Brain-derived neurotrophic factor (BDNF) plays an essential role in neuronal growth and maturation, as well as in maintaining synaptic plasticity. Dysregulated BDNF levels significantly increase the risk of neurological and metabolic disorders. In type 2 diabetes mellitus, several pathological mechanisms, including prolonged hyperglycemia, oxidative damage, chronic inflammation, and impaired insulin sensitivity, are known to drive neurodegenerative processes and deterioration of cognitive function. Impaired BDNF signaling can result in compromised synaptic transmission and gradual loss of neurons, with the hippocampus being particularly vulnerable. A growing body of evidence points to a strong correlation between diminished BDNF levels and diabetes related cognitive decline. Findings from both human clinical trials and animal studies have consistently reported reduced BDNF concentrations in brain tissues and systemic circulation in diabetic conditions. Therapeutic strategies aimed at upregulating BDNF expression and modulating its downstream signaling pathways hold considerable promise for preventing or mitigating diabetes associated cognitive deficits.

This study aimed to investigate the association between serum 25-hydroxyvitamin D (25[OH]D) levels and metabolic dysfunction-associated steatotic liver disease (MASLD) in older patients with type 2 diabetes mellitus.

This retrospective cross-sectional study included 1044 older patients with T2DM who were treated at the Department of Endocrinology of Gansu Provincial Hospital between April 2021 and June 2024. MASLD was diagnosed by abdominal ultrasonography. Demographic, metabolic, and biochemical data were collected, including high-sensitivity C-reactive protein (hs-CRP), sialic acid (SA), and homocysteine (HCY). Binary logistic regression analysis was performed to assess the independent association between 25(OH)D levels and the presence of MASLD.

MASLD was present in 64.0% of participants. Serum 25(OH)D levels were significantly lower in the MASLD group than in the non-MASLD group. After adjusting for age, sex, diabetes duration, body mass index, glycemic parameters, lipid profiles, and inflammatory markers, each 1 ng/mL decrease in 25(OH)D level was associated with 27.6% higher odds of MASLD (odds ratio [OR] = 0.724, 95% confidence interval [CI]: 0.686-0.765, P < 0.001). Receiver operating characteristic (ROC) analysis demonstrated the discriminatory performance of 25(OH)D for MASLD, yielding an area under the curve of 0.856 (95% CI: 0.828-0.884, P < 0.001) and an optimal cutoff value of 19.95 ng/mL.

Low serum 25(OH)D levels were independently associated with higher odds of MASLD in older patients with T2DM. Vitamin D status may have potential value for MASLD risk stratification, but prospective studies are required before treatment recommendations can be made.

Diabetic retinopathy (DR) is increasingly understood as an integrated neurovascular unit (NVU) pathology driven by chronic hyperglycemia, rather than solely a microvascular complication. Anti-vascular endothelial growth factor (anti-VEGF) therapy remains limited by repeated intravitreal injections, treatment resistance, and failure to reverse early neurodegeneration. Lutein, a natural carotenoid, may counter these refractory dimensions by activating the nuclear factor erythroid 2-related factor 2 (Nrf2) antioxidant pathway and suppressing neuroinflammation across NVU components. However, its poor aqueous solubility, chemical instability, and restricted blood-retinal barrier (BRB) permeation limit retinal bioavailability and clinical translation. Nanoscale targeted delivery can improve lutein solubility and stability and enable trans-BRB transport via the enhanced permeability and retention effect or receptor-mediated transcytosis, thereby enhancing precise NVU protection. This review integrates lutein's mechanisms against DR-related NVU injury, design strategies for nanoscale delivery systems and trans-BRB transport, and preclinical efficacy with translational bottlenecks, to support advancement of lutein from dietary supplement to precision adjuvant therapy for DR. Unlike reviews treating lutein as an isolated nutraceutical or materials target, it connects nanomaterial engineering with clinical translation and regulatory science. Preclinical studies show that nanoformulated lutein improves oral bioavailability, retinal accumulation, and oxidative/inflammatory injury in diabetic models. Translation remains hindered by limited long-term safety data, scalable manufacturing, and unclear regulatory classification. Future priorities include stage-adaptive nanoplatforms, standardized preclinical evaluation, and rigorously designed multicenter clinical trials to establish efficacy, safety, and regulatory readiness.

