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
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 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
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
The gastroprotective activity of water extracts from Citrus reticulata'Chachi'leaves(JY)was investigated,and its potential action mechanisms were revealed using network pharmacology.First,the main chemical com...The gastroprotective activity of water extracts from Citrus reticulata'Chachi'leaves(JY)was investigated,and its potential action mechanisms were revealed using network pharmacology.First,the main chemical components of JY were identified using high performance liquid chromatography coupled to quadrupole time-of-flight tandem mass spectrometry,14 compounds were preliminarily identified,with flavonoids being the primary components.Next,the protective effect of JY on ethanol-induced damage was investigated in vitro.An MTT assay showed that JY could significantly promote the proliferation of GES-1 cells and reduce the damage caused by ethanol.A gastric ulcer model was induced in mice using ethanol,and JY(1,2,and 4 mg/kg)was orally administered to the mice to counteract ethanol-induced gastric ulcers.Pretreatment with JY reduced the severity of ethanol-induced gastric injury.Histopathological results showed that JY enhanced the cell structure of gastric tissue,increased the secretion of gastric mucosal mucus,and reduced gastric edema caused by ethanol injury.JY significantly decreased the levels of pro-inflammatory factors,including interleukin(IL)-1β,IL-6,and tumor necrosis factorα,in the serum.Additionally,JY increased the levels of prostaglandin E2 and the activity of total superoxide dismutase,while significantly reducing the levels of the lipid peroxidation product malondialdehyde in gastric tissue.In parallel,JY significantly upregulated the mRNA expressions of copper/zinc superoxide dismutase(Cu/Zn-SOD),manganese superoxide dismutase(Mn-SOD),and glutathione peroxidase(GPx)to alleviate oxidative stress.JY also promoted the healing of gastric ulcers by upregulating the mRNA expressions of vascular endothelial growth factor(VEGF)and epidermal growth factor receptor(EGFR).Finally,network pharmacology was used to analyze the potential bioactive substances in JY and their mechanisms.The results indicated that the protective effect of JY might be related to flavonoids and that JY exerts its gastroprotective effects by participating in the PI3K-Akt and VEGF signaling pathways.These findings suggest that JY could be a valuable natural resource for preventing ethanol-induced gastric injury.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
Early-stage gastric cancer;Extent of lymph node dissection;D1 dissection;D2 dissection;Recurrence rate;Survival rateObjective:To investigate the impact of different lymph node dissection scopes on postoperative recurr...Early-stage gastric cancer;Extent of lymph node dissection;D1 dissection;D2 dissection;Recurrence rate;Survival rateObjective:To investigate the impact of different lymph node dissection scopes on postoperative recurrence and survival rates in patients with early gastric cancer,providing evidence-based support for optimizing clinical surgical plans.Methods:A retrospective analysis was conducted on the clinical data of 100 patients with early gastric cancer who underwent surgical treatment at our hospital from October 2021 to October 2023.Patients were divided into Group D1(n=50)and Group D2(n=50)based on the extent of lymph node dissection.Group D1 underwent limited lymph node dissection(dissection of the first station of lymph nodes around the stomach),while Group D2 underwent standard lymph node dissection(dissection of the first and second stations of lymph nodes around the stomach).Surgical-related indicators,the incidence of postoperative complications,the 2-year recurrence rate,and the 2-year survival rate were compared between the two groups of patients.Results:The operative time,intraoperative blood loss,postoperative hospital stay,and the number of lymph nodes dissected were significantly higher in the D2 group than in the D1 group(all P<0.001).The overall incidence of postoperative complications was higher in the D1 group than in the D2 group,but the difference was not statistically significant(χ^(2)=0.884,P=0.766).After a 2-year follow-up,the recurrence rate was significantly higher in the D1 group than in the D2 group(χ^(2)=4.000,P=0.046).The 2-year survival rate was significantly lower in the D1 group than in