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.Bisphosphonates as a Tacrolimus-Sparing Strategy in Kidney Transplantation: Insights from a Retrospective Analysis
Hee Byung KOH ; Hyo Jeong KIM ; Ga Young HEO ; Namki HONG ; Yaeji LEE ; Seung Hwan SONG ; Hoon Young CHOI ; Chan-Young JUNG ; Hyung Woo KIM ; Jaeseok YANG ; Kyu Ha HUH ; Chung Mo NAM ; Beom Seok KIM
Yonsei Medical Journal 2026;67(1):17-26
Purpose:
Due to chronic toxicity, tacrolimus-sparing is an important issue in kidney transplant recipients (KTRs). Several studies have shown that bisphosphonate use is associated with favorable graft outcomes in KTRs. We investigated whether the association between tacrolimus trough levels (TTLs) and graft outcomes differed according to bisphosphonate use in KTRs.
Materials and Methods:
We conducted a retrospective study encompassing 1441 KTRs who were administered tacrolimus-based immunosuppressants. The primary exposure was a time-dependent cross-product of TTLs (low TTLs vs. normal-high TTLs with a reference of 6 ng/mL) and bisphosphonate use. Two primary outcomes were evaluated: overall graft loss (death or conversion to kidney replacement) and an estimated glomerular filtration rate (eGFR) <30 mL/min/1.73 m 2 .
Results:
During the median follow-up of 6.1 (3.4–9.7) years, overall graft loss occurred in 157 (10.9%) patients. Cox regression revealed that normal-high TTLs without bisphosphonate use were associated with a reduced risk of overall graft loss [adjusted hazard ratio (aHR), 0.65; 95% confidence interval (CI), 0.45–0.95] compared to low TTLs without bisphosphonate use. The use of bisphosphonate in conjunction with normal-high TTLs correlated with an even lower risk of overall graft loss (aHR, 0.25; 95% CI, 0.08–0.80) compared with low TTLs without bisphosphonate use. In patients with low TTLs, bisphosphonate use was associated with a reduced risk of overall graft loss compared with non-use (aHR, 0.20; 95% CI, 0.09–0.43). Similar trends were observed in the eGFR outcome.
Conclusion
The use of bisphosphonate was associated with favorable graft outcomes, even with low TTLs. Incorporating bisphosphonate into a conventional immunosuppressant regimen may potentially reduce tacrolimus requirement.
3.Molecular determinants of outcome to gemcitabine, cisplatin, and nab-paclitaxel in patients with advanced biliary tract cancer
Daeseong KIM ; Nam Suk SIM ; Seonjeong WOO ; Min Hwan KIM ; Choong-kun LEE ; Seung Soo HONG ; Sung Hyun KIM ; Ho Kyoung HWANG ; Chang Moo KANG ; Woo Jung LEE ; Jung Hyun JO ; Taek CHUNG ; Sohyun HWANG ; Beodeul KANG ; Jung Sun KIM ; Chang-Il KWON ; Sangwoo KIM ; Hong Jae CHON ; Chang Gon KIM ; Young Nyun PARK ; Hye Jin CHOI
Clinical and Molecular Hepatology 2026;32(2):721-736
Background/Aims:
Biliary tract cancer (BTC) is a rare malignancy with poor prognosis. We investigated genomic determinants of clinical benefit from gemcitabine, cisplatin, and nab-paclitaxel (GAP) versus gemcitabine and cisplatin (GC) in advanced BTC.
Methods:
Clinical and genomic data using TruSight Oncology 500 were analyzed from patients treated with GAP (N=198) or GC (N=89) as first-line therapy.
Results:
With a median follow-up of 33.0 months, GAP modestly improved progression-free survival (PFS) (hazard ratio [HR] 0.764; 95% confidence interval [CI] 0.591–0.989) without significant overall survival (OS) difference compared to GC. Genomic profiling revealed frequent alterations in TP53 (35.2%), KRAS (16.4%), SMAD4 (10.5%), and TNFRSF14 (10.5%), involving RTK/RAS (44.3%), TP53 (41.8%), and PI3K (20.2%) pathways. Single-gene mutations did not predict treatment benefit. However, pathway-level analysis identified PI3K pathway activation as significantly associated with inferior PFS (HR 2.148; 95% CI 1.478–3.124) and OS (HR 2.096; 95% CI 1.413–3.109) in patients receiving GAP, an effect not observed with GC. Importantly, GAP conferred clinical benefit only in patients without PI3K pathway activation, while no survival advantage was seen in those with such alterations (Pinteraction=0.023 for PFS, Pinteraction=0.003 for OS). Similar results were obtained in the independent validation cohort treated with GAP (N=103) or GC (N=64) for BTC.
