[Objective] To analyze factors influencing the postoperative progression-free survival (PFS) in patients with renal cell carcinoma (RCC), construct a nomogram model for predicting PFS, and compare it with other predictive models. [Methods] A retrospective analysis was conducted on the general and clinical data of 263 RCC patients who underwent surgery at the Department of Urology, the Second Affiliated Hospital of Xi'an Jiaotong University, during Apr.2014 and Nov.2021.Patients were divided into the progression group (n=34) and non-progression group (n=229). The data of the two groups were analyzed to identify prognostic variables associated with PFS, and a nomogram model was constructed.The performance of this model was compared with that of the University of California, Los Angeles Integrated Staging System (UISS) score, tumor staging, tumor size, tumor pathological grade, and tumor necrosis scoring system (SSIGN score), and Leibovich score by plotting receiver operating characteristic (ROC) curve and calculating the area under the curve (AUC). Calibration curve of the nomogram was used to validate the model's performance, and K-fold cross-validation was employed to assess its external validity. [Results] Multivariate Cox regression analysis revealed that age (HR=2.255, 95%CI: 1.032-4.926), T stage (HR=5.766, 95%CI: 2.351-14.142), pathological grade (HR=3.100, 95%CI: 1.445-6.651), and pathological necrosis (HR=2.656, 95%CI: 1.253-5.629) were independent risk factors of PFS (P<0.05). The nomogram model based on these four independent variables had AUCs (95%CI) of 0.750 (0.630-0.870), 0.803 (0.705-0.902), and 0.847 (0.757-0.937) for 1, 3, and 5 years, respectively, which were higher than those of UISS score, SSIGN score, and Leibovich score.The calibration curve of the nomogram showed good consistency between predicted and actual probabilities.In K-fold cross-validation, the average AUCs of the nomogram at 1, 3, and 5 years were 0.761, 0.808, and 0.842, indicating good external validity of the nomogram. [Conclusion] The nomogram based on age, T stage, pathological grade and pathological necrosis can accurately predict the risk of postoperative PFS in RCC patients at 1, 3, and 5 years, which can aid clinicians in the early identification of high-risk progression.

【Objective】 To investigate the effects of preoperative lipid metabolism level on the postoperative prognosis of non-muscular invasive bladder cancer (NMIBC). 【Methods】 Clinical data of NMIBC patients who underwent surgical treatment in our hospital during Mar.2014 and May 2021 were retrospectively analyzed. Based on receiver operating characteristic (ROC) curve, the optimal cutoff values of all lipid metabolism indicators were determined and patients were classified accordingly. The independent risk factors for postoperative recurrence were identified with Cox regression model. The survival was analyzed with Kaplan-Meier, and recurrence-free survival (RFS) was compared using log-rank tests. A recurrence risk prediction model was established based on the high-density lipoprotein (HDL) and other clinic pathological factors and the accuracy of prediction was evaluated with the area under the ROC curve (AUC). 【Results】 Cox multivariate analysis showed HDL, tumor number, tumor size and histological grade were independent risk factors for recurrence (P<0.05). Kaplan-Meier analysis showed that RFS was significantly longer in the high-HDL group than in the low-HDL group (P<0.001). Incorporating HDL, tumor number, tumor size, histological grade, and tumor stage into the recurrence risk model, the AUC was 0.706, and internal cross validation showed the AUC was 0.711. 【Conclusion】 Preoperative HDL is an independent risk factor affecting the RFS of patients with NMIBC, and combining it with clinic pathological factors will improve the prediction of tumor recurrence.

