among groups with different expression patterns.RESULTS Among the 304 patients,155 cases(50.99%)were CD24 positive,including 91 low-expression and 64 highexpression;133 cases(43.75%)were CD133 positive,including 81 low-expression and 52 high-expression.There were 74 cases(24.34%)with double positivity and 81 cases(26.64%)with double negativity.Compared with tumor tissues,the positive rates of CD24 and CD133 in normal gastric tissues and adjacent tissues were significantly lower(P<0.05).Univariate analysis showed that co-expression of CD24 and CD133 in GC tissues was significantly correlated with tumor size,Lauren classification,T stage,N stage,and vascular invasion(P<0.05),but not with patient age,gender,tumor site,World Health Organization histological classification,or M stage(P>0.05).Further multivariate regression analysis suggested that tumor size,T stage,N stage,and vascular invasion were independent risk factors promoting CD24 and CD133 double positivity.Spearman rank correlation analysis indicated a moderate positive correlation between their expression intensities(r=0.420,P<0.001).During follow-up,29 of 304 patients were lost(loss rate 9.54%);146 deaths occurred.According to expression combination,there were 89 cases of CD24 single positivity(39 deaths),68 cases of CD133 single positivity(31 deaths),81 cases of double negativity(25 deaths),and 66 cases of double positivity(51 deaths).Log-rank test showed significant differences in overall survival among the four groups(χ2=20.89,P<0.001),with CD24+/CD133+group showing the worst prognosis.CONCLUSION CD24 and CD133 exhibit high positive detection rates in GC tissues,and their co-positivity is closely associated with tumor stage progression and significantly indicates unfavorable survival outcomes.The co-expression of CD24/CD133 may reflect higher aggressiveness and metastatic potential of GC,serving as a potential prognostic marker and a direction for targeted therapeutic strategies.However,as this is a single-center retrospective study with limitations such as patient loss to follow-up and sample size,further prospective,multicenter,and mechanistic studies are required to validate its clinical applicability and biological role.
文摘BACKGROUND Chemotherapy with an immune checkpoint inhibitor is one of the standard regimens for treating advanced gastric cancer(AGC).Ascites and peritoneal dissemination are common complications and poor prognostic factors of AGC;however,reports regarding its efficacy and safety in patients with AGC and massive ascites are limited.AIM To evaluate the safety and efficacy of nivolumab combined with chemotherapy in patients with AGC and ascites.METHODS We retrospectively collected clinical data from 124 patients with AGC who received chemotherapy plus nivolumab as first-line treatment from July 2017 to December 2024.Based on computed tomography scans,massive or moderate ascites were classified as high ascites burden(HAB),whereas mild or no ascites were classified as low ascites burden.RESULTS Ascites was detected in 47 patients(38%);26(21%)were classified into the HAB group.Patients in the HAB group exhibited a significantly poorer performance status,a higher prevalence of diffuse-type histology,and lower programmed cell death ligand 1(PD-L1)expression.Combination therapy with FOLFOX and neutropenia was significantly more common in the HAB group.Progression-free survival(PFS)(4.4 months vs 9.3 months,P=0.0012)and overall survival(OS)(7.3 months vs 21.2 months,P<0.0001)were significantly poorer in the HAB group.However,an improvement in ascites was observed in 61.5%of patients in the HAB group.PD-L1 expression did not correlate with either PFS or OS in the HAB group.CONCLUSION Nivolumab plus chemotherapy demonstrated modest efficacy and acceptable toxicity in patients with AGC and HAB.
