Objective To investigate the expression of BRCA1 in chemosensitive and chemoresistant ovarian cancer specimens,so as to provide a novel insight into the epigenetic mechanism involved in BRCA1 transcription. Methods Serous ovarian cancer patients(10 chemosensitive and 10 chemoresistant cancer)were enrolled for the study. BRCA1 levels was analyzed by real?time quantitative PCR. The methylation levels of BRCA1 core promoter(sites 1?4)was determined by pyrosequencing. Regression analysis was used to examine the possible relationship between BRCA1 levels and the methylation levels of sites 1?4 in ovarian cancer specimens. Results Compared to chemosensitive ovarian cancer tissues,BRCA1 levels were increased,but the methylation levels of BRCA1 core promoter(sites 1?4)were decreased in chemoresistant ovarian cancer tissues. How?ever,it is interesting to note that only a significant inverse correlation was observed between BRCA1 levels and the methylated levels of site 4 (r=-0.612,P<0.05). Conclusion Our findings imply that the methylation levels of site 4 in the core promoter of BRCA1 may be widely involved in the regulation of BRCA1 expression and chemosensitivity in ovarian cancer.

Objective To study the curative effect and side effect of thalidomide incorporation with NP in treatment of Ⅲ/Ⅳ lung cancer. Methods 36 lung cancer patients were randomly divided into three groups. The patients in experimental group were treated by NP plus thalidomide while without thalidomide in the control group. The difference between the first experimental group and second group is that the above used DDP followed with lobaplatin. The beginning dose of thalidomide was 100 mg/d, increase 50 mg/d every week till 400 mg/d, maintain for at least three months. Results The first experimental group had 4 partial relief cases (34.0 %), 5 improved cases(33 %), total efficacy rate was 34.4 %(4/15), clinical benefice rate 49 %(7/ 15), and the second group was 38 %(4/11), 27 %(3/11), 38 %(4/11), 55 %(6/11). All without significant difference. Conclusion It would be valuable to do clinical research further and widespread popularization study for evaluation of Thalidomide incorporation with NP in treatment of Ⅲ/Ⅳ lung cancer.

Objective To report the functional reconstruction and rehabilitation for a patient who under- went allograft for both of his forearms and hands.Methods One male patient underwent allograft for both of his forearms and hands in October 2002 in our department to reconstruct his hand functions.The allografted hands were intervened with an integrated rehabilitation program,which involved administration of immunosuppressants,post- operative monitoring,postoperative functional training,massage,physiotherapy,orthosis,performance training, sensation training,secondary operation and mental rehabilitation.The patient was followed up for 4 years.Results The forearms and hands of the patient were in good shape and regained nearly normal sensation.The distance of two-point-discrimination was 2.5 cm to 4.0cm.The TAM (total active motion) of fingers was fine.The patient could look after himself well and were healthy in psychology.Conclusion An integrated rehabilitation program can yield satisfactory results in the management of allografted forearms and hands.

