Background: Hemodynamic instability (HI), manifesting as hypotension and/or bradycardia, presents a common complication within 6 h post-CAS. The prolonged HI requires particular attention due to increased risk of neurologic complications. Aims: The study aimed to determine the incidence and potential predictive factors of prolonged hemodynamic instability (HI) after carotid artery stenting (CAS). Methods: From January 2023 to January 2025, patients diagnosed with carotid artery stenosis underwent CAS treatment were recruited. The data of peri-procedural characteristics extracted from the Hospital electronic database. Prolonged HI was defined as post-procedural HI persisting beyond 24 h, with or without associated symptoms. Logistic regression identified predictors of HI. A nomogram was developed based on the regression analysis. The receiver operating characteristic (ROC), Hosmer-Leme and decision curve analyses were used to assess predictive performance. Results: The training cohort consisted of 234 cases, while the validation cohort included 100 cases. The logistic regression identified intraoperative HI (OR = 2.77, p = 0.02), Large balloon (OR = 10.53, p < 0.001), 7-10 mm stent (OR = 12.72, p < 0.001), and post balloon dilatation (OR = 2.60, p = 0.041) as significant independent predictors of HI. The external validation cohort demonstrated strong calibration curves between predicted and observed outcomes (p = 0.21). Decision curves confirmed the nomogram's superiority over the All or None scheme, particularly within threshold probabilities of > 5% to < 95%. The nomogram's performance metrics were: AUC = 0.92, accuracy = 0.89, specificity = 0.94, sensitivity = 0.94, PLR = 5.8, NLR = 0.07, and DOR = 82.25. Conclusion: This study confirms that intraprocedural HI, Large balloon, large-diameter stent use (7-10 mm), and post-balloon dilatation were independent risk factors for prolonged HI following CAS. The integration of these factors into a nomogram provides clinicians with a highly accurate tool for preoperative risk stratification.

Optic neuropathy is characterized by impaired optic nerve function resulting from various pathological processes, often leading to retinal ganglion cell (RGC) degeneration and irreversible vision loss. Several studies have demonstrated the neuroprotective effects of salidroside (Sal). However, its clinical application has been limited by the high dosage required and the short half-life of Sal. To enhance drug efficacy and prolong therapeutic effects, we developed engineered small extracellular vesicles (sEVs) loaded with Sal (sEVs-Sal) for intravitreal administration in a mouse model of optic nerve crush (ONC). Our findings demonstrate that sEV-mediated low-dose Sal administration significantly enhanced visual functional recovery in ONC mice by mitigating RGC degeneration and inhibiting microglial activation. Proteomic profiling indicated that sEVs-Sal concurrently modulate both the TNF-α/IL-1β inflammatory axis and the Caspase-3/Bcl-2 apoptotic pathway, thereby conferring dual anti-inflammatory and antiapoptotic effects. This study establishes an efficient sEV-based drug delivery platform and highlights the considerable therapeutic potential of sEVs-Sal in the treatment of optic nerve injury. By addressing the pharmacokinetic limitations of free Sal and augmenting neuroprotection, this nanoformulation represents a promising translational strategy for optic neuropathies.

BACKGROUND AND PURPOSE:This study aims to assess the safety and efficacy of the Neuroform Atlas stent in treating symptomatic MCA stenosis, hypothesizing that its advanced design may lead to more favorable outcomes in this high-risk patient population. MATERIALS AND METHODS:Consecutive patients who underwent endovascular stenting for symptomatic intracranial atherosclerotic stenosis (ICAS) of the middle cerebral artery (MCA) from January 2020 to December 2025 were screened for inclusion. The Neuroform Atlas stent system was deployed in MCA. All patients were followed up for at least six months with vascular imaging (CTA or DSA). The primary efficacy endpoint was the rate of favorable clinical outcomes, defined as an mRS score ≤3, at six months post-procedure. RESULTS:A total of 165 consecutive patients who underwent endovascular stenting for symptomatic MCA stenosis were included in this analysis. At the 6-month follow-up, 145 patients (87.9%) were classified as having a favorable clinical outcome, while 20 patients (12.1%) had an unfavorable outcome. The multivariate logistic regression analysis confirmed that a higher pre-procedural stenosis rate (OR: 1.14, 95% CI: 1.03-1.26, p = 0.01), greater lesion length (OR: 4.18, 95% CI: 1.32-12.26, p = 0.01), a higher admission NIHSS score (OR: 1.27, 95% CI: 1.04-1.54, p = 0.02), and most importantly, lesion location at the M1 bifurcation (distal third) (OR: 16.21, 95% CI: 2.86-91.96, p = 0.002) were independent risk factors for an unfavorable clinical prognosis. CONCLUSION:The stenting of symptomatic MCA stenosis with the Neuroform Atlas stent system was associated with high technical success, a favorable short-term safety profile, and promising efficacy outcomes.