基金funded by the Key Research and Development and Promotion Project of Henan Province(Grant No.232102310130)。
文摘Background: Cancer-associated fibroblasts (CAFs) play critical roles in tumor progression and immunosuppression;however, their contribution to the functional classification and personalized treatment of gastric cancerremains poorly defined. This study aimed to identify effective therapeutic targets to facilitate individualized treatmentstrategies for patients with gastric cancer. Methods: Single-cell and bulk transcriptomic analyses were integrated tocharacterize gastric cancer fibroblasts. “Seurat”, “Slingshot”, and “CellChat” were used for dimensionality reduction,trajectory inference, and cell-cell communication analyses, respectively. Key metastasis-associated fibroblast moduleswere identified using High-dimensional weighted gene co-expression network analysis (hdWGCNA) to construct aprognostic model, which was further evaluated for immune infiltration, therapeutic response, and mutational features.The expression and function of the core gene tripeptidyl peptidase 1 (TPP1) were validated through immunoblotting, PCR, and functional assays. Results: Eight fibroblast subpopulations associated with gastric cancer metastasisexhibited distinct differentiation trajectories and transcriptional heterogeneity. Prognostic analysis indicated thatmetastasis-associated fibroblasts correlated with poor clinical outcomes. The high-risk subgroup showed markedimmunosuppression, resistance to immunotherapy, and reduced mutational burden, with tumor progression-relatedpathways significantly enriched in this group. In vitro experiments further confirmed that TPP1 knockdown suppressedgastric cancer cell metastasis, invasion, and clonogenic capacity while inducing apoptosis. Conclusion: This studycharacterized the heterogeneity of gastric cancer-associated fibroblasts using single-cell transcriptomic analysis andestablished a prognostic model based on metastasis-related fibroblast markers. The model demonstrated strongpredictive performance for patient prognosis, immune landscape, and immunotherapy response. Furthermore, thefindings highlighted the pivotal role of TPP1 in gastric cancer progression and its potential as a therapeutic target.
文摘Accumulating evidence indicates that the neuro-immune axis is central to gastric cancer pathogenesis.Dynamic,bidirectional signaling between neural circuits and immune cells promotes tumor progression,shapes an immunosuppressive microenvironment,and contributes to therapeutic resistance.We synthesize current knowledge on how autonomic(sympathetic and parasympathetic)and sensory innervation regulate gastric cancer biology.These circuits act through neurotransmitters(catecholamines,acetylcholine)and neuropeptides(substance P[SP],calcitonin gene-related peptide[CGRP])to foster tumor growth and angiogenesis,facilitate perineural invasion,and enable immune evasion by recruiting suppressive myeloid and lymphoid populations and by inducing checkpoint molecule expression.We also examine how chronic stress and the microbiota-gut-brain axis intensify immunosuppression via glucocorticoid signaling and microbially derived metabolites.In parallel,we discuss why current immunotherapies achieve only modest response rates(approximately 10%-20%)in many settings,emphasizing neurally mediated mechanisms of resistance.We evaluate therapeutic strategies that target the neuro-immune axis-including pharmacological neuromodulation,selective neural ablation,and rational combination regimens-and outline how single-cell approaches and neural-tumor-microenvironment organoid models can accelerate mechanism-driven translation.This review aims to integrate current evidence from neuroscience and immuno-oncology to construct a conceptual framework for neuro-immune regulation in gastric cancer and to identify potential therapeutic strategies to overcome treatment resistance by targeting neural-tumor-immune crosstalk.
文摘Delayed wound healing following radical gastrectomy remains an important yet underappreciated complication that prolongs hospitalization,increases costs,and undermines patient recovery.In An et al’s recent study,the authors present a machine learning-based risk prediction approach using routinely available clinical and laboratory parameters.Among the evaluated algorithms,a decision tree model demonstrated excellent discrimination,achieving an area under the curve of 0.951 in the validation set and notably identifying all true cases of delayed wound healing at the Youden index threshold.The inclusion of variables such as drainage duration,preoperative white blood cell and neutrophil counts,alongside age and sex,highlights the pragmatic appeal of the model for early postoperative monitoring.Nevertheless,several aspects warrant critical reflection,including the reliance on a postoperative variable(drainage duration),internal validation only,and certain reporting inconsistencies.This letter underscores both the promise and the limitations of adopting interpretable machine learning models in perioperative care.We advocate for transparent reporting,external validation,and careful consideration of clinically actionable timepoints before integration into practice.Ultimately,this work represents a valuable step toward precision risk stratification in gastric cancer surgery,and sets the stage for multicenter,prospective evaluations.
基金National Science and Technology Major Project,Grant/Award Number:2024ZD0533300Excellent Doctor Program of Zhongnan Hospital of Wuhan University,Grant/Award Number:ZNYB2021009。
文摘Background:Gastric cancer(GC)continues to pose a significant global health challenge due to its high rates of incidence and mortality,with the majority of cases identified at advanced stages.Immunotherapy,particularly immune checkpoint blockades(ICBs),has demonstrated considerable therapeutic potential;however,many patients do not exhibit a favorable response.As a result,constructing a predictive model to assess ICBs'responsiveness is essential for enhancing treatment outcomes.Methods:Using consensus clustering based on anoikis-related gene expression,GC patients were stratified into two subclusters.Differences in tumor immune microenvironment,ICB resistance,genomic alterations,methylation profiles,and transcriptional networks were analyzed.A machine learning-based strategy was employed to develop a consensus anoikis-related gene signature(ARGS).Potential therapeutic targets were identified through single-cell RNA sequencing(scRNA-seq),and validation was conducted using multiplex immunofluorescence and immunohistochemistry in an in-house cohort(n=28),including 14 ICB responders and 14 nonresponders.Results:The anoikis-resistant cluster(Cluster A)was associated with poorer survival,immunosuppressive infiltration,lower tumor mutation burden,and ICB resistance.ScRNA-seq revealed high fibroblast and endothelial infiltration,with GLI3+cancer-associated fibroblasts suggesting Hedgehog pathway involvement.The ARGS model effectively stratified patients,with elevated scores associ-ated with immunotherapy resistance,enhanced AR characteristics,and poorer clinical outcomes.
