Kirsten rat sarcoma viral oncogene homolog(KRAS)gene is one of the most commonly mutated oncogenes.It has been found that KRAS inhibitors have the potential therapeutic effect on cancer patients with this gene mutation.In this study,machine learning was applied to develop a QSAR(quantitative structure-activity relationship)model for KRAS small molecule inhibitors.A total of 1857data points of IC50 and SMILES(simplified molecular input line entry system)for KRAS inhibitors were collected from three databases:ChEMBL,BindingDB,and PubChem.And nine different classifiers were constructed using three different feature screening methods combined with three machine learning models,namely,random forest,support vector machine,and extreme gradient boosting machine.The results showed that the SVM model combined with mutual information feature selection exhibited the best performance:AUCtest=0.912,ACCtest=0.859,F1test=0.890.Moreover,it also demonstrated good predictive performance on the external validation set(AUCExt=0.944,RecallExt=0.856,FPRExt=0.111).This study provides a new technical route for KRAS inhibitor screening in natural product databases using artificial intelligence methods.

Objective:To establish a risk management system of bedside monitor based on risk assessment management model,and to analyze its application value in the clinical management of critically ill patients in neurosurgery department.Methods:Based on the risk assessment management model,the failure risk index was screened,and the risk management system of bedside monitor was established.A total of 150 critically ill neurosurgical patients admitted to The First Affiliated Hospital of Air Force Medical University from December 2021 to December 2022 were selected and divided into control group and observation group by random number table method,with 75 cases in each group.During the hospitalization of the two groups of patients,30 responsible nurses participated in clinical care,and 16 multifunctional bedside monitors were used to monitor patients'vital signs.The control group received routine nursing management intervention.On the basis of routine nursing intervention,the observation group carried out risk assessment management based on the risk assessment management model of bedside monitor risk management system.The differences in patient monitoring quality score,equipment management quality score and responsible nurse ability score were compared between the two groups.Results:The average scores of respiration,blood pressure,blood oxygen saturation and ECG monitoring quality of the patients in observation group were(37.52±0.26)points,(36.61±1.29)points,(36.56±2.57)points and(38.25±0.56)points,respectively,which were higher than those in control group,the difference was statistically significant(t=43.925,33.150,13.655,32.035,P<0.05).The average scores of performance control quality and operation quality of bedside monitor in the observation group were(95.43±0.46)points and(96.51±0.77)points,respectively,which were higher than those in control group,the difference was statistically significant(t=70.976,35.439,P<0.05).The average scores of nurses in terms of ability of equipment collaboration,equipment use mastery and equipment alarm management in the observation group were(9.43±0.25)points,(8.56±0.64)points and(9.25±0.24)points,respectively,which were higher than those in the control group,the differences were statistically significant(t=92.952,24.455,58.024,P<0.05).Conclusion:The bedside monitor risk management system based on the risk assessment management model can realize the efficient management of bedside monitors for critically ill neurosurgical patients,and improve the operating efficiency and quality of the equipment on the basis of ensuring the life safety of patients.

Objective:To evaluate the clinical value of cognitive and motor function in predicting conversion to neurodegenerative disorders in patients with isolated rapid eye movement sleep behavior disorder (iRBD).Methods:Forty-seven patients with iRBD were collected from the Department of Neurology of Tianjin Medical University General Hospital and Tianjin Medical University General Hospital Airport Site during October 2018 and June 2022. All participants received comprehensive evaluations of cognitive and motor function at baseline. The visuospatial function was evaluated by Rey-Osterrieth Complex Figure Test (ROCF)-copy, the memory function was evaluated by Auditory Verbal Learning Test and ROCF-recall, the attention-executive function was evaluated by Trail Making Test (TMT) and Stroop Color-Word Test, and the language function was evaluated by Boston Naming Test. The motor function was evaluated by Unified Parkinson′s Disease Rating Scale-Ⅲ, Alternate-tap Test (ATT), and 3-meter Timed Up and Go Test. The iRBD patients with phenoconversion were identified during follow-up. Receiver operating characteristic curve and generalized linear model Logistic regression were applied to identify the optimal combination of cognitive and motor tests in distinguishing the converters from non-converters in patients with iRBD. Multivariate Cox regression analyses were applied to evaluate the independent risk factors in predicting conversion to neurodegenerative diseases in patients with iRBD.Results:The median follow-up duration was 3 years. Forty-five iRBD patients were included in the analysis eventually, as 2 dropped out at follow-up. Twenty-one iRBD patients developed neurodegenerative disorders, with 14 presenting motor phenotype and 7 cognitive phenotype. Baseline ROCF-copy, TMT-A and ATT were best combination in identifying iRBD patients with phenoconversion [sensitivity: 90.0%, specificity: 87.5%, area under curve (AUC): 0.931, P<0.001]. Baseline TMT-A and ATT were best combination in identifying iRBD patients with motor phenotype conversion (sensitivity: 100.0%, specificity: 66.7%, AUC: 0.872, P<0.001); Baseline TMT-A performed best in identifying iRBD patients with cognitive phenotype conversion (sensitivity: 83.3%, specificity: 91.7%, AUC: 0.917, P<0.001). Multivariate Cox regression analysis showed that individuals with poorer performance of TMT-A (cut-off value: 63.0 s) and ATT (cut-off value: 205.5 taps/min) than the cut-off values at baseline had higher risks for developing to neurodegenerative disorders, with HR values of 5.455 (95% CI 1.243-23.941, P=0.025) and 11.279 (95% CI 1.485-85.646, P=0.019), respectively. Conclusions:In iRBD, ROCF-copy, TMT-A and ATT served as optimum combination in predicting phenoconversion, whereas TMT-A and ATT served as optimum combination in predicting motor phenotype, and TMT-A performed best in predicting cognitive phenotype. The performance in TMT-A and ATT in iRBD could predict the risk of developing to neurodegenerative disorders independently.

