Model-informed drug development (MIDD) in the development of pediatric drugs is drawing more and more attention due to the insufficiency of subjects, lack of research on ontogeny, and the limitation of ethic. The core of MIDD used for dose selection includes the population pharmacokinetic (PopPK) model and physiologically based pharmacokinetic (PBPK) model, as well as model-based simulation and prediction. PBPK model has the advantage of predicting the optimal pediatric dose before the clinical trials and has the ability of extrapolation from adult model to pediatric model. PopPK model characterizes the pediatric PK feature based on the analysis of clinical data and can be used to explore the significant covariates, which is a power tool for individualized medicine in children. With their own advantages and disadvantages, PBPK and PopPK model should be jointly used in the pediatric drug development to refine the dose regimen for children at different ages. In this study, the pediatric drug development of rivaroxaban was taken as an example to introduce the combined application of PBPK model and PopPK model in the design and validation of pediatric dose regimen in Phase Ⅰ, Ⅱ and Ⅲ trials, which may provide reference to MIDD in other pediatric drug development.

The paper covered the development, structure, functionality, effectiveness and goals of the community health information system in the district. It is found that Zhabei district has developed the standard electronic health archives which can be collected by various sources and renewed instantly;regional health information sharing and collaboration platform has been established as well; a sharing and joint service platform has been built for regional health information sharing between communities and secondary hospitals shared; "Health key" has been developed as a model for self-service health management for residents.

Objective To investigate the chang and impaction of TM and D- Dimer on peripherally inserted central catheter (PICC) associated thrombosis in cancer patients. Methods The expression of TM and D-Dimer from 207 cancer patients with PICC was examined using nzyme-linked immunoassay. Paitents were divided into thrombosis group and control group according to Doppler Sonography. Results The thrombosis group had 33 cases and the control group had 174 cases in 207 malignant tumor patients with PICC. Compared with that in control group, the expression of TM (6.806 ± 1.805)μg/L and D-Dimer (0.786 ± 0.294) mg/L was significantly higher in thrombosis group and respectively statistically significant (P<0.05), The expression of TM and D-Dimer was positively correlated with thrombosis respectively (r=0.572 and 0.530, P<0.05). The multi-factor Logistics analysis showed the odd ratio of TM was 1.899 and the odd ratio of D-Dimer was 7.292, and the difference was statistically significant (P<0.05). Patients were dichotomized into elevated and noneelevated groups according to the 50th percentile of the levels of TM and D-Dimer of the total study population. In multivariable analysis, the odd ratio of both elevated TM and elevated D-Dimer was 2.04, which was higher than elevated TM (1.286) alone and elevated D-Dimer (1.044) alone, and there was difference in statistics (P<0.05). The results showed that the risk of PICC associated with thrombosis in both elevated TM and elevated D-Dimer TM increased 2.042 times. The expression of TM and D-Dimer was correlated with clinical stage respectively (r=0.477 and 0.492, P<0.05);but was not correlated with age, sex, site of tumor and concurrent radiochemotherapy (P>0.05). Conclusions The expression of TM, D-Dimer is elevated, which is expected to assess the early diagnosis and clinical value of PICC associated thrombosis in cancer.

Objective:To investigate the role of interleukin-10 (IL-10) and IL-12 in the differential diagnosis of tuberculous and malignant pleural effusion through measuring the serum and pleural effusion IL-10 and IL-12 levels of tuberculous and malignant pleural effusion patients.Methods: Forty-eight inpatients with exudative pleural effusion who didn''t receive any treatment before were selected.According to the pathogeny, the patients were divided into tuberculous pleural effusion group (n=25) and malignant pleural effusion group (n=23).The levels of IL-10 and IL-12 in peripheral blood and pleural effusion of the patients in two groups were detected by Cytometric Bead Array (CBA).The differences in IL-10, IL-12 levels and IL-12/IL-10 ratio were compared between two groups.The ROC curves of the above indexes, cast-off and adenosine deaminase (ADA) were used to compare the effects in differential diagnosis of tuberculous and malignant pleural effusion.Results: There were no statistical differences in the levels of serum IL-10, IL-12 and IL-12/IL-10 ratios of the patients between tuberculous and malignant pleural effusion groups (P>0.05),and the IL-12 level in pleural effusion and the IL-12/IL-10 ratio of the patients in malignant pleural effusion group were lower than those in tuberculous pleural effusion group (P<0.005).The area under the ROC curve for the levels of IL-12 in pleural effusion (0.984) was higher than those for the ratio of IL-12/IL-10, cast-off and ADA (0.744, 0.804 and 0.911, respectively) in the differential diagnosis of tuberculous and malignant pleural effusion.Conclusion: The detection of IL-12 levels in pleural effusion is helpful for the differential diagnosis of tuberculous and malignant pleural effusion, and the pleural effusion is easy to obtain, therefore the detection of IL-12 in pleural effusion is worth to be widely applied in clinic.

