Background: s/Aims: Hepatocellular carcinoma (HCC) is a malignant cancer with an increasing incidence worldwide. Although numerous efforts have been made to identify effective therapies for HCC, current strategies have limitations. We present a new approach for targeting L-arginine and argininosuccinate synthetase 1 (ASS1). Methods: ASS1 expression in HCC cell lines and primary hepatocytes was detected using polymerase chain reaction and western blotting. Proliferation, migration, signaling pathways, and nitric oxide production in HCC cell lines were measured using MTS, colony formation, wound healing, Western blot, and Griess assays. Results: ASS1 expression varied among the HCC cell lines, and cisplatin cytotoxicity was ASS1-dependent. L-arginine alone induced apoptosis in HCC cell lines, regardless of ASS1 expression; however, its effect was enhanced in ASS1-expressing HCC cell lines. Cisplatin cytotoxicity also increased, suggesting that L-arginine acts as a sensitizer to cisplatin in HCC cell lines. ASS1 and L-arginine produced nitric oxide and inhibited key proliferation- and survival-related signaling pathways such as PI3K/Akt and MAPK. Additionally, ASS1 and L-arginine reduced the expression of PKM1 and PKM2 in the glycolysis pathway. Conclusions Our study revealed that ASS1 and L-arginine exhibited anticancer effects in HCC and sensitized cisplatin-resistant HCC cells to chemotherapy. The combination of ASS1 and L-arginine significantly enhanced the anticancer effects, even in HCC cell lines with low or absent ASS1 expression. These findings highlight the critical roles of arginine and ASS1 in HCC and suggest that increasing arginine availability could be a promising therapeutic strategy.

Genetic kidney diseases are caused by mutations in specific genes that significantly affect kidney development and function. Although the underlying pathogenic genes of many kidney diseases have been identified, an understanding of their mechanisms and effective treatments remains limited. Gene editing, particularly using clustered regularly interspaced short palindromic repeats (CRISPR), has recently become a promising approach for studying genetic diseases and the CRISPR/CRISPR-associated protein 9 (CRISPR-Cas9) method has become a prominent research method. It has been shown that CRISPR-Cas9 can be targeted to knock out specific genomic sites, which enables researchers to correct gene mutations, prevent inheritance, and better understand the function of genes and the effectiveness of drugs. However, the application of CRISPR-Cas9 technology in the development of therapeutic agents against genetic kidney disease has been overlooked compared with other genetic diseases. In this paper, we provide an overview of the current research advancements in genetic kidney diseases using CRISPR technology, as well as the diverse preclinical research methods implemented, with particular emphasis on autosomal dominant polycystic kidney disease.

Objective: This study investigated how educational levels modify the relationship between the standard deviation of NN intervals (SDNN) of heart rate variability and the development of post-traumatic stress disorder (PTSD). Methods: Participants with physical injuries were enrolled from a trauma center and monitored over two years. Initial assessments included SDNN and educational attainment, along with socio-demographic and clinical variables. PTSD diagnoses were made at 3, 6, 12, and 24 months post-injury using the Clinician-Administered PTSD Scale for DSM-5.Logistic regression analyses were conducted. Results: Of the 538 participants, 58 (10.8%) developed PTSD during the follow-up period. A significant interaction effect was observed: lower SDNN was significantly linked to PTSD in individuals with higher education, but not in those with lower education. Conclusion The study identified education-dependent associations between SDNN and PTSD development, emphasizing the importance of tailored PTSD prevention strategies that consider both SDNN and educational levels.