基金Supported by China Health&Medical Development Foundation,No.M2021551.
文摘BACKGROUND Inappropriate selection of patients with early gastric cancer(EGC)for endoscopic submucosal dissection(ESD)may lead to non-curative resection,necessitating additional gastrectomy.Conversely,inappropriate selection for gastrectomy may result in overtreatment,adversely affecting patients’quality of life.Few have systematically evaluated the concordance between therapeutic indications under current Japanese guidelines and pathological criteria in EGC.To minimize noncurative resection risks while sparing unnecessary surgery for low-risk patients’,we specifically assess the suitability of Japanese guidelines in non-Japanese populations.This work aims to optimize clinical practice by refining endoscopic treatment criteria for adoption beyond Japan.AIM To evaluate EGC clinical decision accuracy by comparing therapeutic indication with postoperative pathological criteria and analyzing factors influencing discrepancies.METHODS A retrospective analysis was conducted on 796 EGC cases diagnosed at Peking University Third Hospital between January 2010 and December 2022.Cases were categorized into three groups:Same-estimated(preoperative therapeutic indication with postoperative pathological criteria matched),underestimated(preoperative ESD indication but postoperative surgical criteria),and overestimated(preoperative surgical indication but postoperative ESD criteria).The rate of discrepancy and associated risk factors were assessed.RESULTS The accuracy rates of preoperative evaluation for ESD and gastrectomy indications were 73.0%(321/430)and 76.0%(278/366),respectively.The overall discrepancy rate was 25.6%(204/796).Multivariate analysis identified tumor location in the upper-third stomach(odds ratio=2.158,95%confidence interval:1.373-3.390,P=0.001)was significantly associated with a higher likelihood of being underestimated and undifferentiated histologic type on preoperative biopsy(odds ratio=2.005,95%confidence interval:1.036-3.879,P=0.039)was more likely to be overestimated.Significant differences were observed in tumor diameter(P<0.001),depth of infiltration(P<0.001),ulcerative findings(P<0.001),and histologic type(P<0.001)between preoperative and postoperative evaluations.CONCLUSION The accuracy of preoperative EGC indications is 74.4%.Upper-third stomach and undifferentiated histology are primary discrepancy predictors.Upper-third tumors are prone to underestimation,while undifferentiated tumors are prone to overestimation.
基金funded by the Medical and Health Technology Development Programin Shandong Province.Project number:202303031600.
文摘Background:Gastric cancer(GC)remains highly lethal,with metabolic reprogramming as a key hallmark.This study explores Centromere Protein F(CENPF)’s role in GC pathogenesis,specifically its regulation of glutamine metabolism.Methods:The Cancer Genome Atlas-Stomach Adenocarcinoma(TCGA-STAD),GSE19826,and GSE27342 datasets were analyzed by bioinformatics to identify key candidate genes in GC.The function of CENPF was assessed by flow cytometry,colony formation assays,and Cell Counting Kit-8(CCK-8).RNA sequencing,metabolic profiling,chromatin immunoprecipitation(ChIP),western blot(WB),and luciferase reporter assay were employed to investigate the fundamental mechanisms.Results:CENPF was upregulated in GC tumor samples and had a high diagnostic potential.CENPF knockdown declined cell proliferation,caused G2 arrest,and promoted apoptosis in GC cells.RNA sequencing revealed that CENPF was involved in glutamine metabolism.CENPF overexpression enhanced glutamine consumption and glutamate production,while glutamine deficiency reversed CENPF-mediated cell survival.CENPF stabilized cellular myelocytomatosis(c-Myc)by preventing proteasomal degradation,bound to the glutaminase(GLS)promoter,promoting glutamine metabolism.Overexpression of GLS or c-Myc rescued the CENPF knockdown’s inhibitory effect on GC cell growth.Conclusion:Our findings identify a new CENPF/c-Myc/GLS axis that affects glutamine metabolism and cell survival in GC,implying that CENPF might be a novel target for the treatment of GC.