the D2 group(χ^(2)=5.005,P=0.025).A total of 100 patients with early-stage gastric cancer were grouped according to the depth of invasion,degree of differentiation,and lymph node metastasis status,and the recurrence rates of different subgroups were compared.The results showed that the recurrence rate was higher in patients with T1b stage than in those with T1a stage(χ^(2)=5.005,P=0.025),higher in poorly differentiated patients than in moderately and well-differentiated patients(χ^(2)=4.155,P=0.042),and higher in patients with lymph node metastasis than in those without lymph node metastasis(χ^(2)=4.512,P=0.034).Conclusion:Compared with D1 limited lymph node dissection,D2 standard lymph node dissection can significantly reduce the postoperative recurrence rate and improve the 2-year survival rate in patients with early-stage gastric cancer without significantly increasing the risk of postoperative complications.Although the surgical trauma is slightly greater,the overall prognosis is better,making it a preferred surgical treatment option for patients with early-stage gastric cancer.展开更多
Background:This study focused on developing and optimizing a self-microemulsifying drug delivery system(SMEDDS)to improve Lafutidine’s solubility and bioavailability,thereby enhancing its effectiveness in treating ga...Background:This study focused on developing and optimizing a self-microemulsifying drug delivery system(SMEDDS)to improve Lafutidine’s solubility and bioavailability,thereby enhancing its effectiveness in treating gastric ulcers.Traditional formulations are less effective due to their limited water solubility and bioavailability.Methods:The study used solubility tests,pseudo-ternary phase diagrams,and central composite design(CCD)to optimize.The formulation was optimized by varying the oil concentration(10–40%)and surfactant/cosurfactant ratio(0.33–3.00),and then tested for droplet size,drug content,emulsification,phase stability,and in vitro dissolution.Results:The study found that the optimized formulation contained 14%Capmul PG 8NF oil,62%Labrasol surfactant,and 24%Tween 80 cosurfactant.This combination generated an average droplet size of 111.02 nm and improved drug release properties.Furthermore,the formulation was stable without phase separation,with a drug content of 88.2–99.8%.Conclusion:SMEDDS significantly improves lafutidine delivery by increasing solubility and absorption,thereby overcoming oral administration challenges.The system quickly formed small droplets in water and released the drug in 15 min.Enhancing lafutidine’s bioavailability may improve its efficacy in treating gastric ulcers,resulting in better patient outcomes and potentially lower dosing frequency.展开更多
Objectives:Gastric cancer(GC)is among the most prevalent malignancies worldwide,ranking as the fifth most common cancer and the fifth leading cause of cancer-related mortality.This study intends to investigate how Inh...Objectives:Gastric cancer(GC)is among the most prevalent malignancies worldwide,ranking as the fifth most common cancer and the fifth leading cause of cancer-related mortality.This study intends to investigate how Inhibin subunit beta A(INHBA)promotes the progression of GC by activating the mitogen-activated protein kinase(MAPK)signaling pathway via targeting Integrin alpha-6(ITGA6).Methods:Quantitative reverse transcription-Polymerase Chain Reaction(qRT-PCR)and Immunohistochemistry(IHC)were utilised to validate the expression levels of INHBA in GC,which were subsequently correlated with the clinicopathological factors and outcomes.Cellular and animal studies were conducted to ascertain the role of INHBA in GC.RNA-sequencing(RNA-seq)and bioinformatics analysis were used to screen for the downstream target and pathway of INHBA,with Co-immunoprecipitation(Co-IP),Co-Immunofluorescent(Co-IF),Western blot(WB)and Rescue experiments validating their mechanisms of action in GC.Results:IHC and qRT-PCR analysis confirmed that GC tissues exhibited higher INHBA expression than adjacent noncancerous tissues.This elevated INHBA expression was found to be significantly associated with the incidence of tumor lesions,lymph node metastasis,and progression to higher TNM stages.Functional experiments showed that INHBA promoted GC cell proliferation and enhanced their migration and invasion in vitro while inhibiting apoptosis.Animal studies results indicated that INHBA overexpression promoted tumor growth and increased tumor weight and volume.Through a series of experiments,including RNA-seq,Co-IP,Co-IF,WB,and rescue assays,this study demonstrated that INHBA promotes GC progression by targeting ITGA6 to regulate the MAPK signaling pathway.Conclusions:INHBA/ITGA6/MAPK axis can provide new insights into GC therapy.Targeted INHBA inhibition holds promise as a therapeutic approach for GC treatment.展开更多
