BACKGROUND:Glioblastoma stem cells (GSCs), a stem-like tumorigenic subpopulation within glioblastoma (GBM), exhibit remarkable self-renewal capacity and therapeutic resistance. Zinc finger BED domain-containing protein 1 (ZBED1), a dual-function transcription factor and SUMO E3 ligase, has been implicated in oncogenic processes across malignancies, its functional role and regulatory mechanisms in GSCs remain enigmatic. METHODS:Multimodal approaches including, immunohistochemistry, immunoblotting, and immunofluorescence, were employed to evaluate ZBED1 expression patterns in GSCs and clinical GBM specimens. Functional characterization utilized in vitro models (proliferation assays, tumor-sphere formation assays, and limiting dilution analysis) complemented by in vivo orthotopic xenograft models. Mechanistic investigations integrated RNA sequencing, label-free proteomics, chromatin immunoprecipitation (ChIP), immunohistochemistry, and western blotting to delineate the EGFR/ZBED1 regulatory axis. RESULTS:We demonstrated that ZBED1 was significantly upregulated in GSCs and linked to unfavorable prognosis. Genetic ablation of ZBED1 significantly impaired GSC proliferation and self-renewal capacity while extending survival in xenograft models. Mechanistically, EGFR-mediated ZBED1 phosphorylation at tyrosine residues Y160/Y513 enhanced ZBED1-UBC9 interaction, promoting SUMOylation-dependent protein stabilization. Remarkably, ZBED1 reciprocally sustained EGFR expression through transcriptional repression of the E3 ubiquitin ligase PARK2, establishing a self-reinforcing EGFR/ZBED1/PARK2 signaling circuit critical for GSC maintenance. CONCLUSIONS:Our findings elucidate a novel EGFR/ZBED1 positive feedback loop that drives GSC propagation and tumorigenesis, highlighting ZBED1 as an attractive candidate for therapeutic targeting in GBM.

Metabolic reprogramming, particularly the altered nucleotide metabolism, is a critical driver of tumor heterogeneity and malignant progression in gastric cancer (GC). However, the core molecular determinants orchestrating this metabolic shift and its subsequent impact on the tumor microenvironment (TME) remain elusive. We integrated single-cell RNA sequencing (scRNA-seq), spatial transcriptomics, and bulk RNA-seq data to delineate the metabolic landscape of GC. The metabolic vulnerabilities and functional roles of the identified hub gene were systematically validated using in vitro assays, in vivo xenograft models, and pharmacological metabolic interventions. Pathway-level metabolic flux inference via scRNA-seq revealed a pronounced shift toward nucleotide interconversion and pyrimidine synthesis in malignant epithelial cells. We identified GNAS as a key metabolic hub gene, which is consistently upregulated in highly malignant subsets and strongly predictive of poor patient survival. Pseudotime and spatial transcriptomic analyses demonstrated that GNAS⁺ epithelial cells occupy terminally differentiated malignant states and specifically localize within spatial niches characterized by hyperactive nucleic acid metabolism and an immunosuppressive TME driven by cancer-associated fibroblasts (CAFs). Mechanistically, GNAS depletion profoundly impaired pyrimidine nucleotide (UMP/UDP) biosynthesis, which sequentially attenuated the activity of the ATF3-JUN-ETS1 transcriptional network, leading to suppressed GC cell proliferation, migration, and invasion, alongside induced apoptosis. Notably, exogenous uridine supplementation successfully rescued these malignant phenotypes, whereas pharmacological inhibition of pyrimidine synthesis (DHODH inhibitor) abolished the oncogenic advantage conferred by GNAS overexpression. GNAS is associated with the malignant evolution of GC by driving pyrimidine metabolic reprogramming and spatially coordinating TME remodeling. Targeting the GNAS-mediated metabolic-transcriptional axis exposes a novel therapeutic vulnerability, offering a promising translational strategy for precision oncology in GC.

