医学最新文献

Combining radiotherapy with immune checkpoint inhibitors (RT-ICI) triggers systemic antitumor responses, such as abscopal effects (AbE). Predictors of AbE and its impact on survival in real-world settings remain poorly defined. This multicenter, retrospective cohort study assessed the prevalence of AbE in ICI-refractory progressive metastatic patients by evaluating the additive effect of RT on nonirradiated lesions (NIL). We screened 3773 cases to identify patients with stage IV tumors receiving RT during/after ICI. Abscopal benefit (AB) was defined as abscopal response (AR) or control (AC) by measuring NILs according to iRECIST. AB was observed in 61.3% of 142 included patients and associated with improved median overall survival (18 vs. 8 months, p < 0.01) and progression-free survival (7 vs. 3 months, p < 0.01). Logistic regression identified younger age (OR = 0.951, 95% CI: 0.903-0.995, p = 0.039) and longer ICI-RT intervals (OR = 1.077, 95% CI: 1.019-1.171, p = 0.027) as predictors of AB. There was no association between radiation dose or tumor volume and AB. Cox regression identified BMI ≥ 25 kg/m² (HR = 3.348, 95% CI: 1.557-7.202, p = 0.002) and CRP ≥ 5 mg/l (HR = 3.058, 95% CI: 1.211-7.724, p = 0.016) as independent negative prognostic factors for survival in this RT-ICI cohort. Median survival was significantly higher among patients receiving ultrahypofractionated RT, compared to other fractions (21 vs. 11 months; p = 0.024). AbE seems to occur reliably and is prognostically relevant in ICI-refractory patients receiving RT. Patient- and timing-related factors were more predictive than RT details in our cohort. Our findings enhance the understanding of tailored RT-ICI approaches and lay the groundwork for targeted radioimmunotherapy strategies and personalized clinical trial designs.

Background: Circulating microRNA-210-3p (miR-210-3p) is a hypoxia-related regulator implicated in placental maladaptation. Its longitudinal behavior across hypertensive disorders of pregnancy (HDP), and whether low-dose aspirin modifies its trajectory, remain insufficiently understood.

Methods: This prospective case-control study was conducted between October 2021 and November 2024. Circulating miR-210-3p was measured in the first trimester and at delivery. Aspirin use followed routine clinical practice for preeclampsia prevention. Longitudinal trajectories were examined using generalized estimating equations (GEE) as the primary analytic approach and linear mixed effects models (LMM) as a secondary method.

Results: Ninety-four women were enrolled, including 73 controls, 11 with gestational hypertension, and 10 with preeclampsia. miR-210-3p increased significantly from the first trimester to delivery in gestational hypertension (p = 0.003) and preeclampsia (p = 0.006), with no significant change in controls. In the first trimester, gestational hypertension exceeded controls (p = 0.006), and preeclampsia exceeded both groups (both p < 0.001). At delivery, gestational hypertension and preeclampsia remained higher than controls (both p < 0.001), and preeclampsia exceeded gestational hypertension (p = 0.036). GEE demonstrated a significantly slower rise in miR-210-3p among aspirin users with gestational hypertension (p = 0.042), and this association strengthened in sensitivity analysis (p = 0.001). LMM showed a similar, non-significant trend.

Conclusion: miR-210-3p exhibited disorder-specific longitudinal patterns across HDP. Aspirin-associated changes were observed in gestational hypertension but not in preeclampsia, suggesting differences in molecular expression trajectories between the two conditions over the course of gestation, while the underlying biological mechanisms remain to be clarified.

Gamification is increasingly adopted in health professions education to enhance clinical reasoning, a core competency essential for safe patient care. Although many interventions report positive outcomes, the magnitude and consistency of these effects remain uncertain. This meta-analytic review synthesizes quantitative findings on the effectiveness of gamified learning on clinical reasoning in medical and allied health learners across diverse contexts. Following PRISMA 2020 guidelines, we searched MEDLINE, Scopus, and Web of Science (2010-2023) for randomized and non-randomized studies evaluating gamified interventions targeting clinical reasoning. Eligible populations included pre- and post-licensure learners, with traditional or non-gamified instruction as comparators. Quantitative measures of clinical reasoning were required. Risk of bias was assessed using RoB 2.0 and ROBINS-I, and standardized mean differences (SMDs) were pooled using a random-effects model. From 713 records, 26 studies met inclusion criteria and 10 contributed to the meta-analysis. Gamified interventions were associated with improved clinical reasoning compared with traditional instruction (SMD = 1.11; 95% CI: 0.69-1.52). Substantial heterogeneity was observed (I² = 85%). Assessment of publication bias suggested possible overestimation of effects, with an adjusted pooled estimate of 0.75 (95% CI: 0.24-1.27). The certainty of evidence was rated as low due to heterogeneity, risk of bias, and potential publication bias. Gamified learning may support the development of clinical reasoning in health professions education; however, considerable variability across studies and low certainty of evidence warrant cautious interpretation. Future research should employ theory-informed designs, validated reasoning measures, and rigorous methodologies to clarify when and how gamification is most effective.

