BACKGROUND: Bone defects are commonly encountered due to accidents, diseases, or aging, and the demand for effective bone regeneration, particularly for dental implants, is increasing in our aging society. Mesenchymal stem cells (MSCs) are promising candidates for regenerative therapies; however, obtaining sufficient quantities of these cells for clinical applications remains challenging. DW-MSCs, derived from embryonic stem cells and developed by Daewoong Pharmaceutical, exhibit a robust proliferative capacity even after extensive culture. METHODS: This study explores the therapeutic potential of DW-MSCs in various animal models of bone defects. DWMSCs were expanded for over 13 passages for in vivo use in rat and canine models of bone defects and osteomyelitis. The research focused on the in vivo osteogenic differentiation of DW-MSCs, the establishment of a fibrin-based system for bone regeneration, the assessment of bone repair following treatment in animal models, and comparisons with commercially available bone grafts. RESULTS: Results showed that DW-MSCs exhibited superior osteogenic differentiation compared to other materials, and the fibrinization process not only preserved but enhanced their proliferation and differentiation capabilities through a 3D culture effect. In both bone defect models, DW-MSCs facilitated significant bone regeneration, reduced inflammatory responses in osteomyelitis, and achieved effective bone healing. The therapeutic outcomes of DW-MSCs were comparable to those of commercial bone grafts but demonstrated qualitatively superior bone tissue restructuring. CONCLUSION Our findings suggest that DW-MSCs offer a promising approach for bone regeneration therapies due to their high efficacy and anti-inflammatory properties.

To investigate the relationship between depression and AD, water avoidance stress (WAS) was induced for 10 days in both Tg2576 mice and wild-type (WT) mice. After WAS, memory function and depressive-like behavior were investigated in Tg2576 mice. Tg2576 WAS mice exhibited more depressive-like behaviors than WT WAS and Tg2576 control (CON) mice. Strikingly, Tg2576 CON mice showed more depressive-like behaviors than WT mice. Moreover, corticosterone and phospho-glucocorticoid receptor (p-GR) levels were also higher in Tg2576 WAS mice in comparison to Tg2576 CON mice. Spinster homologue 2 (SPNS2) is a member of non-ATP-dependent transporter. The role of SPNS2 was widely known as a sphingosine-1-phosphate (S1P) transporter, which export intracellular S1P from cells. Using GEO database to analyze SPNS2 gene expression changes in patients with AD and depression, we show that SPNS2 gene expression correlates with AD and depression. Interestingly, Tg2576 WAS mice displayed significantly increased levels of SPNS2 w1hen compared to Tg2576 CON counterparts. SPNS2 levels were also higher in Tg2576 CON mice in comparison with WT CON mice. Remarkably, we found a decrease in S1P brain levels and an increase in S1P serum levels of Tg2576 WAS mice in comparison with Tg2576 CON mice. Accordingly, WAS induced group further decreased S1P levels in the brains. However, the level in the serum further increased in comparison with non-induced group. Therefore, these results suggest that AD and depression could be associated, and that Tg2576 transgenic mice are more susceptible to stress-induced depression through the release of S1P by SPNS2 up-regulation.

Purpose: Considering the high disease burden and unique features of Asian patients with breast cancer (BC), it is essential to have a comprehensive view of genetic characteristics in this population. An institutional targeted sequencing platform was developed through the Korea Research-Driven Hospitals project and was incorporated into clinical practice. This study explores the use of targeted next-generation sequencing (NGS) and its outcomes in patients with advanced/metastatic BC in the real world. Materials and Methods: We reviewed the results of NGS tests administered to BC patients using a customized sequencing platform—FiRST Cancer Panel (FCP)—over 7 years. We systematically described clinical translation of FCP for precise diagnostics, personalized therapeutic strategies, and unraveling disease pathogenesis. Results: NGS tests were conducted on 548 samples from 522 patients with BC. Ninety-seven point six percentage of tested samples harbored at least one pathogenic alteration. The common alterations included mutations in TP53 (56.2%), PIK3CA (31.2%), GATA3 (13.8%), BRCA2 (10.2%), and amplifications of CCND1 (10.8%), FGF19 (10.0%), and ERBB2 (9.5%). NGS analysis of ERBB2 amplification correlated well with human epidermal growth factor receptor 2 immunohistochemistry and in situ hybridization. RNA panel analyses found potentially actionable and prognostic fusion genes. FCP effectively screened for potentially germline pathogenic/likely pathogenic mutation. Ten point three percent of BC patients received matched therapy guided by NGS, resulting in a significant overall survival advantage (p=0.022), especially for metastatic BCs. Conclusion Clinical NGS provided multifaceted benefits, deepening our understanding of the disease, improving diagnostic precision, and paving the way for targeted therapies. The concrete advantages of FCP highlight the importance of multi-gene testing for BC, especially for metastatic conditions.

