ABSTRACT
Objective:To compare the efficacy and safety of radium-223 in the treatment of metastatic castration-resistant prostate cancer (mCRPC) patients with and without homologous recombination repair (HRR) gene mutation.Methods:The clinical data of 27 patients with mCRPC bone metastases who received radium-223 therapy from April 2021 to November 2022 in Renji Hospital Affiliated to Shanghai Jiaotong University School of Medicine were retrospectively analyzed. Among the 27 mCRPC patients, 18 patients carrying HRR gene mutations belonged to the HRD(+ ) group, and 9 patients without HRR gene mutation belonged to the HRD(-) group. The age of patients in HRD(+ ) group was 69.5 (63.8, 77.0) years old, alkaline phosphatase (ALP) was 243.0 (82.8, 301.3) U/L, prostate specific antigen (PSA) was 71.6 (7.3, 329.8) ng/ml, pain score was 3.0 (1.0, 5.0) points. Eastern Cooperative Oncology Group (ECOG) score ranged from 0 to 1 points in 7 cases, and 2 points in 11 cases. In the HRD(-) group, the median age was 72.0 (64.5, 76.5) years old, ALP was 88.0 (67.5, 260.6) U/L, PSA was 19.1 (1.1, 117.8) ng/ml, and pain score was 2.0 (0, 4.5) points. The ECOG score ranged from 0 to 1 in 4 cases, and 2 in 5 cases in the HRD(-) group. There was no significant difference in the above general data between the two groups ( P>0.05). All patients received radium-223 treatment every 4 weeks, no more than 6 times. The changes of ALP, PSA, pain score and hematological adverse reactions were compared between the two groups. Results:In the HRD(+ ) group, the median number of radium-223 treatment was 4.5 (3.0, 5.3) couses, 4 patients (22.2%) completed 6 courses, and 6 patients died of prostate cancer during follow-up. In the HRD(-) group, the median number of radium treatment was 4.0 (2.5, 6.0) couses, 3 patients (33.3%) completed 6 courses, and 1 patient died of prostate cancer during follow-up. There was no significant difference in the number of radium treatment courses between the two groups ( P=0.320). ALP in HRD(+ ) group was 101.8 (61.3, 147.0) U/L after radium-223 treatment, which was significantly lower than that before treatment ( P=0.002). ALP in HRD(-) group was 73.0 (64.0, 113.5) U/L after radium-223 treatment, and it was not significantly different from that before treatment ( P=0.327). The rate of ALP response (ALP decrease >10%) in HRD(+ ) group was significantly higher than that in HRD(-) group [83.3% (15/18) vs. 44.4% (4/9), P=0.037]. PSA was 105.9(5.2, 798.4) ng/ml in HRD (+ ) group after radium-223 treatment, and was 25.6(0.8, 1 031.0) ng/ml in HRD(-) group, and they were not significantly different from that before treatment ( P=0.145, P=0.386). There were no significant differences in the rate of PSA response (PSA decrease>10%) between HRD(+ ) group and HRD(-) group [38.9% (7/18) vs. 22.2% (2/9), P=0.386]. The median pain score of HRD(+ ) group was 3.0 (0, 4.0) points after treatment, which was significantly lower than that before treatment ( P=0.028). The pain score of HRD(-) group was 1.0(0, 3.0) points after treatment, and it was not significantly different from that before treatment ( P=0.129). There was no significant difference in pain relief rate between HRD(+ ) group and HRD(-) group [66.7% (12/18) vs. 44.4% (4/9), P=0.411]. The incidence of at least one hematological adverse event during radium-223 treatment in the HRD(+ ) group was higher than that in the HRD(-) group [77.8% (14/18) vs. 33.3% (3/9), P=0.039]. There was no significant difference in the incidence of grade 1-2 hematological adverse events between the two groups [72.2%(13/18) vs. 33.3%(3/9), P=0.097]. Only 1 patient in the HRD(+ ) group experienced grade 3 anemia during treatment which was recovered after blood transfusion. Conclusions:Compared to mCRPC patients without HRR gene mutation, patients with HRR gene mutations had better ALP response and bone pain relief after radium-223 treatment. The overall incidence of adverse events in the HRD(+ ) group is higher than that in HRD(-) group, and there was no significant difference in grade 1-2 hematological adverse events between the two goups. It is necessary to expand the sample size to further verify the conclusion.