【Objective】 To construct an easy-to-use individual survival prognostic tool based on competing risk analyses to predict the risk of 1-, 2- and 3- year recurrence for patients with non-muscle invasive bladder cancer (NMIBC). 【Methods】 The follow-up data of 419 NMIBC patients were obtained. The patients were randomly divided into training cohort (n=293) and validation cohort (n=126). The variables included age at diagnosis, sex, history of smoking, tumor number, tumor size, histolo-gic grade, pathological stage, and bladder perfusion drug. The cumulative incidence function (CIF) of recurrence was estimated using all variables in the training cohort and potential prognostic variables were determined with Gray’s test. The Fine-Gray subdistribution proportional hazard approach was used as a multivariate competitive risk analysis to identify independent pro-gnostic variables. A competing risk nomogram was developed to predict the recurrence. The performance of the competing risk model was evaluated with the area under the receiver operating characteristic curve (AUC), calibration curve, and Brier score. 【Results】 Five independent prognostic factors including age, number of tumors, tumor size, histologic grade and pathological stage were used to construct the competing risk model. In the validation cohort, the AUC of 1-, 2- and 3- year recurrence were 0.895 (95%CI: 0.831-0.959), 0.861(95%CI: 0.774-0.948) and 0.827(95%CI: 0.721-0.934), respectively, indicating that the model had a high predictive performance. 【Conclusion】 We successfully constructed a competing risk model to predict the risk of 1-, 2- and 3-year recurrence for NMIBC patients. It may help clinicians to improve the postoperative management of patients.

Antiviral Agents/pharmacology* ; COVID-19 ; Coronavirus 3C Proteases ; Humans ; Lactams ; Leucine ; Molecular Docking Simulation ; Molecular Dynamics Simulation ; Nitriles ; Proline ; Protease Inhibitors/pharmacology* ; SARS-CoV-2

OBJECTIVE：To provide reference f or the qualit y sta ndard establishment of Amaranthus retroflexus. METHODS ： Taking 7 batches of A. retroflexus medicinal materials as the research object ，the appearance properties of the medicinal materials were investigated ，and the microscopic characteristics of the medicinal powders were observed. TLC method was adopted to qualitatively identify rutin ，valine and leucine in A. retroflexus medicinal materials. According to the relevant methods of the 2015 edition of Chinese Pharmacopoeia （part Ⅳ），water content ，total ash content ，acid-insoluble ash content and water-soluble extract content were determined. HPLC method was used to determine the content of rutin in the medicinal material of A. retroflexus . The determination was performed on Agilent 5 TC-C18（2）column with mobile phase consisted of methanol- 0.3％ phosphoric acid solution（40∶60，V/V），at the flow rate of 1.0 mL/min. The detection wavelength was set at 358 nm，and the column temperature was 30 ℃. The sample size was 10 μL. RESULTS：The appearance and microstructure characteristics of the medicinal materials were consistent with the existing description. The identification results of TLC meth od showed that 7 batches of medicinal materials and each reference substance （rutin，valine，leucine）showed spots of the same color at the same position. The moisture content of 7 batches of A. retroflexus medicinal materials was 7.43％-8.72％，the total ash content was 11.82％-13.78％，the acid-insoluble ash content was 0.15％-0.55％，and the water-soluble extract content was 17.27％-24.74％. The linear range of rutin was 10-200 μg/mL（R 2＝1.000 0）. RSDs of precision test ，stability test （24 h）and repeatability test were all less than 2.0％ （n＝6）. The average recovery rates of rutin were 99.14％，97.98％ and 98.80％ in low ，medium and high concentration of samples，and RSDs were 0.97％，0.95％，0.96％（n＝3）. The contents of rutin in 7 batches of A. retrophylla were 0.314-1.102 mg/g. CONCLUSIONS：In this study ，character observation ，microscopic identification ，moisture content ，total ash content ，acid- insoluble ash content and water-soluble extract content of A. retroflexus are investigated ；TLC method was established for qualitative identification of leucine ，valine and rutin in A. retroflexus ，and the HPLC method was established for content determination of rutin. It provides reference for the quality standard establishment of A. retroflexus .

A new coronavirus (SARS-CoV-2) has been identified as the etiologic agent for the COVID-19 outbreak. Currently, effective treatment options remain very limited for this disease; therefore, there is an urgent need to identify new anti-COVID-19 agents. In this study, we screened over 6,000 compounds that included approved drugs, drug candidates in clinical trials, and pharmacologically active compounds to identify leads that target the SARS-CoV-2 papain-like protease (PLpro). Together with main protease (M
Antiviral Agents/therapeutic use* ; Binding Sites ; COVID-19/virology* ; Coronavirus Papain-Like Proteases/metabolism* ; Crystallography, X-Ray ; Drug Evaluation, Preclinical ; Drug Repositioning ; High-Throughput Screening Assays/methods* ; Humans ; Imidazoles/therapeutic use* ; Inhibitory Concentration 50 ; Molecular Dynamics Simulation ; Mutagenesis, Site-Directed ; Naphthoquinones/therapeutic use* ; Protease Inhibitors/therapeutic use* ; Protein Structure, Tertiary ; Recombinant Proteins/isolation & purification* ; SARS-CoV-2/isolation & purification*

