BACKGROUND/OBJECTIVES: Obesity is a complex metabolic disorder characterized by excessive adipose tissue accumulation, dysregulated lipid metabolism, and insulin resistance, leading to an increased risk of metabolic disease. While Withania somnifera (AS) and Chrysanthemum zawadskii Herbich var. latilobum (Maxim.) Kitamura (C) have traditionally been used for their metabolic regulatory properties, their combined effects on adipogenesis, lipogenesis, lipolysis, and insulin signaling remain unexplored. Therefore, this study aimed to evaluate the anti-obesity effects of AS, C, and their optimal combination (ASC) in 3T3-L1 adipocytes by investigating their impact on lipid metabolism and glucose homeostasis.MATERIALS/METHODS: Following adipogenic differentiation, 3T3-L1 adipocytes were treated with AS, C, and ASC at different concentrations. RESULTS: AS, C, and ASC significantly inhibited adipogenesis by downregulating cyclic adenosine monophosphate (cAMP) response element-binding protein, peroxisome proliferator-activated receptor gamma, CCAAT/enhancer-binding proteins alpha and beta phosphorylation, thereby reducing lipid accumulation in adipocytes. They also suppressed lipogenesis by downregulating the expression of dephosphorylated acetyl-CoA carboxylase, fatty acid synthase, and lipoprotein lipase. In contrast, they markedly enhanced lipolysis, as evidenced by increased hormone-sensitive lipase and protein kinase A expression, along with elevated glycerol release and cAMP levels. Furthermore, AS, C, and ASC activated energy metabolism pathways, as indicated by the upregulation of AMP-activated protein kinase, uncoupling protein 1, and carnitine palmitoyltransferase 1A, suggesting a transition toward enhanced mitochondrial fatty acid oxidation. Notably, AS, C, and ASC significantly improved insulin signaling by restoring insulin receptor substrate 1, phosphoinositide 3-kinase, and Akt phosphorylation, while upregulating glucose transporter type 4 expression, indicating enhanced glucose uptake. Among all treatments, ASC showed relatively greater efficacy compared to AS or C alone, suggesting a potential additive effect. CONCLUSION These findings demonstrate that ASC effectively modulates multiple metabolic pathways in adipocytes, including adipogenesis, lipogenesis, lipolysis, energy metabolism, and insulin signaling, to exert its anti-obesity effects.

Purpose: Postoperative complications following gastric cancer surgery significantly impact patient outcomes, yet standardized definitions for these events have not been consistently applied across institutions in Korea. This study aimed to develop a consensus-based, standardized complication classification system specific to gastrectomy for gastric cancer as part of the Korean Quality Improvement Platform in Surgery (K-QIPS) initiative. Methods: As part of K-QIPS, a dedicated task force team (TFT) was formed with surgical experts from fourteen high-volume hospitals across Korea. The TFT conducted ten formal meetings to review existing literature and international guidelines, and incorporated findings from randomized controlled trials. The final complication list was developed through expert consensus and structured into a standardized framework. A Data Entry Manual was created to support consistent data collection by surgical clinical reviewers. Results: The TFT defined specific postoperative complications following gastrectomy for gastric cancer, including anastomotic leakage, duodenal stump leakage, pancreatic fistula, intra-abdominal and luminal bleeding, delayed gastric emptying, and internal hernia. Notably, internal hernia was described in standardized form for the first time. General complications were developed first and overlapped in part with the gastric cancer-specific list. The task force also produced a Data Entry Manual that provides practical instructions to ensure consistency and accuracy in complication reporting. Conclusion This nationwide consensus initiative established the first standardized complication classification system for gastric cancer surgery in Korea. The proposed definitions and data entry system are expected to improve complication reporting, enable multicenter research, support surgical quality benchmarking, and ultimately enhance patient outcomes.

