The pharmacokinetics of a long-circulating PEGylated Radix Ophiopogonis polysaccharide (ROP) was investigated in rats following i.v. or s.c. administration at three dose levels (9, 20, 50 mg x kg(-1)). A moderate coupling reaction between the hydroxyl-activated ROP and the amino-terminated mPEG was chosen to produce PEGylate ROP. The grafting degree of the prepared conjugate was 1.03, and the molecular mass of mPEG used was 20 kDa. High-performance gel permeation chromatorgraphy with fluorescein isothiocyanate prelabeling was established to determine levels of the conjugate in plasma. The results showed that the elimination half-life of the conjugate following s.c. administration was basically identical to that after iv administration. An accurate linear correlation was observed between administration doses and areas under the curve of plasma conjugate level vs. time profile, regardless of the administration route. The absolute bioavailability of the conjugate following sc administration was approximately 56%, and the mean in vivo residence time was 52.1 h, increased 2.4 times compared to those of iv administration. In general, linear pharmacokinetics was observed for the conjugate within the dose range studied, and sc should be a promising administration route for the conjugate.

The paper is to report the observation of pharmacokinetic changes of the characteristic ingredients in the combinations of different-dose herbs of Shaoyao-Gancao decoction. After the establishment of HPLC analytical method of plasma effective constituents, rats were orally administered with different-dose herbs of Shaoyao-Gancao decoction. Blood samples at different times after administering these decoctions were collected, and then were analyzed by HPLC fingerprints technology. Pharmacokinetic parameters of characteristic peaks were analyzed by SPSS 15.0 software and DAS 2.0. At last, we looked for the correlation of those pharmacokinetic parameters and the dosage of Gancao. The best dose of Shaoyao-Gancao decoction was at the ratio of 4 to 4, which was consistent with the dose commonly used in ancient times. The absorption of characteristic peaks from Shaoyao-Gancao decoction was related with the dosage of Gancao, and there existed interaction between each characteristic ingredients. There existed the right dose-ratio of Shaoyao and Gancao to get the best effect. The absorptions of effective constitutents were mutual waxing and waning in order to increase biological effects together. It's demonstrated the compatibility connotation at a right dose-ratio of Shaoyao-Gancao decoction through the angle of pharmacokinetics.

Objective To analyze unsafely factors of elderly alimentary tract hemorrhage patients,strengthen nursing safety, assure nursing quality, improve patients' satisfaction and avoid adverse events happen to our bestMethods 223 elderly alimentary tract hemorrhage patients were collected from January to December in 2009, and safety factors, corresponding precaution have been made meanwhile.Days in hospital, recurrence of bleeding and passing rate of basic nursing and satisfaction rate of patients and incident of safety problems were compared with those 201 peering patients collected in 2008.Results Of all the physical factors, "suffering chronic disease in elderly patients" is most and accounts for 85.4%.Of all the psychological factors, "low economical status" is most and accounts for 54%. "Less communication between nurses and patients and inadequate instruction" is most (67%) of environmental and nurse staff factors.Average days in hospital were reduced in 2009 than in 2008 [(9.3 ±0.35)d vs(11.5 ±0.50)d, t =52.887, P ＜0.01].Passing rate,satisfaction rate were improved and bleeding recurrence rate were decreased, compared with those in 2008 (P ＜0.05).Conclusions It will gain better nursing efficacy through analyzing security issue carefully, finding out the disadvantage factor influencing patients' security and adopting effectve nursing safety control strategy.

This study was purpose to establish the transgenic mouse models of the truncated platelet integrin β3 by retrovirus-infected hematopoietic stem cells (HSCs) transplantation and to provide the basis for further study of the role of integrin β3 cytoplasmic domain in platelet bi-directional signaling pathways. Wild-type β3, β3-Δ759 (R(760) GT(762) truncated β3) and β3-Δ754 (T(755) NITYRGT(762) truncated β3) cDNAs were subcloned into MSCV MigR1 retroviral vector bearing a GFP gene and packaged into infective retrovirus with BOSC23 cell strain. The bone marrow HSCs of the β3 deficient mice were infected by the retroviruses, and transplanted into lethally-irradiated wild type C57BL/6 mice. GFP positive rate and surface β3 expression of the recipients' platelets at 6 to 8 weeks after transplantation were detected by flow cytometry to evaluate the transgenic efficiency. The results showed that four kinds of transgenic mouse models including vector, wild-type β3, β3-Δ759 and β3-Δ754 were established successfully. GFP positive rates of transgenic mouse platelets ranged from 18% to 66% and the β3 expression of transgenic mouse reached heterozygote (β3(+/-) level of mouse). It is concluded that establishment of transgenic mouse models mediated by retrovirus-infected HSCs transplantation is a feasible, fast, and high throughput transgenic approach and laid a solid foundation for further research on the role of integrin β3 cytoplasmic domain for bi-directional signaling of platelets in vivo, and for the gene therapy of platelet disorders.
Animals ; Blood Platelets ; metabolism ; Genetic Vectors ; Hematopoietic Stem Cell Transplantation ; Integrin beta3 ; metabolism ; Mice ; Mice, Inbred C57BL ; Mice, Transgenic ; Retroviridae ; genetics

AIMTo study the effects of ferulic acid (FA) on E-selectin expression in human umbilical vein endothelial cells (HUVECs) activated by lipopolysaccharide and leukocyte-endothelial cell adhesion.

