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）］

Objective To establish the reference interval of urine Alzheimer-associated neuronal thread protein(AD7c-NTP)for healthy adults in Mianyang area using the indirect method.Methods The detection results of urine AD7c-NTP from 5 093 healthy in-dividuals were collected from the information management database of Medical Laboratory Department of Sichuan Science City Hospital from March 2017 to March 2022.Skewness-kurtosis and Kolmogorov-Smirnov tests were used to determine whether the data followed a normal distribution.After removing outliers using the Box Plots method,the enrolled subjects were grouped by gender and age.The Mann-Whitney U or Kruska-Wallis H tests were used to analyze the between-group differences of urine AD7c-NTP in healthy individu-als with different genders and ages.The adjacent age groups without statistically significant difference(P＞0.05)were combined,and the indirect method(non-parametric test method)was used to calculate the reference intervals for different gender and age groups.Results Skewness-kurtosis and Kolmogorov-Smirnov tests showed that the data followed a non-normal distribution.After removing 293 outliers using the Box Plots method,a total of 4 800 subjects,including 3 199 males and 1 601 females,were enrolled.The enrolled subjects were grouped by gender and age,and the non-parametric test method were used to establish the reference intervals of urine AD7c-NTP in healthy populations with different genders.The Mann-Whitney U test confirmed that urine AD7c-NTP levels existed gen-der differences(Z=14.09,P＜0.01),and the reference intervals for males and females were≤1.10 ng/mL and≤1.40 ng/mL,re-spectively.There were also statistical differences in urine AD7c-NTP levels among different age groups of the same gender.After combi-ning adjacent age groups without statistically significant difference(P＞0.05),the reference intervals of urine AD7c-NTP in healthy populations with different genders and ages were established by the non-parametric test method,which were≤1.00 ng/mL for male 20-39 years old group,≤1.10 ng/mL for male 40-79 years old group,≤1.60 ng/mL for male≥80 years old group,≤1.30 ng/mL for female 20-69 years old group,and≤1.60 ng/mL for female≥70 years old group,respectively.The established reference intervals of urine AD7c-NTP were further verified by healthy individuals,and the results met the standards.Conclusion The reference intervals of urine AD7c-NTP in healthy populations with different genders and ages in Mianyang area are established successfully using the indi-rect method,which may help to predict the risk of Alzheimer's disease in clinical practice and provide support for the diagnosis and treatment of the disease.

Objective:To analyze the electrocardiogram (ECG) data of congenital long QT syndrome (LQTS) patients, and to identify the ECG parameters for prediction of life-threatening arrhythmic events (LAEs).Methods:This cohort study enrolled patients diagnosed with congenital LQTS at the Department of Cardiology, Beijing Tsinghua Changgung Hospital from September 2014 to May 2023. Baseline clinical and ECG data were collected. Patients were followed with LAEs as the primary endpoint. Based on the occurrence of LAEs, patients were divided into two groups: the event group and the event-free group. Cox regression analysis was used to identify independent predictors of LAEs in LQTS patients.Results:A total of 293 patients diagnosed with congenital LQTS were included, aged 32.5 (19.0, 41.8) years, including 201 females (68.6%). Sixty-six patients experienced LAEs and 227 patients did not. Compared to the event-free group, the event group had a younger onset age (13.0 (5.5, 20.5) years vs. 26.0 (13.0, 35.0) years), a slower heart rate (69.0 (59.5, 76.5) beats/min vs. 77.0 (67.0, 88.0) beats/min), a higher proportion with family history of sudden cardiac death (30.3% vs. 14.5%), as well as longer QT intervals (500.0 (467.0, 594.0) ms vs. 428.0 (402.0, 470.0) ms) and QTc intervals (544.0 (502.5, 589.0) ms vs. 489.0 (480.0, 504.0) ms). Additionally, the event group had higher peak T-wave alternans value (65.0 (42.5, 85.3) μV vs. 44.0 (36.0, 54.0) μV), a higher proportion of patients with documented torsades de pointes (TdP) or ventricular fibrillation (VF) on 24-hour Holter monitoring (39.3% vs. 4.9%), and higher rates of pharmacological treatment (100.0% vs. 9.7%) and device therapy or left cardiac sympathetic denervation (45.5% vs. 2.2%) (all P<0.05). Multivariate Cox regression analysis identified that the heart rate<60 beats/min ( HR=2.0, 95% CI: 1.0-3.7) and QTc interval ≥500 ms ( HR=2.9, 95% CI: 1.5-5.6) on 12-lead ECG, as well as peak T-wave alternans value ≥55.5 μV ( HR=3.2, 95% CI: 1.3-7.8) and documented TdP or VF ( HR=2.0, 95% CI: 1.1-3.7) on 24-hour Holter monitoring were independent predictors of LAEs in LQTS patients (all P<0.05). Conclusion:Heart rate <60 beats/min and QTc interval ≥500 ms on 12-lead ECG, along with peak T-wave alternans value ≥55.5 μV and documented TdP or VF on 24-hour Holter monitoring, have been identified as independent predictors of LAEs in patients with LQTS. These ECG parameters may serve as valuable early indicators of sudden cardiac death in LQTS patients.