Objective To discuss the effects of multimodal combination dialysis on Klotho protein, fibroblast growth factor-23 (FGF-23) and brain natriuretic peptide (BNP) in patients with maintenance hemodialysis (MHD). Methods A randomized controlled trial (RCT) was conducted. 120 patients who was diagnosed with chronic renal failure (CRF) uremia receiving MHD over 3 months admitted to Blood Purification Centre of Department of Nephrology of the Second People's Hospital of Guiyang from December 2015 to December 2016 were enrolled, who were randomly divided into hemodialysis (HD) group (HD for 8 times a month), HD + hemofiltration (HF) group (HD for 8 times a month + HF once a month), and HD + HF + hemoperfusion (HP) group (HD for 8 times a month + HF for 4 times a month + HP once a month), with 40 patients in each group. Before and after treatment for 6 months and 12 months, blood was taken from venous circuit tube, the serum Klotho protein and FGF-23 levels were determined by enzyme linked immunosorbent assay (ELISA), and the serum BNP level was determined by electrochemiluminescence. Results 120 patients with MHD were enrolled in the final analysis without withdrawal. There were no significant differences in the levels of Klotho protein, FGF-23, or BNP before enrollment among the three groups (all P > 0.05). Compared with those before enrollment, the levels of serum Klotho protein after enrollment in three groups showed a sustained upward tendency, which were higher in HD + HF + HP group than in HD + HF group and HD group (μg/L: 2.59±0.61, 1.63±0.35, 1.13±0.26 at 6 months, F = 119.374, P = 0.000; 6.98±1.21, 3.57±1.03, 2.12±0.43 at 12 months, F = 275.675, P = 0.000); the levels of FGF-23 showed a sustained downward tendency, which were lower in HD + HF + HP group than in HD + HF group and HD group (ng/L: 69.22±38.26, 132.28±61.18, 178.50±74.64 at 6 months, F = 33.509, P = 0.000; 32.81±17.32, 87.93±43.27, 146.33±69.28 at 12 months, F = 55.466, P = 0.000);the BNP showed a similar tendency as FGF-23 (ng/L: 4083.39±2864.53, 7245.69±4643.81, 7969.12±5360.85 at 6 months, F = 8.758, P = 0.000; 1521.86±894.63, 4554.32±1969.84, 5013.89±2033.64 at 12 months, F = 49.003, P = 0.000). Conclusion Multimodal combination dialysis can increase the Klotho protein level, and decrease the levels of FGF-23 and BNP in MHD patients with CRF uremia.

The effects of angiotensin II receptor antagonist losartan on elastic properties of aorta in patients with mild to moderate essential hypertension were assessed. The ascending aortic distensibility in 26 patients (48 +/- 3 years) with mild to moderate essential hypertension before and after 12 weeks of treatment with losartan (50 mg/day) was evaluated by using two-dimensional echocardiography. M-mode measurements of aortic systolic (Ds) and diastolic diameter (Dd) were taken at a level approximately 3 cm above the aortic valve. Simultaneously, cuff brachial artery systolic (SBP) and diastolic (DBP) pressures were measured. Aortic pressure-strain elastic modulus (Ep) was calculated as Dd x (SBP-DBP)/(Ds-Dd) x 1333 and stiffness index beta (beta) was defined as Dd x Ln (SBP/DBP)/(Ds-Dd). Blood pressure significantly decreased from 148 +/- 13/95 +/- 9 mmHg to 138 +/- 12/88 +/- 8 mmHg (systolic blood pressure, P = 0.001; diastolic blood pressure, P = 0.003). There was no significant difference in pulse pressure before and after treatment with losartan (53 +/- 10 mmHg vs 50 +/- 7 mmHg). The distensibility of ascending aorta increased significantly as showed by the significant decrease in pressure-strain elastic modulus from 4.42 +/- 5.79 x 10(6) dynes/cm2 to 1.99 +/- 1.49 x 10(6) dynes/cm2 (P = 0.02) and stiffness index beta from 27.4 +/- 32.9 to 13.3 +/- 9.9 (P = 0.02). Although there was a weak correlation between the percent changes in pressure-strain elastic modulus and stiffness index beta and that in diastolic blood pressure after losartan treatment (r = 0.40, P = 0.04 and r = 0.55, P = 0.004, respectively), no correlation was found between the percent changes in pressure-strain elastic modulus and stiffness index beta and that in systolic blood pressure (r = 0.04, P = 0.8 and r = 0.24, P = 0.2, respectively). Our study demonstrated that angiotensin II receptor antagonist losartan has a beneficial effect on aortic distensibility in patients with mild to moderate essential hypertension and this effect is partly independent of blood pressure reduction.
Aorta/*physiopathology ; Aorta/ultrasonography ; Echocardiography ; Elasticity ; Hypertension/*drug therapy ; Hypertension/*physiopathology ; Hypertension/ultrasonography ; Losartan/*therapeutic use ; Receptors, Angiotensin/*antagonists & inhibitors

