Objective To explore the feasibility and reference value of allogeneic lung transplantation and postoperative monitoring in miniature pigs for lung transplantation research. Methods Two miniature pigs (R1 and R2) underwent left lung allogeneic transplantation. Complement-dependent cytotoxicity tests and blood cross-matching were performed before surgery. The main operative times and partial pressure of arterial oxygen (PaO₂) after opening the pulmonary artery were recorded during surgery. Postoperatively, routine blood tests, biochemical blood indicators and inflammatory factors were detected, and pathological examinations of multiple organs were conducted. Results The complement-dependent cytotoxicity test showed that the survival rate of lymphocytes between donors and recipients was 42.5%-47.3%, and no agglutination reaction occurred in the cross-matching. The first warm ischemia times of D1 and D2 were 17 min and 10 min, respectively, and the cold ischemia times were 246 min and 216 min, respectively. Ultimately, R1 and R2 survived for 1.5 h and 104 h, respectively. Postoperatively, in R1, albumin (ALB) and globulin (GLB) decreased, and alanine aminotransferase increased; in R2, ALB, GLB and aspartate aminotransferase all increased. Urea nitrogen and serum creatinine increased in both recipients. Pathological results showed that in R1, the transplanted lung had partial consolidation with inflammatory cell infiltration, and multiple organs were congested and damaged. In R2, the transplanted lung had severe necrosis with fibrosis, and multiple organs had mild to moderate damage. The expression levels of interleukin-1β and interleukin-6 increased in the transplanted lungs. Conclusions The allogeneic lung transplantation model in miniature pigs may systematically evaluate immunological compatibility, intraoperative function and postoperative organ damage. The data obtained may provide technical references for subsequent lung transplantation research.

BackgroundThe violent aggressive behaviors of patients with schizophrenia usually have the characteristics of suddenness， unpredictability， high severity， and great difficulty in prevention. Early identification and accurate assessment of their risk of violent aggression have significant clinical significance. ObjectiveTo construct a predictive model for the violence risk in hospitalized patients with schizophrenia， to identify the key factors influencing the occurrence of violent behavior in these patients， so as to provide references for clinical precise quantitative assessment and early intervention. MethodsA total of 200 patients with schizophrenia who were hospitalized at Taiyuan Psychiatric Hospital from March 2022 to September 2024 and met the diagnostic criteria of the International Classification of Diseases， eleventh edition （ICD-11） were collected to form the modeling cohort. They were randomly divided into a training set （n=140） and a test set （n=60） at a ratio of 7∶3. Based on the least absolute shrinkage and selection operator （LASSO） regression algorithm， the feature variables were screened and dimension-reduced. The support vector machine （SVM） from machine learning was selected for model training and prediction. The discrimination efficacy of the model was evaluated by the area under the receiver operating characteristic （ROC） curve （AUC）， accuracy， precision， sensitivity， specificity， F1 value， and Brier value. ResultsLASSO regression screening identified 16 feature variables. Pearson correlation analysis revealed a positive correlation between prior violent behavior frequency and clinical psychiatric symptom scores （r=0.580， P<0.01）， a positive correlation between hospitalization compliance and current disease status （r=0.550， P=0.003）， and a positive correlation between educational level and family per capita monthly income （r=0.367， P<0.01）. The SVM model achieved an AUC of 0.853， accuracy of 0.800， precision of 0.810， sensitivity of 0.895， specificity of 0.636， F1 value of 0.850， and Brier value of 0.168. ConclusionThe SVM model has a relatively high level of applicability and overall predictive performance in the assessment of violent risk in schizophrenia patients， which is helpful for the early identification of violent risks in such patients. ［Funded by Specialized Research Project for Enhancing the Competence of Health Professionals in Taiyuan City （number， Y2023006）］

Background: Delirium in the post-anesthesia care unit (PACU) may be associated with worse outcomes in children with moyamoya disease (MMD). This retrospective study aimed to describe the prevalence of PACU delirium in children with MMD and investigate its risk factors. Methods: Patients with MMD aged < 15 years who underwent indirect revascularization between January 2014 and October 2023 were included in this study. Delirium was assessed using the Pediatric Anesthesia Emergence Delirium Scale. Potential risk factors for PACU delirium were evaluated using multivariate logistic regression. Results: PACU delirium occurred in 245 (33%) of the 750 hemispheric procedures performed in 522 patients. Delirium was associated with a higher incidence in patients undergoing the first revascularization (37%) than in those undergoing the second (25%; P = 0.002). Cerebral infarction as the initial presentation (odds ratio [OR]: 4.64, first revascularization), high pediatric moyamoya magnetic resonance imaging (MRI) score (OR: 2.75, first revascularization; OR: 3.50, second revascularization), and high intraoperative mean arterial pressure variability (mmHg/min) (OR: 9.17, first revascularization; OR: 8.82, second revascularization) were associated with PACU delirium. Conversely, total intravenous anesthesia (TIVA) was associated with a lower incidence of PACU delirium (OR: 0.46, first revascularization; OR: 0.25, second revascularization). Conclusions A significant proportion of patients with MMD developed delirium in the PACU. High intraoperative blood pressure variability and preoperative MRI lesions are independent risk factors for PACU delirium in children with MMD. TIVA may exert a protective effect against PACU delirium. Further studies are required to clarify the causality of these associations.