Conclusions
Genomic profiling using next-generation sequencing identified PI3K pathway activation as key molecular determinant that differentiates patient outcomes between GAP and GC treatments in advanced BTC.
4.Optimizing pediatric liver transplantation allocation: a simulation study on new splittable deceased donor criteria in Korea
Yuyoung OH ; Nam-Joon YI ; Kyung Chul YOON ; Su young HONG ; Suk Kyun HONG ; Kwang-Woong LEE ; YoungRok CHOI
Clinical Transplantation and Research 2026;40(1):68-75
Background:
We analyzed the status of organ distribution in pediatric deceased donor liver transplantation (DDLT) in Korea. Additionally, we estimated how many pediatric patients could have avoided living donor liver transplantation (LDLT) or survived if new criteria for splittable deceased donors were adopted. Based on the findings, we advocate expanding policy to promote the universal adoption of split liver transplantation (SLT).
Methods:
Using the Korean Network for Organ Sharing database, we identified patients who underwent DDLT between January 2000 and December 2020. We considered “po-tential splittable donors” those with a donor-to-recipient weight ratio of ≥1.0 who met the existing SLT criteria (age 10–40 years; weight ≥50 kg). By comparing the numbersof pediatric LDLT recipients and potential splittable donors annually, we estimated how many patients might have avoided LDLT if the left lateral section of each splittable liver had been allocated to a child. Additionally, we compared the number of deaths on the DDLT waiting list with the number of potential splittable donors to estimate possibly preventable deaths.
Results:
Overall, we identified 640 potential splittable donors. Over the 20-year period, 1,210 pediatric patients (<19 years old) received LDLT. If potentially splittable livers had been split, this number could have been nearly halved. Furthermore, 127 patients died while on the DDLT waiting list. Using SLT with potential splittable donors, these deaths might have been prevented.
Conclusions
SLT could reduce avoidable deaths among pediatric patients while decreasing the economic and social burden of LDLT, without compromising survival for adult DDLT recipients.
5.Complete or incomplete revascularization in patients with left main culprit lesion acute myocardial infarction with multivessel disease: a retrospective observational study
Sun Oh KIM ; Hong-Ju KIM ; Jong-Il PARK ; Kang-Un CHOI ; Jong-Ho NAM ; Chan-Hee LEE ; Jang-Won SON ; Jong-Seon PARK ; Sung-Ho HER ; Ki-Yuk CHANG ; Tae-Hoon AHN ; Myung-Ho JEONG ; Seung-Woon RHA ; Hyo-Soo KIM ; Hyeon-Cheol GWON ; In-Whan SEONG ; Kyung-Kuk HWANG ; Seung-Ho HUR ; Kwang-Soo CHA ; Seok-Kyu OH ; Jei-Keon CHAE ; Ung KIM
Journal of Yeungnam Medical Science 2025;42(1):18-
Background:
Complete revascularization has demonstrated better outcomes in patients with acute myocardial infarction (AMI) and multivessel disease. However, in the case of left main (LM) culprit lesion AMI with multivessel disease, there is limited evidence to suggest that complete revascularization is better.
Methods:
We reviewed 16,831 patients in the Korea Acute Myocardial Infarction Registry who were treated from July 2016 to June 2020, and 399 patients were enrolled with LM culprit lesion AMI treated with percutaneous coronary intervention. We categorized the patients as those treated with complete revascularization (n=295) or incomplete revascularization (n=104). The study endpoint was major adverse cardiac and cerebrovascular events (MACCE), a composite of all-cause death, myocardial infarction, ischemia-driven revascularization, stent thrombosis, and stroke. We performed propensity score matching (PSM) and analyzed the incidence of MACCE at 1 year.
Results:
After PSM, the two groups were well balanced. There was no significant difference between the two groups in MACCE at 1 year (12.1% vs. 15.2%; hazard ratio, 1.28; 95% confidence interval, 0.60–2.74; p=0.524) after PSM. The components of MACCE and major bleeding were also not significantly different.
Conclusion
There was no significant difference in clinical outcomes between the groups treated with complete or incomplete revascularization for LM culprit lesion AMI with multivessel disease.
6.A Real-World, Prospective, Observational Study of Rivaroxaban on Prevention of Stroke and Non-Central Nervous Systemic Embolism in Renally Impaired Korean Patients With Non-Valvular Atrial Fibrillation:XARENAL
Il-Young OH ; Chang Hoon LEE ; Eue-Keun CHOI ; Hong Euy LIM ; Yong-Seog OH ; Jong-Il CHOI ; Min-Soo AHN ; Ju Youn KIM ; Nam-Ho KIM ; Namsik YOON ; Martin SANDMANN ; Kee-Joon CHOI
Korean Circulation Journal 2025;55(2):121-131
Background and Objectives:
Several real-world studies have been done in patients with nonvalvular atrial fibrillation (NVAF); however, information on its safety profile in patients with renal impairment is limited. XARENAL, a real-world study, aimed to prospectively investigate the safety profile of rivaroxaban in patients with NVAF with renal impairment (creatinine clearance [CrCl], 15–49 mL/min).
