Background: As nationwide government-led whole-genome sequencing (WGS) projects progress, optimizing the clinical integration of large-scale WGS results is crucial. We explored how the initial analysis from Korea’s First WGS Pilot Study for Rare Diseases was applied in clinical practice, and then we reanalyzed the data comprehensively at Samsung Medical Center (SMC) Seoul, Korea. Methods: A prospective cohort study designed to collect WGS data under a Korean national initiative was conducted from August 2020 to December 2021. We focused on patients with rare diseases recruited from 16 university hospitals. The participants included 5,000 individuals (2,200 probands and 2,800 family members). The initial WGS data and diagnostic reference reports (from 682 probands and 484 family members), generated based on the First Korean WGS Pilot Study for Rare Diseases, were subsequently reanalyzed by SMC. Results: The initial analysis of the First Korean WGS Pilot Study data revealed a diagnostic rate of 17%. Upon receiving these results, the SMC conducted two rounds of reanalysis, increasing the diagnostic rate from 15% in the first analysis, to 18% in the second, and finally to 24% in the third (P = 1.6 × 10 −5 ). Key factors in improving the genetic diagnosis included increased detection of novel (likely) pathogenic variants (P = 1.0 × 10 −4 ), improved diagnostic rates with larger family recruitment (P = 0.004), and refined clinical information for more precise genotype–phenotype correlation analysis (40%). Conclusions Although national WGS projects lay a foundation for rare disease diagnosis, hospital-level reanalysis and multidisciplinary collaborations are crucial for optimizing diagnostic outcomes.

Purpose: This study evaluated long-term trends in gastric cancer epidemiology and survival with a focus on conditional relative survival (CRS). Materials and Methods: Using the Korea Central Cancer Registry, we analyzed 665,184 patients who were newly diagnosed with gastric cancer between 1999 and 2022.The study period was divided into four intervals: Period I (1999–2005), Period II (2006–2011), Period III (2012–2017), and Period IV (2018–2022). Temporal trends in the incidence and mortality were assessed using crude and age-standardized rates. Relative survival was estimated using the Ederer II method, and the 5-year CRS was calculated according to the survival duration after diagnosis. Results: The incidence of gastric cancer increased until 2011 and subsequently declined, with a marked decrease observed in 2020. Individuals aged ≥70 years consistently had the highest incidence rates. Mortality rates showed a sustained decline throughout the study period. The overall 5-year relative survival improved from 69.8% in Period II to 78.4% in Period IV. The 5-year CRS increased from 86.1% at 1 year after diagnosis to 96.3% at 5 years.Patients with localized stage maintained a 5-year CRS above 95% at 1 year after diagnosis, whereas those with regional and distant stages showed 5-year CRS that consistently remained below 95%. Conclusions The incidence and mortality rates of gastric cancer in Korea have declined over the past two decades, accompanied by improved survival outcomes. The CRS analysis suggests that long-term follow-up is warranted, with the optimal duration varying according to patient characteristics.

Background/Aims: Spinal cord injury (SCI) frequently impairs defecation, severely affecting the quality of life. This study examines compensatory neural remodeling after SCI, focusing on basal colonic contractility, neural responses to electrical field stimulation, and alterations in excitatory cholinergic and inhibitory nitrergic pathways. Methods: Female Sprague–Dawley rats underwent either sham surgery or T10 spinal cord transection and were categorized into 3 groups: sham, 1-week post-SCI (acute), and 4-week post-SCI (chronic). Colonic contractility was assessed in an organ bath using electrical field stimulation in the presence of a nitric oxide synthase inhibitor. Neural protein expression was analyzed by immunofluorescence and Western blotting. Results: SCI produced region- and time-dependent impairments in colonic contractility, with distinct alterations in the proximal circular and longitudinal muscles across acute and chronic phases. Neural excitability shifted dynamically, showing enhanced excitatory activity in the proximal longitudinal muscle at 1-week and the distal circular muscle at 4-week post-SCI. Protein analysis revealed increased neuronal nitric oxide synthase in the proximal colon, decreasedsoluble guanylyl cyclase in the distal colon, upregulated muscarinic M3 receptor in the proximal colon, and reduced vaso-active intestinal peptide receptor 1 in both proximal and distal regions. Conclusion SCI induces spatiotemporal remodeling of excitatory and inhibitory neural pathways, contributing to colonic dysmotility and revealing potential targets for therapeutic intervention.

