Knee osteoarthritis (KOA) is a progressive and chronic musculoskeletal condition that continues to be the leading cause of disability worldwide. Conventional treatment approaches for the management of KOA largely focus on symptom alleviation rather than halting or reversing disease progression. However, recent advancements have highlighted the integrated interplay of mechanical stress, inflammation, cellular senescence, and chondrocyte dysfunction in the progression of KOA, in turn prompting new therapeutic strategies. Therefore, emerging interventions such as regenerative medicine, gene therapy, senolytic, platelet-rich plasma (PRP), disease-modifying osteoarthritis drugs (DMODs), and biologics have broadened the therapeutic options. Additionally, natural compounds demonstrated potential in KOA treatment with promising chondroprotective and anti-inflammatory effects.Moreover, digital technologies and clinical and molecular phenotyping enhanced early diagnosis, monitoring, and personalized management of the disease. Therefore, the current narrative review focuses on the molecular insights, clinical outcomes and prospects for the rapidly evolving landscape of current and emerging treatment approaches for the management of knee osteoarthritis (KOA).

Osteoarthritis (OA) is a prevalent, chronic joint disorder characterized by cartilage degradation, synovial inflammation, and extracellular matrix (ECM) remodeling, yet disease-modifying therapies remain elusive. Emerging evidence implicates ferroptosis, an iron-dependent form of regulated cell death driven by lipid peroxidation, and cellular senescence, characterized by growth arrest and a senescence-associated secretory phenotype (SASP), as central contributors to OA pathogenesis. Ferroptotic chondrocytes release reactive lipid species and damage-associated molecular patterns (DAMPs) that induce paracrine senescence in neighboring cells, while senescent cells amplify oxidative stress and ferroptotic susceptibility, forming a self-perpetuating feed-forward loop that accelerates tissue degeneration. Histological, molecular, and in vivo studies demonstrate iron accumulation, lipid peroxidation, glutathione peroxidase 4 (GPX4) depletion, and SASP factor secretion in human OA cartilage, synovium, and animal models, linking these processes to ECM breakdown and joint inflammation. Targeted interventions, alone or in combination, can disrupt this pathological loop, preserve chondrocyte viability, reduce SASP-mediated inflammation, and mitigate cartilage damage. Integration of biomarker-guided patient stratification, advanced imaging, and spatial transcriptomic profiling may enable precision-targeted, disease-modifying therapies. Therefore, elucidating the crosstalk between ferroptosis and senescence offers a conceptual and translational framework for shifting OA management from symptomatic relief toward preservation of joint integrity and long-term disease modification.

Background/Aims: Biliary tract cancer (BTC) is a rare malignancy with poor prognosis. We investigated genomic determinants of clinical benefit from gemcitabine, cisplatin, and nab-paclitaxel (GAP) versus gemcitabine and cisplatin (GC) in advanced BTC. Methods: Clinical and genomic data using TruSight Oncology 500 were analyzed from patients treated with GAP (N=198) or GC (N=89) as first-line therapy. Results: With a median follow-up of 33.0 months, GAP modestly improved progression-free survival (PFS) (hazard ratio [HR] 0.764; 95% confidence interval [CI] 0.591–0.989) without significant overall survival (OS) difference compared to GC. Genomic profiling revealed frequent alterations in TP53 (35.2%), KRAS (16.4%), SMAD4 (10.5%), and TNFRSF14 (10.5%), involving RTK/RAS (44.3%), TP53 (41.8%), and PI3K (20.2%) pathways. Single-gene mutations did not predict treatment benefit. However, pathway-level analysis identified PI3K pathway activation as significantly associated with inferior PFS (HR 2.148; 95% CI 1.478–3.124) and OS (HR 2.096; 95% CI 1.413–3.109) in patients receiving GAP, an effect not observed with GC. Importantly, GAP conferred clinical benefit only in patients without PI3K pathway activation, while no survival advantage was seen in those with such alterations (Pinteraction=0.023 for PFS, Pinteraction=0.003 for OS). Similar results were obtained in the independent validation cohort treated with GAP (N=103) or GC (N=64) for BTC. Conclusions Genomic profiling using next-generation sequencing identified PI3K pathway activation as key molecular determinant that differentiates patient outcomes between GAP and GC treatments in advanced BTC.

Current approaches to regulating osteoarthritis primarily focus on symptom management; however, these methods often have significant side effects and may not be suitable for long-term care. As an alternative to conventional treatments, injecting stem cells into knee joint cartilage is a promising option for repairing damaged cartilage. In this review, we outline the general procedure for stem cell treatment of knee joint cartilage regeneration, emphasizing the potential of intra-articular stem cell injections as a therapeutic option for osteoarthritis. We examined and summarized patient evaluation and preparation for knee joint stem cell therapy, stem cell harvesting, stem cell preparation, injection procedures for stem cell therapy, post-injection care and monitoring, potential outcomes of stem cell therapy, and considerations and risks associated with stem cell therapy. Overall, stem cell injections for knee joint cartilage damage represent a promising frontier in orthopedic care. They offer potential benefits such as pain and inflammation reduction, promotion of cartilage repair and regeneration, and the possibility of avoiding more invasive treatments such as knee surgery. Ongoing collaboration among researchers, clinicians, and regulatory organizations is crucial for advancing this field and translating scientific discoveries into effective clinical applications.