Background: Delirium in the post-anesthesia care unit (PACU) may be associated with worse outcomes in children with moyamoya disease (MMD). This retrospective study aimed to describe the prevalence of PACU delirium in children with MMD and investigate its risk factors. Methods: Patients with MMD aged < 15 years who underwent indirect revascularization between January 2014 and October 2023 were included in this study. Delirium was assessed using the Pediatric Anesthesia Emergence Delirium Scale. Potential risk factors for PACU delirium were evaluated using multivariate logistic regression. Results: PACU delirium occurred in 245 (33%) of the 750 hemispheric procedures performed in 522 patients. Delirium was associated with a higher incidence in patients undergoing the first revascularization (37%) than in those undergoing the second (25%; P = 0.002). Cerebral infarction as the initial presentation (odds ratio [OR]: 4.64, first revascularization), high pediatric moyamoya magnetic resonance imaging (MRI) score (OR: 2.75, first revascularization; OR: 3.50, second revascularization), and high intraoperative mean arterial pressure variability (mmHg/min) (OR: 9.17, first revascularization; OR: 8.82, second revascularization) were associated with PACU delirium. Conversely, total intravenous anesthesia (TIVA) was associated with a lower incidence of PACU delirium (OR: 0.46, first revascularization; OR: 0.25, second revascularization). Conclusions A significant proportion of patients with MMD developed delirium in the PACU. High intraoperative blood pressure variability and preoperative MRI lesions are independent risk factors for PACU delirium in children with MMD. TIVA may exert a protective effect against PACU delirium. Further studies are required to clarify the causality of these associations.

Lung transplantation is the ultimate therapeutic option for end-stage pulmonary diseases such as interstitial pneumonia, chronic obstructive pulmonary disease and pneumoconiosis. Currently, the shortage of allogeneic lung donors significantly limits the opportunity for end-stage lung disease patients to receive lung transplantation. In recent years, with the rapid development of biomedical engineering technologies, especially the major breakthroughs in genetic modification and cloning, xenogeneic lung transplantation has shown important potential for clinical translation. Among them, genetically modified pigs have become the most promising xenogeneic lung source due to the close similarity of organ size and physiological characteristics to humans, and the ability to perform targeted gene knockouts (such as α-Gal antigen knockout) to reduce the occurrence of hyperacute rejection. This article focuses on the research progress of porcine xenogeneic lung transplantation, systematically reviews the latest achievements and challenges in animal experiments and human trials, and introduces the technical experience accumulated by Shenzhen Third People's Hospital in the porcine-to-monkey xenogeneic lung transplantation model, in the hope of providing practical references for future research in this field.

Background: Delirium in the post-anesthesia care unit (PACU) may be associated with worse outcomes in children with moyamoya disease (MMD). This retrospective study aimed to describe the prevalence of PACU delirium in children with MMD and investigate its risk factors. Methods: Patients with MMD aged < 15 years who underwent indirect revascularization between January 2014 and October 2023 were included in this study. Delirium was assessed using the Pediatric Anesthesia Emergence Delirium Scale. Potential risk factors for PACU delirium were evaluated using multivariate logistic regression. Results: PACU delirium occurred in 245 (33%) of the 750 hemispheric procedures performed in 522 patients. Delirium was associated with a higher incidence in patients undergoing the first revascularization (37%) than in those undergoing the second (25%; P = 0.002). Cerebral infarction as the initial presentation (odds ratio [OR]: 4.64, first revascularization), high pediatric moyamoya magnetic resonance imaging (MRI) score (OR: 2.75, first revascularization; OR: 3.50, second revascularization), and high intraoperative mean arterial pressure variability (mmHg/min) (OR: 9.17, first revascularization; OR: 8.82, second revascularization) were associated with PACU delirium. Conversely, total intravenous anesthesia (TIVA) was associated with a lower incidence of PACU delirium (OR: 0.46, first revascularization; OR: 0.25, second revascularization). Conclusions A significant proportion of patients with MMD developed delirium in the PACU. High intraoperative blood pressure variability and preoperative MRI lesions are independent risk factors for PACU delirium in children with MMD. TIVA may exert a protective effect against PACU delirium. Further studies are required to clarify the causality of these associations.

Coronavirus-related diseases pose a significant challenge to the global health system. Given the diversity of coronaviruses and the unpredictable nature of disease outbreaks, the traditional "one bug, one drug" paradigm struggles to address the growing number of emerging crises. Therefore, there is an urgent need for therapeutic agents with broad-spectrum anti-coronavirus activity. Here, we provide evidence that ATV006, an anti-SARS-CoV-2 nucleoside analog targeting RNA-dependent RNA polymerase (RdRp), has broad antiviral activity against human and animal coronaviruses. Using mouse hepatitis virus (MHV) and human coronavirus NL63 (HCoV-NL63) as a model, we show that ATV006 has potent prophylactic and therapeutic activity against murine coronavirus infection in vivo. Remarkably, ATV006 successfully inhibits viral replication in mice even when administered 96 h after infection. Due to its oral bioavailability and potency against multiple coronaviruses, ATV006 has the potential to become a useful antiviral agent against SARS-CoV-2 and other circulating and emerging coronaviruses in humans and animals.

