Although the efficacy of tyrosine kinase inhibitor (TKI) for the treatment of chronic myeloid leukemia (CML) is obvious, the drug resistance is still inevitable, therefore, TKI drug resistance has become one of the reasons for the failure treatment of CML. According to the literature, about 5 % patients have primary resistance to TKI, and 20 %-30 % patients have secondary resistance to TKI. Current TKI drug resistance molecular mechanisms include the over-expression of bcr-abl, gene mutation, defect of DNA repair mechanism, medicine excretion mediated by ATP-binding cassette translocator, abnormal signaling pathway and bone marrow microenvironment. Meanwhile, the occurrence of drugs, based on the drug resistance mechanism development in preclinical or clinic investigation stage, are likely to provide the possibility for the overcoming of TKI drug resistance. This paper will review the progress of molecular mechanism of TKI drug resistance and the therapy strategy after drug resistance.

OBJECTIVETo observe the effect of Bushen Huatan Recipe (BHR) on the Akt signal pathway in polycystic ovarian syndrome (PCOS) model rats with insulin resistance (IR).

METHODSFifty Wistar female PCOS rats were randomly and equally divided into 5 groups, i.e., the control group, the model group, the low dose BHR group (5.406 g/kg), the medium dose BHR group (10.812 g/kg), and the high dose BHR group (21.624 g/kg), 10 in each group. Levels of fasting blood glucose (FBG) and insulin were detected to calculate homeostasis model assessment of insulin resistance (HOMA-IR). The expression of insulin receptor substrate 1 (IRS-1), glycogen synthetase kinase-3beta (GSK-3beta), glucose transporter 4 (GLUT-4), and peroxisome proliferator activated receptor (PPAR-gamma) mRNA were detected by RT-PCR. The expression of insulin signal transduction molecular kinase B (Akt) was detected by Western blot.

RESULTSCompared with the control group, HOMA-IR and the mRNA expression of PPAR-gamma mRNA significantly increased, the mRNA expression of GSK-3beta, GLUT-4, and IRS-1, protein expression of Akt and p-Akt significantly decreased in the model group (P < 0.05). Compared with the model group, HOMA-IR significantly decreased, the mRNA expression of GSK-3beta, GLUT-4, IRS-1, and Akt protein significantly increased in the high dose BHR group (P < 0.05, P < 0.01). The mRNA expression of p-Akt protein increased more obviously (P < 0.05, P < 0.01). mRNA expression of GSK- 3beta and GLUT-4 significantly increased (P < 0.05), while the mRNA expression of PPAR-gamma significantly decreased in the low and middle BHR groups (P < 0.05). The expression of p-Akt significantly increased in the low dose BHR group (P < 0.05).

CONCLUSIONSIR and abnormal insulin signal pathway existed in PCOS model rats. BHR could improve IR of PCOS rats, which was correlated with regulating protein expression of insulin signal transduction molecules.

Animals ; Drugs, Chinese Herbal ; pharmacology ; therapeutic use ; Female ; Insulin Resistance ; Phytotherapy ; Polycystic Ovary Syndrome ; drug therapy ; metabolism ; Proto-Oncogene Proteins c-akt ; metabolism ; Rats ; Rats, Wistar ; Signal Transduction

Objective To investigate the effect of acute hypervolemic hemodilution(AHHD)on the onset and recovery of muscle relaxation induced by vecuronium.Methods Thirty-two ASA Ⅰ orⅡpatients undergoing elective surgery under general anesthesia were randomly divided into 2 groups(n=16 each):control group and AHHD group.A loading dose of vecuronium 0.1 mg/kg Was given at 10 min after AHHD following tracheal intubatiom The muscular relaxation was maintained at Tl/Tc 5% to 15% by supplement with intravenous vecuroninm.Blood samples were taken at various times during AHHD for chemical analysis.The onset and recovery time of muscular relaxation were recorded.Results Compared with control group ,Hct,Hb and the concentration of TP and Alb were decreased,and the onset and recovery time of vecuronium were shortened in group AHHD(P＜0.05).Conclusion Acute hypervolemic hemodihtion can shorten the onset and recovery of muscle relaxation of vecuronium in patients under general anethesia.