基金Supported by the National Natural Science Foundation of China,No.82170406 and No.81970238.
文摘Gastric ulcer(GU)represents a clinically significant manifestation of peptic ulcer disease,driven by a complex interplay of microbial,environmental,and immuneinflammatory factors.A recent cross-sectional study by Shen et al systematically evaluated six complete blood count-derived inflammatory indices:Neutrophil-tolymphocyte ratio,monocyte-to-lymphocyte ratio,platelet-to-lymphocyte ratio,systemic immune-inflammation index,systemic inflammatory response index(SIRI),and aggregate index of systemic inflammation and demonstrated their positive associations with GU prevalence,identifying SIRI as the strongest predictor.This editorial contextualizes these findings within the broader literature,clarifies that these indices reflect systemic rather than GU-specific inflammation,highlights methodological strengths and major limitations,and proposes a conceptual clinical algorithm for integrating SIRI into GU risk assessment.Future multicenter studies incorporating Helicobacter pylori infection,non-steroidal antiinflammatory drug exposure,and prospective design are essential to validate and translate these findings into clinical practice.
文摘Wu et al recently applied multi-region 16S rRNA sequencing to characterize the gastric cancer microbiome,demonstrating improved taxonomic resolution and detection sensitivity over conventional single-region approaches.While the study represents a valuable methodological step forward,it remains limited by singlecenter design,lack of quantitative calibration,and insufficient control for contamination and inter-laboratory variability.This editorial critically appraises these methodological gaps and emphasizes that future efforts must focus on harmonized,consensus-driven workflows to ensure reproducibility and clinical reliability.The translational potential of multi-region 16S lies in moving from descriptive microbial profiling to actionable clinical integration,particularly for recurrence prediction,treatment-response monitoring,and perioperative complication risk assessment.By addressing these methodological,economic,and ethical challenges,the field can advance toward evidence-based and clinically deployable microbiome-guided precision oncology.
文摘Gastric cancer(GC)is the fifth most prevalent malignancy worldwide and remains a leading cause of cancer-related mortality.Major risk factors for GC include Helicobacter pylori infection,increasing age,high dietary salt intake,and diets deficient in vegetables and fruits.Due to the often subtle and nonspecific early symptoms,coupled with the lack of routine screening programs,a significant proportion of GC cases are diagnosed at advanced stages.The etiology of GC is multifactorial,and diagnosis is confirmed histologically through endoscopic biopsy,followed by staging via computed tomography,positron emission tomography,staging laparoscopy,and endoscopic ultrasound.Treatment strategies typically involve a multidisciplinary approach including chemotherapy,surgical resection,radiotherapy,and emerging immunotherapeutic options.Despite advances in diagnostic and therapeutic modalities,the prognosis of advanced GC remains poor,with high rates of recurrence and metastasis.In recent years,increasing attention has been given to the role of tight junction(TJ)proteins in the pathogenesis and progression of GC.TJ proteins,critical components of epithelial barrier function,have been implicated in various stages of gastric carcinogenesis,from intestinal metaplasia to invasion and metastasis.Infection and inflammation,particularly due to Helicobacter pylori,disrupt TJ integrity,compromising the gastric mucosal barrier and facilitating neoplastic transformation.This review synthesizes current evidence from PubMed,EMBASE,Google Scholar,ScienceDirect,SpringerLink,and other reputable databases to provide a comprehensive overview of the involvement of TJ proteins in GC.By elucidating the molecular interplay between TJ dysregulation and gastric tumorigenesis,this work aims to highlight the potential of TJ proteins as novel diagnostic biomarkers and therapeutic targets in GC management.