To compare optic nerve head (ONH) and peripapillary structural OCT parameters between eyes with and without visual field (VF) defects one year after an episode of acute primary angle closure (APAC) in a cohort treated uniformly treated with early clear-lens extraction. Forty-seven eyes of 47 patients with a history of APAC episode who underwent early clear-lens extraction at Chonnam National University Hospital were retrospectively reviewed. Spectral-domain optical coherence tomography (SD-OCT) performed one year after the episode was used to assess Bruch’s membrane opening-minimum rim width (BMO-MRW), retinal nerve fiber layer (RNFL) thickness, lamina cribrosa (LC) thickness and depth, and parapapillary atrophy (PPA) subdivided into PPA+BM and PPA−BM. Patients were classified according to the presence or absence of VF defects. At one year, 23 eyes (48.9%) had variable degrees of visual field (VF) defects. Compared with eyes with normal VF, the VF-defect group showed significantly thinner global BMO-MRW (p<0.001) and peripapillary RNFL (p<0.001), reduced LC thickness (p<0.001), shallower LC depth (p=0.028), and a wider PPA+BM (p<0.001). APAC patients who underwent early lens extraction may develop residual VF defect despite normalization of IOP. These defects were associated with structural damage in the rim, RNFL, LC, and PPA+BM as detected by SD-OCT. Comprehensive OCT analysis may help identify patients at risk of long-term functional sequelae after APAC.

Background: and Purpose To compare the epidemiological and clinical features of the rare patients with cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL) with age- and sex-matched controls in a nationwide cohort from South Korea. Methods: This observational cohort study analyzed newly diagnosed CADASIL patients aged at least 20 years and matched controls using data from the National Health Information Database for 2004–2022. The cumulative incidence of CADASIL was assessed by age and sex, and compared between regions. Neurologic and systemic diseases were compared between the CADASIL and control groups. Results: The study analyzed 816 CADASIL patients and 816 age- and sex-matched controls aged 56.8±15.2 years (mean±standard deviation), among whom 48.3% were male. The cumulative incidence of CADASIL was 1.86 per 100,000 people (95% confidence interval [CI]=1.85– 1.87 per 100,000), and peaked at 60–69 years of age. In terms of regional distribution, the incidence was highest for Jeju, at 39.67 per 100,000 (95% CI 37.84–41.49 per 100,000). Neurologic diseases were more frequent in CADASIL patients, including Alzheimer’s disease (33.1% vs.20.0%), vascular dementia (84.9% vs. 5.0%), epilepsy (34.6% vs. 15.9%), stroke (70.7% vs. 27.6%), parkinsonism (18.9% vs. 11.0%), and depression (60.8% vs. 44.9%). Systemic diseases such as diabetes mellitus (78.9% vs. 68.9%) were also more common in CADASIL patients, while cancer (27.9% vs. 38.7%) and myocardial infarction (10.0% vs. 13.6%) were less common than in controls. The onset ages of all diseases were lower in CADASIL patients. Conclusions This study has provided a precise nationwide estimate of the CADASIL incidence and its regional distribution in South Korea. CADASIL patients showed higher incidence rates and earlier onsets of diverse clinical manifestations.

Background: Primary cutaneous CD30+ lymphoproliferative disorders (pcCD30-LPDs) are a diseases with various clinical and prognostic characteristics. Objective: Increasing our knowledge of the clinical characteristics of pcCD30-LPDs and identifying potential prognostic variables in an Asian population. Methods: Clinicopathological features and survival data of pcCD30-LPD cases obtained from 22 hospitals in South Korea were examined. Results: A total of 413 cases of pcCD30-LPDs (lymphomatoid papulosis [LYP], n=237; primary cutaneous anaplastic large cell lymphoma [C-ALCL], n=176) were included. Ninety percent of LYP patients and roughly 50% of C-ALCL patients presented with multiple skin lesions. Both LYP and C-ALCL affected the lower limbs most frequently. Multiplicity and advanced T stage of LYP lesions were associated with a chronic course longer than 6 months. Clinical morphology with patch lesions and elevated serum lactate dehydrogenase were significantly associated with LPDs during follow-up in LYP patients. Extracutaneous involvement of C-ALCL occurred in 13.2% of patients. Lesions larger than 5 cm and increased serum lactate dehydrogenase were associated with a poor prognosis in C-ALCL. The survival of patients with C-ALCL was unaffected by the anatomical locations of skin lesions or other pathological factors. Conclusion The multiplicity or size of skin lesions was associated with a chronic course of LYP and survival among patients with C-ALCL.

