Background: Elevated active glucocorticoids (GCs) are implicated in skin barrier dysfunction, notably in aging and diabetes. The enzyme 11β-hydroxysteroid dehydrogenase type 1 (11β-HSD1) converts inactive GCs to active forms, potentially exacerbating this dysfunction. Objective: We aimed to investigate the impact of a novel 11β-HSD1 inhibitor on skin inflammation using both in vitro and in vivo models. Methods: To elucidate the efficacy of a new 11β-HSD1 inhibitor in mitigating skin inflammation induced by various triggers, including dexamethasone treatment, ultraviolet B irradiation, and high glucose levels, in cultured human keratinocytes and the db/db mice as a type 2 diabetes murine model. In cultured keratinocytes, we assessed the effects of the 11β-HSD1 inhibitor on cortisol levels, 11β-HSD1 expression, and cytokine production under conditions simulating inflammation. In db/db mice, we evaluated the inhibitor’s impact on skin barrier function, hemoglobin A1c (HbA1c) levels, corticosterone levels, 11β-HSD1 expression, and cytokine profiles following a 2-week treatment regimen. Results: Our results demonstrated that both the novel 11β-HSD1 inhibitor and a known inhibitor reduced cortisol levels, 11β-HSD1 expression, and inflammatory cytokine production in cultured keratinocytes. In db/db mice, treatment with either inhibitor improved skin barrier function, lowered serum HbA1c levels, and decreased corticosterone, 11β-HSD1, and inflammatory cytokine expression. Conclusion A new 11β-HSD1 inhibitor, “11b-0048,” showed a significant inhibitory effect on the expression of 11β-HSD1 in keratinocytes activated by various conditions and diabetic skin.

Background: A systematic evaluation of potential living liver donors is essential to ensure donor safety and optimize recipient outcomes in living donor liver transplantation (LDLT). This study aimed to assess donor acceptance rates and reasons for disqualification among individuals evaluated for LDLT at a high-volume transplant center over a one-year period. Methods: We retrospectively reviewed 1,087 potential living liver donors who presented for LDLT evaluation in 2023. Of these, 991 candidates advanced beyond the initial screening (Stage 1) and underwent comprehensive clinical, imaging, and pathological assessments (Stages 2 and 3). Candidates who discontinued after Stage 1 were excluded due to the absence of documented reasons for non-progression. Results: Among the 991 candidates who proceeded beyond initial screening, 473 (47.7%) completed the full donor evaluation, of whom 466 were judged to be suitable donors. Among suitable donors, 384 (82.4%) proceeded to donor hepatectomy, whereas 82 did not, primarily due to recipient-related factors such as clinical deterioration or withdrawal of consent. Donor ineligibility was determined in 422 candidates (42.6%), most commonly due to inadequate remnant liver volume (52.8%), hepatic steatosis (20.6%), and insufficient graft size (10.2%). Among candidates undergoing Stage 2 evaluation, 162 (16.3%) failed to meet steatosis criteria; 126 were excluded solely for steatosis and advised weight reduction, and 39 subsequently became eligible and successfully donated. Conclusion In this high-volume LDLT center, donor disqualification was primarily driven by remnant liver volume and hepatic steatosis. Targeted interventions such as weight reduction enabled successful donation in a subset of initially ineligible candidates, underscoring the importance of individualized donor evaluation and pre-donation optimization.