BACKGROUND:Tumors are a major threat to human life and health. Neutrophil extracellular traps (NETs) have become a research focus in this context, especially regarding their role in tumor progression. Since the concept of NETs was introduced in 2004, its implications for tumor research have attracted significant scholarly attention. This study aims to explore research trends and cutting-edge hotspots in NETs and tumors through bibliometric analysis and provide new ideas for clinical applications. METHODS:We searched for literature on NETs and tumors published between 2004 and 2023 using the Web of Science database. Microsoft Excel 2019 was used for statistical analysis of influential articles, journals, authors, organizations, countries, and co-cited references. VOSviewer (version 1.6.16) and CiteSpace (V.5.8.R3) were employed for visualizing research data. RESULTS:The analysis covered 790 articles authored by 4768 individuals from 1134 organizations in 56 countries. China and the United States are the leading contributors. The mechanism of NETs in tumor occurrence and development is likely linked to coagulation, inflammation, and infection. Hot topics in research include dendritic cells and thrombosis, with a shift from laboratory studies to clinical applications, suggesting a growing focus on treatment over etiology. CONCLUSION:This study offers the most comprehensive bibliometric analysis of NETs and tumors to date. Future research may focus on developing targeted therapies that block the interaction between NETs and tumors, offering a new direction for cancer treatment.

A close relationship exists between excessive lipids and structural and functional brain dysfunction, with the long non‑coding (lncRNA)‑microRNA (miR)‑mRNA network having an emerging role. Given the increasingly recognized role of the lncRNA taurine upregulated gene 1 (TUG1) in metabolic and neurodegenerative diseases, the present study investigated its function and mechanism in palmitic acid (PA)‑induced neuronal injury. Results showed that lncRNA TUG1 expression was elevated in PA‑treated HT‑22 and SH‑SY5Y cells. Moreover, cell‑based in vitro detection including reverse transcription‑quantitative polymerase chain reaction, western blotting and lactate dehydrogenase cytotoxicity assays demonstrated a positive association between lncRNA TUG1 expression and lactate dehydrogenase release and cleaved caspase‑3 levels, whereas a negative association was observed with the expression levels of Bcl‑2 and synaptic proteins (synapsin‑1, synaptotagmin‑1 and brain‑derived neurotrophic factor) and the ratios of phosphorylated (p‑)Akt/Akt and p‑GSK‑3β/GSK‑3β. The downregulation of lncRNA TUG1 reversed PA‑induced damage in HT‑22 cells. Bioinformatics and dual‑luciferase assays identified miR‑449a‑5p as the direct target of lncRNA TUG1. Rescue experiments revealed that miR‑449a‑5p mediated the effects of lncRNA TUG1 by targeting caspase‑3 via the Akt/GSK‑3β pathway. Collectively, these findings establish a causal axis in which lncRNA TUG1 derepresses caspase‑3 and suppresses Akt/GSK‑3β signaling by sponging miR‑449a‑5p, thereby driving neuronal lipotoxic injury.

Hepato-pancreato-biliary (HPB) cancers affect human health and impose a significant burden on older adults. However, a comprehensive assessment of the global HPB disease burden in older adults is lacking. This research analyzed the trends in the burden of these cancers in older adults (aged 60–89 years) from 1992 to 2021 using data from the Global Burden of Disease Study (GBD) 2021. We examined the incidence, mortality, and disability-adjusted life years (DALYs) of liver cancer (LC), gallbladder and biliary tract cancer (GBTC), and pancreatic cancer (PC) in 204 countries and territories. Temporal trends were assessed using joinpoint regression and decomposition analysis with a focus on key global, regional, and national patterns. The incidence and mortality rates of LC and PC showed a consistent increase, particularly in regions with a high Socio-Demographic Index (SDI), whereas GBTC rates declined globally. Metabolic risk factors such as high Body Mass Index (BMI) were associated with increased DALYs for LC and PC. Projections indicate that the burden of these cancers will continue to increase. Our findings highlight the significant global disparities in the burden of HPB cancers among older adults, underscoring the need for targeted prevention and treatment strategies, particularly in regions with high SDIs. Fully assessed the global disease burden of hepato-pancreato-biliary cancers in older adults. Covered all factor variables and data that can be obtained. Based on the GBD database containing a large deposition of high-quality data. Provided insights for the medical and health management of hepato-pancreato-biliary cancers.

