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 investigate the changes in high performance liquid chromatography （HPLC） fingerprint spectra and nucleoside components between Pinelliae Rhizoma Praeparatum cum Zingibere et Alumine and its processed product Succus bambusae pinella preparata， providing a reference for the quality evaluation of the latter. METHODS HPLC fingerprint was established for 10 batches of Pinelliae Rhizoma Praeparatum cum Zingibere et Alumine and its processed product Succus bambusae pinella preparata following the Similarity Evaluation System of TCM Chromatographic Fingerprints （2012 Edition）. Hierarchical cluster analysis （HCA）， principal component analysis （PCA）， and orthogonal partial least squares-discriminant analysis （OPLS- DA） were conducted on their common peaks. The contents of four nucleoside components， hypoxanthine， uridine， adenine， and guanosine， in both Pinelliae Rhizoma Praeparatum cum Zingibere et Alumine and Succus bambusae pinella preparata were determined. RESULTS The similarity between the fingerprints of the 10 batches of Pinelliae Rhizoma Praeparatum cum Zingibere et Alumine， Succus bambusae pinella preparata， and their corresponding reference fingerprints ranged from 0.851 to 0.990. A total of 10 common peaks were obtained for both samples， and 4 components were identified as hypoxanthine， uridine， adenine， and guanosine. The results of HCA， PCA and OPLS-DA showed that the samples of Pinelliae Rhizoma Praeparatum cum Zingibere et Alumine and Succus bambusae pinella preparata were clustered into separate categories， with OPLS-DA selecting 4 differential components between them， ranked by variable importance projection values as peak 8， peak 1， peak 6 （adenine） and peak 10. The content determination results showed that the average contents of hypoxanthine， uridine， adenine and guanosine in Succus bambusae pinella preparata declined by 15.90%， 12.00%， 26.04% and 22.18% compared to Pinelliae Rhizoma Praeparatum cum Zingibere et Alumine， respectively， with statistically significant differences in the contents of hypoxanthine， adenine and guanosine （P＜0.05 or P＜0.01）. CONCLUSIONS The established fingerprint and content determination methods are simple to operate and have good repeatability， which are suitable for qualitative and quantitative analysis of Pinelliae Rhizoma Praeparatum cum Zingibere et Alumine and Succus bambusae pinella preparata. The average contents of the four nucleoside components decreased after the processing of Succus bambusae pinella preparata.

Objective To investigate the clinical value of prophylactic high-flow nasal cannula oxygen therapy (HFNC) in reducing postoperative pulmonary complication (PPC) in elderly patients with non-small cell lung cancer (NSCLC). Methods The clinical data of elderly patients (over 60 years) with NSCLC who underwent video-assisted thoracoscopic lobectomy or segmental resection at the Department of Thoracic Surgery, Fujian Provincial Hospital from January 2021 to March 2022 were retrospectively analyzed. According to whether receiving HFNC after surgery, they were divided into a conventional oxygen therapy (CO) group and a HFNC group. The CO group were matched with the HFNC group by the propensity score matching method at a ratio of 1 : 1. We compared PPC incidence, white blood cell (WBC) count, procalcitonin and C-reactive protein on postoperative day (POD) 1, 3 and 5 and postoperative hospital stay between the two groups. Results A total of 343 patients (165 males, 178 females, average age of 67.25±4.79 years) were enrolled, with 53 (15.45%) receiving HFNC. Before matching, there were statistical differences in gender, rate of combined chronic obstructive pulmonary disease, pathology type and TNM stage between the two groups (all P<0.05). There were 42 patients successfully matched in each of the two groups, with no statistical difference in baseline characteristics (P>0.05). After propensity score matching, the results showed that the PPC incidence in the HFNC group was lower than that in the CO group (23.81% vs. 45.23%, P=0.039). WBC count on POD 3 and 5 and procalcitonin level on POD 3 were less or lower in the HFNC group than those in the CO group [ (8.92±2.91)×109/L vs. (10.62±2.67)×109/L; (7.68±1.58)×109/L vs. (8.86±1.76)×109/L; 0.26 (0.25, 0.44) μg/L vs. 0.31 (0.25, 0.86) μg/L; all P<0.05]. There was no statistical difference in the other inflammatory indexes or the postoperative hospital stay between the two groups (P>0.05). Conclusion Prophylactic HFNC can reduce the PPC incidence and postoperative inflammatory indexes in elderly patients with NSCLC, but does not shorten the postoperative hospital stay.

