Purpose: Although gastric cancer (GC) exhibits significant genomic heterogeneity, the clinical implications of its immune microenvironment remain poorly understood. Materials and Methods: We retrospectively evaluated patients with GC who underwent gastrectomies between 2011 and 2014. The tumors were analyzed for Epstein–Barr virus (EBV), microsatellite instability-high (MSI-H), tumor-infiltrating lymphocytes (CD3), tumor-associated macrophages (CD68 and CD163), and programmed death-ligand 1 (PD-L1) expression. Tumors were classified using the modified The Cancer Genome Atlas scheme, and their clinical characteristics were compared. Results: A total of 567 patients were classified into EBV (6%), MSI-H (10%), chromosomal instability-like (36%), and genomically stable-like (48%) subtypes. EBV tumors exhibited the highest PD-L1 expression (85%) and immune infiltration by CD3+ T cells (86%), CD68+ macrophages (58%), and CD163+ macrophages (40%). High CD68+ macrophage tumors were associated with advanced stages and worse 5-year disease-free survival (83% vs. 95%; P<0.001);however, this association was not independently significant after adjusting for the tumor-nodemetastasis stage. PD-L1 expression did not significantly affect the survival outcomes. Conclusions GC subtypes have distinct immune microenvironments that influence prognosis. Our findings highlight the prognostic and therapeutic potential of immune profiling in GC.

Objective: This study aimed to compare the therapeutic outcomes of no-touch (NT) radiofrequency ablation (RFA) vs. tumorpuncture microwave ablation (MWA) in the treatment of single hepatocellular carcinomas (HCCs) measuring ≤3 cm. Materials and Methods: This multicenter retrospective study included 304 patients who underwent either NT-RFA (n = 144) or MWA (n = 160) for a single HCC measuring ≤3 cm. Comparative analyses were conducted for the overall cohort, while 81 patients per group were matched using propensity score matching (PSM). The analyzed outcomes included technical success, primary technique efficacy, local tumor progression (LTP), and major complications. Cumulative LTP was estimated using Kaplan–Meier analysis and compared using the log-rank text, while the rate of ablative margin ≥5 mm and ablation time were compared using Chi-squared and Mann–Whitney U tests, respectively. Results: Technical success was achieved in 98.6% (142/144) and 100% (160/160) of in the NT-RFA and MWA patients, respectively before PSM (P = 0.224), and 98.8% (80/81) and 100% (81/81) after PSM (P = 1.000). The primary technique efficacies were 98.6% (142/144) and 100% (160/160) before PSM (P = 0.224), and 97.5 % (79/81) and 100% (81/81) after PSM (P = 0.497), respectively. The 1-, 2-, and 3-year cumulative LTP rates were 1.4%, 1.4%, and 2.3%, respectively, for NTRFA and 5.1%, 8.6%, and 8.6%, respectively, for MWA before PSM (P = 0.013). After PSM, the corresponding rates were 0%, 0%, and 0% for NT-RFA, and 7.6%, 10.4%, and 10.4% for MWA (P = 0.006). Major complications were not observed. NT-RFA achieved a higher proportion, with an ablative margin ≥5 mm (88.7% [126/142] vs. 71.9% [115/160]; P < 0.001), but required longer ablation times (median, 10.0 vs. 6.0 min; P < 0.001). Conclusion NT-RFA showed superior local tumor control compared to MWA, despite greater procedural complexity and longer ablation times.

Chrysoeriol, a flavonoid naturally found in several plants, including Danggui Susan, a traditional herbal medicine, exhibits promising anti-inflammatory and antioxidant properties. Its potential to prevent cardiovascular diseases, primarily through inhibiting platelet activation and aggregation, has attracted significant interest. This study aimed to investigate the molecular mechanisms underlying the antiplatelet effects of chrysoeriol. The compound effectively suppressed collagen-induced platelet aggregation without inducing cytotoxicity. Chrysoeriol elevated intracellular levels of cyclic AMP (cAMP) and cyclic GMP (cGMP), enhanced inositol 1,4,5-trisphosphate receptor (IP 3R) phosphorylation, and reduced cytosolic calcium (Ca2+ ) mobilization, all of which contributed to its antiplatelet action. Furthermore, chrysoeriol inhibited the phosphorylation of PI3K, Akt, JNK, and p38 MAPK, pathways involved in the activation of cytosolic phospholipase A2 (cPLA 2) and thromboxane A2 (TXA2) production. These effects were accompanied by reduced TXA2 production and secretion of dense granules (ATP and serotonin). Chrysoeriol also impaired thrombin-induced clot retraction, further suggesting its capacity to regulate platelet responses and cytoskeletal rearrangements. These findings highlight chrysoeriol’s multi-target mechanisms, including modulation of cyclic nucleotides, kinase pathways, and platelet function, offering potential as a therapeutic agent to prevent thrombotic cardiovascular events.