OBJECTIVE: To observe the time distribution characteristic of silica nanoparticles in rats after one-time intratracheal infusion. METHODS: Specific pathogen free male Wistar rats were randomly divided into one control group and7 experimental groups according to different time of intratracheal infusion( 1,3,5,7,14,21 and 28 days),6 rats in each group. The experiment groups were intratracheally instilled with 1. 0 mL silica nanoparticle suspension( mass concentration 50. 00 g/L). The control group was not given any treatment. Rats were sacrificed and their organ tissue samples such as serum,lung,spleen,liver and kidney were collected at different time points. The silicon levels of tissues were determined by inductively coupled plasma optical-emission spectrometry. The histology of rat's lungs was observed by optical microscope and the location of silica in lungs was observed by polarization microscope. RESULTS: After exposure to silica nanoparticles for 1-7 days,the changes of rats' lung tissue was mainly exudative inflammation. The changes of lung was proliferative inflammatory lesions after 14-28 days of exposure to silica nanoparticles. The visible nodules of cells were observed in the lung tissue in 28 days experiment group. The distribution of silica nanoparticles was observed obviously in the lung tissues of rats of 1 day experiment group under the polarizing microscopy. The tendency decreased with the increase of observation time. Silica nanoparticles were rarely seen 21 and 28 days after intratracheal infusion in rats. The silicon levels of serum,lung and spleen tissues reached the peak in 1 day after silica nanoparticles instillation,then dropped in 3-7 days( serum) or 3-14 days( lung and spleen tissues) and went back to that of the control group's. The level of silicon in the livers and kidneys of rats in the experimental groups showed no significant increase in the level of 1-5 day after the instillation( P > 0. 05),and showed significant increase in the level of 7 day( P < 0. 05). The level reached its peak on time points of 14 and 21 days after the instillation,and subsequently decreased,and didn't returned to normal till the 28 th day. The silicon levels of the lungs,spleens,livers and kidneys were all higher in rats than that of serum( P < 0. 05). The silicon levels of the lungs and spleens were higher than that of the livers and kidneys after instillation for1-5 days( P < 0. 05). The silicon levels of the lungs and spleens were both lower than that of the livers and kidneys after instillation for 14-28 days( P < 0. 05). CONCLUSION: Silica nanoparticles can cause lung injury when instilled intratracheally in rats. After instillation,silica nanoparticles were mainly distributed in the lungs and spleens after 1-5 days and distributed in the livers and kidneys after 14-28 days.

Ebola virus (EBOV) is a key member of Filoviridae family and causes severe human infectious diseases with high morbidity and mortality. As a typical negative-sense single-stranded RNA (-ssRNA) viruses, EBOV possess a nucleocapsid protein (NP) to facilitate genomic RNA encapsidation to form viral ribonucleoprotein complex (RNP) together with genome RNA and polymerase, which plays the most essential role in virus proliferation cycle. However, the mechanism of EBOV RNP formation remains unclear. In this work, we solved the high resolution structure of core domain of EBOV NP. The polypeptide of EBOV NP core domain (NP(core)) possesses an N-lobe and C-lobe to clamp a RNA binding groove, presenting similarities with the structures of the other reported viral NPs encoded by the members from Mononegavirales order. Most strikingly, a hydrophobic pocket at the surface of the C-lobe is occupied by an α-helix of EBOV NP(core) itself, which is highly conserved among filoviridae family. Combined with other biochemical and biophysical evidences, our results provides great potential for understanding the mechanism underlying EBOV RNP formation via the mobility of EBOV NP element and enables the development of antiviral therapies targeting EBOV RNP formation.
Crystallography, X-Ray ; Ebolavirus ; physiology ; Humans ; Nucleoproteins ; chemistry ; genetics ; metabolism ; Protein Structure, Tertiary ; Structure-Activity Relationship ; Virus Assembly ; physiology