Following the publication of the above article and a corrigendum (doi: 10.3892/or.2017.5455) that was issued in 2017 to address issues of incorrect data assembly in Figs. 3 and  7, an interested reader drew to our attention that data also appeared to be duplicated in Fig. 4C, and data featured in Figs. 2 and 5 subsequently appeared in an article published by the same research group in the journal Oncotarget. Additionally, following an independent re‑evaluation of the data in this paper made by the Editorial Office, duplicated data were also noted in Fig. 5A, and some of the data in question subsequently appeared in an article in Journal of Enzyme Inhibition and Medicinal Chemistry in 2022 written by different authors at different institutes, which has since been retracted. In view of these additional findings, even though the possibility of a further corrigendum was originally considered, the Editor of Oncology Reports has decided that the paper should be retracted on account of a lack of confidence in the presented data. The authors were asked for an explanation to account for these concerns, but the Editorial Office did not receive a satisfactory reply. The Editor apologizes to the readrship for any inconvenience caused. [Oncology Reports 32: 205‑212, 2014; DOI: 10.3892/or.2014.3201].

Helicobacter pylori (HP) infection is the strongest environmental driver of gastric cancer, yet the epithelial programs that are progressively disrupted during infection and are associated with malignant transformation remain unclear. Trend-associated genes across HP-infection datasets (GSE60662, GSE60427) were identified using the Jonckheere–Terpstra test and intersected with survival-associated genes in TCGA-STAD. Random-forest modeling, multiple independent validation cohorts, functional analyses, single-cell RNA-seq (GSE249874), ligand–receptor inference, and spatial transcriptomics were integrated to define the biological role and microenvironmental impact of CFAP73. CFAP73 emerged as the top tumor-protective gene progressively downregulated during HP infection and strongly predictive of favorable survival and cisplatin benefit. CFAP73 expression marked a tumor-suppressive epithelial state characterized by reduced proliferation, EMT inhibition, and activation of p53 and apoptotic pathways. Single-cell analysis showed CFAP73 predominantly in non-malignant epithelial cells, with HP infection driving its loss. CFAP73 + epithelial cells displayed increased LCN2 expression and attenuated oncogenic signaling. Microenvironmentally, CFAP73_high tumors were enriched for effector and Th17 T cells and showed reduced exhausted T cells, Tregs, and pro-tumorigenic CAF states (iCAF, apCAF). Ligand–receptor modeling revealed that CFAP73 + epithelial cells received weaker WNT, TGFβ, and PDGF signals from CAFs but stronger cytotoxic interactions from T cells. Spatial transcriptomics confirmed spatial segregation of CFAP73 + epithelial regions from proliferative, hypoxic, immune-checkpoint–active niches. CFAP73 is a previously unrecognized epithelial tumor suppressor suppressed early during HP infection. Loss of CFAP73 may contribute to epithelial malignant reprogramming and reshapes fibroblast and T-cell states toward an immunosuppressive, pro-tumor microenvironment. CFAP73 represents a promising biomarker linking HP-driven mucosal injury to gastric cancer initiation, progression, and therapeutic response.

