Predicting the protein binding rate of drugs in plasma is helpful to us in understanding the pharmacokinetic characteristics of drugs, with much value of reference for early research on drug discovery. In this study, plasma protein binding rate information of 2 452 clinical drugs were collected.Two pieces of software, Molecular Operating Environment (MOE) and Mordred, were used to calculate molecular descriptors, which were used as input features of the model.Extreme gradient boosting (XGBoost) algorithm and random forest (RF) algorithm were then used to build a machine learning model.The results showed that, compared with MOE, the prediction performance of the constructed model was better using the molecular descriptor calculated by Mordred as the input of the model.The prediction performance results of the model constructed using the XGBoost algorithm and the RF algorithm were similar, and the R2 of the optimal model were both 0.715.According to the research results, it can be concluded that the drug plasma protein binding rate is closely related to some physical and chemical properties of the drug molecule, such as water solubility, octanol/water partition coefficient and conjugated double bonds.Using these parameters to predict the plasma protein binding rate of drugs has the advantages of convenience and efficiency, which can provide reference for related pharmacokinetic studies.

A HPLC method was developed for the determination of mangiferin in rat plasma and aqueous humor. 4-Nitrophenol was used as internal standard. Analysis was performed on a Cosmosil ODS C18 analytical column (4.6 mm x 250 mm, 5 microm) with mobile phase consisting of methanol-water (40: 60) with 2% glacial acetic acid at a flow rate of 1.0 mL x min(-1). The calibration curve of mangiferin in rat plasma and aqueous humor showed excellent linear behaviors over the investigated concentration of 0. 50-250.00 mg x L(-1) in plasma and 0.10-10.00 mg x L(-1) in aqueous humor, respectively, and the correlation coefficients were all above 0.995 4. The intra-day and inter-day precisions for all samples were measured to be below 12%. The limit of quantitation was 0.10 mg x L(-1) and low enough for the determination of mangiferin in all samples. The validated method has been successfully applied to preliminary pharmacokinetics study of mangiferin in rat plasma and aqueous humor.
Animals ; Aqueous Humor ; chemistry ; Chromatography, High Pressure Liquid ; Female ; Male ; Nitrophenols ; analysis ; Rats ; Rats, Wistar ; Reproducibility of Results ; Sensitivity and Specificity ; Xanthones ; blood ; pharmacokinetics

Objective:To investigate the value of an MRI and digital pathology images based omics nomogram for the prediction of recurrence risk in soft tissue sarcoma (STS).Methods:This was a retrospective cohort study. From January 2016 to March 2021, 192 patients with STS confirmed by pathology in the Affiliated Hospital of Qingdao University were enrolled, among which 112 patients in the Laoshan campus were enrolled as training set, and 80 patients in the Shinan campus were enrolled as validation set. The patients were divided into recurrence group ( n=87) and no recurrence group ( n=105) during follow-up. The clinical and MRI features of patients were collected. The radiomics features based on fat saturated T 2WI images and pathomics features based on digital pathology images of the lesions were extracted respectively. The clinical model, radiomics model, pathomics model, radiomics-pathomics combined model, and omics nomogram which combined the optimal prediction model and the clinical model were established by multivariate Cox regression analysis. The concordance index (C index) and time-dependent area under the receiver operating characteristic curve (t-AUC) were used to evaluate the performance of each model in predicting STS postoperative recurrence. The DeLong test was used for comparison of t-AUC between every two models. The X-tile software was used to determine the cut-off value of the omics nomogram, then the patients were divided into low risk ( n=106), medium risk ( n=64), and high risk ( n=22) groups. Three groups′ cumulative recurrence-free survival (RFS) rates were calculated and compared by the Kaplan-Meier survival curve and log-rank test. Results:The performance of the radiomics-pathomics combined model was superior to the radiomics model and pathomics model, with C index of 0.727 (95% CI 0.632-0.823) and medium t-AUC value of 0.737 (95% CI0.584-0.891) in the validation set. The omics nomogram was established by combining the clinical model and the radiomics-pathomics combined model, with C index of 0.763 (95% CI 0.685-0.842) and medium t-AUC value of 0.783 (95% CI0.639-0.927) in the validation set. The t-AUC value of omics nomogram was significantly higher than that of clinical model, TNM model, radiomics model, and pathomics model in the validation set ( Z=3.33, 2.18, 2.08, 2.72, P=0.001, 0.029, 0.037, 0.007). There was no statistical difference in t-AUC between the omics nomogram and radiomics-pathomics combined model ( Z=0.70, P=0.487). In the validation set, the 1-year RFS rates of STS patients in the low, medium, and high recurrence risk groups were 92.0% (95% CI 81.5%-100%), 55.9% (95% CI 40.8%-76.6%), and 37.5% (95% CI 15.3%-91.7%). In the training and validation sets, there were statistically significant in cumulative RFS rates among the low, medium, and high groups of STS patients (training set χ2=73.90, P<0.001; validation set χ2=18.70, P<0.001). Conclusion:The omics nomogram based on MRI and digital pathology images has favorable performance for the prediction of STS recurrence risk.