A concerning trend has recently emerged in Libya where cancer patients are seeking unproven herbal remedies derived from local Artemisia species driven by circulating claims on social media. These unregulated traditional medicines can interact with standard cancer treatments such as chemotherapy and radiation therapy. Scientific evidence suggests that Artemisia compounds can alter drug metabolism through enzymatic pathways (notably the CYP450 system), potentially neutralizing treatment efficacy or exacerbating systemic toxicity. This letter evaluates the toxicological profile of Artemisia and proposes an ethical framework for patient protection and public health intervention in Libya.

Liver X receptor β (LXRβ) is a key transcription factor involved in lipid metabolism and immune regulation, yet its functional role in tumor-infiltrating T cells remains largely unresolved. While LXRβ has been shown to suppress NF-κB target gene expression, the mechanistic interaction between LXRβ and NF-κB signaling in the tumor microenvironment (TME) has not been fully established. In this study, we identify LXRβ as a critical regulator of CAR-T cell differentiation, the metabolic state, and effector function within solid tumors. LXRβ overexpression altered the transcriptional and phenotypic landscape of CAR-T cells, including the modulation of stem-like TCF1⁺ populations, proliferative capacity (Ki-67), and cytokine production (IFNγ, TNFα). Through genetic perturbation of NF-κB components, particularly RelB, we further demonstrate that disrupting non-canonical NF-κB signaling enhances CAR-T cell cytotoxicity and attenuates exhaustion-related features such as TOX upregulation. Notably, combined targeting of LXRβ and RelB produced additive and, in some settings, synergistic benefits, improving metabolic fitness, reducing terminal exhaustion, and augmenting anti-tumor activity in vivo. Together, these findings define an LXRβ-NF-κB regulatory axis that shapes CAR-T cell fate and function in the TME and highlight this pathway as a promising target for improving CAR-T cell-based therapies against solid tumors.

By 2050, more than 61 million people worldwide are expected to lose their vision due to conditions like age-related macular degeneration, glaucoma, diabetic retinopathy, and uveitis (Bourne et al. 2021). This anticipated rise highlights the urgent need for more effective treatment options. While progress continues in developing new pharmacological agents, treating ocular diseases with these therapies remains particularly challenging due to the eye's unique and complex anatomy. This is largely due to the limitations of current drug delivery methods, including systemic administration, topical delivery application, transscleral/periocular drug delivery, and intravitreal injections, which are associated with low bioavailability, side effects, and rapid drug clearance. Given these challenges, microneedles have emerged as a promising alternative. Their minimally invasive nature and ability to precisely target the anterior and posterior segments make them well suited for enhancing therapeutic outcomes while reducing systemic exposure and potential side effects, as well as improving patient adherence (Kang-Mieler et al. 2017; Gadziński et al. 2022). The purpose of this review is to discuss recent advancements, key challenges, and strategies for microneedle-based ocular drug delivery systems, with an emphasis on their potential to treat both anterior and posterior eye diseases.

Proniosomes represent an advanced composite vesicular platform that integrates non-ionic surfactants, lipids, and biodegradable carriers to significantly improve drug solubility, stability, and transmembrane delivery. These dry powdery formulations are transformed into multiscale niosomes upon contact with a hydrated medium to achieve controlled release and enhanced drug permeability. This seminal review delineates the transformative potential of proniosomal systems in treating various diseases, detailing diverse routes of administration, formulation techniques, mechanisms of action, as well as their advantages and limitations. Proniosomes address major issues such as systemic toxicity, poor solubility, and erratic absorption while maintaining green chemistry principles owing to their biodegradable constituents. By critically analyzing the potential for industrial translation, this review highlights the knowledge gap on clinical studies, scalability, and regulatory issues. The translation potential has even been further enhanced by recent developments in bioconjugation and nanotechnology, such as ligand-anchored proniosomes that enable active targeting. The topic's relevance is evident, as proniosomes complement next-generation biotechnology tools, such as mRNA delivery, while offering a sustainable alternative to liposomes. By compiling the most recent data, this review strives to catalyze innovation in novel drug delivery, making it essential for researchers and pharmaceutical developers.

