Aged ; Amiodarone ; adverse effects ; Chemical and Drug Induced Liver Injury ; etiology ; Drug-Related Side Effects and Adverse Reactions ; Humans ; Male

OBJECTIVE:To screen the formulations of bioadhesive danazol suppository,and to study its drug release in vitro.METHODS:Hydroxypropyl methylcellulse(HPMC),polyethylene glycol(PEG)6000and PEG600were employed in the bioadhesive sustained-release formulation.Suppositories were prepared and the correlation between drug release rate from suppositories and the ratio of HPMC to PEGs used in the formulae was studied.RESULTS:HPMC retarded drug release,and drug gradually released in the12-hours period when the ratio of HPMC to PEGs was1∶6.5;the law of drug release was conformed to weibull models and mono-exponential models.CONCLUSION:HPMC,PEG6000and PEG600were suitable to the formulation of bioadhesive danazol suppositories,and HPMC could slow down the drug release from the this preparation;the best ratio of HPMC to PEGs was1∶6.5.

Objective To investigate the relationship between UCG changes and syndrome-types of chest stuffiness and pains (CSP). Methods All 305 cases were diagnosed as CSP and received coronary angiography and echocardiography (UCG). The relationship between UCG changes and syndrome-types of TCM was analyzed. Results When coronary arteries were normal and with no abnormal ventricular wall movemoment,the proportions of blood-stasis syndrome (BSS) group and phlegm-turbid syndrome (PTS) group were lower,while higher in the condition of coronary arteries strait and with abnormal ventricular wall movemoment. BSS and PTS were significantly higher in the group with coronary arteries strait and abnormal diastolic function of left ventricle than in the group with no coronary arteries strait. There was no significantlly different symdrome-types distributing between normal and abnormal left ventricle systolic function group. EF was lower in Qi-stagnation syndrome (QSS) group than non-QSS group. FS was lower in Yang-deficiency syndrome (YDS) group than in non-YDS group,the same condition in PTS group and non-PTS group. Conclusion There was no significantly value of dignosing syndrome-types of chest stuffiness and pains in the use of UCG.

Benzene ; isolation & purification ; Environmental Monitoring ; Occupational Exposure ; prevention & control ; Recycling ; Toluene ; isolation & purification ; Xylenes ; isolation & purification

Objective To investigate the MRI findings of the breast fibroadenoma which has a washout type of time signal intensity curve (TIC)for the purpose of improving imaging diagnosis.Methods The MRI findings of 20 cases of the breast fibroadenoma with a washout TIC and 20 cases of breast carcinoma verified by histopathology were analyzed retrospectively.Morphological features,internal signal, ADC value and dynamic enhancement performance of the two groups were compared with each other.Results The shapes of the breast fibroadenomas were more commonly ovoid or round (18/20),and the margins were circumscribed(16/20),Most of the fibroadenomas were high intensity in T2 WI with the non-contrast enhanced separations (9/20).The average minimum ADC value was (1.412±0.332)×10-3 mm2/s,and higher than that of breast cancer (0.888 ±0.1 60)×10 -3 mm2/s with the significant difference (P <0.05).Enhancement scanning showed relatively homogeneous enhancement (16/20).The early enhancement ratio of the breast fibroadenoma was (1.694±0.628)×100% on average,and lower than that of breast cancer (1.849 ±0.430)× 100%.The difference was no statistical significance(P >0.05 ). Conclusion The breast fibroadenoma with washout TIC has a similar performance with the breast cancer in TIC and the early enhancement rate, however,the clear edge,higher T2 WI signal intensity,the non-contrast enhanced internal separations and higher ADC values are helpful to the diagnosis of breast fibroadenoma with washout TIC.

Breast background parenchymal enhancement (BPE) is a special form of breast dynamic contrast enhanced MRI.The diagnosis and research of breast diseases which shows BPE is becoming more and more important.The relationship between BPE and the risk factors of breast cancer is one of the focuses in breast MRI.In this review,the definition and typical manifestations of BPE,the relationship between BPE and fibroglandular tissue,and the influence factors of BPE in the breast MRI were reviewed.