Objective:To investigate the value of 18F-FDG PET/CT imaging signs and metabolic parameters in predicting tumor spread through air spaces (STAS) of stage Ⅰ lung adenocarcinoma. Methods:From January 2019 to December 2021, clinical, imaging and metabolic parameters of 381 patients (126 males, 255 females, age (61.2±9.2) years) with stage Ⅰ lung adenocarcinoma were retrospectively analyzed in the Affiliated Hospital of Qingdao University. According to the postoperative pathological results, patients were divided into STAS positive group and STAS negative group. According to the operation time, patients were divided into training set ( n=254) and verification set ( n=127). χ2 test or Mann-Whitney U test was used to compare the differences of different parameters between patients with STAS positive and negative, and binary logistic regression analysis was used to select the predictors of STAS status. The prediction model was established, and ROC curve was used to evaluate the predictive efficacy. Results:There were 49(19.3%, 49/254) patients with STAS positive and 205(80.7%, 205/254) patients with STAS negative in the training set, while those were 35(27.6%, 35/127) and 92(72.4%, 92/127) in the verification set. In the training set, the differences of age ( z=-2.30, P=0.021), type of lesions ( χ2=6.81, P=0.009), spiculation ( χ2=12.64, P<0.001), bronchus truncation ( χ2=6.98, P=0.008), ground glass ribbon sign ( χ2=26.93, P<0.001) and SUV max ( z=-4.62, P<0.001) between the two groups were statistically significant. Multivariate logistic regression analysis showed that age (odds ratio ( OR)=1.048, 95% CI: 1.004-1.094, P=0.032), ground glass ribbon sign ( OR=3.857, 95% CI: 1.693-8.788, P=0.001) and SUV max ( OR=1.133, 95% CI: 1.001-1.282, P=0.049) were independent predictors of STAS status in stage Ⅰ lung adenocarcinoma patients. The logistic regression model was P=1/(1+ e - x), x=-5.292+ 0.480×age (year)+ 1.493×ground glass ribbon sign+ 0.170×SUV max. The AUCs of the model in the training set and verification set were 0.770 and 0.801, with the sensitivity of 81.6%(40/49) and 82.9%(29/35), and the specificity of 69.8%(143/205) and 65.2%(60/92), respectively. Conclusion:Age, ground glass ribbon sign and SUV max have good predictive effects on the occurrence of STAS in stage Ⅰ lung adenocarcinoma.

As endogenous chemical substances,neurotransmitters play a vital role in maintaining normal life activities.Abnormal levels of neurotransmitters can lead to physical,mental,and some neurodegenerative diseases.However,the ultralow concentration,complex chemical properties,and release modes of neurotransmitters make their accurate detection in vivo a great challenge.To accurately monitor neurotransmitters in the brain and accurately understand the release kinetics of neurotransmitters,we reviewed several method commonly used in the past five years to detect neurotransmitters in vivo and their research progress.The basic principle and applicability of microdialysis,electrochemical sensors,and fluorescence sensors are introduced in detail.