Background: The positive relationship between triiodothyronine (T3) and steatotic liver disease (SLD) demonstrated only in crosssectional study. We aimed to evaluated whether total T3 (TT3) is associated with the development/resolution of SLD in longitudinal design. Methods: This retrospective, longitudinal, population-based cohort study included 1,665 South Korean euthyroid adults with ≥4 thyroid function test. We explored the impact of mean TT3 during follow-up on development/resolution of either SLD (diagnosed by ultrasound) or modified metabolic dysfunction-associated steatotic liver disease (MASLD) using Cox proportional hazards regression models. Results: During about median 5 years follow-up, 807/1,216 (66.3%) participants among participants without SLD at baseline developed SLD, and 253/318 (79.5%) participants among participants with SLD at baseline SLD resolved fatty liver. Mean TT3 rather than thyroid stimulating hormone or mean free thyroxine was significantly related with development (adjusted hazard ratio [HR], 1.01; 95% confidence interval [CI], 1.00 to 1.02; P=0.002) and resolution (adjusted HR, 0.97; 95% CI, 0.96 to 0.99; P=0.005) of SLD. Compared with low mean TT3 group, high mean TT3 group was positively associated with development of SLD (adjusted HR, 1.20; 95% CI, 1.05 to 1.38; P=0.008) and inversely associated with resolution of SLD (adjusted HR, 0.66; 95% CI, 0.51 to 0.85; P=0.001). The statistical significance remained for development (adjusted HR, 1.29; 95% CI, 1.10 to 1.51; P=0.001) and resolution (adjusted HR, 0.71; 95% CI, 0.54 to 0.94; P=0.018) of modified MASLD. Conclusion In Korean euthyroid adults, TT3 level was associated with development and resolution of either SLD or modified MASLD.

Purpose: This study evaluated the postoperative quality of life (QoL) after various types of gastrectomy for gastric cancer. Materials and Methods: A multicenter prospective observational study was conducted in Korea using the Korean Quality of Life in Stomach Cancer Patients Study (KOQUSS)-40, a new QoL assessment tool focusing on postgastrectomy syndrome. Overall, 496 patients with gastric cancer were enrolled, and QoL was assessed at 5 time points: preoperatively and at 1, 3, 6, and 12 months after surgery. Results: Distal gastrectomy (DG) and pylorus-preserving gastrectomy (PPG) showed significantly better outcomes than total gastrectomy (TG) and proximal gastrectomy (PG) with regard to total score, indigestion, and dysphagia. DG, PPG, and TG also showed significantly better outcomes than PG in terms of dumping syndrome and worry about cancer. Postoperative QoL did not differ significantly according to anastomosis type in DG, except for Billroth I anastomosis, which achieved better bowel habit change scores than the others. No domains differed significantly when comparing double tract reconstruction and esophagogastrostomy after PG. The total QoL score correlated significantly with postoperative body weight loss (more than 10%) and extent of resection (P<0.05 for both).Reflux as assessed by KOQUSS-40 did not correlate significantly with reflux observed on gastroscopy 1 year postoperatively (P=0.064). Conclusions Our prospective observation using KOQUSS-40 revealed that DG and PPG lead to better QoL than TG and PG. Further study is needed to compare postoperative QoL according to anastomosis type in DG and PG.