Purpose: Skeletal muscle, accounting for approximately 40% of the total body mass, plays a critical role in movement, postural support, and metabolic homeostasis. Muscle mass is determined by the balance between protein synthesis and degradation, which is closely regulated by the mitochondrial function. Mitochondrial dysfunctions contribute to muscle loss by promoting oxidative stress and cellular damage. This study examined the effects of masutakeside I, a lignan glycoside derived from Styrax japonicus, on the mitochondrial function and muscle differentiation in C2C12 myoblasts. Methods: C2C12 myoblasts differentiated into myotubes in the presence of masutakeside I (0–10 ng/mL). Myogenic differentiation was assessed by myosin heavy chain (MHC) immunofluorescence, and multinucleated myotubes and relative diameters were quantified.The mitochondrial function was evaluated by measuring the mitochondrial reactive oxygen species (ROS), mitochondrial mass, and mitochondrial membrane potential using MitoSOX, MitoTracker Green, and JC-1 staining, respectively. Gene expression related to muscle differentiation, protein degradation, and the mitochondrial life cycle was analyzed using quantitative reverse transcription polymerase chain reaction. Results: Masutakeside I significantly increased the number of multinucleated (≥ 5 nuclei) MHC-positive myotubes and relative myotube diameter compared to the control. In addition, masutakeside I upregulated the myogenic markers, including phosphoinositide 3-kinase and MHC isoforms (Myh2, Myh4, and Myh7), while significantly downregulating protein degradation–related genes, including mothers against decapentaplegic homolog 2/3, forkhead box protein O1, atrogin-1, and muscle RING finger-1. Masutakeside I modulated the mRNA expression of the mitochondrial function and mitophagy-related markers, suggesting its potential involvement in mitochondrial quality control. Consistent with these effects, the mitochondrial ROS levels decreased, whereas mitochondrial mass and membrane potential increased. Conclusion These findings suggest that masutakeside I modulates the markers related to myogenic differentiation, muscle protein degradation, and mitochondrial function.

Legal risks and liability issues in medical practice serve as a primary catalyst for the current collapse of essential healthcare services in Korea. Currently, medical disputes in Korea are disproportionately focused on criminal prosecutions and high-damages civil litigation. This punitive approach fosters a culture of concealment, encourages defensive medicine, and accelerates the exodus of medical professionals from essential fields. Ultimately, this cycle deprives the system of opportunities for improvement and poses a significant threat to patient safety. In contrast, many advanced nations have adopted principles of “Just Culture” and “Safe Space,” prioritizing non-punitive reporting and systemic root-cause analysis over individual retribution. To address these issues, this paper proposes four key strategies: First, the establishment of an independent “Patient Safety Investigation Agency” to objectively investigate incidents and identify systemic flaws. Second, a transition from criminal punishment to licensing board-led management, focusing on re-education and counseling to maintain quality of care. Third, the enactment of “Apology Laws” to ensure that expressions of regret or apologies cannot be used as legal evidence of liability, thereby fostering trust and psychological recovery. Finally, the creation of a “Patient Safety Fund” to provide prompt and sufficient public compensation to victims regardless of proven negligence. In conclusion, it is imperative to shift the paradigm by defining medical accidents as “system failures” rather than individual faults. Strengthening the social safety net will encourage medical professionals to return to essential care and build a sustainable healthcare environment centered on patient safety.

South Korea’s current healthcare system stands at a critical crossroads that will determine whether it can progress in a better direction over the next decade. Behind the relatively stable level of population health that has been maintained until now, it has become clear that the deterioration of patient experiences, the risk of collapse in critical emergency medical services, the burnout of healthcare providers, and the crisis in the sustainability of healthcare finances have all accumulated simultaneously. This crisis can no longer be overcome by partial fixes or short-term measures alone. The answer to what needs to change first must begin with a reaffirmation of what the healthcare system should aim for. Ultimately, what needs to be changed now is not an individual policy, but the criteria and priorities through which we view healthcare. The focus must shift from what to provide more of, to questioning what holds greater social value. If such a shift does not begin now, in ten years we won’t face a better healthcare system, but care enmeshed in a deeper crisis. Now is precisely the time to fundamentally define the direction of the healthcare system.

