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.

Objective:To assess the efficacy and safety profile of antaitasvir phosphate combined with yiqibuvir in the treatment of chronic hepatitis C (CHC) of various genotypes, without cirrhosis or with compensated cirrhosis.Methods:394 cases with CHC from 22 centers were collected from October 2021 to April 2023. They were randomly assigned to receive either the experimental drugs (antaitasvir phosphate 100 mg+yiqibuvir 600 mg) or placebo treatment in a 3∶1 ratio. The patients were administered drugs once a day for 12 consecutive weeks, and then followed up for 24 weeks after treatment cessation. All subjects were unblinded at the four-week follow-up following drug discontinuation, with the experimental drug group continuing to complete subsequent post-discontinuation follow-up. The placebo group was switched to receive the experimental drugs for a repeated 12-week treatment period and followed up for another 24 weeks after discontinuation of the drug (placebo delayed treatment phase).The sustained virologic response rate (SVR12) was observed for subjects in the double-blind phase and the placebo delayed-treatment phase at 12 weeks after treatment cessation.Virological resistance analysis was performed on subjects who failed treatment. The primary efficacy endpoint was SVR12. The number and percentage of subjects who achieved "HCV RNA

Objective:To assess the efficacy and safety profile of antaitasvir phosphate combined with yiqibuvir in the treatment of chronic hepatitis C (CHC) of various genotypes, without cirrhosis or with compensated cirrhosis.Methods:394 cases with CHC from 22 centers were collected from October 2021 to April 2023. They were randomly assigned to receive either the experimental drugs (antaitasvir phosphate 100 mg+yiqibuvir 600 mg) or placebo treatment in a 3∶1 ratio. The patients were administered drugs once a day for 12 consecutive weeks, and then followed up for 24 weeks after treatment cessation. All subjects were unblinded at the four-week follow-up following drug discontinuation, with the experimental drug group continuing to complete subsequent post-discontinuation follow-up. The placebo group was switched to receive the experimental drugs for a repeated 12-week treatment period and followed up for another 24 weeks after discontinuation of the drug (placebo delayed treatment phase).The sustained virologic response rate (SVR12) was observed for subjects in the double-blind phase and the placebo delayed-treatment phase at 12 weeks after treatment cessation.Virological resistance analysis was performed on subjects who failed treatment. The primary efficacy endpoint was SVR12. The number and percentage of subjects who achieved "HCV RNA

Objective:To evaluate the efficacy and safety of antaitasvir phosphate 100 mg or 200 mg combined with yiqibuvir for 12 weeks in patients with various genotypes of chronic hepatitis C, without cirrhosis or compensated stage cirrhosis.Methods:Patients with chronic hepatitis C (without cirrhosis or compensated stage cirrhosis) were randomly assigned to the antaitasvir phosphate 100 mg+yiqibuvir 600 mg group (100 mg group) or the antaitasvir phosphate 200 mg+yiqibuvir 600 mg group (200 mg group) in a 1∶1 ratio. The drugs were continuously administered once a day for 12 weeks and observed for 24 weeks after drug withdrawal. The drug safety profile was assessed concurrently with the observation of the sustained virological response (SVR12) in the two patient groups 12 weeks following the drug cessation. The intention-to-treat concept was used to define as closely as possible a full analysis set, including all randomized cases who received the experimental drug at least once. The safety set was collected from all subjects who received the experimental drug at least once (regardless of whether they participated in the randomization group) in this study. All efficacy endpoints and safety profile data were summarized using descriptive statistics. The primary efficacy endpoint was SVR12. The primary analysis was performed on a full analysis set. The frequency and proportion of cases were calculated in the experimental drug group (antaitasvir phosphate capsules combined with yiqibuvir tablets) that achieved "HCV RNA

Metabolic regulation has been proven to play a critical role in T cell antitumor immunity. However, cholesterol metabolism as a key component of this regulation remains largely unexplored. Herein, we found that the low-density lipoprotein receptor (LDLR), which has been previously identified as a transporter for cholesterol, plays a pivotal role in regulating CD8

