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.

Irritable bowel syndrome (IBS) is a chronic, disabling, and functional bowel disorder that significantly affects social functioning and reduces quality of life and increases social costs. The Korean Society of Neurogastroenterology and Motility published clinical practice guidelines on the management of IBS based on a systematic review of the literature in 2017, and planned to revise these guidelines in light of new evidence on the pathophysiology, diagnosis, and management of IBS. The current revised version of the guidelines is consistent with the previous version and targets adults diagnosed with or suspected of having IBS. These guidelines were developed using a combination of de novo and adaptation methods, with analyses of existing guidelines and discussions within the committee, leading to the identification of key clinical questions. Finally, the guidelines consisted of 22 recommendations, including 3 concerning the definition and risk factors of IBS, 4 regarding diagnostic modalities and strategies, 2 regarding general management, and 13 regarding medical treatment. For each statement, the advantages, disadvantages, and precautions were thoroughly detailed. The modified Delphi method was used to achieve expert consensus to adopt the core recommendations of the guidelines. These guidelines serve as a reference for clinicians (including primary care physicians, general healthcare providers, medical students, residents, and other healthcare professionals) and patients, helping them to make informed decisions regarding IBS management.

Background: Post-transplantation cyclophosphamide (PTCy) and anti-thymocyte globulin (ATG) are common pro‑ phylactic strategies for graft-versus-host disease (GVHD) after haploidentical hematopoietic stem cell transplantation (haplo-HSCT). Interleukin (IL)-6 is a surrogate marker for cytokine release syndrome (CRS) and acute GVHD.Method The clinical outcomes and complications of haplo-HSCT with PTCy plus ATG versus PTCy monotherapy were compared according to serum IL-6 levels at Chungnam National University Hospital (Daejeon, South Korea) from Jan‑ uary 2019 to February 2023. Results: Forty patients who underwent haplo-HSCT were analyzed. A significant difference in IL-6 levels was observed between the PTCy plus ATG and PTCy alone groups (7.47 ± 10.55 vs. 117.65 ± 127.67; p = 0.003). More patients in the PTCy plus ATG group had a CRS grade of 0 than in the PTCy alone group (p < 0.001). Serum IL-6 levels were associated with grades II–IV acute GVHD (r = 0.547, p < 0.001). The cumulative incidence (CI) of grades II–IV acute GVHD was significantly higher in the PTCy alone group (67.9% vs. 4.8%; p < 0.001). No significant difference in the CI for chronic GVHD was detected between the PTCy plus ATG and PTCy alone groups (72.1% vs. 82.0%; p = 0.730). The CI of 1-year non-relapse mortality was significantly higher in the PTCy alone group than in the PTCy plus ATG group (42.2% vs. 15.9%; p = 0.022). The 1-year overall survival (OS) was significantly better in the PTCy plus ATG group (75.9% vs. 35.3%; p = 0.011). The 1-year GVHD-free, relapse-free survival rate was 29.4% in the PTCy alone group and 54.0% in the PTCy plus ATG group (p = 0.038). Conclusion Serum IL-6 levels were higher in the PTCy alone group than in the PTCy plus ATG group. The addition of ATG before stem cell infusion affected IL-6 levels and reduced the incidences of CRS and grade II–IV acute GVHD in haplo-HSCT patients. This study suggests that PTCy plus ATG as GVHD prophylaxis in haplo-HSCT is beneficial in terms of clinical outcomes and complications of HSCT.

Purpose: Extranodal natural killer/T-cell lymphoma (ENKTL) predominantly manifests in East Asia and Latin America. Despite shared intrinsic factors, such as ethnic and genetic backgrounds, the progression of ENKTL can be influenced by extrinsic factors related to changing lifestyle patterns. Materials and Methods: This study collected stool samples from newly diagnosed (ND)–ENKTL patients (n=40) and conducted whole genome shotgun sequencing. Results: ND-ENKTL revealed reduced alpha diversity in ND-ENKTL compared to healthy controls (HCs) (p=0.008), with Enterobacteriaceae abundance significantly contributing to the beta diversity difference between ENKTL and HCs (p < 0.001). Functional analysis indicated upregulated aerobic metabolism and degradation of aromatic compounds in ND-ENKTL. Enterobacteriaceae were associated not only with clinical data explaining disease status (serum C-reactive protein, stage, prognosis index of natural killer cell lymphoma [PINK], and PINK-E) but also with clinical outcomes (early relapse and short progression-free survival). The relative abundance of Enterobacteriaceae at the family level was similar between ENKTL and diffuse large B-cell lymphoma (DLBCL) (p=0.140). However, the ENKTL exhibited a higher abundance of Escherichia, in contrast to the prevalence of Enterobacter and Citrobacter in DLBCL. Linear regression analysis demonstrated a significant association between Escherichia abundance and programmed cell death-ligand-1 (PD-L1) levels in tissue samples (p=0.025), whereas no correlation with PD-L1 was observed for Enterobacteriaceae at the family level (p=0.571). Conclusion ND-ENKTL exhibited an abundance of Enterobacteriaceae and a dominant presence of Escherichia. These microbial characteristics correlated with disease status, treatment outcomes, and PD-L1 expression, suggesting the potential of the ENKTL microbiome as a biomarker and cause of lymphomagenesis, which warrants further exploration.