Background: MUTYH-associated polyposis is an autosomal recessive disorder associated with an increased lifetime risk of colorectal cancer and a moderately increased risk of ovarian, bladder, breast, and endometrial cancers. We analyzed the carrier frequency and estimated the incidence of MUTYH-associated polyposis in East Asian and Korean populations, for which limited data were previously available. Methods: We examined 125,748 exomes from the gnomAD database, including 9,197 East Asians, and additional data from 5,305 individuals in the Korean Variant Archive and 1,722 in the Korean Reference Genome Database. All MUTYH variants were interpreted according to the American College of Medical Genetics and Genomics and Association for Molecular Pathology guidelines and the Sequence Variant Interpretation guidelines from ClinGen. Results: The global carrier frequency of MUTYH-associated polyposis was 1.29%, with Europeans (non-Finnish) having the highest frequency of 1.86% and Ashkenazi Jews the lowest at 0.06%. East Asians and Koreans had a carrier frequency of 0.35% and 0.37% and an estimated incidence of 1 in 330,409 and 1 in 293,304 in Koreans, respectively, which were substantially lower than the global average of 1 in 24,160 and the European (nonFinnish) incidence of 1 in 11,520. Conclusions This was the first study to investigate the frequency of carriers of MUTYH-associated polyposis in East Asians, including specific subgroups, utilizing gnomAD and a Korean genome database. Our data provide valuable reference information for future investigations of MUTYH-associated polyposis to understand the genetic diversity and specific variants associated with this condition in East Asian populations.

Background: Circulating tumor DNA (ctDNA) is a potential biomarker in pancreatic ductal adenocarcinoma (PDAC). However, studies on residual ctDNA in patients post-chemotherapy are limited. We assessed the prognostic value of residual ctDNA in metastatic PDAC relative to that of carbohydrate antigen 19-9 (CA19-9). Methods: ctDNA analysis using a targeted next-generation sequencing panel was performed at baseline and during chemotherapy response evaluation in 53 patients. Progression-free survival (PFS) and overall survival (OS) were first evaluated based on ctDNA positivity at baseline. For further comparison, patients testing ctDNA-positive at baseline were subdivided based on residual ctDNA into ctDNA responders (no residual ctDNA post-chemotherapy) and ctDNA non-responders (residual ctDNA post-chemotherapy). Additional survival analysis was performed based on CA19-9 levels. Results: The baseline ctDNA detection rate was 56.6%. Although clinical outcomes tended to be poorer in patients with baseline ctDNA positivity than in those without, the differences were not significant. Residual ctDNA post-chemotherapy was associated with reduced PFS and OS. The prognosis of ctDNA responders was better than that of non-responders but did not significantly differ from that of ctDNA-negative individuals (no ctDNA both at baseline and during post-chemotherapy). Compared with ctDNA responses to che-motherapy, a ≥ 50% decrease in the CA19-9 level had less effect on both PFS and OSbased on hazard ratios and significance levels. ctDNA could be monitored in half of the patients whose baseline CA19-9 levels were within the reference range. Conclusions Residual ctDNA analysis post-chemotherapy is a promising approach for predicting the clinical outcomes of patients with metastatic PDAC.