Objective:To investigate the relationship of expression of vascular endothelial growth factor (VEGF) and clinical features in patients with intracranial aneurysm and arteriovenous malformation (AVM).Methods:A total of 64 patients with AVM and intracranial aneurysm,who were treated in First Hospital of Shijiazhuang from February 2011 to November 2015,were chosen as research subjects,AVM were 32 cases and intracranial aneurysm were 32 cases.The samples were sectioned for VEGF immunohistochemical staining;the location and intensity of staining were recorded;the positive indexes were computed.The VEGF expression of different age and Hunt&Hess classification in patients with intracranial aneurysms were analysed;the VEGF expression of different diameters,ages,Spetzler classification in patients with AVM were analysed.Results:There were no statistical differences in the VEGF expression of different ages in patients with intracranial aneurysms (P＞0.05);the VEGF expression of different Hunt&Hess classification in patients with intracranial aneurysms was statistical difference (P＜0.05).The positive rate of VEGF in the artery of AVM was lower than that in the vein,the difference was statistically significant (P＜0.05).There were no statistical differences in the VEGF expression of the different Spetzler classification,different diameters and different ages in patients with AVM (P＞0.05).Conclusion:The expression of VEGF in the vein and the artery of patients with AVM is different,the expression of VEGF is not correlated with the age of intracranial aneurysm and the size and age of AVM.VEGF cannot be used as a predictor in the patients with intracranial aneurysms and AVM.

Objective:To explore the correlation between serum level of matrix metalloproteinase 2 (MMP-2)and se-verity of coronary artery disease in aged patients with acute coronary syndrome (ACS)complicated hyperhomocys-teinemia (HHCY).Methods:According to serum level of homocysteine (Hcy),a total of 105 aged ACS patients were selected and divided into ACS+HHCY group (n=56)and pure ACS patients (n=49),another 65 healthy in-dividuals were enrolled as healthy control group.The severity of coronary artery disease was showed by Gensini score ;enzyme linked immunosorbent assay was used to measure serum MMP-2 level in each group.Results:Com-pared with healthy control group,there were significant rise in MMP-2 level [(140.8±50.1)ng/ml vs.(442.5± 98.2)ng/ml,(297.9±86.3)ng/ml]in ACS+HHCY group and pure ACS group,P <0.01. Gensini score in ACS+HHCY group was significantly higher than that of pure ACS group [(1.9±0.2)scores vs.(1.1±0.3)scores,P<0.01].Pearson correlation analysis indicated that Gensini score was positively correlated with MMP-2 level in ACS+HHCY group (r =0.424,P <0.05).Conclusion:The serum MMP-2 level is significantly positively correla-ted with severity of coronary artery disease in aged patients with ACS complicated HHCY.

ObjectiveTo evaluate the effect of the timed “up and go” test (TUGT) on measuring functional mobility of stroke patients.MethodsNinety hemiparetic stroke patients participated in this study. The balance, gait speed and disability of patients were measured by Berg balance scale (BBS), maximal gait speed and functional independence measure (FIM) to find out the critical value of TUGT.ResultsA good relationship existed among TUGT and the BBS,gait speed and FIM (r=-0.926—-0.674,P<0.001).The percentage of independent walking of stroke patients whose TUGT scores <10s or>20s were 100% and 8.3%. The optimal cut off values of TUGT to predict the independent walking of patients were 15.2s, and in stroke group sensitivity and specificity of TUGT were 89.4% and 79.1%.Conclusion TUGT is a reliable instrument with adequate concurrent validity to measure the functional mobility of stroke patients.

