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 establish dynamic nomogram models for postoperative recurrence and survival risk of patients with AFP-negative hepatocellular carcinoma(ANHC)based on multimodal clinical data,to identify ANHC-specific prognostic biomarker combinations by integrating tumor biological characteristics and treatment response parameters through machine learning,and to provide an individualized risk assessment tool for overcoming the limitations of traditional serum biomarkers.Methods A retrospective analysis was performed for 421 ANHC patients who underwent hepatectomy in Eastern Hepatobiliary Surgery Hospital from April 2012 to December 2018,and they were randomly divided into training group with 210 patients and validation group with 211 patients.The univariate and multivariate Cox proportional-hazards regression models were used to identify independent prognostic factors and establish a nomogram model,and the receiver operating characteristic(ROC)curve,the calibration curve,and the decision curve analysis were used to assess the performance of the model.Related indicators were measured,including prealbumin(PA),white blood cell count(WBC),tumor size,and microvascular invasion.The chi-square test or the Fisher's exact test was used for comparison of categorical variables between two groups,and the independent-samples t test or the Mann-Whitney U test was used for comparison of continuous variables between two groups.Results The multivariate analysis showed that multiple tumors(hazard ratio[HR]=3.30,P<0.001),WBC(HR=1.05,P=0.005),blood glucose(HR=1.15,P=0.026),CA19-9(HR=1.17,P=0.005),and tumor size(HR=1.17,P<0.001)were independent risk factors for disease-free survival(DFS),while PA(HR=0.99,P=0.022)was a protective factor.Incomplete tumor capsule(HR=0.60,P=0.009),age(HR=1.02,P=0.035),prothrombin time(PT)(HR=1.27,P=0.023),CA19-9(HR=1.01,P<0.001),and tumor size(HR=1.15,P<0.001)were independent risk factors for overall survival(OS).The DFS nomogram achieved an AUC of 0.74(95%confidence interval[CI]:0.64-0.84)in the training group and 0.67(95%CI:0.57-0.77)in the validation group,while the OS nomogram had an AUC of 0.76(95%CI:0.64-0.88)and 0.73(95%CI:0.60-0.87),respectively.The calibration curve and the decision curve analysis showed that the models had good predictive accuracy and clinical practicability.Conclusion Preoperative indicators,including tumor number,PA,WBC,and tumor size,can effectively predict postoperative recurrence in ANHC patients,while tumor capsule integrity,age,and PT are significantly associated with OS.The nomogram models established have good performance and can provide a basis for individualized prognostic assessment.

[Purpose]To analyze cancer incidence and mortality in Xinjiang cancer registration ar-eas in 2020 and the trends from 2016 to 2020.[Methods]Incidence and mortality data of cancer reported by four cancer registration areas in Xinjiang in 2020 were collected.Crude incidence and mortality rates,age-standardized incidence and mortality rates by Chinese standard population(ASIRC/ASMRC),and world standard population(ASIRW,ASMRW),and cumulative rate(0～74 years old)were calculated.The Chinese standard population(2000 national census)and Segi's world standard population were used for standardization.Joinpoint regression was applied to ana-lyze the trends of incidence and mortality from 2016 to 2020,and the average annual percentage change(AAPC)was calculated.[Results]In 2020,the crude incidence rate of cancer in Xinjiang cancer registration areas was 291.67/105(286.64/105 for male,296.64/105 for female),ASIRC and ASIRW were 190.43/105 and 206.58/105,and the cumulative incidence rate(0～74 years old)was 20.51％.The crude mortality rate was 185.58/105(2 1 8.79/105 for male,152.78/105 for female),ASMRC and ASMRW were 109.13/105 and 126.64/105,and the cumulative mortality rate(0～74 years old)was 11.54％.In 2020,the incidence and mortality rates increased with age,peaking in the age groups of 80～84 and ≥85 years old,respectively.Lung cancer was the leading cause of incidence(crude incidence rate:51.13/10s),followed by female breast cancer,thyroid cancer,colorectal cancer and stomach cancer.Lung cancer was also the leading cause of mortality(crude mortality rate:41.14/105),followed by liver cancer,colorectal cancer,stomach cancer and fe-male breast cancer.There was no significant change in the ASIRC/ASMRC from 2016 to 2020(incidence AAPC=2.95％,mortality AAPC=8.51％,both P＞0.05).[Conclusion]The incidence and mortality of cancer in Xinjiang cancer registration areas were stable from 2016 to 2020.Lung cancer,digestive system cancers(colorectal,gastric,liver cancers),and female breast cancer re-main the main cancers threatening the health of Xinjiang residents,indicating the need to strengthen screening and early diagnosis and treatment.

