Aim To investigate the combined pharmacokinetic-pharmacodynamic(PK-PD) model of irbesartan in healthy Chinese male volunteers. Methods Eighteen healthy male volunteers received 300 mg irbesartan tablet orally. The plasma drug concentration (C_p) was determined by HPLC and pharmacologic effects, including SBP, DBP and HR, were measured simultaneously. The pharmakinetic and PK-PD model parameters were calculated. Results The pharmacokinetic profiles were best fitted a two-compartment open model. There was a hysteresis loop between effects and plasma concentrations. The relationship between effects and effect compartment concentrations of drugs could be represented by the Sigmoid-E_ max model. Conclusion We successfully eatablished the PK-PD model of irbesartan in healthy male volunteers. These findings may provide a more rational basis for patient-specific dosage individualization.

Objective A retrospective study was carried out to investigate the survival rate of nasopharyngeal cancer patients after the combined treatment of chemoradiotherapy and Chinese herbal medicine. Methods Based on the will of the patients, 230 cases were divided into treatment group (N=107) and control group (N=123). Both groups received chemoradiotherapy, and the treatment group was additionally given oral use of Chinese herbal medicine over 180 doses per year, and the treatment lasted over 2 years. The survival rate was calculated by Kaplan-Meier estimator, and the Kaplan-Meier plot for the two groups was compared. Results (1) In the treatment group, the one-year, 3-year and 5-year survival rate was 99.1%, 86.4%, 72.5%, and was 95.9%, 73.5%, 58.3% respectively in the control group. The Kaplan-Meier plot showed that significant difference of patient survival was presented in the two groups ( P<0.01) . ( 2) The results of hierarchical group analysis of 230 nasopharyngeal cancer patients showed higher survival rate can be achieved in the T3-4 and N0 poorly-differentiated squamous carcinoma patients aged 50 years or more at the stage Ⅲ-Ⅳ in the treatment group than that in the control group, and the statistical differences were significant ( P<0.05 or P<0.01). Conclusion Chemoradiotherapy combined with Chinese herbal medicine can increase the survival rate, and prolong life span of the nasopharyngeal carcinoma patinets, in particular for the T3-4 and N0 poorly-differentiated squamous carcinoma patients aged 50 years or more at the stageⅢ-Ⅳ.

Objective To investigate the effects of acidosis on the current change of transient receptor potential channel M7 (TRPM7) and collagen production in mouse cardiac fibroblast (MCFs), and to explore the pathophysiological function of TRPM7 on the cardiac fibrosis. Methods (1) The model of MCFs was established and isolated. (2) MCFs was subcuhured. (3) Patch clamp technique was used to observe the current characteristics of TRPM7 in low PH solutions. (4) The influence of acidic condition on Ca2+ influx in MCFs was recorded by calcium fluorescent indicators. Results (1) There was a high level expression of TRPM7 in MCFs and the electrophysiological characteristics of TRPM7-like (TRPM7L) was similar to that of TRPM7. (2) Ca2+ influx was increased in acidic condition, and the F340/F380 ratio was increased from 1.0 to 4. 6 at pH 4.0 compared with pH 7.0 (t=2.72, P<0.01). Conclusions (1) TRPM7 is the molecular basis of the native TRPM7L in MCFs and TRPM7L plays an important role in Ca2+ influx. (2) The pathophysiological function of MCFs is influenced by regulation of Ca2+ influx mediated by TRPM7L in the condition of acidosis.

Objective To investigate the changes of TRPM 7-like current in mouse cardiac fibroblast(CFs) after myocardial infarction and the effect of myocardial ischemia on the TRPM 7 expression and current. Methods (1) The model of myocardial infarction was made and CFs were isolated;(2) CFs were cultured and infected by TRPM 7 siRNA;(3) The effects of myocardial ischemia on TRPM 7 current were recorded by whole cell patch clamp technique;(4) The influences of myocardial isehemia on Ca2+ influx in CFs were recorded by Ca2+ fluorescence imaging. (5) The effects of ischemia on total collagen content of CFs were studied. Results (1) Ca2+ inward current of CFs was increased after myocardial infarction [(16.2±1.7) vs. (7.4±0.7) pA/pF, P<0.053];(2) TRPM 7 current was reduced by 90% after siRNA infection;(3) The total collagen content of CFs after ischemia was approximately 2.3-fold higher than basic value. Conclusions Ca2+ influx in CFs plays an important role in the pathophysiological process of myocardial fibrosis.

