Objective: To explore the application effectiveness of healthcare failure mode and effect analysis (HFMEA) in optimizing intelligent blood logistics transport pathways for safety assurance. Methods: Data from 1 851 cases of intelligent blood logistics transport were collected between September 2023 and March 2025. Based on the implementation phases of HFMEA measures, the cases were divided into a control group (n=120), observation group 1 (n=219), and observation group 2 (n=1 512). Through systematic analysis of the transport processes, hazard scoring and decision tree analysis were conducted for each process, and phased optimization measures were implemented for high-risk failure modes. Results: The transport duration of intelligent blood logistics was 35.5 (20.8, 71.1) min in the control group, 25.1 (10.9, 40.7) min in observation group 1, and 9.9 (4.2, 44.5) min in observation group 2. Observation group 2 exhibited significantly shorter transport time compared to both observation group 1 and the control group, with statistically significant differences between groups (P<0.000 1). Conclusion: The implementation of HFMEA-driven measures significantly reduced intelligent blood logistics transport duration, thereby fostering the evolution of smart hospital ecosystems while enhancing healthcare service quality and operational efficiency.

Background: To investigate Korean neurologists' perceptions of the non-standard term ‘jayulsingyeongsiljo’ and their actual evaluation and management of such patients. Methods: We performed an anonymous web-based cross-sectional survey of board-certified Korean neurologists by Korean Society of Pain and Autonomic Disorders between August 13 and September 10, 2025. A questionnaire sent by e-mail asked about demographics, experience with patients labeled with ‘jayulsingyeongsiljo,’ use and perceived usefulness of autonomic function tests, the impact of coronavirus disease 2019, and opinions on terminology and the role of neurologists. Results: In total, 109 neurologists responded. Most reported that patients presenting for ‘jayulsingyeongsiljo’ were young or middle-aged adults and that their numbers had increased over the preceding 2 years. Referrals frequently originated from Korean medicine clinics and other non-neurology departments, often after stand-alone heart rate variability testing. Fatigue, orthostatic intolerance, palpitations, sweating abnormalities, gastrointestinal symptoms, and anxiety or insomnia were common, and autonomic testing was generally regarded as helpful. Eighty percent felt that the risks associated with ‘jayulsingyeongsiljo’ are overstated, and 95% preferred replacing the term with standardized expressions such as autonomic dysfunction. Conclusions Korean neurologists view ‘jayulsingyeongsiljo’ as an unrecognized and potentially misleading label and support society-led standardization of terminology and guidance to improve autonomic dysfunction care and resource use.

A unified consensus statement on medication-related osteonecrosis of the jaw (MRONJ) has not yet been established among the Asian member countries or regions of the Asian Federation of Osteoporosis Societies (AFOS). This study aimed to develop a consensus on MRONJ in patients with osteoporosis across these countries and regions. In this study, the term “Asia-Pacific” refers specifically to the Asian member countries and regions of AFOS. A structured survey consisting of nine MRONJ-related questions was distributed across 10 countries and regions to assess the level of agreement and summarize regional perspectives. In addition, a manual literature review and voting were conducted to evaluate the current evidence on MRONJ. The key aspects of MRONJ, including definition, staging, diagnosis, pathogenesis, risk factors, management, and prevention, were generally consistent among the AFOS countries and regions. The annual incidence and incidence rate of MRONJ associated with low-dose antiresorptive therapy in patients with osteoporosis ranged from 0.025% to 0.136% and 21 to 283 cases per 100,000 person-years, respectively. However, evidence regarding the benefits of drug discontinuation before dental surgery, such as tooth extraction, remains insufficient. Large-scale, multinational studies across AFOS countries and regions are warranted to determine the incidence of MRONJ better and evaluate the impact of antiresorptive drug discontinuation before dental procedures. These findings may contribute to the devel opment of effective evidence-based strategies for preventing MRONJ in patients with osteoporosis.

