ObjectivePost-ischemic acute inflammation and the subsequent persistent dysregulation of the immune microenvironment represent major pathological drivers that aggravate neuronal injury and severely restrict functional recovery following ischemic stroke. Although current reperfusion therapies partially restore blood flow, they fail to effectively modulate the secondary inflammatory cascade and oxidative stress, which remain critical barriers to neurological restoration. To address this challenge, this study aimed to engineer and systematically evaluate a biomimetic nanosystem composed of transforming growth factor-β1 (TGF-β1)-loaded platelet membrane-camouflaged lipid nanoparticles (PLP). This nanosystem was designed to achieve dual lesion-targeted delivery and immune microenvironment remodeling. By verifying its spatiotemporal accumulation, anti-inflammatory activity, and neuroprotective efficacy, we sought to establish an integrated therapeutic strategy that simultaneously enables lesion targeting, immune regulation, and functional recovery after ischemic injury. MethodsThe physicochemical properties of PLP, including hydrodynamic particle size, zeta potential, structural stability, and morphology, were characterized using dynamic light scattering, zeta potential analysis, and transmission electron microscopy. The preservation of platelet membrane-derived adhesion and immunoregulatory proteins was confirmed by SDS-PAGE through comparative analysis of protein band profiles between PLP and native platelet membranes. The in vitro biological activities of PLP were evaluated using two complementary cellular models. LPS-induced M1-polarized RAW264.7 macrophages were employed to assess inflammatory modulation, while oxygen glucose deprivation/reperfusion (OGD/R)-induced BV2 microglial cells and SH-SY5Y neuronal cells were utilized to investigate neuroinflammatory regulation and neuronal protection. For in vivo validation, a transient middle cerebral artery occlusion (tMCAO) mouse model was established to mimic ischemia-reperfusion injury. The spatiotemporal biodistribution and lesion-targeting capability of the PLP were monitored through live fluorescence imaging. Therapeutic efficacy was comprehensively evaluated by triphenyltetrazolium chloride (TTC) staining, glial fibrillary acidic protein (GFAP) immunofluorescence analysis, body weight monitoring, and neurological severity score (NSS) assessment. ResultsPLP nanoparticles displayed a uniform spherical morphology, nanoscale particle size distribution, and stable negative surface charge, indicating favorable colloidal stability and circulation potential. SDS-PAGE results confirmed the effective retention of key platelet membrane proteins associated with endothelial adhesion, immune evasion, and inflammatory regulation, demonstrating the successful biomimetic construction. Optimal therapeutic concentrations were determined in OGD/R-induced BV2 cells, where PLP exhibited excellent cytocompatibility and anti-inflammatory activity.In vitro experiments demonstrated that PLP significantly inhibited the polarization of RAW264.7 macrophages toward the pro-inflammatory M1 phenotype and markedly reduced neuronal apoptosis under ischemia-reperfusion conditions. In vivo fluorescence imaging revealed that PLP rapidly accumulated in the ischemic brain hemisphere and maintained prolonged retention for up to 7 d, suggesting enhanced lesion-specific targeting and sustained drug release. Compared with control group, PLP treatment significantly reduced cerebral infarct volume, attenuated reactive astrogliosis, improved weight recovery, and accelerated neurological functional restoration, as reflected by significantly improved NSS scores. ConclusionThis study establishes a multifunctional biomimetic nanoplatform that integrates platelet membrane-mediated active targeting with the anti-inflammatory, antioxidative, and neuroprotective properties of TGF-β1. The PLP system enables rapid lesion homing and long-term retention while synergistically regulating the post-stroke inflammatory microenvironment by suppressing pro-inflammatory immune activation, reducing neuronal apoptosis, and limiting excessive astrocyte reactivity. Importantly, this study proposes a conceptually therapeutic paradigm that combines targeted delivery with immune microenvironment remodeling to achieve comprehensive neurovascular protection. These findings provide strong experimental evidence supporting the translational potential of biomimetic nanotherapeutics as next-generation precision interventions for ischemic stroke.

