Immunotherapy has brought unprecedented breakthroughs to advanced malignant tumors,yet the immune microenvironment shaped by the tumor stroma has often been underestimated in the traditional focus on the“immune check...Immunotherapy has brought unprecedented breakthroughs to advanced malignant tumors,yet the immune microenvironment shaped by the tumor stroma has often been underestimated in the traditional focus on the“immune checkpoint-T cell”axis.Collagen not only constitutes a mechanical barrier that distinguishes between the periphery and core of solid tumors but also systematically remodels the orientation of metabolism,vasculature,and immune cell phenotypic plasticity through its spatial density,fiber arrangement,and crosslinking patterns(F igure 1)[1,2].Abundant evidence suggests that over-accumulated types I and III collagen drive CD8+T cell exhaustion,NK cell functional inhibition,and tumor-associated macrophage polarization through ligand-receptor networks involving LAIR-1,DDR2,andβ1/β3 integrins[3-6].Mechanistically,collagen engagement of LAIR-1 delivers inhibitory signals in effector lymphocytes,promoting dysfunctional or exhausted states[7-9].In parallel,collagen-β1/β3 integrin signaling activates mechanotransduction pathways(e.g.,FAK/SRC),reducing T-cell motility and immune-tumor contact,while DDR2 activation supports matrix-remodeling programs that limit lymphocyte trafficking.展开更多
This systematic review aims to comprehensively examine and compare deep learning methods for brain tumor segmentation and classification using MRI and other imaging modalities,focusing on recent trends from 2022 to 20...This systematic review aims to comprehensively examine and compare deep learning methods for brain tumor segmentation and classification using MRI and other imaging modalities,focusing on recent trends from 2022 to 2025.The primary objective is to evaluate methodological advancements,model performance,dataset usage,and existing challenges in developing clinically robust AI systems.We included peer-reviewed journal articles and highimpact conference papers published between 2022 and 2025,written in English,that proposed or evaluated deep learning methods for brain tumor segmentation and/or classification.Excluded were non-open-access publications,books,and non-English articles.A structured search was conducted across Scopus,Google Scholar,Wiley,and Taylor&Francis,with the last search performed in August 2025.Risk of bias was not formally quantified but considered during full-text screening based on dataset diversity,validation methods,and availability of performance metrics.We used narrative synthesis and tabular benchmarking to compare performance metrics(e.g.,accuracy,Dice score)across model types(CNN,Transformer,Hybrid),imaging modalities,and datasets.A total of 49 studies were included(43 journal articles and 6 conference papers).These studies spanned over 9 public datasets(e.g.,BraTS,Figshare,REMBRANDT,MOLAB)and utilized a range of imaging modalities,predominantly MRI.Hybrid models,especially ResViT and UNetFormer,consistently achieved high performance,with classification accuracy exceeding 98%and segmentation Dice scores above 0.90 across multiple studies.Transformers and hybrid architectures showed increasing adoption post2023.Many studies lacked external validation and were evaluated only on a few benchmark datasets,raising concerns about generalizability and dataset bias.Few studies addressed clinical interpretability or uncertainty quantification.Despite promising results,particularly for hybrid deep learning models,widespread clinical adoption remains limited due to lack of validation,interpretability concerns,and real-world deployment barriers.展开更多
Colorectal cancer(CRC)is ranked as the third most common tumor globally,representing approximately 10%of all cancer cases,and is the second primary cause of cancer-associated mortality.Existing therapeutic approaches ...Colorectal cancer(CRC)is ranked as the third most common tumor globally,representing approximately 10%of all cancer cases,and is the second primary cause of cancer-associated mortality.Existing therapeutic approaches demonstrate limited efficacy against CRC,partially due to the immunosuppressive tumor microenvironment(TME).In recent years,substantial evidence indicates that dysbiosis of the gut microbiota and its metabolic products is closely associated with the initiation,progression,and prognostic outcomes of CRC.In this minireview,we systematically elaborate on how these microbes and their metabolites directly impair intestinal epithelial integrity,activate cancer-associated fibroblasts,remodel tumor vasculature,and critically,sculpt an immunosuppressive landscape by modulating T cells,dendritic cells,and tumor-associated macrophages.We highlight the translational potential of targeting the gut microbiota,including fecal microbiota transplantation,probiotics,and engineered microbial systems,to reprogram the TME and overcome resistance to immunotherapy and chemotherapy.A deeper understanding of the microbiota-TME axis is essential for developing novel diagnostic and therapeutic paradigms for CRC.展开更多
Cervical cancer related to human papillomavirus(HPV)is a leading cause of cancer-related mortality among women worldwide.Cancer cells release fragments of their DNA,known as circulating tumor DNA(ctDNA),which can be d...Cervical cancer related to human papillomavirus(HPV)is a leading cause of cancer-related mortality among women worldwide.Cancer cells release fragments of their DNA,known as circulating tumor DNA(ctDNA),which can be detected in bodily fluids.A PubMed search using the terms“ctHPV”or“circulating tumor DNA”and“cervical cancer”,limited to the past ten years,identified 104 articles,complemented by hand-searching for literature addressing medico-legal implications.Studies were evaluated for relevance and methodological quality.Detection and characterization of circulating tumor HPV DNA(ctHPV DNA)have emerged as promising tools for assessing prognosis and disease recurrence in cervical cancer.Detection techniques include polymerase chain reaction(PCR),digital droplet PCR(ddPCR),and next-generation sequencing(NGS).This review summarizes current knowledge on ctHPV DNA in cervical cancer and explores its clinical and medico-legal implications,including management of discordant results,diagnostic errors,liability,and data protection compliance.展开更多
Liver cancer remains a leading cause of mortality worldwide,and precise diagnostic tools are essential for effective treatment planning.Liver Tumors(LTs)vary significantly in size,shape,and location,and can present wi...Liver cancer remains a leading cause of mortality worldwide,and precise diagnostic tools are essential for effective treatment planning.Liver Tumors(LTs)vary significantly in size,shape,and location,and can present with tissues of similar intensities,making automatically segmenting and classifying LTs from abdominal tomography images crucial and challenging.This review examines recent advancements in Liver Segmentation(LS)and Tumor Segmentation(TS)algorithms,highlighting their strengths and limitations regarding precision,automation,and resilience.Performance metrics are utilized to assess key detection algorithms and analytical methods,emphasizing their effectiveness and relevance in clinical contexts.The review also addresses ongoing challenges in liver tumor segmentation and identification,such as managing high variability in patient data and ensuring robustness across different imaging conditions.It suggests directions for future research,with insights into technological advancements that can enhance surgical planning and diagnostic accuracy by comparing popular methods.This paper contributes to a comprehensive understanding of current liver tumor detection techniques,provides a roadmap for future innovations,and improves diagnostic and therapeutic outcomes for liver cancer by integrating recent progress with remaining challenges.展开更多
