1.Stress Accelerates Depressive-Like Behaviors through Increase of Notch2 Expression in N141I Mutation Presenilin-2 Transgenic Mice
Seung Sik YOO ; Sun Mi GU ; Kyung Tak NAM ; Jeong Soon CHOI ; Yong Sun LEE ; In Jun YEO ; Ji Eun YU ; Sanghyeon KIM ; Dong Won LEE ; Hyeon Joo HAM ; Ju Young CHANG ; Jaesuk YUN ; Dong Ju SON ; Sang-Bae HAN ; Jin Tae HONG
Biomolecules & Therapeutics 2026;34(3):544-555
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.
2.Non-operative Management of Rectal Cancer with Adjuvant Chemotherapy after Chemoradiotherapy (NORMANDY): Prospective Study
Hyebin LEE ; Hyung Ook KIM ; Jason Joon Bock LEE ; In-Gu DO ; Heon-Ju KWON ; Mi Sung KIM ; Soo-Kyung PARK ; Hyo-Joon YANG ; Yoon Suk JUNG ; Jung Ho PARK ; Dong-Il PARK ; Kyung Uk JUNG ; Eo Jin KIM ; Dong-Hoe KOO ; Hungdai KIM ; Ho-Kyung CHUN ;
Cancer Research and Treatment 2026;58(2):573-580
Purpose:
Non-operative management (NOM) has emerged as a promising organ-preserving strategy for patients with rectal cancer who achieve a clinical complete response (cCR) after neoadjuvant chemoradiotherapy (CRT). However, no standardized treatment protocol has been established for watch-and-wait strategies.
Materials and Methods:
This prospective study evaluated oncological outcomes of NOM combined with 4 months of adjuvant capecitabine. Patients with resectable rectal cancer (≤ 8 cm from the anal verge, cT2-4 or N+) underwent CRT (50-54 Gy in 25-27 fractions with capecitabine). Eight weeks post-CRT, a multidisciplinary team assessed cCR. Patients achieving cCR received six cycles of capecitabine (2 weeks on/1 week off) and were actively monitored.
Results:
Among 89 patients receiving CRT (2018-2023), 17 (19.1%) achieved cCR and were included. The median age was 65 years, and 64.7% were male. Eleven (64.7%) completed all six cycles of adjuvant therapy. After a median follow-up of 31.4 months, 11 patients (64.7%) remained disease-free. Local regrowth occurred in six patients (35.3%) with 2- and 4-year rates of 34.5% and 47.6%, respectively. Five underwent radical surgery, and one received transanal excision with systemic chemotherapy. At the time of assessment, 15 patients (88.2%) showed no evidence of disease, while two (11.8%) received palliative chemotherapy. All patients were alive.
Conclusion
NOM with adjuvant capecitabine showed promising oncological outcomes, offering an alternative to passive watch-and-wait approaches. Further refinement through multidisciplinary strategies is warranted.
3.Postoperative Readmission Is Associated With Worse Oncologic Outcomes After Radical Cystectomy for Bladder Cancer: A Multicenter Study of 3,972 Patients
Jungwon PARK ; Jong Ho PARK ; Sangchul LEE ; Seung-Hwan JEONG ; Ja Hyeon KU ; Kyung Hwan KIM ; Jong Kil NAM ; Bumjin LIM ; BumSik HONG ; Wook NAM ; Sung Gu KANG ; Seok Ho KANG ; Tae Gyun KWON ; Tae-Hwan KIM ; Jieun HEO ; Won Sik HAM ; Geehyun SONG ; Ho Kyung SEO ; Wan SONG ; Hyun Hwan SUNG ; Byong Chang JEONG ; Jong Jin OH
Journal of Urologic Oncology 2026;24(1):69-78
Purpose:
Radical cystectomy (RC) is associated with substantial postoperative morbidity, and unplanned readmission remains common despite advances in perioperative management. However, the association between postoperative readmission due to complications and oncologic outcomes after RC for bladder cancer has not been clearly defined. We evaluated the impact of postoperative readmission on overall survival (OS) and cancer-specific survival (CSS) after RC for bladder cancer.