Gastric cancer is one of the most common cancers in both Korea and worldwide. Since 2004, the Korean Practice Guidelines for Gastric Cancer have been regularly updated, with the 4th edition published in 2022. The 4th edition was the result of a collaborative work by an interdisciplinary team, including experts in gastric surgery, gastroenterology, endoscopy, medical oncology, abdominal radiology, pathology, nuclear medicine, radiation oncology, and guideline development methodology. The current guideline is the 5th version, an updated version of the 4th edition. In this guideline, 6 key questions (KQs) were updated or proposed after a collaborative review by the working group, and 7 statements were developed, or revised, or discussed based on a systematic review using the MEDLINE, Embase, Cochrane Library, and KoreaMed database. Over the past 2 years, there have been significant changes in systemic treatment, leading to major updates and revisions focused on this area.Additionally, minor modifications have been made in other sections, incorporating recent research findings. The level of evidence and grading of recommendations were categorized according to the Grading of Recommendations, Assessment, Development and Evaluation system. Key factors for recommendation included the level of evidence, benefit, harm, and clinical applicability. The working group reviewed and discussed the recommendations to reach a consensus. The structure of this guideline remains similar to the 2022 version.Earlier sections cover general considerations, such as screening, diagnosis, and staging of endoscopy, pathology, radiology, and nuclear medicine. In the latter sections, statements are provided for each KQ based on clinical evidence, with flowcharts supporting these statements through meta-analysis and references. This multidisciplinary, evidence-based gastric cancer guideline aims to support clinicians in providing optimal care for gastric cancer patients.

Background: Because of the low prevalence of inherited retinal diseases, reports on the distribution of retinitis pigmentosa (RP)-related genes in Korean patients are scarce. The aim of this study was to determine the mutation spectrum and allele frequency and observe the final diagnoses in a Korean cohort clinically diagnosed with RP. Methods: We used whole-exome sequencing (WES) to analyze a Korean cohort of 100 unrelated patients clinically diagnosed with RP. The possible pathogenicity of each variant was assessed based on the guidelines of the American College of Medical Genetics and Genomics and Association for Molecular Pathology, in-silico prediction tools, known clinical phenotypes, and inheritance patterns. Results: Definite causative genes were detected in 60/100 patients (60.0%). Of these 60 cases, USH2A was the most common causative gene (14/60, 23.3%), followed by EYS (13/60, 21.7%) and RP1 (6/60, 10.0%). The clinical diagnosis was redefined in 9 of the 60 probands (15.0%) with causative genes after WES. Five of the 60 patients (8.3%) carried a causative variant in CHM, and the clinical diagnosis was redefined as choroideremia. Leber congenital amaurosis was diagnosed in 2/60 probands (3.3%), and RDH12 and RPGRIP1 were the causative genes in each patient. One patient (1/60, 1.7%) was diagnosed with Bietti’s crystalline dystrophy, with CYP4V2 identified as the causative gene. In another patient (1/60, 1.7%), ABCA4 variants were detected with clinical findings suggestive of cone-rod dystrophy. Conclusion This study reports the mutational spectrum of a cohort of Korean patients with a clinical diagnosis of RP who were referred for genetic testing. This study adds valuable data regarding the frequency of genes as well as their relation to the age of symptom onset and relation to other inherited retinal degenerations.

Objective: Acute coronary syndrome often requires urgent intervention. The 2023 European Society of Cardiology guidelines recommend invasive procedures within 24 hours for high-risk cases. Nevertheless, there have been limited studies on non-ST-segment elevation myocardial infarction (NSTEMI) in South Korea. This study compared the risk of complications based on the timing of intervention. Methods: A retrospective observational study was conducted on patients with chest pain and elevated high-sensitivity troponin T from January to December 2021 in the emergency department. Patients were categorized into early (≤24 hr) and late (>24 hr) intervention groups. Primary outcomes (death, restenosis, or stroke) at 12 months were compared. Survival and subgroup analyses were performed to examine the factors affecting the outcomes in the two groups. Results: Three hundred seventy six patients were enrolled in the study, and 115 patients were excluded. Among 261 patients, 106 and 155 patients were in the early intervention group (≤24 hr), and late intervention group (>24 hr), respectively. The primary outcome (death or restenosis) showed no significant difference (hazard ratio [HR] in the early intervention group at 12 mo; 1.03; 95% confidence interval [CI], 0.63-1.70; P=0.905). However, risk of stroke was lower in the early intervention group (HR in the early, 0.08; 95% CI, 0.00-0.66; P=0.013). Subgroup analysis showed no significant advantage for early intervention. Conclusion In NSTEMI patients, early intervention does not reduce death or restenosis but lowers stroke incidence. No specific risk factors favored early intervention.