To evaluate dose selection and post-treatment management after Gamma Knife surgery (GKS) for large brain metastases, with a focus on early identification of true progression.

This retrospective single-institution study included 143 patients with large brain metastases (tumor volume ≥ 4 cm³) treated with primary GKS between 2016 and 2024. One dominant lesion per patient was analyzed. Treatment modality (single-session, staged, or hypofractionated) and dose selection were individualized. Radiographic progression was defined as a ≥ 20% increase in longest tumor diameter from nadir. True progression was defined as sustained enlargement or the need for salvage treatment, whereas lesions that stabilized or regressed without intervention were classified as pseudoprogression.

Median overall survival was 15.3 months. During follow-up, 47 lesions showed radiographic progression: 42 true progression, 4 pseudoprogression, and 1 intratumoral hemorrhage. The 6-, 12-, and 24-month cumulative incidences of true progression were 17.4%, 31.5%, and 33.1%, respectively. True progression did not differ by treatment modality or tumor volume. A marginal dose ≥ 57.6 Gy biologically effective dose (BED₁₀) was associated with a lower risk of true progression (subdistribution hazard ratio [SHR], 0.46; p = 0.02). Recurrent peritumoral edema developed earlier in true progression than pseudoprogression (median, 173.5 vs. 564 days; p = 0.001). Lower marginal dose at repeat GKS was associated with subsequent true progression (SHR, 0.82; p = 0.02).

A BED₁₀ ≥ 57.6 Gy improved local control in large brain metastases. Recurrent peritumoral edema accompanying tumor enlargement within 1 year after GKS strongly suggested true progression and should prompt consideration of early salvage intervention.

Clinical trial number: not applicable.

The Hispanic/Latino population is the second largest racial and ethnic group in the United States, accounting for 20% of the total population (68 million), plus approximately 3 million Hispanic Americans residing in Puerto Rico. Herein, the American Cancer Society reports cancer occurrence, risk factors, and screening for US Hispanic people using federally funded, high-quality, population-based cancer registry data and national vital statistics and survey data. In 2026, an estimated 229,900 Hispanic people will be diagnosed with cancer, and 54,200 will die from the disease in the continental United States and Hawaii. Cancer incidence during 1998-2022 rose in Hispanic women (from 345 to 385 per 100,000) and fell in Hispanic men (from 471 to 389 per 100,000), narrowing the male-to-female incidence rate ratio from a peak of 1.40 (95% CI, 1.38-1.42) in 2002 to 1.01 (95% CI, 1.00-1.02; p = .02) in 2022. This pattern is partly driven by declining incidence of lung and prostate cancers among men and increasing incidence of breast and uterine corpus cancers among women. Although temporal trends mirror the general population, the Hispanic cancer distribution is distinct, consistent with relatively lower prevalence of smoking, alcohol drinking, and screening and higher prevalence of obesity and cancer-causing infections. Compared with White people, Hispanic people have one half the incidence of lung and urinary bladder cancers and 24% lower breast cancer but double the rate of liver, stomach, and gallbladder cancers, 61%-65% higher acute lymphocytic leukemia, and 36% higher cervical cancer. The cancer burden in Puerto Rico is distinct, with lower rates of lung cancer but higher rates of cervical, prostate, and colorectal cancers compared with other US Hispanic populations. Residents in Puerto Rico also experience lasting health care system challenges from extreme weather events. Thus, prevention efforts should target the unique cancer profile of the Hispanic population, including infection prevention and control, healthy eating, physical activity, and routine screening, especially for cervical and colorectal cancer that are 11 percentage points lower than White people.

