Adolescent ; Adult ; Aged ; Female ; Humans ; Male ; Middle Aged ; Myelodysplastic Syndromes ; diagnosis ; epidemiology ; Prognosis ; Young Adult

Objective To explore influence of long-term inhaled glucocoticoids(IGS) on soluble intercellular adhesion molecule-1(sICAM-1)) in children with bronchial asthma.Methods Enzyme-linked immunosorbent assay(ELISA) method was used to detect the serum sICAM-1 level in 36 healthy children and 29 children with bronchial asthma(untreated and post-treated for 3,6 and 12 months).Results 1.Serum sICAM-1 level was significantly elevated in children with asthma and significantly higher than that in normal control group(P

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.

BACKGROUND:Previous research has shown that stem cells at different age stages had various proliferation and differentiation in vitro.Therefore,biological characteristics of bone marrow-derived mesenchymal stem cells at different age stages play a key role in evaluating differentiation into myocardial cells and determining proliferation and differentiation parameters in vitro.OBJECTIVE:To compare in vitro proliferation,surface marking,and differentiation into myocardial cells of bone marrow-derived mesenchymal stem cells from different aged rats.DESIGN,TIME AND SETTING:An in vitro contrast cytological observation was performed at the Laboratory of Biochemistry and Molecular Biology,Shanxi Medical University from May 2008 to May 2009.MATERIALS:A total of 15 healthy male Wistar rats were divided into three groups:1-month-old,3-month-old,and 12-month-old groups,with 5 rats in each group.METHODS:Bone marrow-derived mesenchymal stem cells were cultured using adherence screening method.At the third passage,cells differentiated into myocardium-like cells by the induction of 5-azacytidine.MAIN OUTCOME MEASURES:Cell proliferation was observed using MTT;cell surface marking was detected using flow cytometry;cardiac-specific myosin heavy chain mRNA expression was measured using RT-PCR.RESULTS:Bone marrow-derived mesenchymal stem cells were adherent in each group,and the proliferation curve was similar to each other.Under the same culture condition,the proliferation in the 1-month-old and 3-month-old groups was faster than 12-month-old group (F=28.71,P ＜ 0.05).The third-passage cells strongly expressed CD44 and CD71 but weakly expressed CD34 and CD45.At 2 weeks after 5-azacytidine induction,cardiac-specific myosin heavy chain mRNA was observed in all groups;however,the cardiac-specific myosin heavy chain mRNA expression in both 1-month-old and 3-month-old groups was significantly greater than 12-month-old group (t=5.140,2.827,P ＜ 0.05).CONCLUSION:With the age increasing of rats,proliferation,survival time,and differentiation of bone marrow-derived mesenchymal stem cells were weakened.

Articulation Disorders ; surgery

Objective To investigate the mycobactericidal efficacy of linezolid on multidrugresistant tuberculosis (MDR-TB) and nontuberculous mycobacteria (NTM) in vitro.Methods Seven hundred and sixty-two Mycobacterium tuberculosis and 20 NTM isolates from Hangzhou were identified by using hsp65 gene sequencing from March to June,2013.Seventy MDR-TB isolates,which were screened by using proportion method,and twenty NTM isolates were tested the MIC to linezolid,and the differences of MICs to linezolid between MDR-TB and NTM werw analyzed in vitro.Results All 70 MDR-TB isolates were inhibited at concentrations of ≤ 1 mg/L by linezolid,MIC50 was 0.5 mg/L and MIC90 1 mg/L.Of all 8 isolates inhibited at concentration of 1 mg/L,there were 6 isolates resistant to isoniazid,rifampin,streptomycin and ethambutol,suggesting this resistance pattern may reduce sensitivity to linezolid.Among the NTM isolates,18 Mycobacterium intracellulare isolates,whose MICs to linezolid at 8-16 mg/L,were non-resistant isolates,while 2 Mycobacterium abscessus isolates displaying MICs ＞ 32 mg/L,were resistant to linezolid.Conclusions Linezolid showed great activity to MDR-TB and there were no linezolid-resistant MDR-TB isolates identified in this study.However,MICs of MDR-TB against linezolid increased with their resistant numbers to first-line agents.This study also showed that different NTM species have varied sensitivity to linezolid.

