Open Medicine最新文献

Introduction: Cell membrane-derived nanovesicles, particularly those originating from red blood cells (RNVs), have garnered considerable attention as innovative drug delivery vehicles in oncology, owing to their exceptional biocompatibility, immune evasion, and prolonged systemic circulation. Nevertheless, their inherently poor tumor-targeting efficiency and nonspecific biodistribution present major obstacles to their therapeutic translation.

Objectives: This study sought to functionalize RNVs with a diverse array of tumor-targeting ligands - cRGD, transferrin (TRF), folic acid (FA), GE11, and RVG29 - and to systematically compare their tumor-homing efficiency, biodistribution, and biosafety in a breast cancer model.

Results: Functionalized RNVs exhibited markedly enhanced tumor affinity relative to unmodified vesicles in both in vitro and in vivo settings. Among the engineered formulations, RNV@cRGD achieved the most pronounced intratumoral accumulation and cellular uptake, followed sequentially by RNV@GE11, RNV@TRF, RNV@FA, and RNV@RVG29. Fluorescence imaging corroborated the superior tumor selectivity of engineered constructs, all of which also demonstrated robust stability and negligible off-target toxicity in murine models.

Conclusion: This work presents systematic comparative evaluation of ligand-engineered RNVs, underscoring cRGD as the most potent targeting moiety for breast cancer. These findings illuminate critical design principles for the rational development of tumor-directed RNV-based drug delivery systems and strengthen the translational promise of biomimetic nanocarriers for clinical oncology.

Background: Hypoxia and glycolysis play crucial roles in tumor progression, yet their association with kidney renal clear cell carcinoma (KIRC) remains unclear. Here, a novel prognostic model was developed with hypoxia-glycolysis-related genes (HGRGs) in KIRC, providing insights to elucidate the aforementioned uncertainties.

Methods: Transcriptomic information and clinical characteristics of KIRC were acquired from The Cancer Genome Atlas Program, ArrayExpress database, and Gene Expression Omnibus. Significant HGRGs were identified, and a prognostic model was constructed. We performed enrichment analysis, tumor mutational burden (TMB), tumor microenvironment), and drug sensitivity analyses to elucidate potential mechanisms of HGRGs.

Results: The prognostic model based on five HGRGs (ADORA2B, TGFA, FBP1, HK3, PDHB) effectively predicted the clinical outcome. The nomogram, which integrates a prognostic model and clinical information, demonstrated superior performance. Low-risk patients were enriched in fatty acid metabolism and peroxisome pathways, exhibited higher immunotherapy responsiveness, and showed greater sensitivity to Gefitinib and Afatinib. High-risk patients exhibited activation of inflammatory and profibrotic pathways, an elevated TMB, immunosuppressive microenvironments, and greater sensitivity to Topotecan and Irinotecan. RT-qPCR validated the expression of HGRGs across selected cell lines.

Conclusions: The prognostic model derived from five HGRGs demonstrates excellent clinical value in predicting prognosis and guiding therapeutic strategies in KIRC.

Objective: This study aimed to investigate the relationship between serum carbohydrate antigen 50 (CA50), carbohydrate antigen 242 (CA242), and serum amyloid A (SAA) levels and clinical pathological features and prognosis in pancreatic cancer (PC) patients.

Methods: A total of 163 PC patients were divided into a survival group (n = 43) and a deceased group (n = 120). Serum levels of CA50, CA242, and SAA were measured, and patients were categorized into high- and low-expression groups based on median values. Relationships between marker expression, clinical features, and prognosis were analyzed using Cox regression, receiver operating characteristic (ROC) analysis, and Kaplan-Meier curves.

Results: Serum CA50, CA242, and SAA levels were significantly higher in the deceased group than in the survival group (all P < 0.001). High CA50 was linked to advanced TNM stage and distant metastasis; high CA242 to advanced TNM stage and lower differentiation; and high SAA to advanced TNM stage and distant metastasis (all P < 0.05). Multivariate Cox regression showed that advanced TNM stage (hazard ratio [HR] = 1.499, 95% confidence interval [CI] = 1.003-2.238, P = 0.048), distant metastasis (HR = 1.693, 95% CI = 1.157-2.478, P = 0.007), high CA50 (HR = 1.041, 95% CI = 1.019-1.064, P < 0.001), high CA242 (HR = 1.044, 95% CI = 1.018-1.070, P < 0.001), and high SAA (HR = 1.096, 95% CI = 1.044-1.151, P < 0.001) were independent risk factors for poor prognosis. ROC analysis showed that the combined detection of CA50, CA242, and SAA had the highest predictive value for poor prognosis (AUC = 0.989, sensitivity = 93.33%, specificity = 100%), which was significantly superior to single-marker detection (CA50: AUC = 0.872, sensitivity = 78.33%, specificity = 88.37%; CA242: AUC = 0.905, sensitivity = 74.17%, specificity = 88.37%; SAA: AUC = 0.871, sensitivity = 80.00%, specificity = 83.72%; all P < 0.001 vs combination). Kaplan-Meier curves revealed higher mortality risk in high-expression groups.

