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.

Epstein-Barr virus (EBV) associated post-transplant lymphoproliferative disorders (PTLD) are one of the most severe complications after hematopoietic stem cell transplantation (HSCT). This study includes 31 cases of aplastic anemia (AA) patients who developed PTLD after haploidentical transplantation, summarizing their clinical characteristics and categorizing them into either rituximab monotherapy group or combination therapy group based on whether their condition improved by 1 log after a single dose of rituximab. The incidence of PTLD after HSCT in children with AA was 10.16%, and the incidence of PTLD in patients with age >10 years was significantly increased ( χ2=11.336, P=0.010). Of the 31 patients, 27 were clinically diagnosed and 4 were pathologically confirmed. Finally, 15 patients were classified into the rituximab treatment group and 15 patients into the combination treatment groups. Finally three patients died, and the 2-year overall survival rate was (89.7±5.6) %. Standard pre-treatment protocols and EBV reactivation are risk factors affecting the prognosis of PTLD. There was no statistically significant difference in the impact of the two treatment schemes on prognosis.

Objective:To analyze the intervention effect of rehabilitation platform-based online psycho-education on patients with bipolar disorder (BD) in remission stage.Methods:In this randomized controlled study, 91 patients with BD in remission stage who attended the community health center in Xicheng District, Beijing from July to August 2021 were randomly divided into a test group (46 cases) and a control group (45 cases) according to a 1∶1 ratio using the random number table. Baseline data were collected from both groups, and the control group received conventional medication and community telephone follow-up, while the test group was given online mental health education in the form of a WeChat subscription number on this basis, including BD mental health education course push (twice a week) and disease self-management (daily recording of mood, sleep, medication, exercise and gratitude diary), and the intervention period was 6 months in both groups. During the intervention, one patient in the test group was admitted to hospital due to exacerbation of mental illness and the trial was terminated. A total of 90 cases were included in the study. The scores of Medication Adherence Rating Scale (MARS), Hamilton Depression Scale (HAMD), Young Mania Rating Scale (YMRS) and Perceived Devaluation-Discrimination Scale (PDD) were assessed at baseline, after 3 months and 6 months of intervention in both groups, respectively. And the differences in baseline data between the two groups were compared using two independent samples t test and χ2 test, and the repeated-measures ANOVA was used to compare the differences in MARS, HAMD, YMRS, and PDD scores between the two groups before and after the intervention, and to analyze the intervention effects of network mental health education based on the rehabilitation platform on patients in remission stage of BD. Results:After 6 months of intervention, MARS scores in the test group was significantly higher than that in the control group [(8.47±1.75) vs (7.47±1.85)], and was significantly higher than that at baseline (7.36±2.13) and after 3 months of intervention (8.04±1.68) (all P<0.05). YMRS and PDD scores in the test group were significantly lower than those at baseline after 3 and 6 months of intervention [YMRS, 2.0(1.0,4.0),2.0(0,3.0) vs 3.0(1.0,5.5); PDD, (31.18±4.65), (30.13±4.76) vs (32.51±4.51)] (all P<0.05); the differences in YMRS and PDD scores in the control group were not statistically significant (all P>0.05). There was no statistically significant difference in HAMD scores between the two groups before and after the intervention (all P>0.05). Conclusion:Combining mental health education based on rehabilitation platform with conventional medication and community management can significantly improve the medication compliance of patients with BD in remission stage, and improve their manic symptoms and reduce the stigma of the disease.

Objective To develop a nomogram based on pulmonary nodules preoperative CT signs and 3D quantitative parameters for predicting mediastinal lymph node metastases in patients with clinical stage ⅠA lung adenocarcinoma.Methods The imaging data of 164 patients who underwent preoperative CT scan and systematic lymph node dissection were analyzed retrospectively.Commercially available AI software was used to extract 3D quantitative parameters of pulmonary nodules automatically,and CT signs of pulmonary nodules were analyzed.Logistic regression was used to explore the role of these parameters in predicting pathological nodal involvement.A nomogram prediction model was established,then discrimination and calibration of the model were evaluated.Results Among 164 enrolled patients,19(11.6％)were tested positive for mediastinal lymph node metastases at pathology review.The nomogram incorporated spiculation,lobulation,the largest cross-sectional area,and carcinoembryonic antigen(CEA).The model showed great discrimination and calibration,with a C-index of 0.942[95％confidence interval(CI)0.923-0.961].The predicted value of the model fitted well with the actual observed value on the calibration curve.Conclusion The nomogram prediction model based on preoperative CT signs,3D quantitative parameters,and CEA can estimate the probability of mediastinal lymph node metastases in clinical stage ⅠA lung adenocarcinoma.This model may help with clinical decision-making and individualized evaluation.

