Punica granatum L. has been widely used in traditional medicine and is known to contain bioactiveellagitannins with potential antidiabetic properties. The primary objective of this study was to develop and validate a reliable HPLC-DAD method for the quantitative analysis of major compounds isolated from stems and pericarpium of P. granatum, namely pedunculagin (1), flavogallonic acid (2), casuarinin (3), isocorilagin (4), methyl brevifolincarboxylate (5), eschweilenol C (6), ellagic acid-4-O-β-D-xylopyranoside (7), ellagic acid (8), and quercitrin (9), and to futher evaluate their α-glucosidase inhibitory activity. The analytical method demonstrated linearity with correlation coefficients (R²) exceeding 0.9991. The limits of detection (LOD) and limits of quantification (LOQ) ranged from 2.75 to 7.44 μg/mL and 8.33 to 22.54 μg/mL, respectively. Intra-day and inter-day precision showed relative standard deviation (RSD) values below 2.85% and 2.72%, while recovery values ranged from 96.87% to 107.72%, confirming the accuracy and reliability of the method.Quantitative results revealed that ellagitannins were the predominant constituents in both stems and pericarpium of P. granatum. Biological evaluation demonstrated that several isolated compounds exhibited strong αglucosidase inhibitory activity, with compounds 1–3 showing significantly stronger activity than the reference inhibitor acarbose. Enzyme kinetic studies and molecular docking analyses were conducted to clarify their inhibition mechanisms, revealing mixed, uncompetitive and competitive inhibition modes associated with binding to catalytic or allosteric sites of the enzyme. This study integrates quantitative analysis with mechanistic enzyme inhibition evaluation, providing a practical analytical tool for quality control of P. granatum and scientific evidence supporting its potential application in antidiabetic therapy.

Background: With the aging population and advancements in medical care worldwide, the number of older patients with end-stage kidney disease continues to rise. This study aimed to identify factors associated with osteoporosis and osteopenia in older patients undergoing incident hemodialysis and assess their impact on mortality. Methods: We analyzed a large multicenter retrospective cohort of patients aged ≥70 years undergoing incident hemodialysis to identify factors associated with osteoporosis using logistic regression analysis and to assess the association of death with osteoporosis and osteopenia using Cox multivariable analysis. Results: Among 710 patients, 39.0% and 19.6% had osteoporosis and osteopenia, respectively. Osteoporosis was significantly associated with female sex, a history of fractures, and the absence of phosphate binder use. During a median follow-up of 36.8 months, 348 participants (58.8%) died. Mortality rates were the highest in the osteoporosis group (79.8%), followed by the osteopenia (77.2%) and normal bone mineral density (BMD) groups (35.2%). Cox regression analysis revealed that even after adjusting for covariates, the osteoporosis group was significantly associated with a higher mortality risk than the normal BMD group. Osteoporosis at the start of hemodialysis was significantly associated with higher mortality. Conclusion We should consider the importance of bone health in patients undergoing incident hemodialysis and pay attention to the use of phosphate binders and fracture prevention.

Background: The question of whether large language models (LLMs) possess consciousness has been increasingly debated. Integrated information theory (IIT) offers a quantitative framework for assessing consciousness through a measure of integrated information. Methods: This study applied IIT principles to the architecture of transformer-based LLMs, focusing on causal integration, temporal persistence, and system irreducibility. Ablation experiments on Generative Pretrained Transformer 2 (GPT-2) were performed, selectively removing individual attention heads and measuring changes in perplexity as a behavioral proxy for integrated information to empirically approximate the measure of integrated information. Results: The ablation study of a single attention head produced minimal or negative changes in perplexity in four out of five representative sentences, indicating redundancy or noise. Only one sentence revealed a significant increase in perplexity change (ΔPPL +11.29), reflecting a localized but nonessential contribution. A comparison with biological systems demonstrated that LLMs meet the IIT criterion of differentiation, but fail to meet the criteria of integration, causal closure, and temporal persistence. These findings confirm that LLMs are architecturally decomposable, lack persistent internal states, and do not sustain global causal irreducibility. Philosophical considerations, including Searle’s Chinese Room argument, further support the idea that the linguistic fluency of LLMs arises from syntactic manipulation rather than semantic understanding. Conclusion Current LLMs do not satisfy the structural and informational requirements of consciousness under IIT. Although capable of simulating intelligent language, LLMs remain unconscious systems with a negligible amount of integrated information, underscoring the distinction between linguistic competence and conscious experience.