Alzheimer’s disease (AD) is characterized by progressive cognitive deterioration and significant depression. However, the mechanisms linking depression to AD pathology remain unclear. Here, we investigated whether Notch2 signaling mediates depressionlike behaviors in presenilin-2 (PS2) N141I mutant mice, an early-onset AD model. PS2 wild-type (WT) and mutant (MT) mice aged 12-15 months were subjected to unpredictable chronic mild stress (UCMS) for 4 weeks, followed by sucrose preference, tail-hanging, and forced swimming tests. Behavioral assessments showed that UCMS exacerbated anhedonia and immobility only in PS2 MT mice. Molecular analysis revealed concomitant increases in plasma corticosterone, hippocampal γ-secretase activity, and Notch2 expression, and elevated total and phosphorylated glucocorticoid receptor levels in PS2 MT-UCMS mice. Gene expression profiling of human hippocampal datasets confirmed upregulation of NOTCH2 in Alzheimer’s disease and depression.Pharmacological inhibition of γ-secretase and Notch signaling with DAPT normalizes depressive behavior, reduces corticosterone release, attenuates GR phosphorylation, and inhibits Notch2 signaling in PS2 MT mice. These findings identify Notch2 as a pivotal mediator linking chronic stress to molecular changes associated with depression and AD, and suggest that targeting Notch2 signaling may provide therapeutic benefits for comorbid mood and neurodegenerative disorders.

Purpose: This study aimed to report the real-world outcomes of intravesical gemcitabine for bacillus Calmette–Guérin (BCG)–unresponsive, high-risk, non–muscle-invasive bladder cancer (HR-NMIBC) in Korean patients who were unable or unwilling to undergo radical cystectomy (RC). Materials and Methods: This retrospective study included 131 patients (median age, 69 years; 88.5% men) treated with intravesical gemcitabine for BCG-unresponsive HR-NMIBC at nine centers between May 2019 and April 2022. The primary endpoint was 1-year recurrence-free survival (RFS). The secondary endpoints included factors influencing RFS, progression-free survival (PFS), cystectomy- free survival, cancer-specific survival (CSS), overall survival (OS), and safety. Survival analysis was performed using the Kaplan-Meier method, and risk factors for recurrence were assessed using Cox regression models. Results: Patients were followed up for a median duration of 25 months, with carcinoma in situ (CIS) in 41.9% of the patients. The 1-year and 2-year RFS rates were 68% and 42%, while the 1-year and 2-year PFS rates were 87% and 77%, respectively. No significant factors influencing RFS were identified. Seventeen patients underwent RC during a median follow-up of 16 months, with the condition in three patients progressing to muscle-invasive disease on final pathological analysis. The 2-year CSS and OS rates were 98% and 97%, respectively. Intravesical gemcitabine was well-tolerated, with only seven patients (5.3%) unable to complete the full induction course. Conclusion Our research highlights the potential of intravesical gemcitabine as a viable bladder-sparing treatment option for BCG-unresponsive HR-NMIBC, providing real-world evidence on its safety, efficacy, and tolerability.

Purpose: The male predominance in the incidence of gastric cancer (GC) is established; however, sex differences in the prognosis of GC remain controversial. As such, this study analyzed the prognosis of patients with GC based on age and sex. Materials and Methods: Data from 14,739 patients diagnosed with GC at Seoul National University Bundang Hospital between 2003 and 2023 were analyzed. Baseline characteristics, histological types of GC, overall and GC-specific survival rates (age and stage stratification), and associated risk factors were analyzed. Results: Females were significantly younger (p < 0.001) and exhibited more gastric body cancers (p < 0.001) and tumors with diffuse-type or poorly differentiated histology (p < 0.001) than males. Females exhibited an advantage over males in terms of overall survival (p=0.004), but not in GC-specific survival. However, age stratification revealed significant sex differences, that females < 50 years of age exhibited survival disadvantages (p < 0.001); however, this trend was reversed with age, and females > 60 years exhibited survival advantages (p < 0.001) for both overall and GC-specific survival. This may be explained by the lower ratio of diffuse-type GC as females age. Furthermore, in the analysis according to stage, females with stage IV disease exhibited significant survival disadvantages, with significantly younger age and a higher proportion of diffuse-type GC which exhibits aggressive features, resulting in poorer survival than in males. Conclusion Age and stage stratification revealed significant differences in survival between the sexes, which can be helpful for public health strategies.

