医学最新文献

People with underlying diseases are at-increased-risk of suffering from herpes zoster (HZ). However, the economic impact of HZ on these populations is not well described. This study aimed to quantify the clinical and economic impact of HZ in patients with comorbidities (diabetes, chronic obstructive pulmonary disease, heart disease, kidney disease, asthma) and immune disorders (inflammatory bowel disease, rheumatoid arthritis, systemic lupus erythematosus, multiple sclerosis, psoriasis, COVID-19 and psoriatic arthritis) in Spain. This is an observational, retrospective case-control study using the BIG-PAC electronic records from 01 Jan 2014 to 31 Aug 2021. Healthcare resource use and costs over 12 months following HZ diagnosis were compared between patients and controls, matched by propensity scores. The total annual economic burden was estimated using HZ-related costs per patient and HZ crude incidence over the study period, together with the estimated prevalence of each comorbidity in the Spanish population aged ≥18 y. Mean incremental costs per HZ episode were €1,108 in patients with comorbidities and €1,203 in patients with immune disorders. Indirect costs accounted for 4.7% and 22.9% of incremental costs in people with comorbidities and immune disorders, respectively. Mean annual crude HZ incidence rates were 613.6 cases per 100,000 people with comorbidities and 659.0 cases per 100,000 people with autoimmune disorders. Total annual costs due to HZ in these populations were estimated at €121 million. HZ may cause a significant economic burden in Spain from a societal perspective in patients with underlying conditions, highlighting the importance of improving vaccination programs.

In 2015, the United Nations integrated adolescents as a unique category into the Sustainable Development Goals, a recognition the World Health Organization expanded in 2017 with the introduction of the Global Accelerated Action for the Health of Adolescents. This paper examines the emergence of the 'adolescent subject' in global health. Adolescence is a modern concept embedded in Western views that is not universally applicable, hence raising issues in global health practice by embodying a colonial legacy in using categories that may not align with all cultural contexts. Moreover, the paper explores a critical gap in global health research: while the majority of the world's adolescents reside in low- and middle-income countries, most adolescent health research is conducted in high-income settings. This disparity is due, in part, to a lack of funding for adolescent research and barriers like parental consent requirements that prevent adolescents from participating in research. This exclusion inadvertently silences some adolescents' voices and restricts their opportunities for research engagement, perpetuating an epistemic injustice in global health data production. The paper calls for a concerted effort to develop measures to inclusively engage adolescents in global health research, aiming for a fair and representative inclusion of adolescent perspectives.

Background: The frailty index (FI), reflecting cumulative health deficits, is a strong predictor of adverse outcomes in older adults. However, its prognostic value for mortality among patients with testosterone deficiency (TD) remains unclear.

Methods: We analyzed 1,688 adults with TD from three NHANES cycles (2011-2016) with mortality follow-up through 2019. FI was constructed using a 49-item deficit model. Survival differences were evaluated with Kaplan-Meier curves, and survey-weighted Cox models assessed the association between FI and all-cause mortality. Restricted cubic splines and threshold analyses explored dose-response relationships. Mediation analysis examined the role of the platelet-to-HDL-C ratio (PHR).

Results: Frail participants exhibited significantly higher mortality risk than non-frail individuals (log-rank P < 0.001). Per 1-SD increase in FI, mortality risk rose by 76% (HR = 1.76, 95% CI: 1.57-1.96, P < 0.001). Threshold analysis showed a sharp increase in mortality when FI exceeded 0.095, approximating the conventional pre-frailty cut-off. PHR mediated 8.46% of the FI-mortality association.

Conclusion: Higher FI was independently associated with increased all-cause mortality in TD patients, partly mediated by PHR. These findings highlight the prognostic significance of frailty and suggest PHR as a potential marker for personalized risk stratification and targeted intervention.

The pathogenesis of autoimmune thyroiditis (AIT) is intricately linked to immune dysregulation, endocrine imbalance, and gut microbiota dysbiosis. The immune system drives autoimmune attacks against thyroid tissue through Th1/Th2 cell imbalance, Treg dysfunction, and excessive release of proinflammatory cytokines. Thyroid hormone regulation primarily occurs via the hypothalamic-pituitary-thyroid (HPT) axis. Elevated levels of TPOAb and TgAb in AIT patients can lead to hypothyroidism by affecting the HPT feedback loop. Thyroid hormone regulation of immune cell metabolism and differentiation, in turn, affects immune homeostasis, forming a bidirectional regulatory network. Recent studies further reveal that the gut microbiota influences systemic immune tolerance by regulating intestinal barrier integrity and metabolites (e.g. short-chain fatty acids and secondary bile acids). Abnormal abundance of specific genera (e.g. Bacteroides and Prevotella) can promote the production of thyroid autoantibodies (TPOAb/TgAb), and increased intestinal permeability caused by microbiota dysbiosis may facilitate cross-reactivity between microbial antigens and thyroid antigens. Furthermore, the gut microbiota indirectly regulates thyroid function through the HPT axis. This review aims to summarize the current knowledge regarding the specific molecular mechanisms of gut microbiota-immune-endocrine interactions in AIT, offer important references for researching the treatment directions of AIT.

