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 exlplore the association between the baseline luteinizing hormone/follicle stimulating hormone (LH/FSH) ratio of polycystic ovary syndrome (PCOS) and in vitro fertilisation-embryo transfer outcomes.Methods:This was a retrospective cohort study. A total of 2 868 PCOS patients were enrolled, all of the participants were patients in The First Affiliated Hospital of Anhui Medical University Hospital from October 2015 to October 2021. Propensity score matching (1∶2.5) was conducted to regulate the non-random allocation of patients. Data were extracted from the hospital′s medical records. Patients with baseline LH/FSH ratio>2 were deemed as study group, patients with baseline LH/FSH ratio≤2 were deemed as control group. Single factor analysis was applied to compare the differences of pregnancy outcomes between two groups.Results:After propensity score matching (1∶2.5), there were no statistically significant differences in baseline data between the two groups (all P>0.05), indicating that the data were comparable. In the study group, the total dose of gonadotropin (Gn) and duration of Gn were lower than those of the control group ( t=4.989, P<0.001; t=3.267, P=0.001), the rate of in vitro maturation was higher than that of the control group ( χ2=4.938, P=0.026), the number of retrieved oocytes and cleavage were higher than those of the control group ( t=-2.305, P=0.021; t=-2.816, P=0.005), but there were no differences in the number and rate of high-quality embryos between the two groups ( t=-1.636, P=0.102; t=-0.123, P=0.902). The incidence of moderate to severe ovarian hyperstimulation syndrome in the study group was significantly higher than that in the control group ( χ2=17.277, P<0.001). Regardless of fresh embryo transfer or frozen-thawed embryo transfer cycles, the incidences of gestational diabetes mellitus in the study group were higher than those in the control group ( χ2=9.174, P=0.002; χ2=4.204, P=0.040) of singleton pregnancy. In the fresh embryo transfer cycle, the clinical pregnancy rate [30.30% (20/66) vs 47.75% (53/111)] and delivery rate [30.30% (20/66) vs 46.85% (52/111)] in the study group were lower than those in the control group ( χ2=5.198, P=0.023; χ2=4.695, P=0.030). In the frozen-thawed embryo transfer cycle, the delivery rate in the study group was higer than that in the control group [59.41% (423/712) vs 55.04% (1 053/1 913); χ2=7.526, P=0.023]. The clinical pregnancy rate and delivery rate of fresh embryo transfer cycle in the study group were significantly lower than those of frozen-thawed embryo transfer cycle ( χ2=21.308, P<0.001; χ2=20.871, P<0.001), but there were no significant differences in the control group (all P>0.05). Conclusions:PCOS patients with a higher basal LH/FSH ratio are more likely to develop moderate to severe ovarian hyperstimulation syndrome after controlled ovarian stimulation and have a higher incidence of gestational diabetes mellitus. Better pregnancy outcome could be obtained by frozen-thawed embryo transfer.

Objective To explore the predictive value of T cell activation in peripheral blood of patients with hepatocellular carcinoma(HCC) after anti PD-1 therapy and its ratio to tumor burden on the efficacy of immunotherapy. Methods Serum specimens were obtained before and after treatment from 85 patients with HCC who received anti-PD-1 treatment. Indicators such as cell subpopulations and T cell activation were detected by flow cytometry. Combined with imaging analysis, cutoff value was obtained by X-tile software. Survival analysis was used to evaluate patients' outcomes. Results The maximum fold change of Ki-67+/PD-1+/CD8+ T cells in treatment cycles and the tumor burden determined by imaging were associated with prognoses. The ratio of T cell Ki-67+/PD-1+/CD8+ expression to tumor burden ratio greater than 0.6 at the first cycle of anti-PD-1 immunotherapy was associated with improvements in progression-free survival and overall survival (P < 0.05). Conclusion The ratio of activationa in T cells in peripheral blood after immunotherapy to the tumor burden may be related to the clinical efficacy of anti-PD-1 immunotherapy for HCC.