OBJECTIVES: With the increasing detection rate of lung nodules, the qualitative problem of lung nodules has become one of the key clinical issues. This study aims to evaluate the value of combining dynamic contrast-enhanced (DCE) MRI based on time-resolved imaging with interleaved stochastic trajectories-volume interpolated breath hold examination (TWIST-VIBE) with T₁ weighted free-breathing star-volumetric interpolated breath hold examination (T₁WI star-VIBE) in identifying benign and malignant lung nodules. METHODS: We retrospectively analyzed 79 adults with undetermined lung nodules before the operation. All nodules of patients included were classified into malignant nodules (n=58) and benign nodules (n=26) based on final diagnosis. The unenhanced T₁WI-VIBE, the contrast-enhanced T₁WI star-VIBE, and the DCE curve based on TWIST-VIBE were performed. The corresponding qualitative [wash-in time, wash-out time, time to peak (TTP), arrival time (AT), positive enhancement integral (PEI)] and quantitative parameters [volume transfer constant (Ktrans), interstitium-to-plasma rate constant (Kep), and fractional extracellular space volume (Ve)] were evaluated. Besides, the diagnostic efficacy (sensitivity and specificity) of enhanced CT and MRI were compared. RESULTS: There were significant differences in unenhanced T₁WI-VIBE hypo-intensity, and type of A, B, C DCE curve type between benign and malignant lung nodules (all P<0.001). Pulmonary malignant nodules had a shorter wash-out time than benign nodules (P=0.001), and the differences of the remaining parameters were not statistically significant (all P>0.05). After T₁WI star-VIBE contrast-enhanced MRI, the image quality was further improved. Compared with enhanced CT scan, the sensitivity (82.76% vs 80.50%) and the specificity (69.23% vs 57.10%) based on MRI were higher than that of CT (both P<0.001). CONCLUSIONS T₁WI star-VIBE and dynamic contrast-enhanced MRI based on TWIST-VIBE were helpful to improve the image resolution and provide more information for clinical differentiation between benign and malignant lung nodules.
Adult ; Humans ; Retrospective Studies ; Magnetic Resonance Imaging ; Plasma ; Tomography, X-Ray Computed ; Lung

Objective:To investigate the status of Corona Virus Disease 2019 (COVID-19) health literacy and associated factors in Inner Mongolia Autonomous Region.Methods:Based on the multi-stage stratified sampling method, the questionnaire survey of health literacy of COVID-19 were carried out in 55 599 local residents from12 prefecture-level cities of Inner Mongolia Autonomous Region between March 10 and 15, 2020. The questionnaire in details included not only knowledge, attitude and behavior, but also mental health, their scores were calculated using Decimal method. A ≥80% of the correct answer rate of the survey content was regarded as qualified for health literacy. There were 51 722 (93.0%) valid questionnaires, according to the ratio of medical staff to non-medical staff, 32 529 questionnaires were selected for analysis. The health literacy level was defined according to the proportion of qualified people.The credibility and availability of the questionnaires were evaluated by Cronbach′s α coefficient and KMO test. The associated factors were analyzed by Pearson χ 2 test and logistic regression. Results:In Inner Mongolia Autonomous Region, the whole level of health literacy of COVID-19 was 85.7%, and their scores were (26.30±2.48). Knowledge, attitude, and behavioral literacy levels were 61.6%, 95.6%, and 96.8%, respectively. Compared with the population of 15-25 years old, the health literacy level of 46-65 years old was the highest ( OR=2.00, 95% CI: 1.78-2.24). The health literacy level of medical staff group ( OR=2.54, 95% CI: 1.30-4.95) was far higher than the non-medical staff group; the population with college or above education level ( OR=10.22, 95% CI: 9.19-11.36) was significantly higher than the population with education level below college. The degree of anxiety was negatively correlated with education level. Conclusions:The health literacy level of COVID-19 in residents in Inner Mongolia Autonomous Region is relatively high, but the level of knowledge literacy needs to be improved. The main factors affecting the health literacy of COVID-19 among Inner Mongolia residents are age, occupation and education level.