AIM: To evaluate the current state-of-the-art of gastric electrical stimulation to treat obesity. METHODS: Systematic reviews of all studies have been conducted to evaluate the effect of different types of gastric ele...AIM: To evaluate the current state-of-the-art of gastric electrical stimulation to treat obesity. METHODS: Systematic reviews of all studies have been conducted to evaluate the effect of different types of gastric electrical stimulation(GES) on obesity.RESULTS: Thirty-one studies consisting of a total of 33 different trials were included in the systematic review for data analysis. Weight loss was achieved in most studies, especially during the first 12 mo, but only very few studies had a follow-up period longer than 1 year. Among those that had a longer follow-up period, many were from the Transcend(Implantable Gastric Stimulation) device group and maintained significant weight loss. Other significant results included changes in appetite/satiety, gastric emptying rate, blood pressure and neurohormone levels or biochemical markers such as ghrelin or HbA1 c respectively. CONCLUSION: GES holds great promises to be an effective obesity treatment. However, stronger evidence is required through more studies with a standardized way of carrying out trials and reporting outcomes, to determine the long-term effect of GES on obesity.展开更多
Gastric cancer(GC)remains a major global health challenge,because of its poor prognosis and limited treatment options in advanced stages1,2.Recent advancements in immunotherapy,highlighted by the findings of the CHECK...Gastric cancer(GC)remains a major global health challenge,because of its poor prognosis and limited treatment options in advanced stages1,2.Recent advancements in immunotherapy,highlighted by the findings of the CHECKMATE-649,ORIENT-16,and KEYNOTE-859 trials,have markedly transformed the treatment paradigm for advanced gastric cancer(AGC)3-5.展开更多
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.
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(8197347182003937)。
文摘The gastroprotective activity of water extracts from Citrus reticulata'Chachi'leaves(JY)was investigated,and its potential action mechanisms were revealed using network pharmacology.First,the main chemical components of JY were identified using high performance liquid chromatography coupled to quadrupole time-of-flight tandem mass spectrometry,14 compounds were preliminarily identified,with flavonoids being the primary components.Next,the protective effect of JY on ethanol-induced damage was investigated in vitro.An MTT assay showed that JY could significantly promote the proliferation of GES-1 cells and reduce the damage caused by ethanol.A gastric ulcer model was induced in mice using ethanol,and JY(1,2,and 4 mg/kg)was orally administered to the mice to counteract ethanol-induced gastric ulcers.Pretreatment with JY reduced the severity of ethanol-induced gastric injury.Histopathological results showed that JY enhanced the cell structure of gastric tissue,increased the secretion of gastric mucosal mucus,and reduced gastric edema caused by ethanol injury.JY significantly decreased the levels of pro-inflammatory factors,including interleukin(IL)-1β,IL-6,and tumor necrosis factorα,in the serum.Additionally,JY increased the levels of prostaglandin E2 and the activity of total superoxide dismutase,while significantly reducing the levels of the lipid peroxidation product malondialdehyde in gastric tissue.In parallel,JY significantly upregulated the mRNA expressions of copper/zinc superoxide dismutase(Cu/Zn-SOD),manganese superoxide dismutase(Mn-SOD),and glutathione peroxidase(GPx)to alleviate oxidative stress.JY also promoted the healing of gastric ulcers by upregulating the mRNA expressions of vascular endothelial growth factor(VEGF)and epidermal growth factor receptor(EGFR).Finally,network pharmacology was used to analyze the potential bioactive substances in JY and their mechanisms.The results indicated that the protective effect of JY might be related to flavonoids and that JY exerts its gastroprotective effects by participating in the PI3K-Akt and VEGF signaling pathways.These findings suggest that JY could be a valuable natural resource for preventing ethanol-induced gastric injury.