Background: This study aimed to compare the intraoperative stability and early clinical outcomes of 40-mm diameter dual mobility (DM)-total hip arthroplasty (THA) with 36-mm ceramic head (large head) THA in active elderly patients with hip fractures. Methods: A prospective randomized controlled trial was conducted from May 2022 to December 2022. Inclusion criteria were as follows: age ≥ 60 years, displaced femoral neck fracture, Koval grade 1 or 2, planned 54-mm acetabular component, and over 1-year follow-up. Intraoperative stability tests were performed on all patients (internal rotation at 45°, 60°, and 90° of hip fracture). Functional outcomes (Harris Hip Score and University of California, Los Angeles [UCLA] Score) were evaluated at 6 weeks and 3 months postoperatively. Gait analysis using artificial intelligence (AI) techniques was conducted at 3 months postoperatively. Results: The study included 36 DM-THA patients (mean age, 69.6 ± 2.2 years; 44% women) and 37 large head THA patients (mean age, 69.6 ± 1.2 years; 64% women). No statistically significant differences were observed in functional outcomes and hip range of motion between the 2 groups. However, there was a significant difference in the gait speed and stance-swing phase of the large head THA group and the DM-THA group: the DM-THA group demonstrated superior gait speed (2.85 ± 0.83 kph vs. 2.04 ± 1.04 kph, p = 0.003) and higher stance phase ratios (operated side: 63.57% ± 3.82% vs. 48.19% ± 5.50%, p < 0.001; opposite side: 62.77% ± 2.27% vs. 49.93% ± 6.94%, p < 0.001). In the stability test at 90° of hip flexion, the DM-THA group had a measurement of 48.40° ± 5.17°, while the large head THA group had a measurement of 30.94° ± 2.98° (p = 0.012). Despite the lack of statistical significance, the intraoperative stability test showed the dislocation angle was notably different between the groups in the hip flexion position of 60° (51.60° ± 6.09° in the DM-THA group and 40.00° ± 2.80° in the large head THA group, p = 0.072). Conclusions Superior results were observed in the intraoperative stability test and early recovery of gait after DM-THA compared to large head THA. We believe that DM-THA can be a useful surgical option for THA in elderly patients with hip fractures.

Background: and Purpose: This clinical practice guideline provides evidence-based recommendations for treatment of dementia, focusing on cholinesterase inhibitors and N-methyl-D-aspartate (NMDA) receptor antagonists for Alzheimer’s disease (AD) and other types of dementia. Methods: Using the Population, Intervention, Comparison, Outcomes (PICO) framework, we developed key clinical questions and conducted systematic literature reviews. A multidisciplinary panel of experts, organized by the Korean Dementia Association, evaluated randomized controlled trials and observational studies. Recommendations were graded for evidence quality and strength using Grading of Recommendations, Assessment, Development, and Evaluation (GRADE) methodology. Results: Three main recommendations are presented: (1) For AD, cholinesterase inhibitors (donepezil, rivastigmine, galantamine) are strongly recommended for improving cognition and daily function based on moderate evidence; (2) Cholinesterase inhibitors are conditionally recommended for vascular dementia and Parkinson’s disease dementia, with a strong recommendation for Lewy body dementia; (3) For moderate to severe AD, NMDA receptor antagonist (memantine) is strongly recommended, demonstrating significant cognitive and functional improvements. Both drug classes showed favorable safety profiles with manageable side effects. Conclusions This guideline offers standardized, evidence-based pharmacologic recommendations for dementia management, with specific guidance on cholinesterase inhibitors and NMDA receptor antagonists. It aims to support clinical decision-making and improve patient outcomes in dementia care. Further updates will address emerging treatments, including amyloid-targeting therapies, to reflect advances in dementia management.