Materials and Methods:
We retrospectively analyzed 3,972 patients who underwent RC for bladder cancer in a multicenter cohort. Postoperative readmission was defined as unplanned hospitalization within 90 days postsurgery due to surgery-related complications. Survival outcomes were assessed using the Kaplan-Meier method and compared using the log-rank test. Univariable and multivariable Cox proportional hazards regression analyses were performed to identify independent predictors of OS and CSS.
Results:
Among the study population, 916 patients (23.1%) experienced postoperative readmission. Baseline and perioperative characteristics were generally comparable between patients with and without readmission. Kaplan-Meier analyses demonstrated significantly worse OS and CSS among patients who experienced postoperative readmission (both log-rank p<0.001). In multivariable analyses adjusting for clinicopathological factors, postoperative readmission remained independently associated with worse OS (hazard ratio [HR], 1.654; 95% confidence interval [CI], 1.464–1.868; p<0.001) and CSS (HR, 1.761; 95% CI, 1.509–2.055; p<0.001).
Conclusion
Postoperative readmission within 90 days after RC was independently associated with inferior long-term oncologic outcomes. These findings suggest the importance of strategies aimed at preventing postoperative complications and subsequent readmission.
4.Establishing an Active Vaccine Safety Surveillance System Using Large Scale Databases in Korea: Lessons and Scalable Insights for Global Application
Jin Gu YOON ; Eliel NHAM ; Yu Jung CHOI ; Min Joo CHOI ; Won Suk CHOI ; Young Kyung YOON ; Yu Bin SEO ; Hakjun HYUN ; Jung Yeon HEO ; Jin-Soo LEE ; Chung-Jong KIM ; Ji Yun NOH ; Joon Young SONG ; Hee Jin CHEONG
Journal of Korean Medical Science 2026;41(1):e47-
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.
5.Laparoscopic and robotic surgery for colorectal cancer in Korea: a nationwide health insurance database analysis from 2019 to 2023
Eun Ji PARK ; Hyun Gu LEE ; Youn Young PARK ; Sun Jin PARK ; Kil Yeon LEE ; Suk-Hwan LEE
Journal of Minimally Invasive Surgery 2025;28(1):25-35
Purpose:
This study examined nationwide data regarding laparoscopic and robotic surgery for colorectal cancer (CRC) in Korea.
Methods:
Nationwide data concerning patients who underwent surgery for CRC from 2019 to 2023 were obtained from the Health Insurance Review and Assessment Service database.
Results:
From 2019 to 2023, a total of 109,573 patients with CRC underwent surgical resection in Korea. Among these, open, laparoscopic, and robotic surgery comprised 17.2%, 71.5%, and 11.3%, respectively. Open surgery decreased from 18.3% in 2019 to 15.2% in 2023, whereas robotic surgery increased from 10.3% in 2019 to 12.7% in 2023. Regarding rectal cancer, the rate of robotic surgery increased from 23.0% in 2019 to 28.2% in 2023, and the rate of minimally invasive surgery (MIS) increased from 86.9% in 2019 to 89.2% in 2023.Patients with National Health Insurance had significantly shorter lengths of hospital stay after surgery than those with medical aid for all surgical methods (p < 0.0001). With respect to hospital size, 74,282 CRC surgeries (67.8%) were performed in tertiary general hospitals and 33,050 (30.2%) in general hospitals. By the region, 47,140 cases (43.0%) were performed in Seoul, 19,961 (18.2%) in Gyeonggi, and 7,417 (6.8%) in Daegu. Ostomy was created in 16,222 CRC surgeries (14.8%).