A diagnosis of early-stage Breast Cancer (BC) induces significant psychological distress in patients, who are then required to make complex treatment decisions. Evidence-based tools like Patient Decision Aids (PDAs) have been proposed as tools to support communication and Shared Decision-Making (SDM). However, their successful use in clinical practice depends also on real-world consultation dynamics. Existing literature suggests that insufficient attention to contextual and user-centered factors may limit the relevance and uptake of PDAs. A bottom-up approach grounded in clinical reality may therefore be essential to inform their design and future integration into care.

This study aimed to explore experiences, unmet needs and expectations of both patients and healthcare professionals involved in early-stage breast cancer care regarding decision-making support and standard oncological consultations, in order to identify patient- and clinician-derived design requirements for a future PDA supporting shared treatment decision-making in early-stage breast cancer.

We conducted 52 semi-structured interviews with 20 patients and 32 HCPs at the European Institute of Oncology in Milan from 10 January 2025 to 30 August 2025. Interviews were transcribed and analyzed using thematic analysis, with coding performed by two independent researchers and discrepancies resolved through independent discussion with two other authors.

HCPs highlighted three key themes: variability in patient information needs, misconceptions about treatments (especially chemotherapy and radiotherapy), and the multifactorial nature of treatment decisions. Patients emphasized the importance of trust in physicians, the need for practical information on side effects and coping strategies, and the role of peer support, often found through informal networks or social media. These findings identified preliminary requirements for a future PDA: adaptable information depth and timing; plain-language responses to common misconceptions; structured values-clarification prompts; practical preparation and side-effect-management information; signposting to vetted psychosocial and peer-support resources.

Findings highlight communication challenges and unmet psychosocial and informational needs within standard oncological consultations for early-stage breast cancer. By grounding decision support development in the perspectives of both patients and healthcare professionals, this study provides formative, pre-implementation insights to guide the design of PDAs that are responsive to real-world clinical contexts and patient experiences.

clinicaltrials.gov, identifier: NCT06762496. Registered 7th January 2025 -https://clinicaltrials.gov/study/NCT06762496.

&lt;b&gt;Background and Objective:&lt;/b&gt; Ovarian cancer is a highly lethal gynecologic malignancy, often diagnosed at advanced stages due to nonspecific symptoms. The IL-6/STAT3 pathway promotes tumor progression, chemoresistance and poor prognosis. Therefore, this study aimed to evaluate the histologic patterns of ovarian tumors based on the WHO 2020 classification and investigate the role of the IL-6/STAT3 pathway in ovarian cancer progression. &lt;b&gt;Materials and Methods:&lt;/b&gt; A retrospective observational study was conducted using 2,309 ovarian biopsy specimens collected between 2016 and 2025 and classified according to the 2020 WHO Classification of Female Genital Tumours. Histopathological data were analyzed using descriptive statistics and the chi-square test (p<0.05). Bioinformatic analyses of TCGA gene expression data were performed using DESeq2 for differential expression analysis and Kaplan-Meier and Cox regression analyses to evaluate the prognostic significance of the IL-6/STAT3 signaling pathway. &lt;b&gt;Results:&lt;/b&gt; Surface epithelial tumors were the most common ovarian neoplasms (74.08%), followed by germ cell tumors (12.56%). Mucinous ovarian tumors were the predominant epithelial subtype. A significant association between age and malignancy was observed (p<0.001). STAT3 expression was significantly increased in the low-grade group (p = 0.022), while IL-6 expression was not statistically significant. &lt;b&gt;Conclusion:&lt;/b&gt; Ovarian tumors showed diverse histopathological features and STAT3 dysregulation may contribute to ovarian carcinoma prognosis. Integrating histopathological and molecular analysis may improve diagnostic and prognostic assessment.

Transcatheter arterial chemoembolization (TACE) for hepatocellular carcinoma (HCC) is limited by inadequate intratumoral drug penetration. We developed a sequential-delivery composite gel microsphere system integrating hyaluronidase (HAase)-mediated microenvironment remodeling, glycyrrhetinic acid (GA)-mediated active targeting, and pH-responsive drug release as a potential strategy to address this barrier.