Background:The development of relevant and robust large animal models of hepatocellular carcinoma is needed to test new therapeutic strategies for this disease.Transgenic approaches hold promise in addressing this com...Background:The development of relevant and robust large animal models of hepatocellular carcinoma is needed to test new therapeutic strategies for this disease.Transgenic approaches hold promise in addressing this complex problem.One such model,the Oncopig,has been reported to develop tumors of up to 4 cm in diameter within 7-14 days at sites of in situ vector inoculation.However,the resulting lesions reportedly contained an extensive inflammatory component that has not been evaluated in detail.Methods:Herein,we describe our results from multiparametric characterization of the lesions generated using liver biopsy cores incubated in vector solution and re-placed in the tissue.The study consisted of 3 animals in 3 cohorts(total of 9 animals)that were evaluated at 14,21,and 28 days.CT imaging,immunohistochemistry,multiplex immunofluorescence,and comprehensive blood analyses were used to quantify composition of the hepatic masses that developed following AdCre inoculation.Results:The tumors were hypovascular on CT and predominantly composed of CD45+cells with a strong lymphohistiocytic component,with no carcinomas identified.Ki-67 staining showed proliferation of CD45+immune cells but no neoplastic component.To provide further insight,the results are evaluated in the context of tumor growth kinetics.Conclusion:While progress has been made in generating targetable lesions,achieving a robust large animal model of liver cancer that faithfully recapitulates the human disease remains a challenging goal.展开更多
Emerging ferroptosis-immunotherapy strategies,integrating functionalized nanoplatforms with ferroptosis-inducing agents and immunomodulatory therapeutics,demonstrate significant potential in managing primary,recurrent...Emerging ferroptosis-immunotherapy strategies,integrating functionalized nanoplatforms with ferroptosis-inducing agents and immunomodulatory therapeutics,demonstrate significant potential in managing primary,recurrent,and metastatic malignancies.Mechanistically,ferroptosis induction not only directly eliminates tumor cells but also promotes immunogenic cell death(ICD),eliciting damage-associated molecular patterns(DAMPs)release to activate partial antitumor immunity.However,standalone ferroptosis therapy fails to initiate robust systemic antitumor immune responses due to inherent limitations:low tumor immunogenicity,immunosuppressive microenvironment constraints,and tumor microenvironment(TME)-associated physiological barriers(e.g.,hypoxia,dense extracellular matrix).To address these challenges,synergistic approaches have been developed to enhance immune cell infiltration and reestablish immunosurveillance,encompassing(1)direct amplification of antitumor immunity,(2)disruption of immunosuppressive tumor niches,and(3)biophysical hallmark remodeling in TME.Rational nanocarrier design has emerged as a critical enabler for overcoming biological delivery barriers and optimizing therapeutic efficacy.Unlike prior studies solely addressing ferroptosis or nanotechnology in tumor therapy,this work first systematically outlines the synergistic potential of nanoparticles in combined ferroptosis-immunotherapy strategies.It advances multidimensional nanoplatform design principles for material selection,structural configuration,physicochemical modulation,multifunctional integration,and artificial intelligence-enabled design,providing a scientific basis for efficacy optimization.Moreover,it examines translational challenges of ferroptosis-immunotherapy nanoplatforms across preclinical and clinical stages,proposing actionable solutions while envisioning future onco-immunotherapy directions.Collectively,it provides systematic insights into advanced nanomaterial design principles and therapeutic optimization strategies,offering a roadmap for accelerating clinical translation in onco-immunotherapy research.展开更多
Tumor metabolic reprogramming is a core hallmark of cancer,characterized by pathways such as aerobic glycolysis,aberrant lipid metabolism,and glutaminolysis that support rapid proliferation and immunosuppressive micro...Tumor metabolic reprogramming is a core hallmark of cancer,characterized by pathways such as aerobic glycolysis,aberrant lipid metabolism,and glutaminolysis that support rapid proliferation and immunosuppressive microenvironments.Circular RNAs(circRNAs)are highly stable,evolutionarily conserved non-coding RNAs that have emerged as critical modulators of these metabolic shifts.This review aims to systematically elucidate the roles and mechanisms of circRNAs in reprogramming tumor metabolism,and to discuss their clinical potential as biomarkers and therapeutic targets.Through mechanisms including miRNA sponging,protein interactions,regulation of mitochondrial dynamics,and modulation of metabolic enzymes,circRNAs influence key metabolic pathways by targeting glycolytic enzymes,lipid synthesis regulators,and glutaminolysis-related molecules to either facilitate or inhibit their expression.This review systematically summarizes the unique contributions of circRNAs to tumor metabolic reprogramming,highlighting key mechanisms such as regulation of peptide-encoding protein translation,mitochondrial localization function,gene promoter-targeted transcriptional regulation,and cross-pathway metabolic mediation,which underscore their distinct biological advantages and regulatory roles in tumor metabolism.The stability and tissue specificity of circRNAs make them promising diagnostic biomarkers,while their role in drug resistance mediated by metabolic reprogramming highlights their potential as therapeutic targets.Strategies such as circRNA inhibitors,mimics,and nanoparticle-based delivery systems are being explored to modulate tumor metabolism.Despite challenges including complex regulatory networks and limited manipulation tools,advances in high-throughput technologies and clinical trials hold promise for translating circRNA research into novel cancer therapies.展开更多
Background:Bone tumors represent a significant clinical challenge characterized by high morbidity and complex therapeutic requirements.Although Astragali Radix(Huangqi)is recognized for its potential pharmacological b...Background:Bone tumors represent a significant clinical challenge characterized by high morbidity and complex therapeutic requirements.Although Astragali Radix(Huangqi)is recognized for its potential pharmacological benefits in cancer therapy,the specific molecular mechanisms and their influence on vitamin metabolism pathways in bone malignancies are not well defined.Methods:We conducted an integrated analysis of prognostic genes and survival outcomes in osteosarcoma,focusing on the expression of GPC2 and its correlation with tumor progression and patient survival rates.In order to explore the therapeutic relevance of 20 bioactive compounds extracted from Huangqi,molecular docking was performed to quantify their binding free energies to the GPC2 receptor,shedding light on their potential affinity and biological activity.Furthermore,the expression levels of GPC2 in tumor cells compared to normal cells were analyzed using qRT-PCR.Additionally,the effects of GPC2 overexpression and silencing on cellular viability,apoptotic response,and migratory capacity were systematically investigated.Results:In our study,GPC2 emerged as a significant prognostic gene,where high expression levels correlated with reduced overall survival.The molecular interactions between Astragalus components and the GPC2 receptor reveal compounds with strong affinity,suggesting their potential as effective targets.Furthermore,the overexpression of GPC2 enhanced tumor cell viability and migration,while its knockdown resulted in decreased cell viability and expanded apoptosis.Conclusion:This study demonstrates that Huangqi-derived components may exert anticancer effects by regulating the expression of the GPC2 gene within the vitamin metabolism pathway.These findings offer new insights into the therapeutic potential of traditional herbal medicine for improving bone tumor prognosis and provide a scientific foundation for future translational research.展开更多
Experimental therapies targeting immune and stromal cells,such as mast cells,cancer-associated fibroblasts,dendritic cells,and tumor endothelial cells,in the treatment of gastrointestinal solid tumors pose new and com...Experimental therapies targeting immune and stromal cells,such as mast cells,cancer-associated fibroblasts,dendritic cells,and tumor endothelial cells,in the treatment of gastrointestinal solid tumors pose new and complex surgical and medico-legal challenges.These innovative treatments require that informed consent not be limited to simple acceptance of the medical procedure,but instead reflect a true relational and cognitive process grounded in understanding,free choice,and the ability to revoke consent at any time.In particular,it is essential that the patient understands the experimental nature of the therapy,its development stage,potential benefits and risks,as well as the implications for their health and personal dignity.In the case of stromal cell-based treatments,which may exert complex immunomodulatory effects or activate angiogenic pathways that are not yet fully understood,patients must be made fully aware that they are participating in a non-standardized therapy whose outcomes,whether beneficial or harmful,cannot yet be predicted with certainty.This requires particularly careful medical communication,using simple yet scientifically accurate explanations delivered in appropriate language,along with a final verification of the patient’s actual understanding.展开更多
