Objective To observe the changes of c-fos protein expression in brain and beta-endorphin (β-EP) level in blood plasma in rats with diffuse brain injury (DBI) and secondary brain insult (SBI) after intraperitoneal injection of naloxone hydrochloride, and explore the role of c-fos and β-EP in development of SBI in rats. Methods Seventy health male SD rats were enrolled in the present study and randomly divided into group A (intraperitoneally injected with 0.9% saline after DBI and SBI model was reproduced), group B (injected intraperitoneally with 1.0mg/kg naloxone hydrochloride after DBI and SBI model was reproduced), and group C (intraperitoneally injected with 1.0mg/kg naloxone hydrochloride after DBI and before SBI model was reproduced). The animals were sacrificed 3, 24 and 48 hours after injury, and the number of c-fos positive cells in brain and content of β-EP in blood plasma were determined by immunohistochemistry and radioimmunoassay respectively, the water content and number of injured neurons in brain tissue were measured by pathomorphological observation of the brain tissue. Results No significant difference was observed between group B and C for all the detection parameters. In group B and C, the water content in brain tissue at 3h and 24h was found to be decreased, while the number of injured neurons at 24h and 48h increased, number of c-fos positive cells in brain at 3h, 24h and 48h decreased, and content of β-EP in blood plasma at 3h and 24h decreased when compared with group A(P<0.05). Conclusion Naloxone hydrochloride could decrease the c-fos expression in brain and β-EP level in blood plasma, alleviate the nerve injury, and protect neural function. The therapeutic effect of naloxone administered either after DBI and SBI or after DBI and before SBI was similar.

The purpose of this study is to investigate the effects of multiple-trough sampling design and nonlinear mixed effect modeling (NONMEM) algorithm on the estimation of population and individual pharmacokinetic parameters. Oxcarbazepine and tacrolimus were used as one-compartment and two-compartment model drugs, respectively. Seven sampling designs were investigated using various number of trough concentrations per individual ranging from 1-4. Monte Carlo simulations were performed to produce state-steady trough concentrations. One-compartment model was used to fit simulated data from oxcarbazepine and tacrolimus. The accuracy and precision of the estimated parameters were evaluated using the median prediction error (PE), the median absolute PE and boxplot. The results indicated that trough concentrations could yield reliable estimates of apparent clearance (CL/F). For oxcarbazepine, as the number of trough concentrations per subject increased, the accuracy and precision of CL/F, between-subject variability (BSV) of CL/F and residual variability (RUV) tended to be improved. For tacrolimus, however, although no improvement were observed in the accuracy of CL/F and BSV of CL/F, the PE distribution ranges were significantly narrowed and the RUV estimates were less bias and imprecise. In terms of algorithm, Monte Carlo importance sampling (IMP) and IMP assisted by mode a posteriori estimation (IMPMAP) were consistently better than other methods. Additionally, the sampling design had no significant effects on the individual parameter estimates, which were only depended on the interaction between BSV and RUV in various algorithms. Decreased in BSV and RUV levels can improve the accuracy and precision of the estimation for both population and individual pharmacokinetic parameter estimates.
Algorithms ; Bayes Theorem ; Carbamazepine ; analogs & derivatives ; pharmacokinetics ; Humans ; Immunosuppressive Agents ; pharmacokinetics ; Models, Biological ; Monte Carlo Method ; Nonlinear Dynamics ; Regression Analysis ; Tacrolimus ; pharmacokinetics