The neuroactive ligand–receptor signaling pathway is increasingly recognized as a regulator of tumor–immune interactions, yet its contribution to lung adenocarcinoma (LUAD) progression and immune evasion remains poorly defined. We integrated multi‑cohort transcriptomic datasets, including TCGA‑LUAD, GTEx lung tissues, pan‑cancer resources, single‑cell RNA‑seq spanning LUAD progression stages, dendritic‑cell subtype analyses, pySCENIC regulon inference, ligand–receptor interaction modeling, and Visium spatial transcriptomics. Neuroactive ligand–associated genes were evaluated for tumor upregulation, prognostic relevance, pathway activity, immune‑cell associations, transcriptional identity, cell–cell communication profiles, and spatial localization. DLX2 emerged as the top neuroactive‑associated candidate, showing robust tumor‑specific upregulation and strong association with poor overall, progression‑free, disease‑specific, and disease‑free survival in LUAD, with consistent adverse effects across multiple cancer types. DLX2 expression correlated with activation of cell‑cycle, chromatin‑remodeling and metabolic pathways, accompanied by a pronounced shift toward an immunosuppressive microenvironment characterized by enrichment of Tregs, exhausted T cells, and M2 macrophages and depletion of cytotoxic CD8⁺ and NK cells. Single‑cell profiling revealed that DLX2 is predominantly expressed in dendritic cells (DCs), where it defines a tolerogenic and hyper‑activated DC state marked by NF‑κB/TNF‑driven exhaustion signatures and regulon activity dominated by ATF3, FOSL2, FOSB, and ZMIZ1. DLX2+ DCs exhibited enhanced communication with Tregs and exhausted T cells through inhibitory ligand–receptor networks including CTLA4–CD80/CD86, PD‑1–PD‑L1, LGALS9–HAVCR2, and TGF‑β pathways, while reducing interactions with effector lymphocytes. Spatial transcriptomics further demonstrated that DLX2+ DCs are preferentially located within hypoxic, TGF‑β–rich niches co‑occupied by Tregs and Tex populations, indicating that DLX2+ DCs serve as spatial and functional hubs of immune suppression. This study identifies DLX2 as a potential neuroimmune‑associated driver of dendritic‑cell–mediated immune tolerance in LUAD. DLX2 defines a dysfunctional DC phenotype that promotes T‑cell exhaustion, macrophage polarization, and the formation of immunosuppressive tumor niches. These findings reveal a mechanistic link between neuroactive ligand signaling and immune evasion and highlight DLX2 as a promising biomarker and potential therapeutic target for reprogramming antitumor immunity in LUAD.

Background and objectives:Gastric cancer (GC) is a leading cause of cancer-related mortality worldwide and has a poor prognosis. Novel biomarkers are required to predict the survival of patients with this aggressive disease. Although the pan-immune-inflammation value (PIV) has been associated with outcomes in various malignancies, its prognostic role in GC remains unclear. Materials and methods:Clinical data of 793 patients with pT2-4 GC were retrospectively reviewed and analyzed. An optimal cutoff value was determined using receiver operating characteristic (ROC) curve analysis to stratify patients into high- and low-PIV groups. The prognostic performances of PIV and other immune-inflammatory biomarkers (IIBs) were compared using ROC analysis. Associations between the PIV and clinicopathological characteristics were also assessed. Kaplan-Meier survival curves were constructed for progression-free survival (PFS) and overall survival (OS). Univariate and multivariate Cox regression analyses were performed to determine independent prognostic factors. Results:The PIV demonstrated superior predictive value for survival compared to other peripheral blood-derived markers. High PIV values were significantly correlated with the Helicobacter pylori infection status, a larger tumor size, and an advanced TNM stage. Patients in the high-PIV group, particularly those with stages III and IV disease, had significantly worse PFS and OS. In multivariate analysis, the PIV remained an independent prognostic factor for survival outcomes in patients with pT2-4 GC. Conclusion:This study established PIV as a significant and independent prognostic biomarker for pT2-4 GC. PIV exhibits a more sensitive predictive ability for the tumor burden and systemic inflammation than other evaluated IIBs, which provides potential clinical value for patients with pT2-4 GC.