BACKGROUND:Reducing the rate of abnormal fertilization is an effective approach to improving the efficacy of in vitro fertilization and reducing patients'financial strain.However,the current research on abnormal fertilization has focused on exploring the types of prokaryotic nuclei and their generation mechanisms,as well as analyzing embryos formed by abnormal fertilization,chromosomal ploidy and utilization value.There is a lack of clinical prediction models for abnormal fertilization based on retrospective studies. OBJECTIVE:To construct a nomogram model to predict abnormal female factors in in vitro fertilization. METHODS:A total of 5 075 patients undergoing treatment for conventional in vitro fertilization at Nanxishan Hospital of Guangxi Zhuang Autonomous Region from March 2017 to March 2022 were retrospectively analyzed.The male confounders were calibrated on a 1:1 propensity score with a match tolerance of 0.02,and 1 672 cases were successfully matched.According to the Vienna Consensus,patients with≥60%normal fertilization capacity were included in the normal fertilization group(n=836)and those with<60%normal fertilization capacity were included in the abnormal fertilization group(n=836).The model and validation groups were obtained by random sampling at a ratio of 7:3.Factors related to the occurrence of abnormal fertilization following conventional in vitro fertilization in the model group were screened using univariate analysis and the best matching factors were selected using the Least Absolute Shrinkage and Selection Operator(LASSO)and included in a multifactorial forward stepwise Logistic regression to identify their independent influencing factors and plot a nomogram.Finally,the prediction model was validated for discrimination,accuracy and clinical application efficacy using receiver operating characteristic curves,calibration curves,clinical decision curves and clinical impact curves. RESULTS AND CONCLUSION:The univariate analysis indicated the factors influencing the occurrence of abnormal fertilization were age,controlled ovarian hyperstimulation protocol,number of assisted pregnancies,years of infertility,infertility factors,anti-mullerian hormone,sinus follicle count,basal luteinizing hormone,luteinizing hormone concentration on the human chorionic gonadotropin day,and estradiol level on human chorionic gonadotropin injection day(P<0.05).LASSO regression further identified the best matching factors,including age,microstimulation protocol,number of assisted pregnancies,years of infertility,anti-mullerian hormone,luteinizing hormone level on human chorionic gonadotropin injection day,and estradiol level on human chorionic gonadotropin injection day(P<0.05).Multifactorial forward stepwise Logistic regression results showed that age,microstimulation protocol,number of assisted conceptions,years of infertility,anti-mullerian hormone,and estradiol level on human chorionic gonadotropin injection day were independent influencing factors for the occurrence of abnormal fertilization following conventional in vitro fertilization.The receiver operating characteristic curves showed an area under the curve of 0.761(0.746,0.777)for the model group and 0.767(0.733,0.801)for the validation group,indicating that the model has good discrimination.The mean absolute error of the calibration curve was 0.044,and the Hosmer-Lemeshow test indicated that there was no significant difference between the predicted probability of abnormal fertilization and the actual probability of abnormal fertilization(P>0.05),indicating the prediction model has good consistency and accuracy.The clinical decision curves and clinical impact curves showed that the model and validation groups had the maximum net clinical benefit at valve probability values of 0.00-0.52 and 0.00-0.48,respectively,and there was a good clinical application efficacy in this valve probability range.To conclude,the nomogram model has good discrimination and accuracy as well as clinical application efficacy for predicting the occurrence of abnormal fertilization in women undergoing conventional in vitro fertilization based on age,microstimulation protocol,number of assisted conceptions,years of infertility,anti-mullerian hormone,and estradiol level on human chorionic gonadotropin injection day.