Objective: To classify life stages for companion dogs and cats by identifying clusters in age-specific disease proportions derived from medical records, providing a data-driven foundation for health examination programs. Methods: We collected 505,667 medical records from 82 veterinary facilities in South Korea between 2020 and 2023. Diagnoses were standardized using GPT-4o and S-BioBERT. Following preprocessing, data from 27 facilities yielded 222,706 canine and 39,910 feline records for the final analysis. Principal component analysis and K-means clustering (K = 4) were applied to age-specific disease proportions to identify life stages.The 10 most highest-proportion diagnoses diseases were determined for each cluster. Results: Canine life stages were classified as ≤ 1 year, 2–5 years, 6–10 years, and 11–15+ years.Feline life stages were 1–2 years, 3–8 years, 9–12 years, and 13–15+ years. In dogs, developmental diseases were common in the youngest age group, while chronic diseases were more prevalent in older groups. In cats, oral and urinary diseases were high-ranking, conjunctivitis was most common in the early stage, and chronic diseases increased with age. Conclusions and Relevance: Age-specific diagnosis patterns support four practical life stages for dogs and cats in South Korea. These boundaries can inform evidence-based preventive examination schedules, animal health policy, and pet insurance product design.

Background: One-lung ventilation (OLV) during thoracic surgery frequently requires approximately 100% oxygen, imposing the risk of hyperoxemia. This study aimed to assess whether oxygen reserve index (ORI)-guided fraction of inspired oxygen (FiO2) adjustment can reduce the incidence of hyperoxemia in children undergoing lung resection. Methods: This prospective, randomized controlled trial enrolled children aged < 7 years scheduled for thoracoscopic lung resection. The participants were randomly assigned to either a conventional group (FiO2 adjusted based on arterial blood gas analysis [ABGA]) or an ORI group (FiO2 titrated to maintain an ORI target of 0.15). ABGA was performed 10 and 30 min after the start of OLV (T1 and T2). The primary outcome was the incidence of hyperoxemia 30 min after OLV (T2). Results: Data from 64 children (31 conventional, 33 ORI groups) were analyzed. The incidence rate of hyperoxemia at T2 was similar between the conventional and ORI groups (54.8% vs. 60.6%, P = 0.801). However, partial pressure of arterial oxygen at T1 was significantly lower in the ORI group than in the conventional group (214.6 ± 65.5 mmHg vs. 268.8 ± 92.7 mmHg, P = 0.014). The ORI group demonstrated a lower time-weighted average FiO2 during OLV (0.79 ± 0.12 vs. 0.87 ± 0.09, P = 0.004). The ORI group required more rescue interventions than the conventional group and experienced fewer episodes of hypoxia. Conclusions ORI-guided FiO2 adjustment does not significantly reduce the incidence of hyperoxemia in children undergoing OLV but reduces time-weighted FiO2 and hypoxic events.

Vaccines are highly effective, but rare or delayed adverse events following immunization (AEFIs) require post-licensure surveillance beyond clinical trials. Korea lacks a comprehensive, active, database-based framework, yet key assets exist: nationwide claims databases (National Health Insurance Service/Health Insurance Review and Assessment Service), the national immunization registry (Korea Disease Control and Prevention Agency’s Immunization Registry Information System) for National Immunization Program (NIP) and non-NIP vaccines, and increasingly standardized hospital electronic health records.We propose a federated, code to data architecture with data linkages between these data.Implementation should adopt a common data model (CDM), standardized case definitions, latency accounting, and transparent public reporting under strong privacy governance. Major challenges include multi step administrative approvals for data linkage, incomplete capture of adult non-NIP vaccinations, heterogeneous hospital data structures, and strict data protection constraints. Strategic priorities are to streamline statutory and administrative processes for public health use, mandate or enable claims-based capture of adult vaccinations, enhance CDM based interoperability, and develop secure hubs for aggregated outputs. With these measures, Korea will be well positioned to establish a scalable active surveillance system capable of detecting rare AEFIs, supporting transparent and evidence-based communication, and ensuring equitable injury compensation grounded in domestic data.

Composite gangliocytomaeuroma and neuroendocrine tumors (CoGNETs) are extremely rare periampullary neoplasms composed of neuroendocrine epithelial, Schwannian spindle, and ganglion cells. Although endoscopic papillectomy or surgery have been used to treat ampullary CoGNETs, underwater endoscopic mucosal resection (UEMR) for periampullary lesions has not been previously described. In this study, we present a case of a 53-year-old man referred to our hospital with an incidentally detected subepithelial tumor in the second portion of the duodenum. Endoscopic ultrasound revealed a 13×10-mm homogeneous, hypoechoic, and well-demarcated submucosal mass. UEMR was performed under conscious sedation without submucosal injection, achieving safe en bloc resection within 12 min. Histopathology revealed a 2.0×1.5×1.2-cm lesion composed of mixed neuroendocrine epithelial, Schwannian spindle, and ganglion cells. Immunohistochemical staining was positive for chromogranin A, synaptophysin, CD56, neuron-specific enolase, and S-100, confirming CoGNET with a Ki-67 index of <1% and no lymphovascular or perineural invasion. Follow-up endoscopy 3 months later revealed only a post-resection scar without residual or recurrent tumors. This appears to be the first reported case of periampullary CoGNET successfully treated with UEMR. Therefore, UEMR might represent a safe and effective therapeutic option for selected periampullary subepithelial tumors.