Objective To analyse a novel splice mutation in EXT1 gene of hereditary multiple osteochondroma, and study its pathogenic mechanism.Methods In April of 2013, the proband was hospitalized from the outpatient department with multiple joint deformity for more than 20 years, peripheral blood of the proband and his parents were collected and genomic DNA was extracted .Coding regions and adjacent intron sequences of EXT1/EXT2 genes in genomic DNA of the family members were amplified and sequenced.Bioinformatics was used to analyze the mutation from sequencing .cDNA from peripheral blood of the proband ,the mother and normal control was made respectively as a template for amplifying coding regions of EXT1 gene, and the product was T-A cloned and sequenced.The abnormal transcripts of each group were counted and analyzed using chi square test to study the pathogenic mechanism of the mutation .Results Sequencing results of family members revealed that there was a heterozygous deletion mutation ( c.1284 +2del) in the 5′splice site of intron 4 in EXT1 gene of the proband and his mother .Bioinformatics predicted that exon 4 of EXT1 gene was skipping or spliced aberrantly due to the mutation .T-A clone and sequencing results as well as the statistical analysis suggested that there was a significantly higher proportion of transcripts with skipping exon 4 in the proband and his mother compared with the normal control (P=0.000, P<0.01).Conclusions c.1284+2del in EXT1 gene is reported for the first time internationally , which results in a considerable number of abnormal transcripts with skipping exon 4 in EXT1 gene, thereby influences the normal transcription and translation of EXT1 gene.

Objective To investigate the security characteristics of rural young boarding pupils and its influencing factors.Methods 210 boarding and 265 non-boarding rural young pupils of Huojia in Henan were tested by questionnaires,including of a self-developed questionnaire,security questionnaire and adolescent mental resilience scale.Results ①The scores of the interpersonal security (25.99 ± 5.53),the determine control sense factor (24.63 ±6.17) and the total security(50.62 ± 10.37) in the boarding pupils were statistically lower than non-boarding pupils (27.36 ± 6.38,26.00 ± 6.55,53.36 ± 11.77,P ＜0.05).②There were statistically significant difference in the scores of the interpersonal security,the determine control sense factor and the total security among the different grades(P＜0.05),but there were no statistically sex difference in the scores(P ＞ 0.05).③Group regression analysis showed that,no family factors in the young boarding pupils had influence on the score of the security sense factors and the total (P＞0.05),and marital relationship of parents,only child,father' s and mother(')s education background of non-boarding pupils had certain influence on the score of the interpersonal security,the determine control sense factor and the total security (β =-0.43-0.27,P＜ 0.05).④The group regression analysis showed that,the problem solving and self-efficacy,parents'high expectations in mental toughness respectively had some effect on the interpersonal security of boarding and non-boarding pupils(β =-0.15,β =0.25,P＜0.05),and social ability and family care,schools resilience respectively had influence on the determine control sense in boarding and non-boarding pupils (β =-2.91-2.87,P＜0.05),and social ability,parents'high expectations respectively had influence on the total security in boarding and non-boarding pupils (β =-0.17,β=0.22,P＜0.05).Conclusion The security-sense in boarding young pupils are lower than the non-boarding young pupils,and family factors and mental toughness have different effects on security-sense of two kinds pupils.

Adenocarcinoma ; complications ; pathology ; Aged ; Humans ; Male ; Neoplasms, Multiple Primary ; complications ; pathology ; physiopathology

Objective To investigate the value of multi-slice spiral CT image texture analysis in differentiating metastatic (MLN) from non-metastatic lymph nodes (NLN) in patients with rectal cancer.Methods Thirty five patiets with rectal cancer who were pathologically confirmed by total mesorectum excision were included retrospectively,with regional lymph nodes (short-axis diameter of larger than 3 mm)found in preoperative CT images.All the patients underwent preoperative abdominal and pelvic dynamic contrast-enhanced CT scan.Regional lymph nodes were identified according to pathological findings,and were divided into MLN and NLN groups.The short-axis diameter,short-to long-axis diameter ratio of lymph nodes were manually measured and calculated,and the texture features,including skewness,kurtosis,variance,entropy and inverse difference moment,were analyzed.The above parameters between MLN and NLN groups were compared using independent sample t test or Mann-Whitney U test.ROC curve analysis was performed regarding the statistically significant parameters and the areas under curve (AUC) were calculated.Multivariate Logistic regression analysis was accomplished to obtain the independent predictive factor of diagnosing regional lymph nodes.Results A total of 68 regional lymph nodes were obtained and consisted of 31 MLNs and 37 NLNs.The short-axis diameter,kurtosis,and entropy of the MLN group were significantly higher than those of the NLN group (all P＜0.05).Whereas,the short-to long-axis diameter ratio,skewness,variance,and inverse difference moment did not differ significantly between the two groups (all P＞0.05).The AUC for distinguishing MLN from NLN of the short-axis diameter,kurtosis and entropy were 0.79,0.67,and 0.85,respectively.Multivariate logistic regression analysis showed that only entropy (odds ratio=8.48,95％ confidence interval was 3.01 to 23.92,P＜0.01) was screened out as the independent variable,which suggested that the entropy was the unique predictor for characterizing regional lymph nodes of rectal cancer.Conclusion Multi-slice spiral CT images texture analysis can facilitate the accurate differentiation between MLN and NLN in patients with rectal cancer,and especially the entropy has the optimal reference significance.