Objective: To analyze the relationship between pelvic organ prolapse (POP) and menopausal hormone therapy (MHT). Methods: This retrospective cohort study used Korean National Health checkup and insurance data from 2002 to 2019. Women who used MHT for more than 6 months between 2002 and 2011 were included in the MHT group; postmenopausal women with no MHT use comprised the non-MHT group. Results: In the non-MHT group, there were 1,001,350 women, while the MHT group had 353,206 women. Tibolone (adjusted hazard ratio [aHR], 0.87; 99% confidence interval [CI], 0.818-0.926) and combined estrogen plus progestin by the manufacturer (CEPM) (aHR, 0.821; 99% CI, 0.758-0.89) were associated with reduced POP risk. The other oral MHT groups and the transdermal estrogen group showed no significant difference in POP risk compared with the non-MHT group (other oral MHT: aHR, 1.045; 99% CI, 0.941-1.161) (transdermal estrogen: aHR, 1.252; 99% CI, 0.731-2.145). Lower body mass index (BMI) (<18.5) was associated with reduced POP risk (aHR, 0.822; 99% CI, 0.698-0.968), while a BMI between 23 and 29.9 was associated with increased risk (BMI 23-24.9: aHR, 1.143; 99% CI, 1.088-1.2) (BMI 25-29.9: aHR, 1.173; 99% CI, 1.12-1.228). All parities had a higher POP risk than parity 1 (parity 0 or no response: aHR, 1.785; 99% CI, 1.589-2.005; parity 2: aHR, 1.434; 99% CI, 1.292-1.592; parity ≥3: aHR, 1.916; 99% CI, 1.712-2.144). Conclusion Tibolone and CEPM use were associated with reduced POP risk in postmenopausal women. Other MHT types showed no significant association with POP.

Objective: To analyze the relationship between pelvic organ prolapse (POP) and menopausal hormone therapy (MHT). Methods: This retrospective cohort study used Korean National Health checkup and insurance data from 2002 to 2019. Women who used MHT for more than 6 months between 2002 and 2011 were included in the MHT group; postmenopausal women with no MHT use comprised the non-MHT group. Results: In the non-MHT group, there were 1,001,350 women, while the MHT group had 353,206 women. Tibolone (adjusted hazard ratio [aHR], 0.87; 99% confidence interval [CI], 0.818-0.926) and combined estrogen plus progestin by the manufacturer (CEPM) (aHR, 0.821; 99% CI, 0.758-0.89) were associated with reduced POP risk. The other oral MHT groups and the transdermal estrogen group showed no significant difference in POP risk compared with the non-MHT group (other oral MHT: aHR, 1.045; 99% CI, 0.941-1.161) (transdermal estrogen: aHR, 1.252; 99% CI, 0.731-2.145). Lower body mass index (BMI) (<18.5) was associated with reduced POP risk (aHR, 0.822; 99% CI, 0.698-0.968), while a BMI between 23 and 29.9 was associated with increased risk (BMI 23-24.9: aHR, 1.143; 99% CI, 1.088-1.2) (BMI 25-29.9: aHR, 1.173; 99% CI, 1.12-1.228). All parities had a higher POP risk than parity 1 (parity 0 or no response: aHR, 1.785; 99% CI, 1.589-2.005; parity 2: aHR, 1.434; 99% CI, 1.292-1.592; parity ≥3: aHR, 1.916; 99% CI, 1.712-2.144). Conclusion Tibolone and CEPM use were associated with reduced POP risk in postmenopausal women. Other MHT types showed no significant association with POP.