Inteins are unique protein insertion sequences capable of self-excision, enabling the covalent ligation of flanking extein peptides via amide bond formation. This process proceeds spontaneously without requiring external enzymes, cofactors, or chemical reagents, granting inteins exceptional biocompatibility and traceless performance in protein engineering applications. Split inteins represent a specialized and versatile subclass whose splicing domains are encoded by two separate gene fragments rather than a single continuous open reading frame. These fragments, known as the N-terminal (IntN) and C-terminal (IntC) split inteins, associate through non-covalent interactions including hydrophobic forces, hydrogen bonds, and van der Waals forces to assemble into an active three-dimensional structure, which then drives efficient extein ligation and enables protein trans-splicing. Protein trans-splicing mediated by split inteins has become a cornerstone for traceless protein ligation owing to its high specificity and irreversibility, fundamentally reshaping strategies for protein modification, assembly, and functional regulation. Compared with traditional chemical ligation methods, split intein systems require no complex chemical derivatization of peptide fragments and can operate efficiently at micromolar concentrations under physiological conditions, thus avoiding structural and functional damage caused by organic reagents. In contrast to enzymatic ligation tools such as sortase, split inteins eliminate the need for additional enzymes or cofactors, simplifying reaction systems, reducing costs, and minimizing non-specific side products. These distinctive advantages render split inteins highly promising for applications in chemical biology, synthetic biology, and biopharmaceutical development. In recent years, deepened mechanistic understanding has established structure-guided rational design as the primary approach to overcoming key limitations of split inteins, including intrinsic aggregation propensity, strict extein sequence dependence, and limited splicing efficiency. Bioinformatic tools have been used to identify aggregation-prone regions in the IntN fragment, and site-directed mutagenesis of hydrophobic residues, relocation of split sites, or removal of misfolding-prone sequences has substantially reduced in vitro aggregation and improved soluble expression and assembly activity. Rational engineering of catalytic residues and adjacent flexible loops has relaxed strict amino acid preferences at extein junctions, enhancing sequence tolerance and reducing the risk of functional impairment in target proteins. Consensus design based on multiple sequence alignments has yielded ultra-fast splicing variants such as Cfa DnaE and Cat-TerL, which exhibit significantly accelerated kinetics and improved tolerance to denaturing conditions. Meanwhile, advances in structural biology have further clarified the conformational dynamics and catalytic mechanisms of splicing, supporting the precise design of high-performance intein modules. On this basis, electrostatic interaction tuning and metagenomic screening have yielded multiple mutually orthogonal split intein pairs, enabling selective multi-fragment protein ligation and providing new routes for the efficient synthesis of large multi-domain functional proteins. With these engineered split inteins offering continuously improved performance and expanded applicability, protein trans-splicing has been widely applied in numerous cutting-edge areas of protein research and biomedicine. In gene delivery, split intein-based systems overcome the packaging limit of adeno-associated viral vectors, enabling the accurate reconstitution of large therapeutic proteins and base editors in target cells, thereby enhancing the efficacy and scope of gene therapy for genetic diseases. In internal protein sequence editing, split inteins mediate precise sequence replacement and modification in flexible regions or loops of target proteins, without the need for complex multi-step ligation and protein refolding involved in traditional protein semisynthesis. In protein-protein interaction studies, intein-mediated splicing covalently captures transient and weak intracellular complexes, enabling sensitive, high-throughput interaction detection and drug screening. In synthetic biology, conditionally controllable splicing systems support the construction of diverse intracellular and cell-surface biological logic gates for the precise regulation of cellular behavior. In mechanistic biochemical research, split inteins enable photocatalytic proximity labeling and site-specific tagging, allowing the preparation of homogeneous protein samples carrying precise post-translational modifications such as ubiquitination and polyglutamylation for chromatin interactome analysis and epigenetic studies. Moreover, covalent trapping strategies using split inteins stabilize transient enzymatic intermediates, providing unprecedented insights into molecular mechanisms such as nucleosome ubiquitination that are difficult to elucidate using conventional methods. This review systematically summarizes key technological advances in split inteins over the past decade, highlighting engineering strategies, mechanistic insights, and the development of orthogonal components. It comprehensively surveys emerging applications at the frontiers of protein research, analyzes current core challenges, and proposes future directions, particularly emphasizing artificial intelligence-driven de novo design and novel splicing pathways to break existing technical bottlenecks. By enabling traceless, efficient, and versatile protein manipulation, split inteins continue to serve as indispensable tools that drive innovation in protein engineering and fundamental life science research.

