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: Older cancer patients face unique challenges due to age-related physiological changes, increasing their vulnerability to treatment-related toxicities. Geriatric assessment (GA) is a validated tool for optimizing care, yet there is no consensus on integrating geriatric interventions into oncology. This study evaluates the feasibility of a tailored onco-geriatric intervention model incorporating the KG-7 screening tool. Materials and Methods: This prospective study included 30 patients aged ≥ 70 years with solid tumors undergoing adjuvant or palliative chemotherapy. Patients scoring ≤ 5 of KG-7 were eligible. Tailored interventions incorporating KG-7 included polypharmacy, functional status, mobility, nutrition, cognition, emotional well-being, insomnia, social support, and medical problem. KG-7, GA, and quality of life (QoL) were followed at 12 weeks. Results: Participants (median age, 79.5 years) had colon (43.3%), pancreatic (23.3%), or gastric cancer (23.3%). At baseline, most patients showed independent activities of daily living (100%)/instrumental activities of daily living (90%). However, 93.3% had abnormal GA. Particularly, 86.7% were either malnourished or at risk of malnutrition. The most frequently identified intervention needs included polypharmacy (70.0%), nutritional support (60.0%), and emotional well-being (50.0%) with high adherence (100.0%, 88.9%, and 46.7%, respectively). At 12 weeks, KG-7 scores improved in 43.8% of patients, and 69.2% of GA domains were improved. QoL analysis revealed modest improvement in Global Health Status (mean difference, 6.3; p=0.176). One-year survival rates were 92.3% and 79.4% for adjuvant and palliative groups, respectively. Conclusion The onco-geriatric intervention model incorporating KG-7 demonstrated high feasibility and potential to enhance clinical outcomes. Future studies should validate this approach in randomized trials to optimize care for older cancer patients.

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.

Background: and Purpose To compare the epidemiological and clinical features of the rare patients with cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL) with age- and sex-matched controls in a nationwide cohort from South Korea. Methods: This observational cohort study analyzed newly diagnosed CADASIL patients aged at least 20 years and matched controls using data from the National Health Information Database for 2004–2022. The cumulative incidence of CADASIL was assessed by age and sex, and compared between regions. Neurologic and systemic diseases were compared between the CADASIL and control groups. Results: The study analyzed 816 CADASIL patients and 816 age- and sex-matched controls aged 56.8±15.2 years (mean±standard deviation), among whom 48.3% were male. The cumulative incidence of CADASIL was 1.86 per 100,000 people (95% confidence interval [CI]=1.85– 1.87 per 100,000), and peaked at 60–69 years of age. In terms of regional distribution, the incidence was highest for Jeju, at 39.67 per 100,000 (95% CI 37.84–41.49 per 100,000). Neurologic diseases were more frequent in CADASIL patients, including Alzheimer’s disease (33.1% vs.20.0%), vascular dementia (84.9% vs. 5.0%), epilepsy (34.6% vs. 15.9%), stroke (70.7% vs. 27.6%), parkinsonism (18.9% vs. 11.0%), and depression (60.8% vs. 44.9%). Systemic diseases such as diabetes mellitus (78.9% vs. 68.9%) were also more common in CADASIL patients, while cancer (27.9% vs. 38.7%) and myocardial infarction (10.0% vs. 13.6%) were less common than in controls. The onset ages of all diseases were lower in CADASIL patients. Conclusions This study has provided a precise nationwide estimate of the CADASIL incidence and its regional distribution in South Korea. CADASIL patients showed higher incidence rates and earlier onsets of diverse clinical manifestations.

