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.

Hepatitis E virus infection is a common cause of acute viral hepatitis. In recent years, the incidence of hepatitis E has shown an increasing trend, which has gradually become an important cause of acute viral hepatitis worldwide. Age, sex, intensity of immunosuppression and socio-economic factors are all risk factors for hepatitis E virus infection. Liver transplant recipients require long-term use of immunosuppressive drugs for anti rejection treatment, prone to hepatitis E virus infection and at the risk of liver fibrosis and cirrhosis due to immunosuppression status. Therefore, special attention should be paid to liver transplant recipients in clinical practice. Meantime, related risk factors should be identified to assist diagnosis and take stricter preventive measures. According to literature review, the etiological characteristics of hepatitis E virus and the epidemiological characteristics, clinical manifestations, diagnosis and treatment of hepatitis E virus infection in liver transplant recipients were reviewed, aiming to properly monitor, treat and prevent hepatitis E virus infection in liver transplant recipients in clinical practice, improving the prognosis of liver transplant recipients.

Objective To preliminarily evaluate the safety and effectiveness of a novel non-implantable atrial shunt device based on radiofrequency ablation for the treatment of chronic heart failure(CHF).Methods This was a prospective single-arm study.From January 2023 to December 2023,five eligible CHF patients were consecutively enrolled at Beijing Anzhen Hospital,Capital Medical University,and underwent inter-atrial shunt using Shenzhen Betterway atrial shunt device.Pulmonary capillary wedge pressure(PCWP),right atrial pressure(RAP),pulmonary artery pressure(PAP),total pulmonary resistance(TPR),pulmonary vascular resistance(PVR),and pulmonary/systemic blood flow ratio(Qp/Qs)were measured using right heart catheterization before and immediately after procedure.Patients were followed up for 90 days,and echocardiography,right heart catheterization,and cardiac functional indicators were evaluated.The primary endpoint was procedural success.Secondary endpoints included clinical success,echocardiographic changes,6-minute walk distance(6MWD)changes,New York Heart Association(NYHA)class changes,Kansas city cardiomyopathy questionnaire(KCCQ)score changes,and amino-terminal probrain natriuretic peptide(NT-proBNP)level changes at 90 days.The safety endpoint was major cardiovascular and cerebrovascular adverse events and device-related adverse events.Results All five patients successfully achieved left-to-right atrial shunt.Compared with baseline,PCWP decreased significantly immediately after procedure in all five patients,with a procedural success rate of 100％.There were no significant changes in RAP,PAP,TPR,and PVR before and immediately after procedure.After 90 days follow-up,four patients had persistent left-to-right atrial shunt,and PCWP was significantly lower than baseline,with a clinical success rate of 80％.Compared with baseline,LVEF increased,left ventricular end-diastolic diameter decreased,and tricuspid annular plane systolic excursion and right ventricular fractional area change were not impaired in all five patients at 90 days.KCCQ scores and 6MWT improved,NT-proBNP decreased,and NYHA class did not change significantly.There were no deaths,rehospitalizations for heart failure,stroke-related adverse events,or device-related adverse events during the follow-up.Conclusions The novel non-implantable atrial shunt catheter can safely and effectively improve hemodynamic,echocardiographic,and cardiac functional indicators in patients with heart failure.However,larger-scale clinical studies are still needed to validate its long-term clinical effectiveness.

Objective To investigate the feasibility and value of a multi-parametric MRI radiomics-based nomogram model for pretreatment predicting the lymphovascular space invasion(LVSI)of endometrial endometrioid adenocarcinoma(EEA).Methods Preoperative MRI and baseline clinical characteristics of 205 EEA patients were prospectively collected from Oct 2020 to Jan 2022 in the Obstetrics and Gynecology Hospital,Fudan University,and randomly divided into training set(n=123)and validation set(n=82)in a 6∶4 ratio.The whole-tumor region of interest was manually drawn on T2-weighted imaging,diffusion-weighted imaging(apparent diffusion coefficient),and dynamic contrast-enhanced MRI,respectively,for radiomics features extraction.In the training set,univariate and multivariate Logistic regression analysis were used to select independent clinical predictors of LVSI(+)and construct the clinical model.The least absolute shrinkage and selection operator(LASSO)regression and multivariate Logistic regression analysis were used to select optimal radiomics features to form a radiomics signature.A combined nomogram model was established by integrating clinical independent predictors and the radiomics signature,and validated in the validation set.The predicting performance and clinical net benefit were evaluated by using the area under the receiver operating characteristic curve(AUC)and clinical decision curve analysis,respectively.Results Of the 205 EEA cases,144 cases were LVSI(-)and 61 cases were LVSI(+).Menopausal status,CA125,and CA199 were independent clinical predictors for the LVSI(+),and contributing to a clinical model with AUCs of 0.714(training)and 0.731(validation).From 8 240 extracted radiomics features,five were selected to construct a MRI radiomics signature after de-redundancy and LASSO dimensionality reduction,yielding AUCs of 0.860(training)and 0.759(validation).The combined nomogram model showed AUCs of 0.887(training)and 0.807(validation),outperforming others and achieving maximum clinical benefit in a large range of threshold probability in both training and validation sets.Conclusion The multi-parametric MRI-based nomogram model has the potential for pretreatment predicting the LVSI status of EEA,providing valuable information for clinical management decision-making and improving patient's clinical benefits.