Purpose: Thrombosis and bleeding significantly affect morbidity and mortality in myeloproliferative neoplasms (MPNs). The efficacy and safety of direct oral anticoagulants (DOACs) in MPN patients remain uncertain. Materials and Methods: We conducted a large, retrospective, nationwide cohort study using the Korean Health Insurance Review and Assessment Service database from 2010 to 2021. Results: Out of the 368 MPN patients included in the final analysis, 62.8% were treated with DOACs for atrial fibrillation (AF), and 37.2% for venous thromboembolism (VTE). The AF group was statistically older with higher CHA2DS2-VASc (congestive heart failure, hypertension, age ≥ 75 years, diabetes mellitus, prior stroke, transient ischemic attack, or thromboembolism, vascular disease, age 65-74 years, sex category [female]) scores compared to the VTE group. Antiplatelet agents were used in 51.1% of cases, and cytoreductive drugs in 79.3%, with hydroxyurea being the most common (64.9%). The median follow-up was 22.3 months, with 1-year cumulative incidence rates of thrombosis and bleeding at 11.1% and 3.7%, respectively. Multivariate analysis identified CHA2DS2-VASc scores ≥ 3 (hazard ratio [HR], 3.48), concomitant antiplatelet use (HR, 2.57), and cytoreduction (HR, 2.20) as significant thrombosis risk factors but found no significant predictors for major bleeding. Conclusion Despite the limitations of retrospective data, DOAC treatment in MPN patients seems effective and has an acceptable bleeding risk.

Purpose: Some studies suggest that TP53 mutations are associated with the response to immune checkpoint inhibitors (ICI) in patients with non–small cell lung cancer (NSCLC) and also contribute to sex disparities in several cancers. Thus, we hypothesized that TP53 mutations might serve as sex-dependent genomic biomarkers of ICI treatment response in patients with NSCLC. Materials and Methods: Clinical data of 100 patients with metastatic NSCLC treated with ICI monotherapy at Seoul National University Bundang Hospital (SNUBH) were retrospectively reviewed. Genomic and clinical datasets of The Cancer Genome Atlas and an ICI-treated lung cancer cohort (cBioPortal) were also analyzed. Results: In SNUBH cohort, no statistically significant difference was observed in the median progression-free survival (PFS) according to TP53 mutation status (p=0.930); however, female patients with TP53 mutations (MT) had a significantly prolonged median PFS compared to wild-type (WT) (6.1 months in TP53 MT vs. 2.6 months in TP53 WT; p=0.021). Programmed death-ligand 1 (PD-L1) high (≥ 50%) expression was significantly enriched in female patients with TP53 MT (p=0.005). The analysis from publicly available dataset also revealed that females with NSCLC with TP53 MT showed significantly longer PFS than those with TP53 WT (p < 0.001). In The Cancer Genome Atlas analysis, expression of immune-related genes, and tumor mutation burden score in TP53 MT females were higher than in males without TP53 MT. Conclusion Female patients with NSCLC with TP53 mutations had high PD-L1 expression and showed favorable clinical outcomes following ICI therapy, suggesting a need for further research to explore the role of TP53 mutations for sex disparities in response to ICI therapy.

Purpose: This multicenter, open-label, phase II trial evaluated the efficacy and safety of bortezomib combined with dexamethasone for the treatment of relapsed/refractory cutaneous T-cell lymphoma (CTCL) in previously treated patients across 14 institutions in South Korea. Materials and Methods: Between September 2017 and July 2020, 29 patients with histologically confirmed CTCL received treatment, consisting of eight 4-week cycles of induction therapy followed by maintenance therapy, contingent upon response, for up to one year. The primary endpoint was the proportion of patients achieving an objective global response. Results: Thirteen of the 29 patients (44.8%) achieved an objective global response, including two complete responses. The median progression-free survival (PFS) was 5.8 months, with responders showing a median PFS of 14.0 months. Treatment-emergent adverse events were generally mild, with a low incidence of peripheral neuropathy and hematologic toxicities. Despite the trend toward shorter PFS in patients with higher mutation burdens, genomic profiling before and after treatment showed no significant emergence of new mutations indicative of disease progression. Conclusion This study supports the use of bortezomib and dexamethasone as a viable and safe treatment option for previously treated CTCL, demonstrating substantial efficacy and manageability in adverse effects. Further research with a larger cohort is suggested to validate these findings and explore the prognostic value of mutation profiles.