Diabetes is a very complex endocrine disease whose common feature is the increase in blood glucose concentration. Persistent hyperglycemia can lead to blindness, kidney and heart disease, neurodegeneration, and many other serious complications that have a significant impact on human health and quality of life. The number of people with diabetes is increasing yearly. The global diabetes prevalence in 20-79 year olds in 2021 was estimated to be 10.5% (536.6 million), and it will rise to 12.2% (783.2 million) in 2045. The main modes of intervention for diabetes include medication, dietary management, and exercise conditioning. Medication is the mainstay of treatment. Marketed diabetes drugs such as metformin and insulin, as well as GLP-1 receptor agonists, are effective in controlling blood sugar levels to some extent, but the preventive and therapeutic effects are still unsatisfactory. Peptide drugs have many advantages such as low toxicity, high target specificity, and good biocompatibility, which opens up new avenues for the treatment of diabetes and other diseases. Currently, insulin and its analogs are by far the main life-saving drugs in clinical diabetes treatment, enabling effective control of blood glucose levels, but the risk of hypoglycemia is relatively high and treatment is limited by the route of delivery. New and oral anti-diabetic drugs have always been a market demand and research hotspot. Inhibitor cystine knot (ICK) peptides are a class of multifunctional cyclic peptides. In structure, they contain three conserved disulfide bonds (C3-C20, C7-C22, and C15-C32) form a compact “knot” structure, which can resist degradation of digestive protease. Recent studies have shown that ICK peptides derived from legume, such as PA1b, Aglycin, Vglycin, Iglycin, Dglycin, and aM₁, exhibit excellent regulatory activities on glucose and lipid metabolism at the cellular and animal levels. Mechanistically, ICK peptides promote glucose utilization by muscle and liver through activation of IR/AKT signaling pathway, which also improves insulin resistance. They can repair the damaged pancrease through activation of PI3K/AKT/Erk signaling pathway, thus lowering blood glucose. The biostability and hypoglycemic efficacy of the ICK peptides meet the requirements for commercialization of oral drugs, and in theory, they can be developed into natural oral anti-diabetes peptide drugs. In this review, the structural properties, activity and mechanism of ICK pattern peptides in regulating glucose and lipid metabolism were summaried, which provided a reference for the development of new oral peptides for diabetes.

The internal structures of cells as the basic units of life are a major wonder of the microscopic world. Cellular images provide an intriguing window to help explore and understand the composition and function of these structures. Scientific imagery combined with artistic expression can further expand the potential of imaging in educational dissemination and interdisciplinary applications. This study presents an innovative diffusion model-based approach for style transfer in cellular images, combining scientific rigor with artistic expression. By leveraging training-free large-scale pre-trained diffusion models, the proposed method integrates the intricate morphological and textural features of cellular images with diverse artistic styles. Key techniques such as the inversion of denoising diffusion implicit models (DDIMs), adaptive instance normalization (AdaIN), self-attention style injection, and attention temperature scaling ensure the preservation of cellular structures while enhancing visual expressiveness. The results showcase the potential of this strategy for interdisciplinary applications, enriching both the visualization and educational dissemination of cellular imagery through compelling storytelling and aesthetic appeal.
Humans ; Image Processing, Computer-Assisted/methods* ; Cells ; Diffusion

Background: s/Aims: In recent years, many minimally invasive techniques have been introduced to reduce the number of ports in laparoscopic cholecystectomy (LC), offering benefits such as reduced postoperative pain and improved cosmetic outcomes. ArtiSential®is a new multi-degree-of-freedom articulating laparoscopic instrument that incorporates the ergonomic features of robotic surgery, potentially overcoming the spatial limitations of laparoscopic surgery. ArtiSential® LC can be performed using only two ports. This study aims to compare the surgical outcomes of ArtiSential® LC with those of single-fulcrum LC. Methods: This retrospective study compared ArtiSential® LC and single-fulcrum LC among LCs performed for gallbladder (GB) stones at the same center, analyzing the basic characteristics of patients; intraoperative outcomes, such as operative time, estimated blood loss, and intraoperative GB rupture; and postoperative outcomes, such as length of hospital stay, incidence of postoperative complications, and postoperative pain. Results: A total of 88 and 63 patients underwent ArtiSential® LC and single-fulcrum LC for GB stones, respectively. Analysis showed that ArtiSential® LC resulted in significantly fewer cases of surgeries longer than 60 minutes (30 vs. 35 min, p = 0.009) and intraoperative GB ruptures (2 vs. 10, p = 0.007). In terms of postoperative outcomes, ArtiSential® LC showed better results in the respective visual analog scale (VAS) scores immediately after surgery (2.59 vs. 3.73, p < 0.001), and before discharge (1.44 vs. 2.02, p = 0.01). Conclusions ArtiSential® LC showed better results in terms of surgical outcomes, especially postoperative pain. Thus, ArtiSential®LC is considered the better option for patients, compared to single-fulcrum LC.