Colorectal cancer remains one of the leading causes of morbidity and mortality worldwide.Despite notable advances in early detection and therapeutic strategies,the molecular mechanisms underlying tumor survival,chemot...Colorectal cancer remains one of the leading causes of morbidity and mortality worldwide.Despite notable advances in early detection and therapeutic strategies,the molecular mechanisms underlying tumor survival,chemotherapy resistance,and metastasis are not yet fully understood.MicroRNAs(miRNAs)have emerged as pivotal regulators of cancer development,as they modulate gene expression and orchestrate key signaling pathways.However,the epigenetic mechanisms that control miRNA expression and their downstream gene targets remain largely unclear.In this review,we highlight the critical role of the colorectal cancer microenvironment in influencing miRNA expression and discuss how this regulation contributes to tumorigenesis.A better understanding of these processes may lead to the identification of novel therapeutic targets and strategies to prevent recurrence.展开更多
BACKGROUND Gastrointestinal stromal tumors(GISTs)are rare mesenchymal neoplasms primarily originating in the stomach or small intestine.Duodenal GISTs are particularly uncommon,accounting for only a small fraction of ...BACKGROUND Gastrointestinal stromal tumors(GISTs)are rare mesenchymal neoplasms primarily originating in the stomach or small intestine.Duodenal GISTs are particularly uncommon,accounting for only a small fraction of GIST cases.These tumors often present with nonspecific symptoms,making early detection challenging.This case discusses a duodenal GIST misdiagnosed as pancreatic cancer due to obstructive jaundice.CASE SUMMARY A 40-year-old male with jaundice and abdominal symptoms underwent imaging,which suggested a malignant periampullary tumor.Preoperative misdiagnosis of pancreatic cancer was made,and surgery was performed.Postoperative histopathology confirmed a duodenal GIST.The role of artificial intelligence in the diagnostic pathway is explored,emphasizing its potential to differentiate between duodenal GISTs and other similar conditions using advanced imaging analysis.CONCLUSION Artificial intelligence in radiomic imaging holds significant promise in enhancing the diagnostic process for rare cancers like duodenal GISTs,ensuring timely and accurate treatment.展开更多
AIM:To investigate the clinical features and prognosis of patients with orbital inflammatory myofibroblastic tumor(IMT).METHODS:This retrospective study collected clinical data from 22 patients diagnosed with orbital ...AIM:To investigate the clinical features and prognosis of patients with orbital inflammatory myofibroblastic tumor(IMT).METHODS:This retrospective study collected clinical data from 22 patients diagnosed with orbital IMT based on histopathological examination.The patients were followed up to assess their prognosis.Clinical data from patients,including age,gender,course of disease,past medical history,primary symptoms,ophthalmologic examination findings,general condition,as well as imaging,laboratory,histopathological,and immunohistochemical results from digital records were collected.Orbital magnetic resonance imaging(MRI)and(or)computed tomography(CT)scans were performed to assess bone destruction of the mass,invasion of surrounding tissues,and any inflammatory changes in periorbital areas.RESULTS:The mean age of patients with orbital IMT was 28.24±3.30y,with a male-to-female ratio of 1.2:1.Main clinical manifestations were proptosis,blurred vision,palpable mass,and pain.Bone destruction and surrounding tissue invasion occurred in 72.73%and 54.55%of cases,respectively.Inflammatory changes in the periorbital site were observed in 77.27%of the patients.Hematoxylin and eosin staining showed proliferation of fibroblasts and myofibroblasts,accompanied by infiltration of lymphocytes and plasma cells.Immunohistochemical staining revealed that smooth muscle actin(SMA)and vimentin were positive in 100%of cases,while anaplastic lymphoma kinase(ALK)showed positivity in 47.37%.The recurrence rate of orbital IMT was 27.27%,and sarcomatous degeneration could occur.There were no significant correlations between recurrence and factors such as age,gender,laterality,duration of the disease,periorbital tissue invasion,bone destruction,periorbital inflammation,tumor size,fever,leukocytosis,or treatment(P>0.05).However,lymphadenopathy and a Ki-67 index of 10%or higher may be risk factors for recurrence(P=0.046;P=0.023).CONCLUSION:Orbital IMT is a locally invasive disease that may recur or lead to sarcomatoid degeneration,primarily affecting young and middle-aged patients.The presence of lymphadenopathy and a Ki-67 index of 10%or higher may signify a poor prognosis.展开更多
Potassium channels regulate diverse biological processes,ranging from cell proliferation to immune responses.However,the functions of potassium homeostasis and its regulatory mechanisms in adult stem cells and tumors ...Potassium channels regulate diverse biological processes,ranging from cell proliferation to immune responses.However,the functions of potassium homeostasis and its regulatory mechanisms in adult stem cells and tumors remain poorly characterized.Here,we identify Sandman(Sand),a two-pore-domain potassium channel in Drosophila melanogaster,as an essential regulator for the proliferation of intestinal stem cells and malignant tumors,while dispensable for the normal development processes.Mechanistically,loss of sand elevates intracellular K+concentration,leading to growth inhibition.This phenotype is rescued by pharmacological reduction of intracellular K+levels using the K+ionophore.Conversely,overexpression of sand triggers stem cell death in most regions of the midgut,inhibits tumor growth,and induces a Notch loss-of-function phenotype in the posterior midgut.These effects are mediated predominantly via the induction of endoplasmic reticulum(ER)stress,as demonstrated by the complete rescue of phenotypes through the co-expression of Ire1 or Xbp1s.Additionally,human homologues of Sand demonstrated similar ER stress-inducing capabilities,suggesting an evolutionarily conserved relationship between this channel and ER stress.Together,our findings identify Sand as a shared regulatory node that governs Drosophila adult stem cell dynamics and tumorigenesis through bioelectric homeostasis,and reveal a link between the two-pore potassium channel and ER stress signaling.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
BACKGROUND Gastrointestinal(GI)tumors are among the most prevalent malignancies,and surgical intervention remains a primary treatment modality.However,the complexity of GI surgery often leads to prolonged recovery and...BACKGROUND Gastrointestinal(GI)tumors are among the most prevalent malignancies,and surgical intervention remains a primary treatment modality.However,the complexity of GI surgery often leads to prolonged recovery and high postoperative complication rates,which threaten patient safety and functional outcomes.Enhanced recovery after surgery(ERAS)principles have been shown to improve perioperative outcomes through evidence-based,multidisciplinary care pathways.Despite its widespread adoption,there is a paucity of research focusing specifically on optimizing ERAS-guided nursing processes in the post-anesthesia care unit(PACU)and evaluating its impact on perioperative safety in patients undergoing GI tumor surgery.This study aimed to investigate whether an ERASbased PACU nursing protocol could enhance recovery,reduce complications,and improve patient safety in this surgical population.AIM To explore the impact of optimizing the recovery room nursing process based on ERAS on the perioperative safety of patients with GI tumors.METHODS A total of 260 patients with GI tumors who underwent elective surgeries under general anesthesia in our hospital from August 2023 to August 2025 and were then