Methods:
XARENAL is an observational single-arm cohort study in renal impairment NVAF patients. Patients were followed up approximately every 3 months for 1 year or until 30 days following early discontinuation. The primary endpoint was major bleeding events. All adverse events, symptomatic thromboembolic events, treatment duration, and renal function change from baseline were the secondary endpoints.
Results:
XARENAL included 888 patients from 29 study sites. Overall, 713 (80.3%) had moderate renal impairment (CrCl, 30–49 mL/min), and 175 (19.7%) had severe renal impairment (CrCl, 15–29 mL/min) with a mean estimated glomerular filtration rate (eGFR) of 45.2±13.0 mL/min/1.73 m 2 . The mean risk scores were 3.3±1.4 and 1.7±0.9 for CHA 2 DS 2 -VASc score and HAS-BLED score, respectively. An incidence proportion of 5.6% (6.2 events per 100 patient-years) developed major bleeding; however, fatal bleeding occurred in 0.5% (0.5 events per 100 patient-years). The mean change in the eGFR was 2.22±26.47 mL/min/1.73 m 2 per year.
Conclusions
XARENAL observed no meaningful differences in major bleeding events from other previous findings as well as renal function changes in rivaroxaban-treated NVAF patients with renal impairment, which is considered to be acceptable in clinical practice.
7.Sex Differences in Procedural Characteristics and Clinical Outcomes Among Patients Undergoing Bifurcation PCI
Hyun Jin AHN ; Francesco BRUNO ; Jeehoon KANG ; Doyeon HWANG ; Han-Mo YANG ; Jung-Kyu HAN ; Leonardo De LUCA ; Ovidio de FILIPPO ; Alessio MATTESINI ; Kyung Woo PARK ; Alessandra TRUFFA ; Wojciech WANHA ; Young Bin SONG ; Sebastiano GILI ; Woo Jung CHUN ; Gerard HELFT ; Seung-Ho HUR ; Bernardo CORTESE ; Seung Hwan HAN ; Javier ESCANED ; Alaide CHIEFFO ; Ki Hong CHOI ; Guglielmo GALLONE ; Joon-Hyung DOH ; Gaetano De FERRARI ; Soon-Jun HONG ; Giorgio QUADRI ; Chang-Wook NAM ; Hyeon-Cheol GWON ; Hyo-Soo KIM ; Fabrizio D’ASCENZO ; Bon-Kwon KOO
Korean Circulation Journal 2025;55(1):5-16
Background and Objectives:
The risk profiles, procedural characteristics, and clinical outcomes for women undergoing bifurcation percutaneous coronary intervention (PCI) are not well defined compared to those in men.
Methods:
COronary BIfurcation Stenting III (COBIS III) is a multicenter, real-world registry of 2,648 patients with bifurcation lesions treated with second-generation drug-eluting stents.We compared the angiographic and procedural characteristics and clinical outcomes based on sex. The primary outcome was 5-year target lesion failure (TLF), a composite of cardiac death, myocardial infarction, and target lesion revascularization.
Results:
Women (n=635, 24%) were older, had hypertension and diabetes more often, and had smaller main vessel and side branch reference diameters than men. The pre- and post-PCI angiographic percentage diameter stenoses of the main vessel and side branch were comparable between women and men. There were no differences in procedural characteristics between the sexes. Women and men had a similar risk of TLF (6.3% vs. 7.1%, p=0.63) as well as its individual components and sex was not an independent predictor of TLF. This finding was consistent in the left main and 2 stenting subgroups.
Conclusions
In patients undergoing bifurcation PCI, sex was not an independent predictor of adverse outcome.
8.Unhealed Anterolateral Ligament of the Knee is Associated with Residual Pivot-Shift Following Anterior Cruciate Ligament Reconstructions
Nam-Hong CHOI ; Dong-Min LEE ; Uk HUR ; Brian Nicholas VICTOROFF
The Journal of the Korean Orthopaedic Association 2025;60(1):30-37
Purpose:
The association between the healing of an injured anterolateral ligament (ALL) and residual pivot-shift following anterior cruciate ligament (ACL) reconstructions is rarely reported. This study analyzed the relationship between unhealed ALL and residual pivot-shift after an ACL reconstruction.