Objective To investigate the distribution characteristics and risk factors of intracranial and extracranial aterial lesions in Chinese patients with ischemic stroke . Methods In this multi‐center study ,2 310 continuously inpatients with ischemic stroke diagnosed in 20 stroke screening and prevention project base hospitals from June 2015 to M ay 2016 were enrolled . Carotid ultrasonography and transcranial color‐coded sonography or transcranial Doppler were performed in all patients to confirm the presence of cerebral artery stenosis or occlusion . According to the distribution of lesions ,the subjects were divided into 2 groups :the simple intracranial artery stenosis group and the simple extracranial artery stenosis group . T he difference of risk factors between the two groups was compared . Results Of the 2 310 patients with ischemic stroke ,1 516 ( 65 .6% ) had simple intracranial artery stenosis and 794 ( 34 .4% ) had simple extracranial artery stenosis . T he incidence of anterior circulation artery stenosis was higher in the group of intracranial artery stenosis than that in the extracranial artery stenosis group ( 68 .1% vs 48 .7% , P ＜0 .001) . Posterior circulation artery stenosis and combined anterior with posterior circulation artery stenosis were more common in patients with extracranial artery stenosis group than those in intracranial artery stenosis group ( 36 .4% vs 22 .1% ,14 .9% vs 9 .8% ;all P ＜0 .001) . Univariate analysis of risk factors for stroke showed that patients with intracranial arterial stenosis had a higher prevelence of hypertension , diabetes ,obesity ,and family history of stroke ,and their systolic blood pressure ,diastolic blood pressure , body mass index ( BM I) ,fasting blood‐glucose ,glycosylated hemoglobin ,triacylglycerol ,total cholesterol , and low‐density lipoprotein cholesterol were significantly higher than those in the extracranial arterial stenosis group ( all P ＜ 0 .05 ) . T he proportion of elderly ( ≥ 65 years old ) ,male and smokers in the extracranial arterial stenosis group was significantly higher than that in the intracranial arterial stenosis group ( all P ＜0 .05) . Multivariate logistic regression analysis showed that elderly ( ≥65 years old) ,male , and smoking history were independent risk factors for extracranial arterial stenosis ( OR＝ 2 .012 ,1 .637 , 1 .325 ,respectively ;all P ＜0 .05) . While hypertension ,diabetes ,less physical activity ,and high BM I levels were independent risk factors for simple intracranial arterial disease ( OR ＝ 1 .301 ,1 .252 ,1 .248 ,1 .030 , respectively ;all P ＜0 .05) . Conclusions There are significant differences in the distribution characteristics and risk factors of intracranial and extracranial aterial lesions in patients with ischemic stroke in China .

Objective To investigate the distribution and drug resistance of carbapenem-resistant Enterobacteriaceae ( CRE) isolated from children in China. Methods CRE strains were collected in 10 ter-tiary children's hospitals of China from January 1, 2016 to December 31, 2017. Antimicrobial susceptibility of the clinical strains was detected with disk diffusion method ( KB method) and automated method. The re-sults were analyzed according to the Clinical and Laboratory Standards Institute ( CLSI) Standards published in 2017. WHONET 5. 6 software was used to retrospectively analyze the distribution characteristics and drug resistance of these strains. Results A total of 3065 CRE clinical strains were isolated from children with an overall prevalence of 7. 7％ and among them, 13. 5％ were isolated in neonatal group and 5. 8％ in non-neo-natal group. The detection rate of CRE in 2017 was higher than that in 2016 (9. 7％ vs 5. 7％). Among the 3065 CRE strains, there were 1912 strains of Klebsiella pneumoniae (62. 0％), 667 strains of Escherichia coli (22. 0％), 206 strains of Enterobacter cloacae (7. 0％), 56 strains of Klebsiella aerogenes (1. 8％) and 47 strains of Serratia marcescens (1. 5％). Most of the strains were isolate in neonatology departments including neonatal intensive care units (NICU) and intensive care units (ICU), accounting for 44. 8％ and 19. 7％, respectively. Respiratory tract (61. 8％), urine (19. 4％) and blood (5. 7％) specimens were the main sources of CRE isolates. Results of antimicrobial susceptibility test showed that the CRE strains were highly resistant to carbapenem antibiotics such as imipenem, meropenem and ertapenem, as well as penicillins and most cephalosporins (79. 6％-100％), especially those isolated in the neonatal group (P<0. 05). Children had relatively low resistance rates to aminoglycosides such as amikacin (19. 7％) and fos-fomycin (11. 9％), fluoroquinolones such as levofloxacin (37. 7％) and ciprofloxacin (43. 3％), and tige-cycline (3. 8％). Currently, no polymyxin B-resistant strains were isolated. Conclusions The prevalence of common CRE strains in children in 2017 was higher than that in 2016, especially in newborns. Drug re-sistance in CRE strains isolated from neonates to common antibiotics was more severe, suggesting that great attention should be paid to it and timely measures should also be taken.

