Jintan People's Hospital

BACKGROUNDThe liver represents a common site of distant metastasis in patients with esophageal cancer (EC). Conventional chemotherapy (CMT) presents limited efficacy for EC, and EC patients with liver metastases typically experience a poor prognosis, highlighting an urgent need to explore novel treatment approaches. This study evaluated the overall efficacy and safety of CMT vs CMT combined with immune checkpoint inhibitors (ICIs) in the treatment of EC patients with liver metastases. Furthermore, prognostic factors influencing outcomes in this patient population were identified.AIMTo evaluate the efficacy and safety of first-line chemoimmunotherapy for EC patients with liver metastases and to analyze prognostic factors.METHODSThis retrospective study included 126 EC patients with liver metastases at Zhejiang Cancer Hospital between 2014 and 2024. Patients receiving CMT were compared with those receiving CMT + ICI. Analyzed variables included clinicopathological features, treatment history, characteristics of metastasis, systemic and local treatments, overall survival (OS), and treatment-related adverse events (TRAEs). Prognostic factors were evaluated using univariate and multivariate Cox proportional-hazards regression models. Finally, efficacy outcomes and TRAE profiles were compared between the two groups.RESULTSA significant difference in median OS was identified between the two groups (10.8 months in the CMT group vs 20.8 months in the CMT + ICI group, P = 0.004). The CMT + ICI group also demonstrated a significantly longer median progression-free survival of 11.7 months (P < 0.001). Patients receiving combination therapy exhibited significantly improved systemic objective response rate and disease control rate. Multivariate analysis identified key factors significantly influencing OS in EC patients with liver metastases: Karnofsky Performance Status score ≥ 70, receipt of local therapy for liver metastases, and the number of cycles of CMT and immunotherapy received. Furthermore, the incidence of TRAEs did not significantly differ between the CMT + ICI and CMT groups.CONCLUSIONFor EC patients with liver metastases, the combination of CMT and ICIs demonstrates significantly superior efficacy compared with CMT alone, while maintaining manageable TRAEs.

ObjectivesThis study aimed to develop a multimodal predictive model that integrates clinical data, radiomics, and three-dimensional deep learning to forecast acute respiratory distress syndrome in patients with acute pancreatitis.MethodsThis retrospective study analyzed data from 759 patients with acute pancreatitis treated at three hospitals. Radiomics features were extracted from three-dimensional computed tomography images, and a three-dimensional deep learning model was developed using convolutional networks. These components were combined with clinical data using the XGBoost algorithm to construct a multimodal model. The performance of the model was compared with that of single-modal models and traditional scoring systems (Modified Computed Tomography Severity Index, Ranson score, and Bedside Index for Severity in Acute Pancreatitis), using area under the curve as the primary metric. Model interpretability was enhanced using variable importance analysis, SHapley Additive exPlanations, local interpretable model-agnostic explanations, calibration plots, and decision curve analysis.ResultsThe multimodal model achieved area under the curve values of 0.872 (training set) and 0.876 (test set), outperforming traditional scores (Modified Computed Tomography Severity Index: 0.747 and 0.759; Ranson score: 0.575 and 0.568; and Bedside Index for Severity in Acute Pancreatitis: 0.748 and 0.757, respectively) and single-modal models (radiomics: 0.638 and 0.727 and deep learning: 0.756 and 0.727, respectively).ConclusionBy integrating clinical tabular data, radiomics, and deep learning features, the multimodal model can predict the risk of acute respiratory distress syndrome in patients with acute pancreatitis at an early stage.

