Dietary protein is a crucial macronutrient for systemic homeostasis, and the global interest in protein supplements has surged because of their roles in muscle synthesis, immune function, and sarcopenia prevention. In South Korea, the proportion of energy derived from protein has increased steadily over the past decade, reflecting a significant shift in dietary patterns toward greater reliance on protein. Concurrently, a wide range of protein- and amino acidbased processed foods and dietary supplements has been developed and actively consumed.Nevertheless, comprehensive data on the prevalence of protein supplement users, their characteristics across different life stages, and the contribution of supplements to total daily protein requirements are lacking. Unlike other macronutrients, the human body lacks a dedicated reservoir for protein storage, necessitating a continuous dietary supply to support protein turnover, particularly for older adults facing anabolic resistance and individuals with high physical demands. Although clinical evidence highlights that protein supplementation, particularly when combined with resistance exercise, effectively improves muscle mass and physical performance, the magnitude of these benefits remains inconsistent across different life stages and protein sources. Conversely, emerging concerns about the potential metabolic risks from chronic overconsumption suggest that the validity and safety of protein supplementation are unclear, highlighting the need for a precision nutrition approach. Thus, this review evaluates the status of protein supplement intake among Koreans, synthesizes evidence on its physiological benefits and drawbacks and examines international trends and regulatory frameworks. Developed as part of the technical assessment for the 2025 revision of the Dietary Reference Intakes for Koreans, this review addresses the current lack of longterm safety data on chronic protein overconsumption. It provides a foundational framework for evidence-based dietary guidelines and serves as a critical scientific basis for establishing future tolerable upper intake levels and nutrition policies for protein supplement use in Korea.

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.

Replacing the retrohepatic inferior vena cava (IVC) following concurrent resection of the IVC and tumor-involved liver is an emerging surgical technique in living donor liver transplantation (LDLT), particularly for managing hepatocellular carcinomas near the IVC. This approach makes the extent of hepatectomy in LDLT comparable to that of deceased donor liver transplantation. We report a pediatric LDLT case involving IVC and portal vein (PV) replacement with an iliac vein homograft to treat advanced hepatoblastomas. The patient was a 24-month-old girl weighing 9.1 kg, presenting with large, multiple hepatoblastomas infiltrating the retrohepatic IVC and PV. After a 2-week waiting period, a cold-stored iliac vein graft was obtained, and the transplantation was performed using a left lateral section graft from her father.A 4-cm iliac vein homograft was anastomosed between the suprahepatic and suprarenal IVC stumps. The liver graft was implanted following standard procedures, with the PV reconstructed via a telescope-shaped anastomosis using the vein graft interposition. The patient experienced an uncomplicated recovery and is currently receiving scheduled adjuvant chemotherapy. In conclusion, IVC and PV replacement with vein homografts represents a feasible and effective surgical strategy for pediatric LDLT patients with advanced liver malignancies involving vascular invasion.

Purpose: This study aimed to report the real-world outcomes of intravesical gemcitabine for bacillus Calmette–Guérin (BCG)–unresponsive, high-risk, non–muscle-invasive bladder cancer (HR-NMIBC) in Korean patients who were unable or unwilling to undergo radical cystectomy (RC). Materials and Methods: This retrospective study included 131 patients (median age, 69 years; 88.5% men) treated with intravesical gemcitabine for BCG-unresponsive HR-NMIBC at nine centers between May 2019 and April 2022. The primary endpoint was 1-year recurrence-free survival (RFS). The secondary endpoints included factors influencing RFS, progression-free survival (PFS), cystectomy- free survival, cancer-specific survival (CSS), overall survival (OS), and safety. Survival analysis was performed using the Kaplan-Meier method, and risk factors for recurrence were assessed using Cox regression models. Results: Patients were followed up for a median duration of 25 months, with carcinoma in situ (CIS) in 41.9% of the patients. The 1-year and 2-year RFS rates were 68% and 42%, while the 1-year and 2-year PFS rates were 87% and 77%, respectively. No significant factors influencing RFS were identified. Seventeen patients underwent RC during a median follow-up of 16 months, with the condition in three patients progressing to muscle-invasive disease on final pathological analysis. The 2-year CSS and OS rates were 98% and 97%, respectively. Intravesical gemcitabine was well-tolerated, with only seven patients (5.3%) unable to complete the full induction course. Conclusion Our research highlights the potential of intravesical gemcitabine as a viable bladder-sparing treatment option for BCG-unresponsive HR-NMIBC, providing real-world evidence on its safety, efficacy, and tolerability.

Purpose: Accumulating evidence has clarified that gut dysbiosis is involved in lung cancer development and progression. Although the relationship between tumors and gut microbiota has been extensively studied using clinical samples, no studies have examined the association between mutant epidermal growth factor receptor (EGFR)–induced lung carcinogenesis and dysbiosis in gut microbiota. Therefore, we investigated the gut microbiota profiles in stool samples from human lung-specific conditional EGFR-mutant transgenic mice during lung tumor carcinogenesis. Materials and Methods: Stool samples were collected before tamoxifen treatment (V1) and at each time point following mutant EGFR expression in lung tissue (V2) and lung tumor appearance (V3). Fecal 16S rRNA taxonomy was analyzed to assess microbial diversity, composition, and dynamic changes at each time point. Results: We found that microbiota richness and diversity were significantly elevated when tumors developed and grew in the lung. Phylogenetic analysis of the microbial community revealed that Lachnospiraceae, Ruminococcaceae, Porphyromonadaceae, Rhodospirillaceae, Odoribacteraceae, and Desulfovibrionaceae showed a significant increase at the V3 stage compared to the V1 stage at the family level. In contrast, Lactobacillaceae, Bacteroidaceae, Muribaculaceae, Coriobacteriaceae, and Rikenellaceae significantly decreased at the V3 stage compared to the V1 stage. Furthermore, Lactobacillus species, also known as short chain fatty acid-producing bacteria, were relatively abundant at the V1 stage but were depleted with the occurrence of lung tumors at the V3 stage. Conclusion Changes in gut microbiota, such as Lactobacillus species, may be a predictive factor for the emergence and progression of tumors in an animal model of lung adenocarcinoma induced by mutant EGFR.

