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

Object:To find out college students' perceptions about counseling.Methods:By using a questionnaire about college students' view of counseling,875 college students of Zhejiang University from grade 1 to grade 4 were tested.Results:Most students acknowledged that counseling deals with mental issues and disorders. They were willing to help clients,and prefer counselors who are like their friends and family members.They agreed that counseling is helpful and,prefer one-hour sessions,which are free of charge.

Objective To construct digital operating room in the hospital to enhance the efficiencies of operation and anesthesia.MethodsThe overall architecture of digital operating room was designed based on functional requirements survey,which was composed of an operating and anesthesia management system,an operation demonstration system,an operation information notice system and a department management system.Results Digital operating room realized the connection between all the operating and anesthesia devices and whole-course pre-,intra-and post-operative management of the patients,which implemented integration and data sharing with HIS,PACS,LIS and EMRS.Conclusion Digital operating room enhances medical service,teaching,learning and research during operation and anesthesia,facilitates evidence-based medicine and improves doctor-patient relationship.

Objective To explore the mechanism of therapeutic action of needle knife “regulating sinews and treating bones” on knee osteoarthritis (KOA) by observing the effect of needle knife intervention on KOA rabbit behaviors, mechanical characteristics of patellar ligament (PL), and expressions of interleukin-4 (IL-4), matrix metalloproteinase-3 (MMP-3) and aggrecan in knee cartilages.Methods Forty New Zealand rabbits were randomly allocated to blank, model, needle knife and electroacupuncture groups, 10 rabbits each. A rabbit model of KOA was made by the modified Videman method of immobilization in extension position. After model making, the needle knife and electroacupuncture groups received needle knife and electroacupuncture treatments, respectively. A behavioral assessment was made using the modified Lequesne MG knee grade evaluation method in every group after model making and treatment. The samples were taken after treatment. PL tension, stress relaxation and creep state were tested using a Bose Electro Force 3300 protracted test machine. Cartilage cell IL-4 expression was examined by ELISA. MMP-3 mRNA and aggrecan mRNA expressions were detected by real-time PCR.Results After model making, there was a statistically significant difference in the Lequesne MG score between the model and blank groups (P<0.01); there was no statistically significant difference in the Lequesne MG score between the needle knife or electroacupuncture group and the model group (P>0.05). There was a statistically significant post-treatment difference in the Lequesne MG score between the needle knife or electroacupuncture group and the model group (P<0.01,P<0.05) and between the needle knife and electroacupuncture groups (P<0.05). There were statistically significant post-treatment differences in PL maximum stress, maximum displacement, elastic modulus, stress relaxation rate and creep rate between the model and blank groups (P<0.01,P<0.05). There were statistically significant post-treatment post-treatment differences in PL maximum stress, maximum displacement, elastic modulus, stress relaxation rate and creep rate between the needle knife and model groups (P<0.01,P<0.05). There was a statistically significant post-treatment difference in elastic modulus between the electroacupuncture and model groups (P<0.01). The IL-4 content and aggrecan mRNA expression decreased significantly and MMP-3 mRNA expression increased significantly in the model group after model making and there were statistically significant differences compared with the blank group (P<0.01,P<0.05). After treatment, the IL-4 content increased significantly in the needle knife and electroacupuncture groups compared with the model group (P<0.01,P<0.05) and aggrecan mRNA expression tended to increase in the two groups. The regulation of aggrecan mRNA and MMP-3 mRNA expressions was better in the needle knife group than in the electroacupuncture groups, but there was no statistically significant difference compared with the model group (P>0.05).Conclusion The mechanism of action of needle knife treatment on KOA may be that it improves ligament mechanical characteristics, regulates intra-articular stress environment, and modulates aggrecan mRNA and MMP-3 mRNA expressions and inhibits cartilage degeneration through IL-4 mechanical signal pathway, to produce the therapeutic effect of “regulating sinews and treating bones”.

Objective Pathogen and antimicrobial susceptibility in children with bacterial meningitis were reviewed.Methods The positive cultures of cerebrospinal fluid samples or blood samples and its antimicrobial susceptibility were analyzed in 401 patients with the clinical diagnosis of bacterial meningitis.Results 401 cases cerebrospinal fluid samples and blood samples submitted to microbiology laboratory, 97 cases (24%) were microscopically and culturally proven to be bacterial meningitis. The most frequent pathogen was staphylococcus aureus (28%), followed by the streptococcus pneumoniae (19%) and escherichia coli (13%). Pediococci as conditioned pathogen, were found in purulent meningitis patients. One of the isolates of Staphylococcus aureus was simultaneously resistant to both vancomycin and teicoplanin. Three isolates showed simultaneous resistance to imipenem/cilastatin.Conclusions Staphylococcus aureus as the predominant pathogens of pediatric ranks first among pediatric patients of purulent meningitis. Serious drug resistance of isolated pathogenic bacteria and its in antimicrobial susceptibility in the bacterial meningitis should be considered in clinical therapy.

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.

AIM: To study the effect and mechanism of all-trans retinoic acid (atRA) on neural stem cell (NSCs) proliferation and differentiation from new born Sprague- Dawley rat striatum. METHODS: NSCs were isolated from the brains of new born Sprague-Dawley rat striatum, and the features of cells were characterized by immunofluorescence staining. The effects of different culture medium on cell cycle distribution and proliferation of NSCs were determined by flow cytometry (FCM) . The effects of atRA on differentiation of NSCs were determined by immunofluorescence staining and classified count of differentiated cells. RESULTS: FCM assay indicated that atRA inhibited the proliferation of NSCs. The percentage of cells in G0/G1 phase in atRA treatment group was significantly higher than that in control, and the proliferation index (PI) was significantly low. The percentage of neurons differentiated from NSCs in atRA group was 2.5 times of the control group after induced by adding 10% FCS in culture medium. CONCLUSION: atRA counteracts the effects of bFGF on the promotion of mitosis and inhibition of differentiation of NSCs. atRA also promotes NSCs to differentiate into neurons in vitro.

Objective To investigate the relationship between CRP and CK-MB among acute and stable patients with COPD in Nanjing city. Methods Using case-control design, 81 COPD patients and 71 normal controls were selected. Both fasting venous and arterial blood samples were collected for COPD patients at the acute and the stable stage separately, while fasting venous blood samples were collected for controls during medical examination. The concentrations of CRP, CK-MB or PaO2 of all blood samples were examined. Results The concentration of CRP and CK-MB were significantly higher among stable COPD patients (7.18?5.62, 10.92?5.33; respectively) than those among controls(3.00?0.91, 3.11?1.46; respectively), while acute patients (51.22?24.53,30.06?16.68; respectively) got much higher concentration of CRP and CK-MB than stable patients did. However, PaO2 was significantly higher among stable COPD patients than that among acute patients. For acute COPD patients, the concentration of CK-MB positively correlated with CRP, while PaO2 negatively correlated with CRP and CK-MB separately. Conclusions CRP and CK-MB were sensitive predictors of COPD status to the transition from stable to acute stage of COPD, and both negatively correlated with PaO2 among these sample COPD patients.

Bile Duct Neoplasms ; pathology ; surgery ; Bile Ducts, Intrahepatic ; Cholangiocarcinoma ; pathology ; surgery ; Humans