Objective:This study aimed to observe the dynamic changes of NUP98::NSD1 expression before and after allogeneic hematopoietic stem cell transplantation (allo-HSCT) . Moreover, the clinical value of measurable residual disease (MRD) was analyzed.Methods:Sixteen AML patients who were diagnosed with the NUP98::NSD1 fusion gene and received allo-HSCT at Peking University People’s Hospital were included. The NUP98::NSD1 fusion gene and leukemia-associated immunophenotype (LAIP) were monitored before and after transplantation to evaluate their MRD status.Results:The median follow-up time for all patients was 526 days (139-1136 days) , with four patients (25.0%) experiencing hematological recurrence at a median of 474 days (283-607 days) after transplantation. Three patients (18.8%) died, two of whom (12.5%) died of leukemia recurrence. The median expression level of NUP98::NSD1 in newly diagnosed patients with complete data was 78.5% (18.9%-184.4%) at the time of initial diagnosis. The recurrence rate was higher in NUP98::NSD1-positive patients after transplantation, with 44.4% of patients experiencing recurrence, whereas no recurrence occurred in NUP98::NSD1-negative patients after transplantation. The area under the receiver operating characteristic curve predicted by the NUP98::NSD1 level after transplantation was 1.000 (95% confidence interval: 1.000-1.000, P=0.003) . Among the four patients with recurrence, NUP98::NSD1 was more sensitive than flow cytometry residual (FCM) and Wilms’ tumor gene 1 (WT1) . Conclusions:The NUP98::NSD1 fusion gene can be used to evaluate the MRD status of allo-HSCT. NUP98::NSD1-positive patients after transplantation have a high relapse rate and poor prognosis. NUP98::NSD1 was more sensitive than FCM and WT1 in predicting posttransplant relapse.

Objective To analyze the recurrence of breast cancer without use of chest wall bolus during adjuvant intensity modulated radiotherapy after modified radical mastectomy, so as to investigate the necessity of bolus use. Methods A total of 218 patients undergoing adjuvant intensity modulated radiotherapy after modified radical mastectomy during the period from January 2013 to June 2019 were enrolled as the study subjects. The chest wall bolus was not used during the whole period of radiotherapy after modified radical mastectomy, and the recurrence of breast cancer in the chest wall was analyzed after radiotherapy. Results The post-surgical follow-up through outpatient records, inpatients records, local residents’ health system and telephone was performed until June 31, 2021. The proportion of follow-up was 100%, and the mean follow-up period was 48.9 months. There were three cases with breast cancer recurrence in the chest wall, including one case with recurrence in the chest wall alone and two cases with recurrence in the chest wall and regional lymph nodes, and the overall recurrence of breast cancer was 1.4% in the chest wall. Among the 3 cases with breast cancer recurrence in the chest wall, there were two cases with N3 stage and positive for HER2, and one triple-negative breast cancer case, and all three cases developed distal metastases upon local recurrence. Among 218 study subjects, there were 5 cases with grade Ⅰ radioactive skin reaction, 3 cases with grade Ⅱ radioactive skin reaction, and no grade Ⅲ or Ⅳ radioactive skin reaction occurred. In addition, no grade Ⅲ or Ⅳ acute radioactive injury was seen in the chest wall skin among the 218 study subjects. Conclusion No use of chest wall bolus may be considered during adjuvant intensity modulated radiotherapy after modified radical mastectomy in presence of systemic therapy if tumor invasion into skin is not observed prior to therapy.

Objective To investigate the incidence and risk factors of infection in neurosurgical patients in Wuxi people′s hospital,and to provide reference for the prevention of postoperative infection. Methods A total of 53 patients with postoperative infection were collected.The design method of one to three matching case-control study was used controlling age,sex and neurosurgical disease.The risk factors of infection were analyzed by retrospective analysis. Results Among 212 patients, 53 developed infections, the incidence rate was 25.0%(53/212). Respiratory tract infection was the main type of infection (60.4%,32/53).Patients with high blood glucose, high white blood cells, high hemoglobin, preoperative antibiotics in the infection group(t/χ2=3.486, 2.966, 2.196, 30.24, P<0.05). Patients in the infection group had emergency operation,long operation time,intra-operative blood loss,intra-operative blood transfusion(U/χ2=26.39,2.585,3.409,9.792,P<0.05).The infection group patients with postoperative use of antibiotics more than 2 kinds, long hospitalization, The difference between the two groups was statistically significant (U/χ2=85.53, 5.810,P<0.05). Further Logistic regression analysis showed that preoperative high blood sugar, intraoperative blood loss, operative duration and hospitalization time were the risk factors of nosocomial infection. Conclusion Risk factors for infection in department of neurosurgery are multiple and targeted interventions should be taken to reduce postoperative infection rate.

