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.

Background: The management of distal radius fractures (DRFs) has evolved with the introduction of volar locking plate (VLP) fixation.Nevertheless, despite the low occurrence rates, reduction loss following VLP fixation has been reported in several studies. Our objective was to determine the incidence and features of reduction loss in patients despite the appropriate application of VLP fixation for DRF. Methods: This retrospective study was conducted between March 2017 and August 2023, during which a single hand surgeon performed VLP procedures for DRFs. This study included 379 patients (382 wrists) including 3 patients who underwent bilateral surgery. We identified patients who experienced reduction loss after VLP fixation (group 1) and patients without stability problems (group 2) and compared the 2 groups. Results: The mean age of the patients was 63.5 years, with a standard deviation of 13.8. There were 90 male patients (23.6%) and 289 female patients (75.7%). We identified 14 cases of DRFs, in which reduction loss occurred even after VLP fixation during the follow-up period (group 1, 3.7%). The remaining DRFs were assigned to group 2 (n=368, 96.3%). Among the 14 patients, 7 cases of screw breakage were identified as causing the loss of fracture reduction. As the joint surface collapsed and sank down to the distal row locking screw, 4 cases presented with distal locking screws penetrating into the radiocarpal joint. There were no significant differences between the 2 groups in terms of sex, weight, fracture arm direction, and Arbeitsgemeinschaft für Osteosynthesefragen/Orthopaedic Trauma Association (AO/OTA) fracture classification. However, patients in group 1 were statistically significantly older than those in group 2 (average age, 77.5 years vs. 62 years). Among 4 patients experiencing distal screw violation of the radiocarpal joints, 3 underwent partial or complete screw removal immediately after fracture consolidation or union. Conclusions While rare, reduction loss remains a potential complication following VLP fixation, especially in elderly patients with intra-articular DRFs. However, with diligent monitoring and timely intervention, such as implant removal if necessary, acceptable outcomes can still be attained.

This study aims to explore the pharmacodynamic material basis of Jinbei Oral Liquid(JBOL) against idiopathic pulmonary fibrosis(IPF) based on serum pharmacochemistry and network pharmacology. The ultra-high performance liquid chromatography-quadrupole time-of-flight tandem mass spectrometry(UHPLC-Q-TOF-MS/MS) technology was employed to analyze and identify the components absorbed into rat blood after oral administration of JBOL. Combined with network pharmacology, the study explored the pharmacodynamic material basis and potential mechanism of JBOL against IPF through protein-protein interaction(PPI) network construction, "component-target-pathway" analysis, Gene Ontology(GO) functional enrichment, and Kyoto Encyclopedia of Genes and Genomes(KEGG) pathway enrichment analysis. First, a total of 114 compounds were rapidly identified in JBOL extract according to the exact relative molecular mass, fragment ions, and other information of the compounds with the use of reference substances and a self-built compound database. Second, on this basis, 70 prototype components in blood were recognized by comparing blank serum with drug-containing serum samples, including 28 flavonoids, 25 organic acids, 4 saponins, 4 alkaloids, and 9 others. Finally, using these components absorbed into blood as candidates, the study obtained 212 potential targets of JBOL against IPF. The anti-IPF mechanism might involve the action of active ingredients such as glycyrrhetinic acid, cryptotanshinone, salvianolic acid B, and forsythoside A on core targets like AKT1, TNF, and ALB and thereby the regulation of multiple signaling pathways including PI3K/AKT, HIF-1, and TNF. In conclusion, JBOL exerts the anti-IPF effect through multiple components, targets, and pathways. The results would provide a reference for further study on pharmacodynamic material basis and pharmacological mechanism of JBOL.
Drugs, Chinese Herbal/pharmacokinetics* ; Animals ; Tandem Mass Spectrometry ; Network Pharmacology ; Rats ; Chromatography, High Pressure Liquid ; Rats, Sprague-Dawley ; Male ; Idiopathic Pulmonary Fibrosis/metabolism* ; Humans ; Administration, Oral ; Protein Interaction Maps/drug effects* ; Signal Transduction/drug effects*