Oxidative stress and inflammasome-driven inflammation are key contributors to atherosclerotic disease progression. Here, we report a ROS-responsive hyaluronic acid-PEGDA hydrogel designed for the sustained delivery of palmitoleic acid. In the study, catechol-functionalized hyaluronic acid was cross-linked with polyethylene glycol diacrylate to create an extracellular matrix mimic that possessed tunable mechanical strength and redox-sensitive degradability. It showed controlled release of palmitoleic acid under normal physiological conditions and a faster rate of release under oxidative conditions. In vitro studies using vascular endothelial cells and macrophages demonstrated good cytocompatibility and a marked reduction in intracellular reactive oxygen species, lipid peroxidation, and pro-inflammatory cytokine secretion. At the molecular level, treatment with the palmitoleic acid-loaded hydrogel resulted in activation of AMP-activated protein kinase, inhibition of NF-κB nuclear translocation, and suppression of NLRP3 inflammasome activation, as evidenced by decreased caspase-1 cleavage and IL-1β maturation. These findings indicate that ROS-responsive hydrogel-mediated delivery of palmitoleic acid effectively modulates oxidative and inflammatory signalling pathways relevant to atherosclerosis.

Background: The high mortality in end-stage renal disease (ESRD) is driven by a confluence of inflammatory, cardiovascular, and persistent tubulointerstitial injury pathways. We hypothesised that a multi-domain biomarker panel combining Interleukin-6 (IL-6, inflammation), soluble urokinase plasminogen activator receptor (suPAR, immune activation), and Kidney Injury Molecule-1 (KIM1, tubular injury) would provide superior prognostic value for fatal and non-fatal outcomes. Methods: We performed a prospective cohort study of 538 prevalent haemodialysis patients. Serum IL-6, suPAR, and KIM-1 were measured at baseline. The primary endpoint was a composite of all-cause mortality and major adverse cardiovascular events (MACE). Secondary endpoints were cardiovascular mortality and heart failure hospitalisations. Cox proportional hazards models and C-statistics were used for analysis. Results: Over a median follow-up of 36 months, 192 patients (35.7%) experienced the primary composite endpoint. In fully adjusted models, each biomarker independently predicted the primary endpoint: IL-6 (HR 1.85, 95% CI 1.51-2.26), suPAR (HR 2.15, 95% CI 1.70-2.73), and KIM-1 (HR 1.67, 95% CI 1.35-2.06). A model containing all three biomarkers demonstrated significantly improved discrimination (C-index 0.81) over models with any single biomarker (C-indices 0.71-0.74) or a clinical model alone (C-index 0.67; p<0.001). Patients in the highest-risk category (all three biomarkers in the top tertiles) had a 6.8-fold increased risk (HR 6.80, 95% CI 3.85-12.02) for the primary endpoint. Conclusion: The combination of IL-6, suPAR, and KIM-1 - reflecting systemic inflammation, innate immunity, and residual tubular damage - creates a powerful, integrative prognostic tool that significantly improves risk stratification for mortality and cardiovascular events in ESRD.