observed in the recovery unit(PACU)were selected.They were randomly divided into the observation group(the PACU nursing process was optimized based on ERAS)and the control group(the conventional PACU nursing process was adopted)by the random number grouping method,with 130 cases in each group.The time of gastric tube removal,urinary catheter removal,defecation time,hospital stay,time of leaving the room after tube removal,retention time in the recovery room,occurrence of complications,satisfaction and readmission rate were compared between the two groups after entering the room.Compare the occurrence of adverse events in the PACU nursing process between the two groups.RESULTS The time of gastric tube removal,urinary catheter removal,defecation time,hospital stay,retention time in the recovery room,total incidence of complications and readmission rate in the observation group were significantly lower than those in the control group,and the satisfaction rate was higher than that in the control group(P<0.05).The occurrence of adverse events in the PACU nursing process in the observation group was lower than that in the control group(P<0.05).CONCLUSION Optimizing the PACU nursing process based on ERAS can effectively accelerate the recovery process of patients undergoing GI tumor surgery,reduce adverse events,improve nursing satisfaction,and at the same time,lower the incidence of adverse events in the PACU nursing process,providing a more refined management basis for clinical practice.展开更多
Brain tumors require precise segmentation for diagnosis and treatment plans due to their complex morphology and heterogeneous characteristics.While MRI-based automatic brain tumor segmentation technology reduces the b...Brain tumors require precise segmentation for diagnosis and treatment plans due to their complex morphology and heterogeneous characteristics.While MRI-based automatic brain tumor segmentation technology reduces the burden on medical staff and provides quantitative information,existing methodologies and recent models still struggle to accurately capture and classify the fine boundaries and diverse morphologies of tumors.In order to address these challenges and maximize the performance of brain tumor segmentation,this research introduces a novel SwinUNETR-based model by integrating a new decoder block,the Hierarchical Channel-wise Attention Decoder(HCAD),into a powerful SwinUNETR encoder.The HCAD decoder block utilizes hierarchical features and channelspecific attention mechanisms to further fuse information at different scales transmitted from the encoder and preserve spatial details throughout the reconstruction phase.Rigorous evaluations on the recent BraTS GLI datasets demonstrate that the proposed SwinHCAD model achieved superior and improved segmentation accuracy on both the Dice score and HD95 metrics across all tumor subregions(WT,TC,and ET)compared to baseline models.In particular,the rationale and contribution of the model design were clarified through ablation studies to verify the effectiveness of the proposed HCAD decoder block.The results of this study are expected to greatly contribute to enhancing the efficiency of clinical diagnosis and treatment planning by increasing the precision of automated brain tumor segmentation.展开更多
A clear goal in cold tumor research is to identify strategies for converting them into immunologically‘hot’tumors with enhanced immune cell infiltration and activity,thereby improving their responsiveness to immunot...A clear goal in cold tumor research is to identify strategies for converting them into immunologically‘hot’tumors with enhanced immune cell infiltration and activity,thereby improving their responsiveness to immunotherapy.The genesis of cold tumors is exceedingly intricate.In recent times,as the analysis of this phenomenon has been pursued with greater depth,a suite of advanced diagnostic and therapeutic technologies has surfaced.These novel approaches and tactics are anticipated to modulate the tumor immune microenvironment across various dimensions,thereby facilitating the advancement of personalized and precise treatment modalities for cold tumors.The present article addresses the challenge of diminished therapeutic responsiveness to“cold tumors”within clinical settings.It systematically elucidates the multi-faceted regulatory mechanisms underlying immune evasion in cold tumors and offers a detailed analysis of advanced therapeutic strategies that incorporate nanotechnology,gene editing,and artificial intelligence methodologies.Furthermore,the future development trends of immunotherapy were explored in greater depth.It was posited that the convergence of artificial intelligence,multidimensional genomics,and emerging biotechnologies has presented positive prospects for the treatment of cold tumors,and has offered a theoretical foundation and technical framework for the transformation of cold tumors into“hot tumors”.展开更多
Metastatic brain tumors undergo profound metabolic-epigenetic reprogramming driven by the unique constraints of the brain microenvironment.Hypoxia-inducible factor-1α(HIF1α)enhances glycolytic flux,lactate accumulat...Metastatic brain tumors undergo profound metabolic-epigenetic reprogramming driven by the unique constraints of the brain microenvironment.Hypoxia-inducible factor-1α(HIF1α)enhances glycolytic flux,lactate accumulation,and histone lactylation,collectively supporting metastatic colonization and immune evasion.Key metabolites including acetyl-CoA,S-adenosylmethionine(SAM),α-ketoglutarate(α-KG),fumarate,and 2-hydroxyglutarate(2-HG)-directly modify chromatin states by regulating histone acetyltransferases,DNA/histone methyltransferases,andα-KG dependent dioxygenases such as Ten-Eleven Translocation(TET)enzymes and lysine demethylases(KDMs).These metabolic shifts result in aberrant DNA methylation,histone lysine residue at position 27 on Histone H3(H3K27)trimethylation,and depletion of 5-hydroxymethylcytosine(5hmC),all of which are hallmark epigenetic alterations in brain metastasis and primary Central Nervous System(CNS)tumors.Additionally,the blood-brain barrier(BBB)and blood-tumor barrier(BTB)impose nutrient restrictions and induce metabolic dependency on glutamine,acetate,and lactate shuttling,thereby reshaping epigenetic enzyme activity.We synthesize current mechanistic evidence showing how metabolic pressures in the brain microenvironment remodel the epigenome to promote tumor plasticity,stemness,and therapeutic resistance.Understanding these coupled pathways reveals vulnerable nodes such as HIF1αsignaling,α-KG-dependent demethylation,and lactate-driven epigenetic remodeling that may be exploited for targeted treatment of metastatic brain tumors.The present review aims to provide in-depth insights into epigenetic regulation,including chromatin and histone modifications as well as noncoding RNAs and metabolic reprogramming,highlighting how the two interplay in the development and progression of metastatic brain tumors and their therapeutic potential.展开更多
Background:In preclinical research,tumor growth inhibition in subcutaneous models is frequently employed to evaluate therapeutic efficacy;however,such models often lack clinical translatability.Methods:To better appro...Background:In preclinical research,tumor growth inhibition in subcutaneous models is frequently employed to evaluate therapeutic efficacy;however,such models often lack clinical translatability.Methods:To better approximate clinical reality,taking the case of doxorubicin treatment,we utilized an orthotopic transplant and resection(OtR)strategy to systematically assess the effects of neoadjuvant chemotherapy,adjuvant chem-otherapy,and their combination on tumor growth,recurrence,and malignant progression.Results:Surprisingly,none of the treatments improved mouse survival,with adjuvant therapy even shortening it.Although neoadjuvant chemotherapy delayed preopera-tive tumor growth,and all regimens reduced recurrence rates,none effectively pre-vented metastasis.Furthermore,all treatment groups exhibited weight loss,indicative of chemotherapy-induced cachexia.Conclusions:Collectively,these findings demonstrate that reduced tumor growth in preclinical mouse models does not necessarily translate into overall survival benefit.Our results emphasize the critical importance of prioritizing metastasis prevention over tumor growth inhibition as a key efficacy endpoint in antitumor drug evaluation.展开更多
基金supported by the National Natural Science Foundation of China(82472842 and 82473350)and Wuxi Double-Hundred Talent Fund Project(BJ2023075).