Lung cancer is the most common malignant disease and the leading cause of cancer death in China.Non-small cell lung cancer(NSCLC)accounts for over 80％of all lung cancers,and the probability of NSCLC gene mutations is high,with a wide variety of types.With the development of next-generation sequencing(NGS)detection technology,more and more patients with rare fusion gene mutations are detected.Neuregulin 1(NRG1)gene is a rare oncogenic driver that can lead to activation of human epidermal growth factor receptor 3(Her3/ErbB3)mediated pathway,resulting in tumor forma-tion.In this article,we reported a case of mixed NSCLC with CRISPLD2-NRG1 fusion detected by RNA-based NGS,who re-sponsed to Afatinib well after 1 month of treatment,and magnetic resonance imaging(MRI)showed shrinkage of intracranial lesions.Meanwhile,we also compiled previously reported NSCLC patients with NRG1 rare gene fusion mutation,in order to provide effective references for clinical diagnosis and treatment.

Objective To investigate the protective effects of Sulforaphane(SFN)against high glucose(HG)-induced human platelet apoptosis and elucidate the underlying mechanisms in vitro.Methods Purified platelets obtained from healthy individuals were pre-incubated with various concentrations of SFN(5,10,or 20 μmol/L)or a vehicle control(0.05%DMSO)for 40 minutes at 37℃.Subsequently,the platelets were stimulated with normal glucose(NG,5 mmol/L)or high glucose(HG,25 mmol/L)for an additional duration of 90 minutes.Flow cytometry was employed to assess platelet mitochondrial membrane potential depolarization(Δψm),exposure of phosphatidylserine(PS),and generation of total intraplatelet reactive oxygen species(ROS).Phosphorylation levels of PI3K and Akt were determined using Western blot.Results Compared to NG-treated human platelets,HG significantly induced depolarization of platelet Δψm and exposure of PS(P＜0.001).These effects of HG were markedly attenuated by various concentrations of SFN(P＜0.001).Mechanistically,SFN down-regulated the phosphorylation levels of PI3K(P＜0.01)and Akt(P＜0.05),which were increased by HG when compared to the vehicle control,and substantially reduced total intracellular ROS levels(P＜0.001).The inhibitory effects of SFN on HG-induced phosphorylation of PI3K and Akt,as well as its efficacy on total intracellular ROS generation,Δψm depolarization,and PS exposure in HG-stimulated human platelets were completely reversed by a specific agonist for PI3K,740 Y-P.Conclusions The current study demonstrates that SFN exerts a protective effect on platelet apoptosis induced by HG,potentially through the down-regulation of the PI3K/Akt-mediated pathway in human platelets in vitro.These findings suggest that SFN may hold promise for improving thrombosis in diabetes mellitus and related chronic metabolic diseases.

Objective To investigate risk factors of medication non-adherence in elderly patients with hypertension through Meta-analysis.Methods Literatures on medication non-adherence in elderly patients with hypertension were systematically reviewed across various databases,from inception to September 1st 2023,including CNKI,VIP,Wangfong Database,SinoMed,PubMed,Web of Science,Cochrane Library、EMbase.Meta-analysis was conducted using RevMan 5.4.Results A total of 19 articles were included,comprising a total of 18 220 patients in sample size.Meta analysis identified 10 risk factors,showed significant association(P<0.05)with:age[OR=1.36,95%CI=(1.00,1.86)],place of residence[OR=1.91,95%CI=(1.33,2.75)],method of payment for medical expenses[OR=1.60,95%CI=(1.38,1.86)],income level[OR=1.68,95%CI=(1.45,1.95)],occupational status[OR=1.79,95%CI=(1.37,2.36)],social support[OR=1.43,95%CI=(1.27,1.60)],comorbidity[CI=0.33,95%(0.19,0.58)],frequency of blood pressure measurement[CI=1.53,95%(1.14,2.05)],disease awareness[OR=1.70,95%CI=(1.44,2.00)]and dedication frequency[OR=1.44,95%CI=(1.16,1.79)].In addition,the number of influencing factors such as gender,marital status,depression,cognitive impairment,and complications was included in<3 articles,and only descriptive analysis was conducted.Conclusion Healthcare providers should focus on the identification and management of the risk factors associated with medication non-adherence in elderly patients with hypertension,therefore to reduce the incidence of medication non-adherence.