Background: s/Aims: Balancing surgical risks and benefits is crucial for managing non-functional pancreatic neuroendocrine tumors (NF-PNETs). Despite high postoperative pancreatic fistula (POPF) rates, studies on postoperative complications of sporadic NFPNETs are scarce. Thus, this study aimed to investigate postoperative complications and identify risk factors for POPF. Methods: A retrospective review of 166 NF-PNET surgeries performed at Severance Hospital between February 2000 and August 2023 was conducted. Results: Age > 65 years and higher American Society of Anesthesiology (ASA) grade were not significantly correlated with severe complications (odds ratio [OR]: 1.10, p = 0.871 and OR: 1.47, p = 0.491, respectively). Surgical procedures included enucleation (13.9%), distal pancreatectomy (50.0%), central pancreatectomy (4.8%), pancreaticoduodenectomy (PD) (26.5%), and total pancreatectomy (4.8%). Severe complications occurred in 12.05% of surgeries. The overall incidence of all POPFs including biochemical leaks was 53%, while clinically relevant POPF (grade B or C) occurred in 7.8% of patients. Logistic regression showed that PD (OR: 3.94, p = 0.092) tended to be risk factor for POPF and that diameter of the main pancreatic duct (MPD) ≤ 3 mm was a significant risk factor for POPF (OR: 0.22, p = 0.008). A pancreas thickness (PT)/MPD ratio > 4.47 on preoperative computed tomography predicted all POPFs in PD patients (OR: 11.70, p = 0.001). Conclusions Age and comorbidities had no significant impact on surgical outcomes. PD was associated with higher serious complications and POPF rates. The PT/MPD ratio is a valuable preoperative tool for predicting POPF risk in PD patients.

Background: Orbital medial wall fractures, which are more common than inferior wall fractures, have traditionally been difficult to diagnose with conventional radiography. As the fracture extends deep into the bony orbit, accurately visualizing internal structures becomes challenging, increasing the risk of optic nerve compression. In a previous study, the author introduced a technique for treating medial orbital wall fractures using a combined transethmoidal and transcaruncular approach. In this study, the authors hypothesized that the use of surgical navigation could enhance precision, safety, and anatomical reconstruction in this approach and employed navigation during surgery for medial orbital wall fractures and evaluated whether it improved postoperative functional and anatomical outcomes while minimizing complications. Methods: From September 2021 to November 2023, 48 patients with isolated medial wall fractures underwent surgical treatment using a combined transcaruncular approach and transethmoidal packing to repair the orbital fracture. Of these patients, 23 underwent surgery with the use of intraoperative navigation, while the other 25 did not. Intraoperative navigation was employed to facilitate precise fracture reduction and reduce the risk of optic nerve injury. The outcomes were compared by dividing the patients into two groups. Preoperative and postoperative assessments included ophthalmologic evaluations, Hertel exophthalmometry, and computed tomography-based orbital volume measurements. Results: The surgical approach with intraoperative navigation was successfully performed in all patients. Postoperative outcomes showed full recovery without residual symptoms or complications. Orbital volume measurements indicated a significant reduction in the preoperative orbital volume ratio from 109.03% to 104.80% postoperatively (p< 0.001). However, changes in the Hertel scale were not statistically significant (p = 0.086). Conclusion The integration of intraoperative navigation in medial orbital wall fracture surgery enhances the precision of medial orbital wall restoration and minimizes postoperative complications, supporting its use in the surgical management of medial orbital fractures.

The potential causes of cubital tunnel syndrome include trauma, bone deformity, and space-occupying lesions such as tumors. An intraneural ganglion is a cystic tumor composed of a fibrous capsule containing mucinous material within the epineurium of a peripheral nerve, and it most commonly occurs in the peroneal nerve. However, cases of intraneural ganglion cysts occurring at the elbow, leading to cubital tunnel syndrome in the ulnar nerve, have been rarely reported. Cubital tunnel syndrome caused by an intraneural ganglion differs in its pathogenesis from idiopathic nerve entrapment syndrome; thus, it requires distinct approaches for diagnosis and treatment. In this context, the authors report three cases of cubital tunnel syndrome caused by intraneural ganglia. Favorable outcomes were achieved through partial epineurectomy and in situ decompression. Additionally, a review of the literature is presented.