<title>Abstract</title> <bold>Background</bold> Roxadustat is an orally bioavailable hypoxia-inducible factor prolyl hydroxylase inhibitor (HIF-PHI) that regulates iron metabolism in patients with chronic kidney disease (CKD) primarily by reducing hepcidin levels and mobilizing internal iron stores. With increased iron utilization, iron deficiency may occur in some patients, and more data are needed to evaluate the exogenous iron requirements of peritoneal dialysis (PD) patients receiving roxadustat to treat anemia. <bold>Methods</bold> We performed a prospective cohort study of anemic (Hb ≤ 100.0 g/L) patients undergoing PD. One hundred six patients received no iron or oral iron while they were treated with roxadustat for 24 weeks. The primary endpoints included Hb compliance rates, changes in iron biomarker levels and the proportion of patients with absolute iron deficiency and functional iron deficiency. <bold>Results</bold> Compared with no iron supplementation, oral iron supplementation significantly increased Hb levels (difference, 10.20 g/L; 95% CI, 1.93 to 18.48) and Hb compliance rates (oral iron, 70.97%; no iron, 51.28%); attenuated the increase in serum soluble transferrin receptor (sTFR) levels (difference, -5.66 nmol/L; 95% CI, -10.30 to -1.02) and sTFR/logsFt levels (difference, -0.32; 95% CI, -0.54 to -0.11); and reduced the proportion of patients with absolute iron deficiency (oral iron, 16.13%; no iron, 28.21%). Hepcidin levels decreased significantly from baseline in both groups, by 23.94% in PD patients receiving no iron (n = 39) and by 23.33% in PD patients receiving oral iron (n = 31). <bold>Conclusions</bold> Compared with no iron supplementation, oral iron supplementation can significantly reduce the incidence of absolute iron deficiency and significantly improve the efficacy of roxadustat in the treatment of anemia in PD patients. These results suggest that adequate iron supplementation is necessary during roxadustat therapy. <bold>Trial registration</bold> : This study was registered on the Chinese Clinical Trial Registry on March 4, 2022 (registration number: ChiCTR2200057231).

Increasing studies have reported that dysregulated lipid metabolism is an independent risk factor for breast cancer (BC); it would be, therefore, enlightening to investigate the relationship between metabolic reprogramming and the tumor microenvironment in the future. Ferroptosis, a novel form of programmed cell death, is characterized by glutathione (GSH) depletion and inactivation of glutathione peroxidase 4 (GPX4), the central regulator of the antioxidant system. While the close association between fatty acid metabolism and ferroptosis has been studied in various diseases, the interplay between the key fatty acid metabolic enzyme fatty acid synthase (FASN) and ferroptosis in BC remains unexplored. At the beginning of the current study, we demonstrated that FASN expression positively correlates with an immune-cold tumor microenvironment in BC. Subsequent findings revealed that FASN knockdown promotes GPX4 degradation-induced ferroptosis, thereby enhancing the efficacy of anti-programmed cell death protein 1 (PD-1) immunotherapy. Co-immunoprecipitation coupled with mass spectrometry (IP/MS) and co-IP experiments demonstrated that ubiquitin specific protease 5 (USP5) stabilizes GPX4 by binding to and deubiquitinating it. Furthermore, knockdown of FASN inhibited the palmitoylation of USP5, reducing its interaction with GPX4 and consequently increasing GPX4 ubiquitination and degradation. Our results demonstrate that FASN suppresses ferroptosis in BC by stabilizing GPX4 via USP5-mediated mechanisms, highlighting FASN inhibition as a potential therapeutic approach to enhance immunotherapy response.Supplementary InformationThe online version contains supplementary material available at 10.1186/s13046-025-03548-8.