Purpose: Colorectal cancer (CRC) remains a leading cause of cancer-related mortality, necessitating the identification of novel therapeutic targets. The E3 ubiquitin ligase WW domain-containing E3 ubiquitin protein ligase 2 (WWP2) has been implicated in various cancers, yet its specific role and underlying molecular mechanisms in CRC are poorly understood. This study aimed to investigate the functional role of WWP2 in CRC progression and to elucidate its regulatory mechanisms. Methods: WWP2 expression was evaluated in CRC patient tissues and cell lines using immunohistochemistry, quantitative real-time polymerase chain reaction, and western blotting. The biological functions of WWP2 were assessed using in vitro assays for cell proliferation, migration, and invasion following adenovirus-mediated overexpression. The molecular mechanism was investigated by analyzing the protein expression levels of p53 and its downstream target, p21, via western blot. An in vivo xenograft mouse model was used to confirm the oncogenic role of WWP2. Results: WWP2 expression was significantly upregulated in CRC tissues. Overexpression of WWP2 promoted CRC cell proliferation, migration, and invasion. Mechanistically, increased WWP2 expression led to a marked reduction in the protein levels of the tumor suppressor p53. Consequently, the expression of the p53 downstream target, the cell cycle inhibitor p21, was also suppressed. In the xenograft model, WWP2 overexpression significantly enhanced tumor growth. Conclusion Our findings demonstrate that WWP2 functions as an oncogene in CRC. It promotes cancer progression by destabilizing the tumor suppressor p53 and downregulating p21. This study highlights the WWP2-p53-p21 axis as a potential novel therapeutic target for CRC.

Metastatic spine cancer (MSC), a common complication of advanced malignancies, poses significant challenges due to pain, neurological deficits, and mechanical instability. While radiation therapy is a cornerstone of treatment, the role of spine surgery is evolving, fueled by advances in surgical techniques and radiation modalities such as stereotactic body radiation therapy (SBRT). This review examines the evolving role of spine surgery in MSC management, focusing on separation surgery, surgical innovations, and future directions. The treatment paradigm for MSC shifted with the advent of SBRT, which delivers high-dose precision radiation, improving local control even in radioresistant tumors. This advancement enabled the adoption of separation surgery, a technique aimed at creating a safe margin between the tumor and neural structures without extensive tumor resection, followed by SBRT to achieve tumor regression. Separation surgery reduces morbidity, shortens operative times, and achieves comparable local control rates to traditional corpectomy procedures. Innovations like minimally invasive surgery, stereotactic navigation, and cement-augmented instrumentation have improved surgical safety and outcomes. Emerging technologies, such as machine learning for predictive modeling and augmented reality for surgical navigation, hold potential for improving decision-making and procedural accuracy. Spine surgery remains integral to MSC treatment, especially for high-grade metastatic epidural spinal cord compression and mechanical instability. Integrating advanced technologies and multidisciplinary collaboration is key to optimizing patient outcomes. Comprehensive, patient-centered strategies addressing both oncological and mechanical aspects can improve survival and quality of life for patients with MSC.

Background: Degenerative lumbar scoliosis (DLS) alters spinal anatomy, impacting the feasibility and dimensions of surgical corridors for oblique lumbar interbody fusion (OLIF). This study aimed to compare the morphometric characteristics of OLIF corridors between patients with left- and right-apex curves, focusing on corridor dimensions, psoas muscle asymmetry, and segmental artery positioning. Methods: A retrospective analysis of 80 patients with DLS (left apex: n = 43; right apex: n = 37) was conducted. Corridor angles and distances, psoas muscle cross-sectional areas, and segmental artery locations were measured at L2–3, L3–4, and L4–5 using T2-weighted magnetic resonance imaging (MRI). Multivariate regression analysis identified key anatomical predictors of corridor variation at L2–3. Results: Regardless of the apex direction, the left-sided corridor was consistently larger across all levels. Corridor angles were significantly greater on the left side in both groups (left apex: L2–3, 39.7° vs. 13.5°; L3–4, 38.3° vs. 11.9°; L4–5, 38.6° vs. 6.9°;right apex: L2–3, 53.7° vs. 18.1°; L3–4, 43.1° vs. 18.5°; L4–5, 28.6° vs. 11.9°). Psoas muscle areas were larger on the concave side of the curve (left apex: 125.7 mm2 vs. 67.9 mm2 ; right apex: 125.4 mm2 vs. 77.4 mm2 ). Segmental artery positioning exhibited curvedependent asymmetry at L2–3 (left apex: 8.8 mm vs. 7.9 mm; right apex: 9.6 mm vs. 8.0 mm). Multivariate regression analysis revealed that in the left apex group, the left psoas area (β = −0.132) and segmental artery distances were significant predictors of corridor angle variation (R2 = 0.517). In the right apex group, psoas asymmetry (β = 0.123) and sagittal alignment (β = −0.851) were associated with corridor differences. Conclusions OLIF corridors in DLS patients demonstrate consistent left-sided dominance, regardless of apex direction. Psoas muscle asymmetry and segmental artery positioning contribute to corridor variations. While the left-sided approach remains standard, right-sided access may be feasible in select cases, particularly at L4–5. These findings provide insights for optimizing preoperative planning and surgical decision-making in DLS patients.