Background Immunotherapy resistance represents a current research hotspot. Previous studies found that neuroendocrine differentiation (NED) might significantly contribute to the initiation and development of non-small cell lung cancer (NSCLC). However, the interplay between immunotherapy resistance and NED in NSCLC remains unclear. This study explored the relationships between NED-related genes (NEDRGs) and immunotherapy resistance-related genes in NSCLC.Methods Control and NSCLC samples, including NSCLC samples exposed to PD-1 blockade, were selected from public databases to identify differentially expressed genes (DEGs). Then, univariate Cox regression analysis and the proportional hazards assumption test were performed to identify prognostic genes based on the DEGs and NEDRGs, and a risk model was developed and validated. Thereafter, a nomogram was established. Subsequently, gene set enrichment analysis (GSEA), immune analysis, and drug sensitivity analysis were conducted. The key cells were ascertained in a single-cell RNA sequencing dataset. We collected specimens from six patients at Tianjin Medical University General Hospital and validated them using quantitative real-time polymerase chain reaction (RT-qPCR) and immunohistochemistry (IHC).Results Three prognostic genes (RRM2, WDR76, and PLEKHH2) were identified, and the developed risk model could predict the survival of patients with NSCLC. The nomogram had good predictive ability concerning survival rates in NSCLC. Based on the GSEA results, a notable pathway in the two risk groups included cell cycle pathways, and prognostic genes were all enriched in these pathways. Furthermore, activated memory CD4+ T cells might contribute significantly to survival, and 109 drugs, including AZD6738, could be candidate treatments for NSCLC. Epithelial cells were identified as the key population in which the expression of prognostic genes was altered significantly across different developmental stages. RT-qPCR and IHC confirmed that RRM2 and WDR76 expression was higher in cancer tissues than in normal tissues, increasing with disease progression, whereas PLEKHH2 exhibited the opposite trend.Conclusion The developed risk model based on three prognostic genes (RRM2, WDR76, and PLEKHH2) exhibited superior predictive accuracy in NSCLC. These results may provide new insights for investigating novel therapeutic targets in NSCLC.

Although extracorporeal membrane oxygenation (ECMO) has emerged as a pivotal temporary extracorporeal life support in critically ill patients, it is associated with a high risk of mortality. Establishing a risk prediction model for ECMO-related mortality is crucial for early identification and timely intervention to improve survival. This study aimed to develop and validate a machine learning (ML) model to predict the risk of ECMO-related mortality among patients admitted to intensive care units (ICUs). Retrospective cohort study. In the ICUs of the three hospitals in Changsha and Changde, two cities of Hunan Province, China. Patients aged >= 18 years old undergoing ECMO who were admitted to the ICUs, and the duration of ECMO was >= 24 h. The study was conducted among 204 patients undergoing ECMO from January 01, 2020, to December 31, 2023. The patients were randomly divided into a training set (n = 142) and a validation set (n = 62) at a ratio of 7:3. The least absolute shrinkage and selection operator (LASSO) and multivariate logistic regression were used to screen for factors associated with mortality. Three ML classification models and the Shapley Additive exPlanations (SHAP) interpretation were used to identify the optimal model and assess its diagnostic performance. The final model identified the following factors associated with ECMO-related mortality: body mass index (BMI), APACHE II, history of smoking, white blood cell count (WBC), activated partial thromboplastin time (APTT), red blood cell distribution width (RDW), and platelet (Plt). The Gaussian Naive Bayes (GNB) model was the optimal model, with an average area under the ROC curve (AUC) of 0.906 (0.893-0.926) in the training set and 0.888 (0.75-1.00) in the validation set. This study presents an internally validated, explainable machine learning model for predicting ECMO mortality, developed using a specific Chinese cohort. The model demonstrated strong performance within our study population and identified key factors associated with ECMO-related mortality.