Objective To observe the changes of c-fos protein expression in brain and beta-endorphin (β-EP) level in blood plasma in rats with diffuse brain injury (DBI) and secondary brain insult (SBI) after intraperitoneal injection of naloxone hydrochloride, and explore the role of c-fos and β-EP in development of SBI in rats. Methods Seventy health male SD rats were enrolled in the present study and randomly divided into group A (intraperitoneally injected with 0.9% saline after DBI and SBI model was reproduced), group B (injected intraperitoneally with 1.0mg/kg naloxone hydrochloride after DBI and SBI model was reproduced), and group C (intraperitoneally injected with 1.0mg/kg naloxone hydrochloride after DBI and before SBI model was reproduced). The animals were sacrificed 3, 24 and 48 hours after injury, and the number of c-fos positive cells in brain and content of β-EP in blood plasma were determined by immunohistochemistry and radioimmunoassay respectively, the water content and number of injured neurons in brain tissue were measured by pathomorphological observation of the brain tissue. Results No significant difference was observed between group B and C for all the detection parameters. In group B and C, the water content in brain tissue at 3h and 24h was found to be decreased, while the number of injured neurons at 24h and 48h increased, number of c-fos positive cells in brain at 3h, 24h and 48h decreased, and content of β-EP in blood plasma at 3h and 24h decreased when compared with group A(P<0.05). Conclusion Naloxone hydrochloride could decrease the c-fos expression in brain and β-EP level in blood plasma, alleviate the nerve injury, and protect neural function. The therapeutic effect of naloxone administered either after DBI and SBI or after DBI and before SBI was similar.

To compare the difference of total phenol of magnolia solid dispersion prepared by different methods. Hot melt extrusion, solvent evaporation method, and fusion-cooling method were used to prepare total phenol of Magnolia accessory solid dispersion, Plastone S-630 and HPC. The drug dispersion state in the prepared solid dispersion was evaluated with DSC and X-ray diffraction; FT-IR method was used to analyze the possible connections between drug and accessories. Finally, accelerated stability-in vivo dissolution test was use to compare the stability differences between these three processes. The results of DSC and X-ray diffraction showed that all of the drug in solid dispersion processed by three processes can exist in amorphous form; FT-IR results also could not distinguish the difference between the three processes; accelerated stability-in vivo dissolution test showed the stability of solid dispersion prepared by HPC was better than Plastone S-630, and the same kinds of materials solid dispersion prepared by hot melt extrusion showed a better stability than the other two processes.
Chemistry, Pharmaceutical ; methods ; Drugs, Chinese Herbal ; chemistry ; Magnolia ; chemistry ; Phenol ; chemistry ; Spectroscopy, Fourier Transform Infrared ; X-Ray Diffraction

To investigate the epidemic and evolutionary trends of enterovirus (EV) in the external environment of Yunnan Province, China, molecular typing was performed on 4 EV strains that were isolated from environmental sewage in Yunnan. The VP1 region of isolates was amplified by RT-PCR using universal enterovirus primers, and the amplified VP1 region was sequenced for GenBank BLAST search and genotype analysis. The 4 EV strains were identified as ECHO7. Their nucleotide and amino acid homologies with the VP1 sequences of 68 ECHO7 strains retrieved from GenBank were measured by Mega software analysis. Our findings showed that ECHO7 strains from environmental sewage and population samples were in different evolutionary branches. These strains showed typical geographical and temporal differences; In addition, there were different transmission chains at the same time and in the same area. ECHO7 strains isolated from sewage water and patients with acute flaccid paralysis during the same period in Yunnan belonged to different clusters and evolved at different speeds. Special concerns are needed for this problem. Continuous molecular biological surveillance of human EV in the external environment of Yunnan will provide strong support for early warning of EV diseases.
China ; Databases, Genetic ; Enterovirus ; genetics ; isolation & purification ; Evolution, Molecular ; Humans ; Molecular Epidemiology ; Sequence Analysis ; Sewage ; virology

OBJECTIVETo break through the restrictions of the evaluation model and the quantity of compounds by using the two-dimensional zebrafish model combined with chromatographic techniques, and establish a new method for the high-throughput screening of active anti-osteoporosis components.

METHODAccording to the research group-related studies and relevant foreign literatures, on the basis of the fact that the zebrafish osteoporosis model could efficiently evaluate the activity, the zebrafish metabolism model could efficiently enrich metabolites and the chromatographic techniques could efficiently separate and analyze components of traditional Chinese medicines, we proposed that the inherent combination of the three methods is expected to efficiently decode in vivo and in vitro efficacious anti-osteoporosis materials of traditional Chinese medicines.

RESULT AND CONCLUSIONThe method makes it simple and efficient in the enrichment, separation and analysis on components of traditional Chinese medicines, particularly micro-components and metabolites and the screening anti-osteoporosis activity, fully reflects that efficacious materials of traditional Chinese medicines contain original components and metabolites, with characteristic of "multi-components, multi-targets and integral effect", which provides new ideas and methods for the early and rapid discovery of active anti-osteoporosis components of traditional Chinese medicines.