ABSTRACT
The accumulation of protein sequence and structure data allows researchers to obtain large amount of descriptive information, simultaneously it poses an urgent need for researchers to extract information from existing data efficiently and apply it to downstream tasks. Protein design enables the development of novel proteins that are no longer restricted by experimental conditions, which is of great significance for drug target prediction, drug discovery, and material design. As an efficient method for data feature extraction, deep learning can be used to model protein data, and further add a priori information to design novel proteins. Therefore, protein design based on deep learning has become a promising approach despite of many challenges. This review summarizes the deep learning-based modeling and design methods of protein sequence and structure data, highlighting the strategies, principle, scope of application and case studies, with the aim to provide a valuable reference for relevant researchers.
Subject(s)
Amino Acid Sequence , Deep Learning , Drug Development , ProteinsABSTRACT
OBJECTIVE:To reflect the representative problems existing in the medication safety of public from the side,and provide reference for conducting the following public survey in a large area. METHODS:Questionnaires were used to investigate the knowledge of drug and medication habits of teachers in a senior high school in Beijing,and the received data was statistically analyzed. RESULTS:Totally 88 questionnaires were issued in this investigation,84 effective questionnaires were acquired,with ef-fective recovery of 95.45%. A few teachers had blind faith in intravenous infusion and preferred using antibiotics without doctor's di-agnosis when they caught a cold and fever;48.81%of the respondents barely understood or only partly understood the drug instruc-tions;34.52% didn't know that more serious adverse reactions induce by intravenous infusion were more serious than by oral treat-ment;46.43% rarely checked the period of validity of reserved drugs at home;38.10% didn’t following directions when taking drugs;80.95% had never received the education of medication safety,and 21.43% of them had no intention to accept this educa-tion;when taking drugs for a long time,79.76% of them didn’t do regular examinations of blood routine,renal and liver function tests. CONCLUSIONS:The knowledge of drug use of the respondents in the school is poor,there are many misunderstandings ex-isted in the medication habit,which prompts hidden trouble also exists in medication safety,and reflects hidden trouble commonly exists in medication safety for public from the side.
ABSTRACT
<p><b>OBJECTIVE</b>To improve the method of indirubin in serum by HPLC and apply to pharmacokinetics in rats.</p><p><b>METHOD</b>Chromatographic separation was conducted on an C18 column (4.6 mm x 250 mm, 5 microm), using a mixture of methanol-water (75:25) as mobile phase at a flow rate of 1.0 mL min(-1) with UV detection at 289 nm, the column temperature was at 35 degrees C and ethinyl estradiol was used as an internal standard. Rats were administered i. v. bolus of indirubin in doses of 2.0 and 4.0 mg x kg(-1) through a jugular vein catheter, respectively. Serial blood samples (about 100 microL) were individually collected at 2, 5, 10, 20, 30, 60, 90, 120, 180 min after administration, and the concentrations of indirubin determined were in rat serum by HPLC. The pharmacokinetic parameters were calculated with the Winnonlin 5.0 software.</p><p><b>RESULT</b>The calibration curve for indirubin was linear ( R2 = 0.9996) in the range of 0.031-2.48 mg x L(-1) and the limit of detection (LOD) was 31 microg x L(-1). The average recovery of indirubin in rat serum was more than 98% and the relative standard deviations of intra-day and inter-day were both less than 10%. The pharmacokinetics of Indirubin in rats was fitted to two-compartment model.</p><p><b>CONCLUSION</b>The method is simple and accurate with a high sensitivity and a good repeatability, and it can be applied to the evaluation of pharmacokinetic parameters of indirubin in rats and blood concentration of indirubin in clinical controlling.</p>