Background: Pancreatic ductal adenocarcinoma (PDAC) has a poor prognosis and lacks clinical biomarkers. Exosomes are extracellular vesicles that facilitate cell–cell communication by distributing macromolecules, such as small RNAs (smRNAs). We assessed the potential of exosome-derived small RNAs (Ex-smRNAs) as PDAC biomarkers. Methods: Peripheral blood was collected from 51 patients with PDAC and 15 control individuals. Exosomes were isolated using an aqueous two-phase system. Ex-smRNAs were analyzed using smRNA sequencing. smRNA-mediated target gene regulation was verified via The Cancer Genome Atlas analysis and in vitro transfection and wound-healing assays using PDAC organoids. Results: The total Ex-smRNA count was substantially reduced in patients with PDAC compared with that in control individuals. The levels of microRNAs (miRNAs) miR-125a-5p, miR-30e-5p, miR-16-2-3p, miR-98-5p, and the let-7 family were significantly suppressed, whereas that of miR-6731-5p was significantly elevated. Let-7c-5p and miR-98-5p were found to interact with the long non-coding RNA OLMALINC to regulate their common target genes, BACH1 and CCND1, thus controlling PDAC proliferation and migration. The expressions of CARS1-AS1 and miR-142-5p were upregulated in treatment-responsive patients.Multivariable Cox regression analyses, adjusting for potential prognostic factors such as sex, Eastern Cooperative Oncology Group performance status, and tumor size and stage, revealed that CARS1-AS1 (adjusted hazard ratio [HR] 0.33; 95% confidence interval [CI], 0.15–0.73; P = 0.0061) and miR-142-5p (adjusted HR 0.79; 95% CI, 0.61–1.01; P = 0.0581) were associated with improved overall survival. Conclusions We identified potential Ex-smRNA biomarkers involved in PDAC progression and prognosis that reflect key molecular alterations in PDAC and may serve as clinically relevant biomarkers for disease monitoring.

Background: Citrin deficiency is an autosomal recessive disorder caused by pathogenic variants in SLC25A13, presenting with various age-dependent clinical phenotypes and a broad spectrum of severity. However, few studies have examined the frequency and prevalence of citrin deficiency. We aimed to analyze the carrier frequency and disease prevalence in East Asian populations and Koreans. Methods: We comprehensively reviewed the literature and conducted a cross-sectional study to analyze genomic databases, including the Genome Aggregation Database (gnomAD), Korean Variant Archive (KOVA), and Tohoku Medical Megabank Organization (ToMMo), to identify pathogenic SLC25A13 variants in East Asian populations. A founder 3-kilobase (kb) insertion in intron 16 of SLC25A13 was investigated using whole-genome sequencing data from 681 Koreans with the Linux grep command. Results: Twenty-three pathogenic SLC25A13 variants were identified, with c.852_855del being the most common. Analysis of data from 17,501 East Asian individuals in the gnomAD and ToMMo databases revealed a carrier frequency of 1 in 62 people. Analysis of data from 7,214 individuals in the gnomAD and KOVA databases revealed a carrier frequency of 1 in 86, corresponding to an estimated disease prevalence of 1 in 29,502.c.1177+1G > A was identified as the most prevalent pathogenic variant in Koreans. The 3 kb insertion in intron 16 was detected in three out of 681 individuals, indicating a carrier frequency of 1 in 228. Conclusions The high carrier frequency of citrin deficiency in East Asians highlights the need for enhanced genetic screening and counseling, particularly in Korea, providing a valuable reference for future studies on genetic diversity and pathogenic variants in this population.

Objective: This study aims to understand the structure of meaning in life among patients with cancer through the validation of the Meaning in Life Scale among Korean patients (K-MiLS) with cancer. Methods: From August 2021 to November 2022, participants were recruited from multiple sites in South Korea. Participants completed related questionnaires, including the MiLS, on the web or mobile. Test-retest reliability was assessed between 2 and 4 weeks after the initial assessment. Exploratory and confirmatory factor analyses and Pearson’s correlations were used to evaluate the reliability and validity of the MiLS. A multiple regression analysis was conducted to examine the sociodemographic and disease-related variables correlated with the MiLS. Regarding concurrent validity, a hierarchical regression analysis was performed. Results: The results (n=345) indicated that the K-MiLS has a four-factor structure: Harmony and Peace; Life Perspective, Purpose, and Goals; Confusion and Lessened Meaning; and Benefits of Spirituality. Regarding convergent and discriminant validity, K-MiLS was negatively correlated with Patient Health Questionnaire-9, Generalized Anxiety Disorder-7, and Fear of Cancer Recurrence Inventory while showing a significantly positive correlation with the Posttraumatic Growth Inventory, Self-Compassion Scale, Functional Assessment of Cancer Therapy-General, and Functional Social Support Questionnaire. Hierarchical regression analysis revealed that the demographic variable influencing MiLS was religious affiliation. Conclusion The K-MiLS had a multidimensional four-factor structure similar to that of the original version. It is also a reliable and valid measure for assessing cancer survivors’ meaning in life after a cancer diagnosis.