The endoplasmic reticulum (ER) is central to cholesterol biosynthesis and trafficking, yet paradoxically maintains low cholesterol levels, enabling it to sense fluctuations that impact various signalling pathways. However, the role of ER cholesterol in cellular signalling remains unclear. Here we show that the ER-phagy receptor FAM134B interacts directly with both cholesterol and SCAP, a key regulator of cholesterol biosynthesis. When ER cholesterol is high, FAM134B and SCAP are sequestered by cholesterol-tightened interactions, halting ER-phagy, STING activation and cholesterol synthesis. Under low cholesterol conditions, FAM134B dissociates from SCAP, allowing SCAP to activate SREBP2 and upregulate cholesterol synthesis, while FAM134B either facilitates ER-phagy through oligomerization or aids STING trafficking to activate innate immune responses. These findings reveal that the SCAP-FAM134B complex senses ER cholesterol levels, regulating both ER-phagy and immune signalling, with implications for diseases linked to cholesterol imbalance.

BackgroundMicrochromosome maintenance protein-binding protein (MCMBP) is aberrantly expressed in cancers and proposed as a diagnostic marker and therapeutic target, but its role in pancreatic ductal adenocarcinoma (PAAD) remains unclear.MethodsWe performed a comprehensive analysis of MCMBP in PAAD using multi-omics data resources, including TCGA, GTEx, CPTAC, GEO, GDSC, TIDE, HPA, MethSurv, DiseaseMeth, and LinkedOmicsKB. We examined its prognostic characteristics, epigenetic alterations, immune infiltration, immunotherapy response, and drug sensitivity. By integrating transcriptomic, proteomic, and phosphoproteomic data, we explored the biological functions and pathways of MCMBP. Sensitive drugs related to MCMBP were identified through the GDSC and Connectivity Map (CMap) drug libraries, with further functional insights obtained through GO and KEGG enrichment analyses. Potential mechanisms were investigated via gene functional experiments, phos-phorylation site predictions from LinkedOmicsKB, and protein expression validation.ResultsPan-cancer analysis revealed that MCMBP overexpression correlates with poor prognosis, including in PAAD. Cox regression identified MCMBP as an independent prognostic factor for PAAD. Low DNA methylation and high m6A modification of MCMBP may promote PAAD progression and correlate with adverse prognosis. Ge-ne function and immune infiltration analyses indicated that high MCMBP expression is closely associated with immune-related pathways, tumor cell proliferation, survival, and immune cell differentiation, and may promote Treg accumulation and immune ch-eckpoint upregulation. PAAD patients with low MCMBP expression exhibited greate-r sensitivity to anti-PD-L1 immunotherapy, suggesting a potential synergistic effect o-f MCMBP expression with anti-PD-L1 treatment. High MCMBP expression was ass-ociated with sensitivity to Gemcitabine combined with Paclitaxel, as well as small mo-lecules such as Tozasertib and Motesanib. MCMBP knockdown inhibited PAAD cell proliferation, migration, invasion, and G1-S transition. Immunohistochemical results s-howed that high MCMBP expression correlated with elevated PD-L1 levels and redu-ced CD4+ T cell infiltration in PAAD, which significantly associated with poor prog-nosis. MCMBP modulated PD-L1 through activation of the JAK-STAT3 signaling pat-hway, thereby promoting PAAD progression.ConclusionsOverexpression of MCMBP may serve as a prognostic biomarker and p-otential therapeutic target in PAAD. It drives PAAD progression by activating the JAK-STAT3 pathway to upregulate PD-L1.