Myocardial infarction (MI) has high morbidity and mortality, and the macrophage senescence-associated secretory phenotype (SASP) plays a central role in M1 healing. α-Lipoic acid (ALA) alleviates MI by regulating the function of macrophages, although the relationship between ALA and macrophage senescence remains unclear. To investigate macrophage SASP in MI, we performed single-cell RNA sequencing (scRNA-seq) on the GEO GSE163465 dataset, along with qPCR and western blot analyses to assess SASP expression in macrophages subjected to hypoxia and ALA treatment. Immunofluorescence was used to detect SASP distribution. Coculture and animal experiments were performed to assess the therapeutic effects of ALA on macrophage senescence and cardiomyocyte ischemic injury. scRNA-seq revealed an age-independent senescent propensity of macrophages in MI. Increased expression of H2A.X, CCL7, IL1β, and CDKN1A, along with decreased SOD2 expression, confirmed that macrophage SASP occurred after hypoxia, with oxidative stress and energy metabolism involved in the process. ALA inhibited the degradation of SIRT1 and promoted the Nrf2 nuclear translocation, alleviating macrophage senescence and myocardial ischemic injury. Age-independent macrophage SASP occurred during MI. Macrophage SASP was induced by ROS and mitochondrial dysfunction. ALA alleviated SASP by decreasing ROS generation and autophagy flux while increasing SIRT1 levels, and Nrf2 nuclear translocation. ALA ameliorated MI injury.

Balancing high metabolic activity with redox homeostasis is crucial for cancer progression, particularly in high-grade serous ovarian cancer (HGSOC), which thrives in a lipid-rich environment abundance in free fatty acids, yet the key molecular regulators of this balance remain undefined. Through an in vivo genome-wide CRISPR/Cas9 knockout screen in an orthotopic ovarian cancer (OC) mouse model, we identify ACAD9 as a pivotal driver of OC progression, with its elevated expression correlating with poor patient prognosis. Multi-omics integration analysis and mechanism studies reveal ACAD9's dual role in maintaining OC metabolic homeostasis. ACAD9 preserves electron transport chain integrity and regulates linoleic acid (LA) metabolism to sustain energy production while mitigating oxidative stress. ACAD9 deficiency triggers mitochondrial respiratory collapse, inducing metabolic crisis marked by oxidative phosphorylation failure and reactive oxygen species (ROS) accumulation. Strikingly, under LA-enriched condition, ACAD9 loss redirects LA flux from β-oxidation toward membrane lipid biosynthesis, increasing polyunsaturated fatty acids incorporation. This membrane remodeling synergizes with ROS overload to create a "perfect storm" triggering ferroptosis. Our findings elucidate the dual metabolic guardianship of ACAD9 in OC, demonstrating its critical role in orchestrating mitochondrial respiration and lipid homeostasis to evade ferroptosis, which offer a potential target for the treatment of OC.

The study investigates the effectiveness of immersive virtual reality (VR) as a nonpharmaceutical approach to manage postoperative pain in patients following thoracoscopic surgery. In this single-center, triple-arm pilot randomized controlled trial (RCT), 61 postsurgical patients with a postoperative pain numerical rating scale (NRS) score ≥4 after receiving standard analgesia were included and assigned to either a quantum clinics-VR (QTC-VR) group, a Placebo-VR group, or a control group. The QTC-VR group engaged in a daily 10-minute interactive pain relief 3D-VR program, while the Placebo-VR group watched a daily 10-minute relaxation-based 2D film through VR headsets for three days following surgery. 61 postsurgical patients were randomized and allocated (21 in the QTC-VR group, 20 in the Placebo-VR group, and 20 in the control group) in the final intention-to-treat (ITT) analyses. Compared with patients receiving Placebo-VR intervention, patients reported significantly lower pain scores following the daily QTC-VR intervention on postoperative days 1 (mean difference, −0.889; 95% CI, −1.464 to −0.314; P < 0.001), 2 (mean difference, −0.631; 95% CI, −1.211 to −0.051; P = 0.014), and 3 (mean difference, −0.798; 95% CI, −1.345 to −0.251; P < 0.001), respectively. Additionally, patients receiving QTC-VR intervention also reported high satisfaction and tolerable adverse events with their treatment. In conclusion, this pilot RCT demonstrates that QTC-VR might be a promising intervention for pain management post-thoracoscopic surgery, warranting further validation in ongoing phase III trials.