ObjectiveOsteoarthritis (OA) is a degenerative joint disease that affects over 500 million individuals globally, characterized by the degradation of cartilage, subchondral bone sclerosis, and synovitis. A key factor in the progression of OA is synovial inflammation, which is driven by macrophage polarization and inflammasome activation. This inflammation exacerbates cartilage degradation, creating a vicious cycle that accelerates disease progression. Targeting macrophage activity presents a promising therapeutic strategy to alleviate the symptoms and progression of OA.MethodsTo investigate the role of SEMA6D in macrophage polarization and its potential therapeutic implications for OA, we conducted transcriptomic analysis to explore its regulatory functions. In vitro experiments were performed to assess the effects of SEMA6D overexpression on the expression of ASC and NLRP3, as well as on macrophage (RAW264.7) polarization toward the pro-inflammatory M1 phenotype. In vivo studies were conducted using an OA rat model to evaluate the influence of SEMA6D overexpression on synovial macrophage polarization and the levels of inflammatory mediators, including IL-1β and IL-6.ResultsOur transcriptomic analysis indicated that SEMA6D plays a regulatory role in macrophage polarization. Overexpression of SEMA6D resulted in the downregulation of ASC and NLRP3, effectively inhibiting the polarization of macrophages toward the M1 phenotype and downregulate the expression levels of iNOS and IL-6 by more than twofold. In the DMM rat model, SEMA6D overexpression significantly reduced the polarization of synovial macrophages to the M1 phenotype, leading to lower levels of inflammatory mediators such as IL-1β and IL-6, and mitigating cartilage degeneration.ConclusionSEMA6D exerts a protective effect against OA by attenuating synovial macrophage-mediated inflammatory responses through the inhibition of NLRP3 inflammasome activation and endoplasmic reticulum stress.

BackgroundChronic obstructive pulmonary disease (COPD) involves progressive lung function decline, with hypoxia playing a key pathogenic role. However, systematic investigations focusing on hypoxia-related genes (HRGs) in COPD remain limited.MethodsWe applied machine learning to identify HRG-associated diagnostic biomarkers and evaluated their performance via Receiver Operating Characteristic (ROC) analysis. Mendelian randomization (MR) was conducted to assess causal relationships between candidate genes and COPD. A nomogram model was constructed to evaluate clinical utility, and a ceRNA network was developed using ENCORI database.ResultsSix HRG-based diagnostic biomarkers were identified, including SLC2A1, which demonstrated strong diagnostic value (AUC > 0.8). MR analysis revealed a significant causal effect of SLC2A1 expression on COPD risk (OR = 1.32, 95% CI: 1.02–1.71, P < 0.05). Functional evidence suggests SLC2A1 promotes hypoxia-induced metabolic reprogramming in airway epithelial cells. The constructed nomogram showed good clinical applicability. ceRNA analysis highlighted MALAT1, NEAT1, and XIST as potential upstream regulators.ConclusionOur findings identify SLC2A1 as a causal and diagnostically relevant gene in COPD, offering novel insight into hypoxia-driven disease mechanisms and supporting future personalized therapeutic strategies.

To investigate changes in the Effective Optical Zone (EOZ) using a novel method, evaluate visual outcomes within six months following Small Incision Lenticule Extraction (SMILE), and analyze the changes in postoperative visual outcomes.This retrospective study evaluated patients who underwent SMILE and were assessed during a 6-month follow-up. 95 eyes were divided into two groups: low to moderate myopia (LM, SE ranging from - 0.50D to -6.00D) and high myopia (HM, SE ranging from - 6.00D to -9.00D). Postoperative EOZ was automatically distinguished by custom software on the tangential curvature difference map. Higher-order aberrations (HOAs), Q-values, and Strehl ratios (SR) were analyzed for the central 4mm and 6mm corneal zones. Changes in EOZ (△-OZ) and other parameters were monitored and compared between the two groups.The EOZ was significantly larger in LM group than in HM group (25.45 ± 2.19 vs. 23.88 ± 1.53mm2), and the changes in vertical diameter exceeded those in horizontal diameter in both groups (P < 0.01). All patients showed increased HOAs, spherical aberration (SA), and coma compared to preoperative values (all P < 0.01), with higher values in HM group. The changes in Q-value, HOAs, and SA were positively correlated with △-OZ (r = 0.640, r = 0.534, r = 0.680, all P < 0.01). No significant differences in SR, visual acuity, or refractive error between the two groups. EOZ stabilized by 3 months postoperatively while Visual Outcomes at 1 month.Following SMILE surgery, the EOZ decreased and stabilized at around 3 months. Higher preoperative myopia was associated with increased corneal remodeling, larger HOA changes, and greater EOZ reduction, without significantly affecting visual outcomes.