OBJECTIVETo establish a HPLC-DAD method for determining concentrations of betulic acid and phenol red in intestinal circulation liquid, and probe into the absorption kinetic characteristics of betulic acid at different intestine segments in rats and the effect of different drug concentrations on absorption.

METHODThe rat intestinal absorption model was established to detect the impact of absorption site, drug concentration and pH value on drug absorption.

RESULTWithin the range from 75-125 mg x L(-1), the absorption rate and the quality concentration of betulic acid had a linear relation, with Ka value keeping unchanged. The absorption rate for each intestinal segment showed no remarkable difference, with Ka values in duodenum, jejunum, ileum and colon being (0.151 +/- 0.0049), (0.159 +/- 0.0056), (0.156 +/- 6.0083), (0.149 +/- 0.0041) h(-1), respectively.

CONCLUSIONBetulic acid is proved to be well absorbed in intestines marked by no specific absorption site in the intestine. The absorption mechanism of the drug conforms to passive transport mechanism and first-order kinetics. The bioavailability of betulic acid preparation can be increased by enhancing the dissolution rate and the solubility.

Animals ; Anti-HIV Agents ; pharmacokinetics ; Antineoplastic Agents, Phytogenic ; pharmacokinetics ; Chromatography, High Pressure Liquid ; Intestinal Absorption ; Intestines ; metabolism ; Kinetics ; Male ; Rats ; Rats, Sprague-Dawley ; Reference Standards ; Reproducibility of Results ; Sensitivity and Specificity ; Triterpenes ; pharmacokinetics

BACKGROUD/OBEJECTIVES: Arsenic, which causes human carcinogenicity, is ubiquitous in the environment. This study was designed to evaluate modulation of arsenic induced cancer by resveratrol, a phytoalexin found in vegetal dietary sources that has antioxidant and chemopreventive properties, in arsenic trioxide (As2O3)-induced Male Wistar rats. MATERIALS/METHODS: Adult rats received 3 mg/kg As2O3 (intravenous injection, iv.) on alternate days for 4 days. Resveratrol (8 mg/kg) was administered (iv.) 1 h before As2O3 treatment. The plasma and homogenization enzymes associated with oxidative stress of rat kidneys were measured, the kidneys were examined histologically and trace element contents were assessed. RESULTS: Rats treated with As2O3 had significantly higher oxidative stress and kidney arsenic accumulation; however, pretreatment with resveratrol reversed these changes. In addition, prior to treatment with resveratrol resulted in lower blood urea nitrogen, creatinine and insignificant renal tubular epithelial cell necrosis. Furthermore, the presence of resveratrol preserved the selenium content (0.805 +/- 0.059 microg/g) of kidneys in rats treated with As2O3. However, resveratrol had no effect on zinc level in the kidney relative to As2O3-treated groups. CONCLUSIONS: Our data show that supplementation with resveratrol alleviated nephrotoxicity by improving antioxidant capacity and arsenic efflux. These findings suggest that resveratrol has the potential to protect against kidney damage in populations exposed to arsenic.
Adult ; Animals ; Arsenic* ; Blood Urea Nitrogen ; Creatinine ; Epithelial Cells ; Humans ; Kidney ; Male ; Necrosis ; Oxidative Stress ; Plasma ; Rats* ; Rats, Wistar ; Selenium ; Zinc