Animals ; Chromatography ; methods ; Disease Models, Animal ; Drug Evaluation, Preclinical ; methods ; Drugs, Chinese Herbal ; therapeutic use ; Humans ; Medicine, Chinese Traditional ; methods ; trends ; Osteoporosis ; drug therapy ; physiopathology ; Phytotherapy ; methods ; trends ; Reproducibility of Results ; Zebrafish ; physiology

Objective To screen thyroid function among planned pregnant women in Chongqing, to guide prenatal and postnatal care. Methods Proportional multi-stage stratified cluster random sampling method was adopted to enroll 11 953 planned pregnant women for questionnaire, physical examination, and serum samples collection. Results The median TSH was 2. 04 mIU/ L, P25 = 1. 36 mIU/ L,P75 = 2. 99 mIU/ L. TSH levels being normal, higher, and lower than the reference were 91. 47% , 6. 20% , and 2. 33% , respectively. In Northeast Chongqing, the proportions of median TSH level and TSH level above the upper limit were higher than those in other regions(P<0. 05). With improved education, proportions of TSH above the upper limit and below the lower limit declined(P<0. 05). With the increase in body mass index, the proportion of those whose TSH was above the upper limit showed elevated trend(P<0. 05). In women with history of adverse pregnancy outcomes, their median TSH was higher than that in the control group, and those, whose TSH level exceeded the upper limit, yield higher results than those in the control group(P<0. 05). In women with higher fasting blood glucose The median TSH level was lower than that in normal blood glucose group( P<0. 05), with the fasting plasma glucose concentration and TSH negatively correlated(P<0. 05). Conclusion The abnormal rate of TSH level in planned pregnant women was 8. 53% in Chongqing. The abnormal rate varies by different regions, education levels, body mass indexes, and blood glucose levels. Previous history of adverse pregnancy outcomes was related to elevated TSH levels. It is necessary to take pre-pregnancy thyroid function screening investigation.

Objective To compare the efficacy between three-dimensional radiotherapy (3DRT) combined with chemotherapy and radiotherapy alone for patients with esophageal squamous cell carcinoma.Methods A retrospective analysis was performed for 1257 patients with esophageal squamous cell carcinoma who were admitted to our hospital from July 2003 to June 2012 and met the inclusion criteria;362 patients were treated with 3DRT combined with chemotherapy (chemoradiotherapy group) and 895 patients were treated with radiotherapy alone (radiotherapy group).The short-term outcome, overall survival (OS) rate, and causes of death were analyzed.The Kaplan-Meier method was used to calculate survival rates, and the log-rank test was used for survival difference analysis and univariate prognostic analysis.Results The response rate was 99.1%(346/349) in the chemoradiotherapy group and 99.0%(813/821) in the radiotherapy group (P=0.397).The 1-, 3-, and 5-year OS rates were 74.0%,42.0%,and 32.9% in the chemoradiotherapy group and 65.9%,33.0%,and 23.3% in the radiotherapy group (P=0.000), and were 75.6%,43.5%,and 33.2% in the concurrent chemoradiotherapy group and 65.9%,33.0%,and 23.3% in the radiotherapy group (P=0.000).There were no significant differences in 1-, 3-, and 5-year OS rates between the concurrent chemoradiotherapy group and the sequential chemoradiotherapy group (P=0.583).The sequential chemoradiotherapy group had an insignificant increase in 1-, 3-, and 5-year OS rates compared with the radiotherapy group (P=0.065).Tumor recurrence and local control failure were the main causes of death, followed by distant metastasis.The chemoradiotherapy group had a significantly lower proportion of patients who died of local control failure than the radiotherapy group (7.4% vs.14.7%, P=0.003).Conclusions For patients with esophageal squamous cell carcinoma, chemoradiotherapy leads to significantly improved overall survival compared with radiotherapy alone;compared with radiotherapy alone, sequential chemoradiotherapy results in an increasing trend in OS rates, while concurrent chemoradiotherapy results in significantly increased OS rates.Chemoradiotherapy can reduce the deaths due to local control failure compared with radiotherapy alone.

