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 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 evaluate the potential of nanopore sequencing technology for rapid diagnosis of Talaro-myces marneffei(TM)infection.METHODS Nine patients with TM infection admitted to the Fourth People's Hospital of Nanning from May 13,2022 to Aug.3,2023 were retrospectively analyzed.Rapid diagnosis was con-ducted by nanopore sequencing technology,and a comprehensive analysis of their clinical characteristics and treat-ment processes was performed.RESULTS The 9 patients included in the study had infections in various sites such as the lungs,buttocks,blood and cervical lymph nodes.Comorbidities included AIDS,secondary pulmonary tuberculosis,non-tuberculous mycobacterial disease and adult-onset immune deficiency.Patients generally exhibited elevated C-reactive protein levels and erythrocyte sedimentation rates,along with increased neutrophil counts.Some patients had abnormal lymphocyte counts and CD4+/CD8+ratios.Microbiological tests showed positive cultures in 3 cases,positive smears in 2 cases and positive targeted detection in 6 cases.Nanopore sequencing detected various pathogens in the 9 patients.The treatment results indicated that 8 patients improved after medication,with 6 patients having medication regimens adjusted based on nanopore sequencing results.CONCLUSION Nanopore sequencing technology has shown potentials in the auxiliary diagnosis of TM infection,providing timely etiological diagnostic evidence for clinical practice.

Objective:To identify the relevant factors for the first-course remission of acute myeloid leukemia (AML) and to develop a predictive model as well as assess its predictive capability.Methods:Clinical data of 749 patients newly diagnosed with AML admitted to the Department of Hematology, the First Affiliated Hospital, Zhejiang University, School of Medicine from January 1, 2019, to April 30, 2023, were collected and randomly divided into training and validation sets. Multivariate logistic regression analysis was conducted to determine variables associated with complete remission in the first course of induction therapy, and a predictive model was established based on these variables. The receiver operating characteristic (ROC) curve of the predictive model was plotted, and the area under the curve (AUC) was calculated.Results:The indicators predicting the first remission course included peripheral blood white blood cell count during onset, CBF::MYH11 fusion gene, CEBPA bZIP region mutation, myelodysplastic syndrome-related gene mutation, and induction chemotherapy regimen selection as independent factors for the first remission course. The model’s area under the training and validation curves was 0.738 (95% CI: 0.696-0.780) and 0.726 (95% CI: 0.650-0.801), respectively. The Hosmer-Lemeshow test results yielded P-values of 0.993 and 0.335, respectively. Conclusion:In this study, the developed model demonstrates a strong predictive capability for the efficacy of the first course of patients with AML, providing valuable guidance to clinicians in assessing patient prognosis and selecting appropriate treatment strategies.

BACKGROUND:Slow bone repair and poor bone formation quality are still problems during masquelet technique in the treatment of large segment bone defects.H-type vessels can induce osteogenesis,enhance the local angiogenesis and osteogenesis coupling,and promote bone repair.However,there are few reports on the role of H-type blood vessels in the bone induced membrane.OBJECTIVE:To construct a large segment bone defect model of SD rat tibia,observe the expression characteristics of H-type blood vessels in the bone induced membrane,then to identify the expression peak point of H-type blood vessels in the bone induced membrane and determine the optimal period of bone grafting.METHODS:Sixty SD rats were randomly divided into a control group(n=30)and a model group(n=30)by random number table method.The two groups were further divided into three subgroups at 4,6,and 8 weeks after bone cement implantation,with 10 rats in each group.A 4 mm bone defect model of the right tibia was constructed in both the control and the model groups.Polymethyl methacrylate bone cement was implanted in the model group to induce bone biomembrane formation,while bone cement was not implanted in the control group.At 4,6,and 8 weeks after bone cement implantation,6 rats were randomly selected at each time point.The bone induction membrane tissue was cut from the model group,and the non-bone soft tissue of the corresponding part was cut from the control group.The dynamic expressions of H-type blood vessels in the bone induced membrane were identified by immunofluorescence.The morphological changes of the bone induced membrane were observed by hematoxylin-eosin staining.The formation of blood vessels in the bone induced membrane was observed by angiography.The expression levels of osteoblast-specific transcription factor in the bone induced membrane were detected by immunohistochemistry.Four rats remained at each time point.In the model group,the bone induced membrane was cut open and the bone cement was removed and autologous coccyx was implanted.In the control group,autologous coccyx was implanted in the bone defect area.Micro-CT evaluation of the tibial defect was performed 8 weeks after bone grafting.RESULTS AND CONCLUSION:(1)Immunofluorescence staining showed that the expression of H-type vessels in the model group was most obvious 6 weeks after bone cement implantation,and the expression of H-type vessels in the model group at each time point after bone cement implantation was higher than that in the control group(P＜0.05).(2)Hematoxylin-eosin staining and angiography showed that the number and volume of new blood vessels at each time point after bone cement implantation in the model group were greater than those in the control group(P＜0.05).The order of the number and volume of new blood vessels in the model group was:8 weeks after bone cement implantation＞6 weeks after bone cement implantation＞4 weeks after bone cement implantation.(3)Immunohistochemical staining showed that the positive expression of osteoblast-specific transcription factors at each time point after bone cement implantation in the model group was higher than that in the control group(P＜0.05),and the positive expression of osteoblast-specific transcription factors in the model group was most obvious 6 weeks after bone cement implantation.(4)Micro-CT detection showed that the bone repair effect of the three subgroups in the model group was significantly better than that of the corresponding subgroups in the control group,and the bone repair effect of the subgroup in the model group 6 weeks after bone cement implantation was better than that of the subgroups 4 and 8 weeks after bone cement implantation.The results indicate that H-type blood vessels are dynamically expressed in the bone induced membrane and reached a peak 6 weeks after bone cement implantation.Good bone repair effects can be obtained by the bone induced membrane bone grafting 6 weeks after bone cement implantation.

