Myasthenia gravis (MG) is an autoimmune neuromuscular disorder in which approximately 10-15% of patients with generalized AChR antibody-positive MG develop refractoriness to standard immunosuppressive therapies. Advanced therapeutic strategies, including FcRn antagonists and C5 complement inhibitors, have demonstrated early and sustained clinical efficacy in pivotal phase 3 trials. However, evidence supporting their early use in complex clinical scenarios remains limited.

We report two cases of severe generalized MG in which early initiation of advanced therapies was associated with rapid clinical stabilization. In the first case, a 75-year-old man with thymoma-associated MG and severe bulbar involvement refractory (MG-ADL: 11) to plasma exchange (PLEX) and intravenous immunoglobulins (IVIg), and unable to continue azathioprine due to adverse events, received off-label efgartigimod preoperatively. Near-complete resolution of bulbar symptoms was observed within 48 hours, enabling robot-assisted thymectomy on day 4 following the first infusion, with sustained neurological improvement at one-month follow-up (MG-ADL score: 2). In the second case, a 74-year-old man with severe refractory bulbar MG requiring nasogastric tube feeding (MG-ADL: 13) and subsequent percutaneous endoscopic gastrostomy (PEG) was treated with ravulizumab after an incomplete response to PLEX, IVIg, corticosteroids, and azathioprine. MG-ADL decreased from 9 at treatment initiation to 5 after two infusions of ravulizumab, and complete recovery of swallowing function allowed PEG removal at 18-week follow-up, with achievement of minimal symptom expression (MG-ADL score: 0).

These cases highlight the potential role of early and targeted use of advanced immunotherapies in severe, refractory MG, including as a bridging strategy to thymectomy. Further prospective studies are needed to define optimal criteria and timing for early integration of these agents into the therapeutic algorithm.

To assess the association between comorbid Metabolic Dysfunction-Associated Steatotic Liver Disease (MASLD) and the risk of developing severe liver disease and cardiovascular disease (CVD) in patients with Chronic Hepatitis B (CHB).

CHB Patients were continuously recruited from 2012 to 2022 using the electronic medical record system, and divided into CHB-no MASLD and CHB-MASLD groups. Follow-up continued until January 2024, aiming to compare differences of cumulative incidence between the two groups and to analyze associated risk factors.

8,052 patients were included with a median follow-up of 3.9 years. Compared with CHB-no MASLD group, MASLD was independently associated with a 39% lower risk of severe liver disease (adjusted hazard ratio [aHR]=0.61, 95% confidence interval [CI] 0.49-0.76, p < 0.001), with similar effects in cirrhosis (aHR=0.61, 95% CI 0.45-0.82, p=0.001) and hepatocellular carcinoma (HCC) (aHR=0.57, 95% CI 0.41-0.80, p = 0.001). Stratified analyses indicated the protection effect was more significant in the HBsAg-positive group. Conversely, MASLD was associated with higher CVD risk (aHR=1.16, 95% CI 0.96-1.41, p=0.130), driven by coronary artery disease (aHR=1.91, 95% CI 1.34-2.74, p < 0.001) and arrhythmia (aHR=1.44, 95% CI 1.00-2.08, p=0.053). These findings remained consistent after propensity score matching (PSM).

MASLD may reduce the risk of severe liver disease through certain mechanisms, yet it also constitutes a risk factor for CVD, particularly among HBsAg-positive patients.