OBJECTIVE: To investigate the regulatory effects of two traditional mineral medicines (TMMs), Gypsum Fibrosum (Shigao, GF) and Terra Flava Usta (Zaoxintu, TFU), on gut-beneficial bacteria in mice, and preliminarily explore their mechanisms of action. METHODS: Mice were randomly divided into 3 groups (n=10 per group): the control group (standard diet), the GF group (diet supplemented with 2% GF), and the TFU group (diet supplemented with 2% TFU). After 4-week intervention, 16S rRNA gene sequencing was used to analyze the changes in the gut microbiota (GM). Scanning electron microscopy, in combination with coumarin A tetramethyl rhodamine conjugate and Hoechst stainings, was used to observe the bacteria and biofilm formation. RESULTS: Principal coordinate analysis revealed that GF and TFU significantly altered the GM composition in mice. Further analysis revealed that GF and TFU affected different types of gut bacteria, suggesting that different TMMs may selectively modulate specific bacterial populations. For certain bacteria, such as Faecalibaculum and Ileibacterium, both GF and TFU exhibited growth-promoting effects, implying that they may be sensitive to TMMs and that different TMMs can increase their abundance through their respective mechanisms. Notably, Lactobacillus reuteri, a widely recognized and used probiotic, was significantly enriched in the GF group. Random forest analysis identified Ileibacterium valens as a potential indicator bacterium for TMMs' impact on GM. Further mechanistic studies showed that gut bacteria formed biofilm structures on the TFU surface. CONCLUSIONS This study provides new insights into the interaction between TMMs and GM. As safe and effective natural clays, GF and TFU hold promise as potential candidates for prebiotic development.
Animals ; Gastrointestinal Microbiome/drug effects* ; Bacteria/growth & development* ; Mice ; Biofilms/drug effects* ; Male ; RNA, Ribosomal, 16S/genetics*

Cemental tear is a rare and indetectable condition unless obvious clinical signs present with the involvement of surrounding periodontal and periapical tissues. Due to its clinical manifestations similar to common dental issues, such as vertical root fracture, primary endodontic diseases, and periodontal diseases, as well as the low awareness of cemental tear for clinicians, misdiagnosis often occurs. The critical principle for cemental tear treatment is to remove torn fragments, and overlooking fragments leads to futile therapy, which could deteriorate the conditions of the affected teeth. Therefore, accurate diagnosis and subsequent appropriate interventions are vital for managing cemental tear. Novel diagnostic tools, including cone-beam computed tomography (CBCT), microscopes, and enamel matrix derivatives, have improved early detection and management, enhancing tooth retention. The implementation of standardized diagnostic criteria and treatment protocols, combined with improved clinical awareness among dental professionals, serves to mitigate risks of diagnostic errors and suboptimal therapeutic interventions. This expert consensus reviewed the epidemiology, pathogenesis, potential predisposing factors, clinical manifestations, diagnosis, differential diagnosis, treatment, and prognosis of cemental tear, aiming to provide a clinical guideline and facilitate clinicians to have a better understanding of cemental tear.
Humans ; Dental Cementum/injuries* ; Consensus ; Diagnosis, Differential ; Cone-Beam Computed Tomography ; Tooth Fractures/therapy*