Objective:To assess the clinical effectiveness and safety of Omalizumab for treating pediatric allergic asthma in real world in China.Methods:The clinical data of children aged 6 to 11 years with allergic asthma who received Omalizumab treatment in 17 hospitals in China between July 6, 2018 and September 30, 2020 were retrospectively analyzed.Such information as the demographic characteristics, allergic history, family history, total immunoglobulin E (IgE) levels, specific IgE levels, skin prick test, exhaled nitric oxide (FeNO) levels, eosinophil (EOS) counts, and comorbidities at baseline were collected.Descriptive analysis of the Omalizumab treatment mode was made, and the difference in the first dose, injection frequency and course of treatment between the Omalizumab treatment mode and the mode recommended in the instruction was investigated.Global Evaluation of Treatment Effectiveness (GETE) analysis was made after Omalizumab treatment.The moderate-to-severe asthma exacerbation rate, inhaled corticosteroid (ICS) dose, lung functions were compared before and after Omalizumab treatment.Changes in the Childhood Asthma Control Test (C-ACT) and Pediatric Asthma Quality of Life Questionnaire (PAQLQ) results from baseline to 4, 8, 12, 16, 24, and 52 weeks after Omalizumab treatment were studied.The commodity improvement was assessed.The adverse event (AE) and serious adverse event (SAE) were analyzed for the evaluation of Omalizumab treatment safety.The difference in the annual rate of moderate-to-severe asthma exacerbation and ICS reduction was investigated by using t test.The significance level was set to 0.05.Other parameters were all subject to descriptive analysis.A total of 200 allergic asthma patients were enrolled, including 75.5% ( n=151) males and 24.5% ( n=49) females.The patients aged (8.20±1.81) years. Results:The median total IgE level of the 200 patients was 513.5 (24.4-11 600.0) IU/mL.Their median treatment time with Omalizumab was 112 (1-666) days.Their first dose of Omalizumab was 300 (150-600) mg.Of the 200 cases, 114 cases (57.0%) followed the first Omalizumab dosage recommended in the instruction.After 4-6 months of Omalizumab treatment, 88.5% of the patients enrolled ( n=117) responded to Omalizumab.After 4 weeks of treatment with Omalizumab, asthma was well-controlled, with an increased C-ACT score [from (22.70±3.70) points to (18.90±3.74) points at baseline]. Four-six months after Omalizumab administration, the annual rate of moderate-to-severe asthma exacerbation had a reduction of (2.00±5.68) per patient year( t=4.702 5, P<0.001), the median ICS daily dose was lowered [0 (0-240) μg vs. 160 (50-4 000) μg at baseline] ( P<0.001), the PAQLQ score was improved [(154.90±8.57) points vs. (122.80±27.15) points at baseline], and the forced expiratory volume in one second % predicted (FEV 1%pred) was increased [(92.80±10.50)% vs. (89.70±18.17)% at baseline]. In patients with available evaluations for comorbidities, including allergic rhinitis, atopic dermatitis or eczema, urticaria, allergic conjunctivitis and sinusitis, 92.8%-100.0% showed improved symptoms.A total of 124 AE were reported in 58 (29.0%) of the 200 patients, and the annual incidence was 0(0-15.1) per patient year.In 53 patients who suffered AE, 44 patients (83.0%) and 9 patients (17.0%) reported mild and moderate AE, respectively.No severe AE were observed in patients.The annual incidence of SAE was 0(0-1.9) per patient year.Most common drug-related AE were abdominal pain (2 patients, 1.0%) and fever (2 patients, 1.0%). No patient withdrew Omalizumab due to AE. Conclusions:Omalizumab shows good effectiveness and safety for the treatment of asthma in children.It can reduce the moderate-to-severe asthma exacerbation rate, reduce the ICS dose, improve asthma control levels, and improve lung functions and quality of life of patients.