This narrative review synthesizes current evidence on pterostilbene in oxidative stress-related diseases, focusing on its chemical and pharmacokinetic basis, redox-related signaling responses, disease-specific evidence, and translational challenges. Most available evidence comes from preclinical models and suggests that the biological effects of pterostilbene cannot be explained solely by direct reactive oxygen species (ROS) scavenging. Instead, pterostilbene is associated with several redox-sensitive processes, including Nrf2-related antioxidant responses, redox-inflammatory crosstalk, mitochondria-associated stress responses, metabolic regulation, and cell death-related pathways. Evidence from osteoarthritis, neurodegenerative and cognitive dysfunction models, ischemia-reperfusion injury, metabolic diseases, and cancer indicates that these effects vary substantially across pathological contexts. In non-malignant degenerative, ischemic, and metabolic models, pterostilbene is generally associated with attenuation of oxidative stress-, inflammation-, or cellular stress-related injury markers, whereas in selected cancer models it may disrupt redox-adapted tumor-cell stress tolerance and promote apoptosis- or pyroptosis-related responses. Important translational barriers remain, including incomplete direct target validation, heterogeneous dosing and intervention designs, reliance on static oxidative stress endpoints, limited clinical validation, and insufficient integration of negative or context-dependent findings. By applying a redox homeostasis-centered framework, this review clarifies the contexts in which pterostilbene effects have been reported and identifies the evidence needed before disease-specific translational positioning can be established.

Ultrasound-guided high-intensity focused ultrasound (USgHIFU) ablation of uterine fibroids requires conscious sedation to ensure patient comfort while preserving responsiveness for real-time feedback. Remimazolam, an ultra-short-acting benzodiazepine, has faster onset, predictable clearance, and lower respiratory depression risk than midazolam or propofol, making it ideal for conscious sedation. Nevertheless, its optimal maintenance dosage combined with sufentanil remains undetermined. This study was designed to explore the ED50 and ED95 of remimazolam for targeted sedation during the operation.

A total of 40 eligible patients were enrolled in this prospective dose-escalation study. Sedation was induced with remimazolam (0.1 mg/kg) and sufentanil (0.1 μg/kg), both infused over > 30 seconds, followed by continuous infusion of sufentanil (0.3 μg/kg/h) and remimazolam at an initial maintenance dose of 0.1 mg/kg/h. The maintenance dose of remimazolam was adjusted using the Dixon up-and-down sequential allocation method with a 0.02 mg/kg/h stepwise change. Effective sedation was defined as a Ramsay Sedation Scale score ≥ 2 at four or more intraoperative time points without the need for rescue sedation. Probit regression was used to calculate ED50 and ED95, and perioperative safety indicators and satisfaction degrees were recorded.

The estimated ED50 and ED95 of remimazolam were 0.064 (95% CI: 0.025-0.086) mg/kg/h and 0.102 (95% CI: 0.089-0.128) mg/kg/h, respectively. All operations were accomplished smoothly with fast postoperative recovery. The incidences of postoperative nausea and vomiting were 30.0% and 22.5% respectively. High satisfaction was achieved among patients, surgeons and anesthesiologists, and no severe adverse reactions occurred.

The continuous infusion dose of remimazolam ranging from 0.06 to 0.10 mg/kg/h combined with sufentanil can provide satisfactory conscious sedation with quick recovery in USgHIFU treatment. Since single antiemetic prophylaxis fails to effectively reduce postoperative nausea and vomiting, further researches are essential to establish optimized multimodal antiemetic strategies for this sedative regimen.

Chinese Clinical Trial Registry (ChiCTR2400084538), Registration Date: May 20, 2024.

This study aims to systematically evaluate the predictive value of platelet parameters (PLT, PDW, MPV, PCT) before initial ¹³¹I therapy in patients with differentiated thyroid cancer.

This retrospective study included 365 patients with differentiated thyroid cancer (DTC) who underwent initial ¹³¹I therapy at the Department of Nuclear Medicine in a tertiary hospital. Treatment response was assessed according to the 2025 American Thyroid Association Guidelines for the Management of Adult Differentiated Thyroid Cancer, and was categorized as Excellent Response (ER) or Non-Excellent Response (non-ER). Univariate and multivariate analyses were performed to examine the association between PLT, PDW, MPV, and PCT with non-ER, adjusting for confounding factors. Results are presented as odds ratios (OR) and 95% confidence intervals (CI). The stability of the results was verified through interaction tests and subgroup analyses. Receiver operating characteristic (ROC) curves were plotted, and the area under the curve (AUC) was calculated to assess the predictive value of platelet indices for treatment response.