Emerging evidence suggests that systemic inflammation may play a critical role in neurological disorders. Recent studies have shown the connection between inflammatory bowel diseases (IBD) and neurological disorders, revealing a bidirectional relationship through the gut-brain axis.Immunotherapies, such as Treg cells infusion, have been proposed for IBD. However, the role of adaptive immune cells in IBD-induced neuroinflammation remains unclear. In this study, we established an animal model for IBD in mice with severe combined immune-deficient (SCID), an adaptive immune deficiency, to investigate the role of adaptive immune cells in IBD-induced neuroinflammation. Mice were fed 1%, 3%, or 5% dextran sulfate sodium (DSS) for 5 days. We measured body weight, colon length, disease activity index (DAI), and crypt damage. Pro-inflammatory cytokines were measured in the colon, while microglial morphology, neuronal count, and inflammatory cytokines were analyzed in the brain. In the 3% DSS group, colitis symptoms appeared at day 7, with reduced colon length and increased crypt damage showing colitis-like symptoms. By day 21, colon length and crypt damage persisted, while DAI showed recovery. Although colonic inflammation peaked at day 7, no significant increase in inflammatory cytokines or microglial hyperactivation was observed in the brain. By day 21, neuroinflammation was detected, albeit with a slight delay, in the absence of adaptive immune cells. The colitis-induced neuroinflammation model provides insights into the fundamental immune mechanisms of the gut-brain axis and may contribute to developing immune cell therapies for IBD-induced neuroinflammation.

Background: and Purpose Treatments for neuromyelitis optica spectrum disorder (NMOSD) such as eculizumab, ravulizumab, satralizumab, and inebilizumab have significantly advanced relapse prevention, but they remain expensive. Rituximab is an off-label yet popular alternative that offers a cost-effective solution, but its real-world efficacy needs better quantification for guiding the application of newer approved NMOSD treatments (ANTs). This study aimed to determine real-world rituximab failure rates to anticipate the demand for ANTs and aid in resource allocation. Methods: We conducted a nationwide retrospective study involving 605 aquaporin-4-antibody-positive NMOSD patients from 22 centers in South Korea that assessed the efficacy and safety of rituximab over a median follow-up of 47 months. Results: The 605 patients treated with rituximab included 525 (87%) who received continuous therapy throughout the follow-up period (median=47 months, interquartile range=15–87 months). During this period, 117 patients (19%) experienced at least 1 relapse. Notably, 68 of these patients (11% of the total cohort) experienced multiple relapses or at least 1 severe relapse.Additionally, 2% of the patients discontinued rituximab due to adverse events, which included severe infusion reactions, neutropenia, and infections. Conclusions This study has confirmed the efficacy of rituximab in treating NMOSD, as evidenced by an 87% continuation rate among patients over a 4-year follow-up period. Nevertheless, the occurrence of at least one relapse in 19% of the cohort, including 11% who experienced multiple or severe relapses, and a 2% discontinuation rate due to adverse events highlight the urgent need for alternative therapeutic options.

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.

Purpose: Since 1995, the Korean Gastric Cancer Association (KGCA) has been periodically conducting nationwide surveys on patients with surgically treated gastric cancer. This study details the results of the survey conducted in 2023. Materials and Methods: The survey was conducted from March to December 2024 using a standardized case report form. Data were collected on 86 items, including patient demographics, tumor characteristics, surgical procedures, and surgical outcomes. The results of the 2023 survey were compared with those of previous surveys. Results: Data from 12,751 cases were collected from 66 institutions. The mean patient age was 64.6 years, and the proportion of patients aged ≥71 years increased from 9.1% in 1995 to 31.7% in 2023. The proportion of upper-third tumors slightly decreased to 16.8% compared to 20.9% in 2019. Early gastric cancer accounted for 63.1% of cases in 2023.Regarding operative procedures, a totally laparoscopic approach was most frequently applied (63.2%) in 2023, while robotic gastrectomy steadily increased to 9.5% from 2.1% in 2014.The most common anastomotic method was the Billroth II procedure (48.8%) after distal gastrectomy and double-tract reconstruction (51.9%) after proximal gastrectomy in 2023.However, the proportion of esophago-gastrostomy with anti-reflux procedures increased to 30.9%. The rates of post-operative mortality and overall complications were 1.0% and 15.3%, respectively. Conclusions The results of the 2023 nationwide survey demonstrate the current status of gastric cancer treatment in Korea. This information will provide a basis for future gastric cancer research.