Purpose To investigate the predictive value of chest CT-based radiomics for spread through air spaces in stage T1 peripheral type lung cancer.Materials and Methods A total of 173 patients with surgically pathologically confirmed stage T1 non-small cell lung cancer were retrospectively collected and divided into positive group(49 cases)and negative group(124 cases)according to the presence or absence of spread through air spaces.All lesions were randomly divided into training set(122 cases)and validation set(51 cases)according to the ratio of 7∶3.The primary area of lung cancer(the main body of the lesion),the peripheral infiltrative area(a 5-mm annular area expanding outward along the edge of the lesion)and the tumor margin area(a 5-mm annular area retracting inward along the edge of the lesion)were used as areas of interest to extract imaging histological features.Three imaging histological models were established for the primary area of lung cancer,the peripheral infiltrative area and the tumor margin area,and combined with the morphological features of CT to establish three combined models.The efficacy of each model was evaluated and the optimal model was selected.Results The lobulation signs of positive group was significantly more than that of negative group(χ2=9.946,P=0.002).The area under the curve(AUC)of the imaging histological model based on the three regions of interest were 0.899,0.825,0.840 for the training group and 0.876,0.811 and 0.832 for the validation group,respectively.The model with the highest AUC was the primary tumor imaging model(P=0.043,P<0.001,P=0.017),the AUC of the combined model established by adding the lobar sign were 0.917,0.835 and 0.851,respectively.The AUC of the three regions of interest in the validation group were 0.912,0.832,and 0.845 and the highest AUC was found in the primary tumor area(P<0.001,P=0.017,P=0.049).Conclusion It is feasible to study lung cancer with airway metastasis via CT-based radiomics,taken lobulation signs as the risk predictive factor.

Objective:To evaluate the clinical efficacy of the combined diagnosis and management in children with airway allergic diseases(bronchial asthma, allergic rhinitis).Methods:This observational study belongs to cluster sampling cases, which included the clinical data from children with airway allergic diseases in Allergy Department and Otorhinolaryngology Department of Beijing Children′s Hospital from April to December in 2015. They were followed up every three months during 12 months. All the subjects were required to continuously record daily symptom by diary card. ACT/c-ACT, VAS, treatment steps to control asthma, respiratory infections, wheeze, pulmonary function(FEV1%pred,FEV1/FVC,PEF%pred,FEF25%pred,FEF50%pred,FEF75%pred,MMEF%pred), FeNO were assessed in every visiting. The mean±standard deviation was used for the measurement data in accordance with normal distribution. Comparing the pulmonary function indexes at every point, the measurement data with normal distribution and uniform variance were analyzed by single factor analysis of variance, and the measurement data with uneven variance were tested by non-parametric rank sum test.Results:Among 147 recruited participants, 106 completed the combined diagnosis and management. The airway allergic diseases control rate was 87.7% at 12 months after the combined diagnosis and management. At every point, the average daily symptom score and VAS score which were significantly lower than at the baseline( H=35.854, P=0.000)[ 1.2(0.7,2.2),0.6(0.2,1.5),0.4(0.1,1.0),0.5(0.1,1.1) vs 2.0(1.0,3.5)],( H=39.559, P=0.000)[2.5(0.5,4.7),2.2(0.3,4.4),1.8(0.2,4.6),1.6(0.3,3.8) vs 6.9(4.1,9.8)]. ACT/c-ACT score at 3, 6, 9, 12 months were significantly higher than at the baseline ( H=79.695, P=0.000) [25.0(22.5,27.0),26.0(24.0,27.0),25.0(23.0,27.0),25.0(24.0,27.0) vs 20.0(17.0,22.0)]. FEV1%pred and FEF25%pred at 3, 6 months were significantly higher than at the baseline ( F=3.563, P=0.007)(104.7±12.6 vs 96.8±14.5,103.0±10.3 vs 96.8±14.5),( F=2.456, P=0.046)(96.6±22.0 vs 85.0±21.9,93.3±18.0 vs 85.0±21.9). PEF%pred at 3, 6, 9, 12 months after the combined diagnosis and management were significantly higher than at the baseline( F=5.497, P=0.000)(105.1±18.1,101.2±15.3,99.7±17.1,99.8±17.5 vs 90.3±17.8). FeNO at 3, 6, 9, 12 months respectively were no significantly differences at the baseline( F=0.751, P=0.558)(25.7±23.6 vs 30.7±25.6,25.9±16.5 vs 30.7±25.6,27.5±20.2 vs 30.7±25.6,30.6±19.6 vs 30.7±25.6).The respiratory infections rate were 69.8%(74/106),67.0%(71/106),60.4%(64/106),51.9%(55/106) at 3, 6, 9, 12 months respectively. The wheezing rate was 24.5%(26/106),14.2%(15/106),11.3%(12/106),7.5%(8/106) at 3, 6, 9, 12 months respectively. Conclusions:The combined diagnosis and management can significantly improve the control level of children′s airway allergic diseases, which should be implemented in the management of children′s airway allergic diseases.