Over the past 2 decades, remarkable advancements in the screening, diagnosis, and treatment of non-small cell lung cancer (NSCLC) have led to improved patient outcomes. For the treatment of NSCLC with actionable gene mutations, tyrosine kinase inhibitors developed against EGFR, ALK, RET, BRAF, ROS1, NTRK, MET, and KRAS, exhibit substantial antitumor activity and have been incorporated into standard treatment regimens. Additionally, numerous novel therapies, including immunotherapy and antibody-drug conjugate therapy, have been found to benefit patients with NSCLC. This review summarizes current advancements in targeted therapy for NSCLC, according to a systematic search of the PubMed database and synthesis of cutting-edge findings presented at the 2024 American Society of Clinical Oncology Annual Meeting and 2024 World Conference on Lung Cancer.

Background The sex hormones may induce the progression of meningioma during pregnancy. To further explore the causal relationship between sex hormones and the risk of meningioma, we employed Mendelian randomization (MR) and immunohistochemistry for causal inference analysis. Methods We obtained GWAS data relevant to meningioma from FinnGen, which included 314,708 participants. We found substantial evidence suggesting a potential causal relationship between PRLR, IGF, LH and the risk of meningioma using MR method. Results We included 16 cases of meningioma, of which 4 were associated with pregnancy. The average age of meningioma patients with pregnancy was significantly younger at 32.50 ± 1.29 years compared to those without pregnancy (60.58 ± 14.91 years; p = 0.002). Additionally, the proportion of grade II cases among those with pregnancy was found to be significantly higher at 100% compared to only 16.7% in those without pregnancy. The H-score of PRLR, IGF and LH in pregnancy group was significantly higher than that in without pregnancy group (< 0.001). While, there was no significant difference of H-score between two groups in other sex hormones. Conclusion The mendelian randomization analysis and immunohistochemical analysis demonstrated that PRLR, IGF and LH played an important role in the progression of meningioma. The targeted drug for PRLR, IGF and LH may become novel therapeutic methods for meningioma in the future.

BACKGROUND:This study aimed to explore the association between the stress hyperglycemia ratio (SHR) and short- and long-term outcomes in critically ill patients with sepsis. METHODS:This retrospective observational cohort study was conducted using the Medical Information Mart for Intensive Care-IV (MIMIC-IV v2.2) database. Patients were categorized into 4 SHR quartiles. The main focus was on in-hospital mortality and 1-year all-cause mortality as primary endpoints, while intensive care unit and hospital stays were considered as secondary outcomes. Regression and subgroup analyses were used to assess the correlation between SHR and the primary and secondary outcomes. Restricted cubic spline analysis was utilized to explore the nonlinear relationships between SHR and in-hospital and 1-year all-cause mortality. RESULTS:This study included two groups of patients, comprising 7456 and 6564 individuals. The in-hospital and 1-year mortality was 11.96% and 17.96% in Cohort 1 and 2, respectively. SHR was associated with an elevated risk of in-hospital mortality (OR: 2.08, 95%CI 1.66-2.61) and 1-year mortality (HR: 1.70, 95% CI 1.42-2.04). Patients in SHR quartile 4 had a higher risk of in-hospital (OR: 1.86, 95% CI 1.51-2.30) and 1-year (HR: 1.44, 95% CI 1.23-1.69) mortality than those in quartile 2. Restricted cubic spline analysis showed a "J-shaped" relationship between SHR and all-cause mortality in both cohorts. The relationship between high SHR and mortality remained consistent across almost all predefined subgroups. CONCLUSIONS:Our study suggests that high SHR is associated with increased in-hospital and 1-year mortality in critically ill sepsis patients. Further investigations are needed to validate these results.

