OBJECTIVE To study the pharmacokinetic changes in the plasma and cerebrospinal fluid of bronchial asthma model rats after the complication of Ephedra sinica and Prunus armeniaca. METHODS SD male rats were randomly divided into blank group， model group， E. sinica group （12 g/kg， calculated by raw drug， similarly hereinafter）， P. armeniaca group （6 g/kg） and E. sinica-P. armeniaca drug-pair group （12 g/kg of E. sinica+6 g/kg of P. armeniaca）， with 6 rats in each group. Except for the blank group， the bronchial asthma model was induced by spraying rats in each group with an equal volume mixture of 2% acetylcholine chloride and 0.4% histamine phosphate， once a day， for 7 d. One hour before modeling every time， rats in each group were gavaged with the corresponding drug/normal saline， once a day， for 7 d. After the final administration and provocation of asthma， blood and cerebrospinal fluid collection were performed at different time points. The plasma and cerebrospinal fluid samples were pre-treated （with geranylgeranyl as the internal standard）， and the mass concentrations of ephedrine/pseudoephedrine， methyl ephedrine and amygdalin in both samples were determined by liquid chromatography-tandem mass spectrometry. DAS 2.0 pharmacokinetic software was used to determine the main pharmacokinetic parameters through the non-atrial chamber model and to compare the changes of the pharmacokinetic parameters before and after the combination of the two drugs. RESULTS Compared with E. sinica group， cmax and AUC0-21.33 h （or AUC0-10.67 h） of ephedrine/pseudoephedrine and methyl ephedrine in the plasma and cerebrospinal fluid of rats were significantly reduced in E. sinica-P. armeniaca drug-pair group， while CLZ/F and VZ/F were significantly increased （P＜0.05 or P＜0.01）； tmax of methyl ephedrine in the cerebrospinal fluid was significantly shortened （P＜ 0.05）.Compared with P. armeniaca group， the t1/2 of amygdalin in the plasma of rats in E. sinica-P. armeniaca drug-pair group was significantly shortened， and CLZ/F was significantly increased （P＜0.01）； the tmax of bitter amygdalin in the cerebrospinal fluid was significantly shortened， and the AUC0-10.67 h， CLZ/F， and VZ/F were significantly increased （P＜0.01）. CONCLUSIONS The combination of E. sinica and P. armeniaca accelerates the absorption and elimination of ephedra alkaloids， thus reducing the accumulation of ephedra alkaloids in the bronchial asthma model rats.

In clinical practice, radiopharmaceutical dynamic imaging technology requires the bolus injection method to complete injection. Due to the failure rate and radiation damage of manual injection, even experienced technicians still bear a lot of psychological burden. This study combined the advantages and disadvantages of various manual injection modes to develop the radiopharmaceutical bolus injector, and explored the application of automatic injection in the field of bolus injection from four aspects: radiation protection, occlusion response, sterility of injection process and effect of bolus injection. Compared with the current mainstream manual injection method, the bolus manufactured by the radiopharmaceutical bolus injector based on the automatic hemostasis method had a narrower full width at half maximum and better repeatability. At the same time, radiopharmaceutical bolus injector had reduced the radiation dose of the technician's palm by 98.8%, and ensured more efficient vein occlusion recognition performance and sterility of the entire injection process. The radiopharmaceutical bolus injector based on automatic hemostasis has application potential in improving the effect and repeatability of bolus injection.
Radiopharmaceuticals ; Injections ; Hand

Objective: To analyze the survival time of people living with HIV/AIDS and related influencing factors in Sichuan province during 1991-2017. Methods: A retrospective cohort study was conducted to analyze the data of 143 988 HIV/AIDS cases. The data were collected from Chinese HIV/AIDS Comprehensive Information Management System. Life table method was used to calculate the survival proportion of the cases, and Cox proportion hazard regression model was used to identify the factors related with survival time. Results: Among 143 988 HIV/AIDS cases a total of 30 420 cases died of AIDS related diseases (21.1%) and the average survival time was 11.51 years (95%CI: 11.39-11.64). Multivariate Cox regression analysis showed that the influencing factors for the survival of HIV/AIDS cases were gender (male vs. female, HR=1.35, 95%CI: 1.32-1.40), education level (primary school or below vs. junior middle school: HR=1.15, 95%CI: 1.12-1.18), ethnic group (Han vs. other ethnic groups, HR=1.46, 95%CI: 1.41-1.52), occupation (farmer vs. other occupations: HR=1.26, 95%CI: 1.22-1.29), age (≥55 years old vs. 15-24 years old: HR=3.18, 95%CI: 3.02- 3.36), disease phase (AIDS vs. HIV infection: HR=1.44, 95%CI: 1.39-1.48), antiretroviral therapy (ART) (receiving ART vs. receiving no ART: HR=0.20, 95%CI: 0.19-0.20), and CD₄⁺T cell counts at diagnosis (>500 cells/μl vs.<200 cells/μl: HR=0.42, 95%CI: 0.40-0.45). Conclusions The average survival time of HIV/AIDS cases was 11.51 years in Sichuan during 1991- 2017. The risk factors for the survival of the cases were male, education level of primary school or below, Han ethnic group, farmer, old age at diagnosis, disease phase, The protective factors for the survival of HIV/AIDS cases were receiving ART and higher CD₄⁺ T cell counts at diagnosis.