Objective To evaluate the accuracy of MSCT in the pre-operative N-staging and diagnosis of metastatic lymph nodes in each group of gastric cancer.Methods Pathological and CT data of 91 patients with gastric cancer proved by surgery and pathology were analyzed retrospectively.Three-phase dynamic enhancements were performed before surgery in a unified way of hypotonic oral water,N-stage and grouping of lymph nodes of the preoperative CT imaging were evaluated by using the established diagnostic criteria and then compared with the results of surgery and pathology,the accuracy of staging and grouping was analyzed by using Kappa test.Results The accuracy of MSCT diagnosing the N-staging as a whole was 86.3%.The accuracy for N0,N1,N2 and N3 was 83.5%,89.0%,83.5% and 89.0%,respectively.The sensitivity was 86.5%,83.3%,50% and 47.4%,respectively.The specificity was 79.5%,89.4%,89.6% and 100.0%, respectively.The sensitivity for N0 was statistically different from that for N2, N0 and N3(P≤0.007).The detected accuracy for the group of left side of the cardium (No.2), periphery of the splenic hilum (No.10), posterior of the pancreastic head (No.13) were higher than other groups on MSCT with the accuracyof 100%.The sensitivity for the group of No.2,periphery of the coeliac trunk(No.9),No.10,and No.13 was 100%.The specificity for the group of No.2,No.10,and No.13 was 98.9%.Conclusion Relatively high accuracy in the preoperative N-staging and diagnosis of metastatic lymph nodes in each group of gastric cancer can be obtained by MSCT, which provide reliable information for preoperative assessment and intraoperative lymph node dissections.

Objective To investigate the incidence and the related factors of the depression in Parkinson's disease. Methods 52 cases with idiopathic Parkinson's disease were included in this study. Such scales as Hamilton depression scale-24 item (HAMD-24), Non Motor Symptoms Scale for Parkinson's disease (NMSS), 39-item Parkinson's Disease Questionnaire (PDQ-39), unified Parkinson's disease rating scale (UPDRS), revised Hoehn-Yahr rating scale (H-Y), revised Schwab and English daily life event scale (S-E), Minimum Mental State Examination (MMSE), etc. were applied and underwent Spearman correlation analysis. Results Thirty-six patients with Parkinson's disease (69.23%) met the criteria for depression. The spearman rank correlation analysis showed that MMSE (r=-0.294, P=0.036) and S-E (r=-0.506, P<0.001) had negative correlation with depression in Parkinson's disease, and the course of the disease (r=0.274, P=0.049), UPDRS (r=0.485, P<0.001), H-Y (r = 0.459, P = 0.001), NMSE (r = 0.729, P < 0.001) and PDQ-39 (r = 0.619, P < 0.001) had positive correlation with depression in Parkinson's disease. Conclusions The patients with Parkinson's disease had high incidence of depression. The depression in Parkinson's disease is associated with many factors and affected the quality of life of the patients.

Objective To investigate the biological mechanisms and feasibility of collagen/hydroxyapatite scaffolds for repairing articular cartilage and subchondral bone defects. Methods 45 New Zealand white rabbits were included. Full-thickness articular cartilage defect models were established in experiment and control groups and the biomaterial scaffolds were implanted in the experiment group. The animals were sacrificed in the 4th, 6th and 8th week after the operation respectively. Histological scores were performed by semi-quantity cartilage scoring system and the expressions of matrix metalloproteinases (MMPs)-2, 3, 9 and 13 mRNA in the synovialis were detected with RT-PCR. Results The repaired tissues were totally hyaline cartilages in the experiment group 2 weeks after operation and there were no repaired tissues in the control group. There were significant differences between these 2 groups in Wakitani scores (P<0.01). The activation and expression of MMP-2, 3, 9 decreased in the experiment group (P<0.05), but the activation of MMP-13 sustained and the expression of MMP-13 could be detected during the observed period (P>0.05). Conclusion The new biological scaffold can alleviate the inflammatory and protect the cartilages by inhibiting the expression of MMPS, which promote the reconstruction of articular cartilage in rabbits.