BackgroundGastric cancer is a serious disease that threatens human life; early diagnosis and treatment have been the focus of many studies. With advancements in imaging evaluation and machine learning, early detection and treatment of gastric cancer have become feasible. This study aimed to explore research trends and hotspots in the field of gastric cancer and machine learning through bibliometric analysis and to provide new insights for related clinical applications.MethodsLiterature on gastric cancer and machine learning published from 2004 to 2023 was retrieved from the Web of Science database. Microsoft Excel 2019 was used for statistical analysis of influential articles, journals, authors, organizations, countries (regions), and co-citation references in this research domain. VOSviewer (version 1.6.16) and CiteSpace (version 5.8.R3) were utilized to visualize the corresponding data.ResultsWe analyzed and evaluated 425 articles authored by 2,899 researchers from 825 organizations across 52 countries (regions). The People’s Republic of China, the Chinese Academy of Sciences, and the University of the Chinese Academy of Sciences were identified as leaders in this field. The article “Genome-wide cell-free DNA fragmentation in patients with cancer,” published in Nature, was the most frequently cited work. The diagnosis and treatment of gastric cancer have consistently been research hotspots, with a shift in focus from laboratory-based studies to clinical applications. This trend highlights the transition from etiology-oriented research to studies emphasizing treatment and practical applications.ConclusionsThis study offers a comprehensive visual analysis of research on gastric cancer and machine learning, representing the most detailed bibliometric study in this domain. With the continuous advancement of research, artificial intelligence-assisted early diagnostic methods for gastric cancer and corresponding treatment strategies may emerge as a pivotal direction for future research in this area.

IntroductionThe nuclear receptor TR4 binding protein, TRA16, has been implicated in lung carcinogenesis; however, its broader role across diverse human cancers remains poorly understood. Understanding TRA16’s involvement in cancer biology could uncover novel regulatory mechanisms and potential therapeutic targets.MethodsWe conducted a comprehensive pan-cancer analysis of TRA16 expression and function across multiple human malignancies. Gene co-expression networks, pathway enrichment, transcription factor analysis, organoid modeling, and intercellular communication profiling were employed. Tumor mutation burden (TMB) and microenvironmental features were also assessed in relation to TRA16 expression, stratified by TP53 mutation status.ResultsCorrelation analysis identified the cell cycle as the top enriched pathway among TRA16-associated genes, with key transcription factors, including RB-E2F, MYC, and TP53, regulating genes co-expressed with TRA16. In liver cancer organoid models, TRA16 and its co-expressed genes were significantly upregulated. Intercellular communication analysis showed that TRA16-positive cells exhibited increased autocrine signaling and overall signaling activity. Importantly, patients with high TRA16 expression demonstrated elevated TMB and decreased stromal and immune features.DiscussionThese findings highlight TRA16 as a potential master regulator of oncogenic processes, contributing to tumor progression through coordinated regulation of cell cycle genes, intercellular signaling, and genomic instability. Our results provide new insights into TRA16’s role across cancers and support its potential as a novel oncogene.

Background:Synchronous oligometastatic esophageal squamous cell carcinoma (SOESCC), characterized by a limited number of metastases at diagnosis, represents a significant subset of esophageal squamous cell carcinoma. However, the optimal treatment modality for the condition has not been determined. Therefore, we aimed to evaluate the efficacy of local consolidative radiotherapy (cRT) for the primary tumor combined with first-line chemoimmunotherapy (CIT). Methods:This retrospective cohort study included 102 patients with SOESCC who underwent first-line CIT, either alone or in combination with cRT, between 2018 and 2022. We analyzed the progression-free survival (PFS) and overall survival (OS) in the two groups using propensity score matching (PSM). Univariate and multivariate Cox regression analyses were performed to identify prognostic factors associated with PFS and OS. Failure patterns were compared between groups. Results:Patients who received the additional cRT had longer PFS (median PFS, 11.5 vs. 8.3 months, P = 0.009) than did those who received CIT only; however, no significant difference was noted in OS (median OS, 20.0 vs. 17.0 months, P = 0.410) between the two groups. These results remained consistent after PSM and multivariate Cox regression analyses (PFS: hazard ratio [HR] 0.539, 95% confidence interval [CI], 0.312-0.932, P = 0.027; OS: HR, 0.580, 95% CI, 0.307-1.095, P = 0.093). Notably, the pattern of failure in the CIT group was primarily characterized by locoregional failure, in contrast to the distant failure observed in the CIT + cRT group. Locoregional failure-free survival in the CIT + cRT group was significantly lower than that in the CIT group (P < 0.001). Moreover, no statistically significant difference was observed in the incidence of treatment-related adverse events between the two groups. Conclusions:In patients with SOESCC, the combination of local cRT and first-line CIT prolonged PFS without increasing treatment-related toxicity. In addition, cRT for primary tumor significantly reduced the incidence of locoregional failure. This synergistic approach appears to be a viable and potentially superior treatment strategy for the treatment of SOESCC.