Conclusion: Serum CA50, CA242, and SAA levels are closely associated with PC patients' clinical features and prognosis. Their combined detection is a valuable tool for assessing poor prognosis in PC.

Background: Hyperkalemia is a potentially life-threatening electrolyte disorder, especially in patients with chronic kidney disease and those undergoing dialysis. Its management is complex due to the need to balance potassium control with overall patient stability.

Objectives: The aim of this systematic review is to evaluate current therapeutic strategies for hyperkalemia in dialysis patients, including diuretics, ion-exchange resins, and newer agents such as sodium zirconium cyclosilicate (SZC).

Methods: A systematic search was conducted in Scopus and Web of Science, applying filters for language, recency (≤5 years), and journal quality. After removing duplicates and irrelevant records, 11 high-quality studies were included.

Results: New therapies like SZC and patiromer demonstrated efficacy in maintaining safe potassium levels. The potassium binding pack showed promise in acute and resource-limited settings. Evidence challenges strict dietary potassium restrictions, especially regarding plant-based foods, and highlights the importance of individualized nutritional plans. Continuous potassium monitoring is essential to preserve residual kidney function.

Conclusion: Hyperkalemia management in dialysis patients benefits from an integrated approach combining pharmacologic treatment, tailored nutrition, and close monitoring. Novel interventions and evolving dietary guidelines may improve safety, effectiveness, and quality of life in this vulnerable population.

The increased use of next-generation sequencing in clinical genetic testing has resulted in the identification of several genetic variations with possible therapeutic implications. We developed OKAIN (https://szcube.origimed.com), an algorithm tool that assesses clinically actionable mutations using a precision oncology knowledge database. OKAIN employs a weighted evidence analysis system to deliver final clinical annotation outcomes for intricate variations. As of now, OKAIN has amassed over 100,000 variants in 1,239 cancer-associated genes, encompassing 12,409 entries of therapeutic evidence in 471 genes. This collection highlights 2,600 Level A evidence entries in 66 genes, with 864 entries derived from the National Medical Products Administration labels or Chinese guidelines. OKAIN acts as a precision oncology knowledge base for the assessment of clinically actionable alterations, integrating exhaustive data related to cancer-associated genomic variants and therapeutic efficacy. Analyzing patient variants with OKAIN reveals more actionable targeted therapy or immunotherapy options, potentially improving treatment outcomes.

Background and aim: The study used a sequential qualitative-quantitative research design to develop a survey tool that explores the current situation and influencing factors of community nurses' research ability.

Methods: The qualitative research developed the Chinese Community Nurses Research Ability Tool (CCN-RAT) through face-to-face interviews. The quantitative research tests the current situation and influencing factors of research ability among community nurses. One-way ANOVA and Multiple Linear Regression were used to analyze the results.

Results: The Cronbach's α was found to be 0.993, and the Subject-Content Validity Index was 0.99 using CCN-RAT. Most of the community nurses had a low to moderate level of research ability. Age (95%CI: 1.812-9.533, P = 0.004), educational attainment (95%CI: 4.667-11.660, P < 0.001), working experience year (95%CI: 0.274-1.0410, P = 0.001), number of participants in research projects (95%CI: 0.239-11.130, P = 0.041), number of published articles in Chinese core journal or SCI (95%CI: 19.354-36.969, P < 0.001), and number of participants in research training (95%CI: 18.289-28.218, P < 0.001) were significant influencing factors on research ability among community nurses.

Conclusion: CCN-RAT could help nurses, educators, students, and other populations to better understand the current situation and influencing factors of research ability, which could provide targeted research training to improve research ability for public health staff.

Objective: Thrombocytopenia induced by proton pump inhibitors (PPIs) is a relatively uncommon adverse effect of this widely prescribed class of drugs. The objective of this study is to investigate the clinical features of PPIs-induced thrombocytopenia based on published case reports.

Methods: We searched the PubMed, Web of Science, Scopus, China National Knowledge Infrastructure, Wanfang Data, and Chinese VIP databases from inception to August 2024 to identify reported cases of thrombocytopenia associated with PPIs use. Clinical data such as patient demographics, drug use information, adverse reactions, and outcomes were extracted and analyzed.