In this study, we investigated the effects of the flavonoid galangin on the expression of the mucin 5AC (MUC5AC) gene in airway cells. Human pulmonary epithelial NCI-H292 cells were pretreated with galangin for 30 min and then stimulated with phorbol 12-myristate 13-acetate (PMA) for 24 h. We also examined the effects of galangin on the PMA-induced nuclear factor-κB (NF-κB) signaling pathway. Galangin inhibited the production of glycoproteins and the expression of MUC5AC mRNA induced by PMA via prevention of NF-κB inhibitor α degradation and NF-κB p65 nuclear translocation. These findings indicated that galangin suppressed mucin gene expression by modulating the NF-κB signaling pathway in human pulmonary epithelial cells.

This study aimed to evaluate the potential of hederacoside C, an active compound isolated from Hedera helix, which has been used for managing inflammatory respiratory diseases, in attenuating epidermal growth factor (EGF)-induced airway MUC5AC mucin gene expression. Human pulmonary mucoepidermoid NCI-H292 cells were pretreated with hederacoside C for 30 min and subsequently stimulated with EGF for 24 h. The study also examined the effect of hederacoside C on the EGF-induced mitogenactivated protein kinase (MAPK) signaling pathway. The results showed that hederacoside C inhibited MUC5AC mucin mRNA expression and the production of mucous glycoproteins by suppressing the phosphorylation of the EGF receptor (EGFR), as well as the phosphorylation of MAPK/extracellular signal-regulated kinase (ERK) 1/2 (MEK1/2), p38 MAPK, ERK 1/2 (p44/42), and the nuclear expression of specificity protein-1 (Sp1). These findings suggest that hederacoside C has the potential to reduce EGFinduced mucin gene expression by inhibiting the EGFR-MAPK-Sp1 signaling pathway in NCI-H292 cells.

Gastric cancer is one of the most common cancers in both Korea and worldwide. Since 2004, the Korean Practice Guidelines for Gastric Cancer have been regularly updated, with the 4th edition published in 2022. The 4th edition was the result of a collaborative work by an interdisciplinary team, including experts in gastric surgery, gastroenterology, endoscopy, medical oncology, abdominal radiology, pathology, nuclear medicine, radiation oncology, and guideline development methodology. The current guideline is the 5th version, an updated version of the 4th edition. In this guideline, 6 key questions (KQs) were updated or proposed after a collaborative review by the working group, and 7 statements were developed, or revised, or discussed based on a systematic review using the MEDLINE, Embase, Cochrane Library, and KoreaMed database. Over the past 2 years, there have been significant changes in systemic treatment, leading to major updates and revisions focused on this area.Additionally, minor modifications have been made in other sections, incorporating recent research findings. The level of evidence and grading of recommendations were categorized according to the Grading of Recommendations, Assessment, Development and Evaluation system. Key factors for recommendation included the level of evidence, benefit, harm, and clinical applicability. The working group reviewed and discussed the recommendations to reach a consensus. The structure of this guideline remains similar to the 2022 version.Earlier sections cover general considerations, such as screening, diagnosis, and staging of endoscopy, pathology, radiology, and nuclear medicine. In the latter sections, statements are provided for each KQ based on clinical evidence, with flowcharts supporting these statements through meta-analysis and references. This multidisciplinary, evidence-based gastric cancer guideline aims to support clinicians in providing optimal care for gastric cancer patients.

Background/Aims: Although the urea breath test (UBT) is widely used as a representative monitoring test after Helicobacter pylori eradication, false-negative results can occur because of the gray zone related to its cutoff value. This study aimed to compare the diagnostic performances of the rapid urease test (RUT), the RUT with sweeping method, and the UBT, and to investigate the role of the sweeping method in the gray zone of UBT values. Methods: We retrospectively reviewed 216 patients who received standard first-line H. pylori eradication treatments (n=216). All participants underwent to testing using the sweeping method and UBT on the same day. The sensitivity, specificity, and accuracy were analyzed to compare the two methods. Results: The sensitivity (0.537 vs 0.806, p=0.002) and accuracy (0.843 vs 0.870, p=0.026) of the UBT were inferior to those of the sweeping method. A total of 31 individuals tested positive for H. pylori according to the UBT, whereas 54 individuals tested positive according to the sweeping method. In the group for which the gold standard definition indicated H. pylori positivity but UBT results were negative (n=31), all individuals had a UBT value under 2.5‰. In the multivariate logistic regression model, a UBT value of 1.4‰ to 2.5‰ increased the risk of false-negative results by 6.5 times (odds ratio, 6.5; 95% confidence interval, 2.077 to 20.288; p=0.001). Conclusions After H. pylori eradication, false-negative results can occur for individuals undergoing the UBT, primarily for values below the UBT cutoff. The RUT with the sweeping method can potentially help detect H. pylori in the gray zone of the UBT, improving diagnostic accuracy.

Current approaches to regulating osteoarthritis primarily focus on symptom management; however, these methods often have significant side effects and may not be suitable for long-term care. As an alternative to conventional treatments, injecting stem cells into knee joint cartilage is a promising option for repairing damaged cartilage. In this review, we outline the general procedure for stem cell treatment of knee joint cartilage regeneration, emphasizing the potential of intra-articular stem cell injections as a therapeutic option for osteoarthritis. We examined and summarized patient evaluation and preparation for knee joint stem cell therapy, stem cell harvesting, stem cell preparation, injection procedures for stem cell therapy, post-injection care and monitoring, potential outcomes of stem cell therapy, and considerations and risks associated with stem cell therapy. Overall, stem cell injections for knee joint cartilage damage represent a promising frontier in orthopedic care. They offer potential benefits such as pain and inflammation reduction, promotion of cartilage repair and regeneration, and the possibility of avoiding more invasive treatments such as knee surgery. Ongoing collaboration among researchers, clinicians, and regulatory organizations is crucial for advancing this field and translating scientific discoveries into effective clinical applications.