文摘BACKGROUND Early screening,preoperative staging,and diagnosis of lymph node metastasis are crucial for improving the prognosis of gastric cancer(GC).AIM To evaluate the diagnostic value of combined multidetector computed tomography(MDCT)and gastrointestinal endoscopy for GC screening,preoperative staging,and lymph node metastasis detection,thereby providing a reference for clinical diagnosis and treatment.METHODS In this retrospective study clinical and imaging data of 134 patients with suspected GC who were admitted between January 2023 and October 2024 were initially reviewed.According to the inclusion and exclusion criteria,102 patients were finally enrolled in the analysis.All enrolled patients had undergone both MDCT and gastrointestinal endoscopy examinations prior to surgical intervention.Preoperative clinical staging and lymph node metastasis findings were compared with pathological results.RESULTS The combined use of MDCT and gastrointestinal endoscopy demonstrated a sensitivity of 98.53%,specificity of 97.06%,accuracy of 98.04%,positive predictive value of 98.53%,and negative predictive value of 97.06%for diagnosing GC.These factors were all significantly higher than those of MDCT or endoscopy alone(P<0.05).The accuracy rates of the combined approach for detecting clinical T and N stages were 97.06%and 92.65%,respectively,outperforming MDCT alone(86.76% and 79.41%)and endoscopy alone(85.29% and 70.59%)(P<0.05).Among 68 patients with confirmed GC,50(73.53%)were pathologically diagnosed with lymph node metastasis.The accuracy for detecting lymph node metastasis was 66.00%with endoscopy,76.00%with MDCT,and 92.00% with the combined approach,all with statistically significant differences(P<0.05).CONCLUSION The combined application of MDCT and gastrointestinal endoscopy enhanced diagnostic accuracy for GC,provided greater consistency in preoperative staging,and improved the detection of lymph node metastasis,thereby demonstrating significant clinical utility.
基金supported by the National Natural Science Foundation of China(32172257)the Ministry of Science and Technology of the People’s Republic of China(DL2022163005L)+2 种基金the Science and Technology Program of Qingyuan(2022KJJH018)the Postdoctoral Innovative Talent Support Program(BX20230130)the 111 Project(B17018).
文摘The changes and gastric digestive properties of gel were investigated for oxidiz ed myofibrillar protein(MP)(0–1 mmol/L H_(2)O_(2))treated by 30%substitution of NaCl with KCl,MgCl_(2),and KCl/MgCl_(2).Mild oxidation level(0.3 mmol/L H_(2)O_(2))facilitated the protein unfolding,and MgCl_(2)obviously intervened the protein selfassembly by forming the salt bridge and more disulfide bonds.At the same oxidation concentration,the sodium-reduced MP substituted with KCl formed dense network structure with better gel strength(increased by 6%–18%)and water retention in comparision to the gel without sodium reduction.The KCl-substituted gel chewing work was also relatively higher among the low-sodium samples at the first chewing cycle.Reversely,the relatively soft structure and lower gel viscosity in simulated oral chewing were found in MgCl_(2)-substituted gel.These changes decreased the contact limit between pepsin and protein for better gastric disintegration or pepsin diffusivity,and increased the proportion of small molecular weight peptides(25.83%,<5 kDa).Therefore,partial substitution of NaCl with other salt replacers could influence the physicochemical properties of low-sodium MP suspension or gel under different oxidation degree and the subsequent gastric digestion characteristics.
基金funded by the National Natural Science Foundation of China(Grant No.82473566)the Science and Technology Plan Project of Jiangsu Province(Grant No.BE2022728)+2 种基金the Natural Science Foundation of the Higher Education Institutions of Jiangsu Province(Grant No.24KJB320015)the Postgraduate Research&Practice Innovation Program of Jiangsu Province(Grant Nos.SJCX24_1822 and SJCX21_1354)the Soochow University Open Topic from Jiangsu Engineering Laboratory of Novel Functional Polymeric Materials(Grant No.SDGC2312).
文摘Objectives:Chromobox 4(CBX4),a polycomb protein family member linked to tumor pathogenesis via dysregulation,has an incompletely defined role in gastric cancer(GC).The study aimed to investigate the role and mechanism of CBX4 in GC progression and evaluate its potential as a therapeutic target.Methods:CBX4 expression was assessed in GC tissues vs.adjacent non-cancerous tissues and in GC cell lines vs.normal gastric mucosal epithelial cells.Clinicopathological correlations were analyzed.Functional impacts of CBX4 were determined using knockdown and overexpression models in vitro(cell proliferation,migration,invasion)and in vivo(xenograft tumorigenesis in nude mice).Mechanistic studies evaluatedβ-catenin levels(total and nuclear)and transcriptional activity following CBX4 modulation.The functional dependency on Wnt/β-catenin signaling was tested using the pharmacological inhibitor XAV939 in CBX4-overexpressing cells.Results:CBX4 expression was significantly upregulated in GC tissues and cell lines.Elevated CBX4 levels strongly correlated with aggressive tumor characteristics,including larger tumor size,lymph node metastasis,and advanced Tumor,Node,Metastasis(TNM)stage.Functionally,CBX4 knockdown suppressed GC cell proliferation,migration,invasion in vitro,and tumorigenesis in vivo.Conversely,CBX4 overexpression enhanced these malignant traits.Mechanistically,CBX4 depletion reduced total and nuclearβ-catenin levels and inhibited its transcriptional activity,while CBX4 overexpression had the opposite effect.Critically,XAV939-mediated inhibition of Wnt/β-catenin signaling attenuated the oncogenic effects induced by CBX4 overexpression.Conclusion:CBX4 upregulation promotes GC progression viaβ-catenin signaling activation.The CBX4/β-catenin axis emerges as a promising therapeutic target,offering potential for the development of precision treatment strategies in GC management.