Objective To investigate the effect of smoking status after vascular construction on the long term prognosis in the patients with coronary heart disease(CHD).Methods Totally 893 patients with CHD were divided into 3 groups according to the smoking status before and after vascular construction,non-smoking group(n=458),quiting smoking group(n=287) and smoking group(n=148).The occurrence situation of major adverse cardiovascular and cerebrovascular events(MACCE) during follow-up period were recorded in detail.The postoperative cumulative survival rate was described by using Kaplan-Meier survival analysis.The effect of smoking status on the all-cause death and MACCE was compared.The Cox stepwise regression analysis was used to analyze the all-cause death and the influence factors of MACCE.Results The average follow up time was about 27 months,the postoperative smoking rate was significantly lower than the preoperative multivariable smoking rate(16.57 ％ vs.48.71％),the patients in the smoking group were younger (P＜0.01);the patients in the non-smoking group were mainly female (P＜0.01),the body mass index (BMI) was smaller(P＜0.01).The all-cause death in the smoking group was higher (1.53％ vs.1.05％ vs.6.76％,P=0.002) and the occurrence rate of MACCE was higher (4.37％ vs.5.23％ vs.15.54％,P=0.001).The Cox multivariable stepwise regression analysis showed that postoperative persistent smoking was an important risk factor leading to the all-cause death[HR=2.753,95％CI(1.695-4.473),P＜0.01] and MACCE[HR=1.552,95％CI(1.049-1.754),P=0.001].Conclusion Persistent smoking is an independent risk factor leading to all-cause death and MACCE occurrence in CHD patients after vascular construction.

Objective To investigate the situation of prevalence,treatment and control of hypertension in patients with chronic kidney disease(CKD)by CROSS-sectional study. Methods Nine hundred out-patients with CKD in our department from November 2006 to March 2007 were enrolled in the study,including 480 male and 420 female.Among 900 CKD cases,354 patients underwent maintenance dialysis,including 228 on hemodialysis and 126 on peritoneal dialysis.Results The prevalence of hypertension in CKD patients was 80.2%(nude 83.5%vs female 76.4%,P<0.01).The prevalence of hypertension in patients on dialysis was significantly higher than that in non-dialysis patients(90.1%vs 73.8%,P<0.01),but there was no significant difference between hemodialysis and peritoneal dialysis cases.Antihypertensive treatment rate was 92.4%in CKD patients with hypertension.and was significantly higher in patients on dialysis than that in non-dialysis patients(95.6%vs 89.8%.P<0.01).The control rate according to current recommendations for CKD patients (BP<130/80 mm Hg) was very low. Control of both SBP and DBP was only achieved in 20.4% of non- dialysis patients. The control rate of hypertension (BP< 125/75 mm Hg) in patients with proteinuria >1 g/24 h was 8.4%. The proportion of dialysis patients with BP<140/90 mm Hg was significantly lower than that of non-dialysis patients (45.2% vs 55.5%, P<0.01). The percentage of hemodialysis patients with BP < 140/90 mm Hg was significantly higher than that of peritoneal dialysis patients (49.8% vs 36.5%, P<0.05). The prevalence of hypertension was associated with the decrease of renal function and the increase of age. The prevalence of hypertension in diabetic nephropathy was higher than that in primary glomerular diseases. Patients received 1, 2, 3 and 4 or more kinds of antihypertensive drugs accounted for 37.2%, 37.5%, 19.3% and 5.9% respectively. The combination of calcium channel blocker (CCB) and renin-angiotensin-aldosterone system (RAAS) inhibitors was more frequently used in CKD patients. The CCB was the most frequently prescribed drug (74.1% ), followed by angiotensin Ⅱ receptor blockers (ARB) (48.4%), angiotensin-converting enzyme inhibitors (ACEI) (25.6%) and alpha, beta-blockers (24.7%). Conclusions The prevalence of hypertension in CKD patients is quite high, which is associated with the progression of renal function, increase of age, the type of underlying kidney disease, obesity and diabetes mellitus. The control of hypertension is unsatisfied in CKD patients, especially in dialysis patients and those with overt proteinuria.