Osteoarthritis (OA) causes chronic pain that significantly impairs quality of life, with current treatments often proving insufficient and accompanied by adverse effects. Recent research has identified the dorsal root ganglion (DRG) and its resident macrophages as crucial mediators of chronic OA pain through neuroinflammation driven by macrophage polarization. We present a novel injectable thermo-sensitive hydrogel system, KAF@PLEL, designed to deliver an anti-inflammatory peptide (KAF) specifically to the DRG. This biodegradable hydrogel enables sustained KAF release, promoting the reprogramming of DRG macrophages from pro-inflammatory to anti-inflammatory phenotypes. Through comprehensive in vitro and in vivo studies, we evaluated the hydrogel's biocompatibility, effects on macrophage polarization, and therapeutic efficacy in chronic OA pain management. The system demonstrated significant capabilities in preserving macrophage mitochondrial function, suppressing neuroinflammation, alleviating chronic OA pain, reducing cartilage degradation, and improving motor function in OA rat models. The sustained-release properties of KAF@PLEL enabled prolonged therapeutic effects while minimizing systemic exposure and side effects. These findings suggest that KAF@PLEL represents a promising therapeutic approach for improving outcomes in OA patients through targeted, sustained treatment.

Gene regulation relies on the precise binding of transcription factors (TFs) at regulatory elements, but simultaneously detecting hundreds of TFs on chromatin is challenging. We developed cFOOT-seq, a cytosine deaminase-based TF footprinting assay, for high-resolution, quantitative genome-wide assessment of TF binding in both open and closed chromatin regions, even with small cell numbers. By utilizing the dsDNA deaminase SsdAtox, cFOOT-seq converts accessible cytosines to uracil while preserving genomic integrity, making it compatible with techniques like ATAC-seq for sensitive and cost-effective detection of TF occupancy at the single-molecule and single-cell level. Our approach enables the delineation of TF footprints, quantification of occupancy, and examination of chromatin influences on TF binding. Notably, cFOOT-seq, combined with FootTrack analysis, enables de novo prediction of TF binding sites and tracking of TF occupancy dynamics. We demonstrate its application in capturing cell type-specific TFs, analyzing TF dynamics during reprogramming, and revealing TF dependencies on chromatin remodelers. Overall, cFOOT-seq represents a robust approach for investigating the genome-wide dynamics of TF occupancy and elucidating the cis-regulatory architecture underlying gene regulation.
Transcription Factors/genetics* ; Humans ; Chromatin/genetics* ; Animals ; Binding Sites ; Mice ; DNA Footprinting/methods*

Senecavirus A (SVA) is a major viral pathogen causing disease in pigs, and effective monitoring of SVA infection is critical for disease control. In this study, we aimed to develop a reliable ELISA method for rapidly detecting neutralizing antibodies against SVA. We used HEK293F cells to express an SVA-specific porcine Fab antibody and verified the biological activity of the Fab antibody by indirect ELISA, immunofluorescence assay, virus neutralization test, and Western blotting. The Fab antibody was biotinylated and used as a competitive antibody to establish a competitive ELISA (C-ELISA) for detecting neutralizing antibodies against SVA. We then evaluated the C-ELISA in terms of sensitivity, specificity, repeatability, and result agreement rate with the VNT. The results showed that we successfully prepared an SVA-specific porcine Fab antibody, which showed high affinity for SVA. We named this antibody 1M33Fab and designated it as Bio-1M33Fab after biotin labeling. The assay conditions were optimized as follows: the coating concentration of SVA particles being 1 μg/mL, the working concentration of Bio-1M33Fab being 0.5 μg/mL, the optimal serum dilution of 1:10, and the optimal dilution of enzyme-labeled avidin being 1:30 000. At a percent inhibition (PI) of 47%, the assay demonstrated the highest sensitivity (96.88%) and specificity (100%), with no cross-reactivity observed with the positive sera of major porcine viral diseases. The intra-assay coefficient of variation ranged from 1.12% to 7.34%, while the inter-assay coefficient of variation ranged from 1.10% to 8.97%, indicating good repeatability. In the detection of 224 clinical pig serum samples, C-ELISA and VNT showed a result agreement rate of 93.75%. In conclusion, we successfully develop a C-ELISA method for detecting neutralizing antibodies against SVA by using a porcine-derived Fab antibody, which lays a foundation for the development of detection kits.
Animals ; Swine ; Antibodies, Neutralizing/immunology* ; Enzyme-Linked Immunosorbent Assay/methods* ; Immunoglobulin Fab Fragments/immunology* ; Antibodies, Viral/immunology* ; Picornaviridae/immunology* ; Humans ; HEK293 Cells ; Swine Diseases/diagnosis* ; Picornaviridae Infections/diagnosis*