Conclusion
The rate of MIS adoption for CRC in Korea has increased, reaching 84.7% in 2023. The rate of laparoscopic surgery exceeded 70% and has plateaued. In contrast, the rate of robotic surgery adoption has steadily increased, particularly for rectal cancer, where it surpassed 28% in 2023.
6.Microglial galectin-3 increases with aging in the mouse hippocampus
Hyun Joo SHIN ; So Jeong LEE ; Hyeong Seok AN ; Ha Nyeoung CHOI ; Eun Ae JEONG ; Jaewoong LEE ; Kyung Eun KIM ; Bong-Hoi CHOI ; Seung Pil YUN ; Dawon KANG ; Sang Soo KANG ; Gu Seob ROH
The Korean Journal of Physiology and Pharmacology 2025;29(2):215-225
Microglial activation during aging is associated with neuroinflammation and cognitive impairment. Galectin-3 plays a crucial role in microglial activation and phagocytosis. However, the role of galectin-3 in the aged brain is not completely understood. In the present study, we investigated aging-related mechanisms and microglial galectin-3 expression in the mouse hippocampus using female 6-, 12-, and 24-month-old C57BL/6 mice. Western blot analysis revealed neurodegeneration, blood-brain barrier leakage, and increased levels of neuroinflammation-related proteins in 24-month-old mice compared to 6- and 12-month-old mice. Immunohistochemistry revealed an increase in activated microglia in the hippocampus of 24-month-old mice compared to 6- and 12-month-old mice. Furthermore, we found more galectin-3 and triggering receptor expressed on myeloid cells-2-positive microglia in 24-month-old mice compared to 6- and 12-month-old mice. Using primary mouse microglial cells, galectin -3 was also increased by lipopolysaccharide treatment. These findings suggest that galectin-3 may play an important role in microglial activation and neuroinflammation during brain aging.
7.Clinical outcomes and optimal indications for nonoperative management of acute appendicitis in adult patients: a comprehensive literature review
Annals of Coloproctology 2025;41(2):107-118
Appendectomy as the standard treatment for acute appendicitis has been challenged by accumulating evidence supporting nonoperative management with antibiotics as a potential primary treatment. This review aimed to summarize the clinical outcomes and the optimal indications for nonoperative management of acute appendicitis in adults. Current evidence suggests that uncomplicated and complicated appendicitis have different pathophysiologies and should be treated differently. Nonoperative management for uncomplicated appendicitis was not inferior to appendectomy in terms of complications and length of stay, with less than a 30% failure rate at 1 year. The risk of perforation and postoperative complications did not increase even if nonoperative management failed. Complicated appendicitis with localized abscess or phlegmon could also be treated conservatively, with a success rate of more than 80%. An interval appendectomy following successful nonoperative management is recommended only for patients over the age of 40 years to exclude appendiceal malignancy. The presence of appendicoliths increased the risk of treatment failure and complications; thus, it may be an indication for appendectomy. Nonoperative management is a safe and feasible option for both uncomplicated and complicated appendicitis. Patients should be informed that nonoperative management may be a safe alternative to surgery, with the possibility of treatment failure.
8.Clinical outcomes and optimal indications for nonoperative management of acute appendicitis in adult patients: a comprehensive literature review
Annals of Coloproctology 2025;41(2):107-118
Appendectomy as the standard treatment for acute appendicitis has been challenged by accumulating evidence supporting nonoperative management with antibiotics as a potential primary treatment. This review aimed to summarize the clinical outcomes and the optimal indications for nonoperative management of acute appendicitis in adults. Current evidence suggests that uncomplicated and complicated appendicitis have different pathophysiologies and should be treated differently. Nonoperative management for uncomplicated appendicitis was not inferior to appendectomy in terms of complications and length of stay, with less than a 30% failure rate at 1 year. The risk of perforation and postoperative complications did not increase even if nonoperative management failed. Complicated appendicitis with localized abscess or phlegmon could also be treated conservatively, with a success rate of more than 80%. An interval appendectomy following successful nonoperative management is recommended only for patients over the age of 40 years to exclude appendiceal malignancy. The presence of appendicoliths increased the risk of treatment failure and complications; thus, it may be an indication for appendectomy. Nonoperative management is a safe and feasible option for both uncomplicated and complicated appendicitis. Patients should be informed that nonoperative management may be a safe alternative to surgery, with the possibility of treatment failure.
