Colon cancer is a leading cause of cancer-related deaths worldwide. The epithelial-mesenchymal transition (EMT) plays an important role in tumor metastasis of colon cancer. We first evaluated the effects of EMT-related transcription factors on the prognosis of colon cancer through analysis the data obtained from The Cancer Genome Atlas (TCGA). And then we screened a series of Chinese medicine monomers to find effect EMT inhibitors. First, Snail is a more important EMT transcription factors for colon cancer prognosis, compared with Twist and Slug. Then, we found that apigenin effectively inhibits the activity of Snail. Apigenin could inhibit the EMT, migration, and invasion of human colon cancer cells in vitro and in vivo through the NF-κB/Snail pathway. Snail is a key regulator of EMT in colon cancer and Snail inhibitor apigenin may be a therapeutic application for patients with colon cancer.

BACKGROUND:Skull base necrosis can cause life-threatening massive bleeding in patients following radiotherapy and chemotherapy for nasopharyngeal carcinoma. Patients with bilateral internal carotid artery rupture and hemorrhage are especially susceptible, which is a major challenge for clinicians. METHODS:A team at the Eye and ENT Hospital affiliated with Fudan University recently successfully treated a patient with skull base necrosis after radiotherapy and chemotherapy for nasopharyngeal carcinoma. The patient experienced bilateral internal carotid artery rupture with massive nasopharyngeal hemorrhage and was treated with extracranial-intracranial bypass surgery, resection of the nasal skull base necrotic lesions, and bilateral internal carotid artery occlusion. RESULTS:One week after the last surgery, the patient recovered well, and normal activity was restored. CONCLUSIONS:Simultaneous EC-IC bypass and TMF repair increase intracranial blood flow compensation without the need for an additional incision, saving the patient's life and improving their quality of life. These results highlight a promising surgical practice for rescuing patients suffering from skull base necrosis and ICA rupture hemorrhage.

KEY POINTS:Mucosal flap reconstruction can improve the long-term survival rate of patients with recurrent nasopharyngeal carcinoma. Mucosal flap reconstruction also increases the treatment-related risks of ear fullness and dysphagia. This matching study provides preliminary evidence for the use of mucosal flap reconstruction in salvage endoscopic nasopharyngectomy.

To characterize research on inflammation in CRS over the past 23 years, and analyze trends in hotspots, and collaboration networks. We conducted a methodological, objective, and extensive analysis of inflammation in CRS to track research trends and hotspots. Original research literature published between 2000 and 2023 was obtained from The Web of Science Core Collection (WoSCC) database. Data on country/region, institution, author, journal, keywords, and references were extracted using VOSviewer and CiteSpace for analysis. The number of publications on inflammation in CRS has significantly increased over the past 23 years. The United States has been the most prolific contributor in terms of publications and collaborations. The top 10 high-frequency keywords were “chronic rhinosinusitis,” “nasal polyps,” “asthma,” “inflammation,” “sinusitis,” “rhinosinusitis,” “eosinophils,” “nasal polyposis,” “chronic rhinosinusitis with nasal polyps,” and “allergic rhinitis.” The timeline view revealed changes in keywords over time, with endotype and biologics emerging as recent hotspots. Substantial improvement has been made in the study of inflammation in CRS. The United States leads with the most published articles, productive institutions, and influential journals. Strengthening collaborations between institutions and countries is recommended. The current focus is primarily on immunotherapy, and inflammation in CRS is likely to continue being a prominent topic.

Following the publication of this paper, it was drawn to the Editor's attention by a concerned reader that, regarding the confocal microscopic images shown in Fig 3, the top (Sham) and bottom (SCI) data panels appeared to show a small section of overlapping data, such that data which were intended to show the results from differently performed experiments had apparently been derived from the same original source. The authors were contacted by the Editorial Office to offer an explanation for this apparent anomaly in the presentation of the data in this paper; however, up to this time, no response from them has been forthcoming. Owing to the fact that the Editorial Office has been made aware of potential issues surrounding the scientific integrity of this paper, we are issuing an Expression of Concern to notify readers of this potential problem while the Editorial Office continues to investigate this matter further. [Molecular Medicine Reports 18: 2237‑2244, 2018; DOI: 10.3892/mmr.2018.9194].