Background/Aims: Various expanded criteria (EC) for liver transplantation (LT) in patients with hepatocellular carcinoma (HCC) have been proposed to avoid the narrow nature of the Milan criteria (MC). To investigate which EC predicts more favorable outcomes in terms of overall survival (OS) and recurrence-free survival (RFS), we conducted a network meta-analysis (NMA). Methods: A database search was conducted on PubMed, Embase, and the Cochrane Library, to identify studies comparing OS and RFS between patients within the MC and those exceeding the MC but within the EC. Hazard ratios (HRs) were pooled using a random-effects NMA and validated in an in-house cohort of 1,008 LT recipients. Results: Among 22,466 articles identified, 35 studies with 45 pairwise comparisons were included in the NMA along with 8 different EC. The University of California San Francisco (HR, 1.43; 95% CI, 1.19–1.71), Up-to-Seven (HR, 1.50; 95% CI, 1.15–1.97), and Hangzhou criteria (HR, 1.69; 95% CI, 1.11–2.57) showed inferior OS to the MC. The MC ranked highest for both OS and RFS, followed by Metroticket 2.0 for OS and the Asan criteria for RFS. In the validation cohort, both Metroticket 2.0 and AFP model yielded more favorable HCC-specific mortality than other EC. Conclusions Several EC, of which those of Metroticket 2.0 were the best, yielded comparable outcomes to the MC. AFP-based EC such as Metroticket 2.0 and AFP model appeared to be useful in both the NMA and the validation cohort, suggesting a potential role in identifying selected low-risk patients beyond the MC.

Objective: Patients with panic disorder (PD) are approximately four times more likely to experience suicidal thoughts and attempts compared to healthy controls (HCs). Despite the elevated risk compared to HCs, the relationship between cortical thickness (CT) in PD and suicidality remains underexplored. Methods: We recruited 161 right-handed participants, including 82 PD patients and 79 HCs, and assessed them using a comprehensive battery of psychological scales, including the Scale for Suicidal Ideation (SSI), Early Trauma Inventory Self Report-Short Form, Neuroticism-Extraversion-Openness Personality Inventory-Neuroticism (NEO-N), State-Trait Anxiety Inventory-Trait Anxiety (STAI-T), Panic Disorder Severity Scale (PDSS), and Beck Depression Inventory. Results: In whole-brain vertex-wise group comparison, patients with PD demonstrated significantly lower CT values in the insula, lateral occipital sulcus, and precentral gyrus compared to HCs. Notably, paradoxical significant positive correlations were observed between SSI total scores and CT in the above-mentioned regions within the PD cohort.Pearson’s correlation analyses further indicated that CT in these regions may be linked to high levels of early trauma, trait anxiety (e.g., NEO-N, STAI-T), panic symptom severity (e.g., PDSS), and treatment response in patients with PD. Conclusion This study suggest that suicidality in PD may be associated with CT in specific EFN regions related to suicidal brain and that CT in these regions could play a critical role in anxiety symptomatology in PD.