Objective: Precise knowledge regarding the mechanical stress applied to the intervertebral disc following each individual spine motion enables physicians and patients to understand how people with discogenic back pain should be guided in their exercises and which spine motions to specifically avoid. We created an intervertebral disc degeneration model and conducted a finite element (FE) analysis of loaded stresses following each spinal posture or motion. Methods: A 3-dimensional FE model of intervertebral disc degeneration at L4–5 was constructed. The intervertebral disc degeneration model was created according to the modified Dallas discogram scale. The von Mises stress and range of motion (ROM) regarding the intervertebral discs and the endplates were analyzed. Results: We observed that mechanical stresses loaded onto the intervertebral discs were similar during flexion, extension, and lateral bending, which were greater than those occurring during torsion. Based on the comparison among the grades divided by the modified Dallas discogram scale, the mechanical stress during extension was greater in grades 3–5 than it was during the others. During extension, the mechanical stress loaded onto the intervertebral disc and endplate was greatest in the posterior portion. Mechanical stresses loaded onto the intervertebral disc were greater in grades 3–5 compared to those in grades 0–2. Conclusion Our findings suggest that it might be beneficial for patients experiencing discogenic back pain to maintain a neutral posture in their lumbar spine when engaging in daily activities and exercises, especially those suffering from significant intravertebral disc degeneration.

Objective: Precise knowledge regarding the mechanical stress applied to the intervertebral disc following each individual spine motion enables physicians and patients to understand how people with discogenic back pain should be guided in their exercises and which spine motions to specifically avoid. We created an intervertebral disc degeneration model and conducted a finite element (FE) analysis of loaded stresses following each spinal posture or motion. Methods: A 3-dimensional FE model of intervertebral disc degeneration at L4–5 was constructed. The intervertebral disc degeneration model was created according to the modified Dallas discogram scale. The von Mises stress and range of motion (ROM) regarding the intervertebral discs and the endplates were analyzed. Results: We observed that mechanical stresses loaded onto the intervertebral discs were similar during flexion, extension, and lateral bending, which were greater than those occurring during torsion. Based on the comparison among the grades divided by the modified Dallas discogram scale, the mechanical stress during extension was greater in grades 3–5 than it was during the others. During extension, the mechanical stress loaded onto the intervertebral disc and endplate was greatest in the posterior portion. Mechanical stresses loaded onto the intervertebral disc were greater in grades 3–5 compared to those in grades 0–2. Conclusion Our findings suggest that it might be beneficial for patients experiencing discogenic back pain to maintain a neutral posture in their lumbar spine when engaging in daily activities and exercises, especially those suffering from significant intravertebral disc degeneration.

Purpose: We sought to evaluate the time-dependent efficacy and safety of eplerenone for central serous chorioretinopathy. Methods: A systematic search was performed from inception to May 2023 in the Medline, EMBASE, and Cochrane literature databases to find randomized controlled trials that have administered oral eplerenone therapy to central serous chorioretinopathy patients. Results: Five randomized controlled trials were included in the final analysis. Among a total of 252 central serous chorioretinopathy patients, 134 were included in the eplerenone group and 118 were included in the control group. The best-corrected visual acuity was statistically significantly improved in the eplerenone group compared to the control group (95% confidence interval [CI], -0.08 to -0.02; p = 0.001). After meta-analysis was performed at each follow-up point, it was found that eplerenone statistically significantly improved the best-corrected visual acuity compared to the control group at 2 and 3 months after starting oral eplerenone therapy, but there was no statistically significant difference at 6 months. Subretinal fluid, chorioretinal thickness, central macular thickness, and complications showed no statistically significant differences between the eplerenone and control groups (p = 0.43, 0.67, 0.64, and 0.12, respectively). The difference in the risk of complications occurring between the eplerenone and control groups also didn’t show statistical significance (p = 0.12). Conclusions Although eplerenone is not superior to a control protocol when considering anatomical improvements, the best-corrected visual acuity seems to improve up to 3 months superiorly compared to in the control group when oral eplerenone therapy is administered for central serous chorioretinopathy. In addition, the complications of eplerenone are tolerable. Therefore, clinically short-term use of eplerenone up to 3 months in central serous chorioretinopathy patients can be considered.