BACKGROUND:Stroke is a common fatal and disabling disease in the elderly. We investigated the correlation and potential benefits of dietary intake of flavonoid compounds and their subclasses in elderly stroke patients. METHODS:This study analyzed data from the National Health and Nutrition Examination Survey (NHANES) for the cycles 2007-2010 and 2017-2018. Dietary flavonoids intake was calculated based on food frequency questionnaires (FFQ) through a 24-hour dietary recall. To explore the relationship between flavonoids intake and their subclasses with stroke prevalence, we employed multivariable logistic regression models, adjusting for relevant covariates. Restricted cubic splines (RCS) and generalized additive models (GAMs) were applied to explore potential nonlinear relationships between flavonols subclasses and stroke prevalence. Multivariable logistic regression models were conducted both for the overall population and stratified by flavonols subclasses intake. Additionally, we utilized Bayesian kernel machine regression (BKMR) to evaluate the overall effect of flavonols intake levels on stroke status, accounting for potential interaction and correlation between subclasses. Given the high correlation among flavonols subclasses, we incorporated a hierarchical variable selection approach using a Markov Chain Monte Carlo (MCMC) algorithm. Finally, we analyzed the XGBoost model by applying SHAP (SHapley Additive exPlanations) values to assess the specific contribution of different flavonoids intake to stroke. RESULTS:Including 3,806 elderly stroke patients, the study revealed an inverse relationship between dietary flavonoids and their subclasses and stroke prevalence. After adjusting for potential confounders, it was found that higher quartiles of flavonols intake were associated with lower stroke prevalence. Specifically, with each unit increase in flavonols (Q4) intake, the odds of stroke in the elderly decreased by 61 % (OR=0.390, 95 % CI [0.209-0.728]; P = 0.005). Similar results were observed for the subclasses of flavonols. Subgroup analyses indicated that age and poverty index ratio (PIR) were effect modifiers in the relationship between flavonols intake and stroke. We further examined the intake levels of dietary flavonols subclasses such as isorhamnetin, kaempferol, myricetin, and quercetin and their association with stroke status stratified by population characteristics. In addition to age and PIR, hyperlipidemia and body mass index (BMI) were found to be the most common significant influencing factors in the relationship between flavonols subclasses and stroke prevalence. Furthermore, RCS revealed a "U"-shaped nonlinear relationship between flavonols, including their quercetin and kaempferol subclasses, and stroke, whereas the relationship between stroke and myricetin was linear. Our study also assessed the overall impact of dietary flavonols subclasses on stroke in the elderly and the interrelationships among these subclasses. The results consistently indicated a negative joint effect of flavonols subclass mixtures on the stroke status in the elderly. When evaluating the impact of individual flavonols subclasses on stroke status, a potential dose-response relationship was observed, with increasing intake of myricetin being associated with a decreased risk of stroke. Furthermore, SHAP plots show that flavonols intake is predominantly associated with negative SHAP values, indicating that higher dietary flavonols intake corresponds to a lower predicted stroke risk. CONCLUSION:These results emphasize that adhering to an increased dietary intake of flavonoid compounds, particularly flavonols and their subclasses such as myricetin, is inversely associated with the prevalence of stroke among the U.S. elderly population. This offers potential benefits for stroke patients, especially among elderly individuals aged 60-70 and those with higher incomes.

Objective:To investigate the anatomic origin of juvenile nasopharyngeal angiofibroma（JNA） through radiologic analysis of tumor invasion patterns, providing insights into tumor etiology and surgical recurrence prevention. Methods:This retrospective cohort study included primary JNA cases at the Department of Otorhinolaryngology, Eye and ENT Hospital of Fudan University from March 2015 to September 2024. All patients underwent preoperative high-resolution CT（HRCT） scans, and some underwent enhanced magnetic resonance imaging. The study retrospectively analyzed the patients' imaging data to examine tumor invasion into the pterygopalatine fossa and the vidian canal. These sites were categorized into non-invaded, partially invaded, and completely invaded for the pterygopalatine fossa and the vidian canal. The study analyzed the proportions of invasion at these sites to further speculate on the origin of JNA. Results:A total of 105 JNA patients were included in the study. Among them, 100% of the patients had complete tumor invasion in the pterygopalatine fossa. For the vidian canal, the proportions of complete invasion, partial invasion, and non-invasion were 54.3%, 27.6%, and 18.1%, respectively. As the staging of JNA tumors increased, the proportion of vidian canal invasion also increased. Conclusion:Our evidence suggests that the pterygopalatine fossa, rather than the vidian canal, might be the likely origin of JNA, which is enlightening for the study of the etiological mechanisms of JNA.

