Benralizumab efficacy and safety in severe asthma: A randomized trial in Asia.

BACKGROUND: Benralizumab is indicated as add-on therapy in patients with uncontrolled, severe eosinophilic asthma; it has not yet been evaluated in a large Asian population with asthma in a clinical trial. OBJECTIVE: To evaluate the efficacy and safety of benralizumab in patients with severe asthma in Asia. METHODS: MIRACLE (NCT03186209) was a randomized, Phase 3 study in China, South Korea, and the Philippines. Patients aged 12-75 years with severe asthma receiving medium-to-high-dose inhaled corticosteroid/long-acting ß2-agonists, stratified (2:1) by baseline blood eosinophil count (bEOS) (≥300/µL; <300/µL), were randomized (1:1) to benralizumab 30 mg or placebo. Endpoints included annual asthma exacerbation rate (AAER; primary endpoint), change from baseline at Week 48 in pre-bronchodilator (BD) forced expiratory volume in 1 second (pre-BD FEV1) and total asthma symptom score (TASS). Safety was evaluated ≤ Week 56. RESULTS: Of 695 patients randomized, 473 had baseline bEOS ≥300/µL (benralizumab n = 236; placebo n = 237). In this population, benralizumab significantly reduced AAER by 74% (rate ratio 0.26 [95% CI 0.19, 0.36], p < 0.0001) and significantly improved pre-BD FEV1 (least squares difference [LSD] 0.25 L [95% CI 0.17, 0.34], p < 0.0001) and TASS (LSD -0.25 [-0.45, -0.05], p = 0.0126) versus placebo. In patients with baseline bEOS <300/µL, there were numerical improvements in AAER, pre-BD FEV1, and TASS with benralizumab versus placebo. The frequency of adverse events was similar for benralizumab (76%) and placebo (80%) in the overall population. CONCLUSIONS: MIRACLE data reinforces the efficacy and safety of benralizumab for severe eosinophilic asthma in an Asian population, consistent with the global Phase 3 results.

Norcantharidin induces apoptosis through autophagosome accumulation in breast cancer MDA-MB-231 cells / 中国药科大学学报

@#The aim of this study was to investigate the effect of norcantharidin (NCTD) on the proliferation and apoptosis of triple-negative breast cancer cell line MDA-MB-231.Western blot was used to detect the effect of NCTD on the expression levels of apoptosis-related proteins Bax/Bcl-2, cleaved-PARP/PARP/PARP, cleved-caspase-9, cleaved-caspase-3 and MCL-1 in MDA-MB-231 cells.Also, the expression levels of autophagy-related proteins LC3-II/LC3-I, Parkin and PINK1 in MDA-MB-231 cells were measured by Western blot.Flow cytometry was used to measure the effect of NCTD on the changes of mitochondrial membrane potential and mitochondrial reactive oxygen species (ROS).The effect of NCTD on autophagy flow in cells expressing mCherry-EGFP-LC3 was detected by a confocal microscope.Moreover, the effects of NCTD combined with chloroquine (CQ) or 3-methyladenine (3-MA) on the apoptosis of MDA-MB-231 cells were detected by flow cytometry.The results showed that NCTD significantly increased the expression levels of Bax/Bcl-2, cleaved-PARP/PARP, cleaved-caspase-9, cleasved-caspase-3 and LC3-II/LC3-I proteins, and promoted the mitochondrial translocation of Parkin, and blocked the autophagic flow in MDA-MB-231 cells. Moreover, NCTD combined with CQ accelerated apoptosis, while NCTD combined with 3-MA decreased apoptosis.These results suggest that NCTD can induce autophagy accumulation and lead to apoptosis of MDA-MB-231 cells.

EGFR-TKI Combined with Pemetrexed versus EGFR-TKI Monotherapy in Advanced EGFR-mutated NSCLC: A Prospective, Randomized, Exploratory Study / Journal of the Korean Cancer Association, 대한암학회지