Objective To analyze the research status and development trend of post dialysis fatigue(PDF)in dialysis patients at home and abroad,and to provide reference for nursing practice.Methods Relevant literature included in the China Knowledge Network,Wanfang Data Knowledge Service Platform and PubMed database from its inception to November 30,2024 was searched,and bibliometric analysis was performed using CiteSpace 6.2.R6 software.Results A total of 624 papers(347 in English and 277 in Chinese)were published from 1999 to 2024,with the number of articles increasing year by year;International research has formed a stable cooperation network,with hotspots focusing on the validation of the reliability and validity of the fatigue assessment tool and the exploration of nursing interventions.Conclusion Foreign PDF studies started earlier,and domestic studies have increased in recent years,but localization of assessment tools,validation of multiple populations and exploration of interventions need to be strengthened to improve patients' quality of life.

Objective:To compare the diagnostic value of semi-quantitative parameters of fluorine 18-labelled prostate-specific membrane antigen( 18F-PSMA)positron emission tomography /computed tomography(PET/CT)and the Prostate-specific Membrane Antigen Reporting and Data System(PSMA-RADS)score for identifying benign and malignant oligo-PSMA-avid bone lesions(1-5 lesions)in elderly patients with prostate cancer. Methods:A retrospective analysis was conducted on 157 prostate cancer patients who underwent 18F-PSMA PET/CT examinations at Beijing Hospital from October 2022 to August 2024.According to the inclusion and exclusion criteria, a total of 63 patients were selected.All patients underwent 18F-PSMA PET/CT examination for the purpose of initial staging or detecting lesions with biochemical recurrence.PSMA-avid bone lesions were evaluated using the PSMA-RADS version 2.0 scoring system and the semi-quantitative parameters were measured on PSMA PET/CT images.According to the comprehensive diagnostic criteria, PSMA-avid bone lesions were divided into metastatic group and non-metastatic group.The differences in PSMA-RADS scores, semi-quantitative parameters, bone density abnormalities, and lesion distribution were compared between the two groups.Multivariate logistic regression analysis was performed to determine the factors related to the bone metastasis in prostate cancer.By plotting the receiver operating characteristic(ROC)curves and calculating the area under the curve(AUC), factors with better diagnostic performance were evaluated and screened, and the optimal diagnostic threshold for each factor in diagnosing bone metastasis was determined. Results:There were a total of 129 PSMA-avid bone lesions for 63 patients(aged 60-84 years, median age 69 years), including 35 lesions(27.1%)in the metastatic group and 94 lesions(72.9%)in the non-metastatic group.The differences between metastatic group and non-metastatic group in PSMA-RADS scores[5(4, 5) vs.3(3, 3)], maximum standardized uptake value(SUV max)[12.6(7.0, 18.4) vs.4.7(3.5, 5.9)], lesion SUV max/mediastinal blood pool SUV max ratio(lesion-to-blood pool ratio, LBR)[5.4(3.0, 8.3) vs.1.7(1.4, 2.2)], lesion SUV max/liver SUV max ratio(lesion-to-liver ratio, LLR)[2.6(1.6, 4.1) vs.0.8(0.7, 1.1)], PSMA receptor expressing tumor volume(PSMA-TV)[0.6(0.3, 1.0) vs.1.0(0.7, 1.5)], total lesion of PSMA(TL-PSMA)[4.4(2.4, 7.0) vs.2.4(1.7, 3.9)], proportion of changes in osteogenic bone density[77.1%(27/35) vs.2.1%(2/94)], proportion of lesions located in the ribs[14.3%(5/35) vs.46.8%(44/94)], and proportion of lesions located in the pelvis[54.3%(19/35) vs.20.2%(19/94)]were all statistically significant(all P<0.05). Multivariate logistic regression analysis indicated that none of the variables with statistically significant differences between groups above were independent risk factors for osseous metastasis in prostate cancer(all P>0.05). Among them, The PSMA-RADS score, LLR, LBR, and SUV max all had good diagnostic efficacy for osseous metastasis, with 0.995(95% CI: 0.987-1.000), 0.923(95% CI: 0.869-0.977), 0.898(95% CI: 0.828-0.967), and 0.890(95% CI: 0.820-0.961), respectively.The cut-off values for diagnosing osseous metastasis were 4 score for PSMA-RADS score, 0.934 for LLR, 1.990 for LBR, and 5.47 for SUV max, respectively.According to Delong's test, there were statistically significant differences in AUC between PSMA-RADS score and 18F-PSMA PET/CT semi-quantitative parameters(LLR, LBR, and SUV max)( Z-values were 2.677, 2.776, and 2.929, respectively, and P-values were 0.007, 0.006, and 0.003, respectively). Conclusions:The PSMA-RADS score(Version 2.0)and 18F-PSMA PET/CT semi-quantitative parameters(LLR, LBR, and SUV max)both have good diagnostic value in differentiating benign and malignant PSMA-avid bone lesions in elderly patients with prostate cancer, among which the PSMA-RADS score has the best diagnostic efficacy.