Following the initial treatment of nasopharyngeal carcinoma (NPC), tumor progression often portends an adverse prognosis for these patients. MicroRNAs (miRNAs) have emerged as critical regulators of tumor immunity, yet their intricate mechanisms in NPC remain elusive. Through comprehensive miRNA sequencing, tumor tissue microarrays and tissue samples analysis, we identified miR-142-3p as a significantly upregulated miRNA that is strongly associated with poor prognosis in recurrent NPC patients. To elucidate the underlying molecular mechanism, we employed RNA sequencing, coupled with cellular and tissue assays, to identify the downstream targets and associated signaling pathways of miR-142-3p. Our findings revealed two potential targets, CFL2 and WASL, which are directly targeted by miR-142-3p. Functionally, overexpressing CFL2 or WASL significantly reversed the malignant phenotypes induced by miR-142-3p both in vitro and in vivo. Furthermore, signaling pathway analysis revealed that miR-142-3p repressed the RIG-I-mediated immune defense response in NPC by inhibiting the nuclear translocation of IRF3, IRF7 and p65. Moreover, we discovered that ADAR1 physically interacted with Dicer and promoted the formation of mature miR-142-3p in a dose-dependent manner. Collectively, ADAR1-mediated miR-142-3p processing promotes tumor progression and suppresses antitumor immunity, indicating that miR-142-3p may serve as a promising prognostic biomarker and therapeutic target for NPC patients.

Olfactory neuroblastoma (ONB) is a rare malignancy known to originate from the olfactory epithelium. The complex tumor ecosystem of this pathology remains unclear. Here we explored the cellular components within 10 ONB tumors and 1 olfactory mucosa sample based on single cell RNA profiles. We showed the intra-tumoral heterogeneity by identifying five unique expression programs among malignant epithelial cells. A novel three-classification system (Neural/Basal/Mesenchymal) of ONB was established according to the distinguished gene expression patterns. Biomarkers for categorizing bulk tumors into the new subtypes were elucidated. Different responses towards certain chemotherapy regimens could be cautiously inferred according to the molecular features representing three tumor types,thus helping with precision chemotherapy. Herein, we also analyzed subclusters of tumor microenvironment (TME) and the interactions among different cell types in the TME. Relative abundance of immunosuppressive tumor associated macrophages indicated the benefits of immunotherapies targeting macrophages.

Chronic rhinosinusitis with nasal polyps (CRSwNP) is an inflammatory upper airway disease, divided into eosinophilic CRSwNP (eCRSwNP) and noneosinophilic CRSwNP (neCRSwNP) according to eosinophilic levels. Neutrophils are major effector cells in CRSwNP, but their roles in different inflammatory environments remain largely unclear. We performed an integrated transcriptome analysis of polyp-infiltrating neutrophils from patients with CRSwNP, using healthy donor blood as a control. Additional experiments, including flow cytometry and in vitro epithelial cell and fibroblast culture, were performed to evaluate the phenotypic feature and functional role of neutrophils in CRSwNP. Single-cell RNAsequencing analysis demonstrated that neutrophils could be classified into 5 functional subsets, with GBP5+ neutrophils occurring mainly in neCRSwNP and a high proportion of CXCL8+ neutrophils in both subendotypes. GBP5+ neutrophils exhibited significant IFN-I pathway activity in neCRSwNP. CXCL8+ neutrophils displayed increased neutrophil activation scores and mainly secreted oncostatin M (OSM), which facilitates communication with other cells. In vitro experiments showed that OSM enhanced IL-13- or IL-17-mediated immune responses in nasal epithelial cells and fibroblasts. Our findings indicate that neutrophils display transcriptional plasticity and activation when exposed to polyp tissue, contributing to CRSwNP pathogenesis by releasing OSM, which interacts with epithelial cells and fibroblasts depending on the inflammatory environment.

>Aging is the greatest risk factor for cardiovascular disease (CVD),which is the most common cause of death in European countries.[1]It is estimated that during the period from 2020 to 2022,there were 9.0%more excess deaths from CVD than expected.[2]By 2030,approximately 20%of the population will be aged 65 years and older,and CVD will account for 40%of deaths in this age group,[3]imposing a significant burden on the healthcare system and society as a whole.Aging is related to frailty,which represents the dynamic progression of physical and physiological decline in older adults.Frailty limits an individual’s ability to recover from acute stressors and serves as a predictor of clinical adverse outcomes.Despite the uncertainties in screening,assessing,and managing frailty in clinical practice,emphasizing the connections between frailty,aging,and CVD will provide new insights for the prediction,prevention and management of CVD in the aging population.