Materials and Methods:
The inclusion criteria were patients who underwent autologous hamstring ACL reconstructions within 6 weeks after injury from January 2008 to March 2021. Preoperative ALL injuries and postoperative ALL healing were graded according to the magnetic resonance imaging classification, with postoperative magnetic resonance imaging performed 7.8 months after surgery on average. The patients were categorized based on postoperative ALL healing, and the clinical scores (Lysholm score and Tegner activity scale) and knee stability (Lachman test and pivot-shift test) were assessed at the 1-year postoperative follow-up.
Results:
One hundred and forty-five patients were enrolled in this study. One hundred and twenty-eight (88.3%) patients had a concomitant ALL injury. Among 86 patients with preoperative grade B, 16 (18.6%) patients showed grade 1 (good), and 70 (81.4%) showed grade 2 (partial) ALL postoperatively. Among the 42 patients with preoperative grade C (complete tear), 1 (2.4%) patient showed grade 1 (good), 21 (50.0%) showed grade 2 (partial), and 20 (47.6%) showed grade 3 (non-visualized) ALL. Preoperative grade C was significantly associated with a higher incidence of grade 3 (non-visualized) postoperatively than the other groups (p<0.001). Postoperatively, the Lachman test, KT-1000 (MEDmetric Corp.) arthrometer (side-to-side difference), Lysholm score, and Tegner activity scales did not show a significant difference among the intact, grade 1, grade 2, and grade 3 ALL groups. The pivot-shift test showed a significant difference between the ALL grades (p=0.001). Grade 3 ALL group showed a higher incidence of pivot-shift than the intact, grade 1, and grade 2 ALL groups.
Conclusion
Patients with preoperative grade C had a higher rate of grade 3 postoperatively compared to the other groups. In addition, the grade 3 group had a significantly higher incidence of a pivot-shift. Therefore, in cases of ACL injuries with concomitant complete ALL tears, ALL reconstruction should be considered during ACL reconstruction.
9.Risk Factors for the Occurrence of Peripheral Venous Catheter-Related Phlebitis in Hospitalized Patients with Neurosurgery: A Retrospective Study
Yun Hee HONG ; Soon Yeo JOO ; Nam Hee CHAE ; Ji Yoon KIM ; Min-Jung CHOI
Journal of Korean Clinical Nursing Research 2025;31(1):80-90
Purpose:
This study aimed to identify the risk factors for peripheral intravenous catheter-related phlebitis in hospitalized neurosurgery patients.
Methods:
This study involved 443 neurosurgery patients who were admitted to a general hospital in Seoul. The analysis included 982 intravenous lines. Data were retrospectively extracted from electronic medical records for the period between November 1, 2022, and May 31, 2023. Data were analyzed using descriptive statistics, independent t-test, x 2 test, and logistic regression.
Results:
The incidence rate of phlebitis was 13.6%, with the majority of cases classified as grade 2. Gender, present diseases, length of hospital stay, needle gauge size, and cardiovascular drugs were identified as risk factors for phlebitis in neurosurgery patients.
Conclusion
This study is significant as it provides basic data for the prevention and management of peripheral phlebitis in hospitalized neurosurgery patients. The risk factors identified in this study should be incorporated into nursing education to implement a systematic peripheral intravenous management program, and appropriate peripheral intravenous catheter-related nursing interventions are necessary based on the characteristics of each patient.
10.Risk Factors for the Occurrence of Peripheral Venous Catheter-Related Phlebitis in Hospitalized Patients with Neurosurgery: A Retrospective Study
Yun Hee HONG ; Soon Yeo JOO ; Nam Hee CHAE ; Ji Yoon KIM ; Min-Jung CHOI
Journal of Korean Clinical Nursing Research 2025;31(1):80-90
Purpose:
This study aimed to identify the risk factors for peripheral intravenous catheter-related phlebitis in hospitalized neurosurgery patients.
Methods:
This study involved 443 neurosurgery patients who were admitted to a general hospital in Seoul. The analysis included 982 intravenous lines. Data were retrospectively extracted from electronic medical records for the period between November 1, 2022, and May 31, 2023. Data were analyzed using descriptive statistics, independent t-test, x 2 test, and logistic regression.
Results:
The incidence rate of phlebitis was 13.6%, with the majority of cases classified as grade 2. Gender, present diseases, length of hospital stay, needle gauge size, and cardiovascular drugs were identified as risk factors for phlebitis in neurosurgery patients.
Conclusion
This study is significant as it provides basic data for the prevention and management of peripheral phlebitis in hospitalized neurosurgery patients. The risk factors identified in this study should be incorporated into nursing education to implement a systematic peripheral intravenous management program, and appropriate peripheral intravenous catheter-related nursing interventions are necessary based on the characteristics of each patient.

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