This article examines the global issue of vaccine hesitancy in Brazil and South Africa, two economically unequal BRICS nations. Despite their established immunization programs, both countries are grappling with coverage decreases, leading to outbreaks. The role of vaccine hesitancy in this scenario is significant. This qualitative study aims to understand childhood vaccine hesitancy in these contexts, highlighting social and behavioral drivers. In-depth interviews were conducted in Sao Luis (Brazil), Florianopolis (Brazil), and Cape Town (South Africa), involving 42 caregivers from diverse socioeconomic backgrounds, race/color, and gender, with children up to 6 years old. Thematic analysis method was used to analyze the empirical data. The drivers of vaccine hesitancy have been arranged across three domains: 'practical issues', prevalent among lower-income non-white families; 'social processes', as informed decisions reflecting neoliberal parenting values, found among higher-income white families; and, in the 'thinking and feeling about vaccines' domain, common fears of side effects and vaccines components are presented. These findings underscore the necessity of tailored health policies, taking into account the influence of historical, cultural, and social contexts. The study also highlights the crucial role of qualitative research in comprehending the intricate interplay of social and behavioral factors in health decision-making.

Currently, increasing attention is being paid to the extraction and utilization of materials with special biological activities in nature or for medical applications. Owing to their unique biological characteristics and diverse application potential, microalgae are among the most promising materials in the field of biomedicine. Because of their diverse morphology and readily functionalizable surface, they can efficiently carry drugs and achieve targeted drug release. This can avoid major challenges of other methods related to toxicity, biocompatibility, and immunogenicity, which is important for the treatment of various diseases, particularly those related to hypoxia. Despite the distinct advantages of microalgae over other biomaterials, several challenges persist in their practical application. Herein, we comprehensively describe the current state of research on the microalgae drug-delivery system (MDDS). In particular, we explore various microalgae-based strategies and methods to improve the load capacity and stability of DDS, and to achieve target positioning and tracking. With further research on microalgae, their application prospects in DDSs will broaden. In the future, researchers will continue to explore the features and advantages of microalgae; develop more efficient, safe, and accurate DDSs; and provide more options for clinical treatments. Continued progress in microalgal cultivation technology and reduction in large-scale production costs will expand the clinical applications of MDDSs.

Background: Effective disaster management requires healthcare professionals to function not only as responders but also as trainers who can disseminate knowledge and skills. In low-resource settings such as Tanzania, structured train-the-trainer (ToT) programs tailored to physicians remain limited. This study aimed to design, implement, and evaluate a trainer development program for Tanzanian emergency medicine physicians using the ADDIE instructional design framework to transparently link needs assessment to role-adapted objectives, learning activities, and evaluation.

Methods: A mixed-methods design was applied, combining pre-training surveys, post-training assessments, and thematic feedback analysis. The program, conducted on 21-22 November 2024 at the Urla International Emergency Disaster Training and Simulation Centre, followed the ADDIE model (Analysis, Design, Development, Implementation, Evaluation). Twenty Tanzanian physicians (mean age 35.9 years, 60% female, mean experience 8.2 years) participated. Participants were grouped as Emergency Medicine Specialists/Medical Officers (n=8) and General Practitioners/Resident Physicians (n=12), with tailored objectives focusing on leadership, teamwork, disaster planning, and trainer skills.

Results: Participants achieved a mean post-training MCQ score of 17.68 out of 20, corresponding to an overall correct response rate of 88.4%. Scenario-based and interactive learning methods were highly valued, while insufficient training duration and limited technical infrastructure were identified as challenges. Emergency medicine specialists prioritized leadership and coordination skills, whereas general practitioners and residents emphasized educational strategies and program development.The program was feasible and well received, and participants achieved high immediate post-course knowledge scores and reported strong perceived value of scenario-based and trainer-focused learning activities. The findings support role-adapted ToT models for physicians; however, objective measurement of educator and leadership competencies and follow-up assessment of cascade training implementation are needed to determine sustained trainer development.