Postoperative pain can significantly impair functional recovery and diminish the quality of life in patients who have undergone thoracoscopic surgery. Virtual reality (VR), by leveraging cognitive-behavioral intervention techniques and redirecting attention from noxious stimuli, holds promise as a modality to alleviate postoperative pain. Despite this potential, current VR software for postoperative care predominantly emphasizes physical therapy and rehabilitation, often overlooking the integration of pain management strategies. The primary objective of our study is to evaluate the effectiveness and safety of an adjunctive VR-based software for pain control following thoracoscopic surgery. This is a prospective, multicenter, open-label, randomized controlled trial involving 215 patients who have undergone thoracoscopic surgery. Participants will be randomly allocated to one of two parallel groups. The experimental group will receive postoperative adjuvant analgesic software in addition to standard postoperative pharmacological analgesia, while the control group will receive only standard postoperative pharmacological analgesia. Pain intensity will be assessed using the numerical rating scale (NRS) at pre-intervention and at 24 and 48 h post-surgery. The primary outcome measure will be the effectiveness of the VR-based adjuvant analgesic software, as assessed by the reduction in NRS scores after the second intervention at 48 h postoperatively compared to pre-intervention baseline at 24 h postoperatively, and the secondary outcome measure will assess its safety profile. Our study marks a pioneering effort to incorporate VR-based adjuvant software into the postoperative pain management regimen. We endeavor to explore an innovative approach to deliver evidence-based pain treatments. The findings of this trial aim to shed light on the potential benefits of VR as a complementary tool to traditional analgesic therapies in the context of postoperative pain management following thoracoscopic procedures. Our protocol was retrospectively registered in the Chinese Clinical Trial Registry on August 2, 2024. The registration number was ChiCTR2400087741.

Recent research has highlighted the significance of circular RNAs (circRNAs) as pivotal regulators in the progression of tumors and the therapeutic response in non-small cell lung cancer (NSCLC). These circRNAs function through a sponge mechanism, interacting with microRNAs (miRNAs) to modulate mRNA expression levels. Nevertheless, the precise role of the circRNA-miRNA-mRNA regulatory network in immune regulation within lung adenocarcinoma (LUAD) remains inadequately understood. We utilized microarray datasets from the GEO NCBI database (GSE101586) to identify differentially expressed circRNAs (DEcircRNAs) in LUAD. CircBank was employed to predict the target miRNAs of DEcircRNAs, which were subsequently intersected with miRNAs from the GSE36681 database. The identified miRNAs were then predicted to target mRNAs using miRDB and miWalk, and intersections with immune-related genes from the IMMPORT database were analyzed. Protein-protein interaction (PPI) networks were constructed using Cytoscape software. The DAVID functional annotation tool was utilized to explore potential biological processes, molecular functions, and KEGG pathways associated with LUAD. Gene expression and Kaplan-Meier survival analyses were conducted to establish a key regulatory network and to assess immune cell infiltration and Pearson correlation for significant target genes. Finally, we selected the most significantly upregulated circRNA with differential expression for validation through in vitro experiments. Our analysis identified a total of 7 upregulated and 42 downregulated circRNAs, along with 10 significant miRNAs and 20 target mRNAs. KEGG enrichment analysis indicated that these components are primarily enriched in the ErbB signaling pathway. Furthermore, Gene Ontology (GO) analysis revealed significant enrichment in responses to organic substances, cytokine-mediated signaling pathways, cellular responses to cytokines, responses to chemical stimuli, steroid hormone receptor activity, ErbB-3 class receptor binding, oxysterol binding, signal receptor activity, and molecular transducer activity. Notable core mRNAs identified included OAS1, VIPR1, and PIK3R1. Subsequently, we constructed a regulatory network comprising 6 DEcircRNAs, 3 DEmiRNAs, and 3 DEmRNAs. Through ssGSEA and CIBERSORT analyses, we observed significant differences in immune cell infiltration levels between the NSCLC cohort and the control group. Knocking down the expression of hsa_circ_0079557 significantly inhibited the viability, proliferation, migration, and invasion of LUAD cells. We have established a circRNA-miRNA-mRNA regulatory network that offers novel insights into the molecular mechanisms governing immune regulation in LUAD. Future research should aim to translate these findings into clinical applications to enhance patient outcomes.