Olfactory neuroblastoma (ONB) is an uncommon malignant tumor known to originate from the olfactory epithelial. The complex tumor ecosystem of this pathology remained unclear. Here, we explored the cellular components with ONB tumors based on scRNA profiles of 96,325 single-cells derived from 10 tumors and 1 olfactory mucosa sample. We discovered 11 major cell types, including 6 immune cell, 3 stromal cell subtypes and epithelial cluster in the tumor microenvironment (TME), and identified 5 common expression programs from malignant epithelial cells. We analyzed subclusters of TME and the interactions among different cell types in the TME. An innovative three-classification of ONB was established via scRNA analysis. Markers for categorizing tumor samples into new subtypes were elucidated. Different responses towards certain chemotherapy regimens could be inferred according to the molecular features of three tumor types. Relative abundance of immunosuppressive TAMs indicated the benefits of immunotherapies targeting myeloid cells.

Purpose: Adenoid cystic carcinoma (ACC) is an aggressive cancer that often leads to poor prognosis, especially when it has metastasized. The prognostic significance of primary tumor surgery (PTS) for ACC with distant metastasis (DM) at the time of diagnosis has not been extensively studied. Methods: Using data from the surveillance, epidemiology, and end results (SEER) database from 2010 to 2019, we identified patients with ACC in head and neck region and synchronous DM. We evaluated the effect of PTS on different patterns of metastasis using Kaplan-Meier analysis, log-rank tests, and multivariate Cox regression analysis to assess the therapeutic benefit of PTS in the overall cohort and various subgroups. Results: Of the 192 identified patients with synchronous metastatic ACC of head and neck, 91 (47.4%) underwent PTS. Patients who received PTS had significantly better survival than nonsurgical patients (median overall survival: 19 vs 43 months, P = .006). Cox regression analysis also showed that PTS was associated with improved survival (HR = .46, 95% CI: 0.42-0.88; P = .028). In sub-analyses, except for patients with liver metastases [overall survival (OS), P = .107, cancer-specific survival (CSS), P = .153], PTS consistently conferred significant survival benefits in patients with bone metastases (OS, P = .041, CSS, P = .065) and lung metastases (OS, P = .016, CSS, P = .027). PTS also led to better survival in patients who did not receive radiotherapy (median OS: 13 vs 52 months, P = .007). Conclusion: Our study suggests that PTS in metastatic ACC patients of head and neck improved overall and CSS, particularly in those with bone or lung metastases and those who did not receive radiotherapy. However, further prospective studies are needed to confirm these findings, and the indications for PTS in metastatic ACC should be carefully evaluated by a multidisciplinary board.

Autophagy is a highly evolutionary conserved process that degrades cytosolic macromolecules or damaged organelles (e.g., mitochondria), as well as intracellular pathogens for energy and survival. Dysfunction of autophagy has been associated with the pathologies of Alzheimer’s disease (AD), including Aβ plaques and neurofibrillary tangles. Recently, the presence of sustained immune response in the brain has been considered a new core pathology in AD. Accumulating evidence suggests that autophagy activation may suppress inflammation response through degrading inflammasomes or pro-inflammatory cytokines and improving immune system function in both clinical trials and preclinical studies. This review provides an overview of updated information on autophagy and inflammation and their potential mediators in AD. In summary, we believe that understanding the relationship between autophagy and inflammation will provide insightful knowledge for future therapeutic implications in AD.

Background: The aim of this study is to investigate the potential key genes related to Methods: Datasets GSE36830 and GSE72713 were obtained from Gene Expression Omnibus. Dataset GSE36830 was used to identify differentially expressed genes in CRSwNP patients. GO, KEGG analysis, and PPI network analysis were applied to further investigate the function of DEGs in CRSwNP. GSEA was also performed to explore the mechanisms of DEGs. Dataset GSE72713 was applied to validate the key gene. Moreover, to detect the expression of target gene, nasal polyp tissues and middle turbinate specimens were collected from CRSwNP patients (n = 20) and controls (n = 20), respectively. RT-PCR, Western blot, and immunofluorescence staining were applied. HE and AB-PAS staining were used to assess the infiltration of inflammatory cells. The proliferation and migration ability of human nasal epithelial cells (HNEpCs) were tested via Cell Counting kit-8, wound healing assay and Transwell migration assay. Air-liquid interface was used to culture primary human nasal epithelial cells (pHNECs) from health controls and nasal polyp tissues of CRSwNP patients. Results: A total of 1035 DEGs were identified, and 661 genes were up-regulated and 374 genes were down-regulated. According to PPI network analysis, the top 10 scored genes were identified. Among them, only EGF was down-regulated in CRSwNP. Meanwhile, GSEA result shows that EGF is significantly enriched in WNT activated receptor activity. CCK-8, wound healing assay, and transwell migration assay indicated that recombinant human EGF can promote the proliferation and migration of HNEpCs in vitro. Immunofluorescence staining shows that rhEGF can increase the expression of ZO-1 in pHNECs from nasal polyp tissues. Conclusion: Bioinformatics analysis and in vitro experiments were used to explore the pathogenesis of CRSwNP, and the results showed that EGF may play an important role in the protection of nasal epithelial barrier.

