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.

(±)-Talapyrones A-F (1-6), six pairs of dimeric polyketide enantiomers featuring unusual 6/6/6 and 6/6/6/5 ring systems, were isolated from the fungus Talaromyces adpressus. Their structures were determined by spectroscopic analysis and HR-ESI-MS data, and their absolute configurations were elucidated using a modified Mosher's method and electronic circular dichroism (ECD) calculations. (±)-Talapyrones A-F (1-6) possess a 6/6/6 tricyclic skeleton, presumably formed through a Michael addition reaction between one molecule of α-pyrone derivative and one molecule of C₈ poly-β-keto chain. In addition, compounds 2/3 and 4/5 are two pairs of C-18 epimers, respectively. Putative biosynthetic pathways of 1-6 were discussed.
Polyketides/isolation & purification* ; Talaromyces/chemistry* ; Stereoisomerism ; Molecular Structure ; Circular Dichroism ; Pyrones/chemistry*

Objective:To investigate the clinical efficacy and safety of ZR2 (zevalin + lenalidomide + rituximab) regimen in the treatment of elderly patients with diffuse large B-cell lymphoma (DLBCL).Methods:A retrospective case series study was conducted. The clinical data of 16 elderly (>65 years old) non-germinal center B-cell-like DLBCL patients treated with ZR2 regimen at the Taixing People's Hospital from January 2021 to March 2023 were retrospectively analyzed. The efficacy, adverse reactions and prognosis of patients were observed.Results:Of the 16 patients, 11 were male and 5 were female, with the age [ M ( Q1, Q3)] of 76 years old (70 years old, 78 years old), and 10 cases were Ann Arbor stage Ⅲ-Ⅳ. Among the 16 patients, 9 achieved complete remission, 4 patients achieved partial remission. All 16 patients experienced varying degrees of reversible bone marrow suppression, grade Ⅲ-Ⅳ hematologic adverse reactions included neutropenia (7 cases) and thrombocytopenia (2 cases), and the bone marrow hematopoiesis recovered after treatment with granulocyte colony-stimulating factor and thrombopoietin. The main ≥grade Ⅱ non-hematologic adverse reactions were gastrointestinal reactions (5 cases), liver function abnormalities (3 cases) and peripheral neuropathy (2 cases), which were improved after the appropriate treatment. Two patients discontinued the treatment of this regimen due to disease progression, and 1 patient died from complications after 2 cycles of treatment. No deep vein thrombosis, cardiac toxicity or renal toxicity occurred during the treatment process. Conclusions:The ZR2 regimen is effective in the treatment of elderly DLBCL patients with tolerable adverse reactions.

Objective: To investigate the epidemiological characteristics of varicella outbreaks in primary and middle schools, and to establish a risk predictive model, so as to provide scientific guidance for the prevention of varicella outbreaks in schools. Methods: Based on a nested case-control study, primary and middle schools in 4 districts of Shanghai (Yangpu District and Jingan District) and Hangzhou (Xiaoshan District and Linping District) from January to December 2023 were selected to observe the status of varicella outbreaks. Associated factors of varicella outbreaks were investigated and used for establishing the predictive model, which was evaluated by the Hosmer-Lemeshow(H-L) goodness of fit test, receiver operating characteristic (ROC) curve, Calibration curve, decision curve analysis (DCA). Results: A total of 98 varicella outbreaks were included, with 195 schools without varicella outbreaks during the same period as controls. Eight factors, including the availability of warm water in restroom, availability of hand soap in restroom, average class size, duration of student attendance at school per day, presence of a fulltime school doctor, hesitancy of the school principal towards varicella vaccination, and rates of first and second doses of varicella vaccination, were identified as potential factors for school varicella outbreaks, with statistically significant differences (χ2/Z=10.01, 20.49, 17.43, 9.74, 32.17, 6.60, 2.20, 3.39, P<0.05). The 8 variables above were employed to construct a risk predictive model, and Hosmer-Lemeshow goodness of fit test yielded a χ2 value of 5.863 (P>0.05); the area under the ROC curve (AUC) was 0.846 (95%CI=0.799-0.893); Calibration curve analysis indicated good consistency between predicted and actual values of the model. DCA demonstrated favorable predictive performance of the model over a wide range. Conclusions The predictive model for school varicella outbreaks demonstrates satisfactory accuracy and efficacy. It suggested to make good use of this prediction model and take relevant measures to reduce the risk of varicella transmission in schools.