To assess the left ventricular regional relaxation abnormalities in patients with hypertrophic cardiomyopathy (HCM) by quantitative tissue velocity imaging (QTVI), Doppler echocardiography and QTVI were performed in HCM (n=10) and healthy subjects (n=11) at apical long-axis, two-chamber and four-chamber views. Regional early diastolic velocity (rVe) and regional atrial contraction (rVa) were measured at each segment of ventricular middle, basal and annular levels. Mean rVe and mean rVa at three levels as well as mean rVe/rVa ratio were calculated. Our results showed that transmitral inflow peak velocities during early diastole (E) and atrial contraction (A) were also measured and E/A ratio was calculated. The rVe of all left ventricular segments in HCM were lower than those in healthy subjects (P<0.05), but compared with healthy subjects majority of rVa in HCM were not different except inferior wall and anterior wall. E between HCM and healthy subjects was different (P=0.036), while mean rVe between them was significantly different (P<0.0001). Mean rVa and mean rVe/rVa of three levels were lower in HCM than in healthy subjects (P<0.05), but there were no differences in A and E/A between them (P=0.22, P=0.101). Left ventricular regional myocardial relaxation is reduced in HCM. Transmitral inflow E and A are influenced by preload, relaxation of myocardium and atrial contraction, etc., while rVe and rVa reflect myocardial relaxation function independently. QTVI is more sensitive and more accurate than conventional Doppler imaging for characterizingregional diastolic properties in HCM.
Cardiomyopathy, Hypertrophic/*physiopathology ; Cardiomyopathy, Hypertrophic/*ultrasonography ; Diastole ; Echocardiography, Doppler, Color/methods ; Hypertrophy, Left Ventricular/*physiopathology ; Hypertrophy, Left Ventricular/ultrasonography ; Ventricular Function, Left

Related substances in pharmaceutical formulations are associated with their safety, efficacy and stability. However, there is no overall study already published on the assessment of related substances in the Compound Ketoconazole and Clobetasol Propionate Cream. In this work, a reliable HPLC-TOF-MS qua-litative method was developed for the analysis of related substances in this preparation with a quick and easy extraction procedure. Besides the active pharmaceutical ingredients, two compounds named ke-toconazole impurity B′ optical isomer and ketoconazole impurity E were identified. Furthermore, a new HPLC method for qualitative and quantitative assessment on related substances and degradation pro-ducts, which were found in the stability test, was established and validated. The single standard to determine multi-components method was applied in the quantitative analysis, which was an effective way for reducing cost and improving accuracy. This study can provide a creative idea for routine analysis of quality control of the Compound Ketoconazole and Clobetasol Propionate Cream.

OBJECTIVETo explore the effects of arecoline on hepatic insulin resistance in type 2 diabetes rats and to elucidate its possible mechanism.

METHODSForty five Wistar rats were fed with high fructose diet for 12 weeks to induce type 2 diabetic rat model. rats were randomly divided into 5 groups (n = 8): control group, model group and model group were treated with different dose (0, 0.5, 1, 5 mg/kg) of arecoline. After 4 weeks, the fasting blood glucose, blood lipid and insulin level measured , mRNA expression of liver constitutive androstane receptor (CAR), pregnane X receptor (PXR), glucose-6-phosphatase (G6Pase), phosphoenolpyruvate carboxykinase (PEPCK), interleukin-6 (IL-6) and tumor necrosis factor-alpha (TNF-alpha) were detected by reverse transcription polymerase chain reaction (RT-PCR), the protein expression of p-AKT and glucose transporter4 (GLUT4) were detected by Western blot.

RESULTS1.5 mg/kg arecoline could significantly decrease the level of fasting blood glucose, blood lipid, blood insulin level and liver G6Pase, PEPCK, IL-6, TNF-alpha mRNA level in type 2 diabetes rats. 1.5 mg/kg arecoline also could significantly increase CAR, PXR mRNA level and p-AKT and GLUT4 protein expression.

CONCLUSIONArecoline improved hepatic insulin resistance in type 2 diabetes rats by increasing the mRNA levels of CAR and PXR leading to the creased glucose metabolism and inflammation related genes expression.