OBJECTIVE: Recombination events are common and serve as the primary driving force of diverse human adenovirus (HAdV), particularly in children with acute respiratory tract infections (ARIs). Therefore, continual monitoring of these events is essential for effective viral surveillance and control. METHODS: Respiratory specimens were collected from children with ARIs between January 2022 and December 2023. The penton base, hexon, and fiber genes were amplified from HAdV-positive specimens and sequenced to determine the virus type. In cases with inconsistent typing results, genes were cloned into the pGEM-T vector to detect recombination events. Metagenomic next-generation sequencing (mNGS) was performed to characterize the recombinant HAdV genomes. RESULTS: Among 6,771 specimens, 277 (4.09%, 277/6,771) were positvie for HAdV, of which 157 (56.68%, 157/277) were successfully typed, with HAdV-B3 being the dominant type (91.08%, 143/157), and 14 (5.05%, 14/277) exhibited inconsistent typing results, six of which belonged to species B. The penton base genes of these six specimens were classified as HAdV-B7, whereas their hexon and fiber genes were classified as HAdV-B3, resulting in a recombinant genotype designated P7H3F3, which closely resembled HAdV-B114. Additionally, a partial gene encoding L1 52/55 kD was identified, which originated from HAdV-B16. CONCLUSION A novel recombinant, P7H3F3, was identified, containing sequences derived from HAdV-B3 and HAdV-B7, which is similar to HAdV-B114, along with additional sequences from HAdV-B16.
Humans ; Adenoviruses, Human/isolation & purification* ; Respiratory Tract Infections/epidemiology* ; Child, Preschool ; Child ; Recombination, Genetic ; Male ; Beijing/epidemiology* ; Infant ; Female ; Phylogeny ; Adenovirus Infections, Human/epidemiology* ; Acute Disease ; Genome, Viral

Objective:To explore the molecular epidemiological characteristics of human metapneumovirus (HMPV) in children with acute respiratory infection (ARI) in Beijing from 2023 to 2024.Methods:In the longitudinal study, 9 834 children with ARI were enrolled from August 2023 to December 2024, including the influenza-like illness (ILI) group from emergency and outpatient department receiving influenza virus (Flu) and HMPV test and the ARI inpatient group for 13 common respiratory pathogen screening test including HMPV, Flu, respiratory syncytial virus, and so on. All respiratory samples positive with HMPV were genotyped by amplifying and sequencing of G gene and further phylogenetic analysis. The χ2 test and Wilcoxon rank-sum test were used to compare the positive rate and basic clinical data of the 2 groups. Results:Among 9 834 enrolled patient, there were 5 276 male and 4 558 female children, with age 5.4 (1.9, 8.2) years. In ILI group of 1 460 patients, there were 83 cases (5.7%) positive for HMPV, with the age 4.9 (3.6, 6.6) years and children under 6.0 years old 59 cases (71.1%). Among 8 374 ARI inpatients, there were 256 cases (3.1%) positive for HMPV, with age 3.5 (1.3, 6.4) years and children under 6.0 years old 188 cases (73.4%). The HMPV positive rate and the age of children positive for HMPV in ARI inpatient group were significantly lower than that in ILI group (both P<0.001). In December, 2024, the HMPV positive rates of ILI and ARI inpatient group (21.3% (17/80), 15.0% (47/314)) were significantly higher than the total positive rates of each group (both P<0.001). Among 279 subtyped specimens, there were 155 cases (55.6%) belonging to genotype A and 124 cases (44.4%) belonging to genotype B. Sub-lineage A2.2.2 containing 111nt-insertions was predominate one in 2023 with positive ratio 89.2% (91/102), and B2 was predominate in 2024 with positive ratio 64.4% (114/177). Conclusions:From 2023 to 2024, the positive rate of HMPV in the ILI group was higher than that in the ARI inpatient group, suggesting a common epidemic of HMPV infection. Children positive for HMPV in the ARI inpatient group were younger than that in the ILI group. A severe epidemic of HMPV was observed in the winter of 2024, which requires attention. Sub-lineage A2.2.2 with 111nt-duplicate insertions and B2 were the predominant epidemic strains in 2023 and 2024, respectively.