文摘Immunotherapy has brought unprecedented breakthroughs to advanced malignant tumors,yet the immune microenvironment shaped by the tumor stroma has often been underestimated in the traditional focus on the“immune checkpoint-T cell”axis.Collagen not only constitutes a mechanical barrier that distinguishes between the periphery and core of solid tumors but also systematically remodels the orientation of metabolism,vasculature,and immune cell phenotypic plasticity through its spatial density,fiber arrangement,and crosslinking patterns(F igure 1)[1,2].Abundant evidence suggests that over-accumulated types I and III collagen drive CD8+T cell exhaustion,NK cell functional inhibition,and tumor-associated macrophage polarization through ligand-receptor networks involving LAIR-1,DDR2,andβ1/β3 integrins[3-6].Mechanistically,collagen engagement of LAIR-1 delivers inhibitory signals in effector lymphocytes,promoting dysfunctional or exhausted states[7-9].In parallel,collagen-β1/β3 integrin signaling activates mechanotransduction pathways(e.g.,FAK/SRC),reducing T-cell motility and immune-tumor contact,while DDR2 activation supports matrix-remodeling programs that limit lymphocyte trafficking.
文摘This systematic review aims to comprehensively examine and compare deep learning methods for brain tumor segmentation and classification using MRI and other imaging modalities,focusing on recent trends from 2022 to 2025.The primary objective is to evaluate methodological advancements,model performance,dataset usage,and existing challenges in developing clinically robust AI systems.We included peer-reviewed journal articles and highimpact conference papers published between 2022 and 2025,written in English,that proposed or evaluated deep learning methods for brain tumor segmentation and/or classification.Excluded were non-open-access publications,books,and non-English articles.A structured search was conducted across Scopus,Google Scholar,Wiley,and Taylor&Francis,with the last search performed in August 2025.Risk of bias was not formally quantified but considered during full-text screening based on dataset diversity,validation methods,and availability of performance metrics.We used narrative synthesis and tabular benchmarking to compare performance metrics(e.g.,accuracy,Dice score)across model types(CNN,Transformer,Hybrid),imaging modalities,and datasets.A total of 49 studies were included(43 journal articles and 6 conference papers).These studies spanned over 9 public datasets(e.g.,BraTS,Figshare,REMBRANDT,MOLAB)and utilized a range of imaging modalities,predominantly MRI.Hybrid models,especially ResViT and UNetFormer,consistently achieved high performance,with classification accuracy exceeding 98%and segmentation Dice scores above 0.90 across multiple studies.Transformers and hybrid architectures showed increasing adoption post2023.Many studies lacked external validation and were evaluated only on a few benchmark datasets,raising concerns about generalizability and dataset bias.Few studies addressed clinical interpretability or uncertainty quantification.Despite promising results,particularly for hybrid deep learning models,widespread clinical adoption remains limited due to lack of validation,interpretability concerns,and real-world deployment barriers.
基金Supported by National Natural Science Foundation of China,No.82170638Natural Science Foundation of the Science and Technology Commission of Shanghai Municipality,No.23ZR1458300+1 种基金Key Discipline Project of Shanghai Municipal Health System,No.2024ZDXK0004and Pujiang Project of Shanghai Magnolia Talent Plan,No.24PJD098.
文摘Colorectal cancer(CRC)is ranked as the third most common tumor globally,representing approximately 10%of all cancer cases,and is the second primary cause of cancer-associated mortality.Existing therapeutic approaches demonstrate limited efficacy against CRC,partially due to the immunosuppressive tumor microenvironment(TME).In recent years,substantial evidence indicates that dysbiosis of the gut microbiota and its metabolic products is closely associated with the initiation,progression,and prognostic outcomes of CRC.In this minireview,we systematically elaborate on how these microbes and their metabolites directly impair intestinal epithelial integrity,activate cancer-associated fibroblasts,remodel tumor vasculature,and critically,sculpt an immunosuppressive landscape by modulating T cells,dendritic cells,and tumor-associated macrophages.We highlight the translational potential of targeting the gut microbiota,including fecal microbiota transplantation,probiotics,and engineered microbial systems,to reprogram the TME and overcome resistance to immunotherapy and chemotherapy.A deeper understanding of the microbiota-TME axis is essential for developing novel diagnostic and therapeutic paradigms for CRC.
文摘Cervical cancer related to human papillomavirus(HPV)is a leading cause of cancer-related mortality among women worldwide.Cancer cells release fragments of their DNA,known as circulating tumor DNA(ctDNA),which can be detected in bodily fluids.A PubMed search using the terms“ctHPV”or“circulating tumor DNA”and“cervical cancer”,limited to the past ten years,identified 104 articles,complemented by hand-searching for literature addressing medico-legal implications.Studies were evaluated for relevance and methodological quality.Detection and characterization of circulating tumor HPV DNA(ctHPV DNA)have emerged as promising tools for assessing prognosis and disease recurrence in cervical cancer.Detection techniques include polymerase chain reaction(PCR),digital droplet PCR(ddPCR),and next-generation sequencing(NGS).This review summarizes current knowledge on ctHPV DNA in cervical cancer and explores its clinical and medico-legal implications,including management of discordant results,diagnostic errors,liability,and data protection compliance.
基金the“Intelligent Recognition Industry Service Center”as part of the Featured Areas Research Center Program under the Higher Education Sprout Project by the Ministry of Education(MOE)in Taiwan,and the National Science and Technology Council,Taiwan,under grants 113-2221-E-224-041 and 113-2622-E-224-002.Additionally,partial support was provided by Isuzu Optics Corporation.
文摘Liver cancer remains a leading cause of mortality worldwide,and precise diagnostic tools are essential for effective treatment planning.Liver Tumors(LTs)vary significantly in size,shape,and location,and can present with tissues of similar intensities,making automatically segmenting and classifying LTs from abdominal tomography images crucial and challenging.This review examines recent advancements in Liver Segmentation(LS)and Tumor Segmentation(TS)algorithms,highlighting their strengths and limitations regarding precision,automation,and resilience.Performance metrics are utilized to assess key detection algorithms and analytical methods,emphasizing their effectiveness and relevance in clinical contexts.The review also addresses ongoing challenges in liver tumor segmentation and identification,such as managing high variability in patient data and ensuring robustness across different imaging conditions.It suggests directions for future research,with insights into technological advancements that can enhance surgical planning and diagnostic accuracy by comparing popular methods.This paper contributes to a comprehensive understanding of current liver tumor detection techniques,provides a roadmap for future innovations,and improves diagnostic and therapeutic outcomes for liver cancer by integrating recent progress with remaining challenges.