Objective To discuss the correlation of P-glycoprotein(P-gp) and lymphocyte subgroup(CD4+,CD8+) in patients with immune thrombocytopenia.Methods A total of 20 patients with immune thrombocytopenia were selected from August 2015 to September 2016 in the Eighth Hospital Affiliated to Sun Yat-sen University.According to the platelet count,all patients were divided into mild group and severe group,20 cases of health persons were selected at the same period as the healthy group,flow cytometry technique was used to detect the plasma lymphocyte subsets(CD4+,CD8+) and P-gp level of all the objects.Pearson correlation analysis was used to analyze the relationship between plasma P-gp and plasma CD4+,CD8+,CD4+ / CD8+ level,analyzed all the objects plasma platelet count,P-gp and CD4+,CD8+,CD4+ / CD8+ levels.Results Plasma CD4+,CD8+,CD4+ / CD8+ and P-gp level of severe group were significant higher than those of mild group(t=3.587,2.957,2.315,2.646,P<0.05),plasma CD4+,CD8+,CD4+ / CD8+ and P-gp level of mild group patients were significant higher than those of healthy group(t=5.479,2.921,4.536,7.750,P<0.05).Pearson correlation analysis results showed that the plasma levels of P-gp and plasma CD4+,CD8+,CD4+ / CD8+ levels were positively correlated(r=0.683,0.617,0.548,P<0.05).Conclusion Plasma CD4+,CD8+,CD4+/CD8+and P-gp level is associated with immune thrombocytopenia patients condition,plasma levels of P-gp closely links with abnormal immune function in patients with hyperthyroidism,prompting detection the level of change could help doctors to assess patients medication curative effect.

In recent years, Hepatitis B virus (HBV) persistent infection mouse model with recombinant adeno-associated virus 8 carrying 1.3 copies of HBV genome (rAAV8-1.3HBV) is concerned. We studied and compared the efficacy among HBV persistent infection mice models by other serotypes except AAV8. First, we prepared and purified five viruses: rAAV1-1.3HBV, rAAV2-1.3HBV, rAAV5-1.3HBV, rAAV8-1.3HBV and rAAV9-1.3HBV. Then we injected each virus into 3 C57BL/6J mice with the dose of lx 1011 vg (Viral genome, vg) per mouse. We detected HBsAg and HBeAg in sera by enzyme-linked immunosorbent assay (ELISA) at different time points post injection. We killed mice 8 weeks post injection and took blood and livers for assay. We detected copies of HBV DNA by real-time quantitative PCR in sera and livers. Meantime, we detected HBcAg in the livers of mice by immunohistochemistry and further performed pathology analysis of these livers. The five groups of mice, HBeAg and HBsAg expression sustained 8 weeks in serological detection and HBV DNA was both detected in sera and livers at the time of 8 weeks post injection. HBeAg, HBsAg, HBV DNA copies expression levels in descending order were AAV8>AAV9>AAV1>AAV5>AAV2. HBcAg expression was detected in livers as well. Varied degrees of liver damage were shown in five groups of mice. This study provides more alternative AAV vector species to establish a persistent infection with hepatitis B model.
Animals ; Dependovirus ; classification ; Disease Models, Animal ; Enzyme-Linked Immunosorbent Assay ; Genetic Vectors ; Genome, Viral ; Hepatitis B ; virology ; Hepatitis B Core Antigens ; metabolism ; Hepatitis B Surface Antigens ; blood ; Hepatitis B e Antigens ; blood ; Hepatitis B virus ; genetics ; Mice ; Mice, Inbred C57BL ; Serogroup ; Virus Replication

Diagnostic Imaging ; Humans ; Liver Diseases ; pathology ; Portal Vein ; pathology

Objective To assess the psychometric properties of the Chinese Heartburn Version of Quality of Life in Reflux and Dyspepsia Questionnaire (QOLRAD) in patients with gastroesophageal reflux disease.Methods 130 patients with symptoms of heartburn completed the Chinese version of QOLRAD,the Short-Form-36 (SF-36).30 of them received proton pump inhibitors (PPI) for 8 weeks,which was used to test responsiveness of the Chinese heartburn version of QOLRAD.Results The Chinese version of QOLRAD had acceptable internal consistency.The overall Cronbach's alpha was 0.89 and the internal consistency of dimensions ranged from 0.70～0.90.Content validity index (CVI) was 0.82.Confirmation factor analysis revealed a 5 factor solutions accounting for 62.02％ and most of items in their dimensions had acceptable loads (＞0.4).There was acceptable concurrent validity with correlations between the Chinese heartburn version of QOLRAD and Short Form-36 health survey ranging from 0.172～0.613.As to responsiveness,after therapy of PPI for 8 weeks,except the dimension of sleep disturbance,scores for dimensions of vitality,food/drink problems,physical/social functioning,emotional distress had significant changes.Conclusions The Chinese version of QOLRAD has a good reliability,validity and responsiveness to therapy,which can be used to assess the quality of life in patients with gastroesophageal reflux disease.