OBJECTIVE To evaluate the value of matrix-assisted laser desorption ionization time-of-flight-mass spectrometry(MALDI-TOF MS)in direct identification of carbapenem-resistant Escherichia coli and Klebsiella pneumoniae positive for blood culture.METHODS The blood culture bottles that were positive for E.coli or K.pneumoniae were collected from the patients with bloodstream infection who were treated in Zhongshan Hospi-tal,Fudan University from Jul.2021 to Jun.2023.The isolates were collected by using a gel-contact clotting tube,then the tested strains were respectively mixed with 4 μg/ml of imipenem,4 μg/ml of meropenem and 2 μg/ml of ertapenem for coculture and were incubated at 35 ℃ for 4 and 5 hours,finally,the strains were i-dentified by using the mass spectrum.The minimum inhibitory concentrations(MICs)of the three types of drugs were tested by microbroth dilution method and were set as the golden standards for the test.RESULTS Totally 31 strains of E.coli and 28 strains of K.pneumoniae that were positive in blood culture bottles were collected,both of the effective rates of controlled growth of the E.coli strains were 100.00％after the incuba-tion for 4 and 5 hours,and the effective rates of controlled growth of the K.pneumoniae strains were 9 6.43％and 100.00％after the incubation for 4 and hours,respectively.The sensitivity,specificity,positive predictive value and negative predictive value of the K.pneumoniae strains against the three types of drugs were 100.00％after the incubation for 5 hours.The specificity and positive predictive value of the E.coli strains against imipenem,meropenem and ertapenem were 100.00％after the incubation for 5 hours;the sensitivities were 73.58％,78.93％and 78.93％,respectively;the negative predictive values were 70.60％,75.00％and 75.00％,respectively.CONCLUSIONS MALDI-TOF MS is rapid and accurate for direct identification of the carbapenem-resistant E.coli and K.pneumoniae strains positive in blood culture bottles,and the accuracy reaches at 100.00％for the test of drug-resistant K.pneumoniae strains after the incubation for 5 hours.The method may provide evidence for clinical treatment of bloodstream infections induced by carbapenem-resistant Enterobacteriaceae.

Objective To evaluate the impact of setting a 4-day incubation time on the detection performance of bloodstream infection(BSI)pathogens by the BacTALERT VIRTUO blood culture system(VIRTUO).Methods Retrospectively collecting blood culture(BC)results from Zhongshan Hospital,Fudan University,from June 2021 to December 2023,and comparing the time-to-detection for clinically significant microorganisms.Results A total of 87 052 BC bottles were collected,of which 7 167(8.23%)were positive.95%of aerobic and anaerobic bottles were reported positive at 65.67 h and 91.2 h respectively.The average(median)time-to-detection for Staphylococcus aureus(S.aureus)was 21.76(16.08)h,Klebsiella pneumoniae(KP)was 15.32(11.65)h,Escherichia coli(E.coli)was 16.14(10.87)h,and Candida species was 35.2(28.5)h.Only 213 bottles(0.24%)were reported positive after 4 days of incubation;among them,88 bottles(41.31%)cultured Propionibacterium acnes(P.acnse).Medical chart reviews for BC reported positive after 96 h(4 days)showed no clinical significance.Simulated growth experiments were conducted on 11 fastidious bacteria,and the median detection time was only 10.8 h,indicating that an incubation time of 4 days is sufficient for fastidious bacteria.Conclusion A 4-day incubation is adequate for VIRTUO system.Reporting 1 day earlier to the doctors can reduce the positive rate of contaminants and the use of antimicrobial agents.

Objective:To systematically retrieve, extract and summarize the best evidence regarding the prevention and management of perioperative gastrointestinal dysfunction in patients with colorectal cancer, and to provide an evidence-based basis for clinical nursing practice.Methods:All evidence on the prevention and management of perioperative gastrointestinal dysfunction in colorectal cancer patients in various domestic and international databases and websites such as UpToDate, China national knowledge infrastructure, etc. were searched according to the "6S" pyramid model, including clinical decisions, guidelines, expert consensus, systematic evaluations, and randomized controlled trials from the time of database construction to August 15, 2024, on a top-to-bottom basis. Literature screening, quality assessment, and evidence extraction were performed independently by 2 nursing researchers.Results:A total of 19 documents were finally included, included 4 guidelines, 3 expert consensus, 7 systematic evaluations, 1 Meta-analysis, and 4 randomized controlled trials, and 35 pieces of evidence were summarized in 6 areas, including screening and assessment, build a multidisciplinary team, preoperative preparation, intraoperative monitoring, postoperative care, and evaluation of outcomes.Conclusions:The evidence summarized in this study is both scientifically rigorous and practically applicable, and can be used by healthcare professionals to design care plans for colorectal cancer patients that accelerate the recovery of gastrointestinal function, thereby promoting evidence-based clinical nursing practice.