Objective To investigate the correlation between pan-immune inflammatory values(PIV)and clinicopathological char-acteristics of breast cancer patients,and analyze its value in predicting prognosis.Methods The case data of 107 patients with breast cancer admitted to Wuhan Maternal and Child Healthcare Hospital from August 2017 to August 2019 were retrospectively analyzed.The patients were followed up for 3 years,preoperative peripheral blood results were designated as cohort 1 and peripheral blood results ob-tained between 2 and 3 years after postoperative adjuvant therapy were designated as cohort 2;the optimal cut-off values for PIV were de-termined using receiver operator characteristic curve(ROC curve)for cohort 1 and cohort 2,respectively,and 107 patients were divided into PIV high-value group and PIV low-value group,and pathological characteristics were compared and analyzed between groups.Uni-variate analysis was performed and survival curves were plotted by Kaplan-Meier method and Log-rank test to analyze the value of PIV in evaluating the prognosis of breast cancer patients.Results The preoperative PIV was related to tumor size,TNM stage,vascular inva-sion,histological grade,systemic immune-inflammation index before and after operation and systemic inflammation response index(SI-RI)before operation(P＜0.05),and the postoperative PIV was significantly related to lymph node metastasis,TNM stage,histological grade,SII before and after operation and SIRI before and after operation(P＜0.05).TNM stage and histological grade in the patients of PIV high-value group were higher than those of PIV low-value group,overall survival(OS)and disease-free survival(DFS)were lower than those of PIV low-value group.Conclusion The postoperative PIV can be a predictor of OS and DFS in patients with breast cancer,the preoperative PIV can not be an independent factor for predicting OS in patients with breast cancer,but can be a predictor of DFS.

Disruption of the structure of regular sleep is a common cause of neurodegenerative diseases such as Alzheimer′s disease and Parkinson′s disease, and its pathogenesis may be related to the deposition of waste products in the central nervous system. The glymphatic pathway, which is essentially a periarterial cerebrospinal fluid inflow pathway and peripheral venous clearance pathway, is functionally dependent on interstitial bulk flow coupling supported by aquaporin-4 on the astrocyte end-foot, also known as the lymphoid glial system. The glymphatic pathway, which removes waste proteins from the brain, is active primarily during sleep, and sleep quality declines with age, while the glymphatic pathway system also deteriorates with age, suggesting a relationship between sleep disturbances and symptom progression in neurodegeneration, and glymphatic system as a link closely links the two. The interaction of sleep, aging, metabolic waste and glymphatic pathway reticulation provides new clues to the pathogenesis of central nervous system degenerative diseases, and the glymphatic pathway may constitute a new target on treatment. The recent research progress on the effects of sleep and sleep disorders on the circulation of the glymphatic system, and proposes the possibility of sleep intervention to slow down the impairment of the lymphoid system function or even restore the function of the lymphoid system and thus improve the disease development process were reviewed in this paper.

Objective:To construct the standardized training curriculum system for head nurse leadership based on five forces model.Methods:The first draft of the standardized training curriculum system for head nurse leadership was determined through literature review and semi-structured interview. From April to June 2022, 18 clinical experts from 8 provinces/cities across the country were selected for Delphi expert consultation to form a standardized training curriculum system for head nurse leadership.Results:In both rounds of consultation, 18 questionnaires were collected, and the effective response rate were 100.0%. The expert authority coefficients were 0.914 and 0.892, respectively. Based on the results of the expert consultation, the training system content was revised and improved, and all indicators met statistical standards, with expert opinions tending to be consistent. Finally, a standardized training curriculum system for head nurse leadership was formed consisting of 5 training themes, 18 course names and 67 course knowledge points.Conclusions:The standardized training curriculum system for head nurse leadership is scientific and systematic, which can provide reference for the leadership training of head nurses.

Objective:To understand the clinical characteristics and management of children infected with SARS-CoV-2 Omicron.Methods:From April 7 to June 2, 2022, 871 children who were confirmed to be infected with SARS-CoV-2 Omicron by nucleic acid testing and admitted to the designated isolation ward of children infected with SARS-CoV-2 Omicron in Shanghai (the southern hospital of Renji Hospital affiliated to Shanghai Jiaotong University School of Medicine) were selected by convenient sampling as the study subject. The clinical and nursing data of children were analyzed retrospectively.Results:Among the 871 children, 561 (64.4%) were in the low age group (<3 years old) . According to the diagnostic criteria, 572 cases (65.7%) were rated as mild, 298 cases (34.2%) as common, and 1 case (0.1%) as severe. There were 86 children (9.9%) with basic diseases, mainly tumors and nervous system diseases. The main clinical symptoms included fever, cough, diarrhea, vomiting and other digestive symptoms. Nursing strategies were given according to the age structure, disease characteristics and clinical manifestations of children, mainly including isolation ward management, basic disease nursing, symptom nursing, and early identification and evaluation of severe cases.Conclusions:The key population of children infected with SARS-CoV-2 Omicron includes children of low age with basic diseases. Symptoms mainly include fever and respiratory symptoms. It is of great significance to carry out targeted nursing diagnosis and treatment to improve the treatment efficiency of children and reduce the risk of epidemic transmission.