Background Colon adenocarcinoma (COAD) is a fatal disease, and its cases are constantly increasing worldwide. Further, the therapeutic and management strategies for patients with COAD are still unsatisfactory due to the lack of accurate patient classification and prognostic models. Therefore, our study aims to identify prognostic markers in patients with COAD and construct a cell subtype-specific prognostic model with high accuracy and robustness. Methods Single-cell transcriptomic data of six samples were retrieved from the Gene expression omnibus (GEO) database. The cluster annotation and cell-cell communication analysis identified enterocytes as a key player mediating signal communication networks. A four-gene signature prognostic model was constructed based on the enterocyte-related differentially expressed genes (ERDEGs) in patients with COAD of the Cancer Genome Atlas cohort. The prognostic model was validated on three external validation cohorts from the GEO database. The correlation between immune cell infiltration, immunotherapy response, drug sensitivity, and the four-gene signature prognostic model was investigated. Finally, immunohistochemistry (IHC) was performed to determine the expression of the four genes. Results We found that the proportion of epithelial cells was obviously large in COAD samples. Further analysis of epithelial cells showed that the activity of the enterocytes was highest in the cell-cell communication network. Based on enterocyte data, 30 ERDEGs were identified and a 4-gene prognostic model including CPM , CLCA4 , ELOVL6 , and ATP2A3 was developed and validated. The risk score derived from this model was considered as an independent variable factor to predict overall survival. The patients were divided into high- and low-risk groups based on the median riskscore value. The correlation between immune cell infiltration, immunotherapy response, immune status, clinical characteristics, drug sensitivity, and risk score was analyzed. IHC confirmed the expression of signature genes in tissues from normal individuals, patients with polyps, and COAD. Conclusion In this study, we constructed and validated a novel four-gene signature prognostic model, which could effectively predict the response to immunotherapy and overall survival in patients with COAD. More importantly, this model provides useful insight into the management of colon cancer patients and aids in designing personalized therapy.

Circular RNAs (circRNAs) are considered potential biomarkers in the pathogenesis and detection of several types of cancer. The present study aimed to investigate the role of hsa_circ_0000129 in the pathogenesis and molecular mechanism underlying breast cancer. A total of 68 pairs of breast cancer and corresponding paracancerous tissue samples, three different breast cancer cell lines (MCF-7, MDA-MB-231 and MDA-MB-468) and a normal human breast cell line (MCF-10A) were used to investigate the expression of hsa_circ_0000129. The effect of hsa_circ_0000129 on cell proliferation, migration and colony formation was assessed in MCF-7 and MDA-MB-468 cells, along with the expression of enhancer of zeste homolog 2 (EZH2). The results demonstrated that hsa_circ_0000129 expression was significantly higher in breast cancer tissues compared with normal tissues. In addition, high hsa_circ_0000129 expression was significantly associated with lymph node metastasis and a higher tumor-node-metastasis stage. Comparisons between the breast cancer cell lines (MCF-7, MDA-MB-231 and MDA-MB-468) and MCF-10A cells indicated similar results. MCF-7 cells overexpressed with hsa_circ_0000129 significantly increased cell proliferation, migration and colony formation compared with the negative control group, the effects of which were reversed following hsa_circ_0000129 knockdown in MDA-MB-468 cells. Furthermore, EZH2 expression was positively associated with hsa_circ_0000129 expression. Taken together, the results of the present study suggest that hsa_circ_0000129 may represent a promising prognostic biomarker for breast cancer. In addition, the role of hsa_circ_0000129 in breast cancer cell lines indicates a mechanism for tumorigenesis, as well as a potent target for the treatment of malignant progression.