The prevalence of lung cancer has increased significantly in recent years. This malignancy is the most lethal form of tumor and exhibits the highest morbidity and mortality rates among all malignant tumors. Venous thromboembolism (VTE) includes both pulmonary embolism (PE) and deep vein thrombosis (DVT). Although DVT and PE are presentations of VTE at various stages, most PE emboli originate from DVT. DVT is a severe condition as blood clots produced in the veins can detach and enter the lungs, causing a pulmonary embolism. Lung cancer has the highest incidence of DVT, which is one of the most prevalent preventable causes of hospital-associated death. The formation of DVT in lung cancer patients is connected to several factors, including anticoagulants, surgery, chemotherapy, genetics and age. Tissue factors (TFs), platelets, and inflammatory factors have also been reported to play crucial roles. However, no comprehensive study has been conducted to provide a holistic analysis of the specific mechanisms and treatment of DVT in combination with lung cancer. This review offers a thorough analysis of the risk factors contributing to DVT formation and coagulation-related substances in cancer patients with DVT, focusing specifically on the mechanisms underlying DVT in lung cancer. The clinical management of DVT complicated by lung cancer is also discussed.

e16110 Background: Therapeutic options for metastatic esophageal squamous cell carcinoma (ESCC) primarily involve immunotherapy combined with chemotherapy. For locally advanced ESCC, concurrent chemoradiotherapy (CRT) or radiotherapy is the standard regimen. Anti-angiogenic agents hold promise to enhance CRT efficacy. Anlotinib, a multi-target anti-angiogenic agent inhibiting VEGFR, PDGFR, FGFR, and c-KIT, may enhance radiotherapy by alleviating tumor hypoxia. This multi-center, retrospective study evaluates the efficacy and safety of anlotinib combined with radiotherapy in ESCC. Methods: This study screened patients (pts) with locally advanced or metastatic ESCC treated with anlotinib (8-12 mg, p.o., qd, d1-14, q3w) and radiotherapy from June 2018 to June 2024 retrospectively. Two cohorts were included: Cohort 1 (metastatic ESCC) and Cohort 2 (locally advanced ESCC). Cohort 2 was divided into an observational group (OG, anlotinib + radiotherapy ± chemotherapy) and a control group (CG, radiotherapy ± chemotherapy). Radiotherapy doses for primary lesions were 45-60 Gy, while metastatic lesions received either ≥45 Gy or stereotactic body radiotherapy (≥3 Gy/fraction, ≥30 Gy). No limitation of the chemotherapy regimens. Cohort 1 aimed for 50 pts, while Cohort 2 intended to include 100 in the OG and 100 in the CG. The primary endpoint was OS, with secondary endpoints including ORR, DCR, PFS, and safety. Results: By December 24, 2024, 252 pts had been enrolled: 38 in Cohort 1, 112 in the OG, and 102 in the CG of Cohort 2. In Cohort 1, all 38 pts had a median OS of 24.0 months (mo) (95% CI: 21.6-26.4) and a median PFS of 9.2 mo (95% CI: 7.5-11.0). The 24-month OS and PFS rates were 51.5% (95% CI: 25.9-72.2) and 26.8% (95% CI: 6.7-52.8), respectively. In Cohort 2, after propensity score matching, 74 pts in the OG and 102 pts in the CG were analyzed. The preliminary median OS in the CG was 26.4 mo (95% CI: 21.4–32.4), but remained immature in the OG (>36 mo). The 24-month OS rate was 54.6% (95% CI: 44.0–64.1) in the CG and 75.0% (95% CI: 61.2–84.5) in the OG and 36-month OS rate was 41.2% (95% CI: 30.4–51.7) in the CG and 65.6% (95% CI: 47.1–79.0) in the OG, showing a significant difference between the two groups ( P = 0.0297). However, PFS did not differ significantly [median PFS: 13.6 mo in CG vs NA in OG (>20 mo), P = 0.1713]. The incidence of any-grade TEAEs was 71.1% in Cohort 1 and 64.3% in Cohort 2 OG with Grade 3+ TEAEs of 10.5% and 10.7%, respectively. Safety profile in the CG is still being collected. Conclusions: Anlotinib combined with radiotherapy showed a trend toward improved OS in ESCC compared to radiotherapy ± chemotherapy with an acceptable TEAE profile. These findings support its potential therapeutic role, but longer follow-up is needed for confirmation. Clinical trial information: ChiCTR2400094643 .