Objective: To classify life stages for companion dogs and cats by identifying clusters in age-specific disease proportions derived from medical records, providing a data-driven foundation for health examination programs. Methods: We collected 505,667 medical records from 82 veterinary facilities in South Korea between 2020 and 2023. Diagnoses were standardized using GPT-4o and S-BioBERT. Following preprocessing, data from 27 facilities yielded 222,706 canine and 39,910 feline records for the final analysis. Principal component analysis and K-means clustering (K = 4) were applied to age-specific disease proportions to identify life stages.The 10 most highest-proportion diagnoses diseases were determined for each cluster. Results: Canine life stages were classified as ≤ 1 year, 2–5 years, 6–10 years, and 11–15+ years.Feline life stages were 1–2 years, 3–8 years, 9–12 years, and 13–15+ years. In dogs, developmental diseases were common in the youngest age group, while chronic diseases were more prevalent in older groups. In cats, oral and urinary diseases were high-ranking, conjunctivitis was most common in the early stage, and chronic diseases increased with age. Conclusions and Relevance: Age-specific diagnosis patterns support four practical life stages for dogs and cats in South Korea. These boundaries can inform evidence-based preventive examination schedules, animal health policy, and pet insurance product design.

Background: There are limited long-term clinical outcome data comparing first-generation (1G) versus second-generation (2G) drug-eluting stents (DES) in patients with single-vessel disease (SVD). We sought to compare the efficacy and safety of 1G- and 2G-DES in SVD patients who underwent successful percutaneous coronary intervention (PCI) over 10 years of clinical follow-up. Methods: A total of 2,312 consecutive patients with SVD who underwent PCI with 1G-DES (paclitaxel- or sirolimus-eluting stents, n = 811) or 2G-DES (zotarolimus [Endeavor, Endeavor Resolute]- or everolimus-eluting stents [Promus Element, Xience], n = 1,082) were enrolled.After propensity score matching, 2 matched groups (538 pairs) were generated. Study endpoints included individual and composite clinical outcomes through 10 years. Results: During the 10-year follow-up, the 2G-DES group had lower incidences of myocardial infarction (MI; hazard ratio [HR], 0.44; 95% confidence interval [CI], 0.22–0.92; P = 0.028) and target lesion revascularization (TLR; HR, 0.54; 95% CI, 0.32–0.91; P = 0.021) than the 1G-DES group. Rates of total death, cardiac death, non-target vessel revascularization, stroke, major adverse cardiac events, and major adverse cardiac and cerebrovascular events were similar between groups. Conclusions In our single-center, all-comer registry, 2G-DES were associated with lower incidence rates of MI and TLR compared to 1G-DES in SVD patients over 10 years of followup, indicating a safer and more durable effect than 1G-DES.

Background/Aims: Portal vein thrombosis (PVT) frequently occurs in patients with inflammatory bowel disease (IBD), particularly when influenced by factors such as abdominal infections, IBD flare-ups, or surgical procedures. The implications of PVT range from immediate issues such as intestinal ischemia to long-term concerns including portal hypertension and its complications. However, there is a notable gap in comprehensive studies on PVT in IBD, especially with the increasing incidence of IBD in Asia. This research aimed to evaluate the clinical features and outcomes of PVT in patients with IBD at a leading hospital in South Korea. Methods: This retrospective analysis reviewed adult patients diagnosed with both IBD and PVT from 1989 to 2021 at a renowned South Korean medical center. The study focused on patient characteristics, specifics of PVT, administered treatments, and outcomes, all confirmed through enhanced CT scans. Results: A total of 78 patients met the study’s criteria. Notably, only 20.5% (16/78) were treated with oral anticoagulants; however, a vast majority (96.2%; 75/78) achieved complete radiographic resolution (CRR). When comparing patients receiving anticoagulants to those who did not, a significant preference for anticoagulant use was observed in cases where the main portal vein was affected, as opposed to just the left or right veins (p = 0.006). However, multivariable analysis indicated that neither anticoagulant use nor previous surgeries significantly impacted CRR. Conclusions Patients with IBD and PVT generally had favorable outcomes, regardless of anticoagulant use.