Objective:To retrieve, evaluate, and integrate the best evidence for prevention of hemodialysis catheter thrombosis, so as to provide evidence-based basis for catheter thrombosis prevention in hemodialysis patients.Methods:Guidelines, clinical decisions, evidence summaries, systematic reviews, and expert consensus on the prevention of hemodialysis catheter thrombosis were systematically searched on Guidelines International Network, Scottish Intercollegiate Guidelines Network, Agency for Healthcare Research and Quality, Registered Nurses' Association of Ontario, National Institute for Health and Clinical Excellence, UpToDate, British Medical Journal (BMJ) Best Practice, Joanna Briggs Institute Evidence-Based Health Care Center Database, European Renal Association, National Kidney Foundation, UK Kidney Association, Canadian Society of Nephrology, Japanese Society for Dialysis Therapy, Medlive, Cochrane Library, PubMed, Embase, China National Knowledge Infrastructure, VIP, and Wanfang Data and Chinese Biomedical Database. The search period was from database establishment to March 31, 2023. Investigators conducted quality evaluations separately and extracted and summarized evidence based on the theme.Results:A total of 16 articles were included, including five clinical decisions, four guidelines, two evidence summaries, and five expert consensuses. Finally, 15 best pieces of evidence were formed, including four themes of indwelling dialysis catheters, anticoagulation strategies, flushing and sealing techniques, and daily management.Conclusions:Nursing staff should choose the best evidence for preventing thrombosis in hemodialysis catheters based on clinical situations, reduce the occurrence of catheter thrombosis, extend the usage time of catheters, and improve patient outcomes.

Objective:To construct an evaluation index system for the core competence of infection control link nurses.Methods:With the core competence theory as the guiding framework, the literature research method, and the expert meeting method preliminarily drew up the index item pool. After two rounds of expert consultation, the evaluation index of the core competence of infection control link nurses was determined.Results:Two rounds of expert inquiry were conducted, with 23 and 22 questionnaires distributed, respectively. A total of 22 and 20 valid questionnaires were collected, with effective response rates of 95.65% and 90.91%, respectively. The expert authority coefficients were 0.92 and 0.91, respectively. Kendall's harmony coefficients for the overall indicator importance and operability evaluation in the second round of expert inquiry were 0.191 and 0.230, respectively (both P<0.01). Finally, the evaluation index system of infection control link nurses consisted of five primary indexes and 43 secondary indexes. Conclusions:The evaluation index system for core competence of infection control link nurses constructed in this study is scientific, reliable, and practical, which can provide a reference for the training and evaluation of infection control link nurses.

Objective:To explore the expectations of different groups, including the vice president in charge of hospital infection, hospital infection management professionals, nursing managers, and department directors, on the core competence of head nurses in hospital infection prevention and control.Methods:Using the phenomenological research method, purposive sampling method was used to conduct in-depth semi-structured interviews with 25 interviewees from 5 tertiary general hospitals in Hangzhou City, Zhejiang Province, including vice presidents in charge of hospital infection, hospital infection management professionals, nursing managers, department directors, clinical staff and logistics supervisors. A total of 25 interviewers conducted in-depth semi-structured interviews, and the collected data were analyzed by Colaizzi′s 7-step analysis method.Results:Four themes were extracted, including the expectation of the head nurse′s infection control target management ability, the expectation of the head nurse′s infection control professional knowledge ability, the expectation of the head nurse′s infection control clinical practice ability, and the expectation of the head nurse′s infection control influence.Conclusions:In the sensory control management of the department, head nurses should have strong infection control target management ability, continue to learn and update the infection control knowledge and concepts, improve the clinical infection control practice ability, properly authorize, reasonably motivate and improve the infection control management. Team execution ability, create a good atmosphere of department sense control, and promote the development of infection control work.