Objective: Cognitive impairment is common in patients with Parkinson’s disease (PD), and few pharmacological options are available for treating this condition. We evaluated the effects of a digital cognitive training program (SUPERBRAIN), which was previously shown to be effective in populations at risk of Alzheimer’s disease, on cognitive function in individuals with PD. Methods: Twenty-three individuals with PD and mild cognitive impairment (PD-MCI) from four clinics were randomized to the intervention (n=16) or control (n=7) groups. The intervention group completed a 12-week, home-based, tablet-based cognitive training program (25–30 min/day, 7 days/week). Cognitive outcomes were assessed using the Seoul Neuropsychological Screening Battery pre- and post-intervention. Results: The adherence rate was 79.36%. The intervention group showed significant improvements in the Seoul Verbal Learning Test (SVLT) delayed recall and the Controlled Oral Word Association Test, while no changes were observed in the control group. Analysis of covariance confirmed greater SVLT improvement in the intervention group (F statistic=7.15, p=0.015, partial η2=0.28). Conclusion SUPERBRAIN is feasible and can improve cognitive function in individuals with PD-MCI.

Vaccines are highly effective, but rare or delayed adverse events following immunization (AEFIs) require post-licensure surveillance beyond clinical trials. Korea lacks a comprehensive, active, database-based framework, yet key assets exist: nationwide claims databases (National Health Insurance Service/Health Insurance Review and Assessment Service), the national immunization registry (Korea Disease Control and Prevention Agency’s Immunization Registry Information System) for National Immunization Program (NIP) and non-NIP vaccines, and increasingly standardized hospital electronic health records.We propose a federated, code to data architecture with data linkages between these data.Implementation should adopt a common data model (CDM), standardized case definitions, latency accounting, and transparent public reporting under strong privacy governance. Major challenges include multi step administrative approvals for data linkage, incomplete capture of adult non-NIP vaccinations, heterogeneous hospital data structures, and strict data protection constraints. Strategic priorities are to streamline statutory and administrative processes for public health use, mandate or enable claims-based capture of adult vaccinations, enhance CDM based interoperability, and develop secure hubs for aggregated outputs. With these measures, Korea will be well positioned to establish a scalable active surveillance system capable of detecting rare AEFIs, supporting transparent and evidence-based communication, and ensuring equitable injury compensation grounded in domestic data.

AIM To evaluate the quality of Gegen Formula Granules.METHODS Linear calibration with two reference substances(LCTRS)was adopted in the predicting of retention time with puerarin and daidzein as internal standards.UPLC characteristic chromatograms were established.The contents of 3'-hydroxy puerarin,puerarin(internal standard),3'-methoxy puerarin,puerarin 6"-O-xyloside,puerarin apioside and daidzin were determined by quantitative determination analysis multi-components by a single marker(QAMS),after which their transfer rates were calculated.RESULTS Compared with relative retention time method,LCTRS demonstrated higher positional accuracy for characteristic peaks and wider application range for columns.There were 9 characteristic peaks in the characteristic chromatograms for 14 batches of formula granules and 15 batches of standard decoctions with the similarities of more than 0.95.The contents and transfer rates of various constituents in formula granules and standard decoctions were basically consistent.CONCLUSION The chemical constituents in formula granules and their standard decoctions of Puerariae lobatae Radix display good consistency,reliable preparation process is observable in the former.