基金Institutional Research Grant,MD Anderson Cancer CenterUPWARDS Training Program(Undergraduate Students Working Towards Research in Science),Grant/Award Number:1R25CA240137-01A1the CPRIT Research Training Award CPRIT Training Program,Grant/Award Number:RP210028。
文摘Background:The development of relevant and robust large animal models of hepatocellular carcinoma is needed to test new therapeutic strategies for this disease.Transgenic approaches hold promise in addressing this complex problem.One such model,the Oncopig,has been reported to develop tumors of up to 4 cm in diameter within 7-14 days at sites of in situ vector inoculation.However,the resulting lesions reportedly contained an extensive inflammatory component that has not been evaluated in detail.Methods:Herein,we describe our results from multiparametric characterization of the lesions generated using liver biopsy cores incubated in vector solution and re-placed in the tissue.The study consisted of 3 animals in 3 cohorts(total of 9 animals)that were evaluated at 14,21,and 28 days.CT imaging,immunohistochemistry,multiplex immunofluorescence,and comprehensive blood analyses were used to quantify composition of the hepatic masses that developed following AdCre inoculation.Results:The tumors were hypovascular on CT and predominantly composed of CD45+cells with a strong lymphohistiocytic component,with no carcinomas identified.Ki-67 staining showed proliferation of CD45+immune cells but no neoplastic component.To provide further insight,the results are evaluated in the context of tumor growth kinetics.Conclusion:While progress has been made in generating targetable lesions,achieving a robust large animal model of liver cancer that faithfully recapitulates the human disease remains a challenging goal.
基金supported by the National Natural Science Foundation of China(Nos.82302373,81903846)Natural Science Foundation of Sichuan Province(No.2022NSFSC1925)+1 种基金Chengdu Technology Innovation Research and Development Project(No.2022-YF05-01546-SN)the Introduction of Talents Research Project of Chengdu University(No.2081921049)。
文摘Emerging ferroptosis-immunotherapy strategies,integrating functionalized nanoplatforms with ferroptosis-inducing agents and immunomodulatory therapeutics,demonstrate significant potential in managing primary,recurrent,and metastatic malignancies.Mechanistically,ferroptosis induction not only directly eliminates tumor cells but also promotes immunogenic cell death(ICD),eliciting damage-associated molecular patterns(DAMPs)release to activate partial antitumor immunity.However,standalone ferroptosis therapy fails to initiate robust systemic antitumor immune responses due to inherent limitations:low tumor immunogenicity,immunosuppressive microenvironment constraints,and tumor microenvironment(TME)-associated physiological barriers(e.g.,hypoxia,dense extracellular matrix).To address these challenges,synergistic approaches have been developed to enhance immune cell infiltration and reestablish immunosurveillance,encompassing(1)direct amplification of antitumor immunity,(2)disruption of immunosuppressive tumor niches,and(3)biophysical hallmark remodeling in TME.Rational nanocarrier design has emerged as a critical enabler for overcoming biological delivery barriers and optimizing therapeutic efficacy.Unlike prior studies solely addressing ferroptosis or nanotechnology in tumor therapy,this work first systematically outlines the synergistic potential of nanoparticles in combined ferroptosis-immunotherapy strategies.It advances multidimensional nanoplatform design principles for material selection,structural configuration,physicochemical modulation,multifunctional integration,and artificial intelligence-enabled design,providing a scientific basis for efficacy optimization.Moreover,it examines translational challenges of ferroptosis-immunotherapy nanoplatforms across preclinical and clinical stages,proposing actionable solutions while envisioning future onco-immunotherapy directions.Collectively,it provides systematic insights into advanced nanomaterial design principles and therapeutic optimization strategies,offering a roadmap for accelerating clinical translation in onco-immunotherapy research.
基金funded by National Natural Science Foundation of China(82360801).
文摘Tumor metabolic reprogramming is a core hallmark of cancer,characterized by pathways such as aerobic glycolysis,aberrant lipid metabolism,and glutaminolysis that support rapid proliferation and immunosuppressive microenvironments.Circular RNAs(circRNAs)are highly stable,evolutionarily conserved non-coding RNAs that have emerged as critical modulators of these metabolic shifts.This review aims to systematically elucidate the roles and mechanisms of circRNAs in reprogramming tumor metabolism,and to discuss their clinical potential as biomarkers and therapeutic targets.Through mechanisms including miRNA sponging,protein interactions,regulation of mitochondrial dynamics,and modulation of metabolic enzymes,circRNAs influence key metabolic pathways by targeting glycolytic enzymes,lipid synthesis regulators,and glutaminolysis-related molecules to either facilitate or inhibit their expression.This review systematically summarizes the unique contributions of circRNAs to tumor metabolic reprogramming,highlighting key mechanisms such as regulation of peptide-encoding protein translation,mitochondrial localization function,gene promoter-targeted transcriptional regulation,and cross-pathway metabolic mediation,which underscore their distinct biological advantages and regulatory roles in tumor metabolism.The stability and tissue specificity of circRNAs make them promising diagnostic biomarkers,while their role in drug resistance mediated by metabolic reprogramming highlights their potential as therapeutic targets.Strategies such as circRNA inhibitors,mimics,and nanoparticle-based delivery systems are being explored to modulate tumor metabolism.Despite challenges including complex regulatory networks and limited manipulation tools,advances in high-throughput technologies and clinical trials hold promise for translating circRNA research into novel cancer therapies.
文摘Background:Bone tumors represent a significant clinical challenge characterized by high morbidity and complex therapeutic requirements.Although Astragali Radix(Huangqi)is recognized for its potential pharmacological benefits in cancer therapy,the specific molecular mechanisms and their influence on vitamin metabolism pathways in bone malignancies are not well defined.Methods:We conducted an integrated analysis of prognostic genes and survival outcomes in osteosarcoma,focusing on the expression of GPC2 and its correlation with tumor progression and patient survival rates.In order to explore the therapeutic relevance of 20 bioactive compounds extracted from Huangqi,molecular docking was performed to quantify their binding free energies to the GPC2 receptor,shedding light on their potential affinity and biological activity.Furthermore,the expression levels of GPC2 in tumor cells compared to normal cells were analyzed using qRT-PCR.Additionally,the effects of GPC2 overexpression and silencing on cellular viability,apoptotic response,and migratory capacity were systematically investigated.Results:In our study,GPC2 emerged as a significant prognostic gene,where high expression levels correlated with reduced overall survival.The molecular interactions between Astragalus components and the GPC2 receptor reveal compounds with strong affinity,suggesting their potential as effective targets.Furthermore,the overexpression of GPC2 enhanced tumor cell viability and migration,while its knockdown resulted in decreased cell viability and expanded apoptosis.Conclusion:This study demonstrates that Huangqi-derived components may exert anticancer effects by regulating the expression of the GPC2 gene within the vitamin metabolism pathway.These findings offer new insights into the therapeutic potential of traditional herbal medicine for improving bone tumor prognosis and provide a scientific foundation for future translational research.