AIM To investigate the protective effect of Sanfeng Tongqiao Dropping Pills against house dust mite(HDM)-induced allergic asthma in mice.METHODS Compared to the intact BALB/c mice in the blank control group,the BALB/c mice randomly assigned into the model group,the dexamethasone group(0.67 mg/kg),and the low-dose,medium-dose,and high-dose Sanfeng Tongqiao Dropping Pills groups(15,30 and 60 mg/kg),were induced into acute allergic asthma models via weekly intraperitoneal sensitization with 0.1 mL HDM solution(0.5 mg/mL)for three weeks followed by three consecutive daily intranasal challenges with 10 μL HDM solution(2.5 mg/mL)starting in the third week.The drug administered continuously 7 days after the last excitation.The mice had their airway reactive Penh value detected,their pulmonary pathological changes observed by HE staining,their blood eosinophils(EOS)counted,their Th2 cytokines in lung tissue and serum IgE levels detected by ELISA,and their number of peripheral blood mononuclear cells(PBMC)and pulmonary Th2 cells detected by flow cytometry.Chronic allergic asthma was induced in grouped BALB/c mice through repeated intranasal challenges with 10 μL HDM solution(2.5 mg/mL)administered five times weekly for five consecutive weeks.Drug treatment continued for 14 days following the final challenge.After the final treatment,the mice had their pulmonary pathological changes observed by HE staining,and their levels of Th2 cytokines in B ALF and lung tissue and serum IgE detected by ELISA.RESULTS Compared to the blank control group,the acute allergic asthma model group exhibited increases in Penh value,EOS count and IgE level in serum,IL-4 and IL-5 levels in lung tissue(P＜0.01);obvious pulmonary inflammatory cells infiltration,and thickened airway wall;and increase in pulmonary number of Th2 cells(P＜0.01).Compared to the model group,the groups intervened with Sanfeng Tongqiao Dropping Pills demonstrated decreased Penh value,serum EOS count,IgE level and IL-5 level in lung tissue(P＜0.05,P＜0.01);reduced pulmonary inflammatory infiltration and alleviated airway wall thickening;and decreased number of pulmonary Th2 cells.Compared to the blank group,the chronic allergic asthma model group showed obvious pulmonary inflammatory infiltration and airway wall thickening;and increased EOS count and IgE level in serum,IL-4 and IL-13 in lung tissue and IL-14 in BALF(P＜0.05,P＜0.01).Compared to the model group,the groups intervened with either medium-dose or high-dose Sanfeng Tongqiao Dropping Pills demonstrated reduced pulmonary inflammatory infiltration;and decreased serum EOS count,IgE level,IL-13 in lung tissue and IL-14 in BALF(P＜0.05,P＜0.01).CONCLUSION Sanfeng Tongqiao Dropping Pills reduce Th2 cells in peripheral blood and lung tissue,suppress type 2 inflammation,and thereby alleviate allergic asthma.

The analysis presented here is based on the blood components of Guanxin Qiwei tablets, the key anti-atherosclerosis pathway of Guanxin Qiwei tablets was screened by network pharmacology, and the anti-atherosclerosis mechanism of Guanxin Qiwei tablets was clarified and verified by cell experiments. HPLC-Q-Exactive-MS/MS technique was used to analyze the components of Guanxin Qiwei tablets into blood, to determine the precise mass charge ratio of the compounds, and to conduct a comprehensive analysis of the components by using secondary mass spectrometry fragments and literature comparison. Finally, a total of 42 components of Guanxin Qiwei tablets into blood were identified. To better understand the interactions, we employed the Swiss Target Prediction database to predict the associated targets. Atherosclerosis (AS) disease targets were searched in disease databases Genecard, OMIM and Disgent, and 181 intersection targets of disease targets and component targets were obtained by Venny 2.1.0 software. Protein interactions were analyzed by String database. The 32 core targets were selected by Cytscape software. Gene Ontology (GO) enrichment analysis and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis were performed in DAVID database. It was found that the anti-atherosclerosis pathways of Guanxin Qiwei tablets mainly include lipid metabolism and atherosclerosis and AGE-RAGE signaling pathway in diabetic complications and other signal pathways. The core targets and the core compounds were interlinked, and it was found that cryptotanshinone and tanshinone ⅡA in Guanxin Qiwei tablets were well bound to TNF, PPARγ, AKT1, PTG2 and other targets. The lipid metabolism and atherosclerotic pathway was verified using human hl-7702 hepatocytes. This study preliminarily identified the potential pharmacodynamic components of Guanxin Qiwei tablets in the treatment of AS diseases and predicted their pathways of action, and verified the relationship between regulating lipid metabolism and atherosclerosis of Guanxin Qiwei tablets in vitro, providing a reference for the further study of the pharmacodynamic material basis and mechanism of action of this prescription. This experiment was approved by the Medical Ethics Committee of Inner Mongolia Medical University (No. YKD202401262).