Child ; Evidence-Based Medicine ; Humans ; Nephritis ; diagnosis ; etiology ; therapy ; Practice Guidelines as Topic ; Purpura ; complications ; diagnosis ; therapy

Humans ; Infant, Newborn ; Infant, Premature ; Infant, Premature, Diseases ; microbiology ; prevention & control ; Mycoses ; prevention & control

Objective To compare the clinical diagnostic value of ultrasound and magnetic resonance imaging (MRI) in breast cancer.Methods Ultrasound and MRI were performed in patients with breast disease.The postoperative pathological examination results were seemed as diagnostic criteria.The diagnostic accuracy was analyzed in two kinds of imaging examination.Results The diagnostic accuracy of MRI in breast cancer(86.9％) was significantly higher than the accuracy of ultrasonic diagnosis(39.3％),the sensitivity and specificity of MRI were significantly higher than those in ultrasonic diagnosis,the rate of missed diagnosis and misdiagnosis rate of MRI were lower than those of ultrasonic diagnosis,the differences were statistically significant (x2 =6.583,12.573,4.892,23.175,8.649,all P ＜ 0.05).Conclusion Ultrasound and MRI have high ability in diagnosis of breast cancer.MRI diagnostic efficacy has more advantages,but the ultrasound is convenient to operate and repeate inspection,can be used in screening.

Objective To investigate the effects and mechanism of IL-6 on the epithelial to mesenchymal transition of human pancreatic cancer cells.Methods IL-6 was added into the culture media of human pancreatic cancer cells Capan-2,SW1990,and STAT3-siRNA-SW1990.Cell growth was measured by MTT assays.STAT3,p-STAT3,Snail,Twist,and E-cadherin mRNA and protein expression were examined using real-time fluorescence quantitative polymerase chain reaction (RT-PCR)and Western blot,respectively.The invasion abilities of SW1990 and Capan-2 cells were determined by a cell invasion assay in vitro.Results Our results showed that 100 μg/L of IL-6 significantly promoted the growth and invasion abilities of Capan-2 and SW1990 cells (P＜0.05).The use of IL-6 not only markedly increased the protein expression of P-STAT3 and Snail,but also greatly decreased the mRNA and protein expression of E-cadherin.The use of IL-6 can not change the mRNA and protein expression of Snail and E-cadherin.Conclusion Activation of the STAT3 signal transducer pathway with IL-6 can promote the epithelial to mesenchymal transition of pancreatic cancer cells in vitro through up-regulation of Snail and down-regulation of E-cadherin expression.Therefore the STAT3 signal transducer may provide a novel therapeutic target for the treatment of pancreatic cancer.

Objective To investigate the impact of applying patient-centered care concept on easing the negative moods among the parents of the neonates hospitalized in NICU.Methods The parents of neonates (76 people) hospitalized in NICU from March to May in 2012 were selected as the control group,they conducted normal nursing.The parents of neonates hospitalized in NICU during June and August in 2012 were named as the observation group (81 people).In addition to the normal nursing,they were given nursing intervention according to patient-centered care concept.The anxiety and depression moods of the two groups was analyzed.Results Before the patient-centered care concept intervention,there was no statistical difference of SAS,SDS scores for both groups.For the observation group,the SAS,SDS scores after intervention were significantly lower than those before the intervention.While for the control group,there was no statistical difference of SAS,SDS scores.After intervention,the SAS、SDS scores of the observation group were significantly lower than those of the control group,and the difference was statistically significant.Conclusions The negative moods of the parents of hospitalized neonates can be eased significantly by applying patient-centered care concept intervention.

Objective To evaluate the effect of long-term glucocorticoid administration on nondepolarizing muscle relaxants-induced neuromuscular blockade in rat diaphragma in vitro.Methods Forty adult male SpragueDawley rats,aged 8 weeks,weighing 180-220 g,were randomized into 2 groups (n =20 each):control group (group C) and dexamethasone group (group D).In group D,dexamethasone 0.6 mg/kg was injected intraperitoneally once a day for 14 consecutive days,while the equal volume of normal saline was injected instead of dexamethasone in group C.The left phrenic nerve-hemidiaphragm was removed at 24 h after the last injection to evaluate the effect of d-tubocurarine.Different concentrations (0-10 μmol/L) of d-tubocurarine were added.The d-tubocurarine concentration-effect curve was drawn.The half inhibitory concentration and 95 ％ confidence interval of d-tubocurarine were calculated.Right diaphragma was removed for determination of the expression of embryonic nicotinic acetylcholine receptor (nAChRγ) mRNA and adult nicotinic acetylcholine receptor (nAChRε) mRNA by RTPCR.Results Compared with group C,the concentration-effect curve was shifted to the right,the half inhibitory concentration was significantly increased,and the expression of nAChRγ mRNA and nAChRε mRNA was up-regulated in group D (P ＜ 0.05).Conclusion Long-term glucocorticoid administration can weaken nondepolarizing muscle relaxants-induced neuromuscular blockade in rat diaphragma in vitro,and up-regulation of nAChR mRNA expression may be involved in the mechanism.