We evaluated the anti-HBV effects of nucleotide analogues, Entecavir (ETV) and Lamivudine (LAM) targeting mouse model of HBV persistent infection with recombinant adeno-associated virus 8 carrying 1.3 copies of HBV genome (rAAV8-1.3HBV). Ninety percent (27 of 30 mice) of rAAVS-treated mice were chosen as mouse model. Four groups were orally administrated with different doses of ETV (1 mg/(kgd) or 0.1 mg/(kgd)) and LAM (500 mg/(kgd) or 100 mg/(kgd)) once a day for 10 days. The other two groups were set as normal saline treated and untreated control. We detected the levels of HBV DNA, HBeAg and HBsAg in sera at different time. Results indicate that HBV DNA level decreased significantly (P < 0.05) in drug-treated groups compared with normal saline group after drug administration. Fifteen days after the drug withdrawal, HBV DNA level rebounded back obviously (P < 0.05) in groups with low doses of ETV and LAM. However, there was no apparent change of HBeAg and HBsAg in the whole process among all groups. These results showed that our model could reflect the anti-viral effect of nucleotide analogues. This model can be a useful and convenient tool for anti-HBV drug discovery.
Animals ; Antiviral Agents ; pharmacology ; Dependovirus ; genetics ; metabolism ; Disease Models, Animal ; Genetic Vectors ; Genome, Viral ; Guanine ; analogs & derivatives ; pharmacology ; Hepatitis B Antibodies ; blood ; Hepatitis B virus ; genetics ; physiology ; Hepatitis B, Chronic ; virology ; Lamivudine ; pharmacology ; Mice ; Mice, Inbred C57BL ; Nucleotides ; pharmacology ; Transduction, Genetic ; Virus Replication

Activities of 58 miRNAs for BHK21, HEK293, and Vero cell lines were screened using the high-throughput miRNA activity profiling method. miR-206 activity was found specifically high in BHK21. Considering miR-206 was recognized as a muscle-specific miRNA, we further detected the expression and activity level of miR-206 in BHK21 cells, with myoblast cells C2C12 as positive control and HEK293 cells as negative control. Then, we induced BHK21 by culturing with medium containing 2% horse serum (HS) and tested expression level of slow skeletal myosin heavy chain (MHC), activity and expression levels of miR-206, and expression level of Connexin43 (Cx43) which was reported negatively regulated by miR-206. Results demonstrated that activity and expression levels of miR-206 were both higher in BHK21 cells than in C2C12 cells. After induction of HS, MHC expression level was increased in BHK21 cells. The activity and expression levels of miR-206 were further enhanced. The Cx43 expression level was decreased. These results suggested that BHK21 had the characters of myoblast cells. In conclusion, we firstly discovered that miR-206 activity was specifically high in BHK21 cells, suggesting that BHK21 cells were derived from interstitial cells other than parenchyma cells of kidney from miRNA point of view. Our study also indicated that BHK21 cells were able to be used as models in vitro for research of miR-206 function.
Animals ; Cell Line ; Cercopithecus aethiops ; Connexin 43 ; metabolism ; Cricetinae ; Gene Expression Regulation ; HEK293 Cells ; Humans ; MicroRNAs ; genetics ; Myosin Heavy Chains ; metabolism ; Vero Cells

To establish an orthotopic transplant mouse model of hepatocellular carcinoma (HCC) labeled with secretary luciferase and to study its response to anti-tumor treatment with interferon-beta gene therapy. We labeled the murine hepatoma Hepal-6 cells with secretary Gaussia princeps luciferase (Gluc), and then injected Gluc labeled Hepal-6 cells intrasplenically in C57BL/6 mice. We monitored blood Glue to evaluate the tumor development and anti-tumor effects of hydrodynamic injection with interferon-beta expressing plasmid. We successfully established the orthotopic mouse model of HCC by intrasplenic injection of Glue labeled Hepal-6 cells. The Glue blood assay could reflect the amount of cancer cells in vivo, tumor progression, as well as anti-tumor effect of interferon-beta gene therapy. In conclusion, Gluc labeled orthotopic transplant mouse model of HCC can ex vivo real-time monitor the tumor development and tumor response to treatments.
Animals ; Carcinoma, Hepatocellular ; pathology ; therapy ; Cell Line, Tumor ; Genes, Reporter ; Genetic Therapy ; Interferon-beta ; genetics ; therapeutic use ; Liver Neoplasms ; pathology ; therapy ; Luciferases ; blood ; genetics ; secretion ; Mice ; Mice, Inbred C57BL ; Neoplasm Transplantation ; Treatment Outcome