Objective To explore the application value of fiberoptic bronchoscopy in the diagnosis and treatment of chronic cough in children. Methods A total of 113 children with chronic cough were enrolled in our hospital from January 2014 to December 2016. All the cases underwent fiberoptic bronchoscopy,the endoscopic manifestations and clinical symptoms were analyzed,and the pathogens in bronchoalveolar lavage fluid were detected. Results In the 113 children with chronic cough,64 cases (56. 6％) were boys and 49 cases (43. 4％) were girls,with 85 cases (75. 2％) under 5 years old. After fiberoptic bronchoscopy,30 cases (26. 5％) were diagnosed with bronchial foreign body,20 cases (17. 7％) were post-infection cough, 19 cases (16. 8％) with cough variant asthma,14 cases (12. 4％) with upper airway cough syndrome,14 cases ( 12. 4％) had airway abnormality, 9 cases ( 7. 9％) had protracted bacterial bronchitis, 4 cases (3. 6％) had bronchiolitis obliterans,and 3 cases (2. 7％) had bronchial tuberculosis. The most common pathogen was Streptococcus pneumonia in bronchoalveolar lavage fluid. The main adverse reactions in the operations was hypoxemia caused by airway obstruction. Conclusion Fiberoptic bronchoscopy is a very safe and reliable operation in the diagnosis and treatment of respiratory diseases in pediatrics, and plays an important role in the diagnosis of congenital developmental airway diseases,the detection of pathogens and the treatment of bronchial foreign bodies. For the chronic cough children who had repeated visits and poor treatment should accept fiberoptic bronchoscopy examination.

Histone acetylation is a critical process in the regulation of chromatin structure and gene expression. Histone deacetylases (HDACs) remove the acetyl group, leading to chromatin condensation and transcriptional repression. HDAC inhibitors are considered a new class of anticancer agents and have been shown to alter gene transcription and exert antitumor effects. This paper describes our work on the structural determination and structure-activity relationship (SAR) optimization of tetrahydroisoquinoline compounds as HDAC inhibitors. These compounds were tested for their ability to inhibit HDAC 1, 3, 6 and for their ability to inhibit the proliferation of a panel of cancer cell lines. Among these, compound 82 showed the greatest inhibitory activity toward HDAC 1, 3, 6 and strongly inhibited growth of the cancer cell lines, with results clearly superior to those of the reference compound, vorinostat (SAHA). Compound 82 increased the acetylation of histones H3, H4 and tubulin in a concentration-dependent manner, suggesting that it is a broad inhibitor of HDACs.

Aim To investigate the anti-tumor effects of FS-108 an Hsp90 inhibitor, on oncogene addicted EBC-1 and A375 cells. Methods SRB assay was performed to investigate cell proliferation. Immunoblot was conducted to investigate the specific proteins. FACS was conducted to test cell cycle distribution and apoptosis. Transwell assay was conducted to investigate cell motility. Results FS-108 significantly suppressed cell proliferation of EBC-1 and A375 cancer cells with IC50 at 25. 53 nmol · L-1 and 30. 02 nmol · L-1 re-spectively. FS-108 treatment triggered the degradation of key client proteins such as c-Met and B-Raf and thereby reduced their downstream AKT and ERK signa-ling pathways. The FACS analysis results demonstrated that FS-108 treatment induced G2/M phase arrest and apoptosis significantly. Furthermore, FS-108 inhibited the migration of EBC-1 and A375 cells. Conclusion As a potent Hsp90 inhibitor, FS-108 can inhibit onco-gene addicted cancer cells proliferation through induc-tion of G2/M phase arrest and apoptosis.

Objective To explore and analyze the application effect of scenario simulation combined with PBL in the clinical teaching of intracranial aneurysm disease. Methods Totally 60 student nurses in Xijing Hospital were selected and divided into the observation group and the control group according to random number table method, with 30 student nurses in each group. Student nurses in the observation group were given scenario simulation combined with PBL method, while student nurses in the control group given traditional nursing teaching method. At the end of their intership, the scores of theory and practice of student nurses in two groups were compared, and their evaluations of teaching effect were collected. Results After teaching, the theoretical score of student nurses in the observation group was (89.2±4.39), and the practical score was (85.9±2.50), they were all higher than the scores in the control group ( t=4.114,5.092;P<0.05) . The score of evaluation in the observation group was also higher than that in the control group ( P<0. 05 ) . Conclusions The use of scenario simulation and PBL is helpful in improving the learning effect student nurses in the clinical teaching of intracranial aneurysm disease and enhancing the clinical practice ability, and it is worth of popularization.