文摘Experimental therapies targeting immune and stromal cells,such as mast cells,cancer-associated fibroblasts,dendritic cells,and tumor endothelial cells,in the treatment of gastrointestinal solid tumors pose new and complex surgical and medico-legal challenges.These innovative treatments require that informed consent not be limited to simple acceptance of the medical procedure,but instead reflect a true relational and cognitive process grounded in understanding,free choice,and the ability to revoke consent at any time.In particular,it is essential that the patient understands the experimental nature of the therapy,its development stage,potential benefits and risks,as well as the implications for their health and personal dignity.In the case of stromal cell-based treatments,which may exert complex immunomodulatory effects or activate angiogenic pathways that are not yet fully understood,patients must be made fully aware that they are participating in a non-standardized therapy whose outcomes,whether beneficial or harmful,cannot yet be predicted with certainty.This requires particularly careful medical communication,using simple yet scientifically accurate explanations delivered in appropriate language,along with a final verification of the patient’s actual understanding.
文摘Colorectal cancer remains one of the leading causes of morbidity and mortality worldwide.Despite notable advances in early detection and therapeutic strategies,the molecular mechanisms underlying tumor survival,chemotherapy resistance,and metastasis are not yet fully understood.MicroRNAs(miRNAs)have emerged as pivotal regulators of cancer development,as they modulate gene expression and orchestrate key signaling pathways.However,the epigenetic mechanisms that control miRNA expression and their downstream gene targets remain largely unclear.In this review,we highlight the critical role of the colorectal cancer microenvironment in influencing miRNA expression and discuss how this regulation contributes to tumorigenesis.A better understanding of these processes may lead to the identification of novel therapeutic targets and strategies to prevent recurrence.
文摘BACKGROUND Gastrointestinal stromal tumors(GISTs)are rare mesenchymal neoplasms primarily originating in the stomach or small intestine.Duodenal GISTs are particularly uncommon,accounting for only a small fraction of GIST cases.These tumors often present with nonspecific symptoms,making early detection challenging.This case discusses a duodenal GIST misdiagnosed as pancreatic cancer due to obstructive jaundice.CASE SUMMARY A 40-year-old male with jaundice and abdominal symptoms underwent imaging,which suggested a malignant periampullary tumor.Preoperative misdiagnosis of pancreatic cancer was made,and surgery was performed.Postoperative histopathology confirmed a duodenal GIST.The role of artificial intelligence in the diagnostic pathway is explored,emphasizing its potential to differentiate between duodenal GISTs and other similar conditions using advanced imaging analysis.CONCLUSION Artificial intelligence in radiomic imaging holds significant promise in enhancing the diagnostic process for rare cancers like duodenal GISTs,ensuring timely and accurate treatment.
基金Supported by the National Key R&D Program of China(No.2023YFC2410203)Beijing Hospitals Authority Clinical Medicine Development of Special Funding Support(No.ZLRK202503).
文摘AIM:To investigate the clinical features and prognosis of patients with orbital inflammatory myofibroblastic tumor(IMT).METHODS:This retrospective study collected clinical data from 22 patients diagnosed with orbital IMT based on histopathological examination.The patients were followed up to assess their prognosis.Clinical data from patients,including age,gender,course of disease,past medical history,primary symptoms,ophthalmologic examination findings,general condition,as well as imaging,laboratory,histopathological,and immunohistochemical results from digital records were collected.Orbital magnetic resonance imaging(MRI)and(or)computed tomography(CT)scans were performed to assess bone destruction of the mass,invasion of surrounding tissues,and any inflammatory changes in periorbital areas.RESULTS:The mean age of patients with orbital IMT was 28.24±3.30y,with a male-to-female ratio of 1.2:1.Main clinical manifestations were proptosis,blurred vision,palpable mass,and pain.Bone destruction and surrounding tissue invasion occurred in 72.73%and 54.55%of cases,respectively.Inflammatory changes in the periorbital site were observed in 77.27%of the patients.Hematoxylin and eosin staining showed proliferation of fibroblasts and myofibroblasts,accompanied by infiltration of lymphocytes and plasma cells.Immunohistochemical staining revealed that smooth muscle actin(SMA)and vimentin were positive in 100%of cases,while anaplastic lymphoma kinase(ALK)showed positivity in 47.37%.The recurrence rate of orbital IMT was 27.27%,and sarcomatous degeneration could occur.There were no significant correlations between recurrence and factors such as age,gender,laterality,duration of the disease,periorbital tissue invasion,bone destruction,periorbital inflammation,tumor size,fever,leukocytosis,or treatment(P>0.05).However,lymphadenopathy and a Ki-67 index of 10%or higher may be risk factors for recurrence(P=0.046;P=0.023).CONCLUSION:Orbital IMT is a locally invasive disease that may recur or lead to sarcomatoid degeneration,primarily affecting young and middle-aged patients.The presence of lymphadenopathy and a Ki-67 index of 10%or higher may signify a poor prognosis.
基金supported by the National Natural Science Foundation of China to L.H.(32470754 and 32070750)to X.M.(32170824 and 32322027)HRHl program of Westlake Laboratory of Life Sciences and Biomedicine to X.M.(1011103360222B1).
文摘Potassium channels regulate diverse biological processes,ranging from cell proliferation to immune responses.However,the functions of potassium homeostasis and its regulatory mechanisms in adult stem cells and tumors remain poorly characterized.Here,we identify Sandman(Sand),a two-pore-domain potassium channel in Drosophila melanogaster,as an essential regulator for the proliferation of intestinal stem cells and malignant tumors,while dispensable for the normal development processes.Mechanistically,loss of sand elevates intracellular K+concentration,leading to growth inhibition.This phenotype is rescued by pharmacological reduction of intracellular K+levels using the K+ionophore.Conversely,overexpression of sand triggers stem cell death in most regions of the midgut,inhibits tumor growth,and induces a Notch loss-of-function phenotype in the posterior midgut.These effects are mediated predominantly via the induction of endoplasmic reticulum(ER)stress,as demonstrated by the complete rescue of phenotypes through the co-expression of Ire1 or Xbp1s.Additionally,human homologues of Sand demonstrated similar ER stress-inducing capabilities,suggesting an evolutionarily conserved relationship between this channel and ER stress.Together,our findings identify Sand as a shared regulatory node that governs Drosophila adult stem cell dynamics and tumorigenesis through bioelectric homeostasis,and reveal a link between the two-pore potassium channel and ER stress signaling.
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.
基金Supported by 2025 Henan Medical Education Research Project,No.WJLX2025038.