Multidrug-resistant (MDR) bacterial infections have emerged as a serious challenge of global public health crisis. The overuse and misuse of conventional antibiotics have dramatically accelerated the emergence, evolution and worldwide spread of drug-resistant bacterial strains, necessitating urgent exploration of novel antibacterial strategies. Bacteriophages serve as natural bacterial predators offering distinct advantages including high host specificity, autonomous self-replication capabilities and cost-effective large-scale production. However, wild-type phages present significant clinical limitations due to their narrow host ranges, susceptibility to rapid immune clearance and poor penetration of bacterial biofilms, which severely restrict their therapeutic applications. The convergence of synthetic biology, nanotechnology and advanced gene editing technologies has accelerated the development of engineered bacteriophage platforms, providing programmable, scalable and clinically translatable pathways to overcome these inherent biological constraints. Here, we systematically delineate four fundamental strategies for engineered bacteriophage development. Chemical modification utilizes reactive functional groups such as amino, carboxyl and thiol moieties on capsid proteins through esterification, amidation or click chemistry reactions to achieve precise drug conjugation and surface functionalization. In vivo editing encompasses ultraviolet or chemical mutagenesis for random mutation induction, homologous recombination for targeted genetic alterations, recombineering methodologies including electroporation-mediated bacteriophage recombination engineering, and CRISPR-Cas systems for precise genome editing to enable exact genetic reconstruction and host range reprogramming. In vitro synthesis leverages genome engineering platforms where intact phage genomes are transferred into yeast or host bacteria to facilitate highly efficient homologous recombination, enabling large DNA fragment assembly and cross-gene host range expansion without bacterial toxicity constraints. Directed evolution combines artificial selection through mutation library screening with rational design approaches involving chimeric receptor binding protein construction or site-specific mutagenesis, effectively balancing the discovery of unknown adaptive pathways with targeted host specificity modification. Moreover, we comprehensively discuss therapeutic applications across diverse clinical scenarios. Engineered bacteriophage effectively disrupt bacterial biofilms through sophisticated functionalized delivery platforms including nanozyme-conjugated phages, phage-liposome nanoconjugates and bio-responsive hydrogels, demonstrating significantly enhanced bactericidal efficiency compared to unmodified free phages. These bioengineered vectors attenuate bacterial virulence and resensitize pathogens to antibiotics by delivering CRISPR-Cas systems or base editors to disrupt critical virulence factors such as pili, capsule synthesis machineries and quorum sensing systems, or by inactivating antibiotic resistance determinants including beta-lactamase genes. As an intelligent nanomedicine delivery platform, engineered bacteriophage enable precise pathogen elimination an through photocatalytic reactive oxygen species generation, immunomodulatory interventions, or controlled release of antibacterial drugs. Furthermore, oral administration of engineered bacteriophage facilitates microbiota modulation, which selectively eliminate intestinal pathogens while preserve beneficial commensal microbiota, thereby restoring microbial community balance and preventing complications associated with dysbiosis. Finally, we critically analyze persistent challenges including host strain matching complexity, evolution of bacterial resistance mechanisms, pharmacokinetic optimization requirements, optimal administration route selection, large-scale production quality control standards and clinical dosing determination protocols. Through multidisciplinary integration of synthetic biology, infectious disease medicine and immunology, future translational medicine studies of bacteriophage should establish comprehensive technical platforms encompassing rapid phage screening, intelligent rational design, rigorous in vivo evaluation and standardized clinical validation processes, ultimately advancing engineered bacteriophage from laboratory innovations to clinically approved therapeutics for effectively combating MDR bacterial infections.