Objective:To evaluate the clinical efficacy of the combined diagnosis and management in children with airway allergic diseases(bronchial asthma, allergic rhinitis).Methods:This observational study belongs to cluster sampling cases, which included the clinical data from children with airway allergic diseases in Allergy Department and Otorhinolaryngology Department of Beijing Children′s Hospital from April to December in 2015. They were followed up every three months during 12 months. All the subjects were required to continuously record daily symptom by diary card. ACT/c-ACT, VAS, treatment steps to control asthma, respiratory infections, wheeze, pulmonary function(FEV1%pred,FEV1/FVC,PEF%pred,FEF25%pred,FEF50%pred,FEF75%pred,MMEF%pred), FeNO were assessed in every visiting. The mean±standard deviation was used for the measurement data in accordance with normal distribution. Comparing the pulmonary function indexes at every point, the measurement data with normal distribution and uniform variance were analyzed by single factor analysis of variance, and the measurement data with uneven variance were tested by non-parametric rank sum test.Results:Among 147 recruited participants, 106 completed the combined diagnosis and management. The airway allergic diseases control rate was 87.7% at 12 months after the combined diagnosis and management. At every point, the average daily symptom score and VAS score which were significantly lower than at the baseline( H=35.854, P=0.000)[ 1.2(0.7,2.2),0.6(0.2,1.5),0.4(0.1,1.0),0.5(0.1,1.1) vs 2.0(1.0,3.5)],( H=39.559, P=0.000)[2.5(0.5,4.7),2.2(0.3,4.4),1.8(0.2,4.6),1.6(0.3,3.8) vs 6.9(4.1,9.8)]. ACT/c-ACT score at 3, 6, 9, 12 months were significantly higher than at the baseline ( H=79.695, P=0.000) [25.0(22.5,27.0),26.0(24.0,27.0),25.0(23.0,27.0),25.0(24.0,27.0) vs 20.0(17.0,22.0)]. FEV1%pred and FEF25%pred at 3, 6 months were significantly higher than at the baseline ( F=3.563, P=0.007)(104.7±12.6 vs 96.8±14.5,103.0±10.3 vs 96.8±14.5),( F=2.456, P=0.046)(96.6±22.0 vs 85.0±21.9,93.3±18.0 vs 85.0±21.9). PEF%pred at 3, 6, 9, 12 months after the combined diagnosis and management were significantly higher than at the baseline( F=5.497, P=0.000)(105.1±18.1,101.2±15.3,99.7±17.1,99.8±17.5 vs 90.3±17.8). FeNO at 3, 6, 9, 12 months respectively were no significantly differences at the baseline( F=0.751, P=0.558)(25.7±23.6 vs 30.7±25.6,25.9±16.5 vs 30.7±25.6,27.5±20.2 vs 30.7±25.6,30.6±19.6 vs 30.7±25.6).The respiratory infections rate were 69.8%(74/106),67.0%(71/106),60.4%(64/106),51.9%(55/106) at 3, 6, 9, 12 months respectively. The wheezing rate was 24.5%(26/106),14.2%(15/106),11.3%(12/106),7.5%(8/106) at 3, 6, 9, 12 months respectively. Conclusions:The combined diagnosis and management can significantly improve the control level of children′s airway allergic diseases, which should be implemented in the management of children′s airway allergic diseases.

H 1-antihistamines are widely used in the treatment of various allergic diseases, but there are still many challenges in the safe and rational use of H 1-antihistamines in pediatrics, and there is a lack of guidance on the prescription review of H 1-antihistamines for children.In this paper, suggestions are put forward from the indications, dosage, route of administration, pathophysiological characteristics of children with individual difference and drug interactions, so as to provide reference for clinicians and pharmacists.

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.