Thrombocytopenia is one of the common complications after liver transplantation,with pathophysiological mechanisms including insufficient platelet production and increased platelet consumption,which severely affects the prognosis of liver transplant recipients.Various factors such as preoperative hepatitis virus infection,intraoperative ischemic injury,and postoperative use of immunosuppressive drugs may lead to thrombocytopenia after liver transplantation.Early detection and effective treatment of thrombocytopenia after liver transplantation are currently hot topics of research.Based on the existing literature,this article reviews the definition,pathophysiological mechanisms,risk factors,treatment,and prevention of thrombocytopenia,and discusses the occurrence and development of thrombocytopenia after liver transplantation and related diagnosis and treatment strategies,aiming to optimize the existing treatment opinions,reduce the risk of thrombocytopenia after transplantation and improve the prognosis of liver transplant recipients.

Humans ; Atrial Fibrillation/surgery* ; Recovery of Function ; Radiofrequency Ablation ; Heart ; Heart Transplantation ; Catheter Ablation ; Treatment Outcome

Humans ; Atrial Fibrillation/surgery* ; Recovery of Function ; Radiofrequency Ablation ; Heart ; Heart Transplantation ; Catheter Ablation ; Treatment Outcome

Objective:To analyze the clinical characteristics of novel coronavirus (COVID-19) infection in liver transplant recipients.Methods:Clinical data of 130 liver transplant recipients with COVID-19 infection followed in Hebei Medical University Third Hospital from November 2022 to January 2023 were retrospectively collected, including 103 males and 27 females, aged (53.6±11.4) years. The severity of COVID-19 infection, its clinical symptoms, and negative conversion time for each recipient were analyzed and compared.Results:For the disease severity, 121 (93.1%) were mild, 5 (3.8%) were moderate, 3 (2.3%) were severe, and 1 (0.8%) was critically severe. The most common symptoms in the 126 patients with mild to moderate COVID-19 infection were successively fever, fatigue, cough and myalgia, with a negative conversion time of (10.1±4.5) (3.0-29.0)d. In those who underwent transplantation less than 12 months ( n=28), those who were taking mycophenolate mofetil ( n=53) and those who were taking methylprednisolone ( n=10), the negative conversion time was (11.6±5.1) d, (11.4±5.4) d, and (13.4±6.4) d, respectively, longer compared to those who underwent transplantation more than 12 months (9.7±4.2 d, n=98), and who were not taking mycophenolate mofetil (9.2±3.4 d, n=73) or methylprednisolone (9.8±4.2 d, n=116, all P<0.05). The negative conversion times were longer in recipients with symptoms (eg. fatigue and cough) than those in asymptomatic recipients (11.0±5.1 d vs. 9.0±3.3 d, t=2.64, P=0.009, and 11.4±5.2 d vs. 9.0±3.4 d, t=2.92, P=0.004). Conclusion:The COVID-19 infection in liver transplant recipients was mainly mild and moderate. The most common symptoms are fever, fatigue, cough and myalgia. The short time (less than 12 months) after liver transplantation, oral mycophenolate mofetil and methylprednisolone, with symptoms (fatigue and cough) could be associated with a prolonged negative conversion time.

Humans ; Heart Failure/therapy* ; Kidney/physiology* ; Renal Insufficiency ; Glomerular Filtration Rate

PURPOSE: This study aims to elucidate the electrotaxis response of alveolar epithelial cells (AECs) in direct-current electric fields (EFs), explore the impact of EFs on the cell fate of AECs, and lay the foundation for future exploitation of EFs for the treatment of acute lung injury. METHODS: AECs were extracted from rat lung tissues using magnetic-activated cell sorting. To elucidate the electrotaxis responses of AECs, different voltages of EFs (0, 50, 100, and 200 mV/mm) were applied to two types of AECs, respectively. Cell migrations were recorded and trajectories were pooled to better demonstrate cellular activities through graphs. Cell directionality was calculated as the cosine value of the angle formed by the EF vector and cell migration. To further demonstrate the impact of EFs on the pulmonary tissue, the human bronchial epithelial cells transformed with Ad12-SV40 2B (BEAS-2B cells) were obtained and experimented under the same conditions as AECs. To determine the influence on cell fate, cells underwent electric stimulation were collected to perform Western blot analysis. RESULTS: The successful separation and culturing of AECs were confirmed through immunofluorescence staining. Compared with the control, AECs in EFs demonstrated a significant directionality in a voltage-dependent way. In general, type Ⅰ alveolar epithelial cells migrated faster than type Ⅱ alveolar epithelial cells, and under EFs, these two types of cells exhibited different response threshold. For type Ⅱ alveolar epithelial cells, only EFs at 200 mV/mm resulted a significant difference to the velocity, whereas for, EFs at both 100 mV/mm and 200 mV/mm gave rise to a significant difference. Western blotting suggested that EFs led to an increased expression of a AKT and myeloid leukemia 1 and a decreased expression of Bcl-2-associated X protein and Bcl-2-like protein 11. CONCLUSION EFs could guide and accelerate the directional migration of AECs and exert antiapoptotic effects, which indicated that EFs are important biophysical signals in the re-epithelialization of alveolar epithelium in lung injury.
Humans ; Rats ; Animals ; Alveolar Epithelial Cells ; Lung ; Lung Injury ; Cell Movement/physiology*