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.

Alzheimer’s disease (AD) is characterized by progressive cognitive deterioration and significant depression. However, the mechanisms linking depression to AD pathology remain unclear. Here, we investigated whether Notch2 signaling mediates depressionlike behaviors in presenilin-2 (PS2) N141I mutant mice, an early-onset AD model. PS2 wild-type (WT) and mutant (MT) mice aged 12-15 months were subjected to unpredictable chronic mild stress (UCMS) for 4 weeks, followed by sucrose preference, tail-hanging, and forced swimming tests. Behavioral assessments showed that UCMS exacerbated anhedonia and immobility only in PS2 MT mice. Molecular analysis revealed concomitant increases in plasma corticosterone, hippocampal γ-secretase activity, and Notch2 expression, and elevated total and phosphorylated glucocorticoid receptor levels in PS2 MT-UCMS mice. Gene expression profiling of human hippocampal datasets confirmed upregulation of NOTCH2 in Alzheimer’s disease and depression.Pharmacological inhibition of γ-secretase and Notch signaling with DAPT normalizes depressive behavior, reduces corticosterone release, attenuates GR phosphorylation, and inhibits Notch2 signaling in PS2 MT mice. These findings identify Notch2 as a pivotal mediator linking chronic stress to molecular changes associated with depression and AD, and suggest that targeting Notch2 signaling may provide therapeutic benefits for comorbid mood and neurodegenerative disorders.

Purpose: The triggering receptor expressed on myeloid cells 2 (TREM2) creates an immunosuppressive environment, but the effects of anticancer treatment on TREM2 and the tumor microenvironment (TME) are not well established. This study investigates the impact of chemotherapy on TREM2-expressing macrophages within the lung adenocarcinoma TME. Materials and Methods: Using single-cell RNA sequencing datasets of paired normal-appearing lung tissue (NL) and tumor (Tu), human and mouse lung cancer tissue, and THP-1 cells, we observed the effects of anticancer drugs on them. Results: Myeloid cells (MY) were the second-most abundant non-epithelial component in the Tu, though less prevalent than in NL. Specific MY subclusters abundant in Tu showed overexpression of TREM2. In lung cancer-induced Kras-G12D mice, M2 proportion increased in Tu compared to NL; cisplatin increased TREM2+ M2 proportion in Tu. TREM2+ cells in Tu showed interactions with cell clusters showing characteristics of interstitial macrophage such as mo-lineage, mono-Mc, and CD163/LGMN cells via FN:CD44 and MIF:CD74+CXCR4, suggesting that they influence the recruitment of those cells to Tu and TME reshape. In M0-state THP-1 cells, cisplatin and osimertinib treatments induced polarization towards M1 and M2 states and increased TREM2 expression. Cisplatin promoted uptake of phosphatidylserine-coated latex beads by M0 cells, whereas osimertinib reduced uptake by polarized macrophages. These findings suggest anticancer treatments impact the lung immune microenvironment by altering the TREM2+ cells. Conclusion Given TREM2’s central inhibitory role in the tumor immune environment, effects of chemotherapeutic agents should be considered in developing TREM2-targeting therapies.

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.

Purpose: To develop the 2025 update to the Korean colorectal cancer (CRC) screening guidelines by systematically evaluating recent evidence, integrating domestic data, and addressing changes since the 2015 guideline revision, thereby providing an evidence-based standard for clinicians and policymakers. Methods: A multidisciplinary committee developed the guidelines using the Grading of Recommendations, Assessment, Development and Evaluation (GRADE) methodology. The process included formulation of three key questions addressing screening efficacy, diagnostic accuracy, and optimal screening age and interval. A systematic review of international guidelines and primary literature was conducted, yielding 327 eligible studies. In addition, a utility-based analysis using a Markov model was performed to determine optimal screening ages and intervals. Results: The evidence synthesis identified high-certainty evidence supporting the use of the fecal immunochemical test (FIT) for reducing CRC mortality and moderate-certainty evidence for colonoscopy. Evidence for computed tomographic colonography (CTC) and stool DNA testing was rated as very low certainty. Based on the evidence review and cost-utility analysis, the committee conditionally recommends CRC screening for asymptomatic, average-risk adults aged 45–74 years using either colonoscopy every 10 years or FIT every 1–2 years. CTC and stool DNA testing were not recommended owing to insufficient evidence. Conclusion The 2025 Korean Guidelines for Colorectal Cancer Screening present updated, evidence-based recommendations tailored to the domestic healthcare context. By conditionally endorsing both colonoscopy and FIT for individuals aged 45–74 years, these guidelines aim to improve population-level screening effectiveness and reduce the burden of CRC in South Korea.