Objective:To investigate the protective effect of N-acetylcysteine (NAC) against α-amanitin (α-AMA)-induced liver injury via regulation of mitochondrial dynamic imbalance.Methods:Thirty-two ICR mice were randomly (random number) assigned to four groups ( n = 8 per group): normal control, NAC control, α-AMA poisoning, and α-AMA + NAC treatment group. After modeling, behavioral changes were observed and survival curves were plotted. Liver function markers and oxidative stress indicators were measured using ELISA. Pathological damage in liver tissue was examined, and mitochondrial ultrastructural changes were observed via transmission electron microscopy, followed by mitochondrial injury scoring. Survival rates were analyzed using the Kaplan–Meier method. One-way ANOVA was used for intergroup comparisons, followed by pairwise comparisons. Results:Compared with the control group, α-AMA intoxication significantly reduced survival rates and increased serum ALT and AST levels ( P < 0.05). Liver tissues exhibited disordered hepatic cord arrangement, cytoplasmic loosening, and edema. Mitochondria showed moderate to severe swelling, cristae fragmentation, matrix dissolution, and vacuolation, along with increased injury scores ( P < 0.05). Oxidative markers MDA and ROS were elevated, while antioxidant enzymes SOD and CAT were decreased (all P < 0.05). Mitochondrial activity was impaired, expression of fusion proteins OPA1, MFN1, and MFN2 was downregulated, and fission protein DRP1 was upregulated (all P < 0.05). Compared with the α-AMA group, NAC treatment significantly improved survival, reduced ALT and AST levels ( P < 0.05), alleviated pathological and mitochondrial ultrastructural damage, decreased MDA and ROS, increased SOD and CAT (all P < 0.05), enhanced mitochondrial activity, upregulated OPA1, MFN1, and MFN2, and downregulated DRP1 (all P < 0.05). No significant differences were observed between the normal and NAC control groups. Conclusions:NAC may attenuate α-AMA-induced acute liver injury by maintaining mitochondrial dynamic homeostasis.

Chrysophanol(Chr)and physcion(Phy)are primary active ingredients of a well-known traditional Chinese medicine namely rhubarb(Chinese name:Dahuang),and their glucuronides have been revealed as the dominant forms presenting in rats after oral administration.Either Chr or Phy has two glycosylation sites,resulting in a pair of positional isomers for glucuronides of either compound(CG1&CG2 and PG1&PG2).To confirmatively identify these glucuronides,energy-resolved mass spectrometry(ER-MS)was used to pursue the fragmentation trajectories of the targeted fragment ions,and the resultant breakdown graphs that were described by the optimal collision energy(OCE)were expected to exhibit the differences of glycosidic bond cleavage between the isomers.Quantum chemical calculation was thereafter conducted to produce the bond dissociation energy(BDE)of the glycosidic bonds.The isomers were unambiguously identified through applying the positive correlation rule between OCE and BDE.Fortunately,the glucuronides of Chr and Phy in vivo were observed through liver microsomes incubationin vitro.ER-MS was utilized to collect the Gaussian-shaped breakdown graphs in response to the neutral loss of 176 Da,and the absolute values of OCE were compared between positional isomers.The results revealed that CG1(-32.31 eV)>CG2(-31.61 eV),and nonetheless,PG1(-30.00 eV)Chr-8-GluA(-48.787 kJ/mol),and nonetheless,Phy-1-GluA(-48.672 kJ/mol)

The stability of ammonium ion selective electrode is an important indicator to ensure accurate monitoring of ammonia nitrogen concentration in drinking water.However,in long-term monitoring process,interfering ions and water molecules in water samples may penetrate into the interior of the ammonium ion selective electrode to form a water layer,which affects the potential response and stability of the electrode.Perfluorooctanoic acid is a low surface energy material,and doping it in polyaniline can reduce surface energy of the composite and improve surface roughness.In this work,five ammonium ion selective electrodes were prepared by doping polyaniline with different concentrations of perfluorooctanoic acid as a solid contact layer,which made the solid contact layer of electrode had hydrophobic properties,thereby improving stability of the ammonium ion selective electrode.The stability of the ion-selective electrode was evaluated by potential drift experiment,and the optimal doping concentration of perfluorooctanoic acid in the sediment solution was determined to be 5 mmol/L.The experiment results showed that the solid contact layer had a water contact angle of 132o under the doping concentration,the potential drift rate was 41.66 μV/h,and potential drift rate in the aqueous layer test was 1.31 mV/h,which were all better than those of the unmodified electrode.The standard deviation of the electrode potential was 1.42 mV,which was obviously superior to that of the unmodified electrode.The characteristics of high stability of the electrode made it suitable for long-term monitoring of ammonia nitrogen content in water samples.