Entinostat, a class I selective histone deacetylase inhibitor, plus exemestane for Chinese patients with hormone receptor-positive advanced breast cancer: A multicenter, randomized, double-blind, placebo-controlled, phase 3 trial

Entinostat plus exemestane in hormone receptor-positive (HR+) advanced breast cancer (ABC) previously showed encouraging outcomes. This multicenter phase 3 trial evaluated the efficacy and safety of entinostat plus exemestane in Chinese patients with HR + ABC that relapsed/progressed after ≥1 endocrine therapy. Patients were randomized (2:1) to oral exemestane 25 mg/day plus entinostat (n = 235) or placebo (n = 119) 5 mg/week in 28-day cycles. The primary endpoint was the independent radiographic committee (IRC)-assessed progression-free survival (PFS). The median age was 52 (range, 28-75) years and 222 (62.7%) patients were postmenopausal. CDK4/6 inhibitors and fulvestrant were previously used in 23 (6.5%) and 92 (26.0%) patients, respectively. The baseline characteristics were comparable between the entinostat and placebo groups. The median PFS was 6.32 (95% CI, 5.30-9.11) and 3.72 (95% CI, 1.91-5.49) months in the entinostat and placebo groups (HR, 0.76; 95% CI, 0.58-0.98; P = 0.046), respectively. Grade ≥3 adverse events (AEs) occurred in 154 (65.5%) patients in the entinostat group versus 23 (19.3%) in the placebo group, and the most common grade ≥3 treatment-related AEs were neutropenia [103 (43.8%)], thrombocytopenia [20 (8.5%)], and leucopenia [15 (6.4%)]. Entinostat plus exemestane significantly improved PFS compared with exemestane, with generally manageable toxicities in HR + ABC (ClinicalTrials.gov #NCT03538171).

Influencing factors of obstructive sleep apnea hypopnea syndrome patients′ delay on health seeking behaviour: a literature review / 中国实用护理杂志

In order to provide scientific basis for health education and patient timely seeking behavior, this article summarizes the definition, the status quo and influencing factors of delayed on health seeking behavior of patients with obstructive sleep apnea hypopnea syndrome. Influencing factors mainly include clinical character, individual and environment.

Quantification and genotyping of hepatitis B virus in a single reaction based on dual molecular beacon real-time PCR / 中华检验医学杂志

Objective To develop a new method for simultaneous quantifying and genotyping of HBV in a single reaction based on dual molecular beacon real-time PCR.Methods Genotype B and C recombinant plasmids were constructed as the standards and genotype-specific primers and molecular beacons were designed for each genotype.The molecular beacons of genotype B and C were labeled with FAM and Hex respectively.In this way,a simultaneous qualification and genotyping method for HBV DNA in a single real-time PCR reaction system was developed.Firstly,10-fold gradient dilution of genotype B and C standard plasmids (103-1011 kIU/L) were utilized to evaluate the linear ranges and sensitivity of this approach.The clinical specificity was tested with twenty different serum specimens (5 cases with hepatitis C virus,5 cases with herpes simplex virus and 5 cases with human papilloma virus as well as 5 healthy volunteers) ; the reproducibility was assessed by intra-assay and inter-assay coefficient of variation (CV) of cycle threshold (Ct) value through 10 repeated detections within a batch and between batches of the B,C standard plasmids (108,106 and 104 kIU/L).Then the accuracy of qualifying and genotyping of the self-built method was evaluated by a parallel examination with 132 HBV infected patients by use of two commercial kits as the references.Finally,these HBV-positive patients were divided into 4 groups:asymptomatic carrier (n =21),chronic hepatitis (n =77),liver cirrhosis (n =25) and hepatocellular carcinoma (n =9) to investigate the relationship of genotypes,stages of disease progression and HBV DNA load.Results A simultaneous qualification and genotyping assay was successfully built and its genotyping sensitivity was 103 kIU/L and the linear range was 103-1011 kIU/L.The intra-assay CV of B genotyping was 1.51％ to 1.80％ and the interassay CV was 2.11％ to 3.03％,while the intra-assay CV of C genotyping was 1.79％ to 1.95％ and the inter-assay CV was 2.53％ to 2.91％.The results of non HBV infected cases and healthy volunteers showed negative.In the test of 132 HBV infected patients,the general coincident rate of genotyping results comparing our assay and HBV DNA genotyping kit was 90.9％ (120/132,Kappa =0.832,P ＜ 0.05).The HBV DNA quatitive results between the assay[5.07 (3.89-6.33)] and HBV DNA quatitive kit [5.19 (4.15-6.32) lg kIU/L] were well correlative (R2 =0.8477,P ＜ 0.05).69 genotype B cases,51 genotype C cases and 12 B/C mixed-genotype cases were detected by dual molecular beacon real-time PCR method and their HBV DNA load were 4.54 (3.83-6.17),5.53 (4.02-6.55),4.58 (3.68-4.98) lg kIU/L respectively.Where the patients with genotype C had higher DNA load than the patients with other two genotypes (Z =-2.195and-2.162,P ＜ 0.05).The HBV DNA load of asymptomatic group,chronic hepatitis group,liver cirrhosis group and hepatocellular carcinoma group were 7.02 (6.35-7.84),4.94 (4.16-6.25),4.37(3.50-5.17) and 3.45 (3.25-4.92) lg kIU/L,respectively.Among them,the asymptomatic group was significantly higher than those of other three groups (Z =-4.244,-4.568 and-3.489,P ＜0.001) and DNA load comparing with the chronic hepatitis group,liver cirrhosis group and hepatocellular carcinoma group also showed statistically different (Z =-2.894 and-2.413,P ＜ 0.05).However,compared with the liver cirrhosis group and hepatocellular carcinoma group there was no significant difference (Z =-0.995,P =0.335).Conclusion A dual molecular beacon real-time PCR assay which can simultaneously quantifying and genotyping HBV DNA with highly accuracy,sensitive and specificity is successfully developed.(Chin J Lab Med,2013,36:333-338)