Dental Bonding ; methods ; Dentin ; Dentin-Bonding Agents ; chemistry ; Electricity ; Humans

Objective To compare the efficacy and safety of thrombolysis and anticoagulant therapy for post-traumatic acute submassive pulmonary embolism (PE) in middle-aged and elderly patients.Methods Totally 45 patients with post-traumatic acute submassive pulmonary embolism in our hospital were selected.Patients were divided into thrombolysis group (n =22) and anticoagulation group (n=23) according to their conditions.Symptoms and signs,blood gas analysis,D-dimer,echocardiography,CT pulmonary angiography (CTPA) were performed before and after thrombolysis or anticoagulant therapy.Results There were no significant differences in clinical curative rate between thrombolysis group and anticoagulation group [95.5％ (21/22) vs.91.3％ (21/23),x2 =0.32,P＞0.05],and no case was found dead in both two groups.There was a significant difference in hemorrhage rate between thrombolysis group and anticoagulation group [27.3％ vs.4.3％,x2 =4.53,P ＜ 0.05].At 24 hours after thrombolysis or anticoagulant therapy,the improvement rate of dyspnea,PaO2 level was significantly higher and the pulmonary arterial pressure was significantly lower in thrombolysis group than in anticoagulation group [45.5％ (10/22) vs.17.4％ (4/23),(80.4±8.1) mm Hg vs.(73.6±9.3) mm Hg,(51.2±6.2) mm Hgvs.(60.3±5.7) mm Hg,respectively,all P＜0.05],and there were no statistical significances at other time points between the two groups.Conclusions The clinical curative rate and fatality rate are similar in thrombolysis group versus anticoagulation group.Hemorrhage rate is higher in thrombolysis group than in anticoagulation group.Thrombolysis can relieve dyspnea rapidly,reduce pulmonary artery pressure and make the embolized blood vessels recanalized.Patients with low bleeding risk in a critical condition are suggested to take thrombolysis therapy,while patients with high bleeding risk in a light condition are suggested to take anticoagulant therapy.

Objective To investigate the effect of microRNA-101 (miRNA-101) on atrial fibrosis in human chronic atrial fibrillation (AF). Methods Right atrial appendages were obtained from 59 patients (30 with AF) undergoing cardiac surgery, including 47 patients with valve heart disease and 12 patients with congenital heart disease. The expression of miRNA-101 was determined by quantitative real-time PCR in the right atrial appendages of patients with and without AF. The cell-specific localization of miRNA-101 was detected by in situ hybridization assay. The mRNA and protein expression levels of transforming growth factor β typeⅠreceptor (TGFβRⅠ) and collagen type I (COL1) were determined by quantitative real-time PCR and Western-blot assay, respectively. Collagen in the right atrial appendages was observed by Masson staining assay. Results The expression of miRNA-101 was found to be significantly down-regulated in AF patients compared with patients with sinus rhythm (SR) (P < 0.05). The result of miRNA-ISH showed that miRNA-101, which was highly distributed within the connective tissues of heart, was down-regulated at about 24.9% in patients with AF compared with patients with SR. No significant differences at the mRNA expression level of TGFβRI was found between patients with AF and patients with SR (P > 0.05). But the protein expression of TGFβRI in patients with AF was significantly higher than that of patients with SR (P < 0.05). The mRNA and protein expressionsl of COL1 were significantly higher in patients with AF than thoset of patients with SR (P < 0.05). The collagen was significantly increased in patients with AF than that of patients with SR (P < 0.05). Conclusions Downregulation of miRNA-101 may contribute to atrial fibrosis in human atrial fibrillation by targeting TGFβRⅠ.

Dust ; prevention & control ; Humans ; Occupational Exposure ; prevention & control ; United States ; Workplace

Two-dimensional electrophoresis(2-DE) is an important technique in proteomics research.The 2-DE system for proteome of Monascus ruber was established by comparing and analyzing the infection caused by different kinds of mediums,lysis buffer and the condition of rehydration.By cultivating the Monascus ruber with YES for 6 days,extracting total protein by TCA-acetone,lysis buffer with 8 mol/L urea,2 mol/L thiourea,4 % CHAPS,1 % DTT and 2 % Bio-lyte,an ideal 2-DE map with higher resolution and better legibility was obtained,which laid a foundation for the further studies on proteome of Monascus ruber.