基金supported by the National Natural Science Foundation of China(grant no.81602426).
文摘Objectives:Gastric cancer(GC)remains a major global health concern,and Phosphoinositide-3-Kinase Regulatory Subunit 1(PIK3R1),a regulatory subunit of the PI3K signaling pathway,may play a critical yet underexplored role in GC progression.This study aimed to investigate the prognostic significance of PIK3R1 in GC and its association with the tumor immune microenvironment.Methods:PIK3R1 expression and its clinical relevance were analyzed using datasets from GC patients who underwent gastrectomy,including cohorts from The Cancer Genome Atlas(TCGA)and the Sun Yat-sen University Cancer Center(SYSUCC).Prognostic models integrating PIK3R1 expression with clinical parameters were constructed for both cohorts.The immune microenvironment associated with PIK3R1 expression was assessed through immunohistochemistry and single-cell RNA sequencing.In vitro assays were conducted to evaluate the effects of PIK3R1 on GC cell proliferation and migration.Results:PIK3R1 was significantly overexpressed in GC tissues and was closely associated with aggressive tumor characteristics and poor clinical outcomes.A nomogram combining PIK3R1 expression with clinicopathological features effectively predicted patient prognosis.Knockdown of PIK3R1 in GC cells reduced proliferation and migration in vitro.Immunological profiling revealed that high PIK3R1 expression correlated with increased infiltration of forkhead box protein P3(Foxp3^(+))and cluster of differentiation 73(CD73^(+))T cells.Patients with low PIK3R1 expression and low CD73^(+)T cell infiltration had significantly better survival.Conclusions:PIK3R1 overexpression is linked to poor prognosis in GC and influences the extent of immune cell infiltration within the tumor microenvironment.A novel prognostic model integrating PIK3R1 and CD73 expression with clinical parameters was established to stratify GC patients into distinct risk groups,offering potential value for personalized therapeutic strategies.
基金supported by National Key Research and Development Program of China(No.2023YFC2507406)National Natural Science Foundation of China(No.82300646)+6 种基金Beijing Natural Science Foundation(No.7232334)Beijing Municipal Administration of Hospitals Incubating Program(No.PX2024002,PX2020001)Capital Fund for Health Development Scientific Research(No.2024-2-2028)Beijing Municipal Science&Technology Commission AI+Health Collaborative Innovation Cultivation Project(No.Z241100007724004)Research Ward Excellence Program of Beijing Municipal Health Commission(No.BRWEP2024W162020100,BRWEP2024W162020112,BRWEP2024W162020114)Excellent Plan for Capital Medicine Scientific and Technological Innovation Achievement Transformation Promotion Plan(No.YC202401QX0824)Clinical Scientific Research Fund of Beijing Integrated Medical Association[No.ZHKY-2025-1869(B012)]。
文摘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(LECSSNNS)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.
基金supported by the National Natural Science Foundation of China(82573571,82470594)National Science and Technology Major Project(2025ZD0545300)+2 种基金Shanghai 2025 Basic Research Plan Natural Science Foundation(25ZR1401393)Key Project of Heilongjiang Provincial Joint Fund of Natural Science Foundation(ZL2025H017)the First Batch of Open Topics of the Shanghai Key Laboratory of Nautical Medicine and Translation of Drugs and Medical Devices(2025QN13).
文摘Gastric cancer is a significant global and Chinese health issue,primarily linked to Helicobacter pylori(H.pylori)infection[1],classified as a carcinogen by the U.S.in 2022.The Correa cascade model outlines the progression from H.pylori gastritis cancer via precancerous stages[2].Current antibiotic-based treatment regimens are facing increasingly severe challenges of drug resistance[3].