Animals ; Arecoline ; pharmacology ; Diabetes Mellitus, Experimental ; metabolism ; Diabetes Mellitus, Type 2 ; metabolism ; Glucose Transporter Type 4 ; metabolism ; Glucose-6-Phosphatase ; metabolism ; Insulin Resistance ; Interleukin-6 ; metabolism ; Intracellular Signaling Peptides and Proteins ; metabolism ; Liver ; drug effects ; metabolism ; Male ; Phosphoenolpyruvate Carboxykinase (GTP) ; metabolism ; Proto-Oncogene Proteins c-akt ; metabolism ; Rats ; Rats, Wistar ; Receptors, Cytoplasmic and Nuclear ; metabolism ; Receptors, Steroid ; metabolism ; Tumor Necrosis Factor-alpha ; metabolism

To explore the effect of sinomenine on the nitric oxide (NO)/neural nitric oxide synthase (nNOS) system in the cerebellum and spinal cord of morphine-dependent and morphine-withdrawal Kunming mice, mice were subjected to injection of morphine with an increasing dose for 5 d, and then were treated with sinomenine (40 mg/kg, i.p.) for another 5 d. Naloxone was used to develop acute withdrawal, and the withdrawal syndromes, including teeth chattering, twisting, straightening, sneezing and ptosis, were investigated. nNOS mRNA expressions in the cerebellum and spinal cord were determined by semi-quantitative RT-PCR. nNOS activity and NO level were determined by the chemistry-colorimetry and nitrate reductase-reduction, respectively. The results obtained were as follows: (1) Sinomenine restored the decrease in body weight and alleviated the signs of morphine-withdrawal in mice. (2) Sinomenine also reduced the increases in nNOS mRNA expression and nNOS activity resulting from morphine-dependence, and simultaneously attenuated the high level of NO in both tissues following morphine-withdrawal. (3) Administration of sinomenine alone did not develop physical dependence in mice. The results obtained indicate that sinomenine may attenuate morphine addiction and significantly alleviate morphine-withdrawal symptoms, and the mechanism may be associated with the effect of sinomenine on the NO/nNOS system in the cerebellum and spinal cord.
Animals ; Body Weight ; drug effects ; Cerebellum ; drug effects ; metabolism ; Male ; Mice ; Morphinans ; pharmacology ; therapeutic use ; Nitric Oxide ; analysis ; Nitric Oxide Synthase Type I ; genetics ; metabolism ; RNA, Messenger ; analysis ; Reverse Transcriptase Polymerase Chain Reaction ; Spinal Cord ; drug effects ; metabolism ; Substance Withdrawal Syndrome ; drug therapy ; metabolism

Objective To investigate the accuracy of low-dose dual-source computed tomography (DSCT) coronary angiography in the step-and-shoot (SAS) mode for the diagnosis of coronary artery stenosis in comparison with conventional coronary angingraphy (CCA).Methods Prospective multiple-center study, 46 patients[mean age(58±9) years;bedy mass index(BMI) (25±3) kg/m2]underwent both DSCT in the SAS mode and CCA within 14 days.The inclusion criteria for contrast-enhanced CT: (1) heart rate less than 65 times/rain (bpm).(2) regular sinus rhythm, heart rate fluctuations within the range of 6 bpm. (3) holding breath well, breath-hold time is about 12-15 s.The exclusion criteria:(1) allergy to iodinecontaining contrast medium, nephropathy (serum creatinine level 120 μmol/L), heart failure and serious arrhythmias.(2) patients with coronary stents or bypass grafts.(3) heart rate can not be controlled very well (4)the patient could not take nitroglycerin.(5)BMI 30 kg/m2.(6) other heart disease: carcliomyopathy, valvular disease etc.Sensitivity, specificity, negative (NPV) and positive predictive value (PPV) were determined with CCA as standard of reference.The Kappa value between the two modalities and the two observers was calculated.Radiation dose values were measured.Results Mean heart rate during scanning was (61±6)bpm.99.19% (614/619) coronary segments were depicted with a diagnostic image quality. The vessel-based sensitivity, specificity, PPV, and NPV for the diagnosis of coronary artery stenosis were 96.2% (75/78), 88.2% (60/68), 90.4% (75/83), and 95.2% (60/63), respectively.The Kappa value between the two modalities was 0.848 (P=0.000).The mean effective dose of the SAS-CTCA was (2.95± 0.96) rosy(1.26-4.32 mSy).Conclusion In selected patients, DSCT coronary angiography in the SAS mode have good image quality, which allows for the accurate diagnosis of coronary stenosis at a low radiation dose.