METHODSThe effects of FA on E-selectin and E-selectin mRNA expression were determined by flow cytometry and reverse transcription polymerase chain reaction. The effect of FA on HL60-HUVEC adhesion was evaluated with the method of staining the cells by Rose Bengal.

RESULTSThe expression of E-selectin and E-selectin mRNA were down regulated by FA (0.62 and 0.41 mmol x L(-1), respectively). HL60 cells adhered to activated HUVECs were also reduced by FA (0.62 and 0.41 mmol x L(-1), respectively).

CONCLUSIONFA can inhibit the expression of E-selectin and E-selectin mRNA and HL60-HUVEC adhesion. This may contribute to its protective effect against ischemia-reperfusion injury.

Cell Adhesion ; drug effects ; Cells, Cultured ; Coumaric Acids ; pharmacology ; E-Selectin ; biosynthesis ; genetics ; Endothelial Cells ; metabolism ; HL-60 Cells ; physiology ; Humans ; RNA, Messenger ; biosynthesis ; genetics ; Umbilical Veins ; cytology

The pharmacokinetics of a long-circulating PEGylated Radix Ophiopogonis polysaccharide (ROP) was investigated in rats following i.v. or s.c. administration at three dose levels (9, 20, 50 mg x kg(-1)). A moderate coupling reaction between the hydroxyl-activated ROP and the amino-terminated mPEG was chosen to produce PEGylate ROP. The grafting degree of the prepared conjugate was 1.03, and the molecular mass of mPEG used was 20 kDa. High-performance gel permeation chromatorgraphy with fluorescein isothiocyanate prelabeling was established to determine levels of the conjugate in plasma. The results showed that the elimination half-life of the conjugate following s.c. administration was basically identical to that after iv administration. An accurate linear correlation was observed between administration doses and areas under the curve of plasma conjugate level vs. time profile, regardless of the administration route. The absolute bioavailability of the conjugate following sc administration was approximately 56%, and the mean in vivo residence time was 52.1 h, increased 2.4 times compared to those of iv administration. In general, linear pharmacokinetics was observed for the conjugate within the dose range studied, and sc should be a promising administration route for the conjugate.
Animals ; Area Under Curve ; Biological Availability ; Drug Carriers ; Drugs, Chinese Herbal ; administration & dosage ; chemistry ; isolation & purification ; pharmacokinetics ; Half-Life ; Injections, Intravenous ; Injections, Subcutaneous ; Ophiopogon ; chemistry ; Plant Roots ; chemistry ; Plants, Medicinal ; chemistry ; Polyethylene Glycols ; chemistry ; Polysaccharides ; administration & dosage ; chemistry ; isolation & purification ; pharmacokinetics ; Rats ; Rats, Sprague-Dawley

Objective:To evaluate the gene mutation profile and prognostic significance of adult cytogenetically normal acute myeloid leukemia (CN-AML) with CEBPA-bZIP mutation. Methods:Targeted sequencing was implemented on the diagnostic bone marrow DNA samples of 141 adult CN-AML subjects with CEBPA-bZIP mutation. The nomogram model for leukemia-free survival (LFS) rate was generated by combining genetic abnormalities and clinical data. Risk stratification was conducted based on prognostic variables and the effect of risk-adjusted consolidation therapy was investigated by Kaplan-Meier method. Results:Four variables were finally included in our nomogram model after multivariate Cox analysis,and an equation for risk score calculation was obtained,risk score=1.3002×white blood cell (WBC) (≥18.77×109/L)+1.4065×CSF3R mutation positive+2.6489×KMT2A mutation positive+1.0128×DNA methylation-related genes mutation positive. According to the nomogram model,patients were further divided into low-risk group (score=0,n=46) and high-risk group (score>0,n=95). Prognostic analysis showed that the 5-year LFS rate,5-year overall survival (OS) rate,and 5-year cumulative incidence of relapse (CIR) of patients who received allogeneic hematopoietic stem cell transplantation (allo-HSCT) in the high-risk group were 93.5％,97.1％,and 3.5％,while those in patients who received maintenance chemotherapy were 32.9％,70.5％,and 63.4％,respectively. The differences were statistically significant (all P<0.05). Allo-HSCT could significantly improve the prognosis of patients in high-risk group. However,no corresponding benefit was observed in the low-risk group. Conclusion:Adult CN-AML with CEBPA-bZIP mutation has a complex co-mutation pattern. The nomogram model based on mutations of CFS3R,KMT2A and DNA methylation-related genes together with WBC count can further divide this subset of patients into a relatively low-risk group and a relatively high-risk group. For individuals in the high-risk group,allo-HSCT is proposed as post-remission therapy. The above data will benefit the prognosis estimation and treatment decision for adult CN-AML with CEBPA-bZIP mutation.