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Shaanxi Provincial People’s Hospital Science and Technology Development Incubation Fund,“Research on the Role and Mechanism of PIGU in Regulating MUC-1 in Gastric Cancer Immune Escape”(Project No.:2023YJY-29)Shaanxi Provincial Natural Science Basic Research Program,“Research on the Mechanism and Clinical Significance of miR-140-5p Related to Gastric Cancer Recurrence and Metastasis”(Project No.:2023-JC-YB-639)。
文摘Early-stage gastric cancer;Extent of lymph node dissection;D1 dissection;D2 dissection;Recurrence rate;Survival rateObjective:To investigate the impact of different lymph node dissection scopes on postoperative recurrence and survival rates in patients with early gastric cancer,providing evidence-based support for optimizing clinical surgical plans.Methods:A retrospective analysis was conducted on the clinical data of 100 patients with early gastric cancer who underwent surgical treatment at our hospital from October 2021 to October 2023.Patients were divided into Group D1(n=50)and Group D2(n=50)based on the extent of lymph node dissection.Group D1 underwent limited lymph node dissection(dissection of the first station of lymph nodes around the stomach),while Group D2 underwent standard lymph node dissection(dissection of the first and second stations of lymph nodes around the stomach).Surgical-related indicators,the incidence of postoperative complications,the 2-year recurrence rate,and the 2-year survival rate were compared between the two groups of patients.Results:The operative time,intraoperative blood loss,postoperative hospital stay,and the number of lymph nodes dissected were significantly higher in the D2 group than in the D1 group(all P<0.001).The overall incidence of postoperative complications was higher in the D1 group than in the D2 group,but the difference was not statistically significant(χ^(2)=0.884,P=0.766).After a 2-year follow-up,the recurrence rate was significantly higher in the D1 group than in the D2 group(χ^(2)=4.000,P=0.046).The 2-year survival rate was significantly lower in the D1 group than in the D2 group(χ^(2)=5.005,P=0.025).A total of 100 patients with early-stage gastric cancer were grouped according to the depth of invasion,degree of differentiation,and lymph node metastasis status,and the recurrence rates of different subgroups were compared.The results showed that the recurrence rate was higher in patients with T1b stage than in those with T1a stage(χ^(2)=5.005,P=0.025),higher in poorly differentiated patients than in moderately and well-differentiated patients(χ^(2)=4.155,P=0.042),and higher in patients with lymph node metastasis than in those without lymph node metastasis(χ^(2)=4.512,P=0.034).Conclusion:Compared with D1 limited lymph node dissection,D2 standard lymph node dissection can significantly reduce the postoperative recurrence rate and improve the 2-year survival rate in patients with early-stage gastric cancer without significantly increasing the risk of postoperative complications.Although the surgical trauma is slightly greater,the overall prognosis is better,making it a preferred surgical treatment option for patients with early-stage gastric cancer.
文摘Background:This study focused on developing and optimizing a self-microemulsifying drug delivery system(SMEDDS)to improve Lafutidine’s solubility and bioavailability,thereby enhancing its effectiveness in treating gastric ulcers.Traditional formulations are less effective due to their limited water solubility and bioavailability.Methods:The study used solubility tests,pseudo-ternary phase diagrams,and central composite design(CCD)to optimize.The formulation was optimized by varying the oil concentration(10–40%)and surfactant/cosurfactant ratio(0.33–3.00),and then tested for droplet size,drug content,emulsification,phase stability,and in vitro dissolution.Results:The study found that the optimized formulation contained 14%Capmul PG 8NF oil,62%Labrasol surfactant,and 24%Tween 80 cosurfactant.This combination generated an average droplet size of 111.02 nm and improved drug release properties.Furthermore,the formulation was stable without phase separation,with a drug content of 88.2–99.8%.Conclusion:SMEDDS significantly improves lafutidine delivery by increasing solubility and absorption,thereby overcoming oral administration challenges.The system quickly formed small droplets in water and released the drug in 15 min.Enhancing lafutidine’s bioavailability may improve its efficacy in treating gastric ulcers,resulting in better patient outcomes and potentially lower dosing frequency.
基金funded by Medical Science Foundation of Hebei University 2024B03Hebei Provincial Government-funded Provincial Medical Excellent Talent Project ZF2023025,ZF2024134,ZF2025045,ZF2025048,and ZF2025051+3 种基金Hebei Natural Science Foundation H2022206292,H2024206140Key R&D Program of Hebei Province 223777103D and 223777113DHebei Province County General Hospital Appropriate Health Technology Promotion Project 20220018other projects of Hebei Province SGH201501.