Objective:To differentiate the methamphetamine users according to the developmental stages of addictive behavior, and explore the characteristics of different stages in order to provid a theoretical reference for our clinical intervention.Methods:Take the male methamphetamine users in compulsory detoxification institute whom were admitted from September 2018 to December 2019 as research objects.All the objects were asked to complete clinical diagnosis, interview and questionnaire evaluation in one week.According to the developmental stages of addictive behavior, the subjects were divided into occasional use group ( n=51), regular use group ( n=95) and compulsive use group ( n=157).All subjects were evaluated using visual analogue scale(VAS), Barrett impulsiveness scale(BIS)and CogState scale.SPSS 20.0 software was used for statistical analysis, AVOVA or Kruskal-Wallis H test was used for group comparison.Multiple Logistic regression analysis was used to explore the factors associated with the development of addictive behavior. Results:(1)The compulsive use group had higher cumulative duration(24(8, 48), 12(4, 24), 22(10, 36)), average dose(6.6±3.8, 2.8±1.4, 4.5±3.4) and craving score(1(0, 5), 0(0, 1), 1(0, 3)) than the other two groups(all P<0.05).And individuals in compulsive use group had more previous heroin use experience(20.4%, 9.8%, 14.8%, P<0.05).The regular use group had more withdrawal times than the other two groups(1(1, 3), 1(0, 1), 1(1, 2), P<0.05).The total scores of Barrett impulsiveness scale(42.8±13.3, 34.5±13.6, 36.1±14.9) and the scores in all dimensions in the compulsive use group were significantly higher than those in the other two groups(motor impulsiveness: 37.5±15.8, 27.8±13.4, 29.2±17.8; attentional impulsiveness: 43.2±18.0, 39.4±17.0, 37.2±18.1; non-planning impulsiveness: 47.2±19.8, 38.8±18.7, 40.7±20.8; P<0.05) .In the compulsive use users, the ISL(16.50±4.87, 19.30±4.78, 18.33±4.91) and SEC(0.76±0.21, 0.89±0.22, 0.81±0.21) scores about cognitive assessment were significantly lower than other two groups(both P<0.05).(2)The results of multiple Logistic regression analysis showed that cumulative duration ( β=0.022, OR=1.022, 95% CI: 1.003-1.042), dosage( β=0.625, OR=1.869, 95% CI: 1.196-2.921), craving ( β=0.194, OR=1.214, 95% CI: 1.002-1.215), the total scores of Barrett impulse scale( β=0.036, OR=1.037, 95% CI: 1.013-1.061), scores of non-planning impulsiveness( β=0.040, OR=1.041, 95% CI: 1.004-1.038), scores of motor impulsiveness( β=0.033, OR=1.214, 95% CI: 1.001-1.068) were associated with the periodic grouping of addictions. Conclusions:Addictive behavior is a progressive process and methamphetamine users at different stages have different characteristics in substance use, impulsiveness and cognitive function.The development of addictive behavior is associated with the time, dosage and craving of substance use, as well as the personality impulsivity of users.And the compulsive users suffered more cognitive impairment than the other two groups. The methamphetamine users should be identified dynamically and targeted therapeutic intervention measures should be carried out to block the addictive process to achieve the goal of harm reduction.

Gliomas are the most common primary intracranial neoplasms among all brain malignancies, and the microtubule affinity regulating kinases (MARKs) have become potential drug targets for glioma. Here, we report a novel dual small-molecule inhibitor of MARK3 and MARK4, designated as PCC0208017. PCC0208017 strongly inhibited kinase activity against MARK3 and MARK4, and strongly reduced proliferation in three glioma cell lines. This compound attenuated glioma cell migration, glioma cell invasion, and angiogenesis. Molecular mechanism studies revealed that PCC0208017 decreased the phosphorylation of Tau, disrupted microtubule dynamics, and induced a G2/M phase cell cycle arrest. In an glioma model, PCC0208017 showed robust anti-tumor activity, blood-brain barrier permeability, and a good oral pharmacokinetic profile. Molecular docking studies showed that PCC0208017 exhibited high binding affinity to MARK3 and MARK4. Taken together, our study describes for the first time that PCC0208017, a novel MARK3/MARK4 inhibitor, might be a promising lead compound for treatment of glioma.