The effect of adventitia on the occurrence and development of atherosclerosis (As) is getting more attentions. Fibroblasts, mast cells, dendritic cells, vasa vasorums, vascular-associated lymphoid tissues, and vascular peripheral nerves are related to the occurrence and development of As. This essay summarizes studies on the changes in adventitia in As process and its effect on the occurrence and development of As, as well as the latest progress.
Adventitia ; drug effects ; metabolism ; pathology ; Animals ; Atherosclerosis ; drug therapy ; metabolism ; pathology ; Disease Progression ; Humans

OBJECTIVE: To study the long-term clinical effect of CCLG-ALL2008 regimen in the treatment of children and adolescents, aged >10 years, with newly diagnosed acute lymphoblastic leukemia (ALL). METHODS: A retrospective analysis was performed for the clinical data of 150 ALL children and adolescents aged >10 years who were treated with CCLG-ALL2008 regimen from April 2008 to April 2015. The Kaplan-Meier method was used to analyze overall survival (OS) rate and event-free survival (EFS) rate. RESULTS: Among the 150 children and adolescents, there were 87 (58.0%) boys and 63 (42.0%) girls, with a median age of 11 years (range 10-15 years). Of the 150 children and adolescents, 84 (56.0%) had intermediate risk and 66 (44.0%) had high risk; 122 (81.3%) had B-lineage acute lymphoblastic leukemia (B-ALL) and 28 (18.7%) had T-lineage acute lymphoblastic leukemia (T-ALL). The fusion gene test yielded positive results in 51 children and adolescents (34.0%), among whom 16 (31%) had positive BCR-ABL, 11 (22%) had positive TEL-AML1, 8 (16%) had positive E2A-PBX1, and 16 (31%) were positive for other fusion genes. The complete remission rate was 96.0% (144/150) after one course of treatment with CCLG-ALL2008 regimen. The median follow-up time was 52 months (range 3-122 months). The 5-year OS rate was 79.0%±3.5%, and the 5-year EFS rate was 67.3%±4.1%. There were no significant differences in 5-year OS and EFS rates between the children with intermediate or high risk, as well as between the children with B-ALL or T-ALL (P>0.05). The children and adolescents who achieved complete remission of bone marrow at the end of induction therapy had significantly higher 5-year OS and EFS rates than those who did not achieve complete remission (P<0.05). CONCLUSIONS In ALL children and adolescents aged >10 years, CCLG-ALL2008 regimen can help to achieve high complete remission rate, 5-year OS rate and 5-year EFS rate. The children and adolescents failing to achieve complete remission at the end of induction therapy tend to have a poor prognosis.
Adolescent ; Antineoplastic Combined Chemotherapy Protocols ; Child ; Disease-Free Survival ; Female ; Humans ; Male ; Precursor Cell Lymphoblastic Leukemia-Lymphoma ; drug therapy ; Prognosis ; Remission Induction ; Retrospective Studies

OBJECTIVETo investigate the prevalence, current treatment, and clinical characteristics of asthma, as well as the risk factors for this disease, among children aged 0-14 years in 2010 in urban Zhongshan, China.

METHODSA total of 10 336 children aged 0-14 years were selected from urban Zhongshan by cluster random sampling. The Third National Childhood Asthma Epidemiological Questionnaire 2010 was used to analyze the prevalence, current treatment, and clinical characteristics of childhood asthma, as well as the risk factors for this disease.

RESULTSAsthma was diagnosed in 179 cases (1.73%). The prevalence of asthma in male children was significantly higher than that in female children (2.25% vs 1.16%; P<0.01). Of the 179 patients, severe attacks were common in 104 cases (58.1%), 110 cases (61.5%) had slow onset, 102 cases (57.0%) had gradually relieved conditions, 61 cases (34.1%) suffered from asthma during seasonal transition, and 150 cases (83.8%) developed asthma due to respiratory tract infection. Among all asthmatic children, 71.5% had been treated with inhaled corticosteroids, and 71.5% had been treated with bronchodilator. The multivariate logistic regression analysis showed that a history of penicillin allergy, a family history of allergy, food allergy, eczema, allergic rhinitis, cesarean delivery, family mould, and perinatal passive smoking were independent risk factors for childhood asthma.

CONCLUSIONSThe prevalence of childhood asthma in urban Zhongshan is on a high level, and is associated with gender. The treatment of asthma has been standardized, but still needs further improvement. The onset of asthma attack is influenced by various factors.

Adolescent ; Asthma ; epidemiology ; etiology ; Child ; Child, Preschool ; China ; epidemiology ; Female ; Humans ; Infant ; Infant, Newborn ; Male ; Risk Factors ; Seasons ; Time Factors