As a new type of pollutant, the harm caused by microplastics (MPs) to organisms has been the research focus. Recently, the proportion of MPs ingested through the digestive tract has gradually increased with the popularity of fast-food products, such as takeout. The damage to the digestive system has attracted increasing attention. We reviewed the literature regarding toxicity of MPs and observed that they have different effects on multiple organs of the digestive system. The mechanism may be related to the toxic effects of MPs themselves, interactions with various substances in the biological body, and participation in various signaling pathways to induce adverse reactions as a carrier of toxins to increase the time and amount of body absorption. Based on the toxicity mechanism of MPs, we propose specific suggestions to provide a theoretical reference for the government and relevant departments.

Tumors are one of the major diseases affecting human life and health with an increasing incidence worldwide. Drug therapy is the most commonly used treatment for tumors. Therefore, screening for antitumor drugs has always been a focus of tumor research. Tumor organoids are an emerging screening drug model. As a 3D in vitro model, organoids not only retain the characteristics of the parent tumor well, but also reflect the role of the tumor microenvironment, making them an excellent platform for screening antitumor drugs. In recent years, organoid culture technology has developed rapidly and several tumor organoid libraries have been gradually established for research using cryopreservation and transgeneration methods. However, a lack of systematic summaries of organoids and tumor-screening drugs still exists. This review outlines the development of antitumor drug screening methods and summarizes common organoid models used for antitumor drug screening, including patient-derived tumor organoids and patient-derived organoids-based xenograft and subcutaneous transplantation models. In addition, the clinical application status of organoid technology in drug screening for various tumors is summarized, and the advantages and bottlenecks of organoid technology are objectively analyzed. In future, the combination of organoids and tumor-screening drugs will provide significant value in the treatment of tumors.

Cancer is characterized by unlimited proliferation and metastasis, and traditional therapeutic strategies usually result in the acquisition of drug resistance, thus highlighting the need for more personalized treatment. mRNA vaccines transfer the gene sequences of exogenous target antigens into human cells through transcription and translation to stimulate the body to produce specific immune responses against the encoded proteins, so as to enable the body to obtain immune protection against said antigens; this approach may be adopted for personalized cancer therapy. Since the recent coronavirus pandemic, the development of mRNA vaccines has seen substantial progress and widespread adoption. In the present review, the development of mRNA vaccines, their mechanisms of action, factors influencing their function and the current clinical applications of the vaccine are discussed. A focus is placed on the application of mRNA vaccines in cancer, with the aim of highlighting unique advances and the remaining challenges of this novel and promising therapeutic approach.

Incidence of a number of liver diseases has increased. Gut microbiota serves a role in the pathogenesis of hepatitis, cirrhosis and liver cancer. Gut microbiota is considered 'a new virtual metabolic organ'. The interaction between the gut microbiota and liver is termed the gut‑liver axis. The gut‑liver axis provides a novel research direction for mechanism of liver disease development. The present review discusses the role of the gut‑liver axis and how this can be targeted by novel treatments for common liver diseases.