Triple-negative breast cancer (TNBC) is an aggressive cancer subtype lacking targeted therapies and is characterized by highrecurrence rates and poor prognosis. Recent advances in targeting DNA damage response (DDR) pathways using poly (ADP‒ri-bose) polymerase (PARP) inhibitors offer promising therapeutic strategies, especially for TNBC patients with BRCA1/2 mutations.This study reports the development and characterization of ART-446, a novel and selective CHK2 inhibitor. ART-446 showed potent activity against TNBC, regardless of BRCA deficiency, and it also reversed PARP inhibitor resistance. ART-446 potentlyinhibited CHK2 (IC50 : 9.06 nM) with high selectivity over other kinases; it synergized with the PARP inhibitor olaparib, enhancingDNA damage, inducing G2/M cell cycle arrest, and promoting apoptosis in both BRCA-mutant and wild-type TNBC cells. Mechanistic analyses revealed that ART-446 sensitized BRCA mutant and WT cells to PARP inhibitors by impairing DNA repair and increasing the accumulation of DNA damage. Importantly, ART-446 disrupted both homologous recombination and nonhomologous end-joining repair pathways, addressing a key limitation of PARP inhibitor monotherapy—resistance in BRCA-proficient cancers.In vivo, the combination of ART-446 and olaparib significantly reduced tumor growth in TNBC xenograft models without noticeable toxicity. The combined treatment increased DNA damage signaling, as evidenced by elevated γH2AX levels, and enhanced the sensitivity of BRCA2-deficient cells to ART-446. These findings underscore the potential of ART-446 to exploit DNA repair deficiencies and overcome resistance mechanisms associated with PARP inhibitors. By addressing the limitations of current treatments and expanding the utility of PARP inhibitors, ART-446 represents a promising candidate for DDR-targeted therapies, offering a novel approach to improve the outcomes of patients with TNBC.

Purpose: This study compared the outcomes of haploidentical-related donor (HRD) and umbilical cord blood (UCB) hematopoietic stem cell transplantation (HSCT) in pediatric patients with hematologic malignancies. Methods: Data on patients who underwent HRD HSCT with post-transplant cyclophosphamide (n = 41) and UCB HSCT (n = 24) after targeted busulfan-based myeloablative conditioning with intensive pharmacokinetic monitoring between 2009 and 2018 were retrospectively analyzed. Results: The median follow-up durations in the HRD and UCB groups were 7.0 and 10.9 years, respectively. The cumu‑ lative incidence of acute graft-versus-host disease (GVHD) grades II–IV and moderate-to-severe chronic GVHD did not differ significantly between the groups. However, the HRD group demonstrated significantly lower rates of acute GVHD grades III–IV (4.9% vs. 29.2%, p = 0.009) and non-relapse mortality (2.6% vs. 34.2%, p < 0.001) but a higher relapse incidence (32.1% vs. 8.8%, p = 0.004) than the UCB group. The 5-year event-free and overall survival rates were 65.8% and 54.2% (p = 0.204) and 78.0% and 65.7% (p = 0.142) for the HRD and UCB groups, respectively. Multivariate analysis identified disease status as a significant risk factor for overall survival (hazard ratio, 3.24; p = 0.016). Additionally, UCB HSCT exhibited a trend toward worse event-free survival compared to HRD HSCT (hazard ratio, 2.63; p = 0.05). Conclusions These findings indicate that HRD HSCT with post-transplant cyclophosphamide provides promising outcomes compared to UCB HSCT in pediatric patients, with a trend toward improved survival over a long-term follow-up period exceeding a median of 7 years. Thus, HRD HSCT may be a valuable option for pediatric patients with‑ out human leukocyte antigen-matched donors.

The common data model (CDM) has found widespread application in healthcare studies, but its utilization in cancer research has been limited. This article describes the development and implementation strategy for Cancer Clinical Library Databases (CCLDs), which are standardized cancer-specific databases established under the Korea-Clinical Data Utilization Network for Research Excellence (K-CURE) project by the Korean Ministry of Health and Welfare. Fifteen leading hospitals and fourteen academic associations in Korea are engaged in constructing CCLDs for 10 primary cancer types. For each cancer type-specific CCLD, cancer data experts determine key clinical data items essential for cancer research, standardize these items across cancer types, and create a standardized schema. Comprehensive clinical records covering diagnosis, treatment, and outcomes, with annual updates, are collected for each cancer patient in the target population, and quality control is based on six-sigma standards. To protect patient privacy, CCLDs follow stringent data security guidelines by pseudonymizing personal identification information and operating within a closed analysis environment. Researchers can apply for access to CCLD data through the K-CURE portal, which is subject to Institutional Review Board and Data Review Board approval. The CCLD is considered a pioneering standardized cancer-specific database, significantly representing Korea’s cancer data. It is expected to overcome limitations of previous CDMs and provide a valuable resource for multicenter cancer research in Korea.