Objective: To investigate the knowledge regarding clinical research among children at 8-18 years of age. The survey results will form the basis for developing public education program for this population. Methods: The survey was conducted among children at 8-18 years of age using WeChat and spot investigation between January 2016 and January 2017. According to different developmental stages, the survey population was divided into four groups: age 8-10, 11-13, 14-15 and 16-18 years. The level of knowledge regarding clinical research was analyzed. Results: Totally 1 329 questionnaires were issued and 1 233 effective questionnaires were returned with a recovery rate of 92.8%. The overall awareness rate regarding clinical research was 32.8% (405/1 233) . It revealed that 282 (22.9%) individuals thought that clinical research was to treat people like experimental rats. When asked "who have the final decision on research participation", the percentages of those who chose oneself, parents or guardian and doctor were 44.6% (550/1 233), 74.2% (915/1 233) and 36.8% (454/1 233) respectively. When asked "If you want to participate a study, but your parents or guardian do not agree, what would you do?", 33.9% (418/1 233) of individuals will "give up". As to "If you do not want to participate a study, but your parents or guardian think you should, what would you do?", 51.3% (632/1 233) chose "listen to parents" and 28.8% (355/1 233) chose "refuse the suggestions of parents or guardian". As to "what are your greatest concerns of participating an investigation?" , 68.1% (840/1 233) chose "worry about added pain or discomfort". but 58.0% (715/1 233) thought if "doctors and nurses take good care of me" their "concerns will reduce" or "feel better to participate in the research?". 55.6% (686/1 233) and 49.3% (608/1 233) individuals responded that they will "participate in an research?" when they "know that other people also participate the research" and when they "know the details regarding what will happen after the enrollment". Conclusions The knowledge level of clinical research among children aged 8-18 years were not high. It is very necessary to promote the public education of clinical research for this population and also very necessary to address their concern regarding the research.

To investigate the knowledge regarding clinical research among children at 8-18 years of age. The survey results will form the basis for developing public education program for this population. Methods The survey was conducted among children at 8-18 years of age using WeChat and spot investigation between January 2016 and January 2017. According to different developmental stages, the survey population was divided into four groups: age 8-10, 11-13, 14-15 and 16-18 years. The level of knowledge regarding clinical research was analyzed. Results Totally 1 329 questionnaires were issued and 1 233 effective questionnaires were returned with a recovery rate of 92.8%. The overall awareness rate regarding clinical research was 32.8% (405/1 233). It revealed that 282 (22.9%) individuals thought that clinical research was to treat people like experimental rats. When asked"who have the final decision on research participation", the percentages of those who chose oneself, parents or guardian and doctor were 44.6% (550/1 233), 74.2% (915/1 233) and 36.8% (454/1 233) respectively. When asked "If you want to participate a study, but your parents or guardian do not agree, what would you do?", 33.9% (418/1 233) of individuals will "give up". As to "If you do not want to participate a study, but your parents or guardian think you should, what would you do? ", 51.3% (632/1 233) chose"listen to parents" and 28.8% (355/1 233) chose"refuse the suggestions of parents or guardian". As to "what are your greatest concerns of participating an investigation?", 68.1% (840/1 233) chose"worry about added pain or discomfort". But 58.0%(715/1 233) thought if"doctors and nurses take good care of me"their "concerns will reduce" or "feel better to participate in the research? ". 55.6% (686/1 233) and 49.3% (608/1 233) individuals responded that they will"participate in an research? "when they"know that other people also participate the research" and when they"know the details regarding what will happen after the enrollment". Conclusions The knowledge level of clinical research among children aged 8-18 years were not high. It is very necessary to promote the public education of clinical research for this population and also very necessary to address their concern regarding the research.