Bufalin (BUF)-loaded GA-PEG-HYD-PLGA nanoparticles and HAase were co-encapsulated within carboxymethyl chitosan/sodium alginate gel microspheres containing BaSO₄ for radiopacity (HAase/BUF NPs-GM). The system was characterized for particle size, drug loading, pH-responsive release, and hemocompatibility. Antitumor efficacy, deep tumor penetration, and mechanisms were evaluated in Huh-7 cells and a rabbit VX2 orthotopic liver tumor model via TACE-guided arterial delivery.

HAase/BUF NPs-GM exhibited a favorable size (270 ± 61.89 μm), pH-dependent BUF release, and good biocompatibility, with an IC_{5 0} of 55.07 nM against Huh-7 cells. The system reduced hyaluronic acid content across all tumor regions, consistent with enhanced penetration of the therapeutic payload into the tumor core. Compared with controls, HAase/BUF NPs-GM combined with TACE suppressed tumor growth and angiogenesis, induced apoptosis, inhibited proliferation, and was associated with increased intratumoral CD3⁺ T cell infiltration and reduced expression of EMT-related markers. Mechanistically, the system induced ROS overproduction, mitochondrial membrane potential decrease, and G2/M cell cycle arrest.

This strategy, which combines microenvironment remodeling, active targeting, and responsive release, provides a promising preclinical proof-of-concept for addressing the penetration limitations of conventional TACE. Further translational investigation, including validation in orthotopic or patient-derived xenograft models and long-term toxicity assessment, is warranted.

Evidence for adding dexketoprofen trometamol to sufentanil-based patient-controlled intravenous analgesia (PCIA) after thoracoscopic radical resection of lung cancer remains limited.

To evaluate 48-hour opioid consumption, pain outcomes, and short-term adverse events with dexketoprofen trometamol plus sufentanil versus sufentanil-based PCIA alone.

In this randomized, double-blind, placebo-controlled trial, 108 patients scheduled for thoracoscopic radical resection of lung cancer were randomized preoperatively (54 per group). After 18 post-randomization exclusions before PCIA initiation, 45 patients per group received the allocated intervention and were analyzed. All underwent unilateral uniportal anatomical segmentectomy with mediastinal lymph node dissection or sampling and received a standardized intercostal nerve block. Group S received sufentanil-based PCIA, and Group R additionally received dexketoprofen trometamol. The primary outcome was total 48-hour postoperative sufentanil consumption, including rescue doses.

Sufentanil consumption was lower in Group R than in Group S (78.03 ± 10.66 vs 96.78 ± 13.69 μg; reduction 18.75 μg, 95% CI 13.61 to 23.89; P<0.001), representing an approximately 19% reduction. Resting pain scores were lower at 12 and 24 hours (both P=0.004), meeting the revised Bonferroni threshold of P<0.005 for 10 time-point comparisons; the coughing-pain difference at 12 hours (P=0.006) did not meet this threshold. Resting-pain area under the curve was lower (P=0.009), but generalized estimating equations showed no significant overall group effect or group-by-time interaction for resting or coughing pain. Nausea occurred in 11.1% versus 28.9% (Pearson χ² P=0.035).

Adding dexketoprofen trometamol reduced 48-hour sufentanil consumption in the analyzed population. Pain differences were time-specific secondary findings and did not establish sustained analgesic superiority. The nausea finding requires confirmation, and the trial was insufficient to establish safety for uncommon adverse events.

Schwannomas are benign tumors arising from Schwann cells. Lingual schwannomas are exceedingly rare and usually present as painless, slow-growing masses, usually of the oral tongue or tongue base, with symptoms such as dysphagia, discomfort, and, in some cases, airway compromise. The standard of care is surgical excision via a transoral approach. In this case, we discuss an intralingual ancient schwannoma presenting with dysphagia, discomfort, and throat fullness that was subsequently excised with excellent functional outcomes.