This study aimed to investigate changes in candidemia incidence, species distribution, antifungal susceptibility, initial antifungal use, and mortality trends in Korea before and during the COVID-19 pandemic. A retrospective analysis was conducted on candidemia cases from two tertiary care hospitals in Korea between 2017 and 2022. Data were compared between the pre-pandemic (2017-2019) and pandemic (2020-2022) periods. Statistical methods included incidence rate ratios (IRRs) and multivariate Cox regression to assess 30-day mortality risk factors. A total of 470 candidemia cases were identified, with 48.7% occurring pre-pandemic and 51.3% during the pandemic. While the overall incidence of candidemia remained similar across the two periods (IRR 1.15;p=0.13), the incidence in intensive care units (ICUs) significantly increased during the pandemic (IRR 1.50; p<0.01). The distribution of Candida species did not differ significantly between the two periods. Fluconazole non-susceptibility in C. albicans markedly decreased (10.0% vs. 0.9%, p<0.01), whereas C. glabrata exhibited a significant rise in caspofungin non-susceptibility during the pandemic (0% vs. 22.4%, p<0.01).Echinocandin use increased (21.8% vs. 34.4%; p<0.01), while fluconazole use declined (48.0% vs. 32.8%; p<0.01). Although the 30-day mortality rate was higher during the pandemic (60.2% vs. 57.2%), the difference was not statistically significant (p=0.57).The findings highlight the need for region-specific surveillance and tailored management strategies to improve candidemia outcomes, especially during healthcare disruptions like the COVID-19 pandemic.

Objective: Several miRNAs have been identified as differentially expressed in patients with poor ovarian response (POR) compared to those with normal responses. This study aims to assess the potential of serum miR-329-3p as a biomarker for diagnosing POR. Methods: We conducted a Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis to confirm the target genes of miR-329-3p. KGN cells were transfected with both miR-329-3p mimic and inhibitor to assess the differential expression of these target genes. In accordance with the Bologna criteria, we enrolled 16 control patients and 16 patients with POR. We collected patient samples, including serum from day 2 and the human chorionic gonadotropin (hCG) day, as well as granulosa and cumulus cells, to validate the expression of miR-329-3p using quantitative real-time polymerase chain reaction. Results: KEGG pathway analysis revealed that miR-329-3p targeted adenylyl cyclase 9 (ADCY9) and protein kinase A subunit beta (PRKACB), both of which are involved in ovarian steroidogenesis. In KGN cells treated with a miR-329-3p mimic, ADCY9 and PRKACB expression levels were significantly reduced (p<0.05). Elevated levels of miR-329-3p suppressed aromatase expression and 17β-estradiol production by modulating ADCY9 and PRKACB in KGN cells. These effects were also observed in POR patients. Follicle-stimulating hormone receptor (FSHR) expression was diminished in the granulosa cells of POR patients. On day 2, on hCG day, and in granulosa cells, miR-329-3p exhibited high expression levels in the serum of POR patients. Conclusion miR-329-3p exhibited increased expression in granulosa cells and in the sera of POR patients. Consequently, we propose that miR-329-3p may be a potential biomarker for the diagnosis of POR.

Objective: We aimed to investigate the effectiveness of buspirone as an adjunctive therapy for alleviating anxiety symptoms in patients with depressive disorders who are already taking antidepressants. Methods: This was an open-label prospective multicenter non-interventional observational study conducted over 12 weeks. We enrolled 180 patients diagnosed with depressive disorders according to DSM-5 criteria and Hamilton Anxiety Rating Scale (HAMA) scores ≥ 18. Participants were already taking selective serotonin reuptake inhibitors or serotoninnorepinephrine reuptake inhibitors and were prescribed adjunctive buspirone. Efficacy was assessed using HAMA, Hamilton Depression Rating Scale (HAMD), Clinical Global Impression Scale-Improvement, Clinical Global Impression Scale-Severity, Sheehan Disability Scale (SDS), and WHO-5 Well-Being Index. Results: The efficacy analysis included 161 patients. HAMA scores decreased significantly from 25.2 ± 6.7 at baseline to 15.4 ± 8.6 at 12 weeks (p ＜ 0.001), whereas HAMD scores decreased from 19.4 ± 4.6 to 12.7 ± 5.7 (p ＜ 0.001).WHO-5 and SDS scores showed significant improvements. The HAMA response rate was 39.1% and the remission rate was 13.7% at 12 weeks. Adverse drug reactions were reported in 3.7% of participants. Subgroup analyses showed no significant differences in treatment response based on buspirone dosage, baseline anxiety/depression severity, or benzodiazepine use. Conclusion Adjunctive buspirone therapy effectively improved anxiety symptoms in depressed patients taking antidepressants, regardless of baseline symptom severity or buspirone dosage. The treatment was well-tolerated with few adverse events. Future studies using a control group are needed.