Preoperative delirium is common and associated with poor clinical outcomes in elderly hip fracture patients. Although inflammatory markers have shown potential in predicting postoperative delirium, their relevance to preoperative delirium remains unclear. This study aimed to investigate the relationship between inflammatory markers and preoperative delirium to improve risk prediction and management strategies. We retrospectively studied 548 elderly hip fracture patients aged 70 years or older. The primary outcome was preoperative delirium diagnosed using the Confusion Assessment Method (CAM). Explanatory variables included inflammatory markers (neutrophil-to-lymphocyte ratio [NLR], platelet-to-lymphocyte ratio [PLR], systemic immune-inflammation index [SII], inflammatory burden index [IBI], and systemic inflammation response index [SIRI]). About 7.66% of patients developed preoperative delirium in the study. These patients were more likely to be older, have comorbid cardiovascular disease, and be transferred to an internal medicine ward for further treatment (P < .001). Multivariate analysis further revealed that older age (OR = 1.11, 95% CI = 1.04-1.18) and comorbid cardiovascular disease (OR = 2.94, 95% CI = 1.51-5.67) were independently associated with the occurrence of preoperative delirium. No significant differences were observed between groups for inflammatory markers: NLR (P = .70), PLR (P = .09), IBI (P = .09), SII (P = .21), or SIRI (P = .80). Older age and cardiovascular comorbidities were independent risk factors for preoperative delirium. No significant associations were found with inflammatory markers. Future research should explore additional biomarkers to refine risk stratification in this population.

Background This study endeavored to develop a nicotinamide adenine dinucleotide (NAD+) metabolism-related biomarkers in gastric cancer (GC), which could provide a theoretical foundation for prognosis and therapy of GC patients. Methods In this study, differentially expressed genes (DEGs1) between GC and paraneoplastic tissues were overlapped with NAD+ metabolism-related genes (NMRGs) to identify differentially expressed NMRGs (DE-NMRGs). Then, GC patients were divided into high and low score groups by gene set variation analysis (GSVA) algorithm for differential expression analysis to obtain DEGs2, which was overlapped with DEGs1 for identification of intersection genes. These genes were further analyzed using univariate Cox and least absolute shrinkage and selection operator (LASSO) regression analyses to obtain prognostic genes for constructing a risk model. Enrichment and immune infiltration analyses further investigated investigate the different risk groups, and qRT-PCR validated the prognostic genes. Results Initially, we identified DE-NMRGs involved in NAD biosynthesis, with seven (DNAJB13, CST2, THPO, CIDEA, ONECUT1, UPK1B and SNCG) showing prognostic significance in GC. Subsequent, a prognostic model was constructed in which the risk score, derived from the expression profiles of these genes, along with gender, emerged as robust independent predictors of patient outcomes in GC. Enrichment analysis linked high-risk patients to synaptic membrane pathways and low-risk to the CMG complex pathway. Tumor immune infiltration analysis revealed correlations between risk scores and immune cell abundance, suggesting a relationship between NAD+ metabolism and immune response in GC. The prognostic significance of our identified genes was validated by qRT-PCR, which confirmed their upregulated expression in GC tissue samples. Conclusion In this study, seven NAD+ metabolism-related markers were established, which is of great significance for the development of prognostic molecular biomarkers and clinical prognosis prediction for gastric cancer patients.

OBJECTIVE AND DESIGN:This study aimed to investigate Axin2 effects on myocardial infarction (MI) using a macrophage Axin2 conditional knockout (cKO) mouse model, RAW264.7 cell line, and human subepicardial tissues from patients with coronary artery bypass graft (CABG).MATERIAL OR SUBJECTS:Axin2 cKO mice showed decreased cardiac function, reduced edema, increased lymphangiogenesis, and improved repair in MI Few studies border zones. Hypoxic macrophages with Axin2 depletion exhibited decreased senescence, elevated IL6 expression, and increased LYVE1 transcription. Senescent macrophages decreased in patients with CABG and low Axin2 expression.TREATMENT:Treatment options included in this study were MI induction in Axin2 cKO mice, in vitro experiments with RAW264.7 cells, and analysis of human subepicardial tissues.METHODS:Assays included MI induction, in vitro experiments, and tissue analysis with statistical tests applied.RESULTS:Axin2 cKO improved cardiac function, reduced edema, enhanced lymphangiogenesis, and decreased senescence. Hypoxic macrophages with Axin2 depletion showed reduced senescence, increased IL6 expression, and elevated LYVE1 transcription. Senescent macrophages decreased in patients with CABG and low Axin2 expression.CONCLUSION:Targeting Axin2 emerges as a novel therapeutic strategy for regulating cardiac lymphatics and mitigating cell senescence post-MI, evidenced by improved outcomes in Axin2-deficient conditions.