Results: Overall, 16 publications describing 18 cases (12 males and 6 females) were included in this study, comprising a neonate and 17 adults with a median age of 62 years (range 23-98). The PPIs associated with thrombocytopenia included pantoprazole (11 cases), lansoprazole (4 cases), omeprazole (2 cases), and esomeprazole (1 case). The median time to symptoms onset was 3 days (range 2-7) after the initiation of PPI therapy. After discontinuation of PPIs and interventions such as platelet transfusion, 11 patients achieved recovery, and the remaining 7 patients experienced symptomatic improvement.

Conclusion: Thrombocytopenia induced by PPIs appears to be a rare adverse event. Clinicians should enhance their awareness when evaluating potential cases of thrombocytopenia. Once PPIs are suspected, immediate discontinuation of the drugs and initiation of appropriate treatments are recommended.

Sepsis is an inflammatory disease caused by a severe infection, and its pathological process involves complex immune reactions and inflammatory cascades. This condition often leads to multiple organ dysfunction syndrome, which is one of the main causes of patient mortality. In recent years, researchers have paid extensive attention to the protective role of selenium (Se) in sepsis. Se is believed to potentially counteract organ dysfunction caused by sepsis through various mechanisms and is considered a potential therapeutic strategy. This review extensively discusses the potential mechanisms of Se in sepsis. We explore the antioxidant and anti-inflammatory properties of Se, as well as its regulatory effects on immune cell activity, expression of inflammatory mediators, and oxidative stress. In addition, we examine the impact of Se on organ damage and organ dysfunction caused by sepsis, with a focus on its protective effects on important organs such as the cardiovascular system, respiratory system, kidneys, and liver. We evaluate relevant preclinical and clinical studies to assess the potential of Se as a treatment for sepsis-related organ dysfunction. We discuss the optimization of Se administration routes, dosages, and timing, and summarize the impact of Se on clinical outcomes and survival rates. In summary, Se demonstrates significant potential as a therapeutic strategy in sepsis-related organ dysfunction. However, further research is still needed to delve into the mechanisms of Se and optimize its application in clinical practice. This will provide breakthroughs in the treatment of sepsis patients, improving their prognosis and survival rates.

Objective: To investigate the role and underlying mechanisms of colony-stimulating factor 2 (CSF2) in the progression of kidney renal clear cell carcinoma (KIRC).

Methods: Transcriptomic and clinical data from The Cancer Genome Atlas were analyzed to assess the correlation between CSF2 expression, clinicopathological features, and patient prognosis. A neutrophil-tumor co-culture system was established to examine the effects of CSF2 on neutrophil polarization, tumor cell proliferation, migration, apoptosis, and autophagy. Protein expression was evaluated by flow cytometry, Western blot, and immunofluorescence. PD-L1 knockout and autophagy inhibitors (3-methyladenine and chloroquine) were used to explore regulatory mechanisms.

Results: CSF2 expression was significantly upregulated in KIRC tissues and was positively associated with advanced tumor stage and poor prognosis. In vitro, CSF2 promoted neutrophil polarization toward the tumor-supportive N2 phenotype and enhanced the proliferation and migration of renal cancer cells while inhibiting apoptosis and reactive oxygen species production. Additionally, CSF2 upregulated PD-L1 expression in tumor cells and activated autophagy by increasing LC-3, Beclin1, and ATG7 levels. These effects were reversed by PD-L1 knockout or treatment with the autophagy inhibitor 3-methyladenine.

Conclusion: CSF2 promotes KIRC progression through PD-L1-mediated neutrophil polarization and autophagy activation, representing a potential therapeutic target.

Objective: This study investigates the association between serum SLC31A1, a copper death-promoting factor, and clinicopathological features/prognosis in papillary thyroid carcinoma (PTC).

Methods: A cohort of 250 PTC patients was stratified into good (n = 205) and poor (n = 45) prognosis groups. Clinicopathological parameters (age, sex, tumor diameter, differentiation, TNM stage, thyroid exocapsular invasion, lymph node metastasis) and serum SLC31A1 levels (measured via ELISA) were analyzed. Patients were further categorized into high/low SLC31A1 expression groups based on median values. Prognostic correlations were evaluated using Kaplan-Meier survival analysis, Cox regression, and receiver operating characteristic (ROC) curve assessment.

Results: Elevated serum SLC31A1 levels were significantly associated with poor prognosis, advanced TNM stages (III/IV), poor differentiation, thyroid exocapsular invasion, and lymph node metastasis. Multivariate Cox analysis identified high SLC31A1 as an independent predictor of poor prognosis (HR = 1.235, 95% CI 1.158-1.317). ROC analysis demonstrated strong predictive accuracy for SLC31A1 in prognosis assessment (AUC = 0.859).

Conclusion: High serum SLC31A1 expression correlates with aggressive clinicopathological features and independently predicts adverse outcomes in PTC patients, suggesting its potential as a prognostic biomarker for clinical stratification.