Objective: To investigate the diagnosis and treatment of rapidly growing mycobacteria bloodstream infections.Methods: Based on the two pharmaceutical consultation practice for one case of rapidly growing mycobacteria bloodstream infections after fracture operation, the paper summarized and analyzed the problems in different stages of treatment.Results: The first consultation optimized the dosage of vancomycin according to the patient''s serum concentration and creatinine clearance rate.The second consultation suggested doctors actively perform anti-infection treatment for rapidly growing mycobacteria after the patient''s clinical symptoms and examination results were improved significantly.It is recommended to withdraw anti TB drugs, and the use of clarithromycin combined with amikacin was suitable.The patient was discharged with improved health conditions.Conclusion: Positive intervention and correct diagnosis are the keys for the successful treatment of suspected or definite mycobacteria infection in surgical sites.

Objective: To investigate the effect of electroacupuncture (EA) on cognitive function in D-galactose (D-gal)-induced aging rats, and the correlation between the effect and nucleotide-binding oligomerization domain (NOD)-like receptor protein 3 (NLRP3)-ASC-Caspase-1 signaling pathway. Methods: Forty-six male Sprague-Dawley (SD) rats were randomly divided into a control group (n=10), a model group (n=12), an EA-7 d group (n=12) and an EA-21 d group (n=12). Except the control group, the other three groups received 42 consecutive days of intraperitoneal injection of D-gal to establish aging rat models with cognitive dysfunction. The control group received the same amount of normal saline via intraperitoneal injection. Two EA groups were given EA therapy for 21 consecutive days (began from the 22nd day of modeling) or 7 consecutive days (began from the 36th day of modeling) accordingly at Dazhui (GV 14), Baihui (GV 20), Shenshu (BL 23) and Zusanli (ST 36). After modeling/ intervention, all four groups received behavioral evaluations by Morris water maze (MWM) test, novel object recognition (NOR) test and step-down passive avoidance (SDPA) test followed by the Western blot (WB) detection of the expression levels of hippocampal NLRP3 inflammasome-associated proteins NLRP3, ASC and Caspase-1. Results: MWM (place navigation test, PNT) results showed that the escape latency in the model group was significantly longer than that in the other three groups (P<0.05), and there was no significant difference among the other three groups on the 1st day of the test (P>0.05). From the 2nd day to the 4th day of the test, there was no significant difference between the EA-21 d group and the control group (P>0.05) in the escape latency; the escape latency was significantly shorter in the EA-21 d group than in the model group and the EA-7 d group (P<0.05). MWM (spatial probe test, SPT) results showed that the time spent in the target quadrant was significantly shorter and platform crossover number was significantly lower in the model group than in the other three groups (P<0.05). The time spent in the target quadrant was longer in the EA-7 d group than in the model group (P<0.05), but was shorter than that in the control group and the EA-21 d group (P<0.05). There was no significant difference in the swimming speed among the four groups (P>0.05). NOR results showed that there was no significant difference in the recognition ratio between the EA-7 d group and the EA-21 d group (P>0.05), and the recognition ratio was significantly higher in the two EA groups than in the model group (P<0.05), but was lower than in the control group (P<0.05). SDPA results showed that the electric shock number was higher in the model group than in the other three groups (P<0.05), and the differences among the other three groups were statistically insignificant (P>0.05). The model group had the shortest step-down latency, followed by the EA-7 d group, the EA-21 d group and the control group in order (P<0.05). The WB results indicated that the expression level of NLRP3 was significantly lower in the control group and the EA-21 d group than in the model group and the EA-7 d group (P<0.05). The expression levels of ASC and Caspase-1 were significantly higher in the model group than in the other three groups (P<0.05), and there was no significant difference among these three groups (P>0.05). Conclusion: NLRP3 inflammasome may be involved in the development of cognitive decline in aging rats; 7 consecutive days of EA intervention can partially improve the cognitive impairment in aging rats though the effect is rather limited; 21 consecutive days of EA intervention may improve the learning and memory abilities in aging rats via downregulating the expression levels of NLRP3 inflammasome-associated proteins in hippocampus.