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: Pre-transplant exposure to immune checkpoint inhibitors (ICIs) significantly increases the risk of allograft rejection after liver transplantation (LT); however, whether ICI-related rejection leads to increased graft loss remains controversial. Therefore, this study aimed to investigate the association between ICI-related allograft rejection and perioperative graft loss. METHODS: This was a retrospective analysis of adult liver transplant recipients with early biopsy-proven T-cell-mediated rejection (TCMR) at Liver Transplantation Center of Sun Yat-sen Memorial Hospital from June 2019 to September 2024. The pathological features, clinical characteristics, and perioperative graft survival were analyzed. RESULTS: Twenty-eight patients who underwent early TCMR between June 2019 and September 2024 were included. Based on pre-LT ICI exposure, recipients were categorized into ICI-related TCMR (irTCMR, n = 12) and conventional TCMR (cTCMR, n = 16) groups. Recipients with irTCMR had a higher median Banff rejection activity index (RAI) (6 vs . 5, P = 0.012) and more aggressive tissue damage and inflammation. Recipients with irTCMR showed higher proportion of treatment resistance, achieving a complete resolution rate of only 8/12 compared to 16/16 for cTCMR. Graft loss occurred in 5/12 of irTCMR recipients within 90 days after LT, with no graft loss in cTCMRs recipients. Cox analysis demonstrated that irTCMR with an ICI washout period of <30 days was an independent risk factor for perioperative graft loss (hazard ratio [HR], 6.540; 95% confidence interval [CI], 1.067-40.067, P = 0.042). CONCLUSION IrTCMR is associated with severe pathological features, increased resistance to treatment, and higher graft loss in adult liver transplant recipients.
Humans ; Liver Transplantation/adverse effects* ; Male ; Female ; Middle Aged ; Retrospective Studies ; Graft Rejection/immunology* ; Immune Checkpoint Inhibitors/therapeutic use* ; Adult ; T-Lymphocytes/drug effects* ; Graft Survival/immunology* ; Aged

Three taraxerane nortriterpenoids were isolated from mastic by using various modern chromatographic separation techniques. They were identified as(5R,8R,9R,10S,11S,12R,13S,17R,18R)-28-norlupa-11,12-epoxy-14-taraxerene-3,16-dione(1),(5R,8R,9R,10S,11S,12R,13S,17S,18S)-17-hydroxy-28-norlupa-11,12-epoxy-14-taraxerene-3-one(2), and(5R,8R,9R,10R,11S,12R,13R,14S,17S,18S)-14,17-epoxy-28-norlupa-11,12-oxidotaraxerone(3) through the high-resolution electrospray ionization mass spectrometry(HR-ESI-MS), infrared(IR), ultraviolet(UV), nuclear magnetic resonance(NMR), and single-crystal X-ray diffraction techniques as well as comparison with literature data. Compounds 1-3 were C-28 nortriterpenoids and isolated from mastic for the first time, and compounds 1-2 were new ones. In the model for RAW264.7 cell anti-inflammation induced by lipopolysaccharide(LPS), compound 1 demonstrates an inhibitory effect on nitric oxide(NO) [IC_(50)=(13.38±0.68) μmol·L~(-1)], comparable to the activity of the positive control dexamethasone [IC_(50)=(14.59±1.49) μmol·L~(-1)]. Compounds 2 and 3 exhibit weaker inhibitory effects, with IC_(50) values of(24.17±2.56) and(22.25±2.84) μmol·L~(-1), respectively.
Animals ; Mice ; Triterpenes/isolation & purification* ; Drugs, Chinese Herbal/isolation & purification* ; Mastic Resin/chemistry* ; Nitric Oxide ; Molecular Structure ; Macrophages/immunology* ; RAW 264.7 Cells

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.