Objective:To study the protective effect and the mechanism of esculetin on oxidative-stressed human retinal pigment epithelial cells (ARPE-19) induced by tert-butyl hydroperoxide (t-BHP).Methods:The ARPE-19 cells were divided into blank control group, model control group, 20 μmol/L esculetin group, 40 μmol/L esculetin group, 80 μmol/L esculetin group and 100 μmol/L esculetin group.The cells in the blank control group were normally cultured.The cells in the model control group were treated with 900 μmol/L t-BHP for 4 hours.The rest four groups were treated with 900 μmol/L t-BHP+ different molar concentrations of esculetin respectively for 4 hours.The cell viability of the each group was detected by MTS method.The activity of reactive oxygen species (ROS) was detected by fluorescence staining, and the activity of superoxide dismutase (SOD), catalase (CAT) and glutathione peroxidase (GSH-Px) as well as the levels of malondialdehyde (MDA) of the cells from each group were measured with each corresponding assay kit, respectively.Results:The relative viabilities of the cells in the blank control group, model control group, 20 μmol/L esculetin group, 40 μmol/L esculetin group, 80 μmol/L esculetin group and 100 μmol/L esculetin group were (100.00±1.58)%, (49.19±1.06)%, (76.82±3.48)%, (103.90±1.60)%, (111.70±3.36)% and (113.40±3.08)%, respectively.There was a significant difference among the groups ( F=95.44, P<0.01). Compared with the blank control group, the viability of the cells in the model control group was decreased significantly ( P<0.01). Compared with the model control group, the cell viabilities in different concentrations of esculetin groups were increased significantly (all at P<0.01). There were significant differences between the groups in the relative value of ROS fluorescence intensity, MDA level, SOD activity, CAT activity and GSH-Px activity ( F=575.20, 40.61, 1 802.00, 41.62, 38.31; all at P<0.01). Compared with the model control group, the levels of ROS and MDA were decreased significantly, while the activities of SOD, CAT and GSH-Px were increased significantly in different concentrations of esculetin-treated groups (all at P<0.01). Conclusions:Esculetin can protect the oxidative damaged ARPE-19 cells by up-regulating the expression of antioxidant enzymes or antioxidant proteins.

Objective To explore the strategies of using psychological crisis intervention in public emergencies.Methods In the early stage,psychological crisis intervention concepts and behavioral responses were formed through literature research and qualitative research methods.Use three rounds of Delphi for expert advice.Three indexes including positive coefficient,authority and coordination were used to test the reliability of expert consultation.Results Overall,it passed 239 out of 269 entries.The first round passed item 210,modified item 18,no consensus item 41;In the second round,8 new entries were added,and 22 entries were deleted through 24 entries.In the third round,there were 5 entries and 16 entries were deleted.The authority coefficient was 0.859,indicating that the experts were very familiar with the items.The coordination coefficient of three rounds of consultations were 0.464,0.696,and 0.407 (P＜0.001)respectively,showing that the coordination degree of experts was excellent,the credibility of feedback was high,and results were highly reliable.Conclusions The strategies of field psychological crisis intervention for public emergencies developed in this study received the consensus by domestic psychological crisis intervention experts,it is will provide a basis for systematic,comprehensive and effective guidance for this work.

Objective To investigate the significance of albumin-bilirubin (ALBI) score in predicting prognosis of hepatocellular carcinoma (HCC).Methods The clinical data of 644 HCC patients were retrospectively analyzed from May 2010 to May 2013 in the First People's Hospital of Changde City and the Affiliated Tumor Hospital of Guangxi Medical University.Peripheral blood test results were used to calculate ALBI score,and ALBI score was categorized into the following 3 groups:grade 1,grade 2,grade 3.Overall survival(OS) and disease free survival(DFS) were evaluated by the Kaplan-Meier method.And independent prognostic predictors were determined by the Cox proportional hazard model.Results Multivariate analysis showed that ALBI grade 2 was an independent risk factor for OS(P＜0.05).The ALBI grade stratified patients into at least two distinct overall survival cohorts (P＜0.05),whereas the CP grade did not.The ALBI grade also classified patients with CP grade A patients into two distinct overall survival cohorts (P＜0.05).In the subgroup analysis,the ALBI grade seemed to be an independent factor in terms of Barcelona Clinical Liver Cancer staging system(BCLC) 0-C.Conclusion For patients with HCC who underwent R0 resection,the ALBI grade is a good predictor of OS in HCC patients,and the above conclusions is true in patients with BCLC stage 0-C.

Objective To compare the clinical significance of peripheral blood neutrophil to lymphocyte ratio (NLR) and platelet to lymphocyte ratio (PLR) in predicting prognosis of patients with hepatocellular carcinoma (HCC).Methods The clinical data of 661 patients with HCC were retrospectively analyzed.Routine peripheral blood test results were used to calculate the NLR and PLR,and the receiver operating characteristic (ROC) curves were drawn.Using the thresholds of NLR and PLR,the patients were divided into the low NLR group and the high NLR group,and the low PLR group and the high PLR group.Overall survival (OS) and disease free survival (DFS) were evaluated by the Kaplan-Meier method.Independent prognostic predictors were determined by the Cox proportional hazard model.Results The NLR and PLR thresholds were 2.790 and 99,respectively.Analysis of the ROC curves showed higher NLR and PLR were significantly associated with poorer OS and DFS (all P ＜ 0.05).Multivariate analysis showed that NLR was an independent risk factor of OS and DFS (both P ＜ 0.05).The results remained unchanged when the NLR was further analyzed by applying different cut-off values of 2.810 and 3.In subgroup analysis,NLR remained an independent factor of Barcelona Clinical Liver Cancer staging system (BCLC) 0/A/B (P ＜ 0.05 for all measurements).Conclusion An elevated preoperative NLR could be a better prognostic predictor for HCC patients in comparison with PLR,especially for BCLC 0/A/B patients.