Purpose@#We aimed to evaluate whether the addition of pemetrexed is effective in improving progression-free survival (PFS) in epidermal growth factor receptor (EGFR)–mutated patients with or without concomitant alterations. @*Materials and Methods@#This multicenter clinical trial was conducted in China from June 15, 2018, to May 31, 2019. A total of 92 non–small cell lung cancer (NSCLC) patients harboring EGFR-sensitive mutations were included and divided into concomitant and non-concomitant groups. Patients in each group were randomly treated with EGFR–tyrosine kinase inhibitor (TKI) monotherapy or EGFR-TKI combined with pemetrexed in a ratio of 1:1. PFS was recorded as the primary endpoint. @*Results@#The overall median PFS of this cohort was 10.1 months. There were no significant differences in PFS between patients with and without concomitant and between patients received TKI monotherapy and TKI combined with pemetrexed (p=0.210 and p=0.085, respectively). Stratification analysis indicated that patients received TKI monotherapy had a significantly longer PFS in non-concomitant group than that in concomitant group (p=0.002). In concomitant group, patients received TKI combined with pemetrexed had a significantly longer PFS than patients received TKI monotherapy (p=0.013). Molecular dynamic analysis showed rapidly emerging EGFR T790M in patients received TKI monotherapy. EGFR mutation abundance decreased in patients received TKI combined chemotherapy, which supports better efficacy for a TKI combined chemotherapy as compared to TKI monotherapy. A good correlation between therapeutic efficacy and a change in circulating tumor DNA (ctDNA) status was found in 66% of patients, supporting the guiding role of ctDNA minimal residual disease (MRD) in NSCLC treatment. @*Conclusion@#EGFR-TKI monotherapy is applicable to EGFR-sensitive patients without concomitant alterations, while a TKI combined chemotherapy is applicable to EGFR-sensitive patients with concomitant alterations. CtDNA MRD may be a potential biomarker for predicting therapeutic efficacy.

Influence of Jianpizhidong decoction on the behavioral record an bilateral striatal amino acid neurotransmitters in mice with Tourette syndrome disease / 中华行为医学与脑科学杂志

Objective To study the influences of Jianpizhidong decoction(JPZDD) on bilateral striatal amino acid neurotransmitters in mice with Tourette Syndrome (TS) disease and discuss the mechanism of JPZDD.Methods Thirty mice were injected 3,3-iminodipropionitrile (IDPN) with 350 mg· kg-1 once a day for 7 consecutive days except ten mice of the blank control group which were injected with saline.TS mice were randomly divided into three groups:TS model group,JPZDD group (the Chinese herbal group),Tiapride group (the western medicine group).The TS model group and the blank control group were gavaged with saline(0.9％)at 20 ml ·Kg-1,the Tiapride group with Tiapride at 50 mg · kg-1,and JPZDD group with JPZDD at 20 g · kg-1,respectively,once a day for six weeks.Then behavioral recordings were conducted,and the content of glumatic acid (Glu) and γ-aminobutyric acid (GABA) in the bilateral striatum of the mice were detected by using HPLC.Results Behavioral recording indicated that there were significant differences in the Chinese herbal group and the Tiapride group before(1.90 ± 1.80,2.05 ± 1.40) and after(1.15 ± 1.67,1.00 ± 1.08) treatment (P ＜ 0.05).The content of Glu and GABA in TS model group (1858.33 ± 203.00,261.24 ± 47.31) and Tiapride group (1744.53 ± 234.01,258.57 ± 57.64) were higher compared with the blank control group (P ＜ 0.05),and the content of Glu in JPZDD was significantly higher than that in TS model group.There was no statistical difference between other groups(P＞0.05).The ratio of Glu and GABA were lower in the JPZDD,the Tiapride and the model groups than that in the blank control group,but there were no statistical differences between these groups (P＞ 0.05).Conclusion JPZDD can regulate the content of Glu and GABA in the striatum,and keep the dynamic equilibrium,which might be its pharmacodynamic mechanisms for treating TS.

Study on the effect of neutrophil and interleukin-8 on exercise-induced asthma / 中国实用内科杂志

Objective To explore the relationship of neutrophil and interleukin-8(IL-8)with exercise-induced asthma(EIA).Methods From May 15,2001 to Dec 19.2005 the levels of peripheral neutrophil superoxide anion and IL-8 in the blood and the induced sputum from patients with EIA,non EIA and normal control subjects were measured respectively before and after exercises,meanwhile a comparison was made among them.Results Before exercise:the level of neutrophil superoxide anion was slightly higher in EIA group and non EIA group than that in control group;however,the differences were insignificant;the IL-8 and MDA levels in blood and induced sputum were higher in EIA group and non EIA group than those in control group,but there was no significant difference between EIA group and non EIA group;however,they were significantly different between EIA group and control group,non EIA group and control group respectively( P 0.05).Conclusion Oxyradical produced by neutrophil and IL-8 has significant effect on the production of EIA.