Background: A systematic evaluation of potential living liver donors is essential to ensure donor safety and optimize recipient outcomes in living donor liver transplantation (LDLT). This study aimed to assess donor acceptance rates and reasons for disqualification among individuals evaluated for LDLT at a high-volume transplant center over a one-year period. Methods: We retrospectively reviewed 1,087 potential living liver donors who presented for LDLT evaluation in 2023. Of these, 991 candidates advanced beyond the initial screening (Stage 1) and underwent comprehensive clinical, imaging, and pathological assessments (Stages 2 and 3). Candidates who discontinued after Stage 1 were excluded due to the absence of documented reasons for non-progression. Results: Among the 991 candidates who proceeded beyond initial screening, 473 (47.7%) completed the full donor evaluation, of whom 466 were judged to be suitable donors. Among suitable donors, 384 (82.4%) proceeded to donor hepatectomy, whereas 82 did not, primarily due to recipient-related factors such as clinical deterioration or withdrawal of consent. Donor ineligibility was determined in 422 candidates (42.6%), most commonly due to inadequate remnant liver volume (52.8%), hepatic steatosis (20.6%), and insufficient graft size (10.2%). Among candidates undergoing Stage 2 evaluation, 162 (16.3%) failed to meet steatosis criteria; 126 were excluded solely for steatosis and advised weight reduction, and 39 subsequently became eligible and successfully donated. Conclusion In this high-volume LDLT center, donor disqualification was primarily driven by remnant liver volume and hepatic steatosis. Targeted interventions such as weight reduction enabled successful donation in a subset of initially ineligible candidates, underscoring the importance of individualized donor evaluation and pre-donation optimization.

Background: Inferior orbital blowout fractures (BOF) cause ocular symptoms like diplopia and extraocular muscle limitation, influenced by inferior rectus muscle (IRM) status. This study evaluated the relationship between preoperative IRM status on computed tomography (CT) and ocular symptom recovery time. Methods: This retrospective study analyzed 127 patients with inferior BOF and ocular symptoms (2012–2024). Inclusion criteria included age 18–80 years and preoperative CT availability. IRM status was assessed for bone interruption, herniation extent, and swelling (short/ long axis ratio < 0.54 or ≥ 0.54). Recovery times were analyzed using t-tests and Kaplan-Meier survival analysis (p< 0.05). Results: Of 127 patients (mean age, 35 years; 67.7% male), 66 (52.0%) recovered from ocular symptoms within 7 days, 53 (41.7%) within 30–90 days, and eight (6.3%) had diplopia that remained as a permanent sequela at the last follow-up. Diplopia recovery time was longer in IRM–bone contact (16.9± 5.5 days, n= 35) and bone-pierced IRM (29.4± 10.3 days, n= 15) groups versus no-contact (5.1± 4.2 days, n= 77; p= 0.02, t-test). Herniation and swelling showed no significant correlation (p> 0.05). Conclusion Preoperative CT-based assessment of the IRM–bone interface predicts diplopia recovery time, with bone-pierced IRM linked to prolonged recovery. Patients with bone-pierced IRM may require closer follow-up and careful consideration of timely surgical management.

Chrysoeriol, a flavonoid naturally found in several plants, including Danggui Susan, a traditional herbal medicine, exhibits promising anti-inflammatory and antioxidant properties. Its potential to prevent cardiovascular diseases, primarily through inhibiting platelet activation and aggregation, has attracted significant interest. This study aimed to investigate the molecular mechanisms underlying the antiplatelet effects of chrysoeriol. The compound effectively suppressed collagen-induced platelet aggregation without inducing cytotoxicity. Chrysoeriol elevated intracellular levels of cyclic AMP (cAMP) and cyclic GMP (cGMP), enhanced inositol 1,4,5-trisphosphate receptor (IP 3R) phosphorylation, and reduced cytosolic calcium (Ca2+ ) mobilization, all of which contributed to its antiplatelet action. Furthermore, chrysoeriol inhibited the phosphorylation of PI3K, Akt, JNK, and p38 MAPK, pathways involved in the activation of cytosolic phospholipase A2 (cPLA 2) and thromboxane A2 (TXA2) production. These effects were accompanied by reduced TXA2 production and secretion of dense granules (ATP and serotonin). Chrysoeriol also impaired thrombin-induced clot retraction, further suggesting its capacity to regulate platelet responses and cytoskeletal rearrangements. These findings highlight chrysoeriol’s multi-target mechanisms, including modulation of cyclic nucleotides, kinase pathways, and platelet function, offering potential as a therapeutic agent to prevent thrombotic cardiovascular events.

Autophagy is a conserved catabolic process that degrades proteins and damaged organelles to maintain cellular homeostasis, and its role in cancer depends on stage and context. Farnesyl-diphosphate farnesyltransferase 1 (FDFT1) is an essential enzyme in the sterol branch of the mevalonate pathway, but its functions in hepatocellular carcinoma (HCC) and in the regulation of autophagy remain poorly understood. In this study, we show that FDFT1 acts as a negative regulator of autophagy in HCC cells. Loss of FDFT1 led to increased autophagosome formation and fusion with lysosomes, whereas its overexpression suppressed both basal and induced autophagy. These changes were associated with AMPK–ULK1 signaling, suggesting that FDFT1 influences a central pathway controlling autophagy. Our findings connect cholesterol metabolism with autophagy regulation and tumor growth, highlighting FDFT1 as a potential prognostic marker and therapeutic target in liver cancer.