9.Risk-adapted scoring model to identify candidates benefiting from adjuvant chemotherapy after radical nephroureterectomy for localized upper urinary tract urothelial carcinoma: A multicenter study
Sung Jun SOU ; Ja Yoon KU ; Kyung Hwan KIM ; Won Ik SEO ; Hong Koo HA ; Hui Mo GU ; Eu Chang HWANG ; Young Joo PARK ; Chan Ho LEE
Investigative and Clinical Urology 2025;66(2):114-123
Purpose:
Adjuvant chemotherapy (AC) is recommended for muscle-invasive or lymph node-positive upper urinary tract urothelial carcinoma (UTUC) after radical nephroureterectomy (RNU). However, disease recurrences are frequently observed in pT1 disease, and AC may increase the risk of overtreatment in pT2 UTUC patients. This study aimed to validate a risk-adapted scoring model for selecting UTUC patients with ≤pT2 disease who would benefit from AC.
Materials and Methods:
We retrospectively analyzed 443 ≤pT2 UTUC patients who underwent RNU. A risk-adapted scoring model was applied, categorizing patients into low- or high-risk groups. Recurrence-free survival (RFS) and cancer-specific survival (CSS) were analyzed according to risk group.
Results:
Overall, 355 patients (80.1%) and 88 patients (19.9%) were categorized into the low- and high-risk groups, respectively, with the latter having higher pathological stages, concurrent carcinoma in situ, and synchronous bladder tumors. Disease recurrence occurred in 45 patients (10.2%), among whom 19 (5.4%) and 26 (29.5%) belonged to the low- and high-risk groups, respectively (p<0.001). High-risk patients had significantly shorter RFS (64.3% vs. 93.6% at 60 months; hazard ratio [HR] 13.66; p<0.001) and worse CSS (80.7% vs. 91.5% at 60 months; HR 4.25; p=0.002). Multivariate analysis confirmed that pT2 stage and the high-risk group were independent predictors of recurrence and cancer-specific death (p<0.001). Decision curve analysis for RFS showed larger net benefits with our model than with the T stage model.
Conclusions
The risk-adapted scoring model effectively predicts recurrence and identifies optimal candidates for AC post RNU in non-metastatic UTUC.
10.Clinical outcomes and optimal indications for nonoperative management of acute appendicitis in adult patients: a comprehensive literature review
Annals of Coloproctology 2025;41(2):107-118
Appendectomy as the standard treatment for acute appendicitis has been challenged by accumulating evidence supporting nonoperative management with antibiotics as a potential primary treatment. This review aimed to summarize the clinical outcomes and the optimal indications for nonoperative management of acute appendicitis in adults. Current evidence suggests that uncomplicated and complicated appendicitis have different pathophysiologies and should be treated differently. Nonoperative management for uncomplicated appendicitis was not inferior to appendectomy in terms of complications and length of stay, with less than a 30% failure rate at 1 year. The risk of perforation and postoperative complications did not increase even if nonoperative management failed. Complicated appendicitis with localized abscess or phlegmon could also be treated conservatively, with a success rate of more than 80%. An interval appendectomy following successful nonoperative management is recommended only for patients over the age of 40 years to exclude appendiceal malignancy. The presence of appendicoliths increased the risk of treatment failure and complications; thus, it may be an indication for appendectomy. Nonoperative management is a safe and feasible option for both uncomplicated and complicated appendicitis. Patients should be informed that nonoperative management may be a safe alternative to surgery, with the possibility of treatment failure.

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