The primer sequences for qRT-PCR and RIP-PCR

Esophageal squamous cell carcinoma (ESCC) remains a highly aggressive malignancy with dismal clinical outcomes and limited treatment options. NAD(P)H quinone oxidoreductase 1 (NQO1) is classically characterized as a cytosolic oxidoreductase that prevents the formation of reactive oxygen species. In this study, we demonstrated that NQO1 promoted ESCC progression and lung colonization via an enzymatic activity-independent mechanism. Integrated transcriptomic and direct RNA-binding analyses revealed that NQO1 acted as an RNA-binding protein to stabilize the mRNA encoding agrin (AGRN), thereby increasing AGRN expression. Upregulation of AGRN enhanced endothelial cytoskeletal organization by interacting with filamin A and stimulated angiogenesis through selective extracellular vesicle-mediated transfer. Structure-based screening identified the clinically approved agent panobinostat as a direct NQO1-binding compound that destabilized NQO1 and suppressed AGRN-dependent angiogenic signaling. Importantly, combined treatment with panobinostat and the antiangiogenic agent anlotinib resulted in superior inhibition of tumor growth and vascularization compared with either monotherapy in patient-derived organoid xenograft models. Together, these findings uncover an enzymatic activity-independent RNA-regulatory function of NQO1 in ESCC and provide a mechanistic rationale for targeting the NQO1/AGRN axis. SIGNIFICANCE:The enzyme-independent RNA regulatory function of NQO1 enhances extracellular vesicle-mediated AGRN signaling to drive angiogenesis in esophageal cancer, which induces a therapeutic vulnerability to combinatorial anti-angiogenic treatment with panobinostat and anlotinib.

OBJECTIVE:General anesthesia (GA) has consistently served as the predominant anesthesia modality in thoracic endovascular aortic repair (TEVAR). The objective of this retrospective study was to systematically evaluate and compare the short and midterm outcomes of local anesthesia (LA) versus GA for non-emergency TEVAR in acute Type B aortic dissection (TBAD). METHODS:This single-center, retrospective study analyzed 441 consecutive patients who underwent non-emergent TEVAR between January 2016 and December 2020. Following 1:1 propensity score matching, 410 patients were enrolled and allocated into LA group (n=205) and GA group (n=205) based on anesthesia type. Baseline demographics, intraoperative details, postoperative outcomes, and follow-up data were systematically collected and analyzed. Patients were prospectively followed for 5 years post-discharge to monitor long-term outcomes. RESULTS:Compared with the GA group, the LA group showed significantly shorter anesthesia duration (75 vs 125 minutes, p<0.001), procedure time (60 vs 95 minutes, p<0.001), intensive care unit (ICU) stay (4 vs 18 hours, p<0.001), and hospital stay (25 vs 29 days, p<0.001). However, no significant differences were found in in-hospital mortality (2.0% vs 2.9%, p=0.751) and late mortality (1.4% vs 2.5%, p=0.724) during the 5-year follow-up. Multivariable Cox-regression analysis revealed that chronic heart failure was an independent risk factor for death (HR=4.253, 95% CI 1.243-14.554, p=0.021). CONCLUSION:Local anesthesia may be considered non-inferior to GA in patients with acute TBAD undergoing non-emergency TEVAR, with shorter length of ICU and hospital stay. Moreover, it exhibited equivalent 5-year survival rates to GA.Clinical ImpactThese findings demonstrate that LA offers a resource-sparing alternative without compromising survival, thereby supporting a paradigm shift toward LA as a potential primary anesthetic strategy for TEVAR in appropriately selected patients.

NQO1 promotes ESCC progression and metastasis through a mechanism independent of its enzymatic activity.

The sequences of shRNA, sgRNA and siRNAs

AGRN-binding proteins identified by LC–MS/MS.

Panobinostat directly targets NQO1 to suppress the malignant progression of ESCC.

NQO1 promotes ESCC progression by inducing angiogenesis.

NQO1 is significantly upregulated in esophageal cancer tissues.

AGRN interacts with FLNA to stabilize the cytoskeleton.

The clinicopathological characteristics of the ESCC patients (tissue microarray).

NQO1 facilitates ESCC progression and metastasis in vitro and in vivo.