Background: Previous research has demonstrated that glycyrrhizic acid (GA) exhibits antioxidant, antiinflammatory, and antiapoptotic characteristics. Using myocardial ischemia/reperfusion injury as a case study, this study aims to clarify the functional significance of GA and to elucidate the mechanisms involved. Materials and methods: In this study, an MI/R injury model was established both in vivo and in vitro to investigate the impact of GA on MI/R injury. The viability of H9c2 cells was evaluated using the Cell Counting Kit -8. Myocardial damage was assessed through the measurement of creatine kinase myocardial band (CK-MB) levels and lactate dehydrogenase (LDH), HE staining, and MASSON staining. Inflammatory cytokine levels (IL -6, IL-1 beta, IL -10, and TNF-alpha) were measured to determine the presence of inflammation. Cellular oxidative stress was evaluated by measuring ROS and MMP levels, while cardiac function was assessed using cardiac color Doppler ultrasound. Immunofluorescence staining to determine the nuclear translocation of YAP, TUNEL to determine apoptosis, and western blotting to determine gene expression. Results: GA treatment effectively alleviated myocardial injury induced by MI/R, as evidenced by reduced levels of inflammatory cytokines (IL-1 beta, IL -6, IL -10, and TNF-alpha) and cardiac biomarkers (CK-MB, LDH) in MI/R rats. Moreover, There was a significant increase in cell viability in vitro after GA treatment and inhibited reactive oxygen species (ROS) during oxidative stress, while also increasing mitochondrial membrane potential (MMP) in vitro. The Western blot findings indicate that GA treatment effectively suppressed apoptosis in both in vivo and in vitro settings. Additionally, GA demonstrated inhibitory effects on the activation of the Hippo/YAP signaling pathway triggered by MI/R and facilitated YAP nuclear translocation both in vitro and in vivo. It has been found, however, in vitro, that silencing the YAP gene negates GA's protective effect against hypoxia/reoxygenationinduced myocardial injury. Conclusion: This study suggests that GA regulates YAP nuclear translocation by inhibiting the Hippo/YAP signaling pathway, which protects ists against MI/R injury. This finding may present a novel therapeutic approach for the treatment of MI/R.

Background: Lung cancer screening is not limited to low dose computed tomography (LDCT). Recently, molecular biomarkers have been shown to have the potential to improve the current state of early lung cancer detection. The current study determined the efficiency of seven autoantibodies against tumor-associated antigens (7-AABs) and tumor markers in patients with lung cancer. Materials and Methods: An enzyme-linked immunosorbent assay (ELISA) was used to determine the levels of 7-AABs and tumor markers in 354 patients with lung cancer and 108 patients with benign pulmonary disease under care at Ethics Committee of Tianjin Medical University General Hospital. Results: The sensitivity, specificity, positive predictive value (PPV), and area under the receiver operating characteristic (ROC) curve of 7-AABs were 30.0%, 84.3%, 86.3%, and 0.61, respectively. When combining the 7-AABs and tumor markers, the sensitivity was 68.6%, the specificity was 52.8%, and the area under the ROC curve was 0.72. The 7-AABs positive expression rate in lung cancer patients was significantly higher than patients with benign pulmonary diseases (30.1% vs 15.7%); however, the 7-AABs positive expression rate was affected by clinical features and pathologic stages. When combining 7-AABs and tumor markers, the combined 7-AABs and tumor marker positive expression rate increased to 68.6%. Conclusion: Based on this study and previous literature, the supplemental diagnostic value of 7-AABs has been confirmed; however, due to the low sensitivity, the value of 7-AABs alone in lung cancer screening is limited. The combination of 7-AABs and tumor markers has improved sensitivity and positivity, but decreased specificity, which makes their performance in cancer screening and early detection worthy of further research.