Objective: To analyze the effects of melatonin on angiogenesis in cultured granulosa cells from women undergoing in vitro fertilization, comparing those with female-factor versus male-factor infertility.

Methods: Granulosa cells were obtained from 47 women undergoing in vitro fertilization treatment, including 31 women with female-factor (FFG) and 16 women with male-factor infertility (MFG). Cells from both groups were cultured and divided into four treatment conditions for 96 h: a) control (culture medium without melatonin); b) vehicle (melatonin diluent-ethanol); c) 0.1 µM melatonin; and d) 10 µM melatonin. Expression of 84 genes involved in angiogenesis signaling pathway was analyzed by real-time PCR.

Results: Cultured granulosa cells from both groups expressed aromatase and melatonin receptors. In both groups, cell proliferation peaked at 72 h when exposed to 10 µM melatonin. Of the 84 analyzed genes, three showed significant differential mRNA expression. In the MFG, melatonin at 10 µM upregulated VEGF-B mRNA expression in granulosa cells but downregulated PDGFA and HGF mRNA expression, in contrast to the higher expression of these genes in the FFG under identical conditions.

Conclusion: Melatonin differentially modulates angiogenesis-related gene expression in granulosa cells, indicating that its effects may depend on infertility type and melatonin dose in women undergoing in vitro fertilization.

Aim: "Empathy" is a key concept in dementia care and considered important to improve the quality of care. However, how empathy should be promoted among dementia care nurses remains unclear. Thus, this study aimed to clarify the role of nurses' empathy in caring for people with dementia.

Methods: Certified nurse specialists in gerontological and dementia nursing were recruited as participants using snowball sampling. Data were collected from seven participants in March 2023 through focus-group interviews and analyzed qualitatively and inductively.

Results: Six categories related to care experiences were formed using fifty-six codes in five stages. The categories were as follows: i) Turn toward each other, considering personal diversity; ii) Actively approach them by understanding and acknowledging their thoughts; iii) Experience feelings of warmth after comprehending their personalities; iv) Experience an emotional resonance with them; v) Sharpen own senses to deeply understand their experiences; and vi) Work as a team to provide the most suitable care.

Conclusion: The results demonstrated that empathy is a key element in the interactions between nurses and people with dementia that contributes to more harmonious relationships. These findings can be used to educate nurses on dementia care, which may help reduce nurses' burnout.

Interleukin (IL)-37 is one of the "youngest" IL-1 family members and one of the few molecules exerting anti-inflammatory activity. Upon inflammasome activation, the cytokine precursor is converted into its mature form, which acts intracellularly as a nuclear transcription factor, impairing the production of pro-inflammatory cytokines, and extracellularly by forming the IL-37/IL-18Rα/IL-1R8 complex, favoring IL-1R8 inhibitory signaling with immunosuppressive function. IL-1R8, which is mostly expressed in a number of cell types, negatively regulates both IL-1R/TLR signaling, blocking the NF-kB/JNK pathway and the production of pro-inflammatory cytokines. Owing to its ability to inhibit both innate and adaptive immunity, IL-37 has been reported to control inflammation in many chronic disorders, including cancer. IL-37 impairs the proliferation and migration of tumor cells, mediates anti-angiogenetic mechanisms, and favors immunoregulation in the tumor microenvironment (TME). This review aims to provide a current overview of IL-37 genetic and biological features and of its active interaction with IL-1R8, inducing anti-inflammatory effects on the immune system and affecting cancer cell dynamics in the TME. Moreover, it analyzes the rare pro-tumoral effects of IL-37 in some tumors and discusses their possible mechanisms. It concludes that, due to its strong anti-inflammatory property, IL-37 can be considered a potential regulator in the pathogenesis of a variety of cancers, slowing tumor progression through multiple pathways and providing valuable information for tumor immune target therapy.