Modulating the immune system represents a pivotal mechanism through which the gut microbiome (GM) exerts influence over disease progression. However, Further investigation is necessary to ascertain the causal role of GM in Esophageal Adenocarcinoma (EAC) and the potential for immune cell mediation. Initially, a two-stage, two-sample Mendelian randomization (MR) analysis using the Inverse Variance Weighted (IVW) method was performed to assess the causal effects of GM conditions on EAC, while exploring the potential mediating role of immune cells in the GM-EAC association. A MR analysis identified 5 types of GM and 9 types of GM metabolic pathway abundances with potential causal relationships to EAC. Furthermore, 26 immune cell characteristics(ICTs) were identified as closely associated with EAC. Mediation MR analysis revealed that ICTs negatively influenced the relationship between Rothia and EAC. Our MR and mediation analyses suggest that specific gut microbes, microbial pathway abundances, and peripheral immune traits are associated with EAC susceptibility. Immune mediation was modest (-6–15

Background:Immune checkpoint inhibitors (ICIs) have become an important treatment option for patients with advanced non-small cell lung cancer (NSCLC). However, the association between proton pump inhibitor (PPI) use and clinical outcomes remains uncertain, particularly in the setting of short-term peri-treatment exposure. This retrospective study aimed to evaluate the association between PPI use and clinical outcomes in patients with advanced NSCLC receiving ICI therapy. Methods:This single-center retrospective study included 229 patients with advanced NSCLC who received first-line treatment with either ICI monotherapy or ICI combined with chemotherapy between January 1 and December 31, 2023. Follow-up was censored on December 31, 2024. Clinical data were collected, including age, sex, Eastern Cooperative Oncology Group (ECOG) performance status, PD-L1 expression, treatment regimen, and PPI use. Progression-free survival (PFS) and overall survival (OS) were evaluated. Results:Among the 229 patients, 131 (57.2%) received PPI during the peri-treatment period. In patients without PPI use, no significant differences in PFS or OS were observed between ICI monotherapy and ICI combined with chemotherapy. However, among patients with PPI exposure, those treated with ICI plus chemotherapy had significantly longer PFS and OS compared with those receiving ICI monotherapy (both P<0.01). In addition, within the ICI monotherapy subgroup, PPI use was associated with significantly shorter PFS and OS. Inverse probability of treatment weighting (IPTW) analysis demonstrated that this association remained significant after adjustment for baseline confounders. Duration-based analysis further showed that even short-term PPI exposure (≤1 day) was associated with poorer outcomes. Conclusions:PPI use was associated with poorer outcomes in patients with advanced NSCLC, particularly among those receiving ICI monotherapy. This association appeared attenuated in patients treated with ICI combined with chemotherapy, suggesting a treatment-dependent interaction rather than a uniform drug effect.

AGRN promotes angiogenesis in ESCC.

Serum biochemical parameters in nude mice following indicated treatments.

Carcinoembryonic antigen (CEA), a pan-cancer biomarker, holds critical clinical value in aiding diagnosis and prognostic assessment of various malignancies. The development of a facile, accurate, and selective CEA detection method remains an urgent need. Herein, we developed a facile colorimetric sandwich immunoassay based on a highly defective Fe-based single-atom nanozyme (dFeSA) for detecting CEA. The dFeSA with an Fe-N3-C active site exhibited remarkable oxidase-like activity, enabling the catalytic conversion of O2 to superoxide radicals and subsequent oxidation of chromogenic substrates. This method achieved high sensitivity and specificity for CEA detection over a wide range (0.05-300 ng mL-1) and a low detection limit of 0.017 ng mL-1. Notably, the immunoassay demonstrated exceptional performance for CEA detection in real serum samples with recovery rates of 92.7%-102.6%. This colorimetric immunoassay represents a robust analytical platform for CEA detection, offering a cost-effective alternative to conventional methods and holding significant potential for early cancer diagnosis and prognostic monitoring in clinical practice.