Background: Various perioperative therapeutic strategies have been used to minimize postoperative complications and enhance recovery. Music intervention has attracted increasing attention as a safe, noninvasive, and cost-effective approach with potential benefits for patient-centered postoperative outcomes. Accordingly, this study investigated the effect of intraoperative music on postoperative recovery quality, as assessed using the Quality of Recovery-40 (QoR-40) questionnaire, as well as its potential analgesic and antiemetic effects in patients undergoing arthroscopic knee surgery. Methods: Eighty-two patients were enrolled and allocated to either the music or control group. In the music group, patient-selected tracks were delivered intraoperatively via headphones. Postoperative recovery quality was assessed using the QoR-40 at 24 hours. Pain was evaluated 30 minutes, 2 hours, and 24 hours after arrival in the post-anesthesia care unit. The incidence of postoperative nausea and vomiting (PONV) was recorded at all time points. Results: Although the total QoR-40 scores did not differ between the groups, the music group demonstrated significantly higher physical comfort scores (p=0.006). The incidence of PONV at 24 hours was lower in the music group (p=0.048), whereas the postoperative pain scores and rescue analgesic requirements showed no significant differences at any assessment point. Conclusion In patients undergoing arthroscopic surgery, intraoperative music was associated with improvements in physical comfort and PONV, despite no significant difference in the total QoR-40 score.

Objectives: Large language models (LLMs) demonstrate remarkable potential in healthcare communication. However, whether they can process complex, high-volume medical information, such as stroke-related content, remains insufficiently validated. This study aimed to evaluate the natural language processing capabilities of LLMs in handling such content and to develop an evaluation instrument. Methods: A survey compared educational materials generated by two LLMs (ChatGPT 4.0 and Claude 3) with neurologist-authored content on stroke. The materials were based on two clinical scenarios representing distinct stroke etiologies: cardioembolism and large-artery atherosclerosis. They were evaluated in terms of accuracy, legality, ethics, comprehensiveness, and information delivery. Scores for comprehensiveness and information delivery were compared according to participants’ agreement with the use of LLMs in healthcare. Results: ChatGPT received the highest scores across all domains, except for legality in Scenario 2. In Scenario 1, the ranking for accuracy and summarization of clinical information was, from highest to lowest, ChatGPT, Claude, and the neurologist (η2 = 0.140, p < 0.001; η2 = 0.175, p < 0.001). The same hierarchy was observed in Scenario 2 for accuracy (η2 = 0.077, p < 0.001) and summarization (η2 = 0.194, p < 0.001). Participants who agreed with the use of LLMs in healthcare assigned higher scores for the comprehensiveness (Scenario 1, p = 0.005; Scenario 2, p = 0.007) and information delivery (Scenario 1, p = 0.003; Scenario 2, p = 0.026) of ChatGPT-generated materials than participants who did not agree. Conclusions LLMs demonstrated adequate capability to convey complex content, such as stroke-related information, in an accessible and understandable manner for non-experts.

Although aspartate aminotransferase (AST) is a serum marker of hepatocellular damage in chronic hepatitis, it is difficult to interpret very high AST levels with concurrent low alanine aminotransferase (ALT) levels. Macro-AST is an immunoglobulin-AST complex that can present as aberrant high enzymatic activity without significant inflammation in the liver. Two patients with chronic hepatitis B presented with disproportionate AST elevations. Their plasma samples were precipitated with polyethylene glycol (PEG) and stored at 4°C for macro-AST determinations. In Case 1, PEG precipitation showed 100% removal of AST activity, and refrigerated storage resulted in a ~70% decline over seven days, confirming macro-AST. In Case 2, both tests showed minimal changes, suggesting that macro-AST was unlikely. The AST levels normalized after antiviral therapy, suggesting immune-active hepatitis as the probable cause, but the other contributing factors could not be completely excluded. The abrupt decrease in AST activity after PEG precipitation and during refrigeration storage suggests that relatively high AST values compared to ALT might be attributed to the presence of macro-AST.These non-invasive methods for detecting macroenzymes might help the patient avoid unnecessary further work-ups.

The sixth edition of the Korean Medication Algorithm Project for Depressive Disorder (KMAP-DD) was published in 2025. This review compared KMAP-DD 2025 with four major international clinical practice guidelines: Canadian Network for Mood and Anxiety Treatments Clinical Guidelines for the Management of Major Depressive Disorders, National Institute for Health and Care Excellence Depression Guideline, Royal Australian and New Zealand College of Psychiatrists Clinical Practice Guidelines for Mood Disorders, and British Association for Psychopharmacology Guideline. While KMAP-DD is based on expert consensus, and others on evidence-based methods, overall treatment strategies for depressive episodes were fairly consistent. Especially, KMAP-DD 2025 offers more structured recommendations in areas lacking strong evidence, such as premenstrual dysphoric disorder, perinatal depression, and depression with medical comorbidities. KMAP-DD 2025 also reflected Korean clinical practice patterns emphasizing rapid symptom relief and early use of combination strategies. Despite limitations as a consensus-based guideline, KMAP-DD 2025 complements evidence-based approaches and provides practical, situation-specific guidance for real-world clinical decision-making in Korea.