After adjusting for confounding factors, MPV was independently and negatively associated with non-ER (OR = 0.40, 95% CI 0.28-0.58). Interaction analysis suggested that age and ps-Tg influence the association between MPV and non-ER (P = 0.042 and P = 0.031). The ROC curve showed that MPV had a moderate predictive value for non-ER (AUC = 0.664). Based on the maximum Youden index, the optimal cutoff value was determined to be 9.95 fL, with a sensitivity of 0.595 and a specificity of 0.657.

MPV demonstrated moderate predictive value in forecasting the response of DTC patients to initial ¹³¹I therapy (AUC = 0.664). In clinical practice, MPV may be of adjunctive value in helping to identify patients with poor treatment response at an early stage. However, it is insufficient to be used as the sole basis for clinical decision-making.

Chondroid syringoma, also known as mixed tumor of the skin, is a rare benign cutaneous adnexal neoplasm characterized by both epithelial and mesenchymal differentiation. It most commonly occurs in the head and neck region and usually presents as a solitary, slow-growing, painless dermal or subcutaneous nodule. Because of its nonspecific clinical and dermoscopic presentation, the diagnosis is rarely suspected before histopathological examination. We report a case of a 73-year-old male with no significant medical history who presented with a progressively enlarging flesh-colored nodule of the nasal ala evolving over one year. Clinical examination revealed a well-demarcated, firm, painless, round nodule measuring 7 mm in diameter, adherent to the overlying skin, with a smooth surface. Dermoscopic examination revealed a central pigmented structureless area, peripheral white dots, linear vessels, and whitish areas, resulting in a nonspecific dermoscopic pattern. The main clinical differential diagnoses included nodular basal cell carcinoma, epidermal inclusion cyst, amelanotic nevus, neurofibroma, and chondroid syringoma. An excisional biopsy was performed. Histopathological examination showed a benign adnexal tumor composed of numerous ductal and tubular epithelial structures embedded within a myxoid to chondromyxoid stroma, consistent with chondroid syringoma. Surgical margins were free of tumor. No recurrence was observed after two years of follow-up. This case highlights the importance of considering chondroid syringoma in the differential diagnosis of long-standing nodular lesions of the nose and emphasizes the role of complete surgical excision and histopathological confirmation.

Rural-urban disparities in mortality persist across high-income countries but whether these differences reflect geographic barriers, socioeconomic disadvantage or both remains unclear. Disentangling these pathways is important for designing effective interventions but nationwide Japanese evidence that jointly models geographic remoteness and area deprivation in relation to cause-specific mortality remains limited.

This municipality-level ecological study analysed 4 078 801 deaths during 2017-2019 across 1890 municipalities in Japan. Rurality was measured using the Rurality Index for Japan, and socioeconomic deprivation using the Area Deprivation Index (ADI). Bayesian spatial Poisson models estimated rate ratios (RRs) for all-cause mortality and 34 cause-specific outcomes (35 outcomes in total) with and without ADI adjustment. Percentage attenuation was interpreted descriptively.

After ADI adjustment, rural excess persisted for all-cause mortality overall (adjusted RR 1.010 (95% credible interval (CrI) 1.003 to 1.016)) and in females (1.009 (95% CrI 1.002 to 1.016), while the male estimate was close to the null. Rural excess also persisted for selected cardiovascular and cerebrovascular outcomes in the total population, including heart diseases, acute myocardial infarction, arrhythmias and conduction disorders, heart failure, cerebrovascular diseases and cerebral infarction (RRs 1.023-1.052), plus senility, unintentional injuries, traffic accidents and suicide. Aggregate malignant neoplasms, which overlapped with site-specific cancers, were near null in the total population, whereas tuberculosis, pneumonia, several site-specific cancers, asthma and liver disease showed urban excess, most notably tuberculosis (0.858 (95% CrI 0.814 to 0.905)).

Municipal rurality showed heterogeneous cause-specific associations with mortality after ADI adjustment. Higher rurality was associated with excess mortality for several time-sensitive or access-sensitive causes whereas infectious, respiratory, liver and site-specific cancer outcomes showed urban excess. Because the ecological design precludes causal inference about specific pathways reducing disparities requires cause-specific strategies addressing geographic access, socioeconomic disadvantage and urban-context risks, rather than uniform rural-urban policies.