In children with biliary atresia, recurrent episodes of cholangitis often lead to portal vein (PV) phlebosclerosis. We report a case of pediatric living donor liver transplantation (LDLT) for biliary atresia with PV occlusion and a large splenorenal shunt. A 3-year-5-month-old girl was diagnosed with syndromic biliary atresia and polysplenia. Because the patient’s condition progressively deteriorated with worsening jaundice, we opted to perform LDLT using a left lateral section graft from her father. The recipient’s native PV was severely atrophic and completely occluded, and the collateral veins around the hepatoduodenal ligament were too small to serve as a viable source of portal inflow.Consequently, renoportal anastomosis (RPA) was selected as an alternative approach.Iliac vein interposition was performed to provide a new portal inflow source, and anatomy-compliant PV reconstruction was performed. The patient recovered from transplant surgery, but PV conduit stenosis occurred with the development of ascites 2 months posttransplant. This RPA-related vascular complication was resolved through percutaneous balloon angioplasty of the PV conduit. The patient has been doing well for 6 months posttransplantation. This case demonstrates that RPA can represent a viable reconstructive option for PV inflow in liver transplantation for pediatric patients with phlebosclerotic PV and prominent splenorenal shunt.

Purpose: This study evaluated the clinical outcomes and prognostic factors in patients with borderline resectable pancreatic cancer (BRPC) and locally advanced pancreatic cancer (LAPC) treated with upfront FOLFIRINOX followed by local-regional therapy (LRT), surgical resection (SR), and radiotherapy (RT). We aimed to identify specific patient subgroups for which RT may serve as a reasonable alternative to SR for local tumor control. Methods: We retrospectively analyzed 116 patients (SR group, n= 70; RT group, n= 46) at a single center between 2015 and 2020. Survival outcomes were compared based on LRT modalities, focusing on identifying subgroups in which RT provided an efficacy comparable to that of SR. Results: Among 116 patients, the SR group achieved a significantly higher 5-year overall survival (OS) than the RT group (27.1% vs. 8.7%, P< 0.0001), despite similar progression-free survival (P= 0.23). Significant prognostic factors for OS included carbohydrate antigen 19-9 (CA19-9) response in BRPC (P= 0.02) and radiologic partial response in LAPC (P= 0.05). Subgroup analysis revealed that, while SR provided a survival advantage in CA19-9 responders, no significant difference in OS was observed between SR and RT in CA19-9 non-responders (P= 0.37). Conclusion Although surgery remains the gold standard, RT may be considered a justifiable local alternative for CA19-9 non-responders and surgically ineligible patients with LAPC, yielding comparable outcomes in these specific, biologically unfavorable subgroups.

Replacement of the retrohepatic inferior vena cava (IVC) after concurrent resection of IVC and tumor-bearing liver is regarded as a feasible living donor liver transplantation (LDLT) technique to cope with tumors around the IVC. This method can make the resection extent of LDLT comparable to that of deceased-donor liver transplantation. We present one pediatric LDLT case with IVC replacement using an enlarged iliac vein conduit to treat advanced hepatoblastoma. The patient was a 33-monthold and 12 kg-weighing girl suffering from large multiple hepatoblastomas invading the retrohepatic IVC. At 2-month waiting after deciding LDLT, we obtained a coldstored iliac vein graft and LDLT was performed with the father’s left lateral section graft. A 1.3 cm-wide and 10 cm-long iliac vein was transformed to be a 2 cm-wide and 5 cm-long vein graft through a double-barrel unification venoplasty. The left lateral section graft was implanted along the standard procedure of LDLT. The patient recovered uneventfully and is undergoing scheduled adjuvant chemotherapy. IVC replacement with vein homograft is a feasible option for LDLT in pediatric patients with advanced liver malignancy.

Background/Aims: Fexuprazan, a novel potassium-competitive acid blocker, was developed for treating acid-related disorders. Pharmacokinetic and pharmacodynamic properties of fexuprazan, unlike those of proton pump inhibitors, are independent of food effect. This study aims to evaluate differences in efficacy and safety of fexuprazan in patients with erosive esophagitis (EE) according to the timing of dosing. Methods: In this multicenter, open-label noninferiority study, patients who had typical reflux symptoms with endoscopically confirmed EE were randomized 1:1 to receive fexuprazan 40 mg daily 30 minutes before or after meal. Treatment was completed after 2 weeks or 4 weeks when healing was endoscopically confirmed. The primary endpoint was the proportion of patients with healed EE confirmed by endoscopy up to week 4. Safety endpoints included treatment-emergent adverse events (TEAEs). Results: In the prior-to-meal group (n = 89) and after-meal group (n = 86), 4-week EE healing rates were 98.77% and 100.00% (difference, 0.01%; 95% CI, –0.01% to 0.04%) and 2-week EE healing rates were 95.77% and 97.14% (difference, 0.01%; 95% CI, –0.05% to 0.07%), respectively. TEAEs were 9.78% and 8.70% in the prior-to-meal group and the after-meal group, respectively. Conclusions Non-inferiority analysis revealed that taking fexuprazan after meal was non-inferior to taking fexuprazan before meals in patients with EE. The frequency of adverse events was similar between the 2 study groups. The drug is safe and effective for healing EE regardless of the timing of dosing.