Background: Gliomas, including glioblastomas (GB) and high-grade astrocytomas (HGA), are the most common brain tumors in adults, with poor survival rates around 15 months. Hormonal factors, particularly progesterone receptor (PR) activation, promote tumor growth. Current treatment involves surgery, radiotherapy and chemotherapy (temozolomide), but survival rates remain low. Repurposing mifepristone (MF), a contraceptive drug, shows promise for GB treatment, warranting further study.

Methods: PR expression in U87, U251 and C6 cell lines were assessed using immunofluorescence and Western Blot. PR isoforms were quantified by densitometry. Progesterone (P4) and 5α-dihydroprogesterone (5α-DHP) synthesis were evaluated using LC/MS. MF's effect on cell viability was determined by IC₅₀ and IC₂₀ values. Its impact on non-tumoral cells and 3D glioma sphere formation was also analyzed. The effects of in situ administration of MF were assessed in vivo using a rat model with C6 glioma implants. Clinical outcomes were evaluated in GB patients receiving MF alongside standard treatment.

Results: PR was predominantly nuclear in all cell lines, with U87 showing the highest PR-B isoform levels. Only U251 synthesized 5α-DHP significantly. MF reduced viability in U251, U87 and C6 cells without affecting non-tumoral cells. Sphere formation efficiency decreased with MF treatment. In rats, MF reduced tumor volume dose-dependently. Clinically, MF improved patient survival from 165 to 588days and enhanced quality of life without severe adverse effects.

Conclusion: MF effectively reduces GB cell viability, sphere formation efficacy and tumor volume. These findings support further investigation of MF as a therapeutic strategy in GB treatment.

Précis (condensed abstract): Our research highlights the critical role PR in GB progression using in vitro and in vivo models. MF, a PR modulator, effectively reduced cell viability and sphere formation in cellular assays and significantly decreased tumor volume in an in vivo study. The pilot trial demonstrated the pharmacological safety of using MF as an adjuvant in GB treatment. Patients treated with MF showed a significant increase in survival, with an 80% survival rate at 1 year compared to 0% in those who were treated with the standard treatment.

Background: The potential of Lenvatinib to synergize with combined radiotherapy and immunotherapy in LUAD remains incompletely characterized.

Methods: We investigated Lenvatinib's effects on radiation-induced PD-L1 in LUAD cells and VEGFR2 in HUVECs via Western blot, VEGFA expression via RT-qPCR/ELISA, and angiogenesis via immunofluorescence. LUAD-HUVEC crosstalk was modeled in vitro. In C57BL/6 mice bearing LUAD tumors, we evaluated the efficacy of RT and anti-PD-L1 with or without Lenvatinib, monitoring tumor growth, survival, and profiling the tumor microenvironment by mIHC and flow cytometry.

Results: Lenvatinib suppressed radiation-induced PD-L1 and VEGFR2 expression, inhibited angiogenesis, and disrupted HUVEC-facilitated LUAD proliferation. The triple-combination (RT + anti-PD-L1 + Lenvatinib) significantly suppressed tumor progression (P < 0.05) and extended median survival (34 vs. 29.5 days, P < 0.05) versus dual therapy. It also enhanced intratumoral CD8⁺ T-cell infiltration and cytotoxicity, promoted M1-like macrophage polarization, and reduced regulatory T cell frequency and microvessel density.

Conclusions: Lenvatinib potentiates RT and anti-PD-L1 therapy in LUAD through dual immune-vascular modulation, supporting the clinical translation of this triple-combination strategy.

Receptor-mediated transcytosis (RMT) represents a promising strategy for delivering macromolecular and colloidal therapeutics across the blood-brain barrier (BBB). However, mechanistic elucidation of RMT remains limited by the difficulty of visualizing subcellular trafficking pathways. Conventional imaging approaches either lack sufficient spatial resolution or require costly, technically complex instrumentation. Here, we report a cell swelling and upright mounting-based (CSUM-based) imaging approach that reorients the Z-axis into the high-resolution XY-plane using standard confocal microscopy, enabling direct RMT visualization without computational reconstruction or specialized hardware. We tracked intracellular trafficking of transferrin (Tf) and anti-transferrin receptor antibody (anti-TfR Ab) as model cargos using our CSUM-based imaging approach via compartment-specific markers and time-resolved co-localization analysis. This approach resolved cargo-containing vesicles traversing from the apical to basolateral membranes. Tf completed transcytosis within 15 min, whereas anti-TfR Ab initially entered the endolysosomal pathway before rerouting to transcytosis under receptor saturation conditions. The CSUM approach provides a simple yet effective platform for high-resolution visualization of membrane transport and vesicle dynamics, offering broad applicability to drug delivery research and the design of brain-targeted therapeutics.