文摘Objectives:Gastric cancer(GC)is among the most prevalent malignancies worldwide,ranking as the fifth most common cancer and the fifth leading cause of cancer-related mortality.This study intends to investigate how Inhibin subunit beta A(INHBA)promotes the progression of GC by activating the mitogen-activated protein kinase(MAPK)signaling pathway via targeting Integrin alpha-6(ITGA6).Methods:Quantitative reverse transcription-Polymerase Chain Reaction(qRT-PCR)and Immunohistochemistry(IHC)were utilised to validate the expression levels of INHBA in GC,which were subsequently correlated with the clinicopathological factors and outcomes.Cellular and animal studies were conducted to ascertain the role of INHBA in GC.RNA-sequencing(RNA-seq)and bioinformatics analysis were used to screen for the downstream target and pathway of INHBA,with Co-immunoprecipitation(Co-IP),Co-Immunofluorescent(Co-IF),Western blot(WB)and Rescue experiments validating their mechanisms of action in GC.Results:IHC and qRT-PCR analysis confirmed that GC tissues exhibited higher INHBA expression than adjacent noncancerous tissues.This elevated INHBA expression was found to be significantly associated with the incidence of tumor lesions,lymph node metastasis,and progression to higher TNM stages.Functional experiments showed that INHBA promoted GC cell proliferation and enhanced their migration and invasion in vitro while inhibiting apoptosis.Animal studies results indicated that INHBA overexpression promoted tumor growth and increased tumor weight and volume.Through a series of experiments,including RNA-seq,Co-IP,Co-IF,WB,and rescue assays,this study demonstrated that INHBA promotes GC progression by targeting ITGA6 to regulate the MAPK signaling pathway.Conclusions:INHBA/ITGA6/MAPK axis can provide new insights into GC therapy.Targeted INHBA inhibition holds promise as a therapeutic approach for GC treatment.
文摘AIM: To evaluate the current state-of-the-art of gastric electrical stimulation to treat obesity. METHODS: Systematic reviews of all studies have been conducted to evaluate the effect of different types of gastric electrical stimulation(GES) on obesity.RESULTS: Thirty-one studies consisting of a total of 33 different trials were included in the systematic review for data analysis. Weight loss was achieved in most studies, especially during the first 12 mo, but only very few studies had a follow-up period longer than 1 year. Among those that had a longer follow-up period, many were from the Transcend(Implantable Gastric Stimulation) device group and maintained significant weight loss. Other significant results included changes in appetite/satiety, gastric emptying rate, blood pressure and neurohormone levels or biochemical markers such as ghrelin or HbA1 c respectively. CONCLUSION: GES holds great promises to be an effective obesity treatment. However, stronger evidence is required through more studies with a standardized way of carrying out trials and reporting outcomes, to determine the long-term effect of GES on obesity.
基金supported by The National Key Research and Development Program of China(Grant no.2021YFA0910100)Healthy Zhejiang One Million People Cohort(Grant no.K-20230085)+5 种基金Post-doctoral Innovative Talent Support Program(Grant no.BX2023375)Lingyan Project of Zhejiang Provincial Department of Science and Technology(Grant no.2025C02059)the National Natural Science Foundation of China(Grant nos.82304946,82473489,and 82403546)Natural Science Foundation of Zhejiang Province(Grant nos.LR21H280001,LGF22H160056,ZCLQN25H1602,and LMS25H160006)Medicine and Health Science Fund of Zhejiang Province Health Commission(Grant nos.2025KY047 and 2022KY658)Traditional Chinese Medicine Science and Technology Project of Zhejiang Provincial Health Commission(Grant no.2022ZA023).
文摘Gastric cancer(GC)remains a major global health challenge,because of its poor prognosis and limited treatment options in advanced stages1,2.Recent advancements in immunotherapy,highlighted by the findings of the CHECKMATE-649,ORIENT-16,and KEYNOTE-859 trials,have markedly transformed the treatment paradigm for advanced gastric cancer(AGC)3-5.