BACKGROUND:Treatment strategies for patients with early esophageal cancer are diverse, and lymph node metastasis (LNM) remains a critical determinant in therapeutic decision-making and prognosis. However, current methods for predicting LNM in early esophageal cancer are limited. AIM:To evaluate the impact of body composition parameters on LNM in early esophageal squamous cell carcinoma (ESCC) and to develop a nomogram based on body composition and tumor burden indicators for assessing LNM in T1 ESCC. METHODS:A retrospective analysis was conducted on clinical data and CT imaging of 243 patients with histologically confirmed T1 ESCC who underwent radical surgery. Cross-sectional areas of skeletal muscle, subcutaneous fat, and visceral fat at the level of the L3 vertebra were quantified using ImageJ software. Univariate and multivariate analyses were conducted to identify risk factors associated with LNM. A predictive nomogram was then constructed based on the multivariate results and evaluated using receiver operating characteristic (ROC) curves, calibration plots, and decision curve analysis (DCA). RESULTS:Among the 243 patients, 38 cases exhibited LNM, yielding an incidence rate of 15.64%. Multivariate analysis identified tumor size, lymphovascular invasion (LVI), visceral fat area (VFA), and T1 substage as independent risk factors. The AUC values for size, LVI, VFA, and T1 substage were 0.628, 0.651, 0.767, and 0.619, respectively. The nomogram constructed based on these four variables demonstrated strong predictive performance, with AUCs of 0.8331 in the training set and 0.8343 in the validation set, both surpassing the predictive capacity of individual indicators. These findings underscore the nomogram's superior prognostic accuracy compared to any single pathological parameter. The calibration curve and DCA demonstrated its considerable potential for clinical application. CONCLUSION:This nomogram, integrating body composition and tumor burden indicators, provides an individualized and practical tool for predicting LNM in early ESCC, supporting more informed clinical decision-making.

This study investigates the impact of Bacillus Licheniformis Capsules (live) on patients with non-small cell lung cancer (NSCLC) undergoing chemotherapy. Clinical data from 79 NSCLC patients who developed grade 2-3 diarrhea during the first cycle of chemotherapy and admitted to our hospital between March 2020 and February 2023 were retrospectively analyzed and assigned to a control group (n = 42, treated from March 2020 to June 2022 with Pemetrexed + Cisplatin regimen) and a study group (n = 37, treated from July 2022 to February 2023 with Pemetrexed + Cisplatin regimen + Bacillus Licheniformis Capsules) based on their treatment regimens. The study group exhibited significantly higher overall response rate compared to the control group (P < 0.05). Post-treatment, both groups exhibited decreased levels of Enterococcus, Enterobacteriaceae, interleukin (IL)-4, IL-17, high-sensitivity C-reactive protein, and improved Functional Assessment of Cancer Therapy-Lung scores, with more pronounced improvements in the study group. Levels of Lactobacillus, Bifidobacterium, and interferon gamma increased significantly, with greater increases in the study group (P < 0.05). Both groups showed reductions in CD3+, CD4+, CD4+/CD8+ ratio, waist-to-hip ratio, and body mass index post-treatment, but these markers remained higher in the study group. CD8+ levels increased in both groups post-treatment but were much lower in the study group (P < 0.05). No significant difference was noted in the complication rates between the 2 groups. Bacillus Licheniformis Capsules (live) enhances the efficacy of chemotherapy in NSCLC patients by modulating gut microbiota, reducing inflammatory responses, and improving immune function and quality of life, without compromising safety.

BACKGROUND The relationship between patient nutritional, immune, and inflammatory status is linked to tumor progression and prognosis. However, there are limited studies on the prognosis of esophageal squamous cell carcinoma (ESCC) after surgery based on the comprehensive indicators of these factors. AIM To develop and validate a novel nomogram based on a nutritional immune-inflammatory status (NIIS) score for predicting postoperative outcomes in ESCC. METHODS This retrospective study examined 829 patients with ESCC who underwent radical surgery between June 2016 and June 2020, with 568 patients in the training cohort and 261 patients in the validation cohort. We incorporated comprehensive indicators related to nutrition, immunity, and inflammation to develop the NIIS score, using LASSO regression. Subsequently, a nomogram combining the NIIS score and other clinicopathological parameters was developed and validated using calibration curves, time-dependent area under curves, and decision curve analysis. RESULTS We identified eight indicators that constitute the NIIS score. High-risk scores emerged as an independent risk factor for overall survival [training set HR 2.497 (1.802, 3.458), P < 0.001]. A NIIS nomogram for personalized prognostic prediction was developed by integrating the NIIS score with clinicopathological variables, yielding enhanced predictive value relative to individual indicators and the UICC/TNM staging system. CONCLUSION The NIIS score provides strong predictive value for postoperative outcomes in ESCC, thus offering a valuable tool for clinical decision-making.