Malignant brain tumors, particularly glioblastoma, remain one of the greatest challenges in oncology due to their invasive nature, therapeutic resistance, and protection by the blood-brain barrier. Decades of limited therapeutic progress underscore the need for new treatment strategies beyond conventional modalities. Magnetic nanoparticles have emerged as a promising theranostic platform that integrates high-precision imaging, targeted delivery, and synergistic therapy. In this review, we outline a mechanistic framework for magnetic nanoparticle applications, with a focus on the link between ferroptosis and immune activation. We discuss how the intrinsic properties of magnetic nanoparticles can be engineered to induce iron-dependent ferroptotic cell death, which may help overcome apoptosis resistance and also trigger immunogenic cell death. This magnetic nanoparticle-induced immunogenic cell death may shift the immunosuppressive brain tumor microenvironment from a "cold" state toward a more immune-active phenotype, thereby supporting combination immunotherapy. We also examine key translational challenges and potential solutions, including quantitative magnetic particle imaging-guided therapeutic dosimetry, focused ultrasound-mediated delivery strategies, and issues related to Chemistry, Manufacturing, and Controls and regulatory science. By analyzing these translational challenges, this review aims to highlight practical considerations for advancing magnetic nanoparticle-based therapies toward clinical neuro-oncology.

Treatment of advanced breast cancer has proven to be difficult. Routine chemotherapy has limitations due to unavoidable and dreaded adverse effects during and after treatment, necessitating the development of tailored therapies. Capecitabine is a commonly used anticancer drug that comes in tablet form for oral administration. However, high doses and frequent administration-related toxicities limit its efficacy in HER2-positive breast cancer patients.

The current work seeks to target capecitabine using experimental nanoliposomes coupled to trastuzumab (TZ) (HER2-targeting monoclonal antibody) and assess anticancer activity in a NOD SCID mice xenograft model of breast cancer. Experimental capecitabine-loaded trastuzumab-nanoliposomes (TZ-CNLs) were developed by a previously reported method. FESEM, AFM, TEM, zeta potential, and drug release studies were used to characterize TZ-CNLs. In vivo effectiveness of CNLs/TZ-CNLs was carried out in experimental mice and compared with the free capecitabine-treated group. Hematological, biochemical, and histopathological analyses of experimental CNLs/TZ-CNLs were conducted across different treatment groups compared with the control.

Experimental TZ-CNLs were spherical, smooth, and uniformly distributed, with an average size (198.6 nm), a zeta potential (-27.91 mV), and a drug loading (9.6±0.51%). The AFM indicated that TZ conjugation had no effect on texture. TZ-CNLs released 81.5 ± 3.05% capecitabine after 96 h, compared to CNLs/free capecitabine. After 12 days of treatment, TZ-CNLs significantly reduced tumor development (97.91 ± 3.0 mm³) compared to unconjugated CNLs/free capecitabine in NOD SCID mice xenografts. The enhanced antitumor activity observed with TZ-CNLs is consistent with HER2-targeted delivery mediated by TZ conjugation. Furthermore, TZ-CNL-treated animals maintained a healthier body-weight profile compared with free capecitabine and CNL-treated groups, suggesting improved treatment tolerability and reduced systemic toxicity. Plasma pharmacokinetic analysis indicated that administration of TZ-CNL-3 resulted in greater systemic availability of capecitabine, as well as prolonged mean residence time and increased volume of distribution, compared to free capecitabine and CNL-3. The study depicted an overall improvement in key biochemical parameters toward normal in animals treated with TZ-CNLs.

Overall, the promising preclinical outcomes, including tumor inhibition, improved hematologic and biochemical safety indices, and maintenance of organ histopathology, support the need for future preclinical investigations to determine whether TZ-CNLs may have application in HER2-positive breast cancer therapy.

This report highlights a collaboration between an Indigenous and rural patient navigation program and community partners in Western New York providing navigation across the cancer care continuum with an emphasis on cancer screening and access to cancer care. This included a geographically distributed team of patient navigators focused on reducing cancer disparities.