Objective To explore the distribution characteristics and influencing factors of nasal colonized bacteria of healthcare workers(HCWs)in pediatric intensive care unit(PICU).Methods A cross-sectional study was con-ducted.Nasal swab specimens from 104 HCWs in the PICU of a hospital were collected for bacterial culture and an-timicrobial susceptibility testing.According to the identification and antimicrobial susceptibility testing results of strains,distribution characteristics of colonized bacteria was analyzed.Basic information of studied subjects were collected through questionnaire survey,and risk factors for colonized bacterial infection were conducted using logis-tic regression analysis.Results Among 104 specimens,colonized bacteria were detected from 66 specimens,with an overall detection rate of 63.46％.Gram-positive bacteria was mainly Staphylococcus aureus,with a detection rate of 34.62％(n=36),out of which methicillin-resistant Staphylococcus aureus(MRSA)accounted for 2.88％(n=3).Gram-negative bacteria was mainly Klebsiella spp.,with a detection rate of 21.15％(n=22).Multiva-riate logistic regression analysis showed that HCWs with junior professional titles(OR=11.400,95％CI:2.329-55.801,P=0.003)was an independent risk factor for Staphylococcus aureus colonization,and male(OR=4.260,95％CI:1.160-15.653,P=0.029)was an independent risk factor for Klebsiella spp.colonization.Conclusion Nasal cavity of HCWs in PICU has a high detection rate of colonized bacteria,with Staphylococcus aureus and Klebsiella spp.being the major colonized bacteria.

Objective:To detect the expression levels of 12 cytokines in the plasma of patients with primary biliary cholangitis (PBC) and explore their association with PBC disease activity and ursodeoxycholic acid (UDCA) therapeutic response.Methods:This study enrolled 127 patients with PBC who visited Peking Union Medical College Hospital between December 2021 and November 2023 (PBC group) and 32 healthy controls who underwent physical examinations during the same period (control group). The expression of 12 cytokines was measured using flow cytometry, and compared between groups. Spearman correlation analysis was performed to assess the relationship between cytokine levels and five laboratory indicators reflecting PBC disease activity [alkaline phosphatase (ALP), glutamyl transpeptidase (GGT), total bilirubin (TBil), aspartate aminotransferase (AST), and total bile acid (TBA)]. Furthermore, the receiver operating characteristic (ROC) curve analysis was performed to evaluate the effectiveness of cytokines in distinguishing between patients who responded to UDCA treatment and those who did not.Results:The plasma interleukin (IL)-8 levels between the PBC group and healthy controls showed no significant differences, and the plasma IFN-γ levels in PBC patients were significantly higher than those in health controls ( P<0.05). Spearman analysis showed that IL-8 was positively correlated with ALP, GGT, TBil, AST, and TBA ( R2=0.348, 0.401, 0.406, 0.495, 0.417; all P<0.01), and negative correlation was observed between IFN-γand ALP, GGT, and TBA levels ( R2=-0.265, -0.253, -0.232; all P<0.05). The plasma IL-8 level in 52 PBC patients who did not respond to UDCA treatment was significantly higher, while the IFN-γ level was significantly lower than those in 56 PBC patients who responded to UDCA treatment (both P<0.05). ROC analysis showed that the area under the curve for distinguishing plasma IL-8 and IFN-γlevels between PBC patients responding to UDCA treatment and not is 0.631 and 0.783, respectively. The sensitivities were 87.5% and 90.5%, and the specificities were 44.2% and 57.9%, respectively. Conclusion:The levels of plasma IL-8 and IFN-γ are correlated with the disease activity of PBC and can be used to reflect the therapeutic responses to UDCA in PBC patients.

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.

A tertiary public general hospital in Guangdong has innovated its inpatient bed scheduling system by integra-ting multiple models,including"Hospital-Wide Bed Pooling,"outpatient chemotherapy,day surgery,pre-admission,and pre-discharge programs.Supported by policy guidance,this initiative optimizes clinical operations,enhances patient admission struc-tures and processes,and improves bed utilization efficiency through a multi-dimensional centralized bed management approach.By rationally allocating hospital-wide bed resources and maximizing their operational effectiveness,the hospital advances high-quality development in healthcare delivery.

Objective To explore and analyze the characteristics and transmission routes of carbapenem-resistant Klebsiella pneumoniae(CRKP)strains in intensive care unit(ICU).Methods From January to October 2023,17 clinical infection isolates(clinical infection group),5 active screening isolates(active screening group),and 7 envi-ronmental isolates(environmental group)of CRKP in the liver surgery ICU of a hospital were selected and analyzed by whole-genome sequencing.The differences in resistance genes,virulence genes,and sequence typing(ST)were compared,and transmission routes were analyzed based on the phylogenetic tree.Results 29 strains of CRKP car-ried 4-18 resistance genes and 52-98 virulence genes,respectively.There were no statistically significant diffe-rences in genotype distribution of resistance genes,the number of virulence genes,and gene types among three groups of CRKP(all P＞0.05).ST showed that 29 CRKP strains mainly consisted of two categories:ST11 and ST15.Based on the phylogenetic tree constructed from the core genome,there were 7 highly homologous groups of CRKP,among which 4 groups had clear epidemiological associations.Conclusion CRKP in ICU carries more re-sistance and virulence genes,and some strains are highly homologous in ST and phylogenetic tree,which may lead to cross transmission.In the future,prevention and control measures should be strengthened to reduce the trans-mission of CRKP.