Objective To assess the characterization and usefulness of contrast enhanced ultrasound (CEUS) to diagnose focal lesions of pancreas in comparison to contrast enhanced computed tomography (CECT).Methods 177 cases of focal solid lesions of the pancreas confirmed by pathology were collected.The enhanced patterns and diagnostic capability of CEUS were analyzed,and these results were compared with those of CECT.Results The diagnostic accuracies of ultrasound,CEUS and CECT were 61.6％ (109/177),89.3％ (158/177),and 92.1％ (163/177),respectively.There was no significant difference between the diagnostic accuracies of CEUS and CECT (P =0.071).The sensitivity,specificity,positive predictive value (PPV),negative predictive value (NPV),and accurate rate for CEUS were 90.9％,63.6％,73.8％,86.2％,82.5％ (the areas under the curve,AUC =0.820),and 89.8％,69.3％,76.7％,85.9％,84.7％ for CECT (AUC =0.847),respectively,when the hypo-enhanced was regarded as the cut value.No significant difference was found between these results from CEUS and CECT (P =0.071).Conclusions The diagnostic ability of CEUS in focal lesions of the pancreas is similar to that of CECT.

Objective To explore the effects of acupoint application combined with modified Xiaoqinglong decoction on airway remodeling and serum C-reactive protein (CRP), interleukin-8 (IL-8) and eosinophil chemotactic factor (eotaxin) levels in patients with bronchial asthma. Methods A total of 78 patients with bronchial asthma were randomly divided into two groups, 39 cases each group. The control group was treated with conventional western medicine therapy, and the study group was treated with acupoints plus Xiaoqinglong decoction on the basis of the control group.The treatment effect,adverse reaction were observed, and airway remodeling associated indicators like Transforming growth factor-β1 (TGF-β1), vascular endothelial growth factor (VEGF), basic fibroblast growth factor (bFGF), and serum CRP, IL-8, Eotaxin levels were detected as well. Results After treatment, the clinical asthma control rate was 87.18% (34/39) in the study group and 58.97% (23/39) in the control group, and the difference was statistically significant (χ2=7.885,P<0.05).After treatment,the TGF-β1(6.74 ± 2.21 μmol/L vs.10.90 ± 2.24 μmol/L,t=8.256),VEGF(27.63 ± 5.14 ng/ml vs.35.76 ± 5.82 ng/ml,t=6.539),bFGF(7.15 ± 1.54 μmol/L vs.12.62 ± 2.23μmol/L,t=12.605)in the study group were significantly lower than those of the control group (P<0.05). After treatment, the CRP (9.16 ± 1.85 mg/L vs.16.74 ± 2.20 mg/L,t=16.468),IL-8(51.26 ± 17.25 pg/L vs.114.32 ± 20.15 pg/L,t=14.847),IL-8 (98.59 ± 34.12 pg/ml vs.159.62 ± 52.74 pg/ml,t=6.068)in the study group were significantly lower than those of the control group (P<0.05). There was no significant difference in the incidence of adverse reaction between the study group 20.5%(8/39) and the control group12.8%(5/39) during treatment (χ2=0.831, P>0.05). Conclusions The acupoint application combined with modified Xiaoqinglong decoction can significantly improve the clinical effect, inhibit airway remodeling, decrease the level of serum CRP, IL-8 and Eotaxin in patients with bronchial asthma, and its safety is high.

Objective: To assess value of contrast enhanced ultrasound (CEUS) in TN staging of pancreatic cancer and compared with contrast enhanced computed tomography(CECT). Methods: Seventy-eight cases with pancreatic cancer confirmed by pathology were enrolled in this study. All patients were examined using CEUS and CECT and staged according to the 8th guideline of pancreas tumors of AJCC. The diagnostic accuracies of CEUS in TN staging of pancreas tumors were compared with CECT. Results: The diagnostic accuracies of CEUS in T staging and N staging of pancreatic cancer were 80.8%, and 78.2%, respectively. For CECT, the diagnostic accuracies in T staging and N staging were 88.5%, and 88.5%, respectively. There was no significant difference in the diagnostic accuracies between CEUS and CECT in T staging(χ²=1.56, P=0.21). The diagnostic accuracy of CEUS in N staging was significantly lower than that of CECT(χ²=3.86, P=0.04). Conclusions The diagnostic accuracy of CEUS in T staging of pancreatic cancer is similar to that of CECT, while in its N staging is lower than that of CECT.