ABSTRACT
Objective:To observe the efficacy of Dabigatran etexilate anticoagulation therapy and analyze its influencing factors in elderly patients.Methods:The clinical data of the elderly patients using Dabigatran etexilate anticoagulation for prevention or treatment of thrombosis in the Department of Geriatrics, Peking University First Hospital were collected.Changes of coagulation indexes and its influencing factors were analyzed when taking Dabigatran in different doses.Results:A total of 142 patients receiving Dabigatran therapy were collected, with an average age of(79.0±7.5)years.Among them, 128 patients had atrial fibrillation and 14 had deep venous thrombosis and/or pulmonary embolism.After taking Dabigatran, the trough values of activated partial thromboplastin time(APTT)and thrombin time(TT)were increased significantly in all patients compared with that before administration( P<0.001). In patients taking Dabigatran 110 mg once a day, APTT was(32.4±3.0)s before administration, with a trough value of(41.4±5.4)s and a peak value of(53.9±9.8)s.In patients taking Dabigatran 110 mg twice a day, APTT was(31.0±3.1)s before administration, with a trough value of(42.4±5.5)s and a peak value of(48.7±7.3)s.Compared with patients taking Dabigatran 220 mg/d, those who took Dabigatran 110 mg/d were older( P<0.0001), often women( P<0.0001), had lower body weight( P=0.001), body mass index( P=0.018)and creatinine clearance rate( P<0.001), and higher basal( P=0.008)and peak values( P=0.002)of APTT, but with similar trough values.Multivariate analysis showed that the APTT trough values were significantly related with APTT basal value( β=0.885, P<0.001), creatinine clearance rate( β=-0.121, P<0.001), dosage of Dabigatran( β=0.037, P<0.001)and combined amiodarone( β=3.784, P=0.022). Conclusions:There are individual differences in the anticoagulant effect of Dabigatran etexilate.The APTT trough value is higher in patients with high APTT basal value, high Dabigatran dose, low creatinine clearance rate and combined use of amiodarone.Dabigatran 110 mg/d was often used in women, elderly patients, and those with low body weight, and decreased renal function, and with a similar trough value and a high peak value of APTT compared with patients on Dabigatran 220 mg/d.
ABSTRACT
Targeted therapy of epidermal growth factor receptor tyrosine kinase inhibitor (EGFR-TKIs) has been the standard modality as first-line treatment of advanced EGFR-mutated non-small cell lung cancer (NSCLC). The third-generation EGFR-TKIs has been approved to overcome the EGFR T790M mutation in patients resistant to the first-or second-generation TKIs, which brings more survival benefits for patients with advanced NSCLC. Unfortunately, acquired resistance inevitably develops after application of approximately 10 months. Heterogeneities of the tumor determines the diversity of resistance. Mechanisms of resistance to the third-generation TKIs includs EGFR-dependent pathway (such as new EGFR mutations, T790M reduction/disappearance and EGFR amplification, etc.) and EGFR-independent pathway (such as bypass pathway activation and histological transformation, etc.). In this paper, we reviewed principle mechanisms of acquired resistance to third-generation EGFR-TKIs.
Subject(s)
Humans , Carcinoma, Non-Small-Cell Lung , Drug Therapy , Genetics , Pathology , Drug Resistance, Neoplasm , ErbB Receptors , Genetics , Metabolism , Lung Neoplasms , Drug Therapy , Genetics , Pathology , Protein Kinase Inhibitors , Pharmacology , Therapeutic Uses , Signal TransductionABSTRACT
Objective:To evaluate the expression of peroxisome proliferator-activated receptor ?(PPAR?) and nuclear factor-?B(NF-?B) in lungs in patients with pulmonary fibrosis,and to explore their effect on the pathogenesis of pulmonary fibrosis.Methods: Immunohistochemical technology was performed to investigate the PPAR? and NF-?B expression in lung specimens from 16 cases of pulmonary fibrosis and 10 cases of normal controls.Results: The positive score of PPAR?(0.35?0.08) in fibrosis group was lower than that in control group(0.42?0.04,P
ABSTRACT
Objective:To explore the expression levels of MHCⅡ molecules and its regulator genes CⅡTA on bleomycin-induced pulmonary fibrosis in rats,and to investigate the underlying immunologic mechanisms of pulmonary fibrosis.Methods:The rats were treated with either a single intratracheal bleomycin injection(fibrosis group)or a normal saline injection(control group).The pathologic changes of lung tissues stained with HE and Masson were observed,and the contents of hydroxyproline were detected on the 7th and 28th day respectively after bleomycin administration.The expression of MHCⅡ molecules in the lung tissues was evaluated with immunohistochemistry techniques,and the percentage of MHCⅡ+ cells was measured.The amounts of total CⅡTA and typeⅠ,Ⅲ and Ⅳ CⅡTA mRNA of lung tissues were measured by real-time PCR using Taqman probe.Results:(1)The percentage of MHCⅡ+ cells in lung tissues increased significantly in fibrosis group compared with that of control group on the 7th day and the 28th day[(0.10?0.03)vs(0.06?0.02),P0.05];In fibrosis group,type Ⅳ CⅡTA mRNA was 667.3% [(2.98?0.92)vs(0.39?0.15),P