Objective:To construct a prognostic model of hepatocellular carcinoma (HCC) with differential expression of autophagy genes.Method:Autophagy genes expression data of HCC and normal liver tissues were obtained from The Cancer Genome Atlas (TCGA) database and The Genotype-Tissue Expression (GTEx) database respectively. The gene expression data from different platforms is normalized into log 2(FPKM value + 1). Differentially expressed autophagy-related genes of HCC were identified by using R program limma package from the TCGA-GTEx combined data set, the criteria of |logFC| > 1 and FDR < 0.05 was deemed to be of statistically significance. The Gene Ontology (GO) analyses and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analyses were performed by using R program clusterProfiler package, as criteria of P<0.05. Univariate and multivariate Cox proportional hazards regression analyses were performed by using R program survival package to identify the HCC potential prognostic differentially expressed autophagy-related genes. Furthermore, the statistically significant ( P<0.05) autophagy genes in the univariate Cox regression analysis were included in the multivariate Cox regression analysis, and the expression of each differentially expressed autophagy gene and the corresponding regression coefficient coef value based on this, the autophagy gene prognosis model of HCC was constructed: expmRNA1×βmRNA1+ expmRNA2×βmRNA2+ …+ expmRNAn×βmRNAn (exp: gene expression level; β: regression coefficient coef of multivariate Cox regression analysis). Draw the receiver operating characteristic (ROC) curve of the predictive model and calculate the area under curve (AUC) to evaluate the predictive value of the model. Results:The genes expression data and clinical information of 374 HCC samples and 160 normal liver tissue samples were obtained from TCGA and GTEx databases. Total 205 autophagy genes expression data was obtained from the TCGA-GTEx combined sequence. Among them, SPNS1, DIRAS3, TMEM74, NRG2, NRG1, IRGM, IKBKE, NKX2-3, BIRC5, CDKN2A, TP73 are differentially expressed autophagy genes that meet the screening criteria. GO analysis mainly enriched in "regulation of protein serine/threonine kinase activity" , "ErbB 2 signaling pathway" , "protein kinase regulator activity" and "kinase regulator activity" ; KEGG analysis enriched frequently in "EGFR tyrosine kinase inhibitor resistance" , "Hippo signaling pathway" . After integrating and deleting samples with missing survival information, a total of 418 sample expressions were included in the Cox regression analysis. After univariate and multivariate Cox risk regression analysis, the two autophagy genes NRG1 ( HR=1.5565, 95% CI: 1.1793-2.0543) and IKBKE ( HR=1.7502, 95% CI: 1.2093-2.5330) were screened out and a prognostic prediction model was established: (0.44247 × NRG1 expression level) + (0.55977 × IKBKE expression level). The ROC of the prognosis model shows that the AUC of the overall seven-year survival is 0.711. Conclusion:The prognosis model of HCC based on NRG1 and IKBKE has high predictive value for the long-term survival rate of hepatocellular carcinoma patients.

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 investigate the effects of ulinastatin on the expression of NF-κB in lung tissues during limb ischemia-reperfusion(I/R) in rats.Methods Forty-eight male SD rats weighing 230-260 g were randomly divided into 3 groups (n=16 each):sham operation group (group S);I/R group; ulinastatin group (group U).A rat model of lung injury induced by I/R of hind limbs which was produced by occlusion of the bilateral femoral arteries for 2 h followed by reperfusion was established.The rats were sacrificed at 2 and 4 h of reperfusion(8 rats at each time point) and the lung tissues removed for determination of NF-κB expression (by immuno-histochemistry) and microscopic examination.W/D lung weight ratio was calculated.Results W/D lung weight ratio was significantly increased and NF-κB expression was up-regulated in group I/R compared with group S(P＜ 0.05). W/D lung weight ratio was significantly decreased and NF-κB expression was down-regulated in group U compared with group I/R (P＜0.05). The lung injury induced by I/R was reduced in group U compared with group I/R. Conclusion Ulinastatin can reduce the lung injury induced by limb I/R by down-regulating the expression of NF-κB in rat lung tissues.

Objective To explore the image characteristics of the opening of the blood brain barrier (BBB) at the early stages of severely scalded rabbits. Methods Twenty-six rabbits inflicted with 50% total burn surface area (TBSA) of Ⅲ degree were randomized into 7 groups: pre-scald, post-scald at 1, 2, 3, 4, 5, and 6 h groups. The spiral CT (SCT) and MRI were used to observe the image changes during the corresponding phases. Samples from the anterior cortex, temporal lobe, posterior cortex, cerebellum, and brain stem were examined by light and transmission electron microscopy (TEM), respectively. Results The pathological features showed that neurons and oligodendrocytes swelled lightly and blood vessels were congested and dilated at 3-4 h after scald. CT image changes were found at 5 h after scald and became more remarkable at 6 h after scald. MRI image changes could not be found within 6 h after scald. Conclusion The opening of BBB is earlier than the formation of edema. Enhanced CT plays an important role in manifesting the opening of BBB at the early stages of severely scalded rabbits.