Objective: Precise knowledge regarding the mechanical stress applied to the intervertebral disc following each individual spine motion enables physicians and patients to understand how people with discogenic back pain should be guided in their exercises and which spine motions to specifically avoid. We created an intervertebral disc degeneration model and conducted a finite element (FE) analysis of loaded stresses following each spinal posture or motion. Methods: A 3-dimensional FE model of intervertebral disc degeneration at L4–5 was constructed. The intervertebral disc degeneration model was created according to the modified Dallas discogram scale. The von Mises stress and range of motion (ROM) regarding the intervertebral discs and the endplates were analyzed. Results: We observed that mechanical stresses loaded onto the intervertebral discs were similar during flexion, extension, and lateral bending, which were greater than those occurring during torsion. Based on the comparison among the grades divided by the modified Dallas discogram scale, the mechanical stress during extension was greater in grades 3–5 than it was during the others. During extension, the mechanical stress loaded onto the intervertebral disc and endplate was greatest in the posterior portion. Mechanical stresses loaded onto the intervertebral disc were greater in grades 3–5 compared to those in grades 0–2. Conclusion Our findings suggest that it might be beneficial for patients experiencing discogenic back pain to maintain a neutral posture in their lumbar spine when engaging in daily activities and exercises, especially those suffering from significant intravertebral disc degeneration.

Objective: Precise knowledge regarding the mechanical stress applied to the intervertebral disc following each individual spine motion enables physicians and patients to understand how people with discogenic back pain should be guided in their exercises and which spine motions to specifically avoid. We created an intervertebral disc degeneration model and conducted a finite element (FE) analysis of loaded stresses following each spinal posture or motion. Methods: A 3-dimensional FE model of intervertebral disc degeneration at L4–5 was constructed. The intervertebral disc degeneration model was created according to the modified Dallas discogram scale. The von Mises stress and range of motion (ROM) regarding the intervertebral discs and the endplates were analyzed. Results: We observed that mechanical stresses loaded onto the intervertebral discs were similar during flexion, extension, and lateral bending, which were greater than those occurring during torsion. Based on the comparison among the grades divided by the modified Dallas discogram scale, the mechanical stress during extension was greater in grades 3–5 than it was during the others. During extension, the mechanical stress loaded onto the intervertebral disc and endplate was greatest in the posterior portion. Mechanical stresses loaded onto the intervertebral disc were greater in grades 3–5 compared to those in grades 0–2. Conclusion Our findings suggest that it might be beneficial for patients experiencing discogenic back pain to maintain a neutral posture in their lumbar spine when engaging in daily activities and exercises, especially those suffering from significant intravertebral disc degeneration.

Background: s/Aims: Reported incidence of extrahepatic bile duct cancer is higher in Asians than in Western populations. Korea, in particular, is one of the countries with the highest incidence rates of extrahepatic bile duct cancer in the world. Although research and innovative therapeutic modalities for extrahepatic bile duct cancer are emerging, clinical guidelines are currently unavailable in Korea. The Korean Society of Hepato-Biliary-Pancreatic Surgery in collaboration with related societies (Korean Pancreatic and Biliary Surgery Society, Korean Society of Abdominal Radiology, Korean Society of Medical Oncology, Korean Society of Radiation Oncology, Korean Society of Pathologists, and Korean Society of Nuclear Medicine) decided to establish clinical guideline for extrahepatic bile duct cancer in June 2021. Methods: Contents of the guidelines were developed through subgroup meetings for each key question and a preliminary draft was finalized through a Clinical Guidelines Committee workshop. Results: In November 2021, the finalized draft was presented for public scrutiny during a formal hearing. Conclusions The extrahepatic guideline committee believed that this guideline could be helpful in the treatment of patients.

Thyroid nodules represent a prevalent condition that is detectable via palpation or ultrasound. In recent years, there has been a paradigm shift toward enhanced diagnostic precision and less aggressive therapeutic approaches, highlighting the growing necessity for tailored clinical recommendations to optimize patient outcomes. The Korean Thyroid Association (KTA) has developed guidelines for managing patients with thyroid nodules, following a comprehensive review by task force members of the relevant literature identified via electronic database searches. The recommendations are provided with a level of recommendation for each section. The guidelines encompass thyroid cancer screening in high-risk groups, appropriate diagnostic methods for thyroid nodules, role of pathologic and molecular marker testing in making a diagnosis, long-term follow-up and treatment of benign thyroid nodules, and special considerations for pregnant women. The major revisions that were made in the 2023 guidelines were the definition of high-risk groups for thyroid cancer screening, application of the revised Korean Thyroid Imaging Reporting and Data System (K-TIRADS), addition of the role of core needle biopsy and molecular marker tests, application of active surveillance in patients with low-risk papillary thyroid microcarcinoma, and updated indications for nonsurgical treatment of benign thyroid nodules. In the 2024 revision of the KTA guidelines for thyroid cancer, the evidence for some recommendations has been updated to address the tumor size in the context of active surveillance in patients with low-risk thyroid cancer and the surgical size cutoff. These evidence-based recommendations serve to inform clinical decision-making in the management of thyroid nodules, thereby facilitating the delivery of optimal and efficacious treatments to patients.