Purpose: In pancreatic cancer, therapeutic investigations targeting liver metastases could improve survival. However, the use of local treatment for oligometastasis in pancreatic cancer remains controversial. This study aimed to investigate the oncological role of local therapy in patients who underwent curative pancreatectomy and subsequently developed liver metastases. Materials and Methods: Data concerning patients who underwent curative pancreatectomy for pancreatic cancer at Severance Hospital in Seoul, South Korea between 2006 and 2018 were retrospectively reviewed. We included patients with one or two liver metastases, as confirmed on imaging. We excluded those with metastases in other organs. The patients were divided into two groups: the NT group, receiving conventional therapy without local treatment; and the LT group, receiving local treatments for liver metastases alongside standard therapy. Results: Of the 43 included patients (NT group, n=33; LT group, n=10), no significant differences were observed in overall survival (OS) [hazard ratio (HR) 0.846; 95% confidence interval (CI) 0.397–1.804; p=0.665] or post-recurrence survival (HR 0.932; 95% CI 0.437–1.985, p=0.855) between the two groups. In multivariate analysis, early recurrence within 6 months (p<0.001) and the use of 5-fluorouracil (FU)-based adjuvant chemotherapy (CTx) (p=0.011), as well as 5-FU-based CTx after liver metastasis (p=0.008) when compared with gemcitabine-based regimens, were significant predictors of poor OS. Conclusion The oncologic role of local treatment for hepatic metastasis remains controversial in patients with hepatic metastasis after radical pancreatectomy. In the era of potent chemotherapeutic regimens, further research is needed to clarify the efficacy of such regimens.

Purpose: In pancreatic cancer, therapeutic investigations targeting liver metastases could improve survival. However, the use of local treatment for oligometastasis in pancreatic cancer remains controversial. This study aimed to investigate the oncological role of local therapy in patients who underwent curative pancreatectomy and subsequently developed liver metastases. Materials and Methods: Data concerning patients who underwent curative pancreatectomy for pancreatic cancer at Severance Hospital in Seoul, South Korea between 2006 and 2018 were retrospectively reviewed. We included patients with one or two liver metastases, as confirmed on imaging. We excluded those with metastases in other organs. The patients were divided into two groups: the NT group, receiving conventional therapy without local treatment; and the LT group, receiving local treatments for liver metastases alongside standard therapy. Results: Of the 43 included patients (NT group, n=33; LT group, n=10), no significant differences were observed in overall survival (OS) [hazard ratio (HR) 0.846; 95% confidence interval (CI) 0.397–1.804; p=0.665] or post-recurrence survival (HR 0.932; 95% CI 0.437–1.985, p=0.855) between the two groups. In multivariate analysis, early recurrence within 6 months (p<0.001) and the use of 5-fluorouracil (FU)-based adjuvant chemotherapy (CTx) (p=0.011), as well as 5-FU-based CTx after liver metastasis (p=0.008) when compared with gemcitabine-based regimens, were significant predictors of poor OS. Conclusion The oncologic role of local treatment for hepatic metastasis remains controversial in patients with hepatic metastasis after radical pancreatectomy. In the era of potent chemotherapeutic regimens, further research is needed to clarify the efficacy of such regimens.

Digital therapeutics (DTx) are emerging as a transformative innovation in healthcare offering evidence-based digital interventions for the treatment, management, and prevention of various diseases and disorders. In Korea, DTx have gained significant attention as potential solutions to the increasing burden of chronic diseases and mental health conditions. However, the Korean DTx market faces several challenges that hinder its widespread adoption and integration into the national healthcare system. This study provides a comprehensive analysis of the current state of the DTx market in Korea, identifies the key challenges impeding its growth, and proposes strategies for overcoming these obstacles. This study utilized a literature review and market analysis approach to examine the latest research, industry reports, and regulatory documents related to DTx. The analysis focused on three primary areas: (1) the current regulatory landscape, (2) technological advancements and challenges, and (3) economic and commercial factors influencing DTx adoption in Korea. A comparative analysis of global regulatory practices was also conducted to identify best practices. The findings revealed that while Korea has made significant strides in supporting DTx development, the market remains in its early stages. The key challenges include underdeveloped regulatory frameworks, issues with data quality and security, and a lack of established reimbursement pathways. We recommend developing tailored regulatory frameworks for DTx, enhancing policy support for small and medium-sized enterprises involved in DTx development, and increasing investments in technological infrastructure. By addressing these challenges, Korea could position itself as a leader in the global DTx market, delivering innovative and effective treatments to enhance patient care and outcomes.