文摘BACKGROUND Gastrointestinal(GI)tumors are among the most prevalent malignancies,and surgical intervention remains a primary treatment modality.However,the complexity of GI surgery often leads to prolonged recovery and high postoperative complication rates,which threaten patient safety and functional outcomes.Enhanced recovery after surgery(ERAS)principles have been shown to improve perioperative outcomes through evidence-based,multidisciplinary care pathways.Despite its widespread adoption,there is a paucity of research focusing specifically on optimizing ERAS-guided nursing processes in the post-anesthesia care unit(PACU)and evaluating its impact on perioperative safety in patients undergoing GI tumor surgery.This study aimed to investigate whether an ERASbased PACU nursing protocol could enhance recovery,reduce complications,and improve patient safety in this surgical population.AIM To explore the impact of optimizing the recovery room nursing process based on ERAS on the perioperative safety of patients with GI tumors.METHODS A total of 260 patients with GI tumors who underwent elective surgeries under general anesthesia in our hospital from August 2023 to August 2025 and were then observed in the recovery unit(PACU)were selected.They were randomly divided into the observation group(the PACU nursing process was optimized based on ERAS)and the control group(the conventional PACU nursing process was adopted)by the random number grouping method,with 130 cases in each group.The time of gastric tube removal,urinary catheter removal,defecation time,hospital stay,time of leaving the room after tube removal,retention time in the recovery room,occurrence of complications,satisfaction and readmission rate were compared between the two groups after entering the room.Compare the occurrence of adverse events in the PACU nursing process between the two groups.RESULTS The time of gastric tube removal,urinary catheter removal,defecation time,hospital stay,retention time in the recovery room,total incidence of complications and readmission rate in the observation group were significantly lower than those in the control group,and the satisfaction rate was higher than that in the control group(P<0.05).The occurrence of adverse events in the PACU nursing process in the observation group was lower than that in the control group(P<0.05).CONCLUSION Optimizing the PACU nursing process based on ERAS can effectively accelerate the recovery process of patients undergoing GI tumor surgery,reduce adverse events,improve nursing satisfaction,and at the same time,lower the incidence of adverse events in the PACU nursing process,providing a more refined management basis for clinical practice.
基金supported by Institute of Information&Communications Technology Planning&Evaluation(IITP)under the Metaverse Support Program to Nurture the Best Talents(IITP-2024-RS-2023-00254529)grant funded by the Korea government(MSIT).
文摘Brain tumors require precise segmentation for diagnosis and treatment plans due to their complex morphology and heterogeneous characteristics.While MRI-based automatic brain tumor segmentation technology reduces the burden on medical staff and provides quantitative information,existing methodologies and recent models still struggle to accurately capture and classify the fine boundaries and diverse morphologies of tumors.In order to address these challenges and maximize the performance of brain tumor segmentation,this research introduces a novel SwinUNETR-based model by integrating a new decoder block,the Hierarchical Channel-wise Attention Decoder(HCAD),into a powerful SwinUNETR encoder.The HCAD decoder block utilizes hierarchical features and channelspecific attention mechanisms to further fuse information at different scales transmitted from the encoder and preserve spatial details throughout the reconstruction phase.Rigorous evaluations on the recent BraTS GLI datasets demonstrate that the proposed SwinHCAD model achieved superior and improved segmentation accuracy on both the Dice score and HD95 metrics across all tumor subregions(WT,TC,and ET)compared to baseline models.In particular,the rationale and contribution of the model design were clarified through ablation studies to verify the effectiveness of the proposed HCAD decoder block.The results of this study are expected to greatly contribute to enhancing the efficiency of clinical diagnosis and treatment planning by increasing the precision of automated brain tumor segmentation.
文摘A clear goal in cold tumor research is to identify strategies for converting them into immunologically‘hot’tumors with enhanced immune cell infiltration and activity,thereby improving their responsiveness to immunotherapy.The genesis of cold tumors is exceedingly intricate.In recent times,as the analysis of this phenomenon has been pursued with greater depth,a suite of advanced diagnostic and therapeutic technologies has surfaced.These novel approaches and tactics are anticipated to modulate the tumor immune microenvironment across various dimensions,thereby facilitating the advancement of personalized and precise treatment modalities for cold tumors.The present article addresses the challenge of diminished therapeutic responsiveness to“cold tumors”within clinical settings.It systematically elucidates the multi-faceted regulatory mechanisms underlying immune evasion in cold tumors and offers a detailed analysis of advanced therapeutic strategies that incorporate nanotechnology,gene editing,and artificial intelligence methodologies.Furthermore,the future development trends of immunotherapy were explored in greater depth.It was posited that the convergence of artificial intelligence,multidimensional genomics,and emerging biotechnologies has presented positive prospects for the treatment of cold tumors,and has offered a theoretical foundation and technical framework for the transformation of cold tumors into“hot tumors”.
文摘Metastatic brain tumors undergo profound metabolic-epigenetic reprogramming driven by the unique constraints of the brain microenvironment.Hypoxia-inducible factor-1α(HIF1α)enhances glycolytic flux,lactate accumulation,and histone lactylation,collectively supporting metastatic colonization and immune evasion.Key metabolites including acetyl-CoA,S-adenosylmethionine(SAM),α-ketoglutarate(α-KG),fumarate,and 2-hydroxyglutarate(2-HG)-directly modify chromatin states by regulating histone acetyltransferases,DNA/histone methyltransferases,andα-KG dependent dioxygenases such as Ten-Eleven Translocation(TET)enzymes and lysine demethylases(KDMs).These metabolic shifts result in aberrant DNA methylation,histone lysine residue at position 27 on Histone H3(H3K27)trimethylation,and depletion of 5-hydroxymethylcytosine(5hmC),all of which are hallmark epigenetic alterations in brain metastasis and primary Central Nervous System(CNS)tumors.Additionally,the blood-brain barrier(BBB)and blood-tumor barrier(BTB)impose nutrient restrictions and induce metabolic dependency on glutamine,acetate,and lactate shuttling,thereby reshaping epigenetic enzyme activity.We synthesize current mechanistic evidence showing how metabolic pressures in the brain microenvironment remodel the epigenome to promote tumor plasticity,stemness,and therapeutic resistance.Understanding these coupled pathways reveals vulnerable nodes such as HIF1αsignaling,α-KG-dependent demethylation,and lactate-driven epigenetic remodeling that may be exploited for targeted treatment of metastatic brain tumors.The present review aims to provide in-depth insights into epigenetic regulation,including chromatin and histone modifications as well as noncoding RNAs and metabolic reprogramming,highlighting how the two interplay in the development and progression of metastatic brain tumors and their therapeutic potential.
文摘Background:In preclinical research,tumor growth inhibition in subcutaneous models is frequently employed to evaluate therapeutic efficacy;however,such models often lack clinical translatability.Methods:To better approximate clinical reality,taking the case of doxorubicin treatment,we utilized an orthotopic transplant and resection(OtR)strategy to systematically assess the effects of neoadjuvant chemotherapy,adjuvant chem-otherapy,and their combination on tumor growth,recurrence,and malignant progression.Results:Surprisingly,none of the treatments improved mouse survival,with adjuvant therapy even shortening it.Although neoadjuvant chemotherapy delayed preopera-tive tumor growth,and all regimens reduced recurrence rates,none effectively pre-vented metastasis.Furthermore,all treatment groups exhibited weight loss,indicative of chemotherapy-induced cachexia.Conclusions:Collectively,these findings demonstrate that reduced tumor growth in preclinical mouse models does not necessarily translate into overall survival benefit.Our results emphasize the critical importance of prioritizing metastasis prevention over tumor growth inhibition as a key efficacy endpoint in antitumor drug evaluation.