Rhynchosia volubilis Lour has been a major drug in a folk prescription for contraception in China, whereas its mechanism remains unknown. Its antifertility effects on male mice and antimicrobial activities on sexually transmitted infection (STI) pathogens were previously reported. This study was undertaken to develop the n-Butanol extract of Rhynchosia volubilis Lour (BERVL) as a spermicidal agent with STI prevention. The spermicidal activities of BERVL with different doses were assessed using selected high-motile sperms of normal human semen samples, and their inhibitory effects on Lactobacillus acidophilus were determined. The mechanism of the spermicidal activity was explored by aqueous Eosin Y and Hoechst 33342/PI staining. The results showed spermicidal activities and inhibitory effects of BERVL on Lactobacillus acidophilus were dose-dependent. Dose of 90 mg/mL BERVL terminated all progressive sperm motility within 2 min, and had slight inhibitory effect on Lactobacillus acidophilus, suggesting it was an effective and safe dose for contraception use. About 80% sperms exposed to BERVL displayed changes consistent with high permeability of head membrane. It is concluded that BERVL as spermicide has advantages over N-9 with strong ability to instantaneously kill human sperm and possesses light inhibitory effect on Lactobacillus acidophilus.

Objective To evaluate the roles of positron emission tomography (PET) with N-methyl [11C]2-(4' -methylaminophenyi-6-hydroxybenzathiazole) (11C-PIB) in the early diagnosis of Alzheimer's disease (AD).Methods Six AD patients,7 mild cognitive impairment (MCI) patients and 6 normal controls (NC) were diagnosed and assessed with brain PET with 11C-PIB.The emission images obtained at 5,25 and 45 min after 11C-PIB administration were analysed.Results Using visual analysis to summarize the characteristics of the imagings of each group: comparing to NC,the AD patients show high 11C -PIB up take,and low clearance rate of 11C-PIB at 45 min.The imagings of MCI group show heterogeneous,overlapping with AD and NC group.The statistical analysis shows: in AD group,the standard uptake value (SUV) ratio of parietal lobe,frontal lobe,temporal lobe,occipital lobe and hippocampal at 45 min was 1.91±0.21,2.09±0.41,1.92±0.35,1.66±0.41,1.55±0.28 respectively,and were higher than that of NC group (value being 1.48±0.53,1.57±0.64,1.36±0.53,1.27±0.40,1.17±0.33) with statistical significance,t=8.114,5.620,5.705,3.650 and 2.866,P=0.0001,0.0002,0.0002,0.0045 and 0.0170 respectively.In MCI group,the SUV ratio of parietal lobe,frontal lobe,temporal lobe,occipital lobe and hippocampal at 45 min was 1.48 ± 0.53,1.57 ± 0.64,1.36±0.53,1.27 ± 0.40,1.17±0.33 respectively,and were higher than that of NC group,but there was no statistical significance.Conclusion 11C-PIB PET imaging can differentiate AD patients from normal and anticipate the transformation of MCI patients.

Objective To explore the relationship between the index of SPECT myocardial viability teat of the left ventricle and long-term cardiovascular adverse events following the coronary artery bypass graft.Methods Clinical data were selected from the coronary-heart-disease patients with CABG and the isotopic SPECT test of myocardial viability prior to the operation in the Fuwai Cardiovascular Hospital,the Chinese Academy of Medical Science from January 1,1999 to December 31,2005.Total 709 patients were included in this study.Regular follow-up in patients was performed following operation.Investigate the nuclear medicine documents of the patients above;make the semi-quantitative scores of myocardial viability prior to operation by the 17-segment method of ventricle.Through the COX multi-factor analysis of the statistical methods to explore the relationship between the index of the myocardial viability and the long-term cardiac adverse events selected in advance.Results The mean duration of follow-up was(3.43±2.42)years.The COX multi-analysis revealed that the total score of left ventricular myocardial viability is the independent impact factors for long term cardiac death,long terrm re-hospitalization rate and long term composite end points events.The cut off values of total score of left ventricular myocardial viability for long term cardiac death,long term re-hospitalization rate and long term composite end points events is 15,9,13 respectively.Conclusion The total score of left ventricular myocardial viability of SPECT is independently associated with long-term events,and the cut values of myocardial viability total score for long-term cardiac death,re-hospitalization and composite MACE events are 15,9,and 13 respectively.For the groups with total scores above and below the cut off values,there is significant difference of long term cardiac events risk between groups.