This study is to investigate the anti-tumor activities of a novel cyclophosphamide derivate 4, 6-diphenyl cyclophosphamide (9b) in vivo and in vitro, and its possible mechanism of action. The inhibitory effects of 9b on human hepatoma cell line HepG2, human breast carcinoma cell line MCF-7 and human myeloid leukemia cell line K562 were measured by MTT assay in vitro. Cell cycle distribution and apoptotic rate were evaluated by flow cytometry. To evaluate the anti-tumor effect of 9b in vivo, mouse model bearing inoculated H22 tumor was established. The results indicated that 9b could inhibit the proliferation of HepG2, MCF-7 and K562 cells in a dose and time dependent manner. The ICo50 values of 9b were 32.34 micromol.L-1 to HepG2 cells, 87.07 micromol.L-1 to MCF-7 cells and 149.10 micromol.L-1 to K562 cells after incubation for 48 h. The results of flow cytometry indicated that after being treated for 48 h with different concentrations of 9b, the ratios of HepG2, MCF-7 cells at the Go/G1 phase and K562 cells at the G0/Gl phase and G2/M phase increased significantly compared with control group, and the apoptotic rate increased with the increase of the concentration of 9b. 9b could significantly reduce tumor weight of H22 solid tumor mouse model in vivo. To summarize, 9b showed significantly anti-tumor activity in vivo and in vitro, of which the mechanism might be associated with the change of cell cycle distribution and induction of tumor cell apoptosis.
Animals ; Antineoplastic Agents, Alkylating ; chemistry ; pharmacology ; Apoptosis ; drug effects ; Cell Cycle ; drug effects ; Cell Line, Tumor ; Cell Proliferation ; drug effects ; Cyclophosphamide ; analogs & derivatives ; chemistry ; pharmacology ; Dose-Response Relationship, Drug ; Female ; Humans ; Inhibitory Concentration 50 ; Liver Neoplasms, Experimental ; pathology ; Male ; Mice ; Molecular Structure ; Random Allocation ; Tumor Burden ; drug effects

OBJECTIVE: To investigate the anti-tumor activity of a novel cyclophosphamide derivate 4, 6-diphenyl cyclophosphamide (9b) on cultured SK-OV3 (human ovarian cancer cell line) and 143B (human osteosarcoma cell line) cells in vitro aid S180 (mouse sarcoma cell line) and B16 (murine melanoma cell line) solid tumors in vivo, and its possible anti-tumor mechanism. METHODS: The inhibitory effects of 9b on SK-OV3 and 143B cells proliferation were analyzed by MTT assay in vitro. The effect of 9b on cell cycle distribution and apoptosis were evaluated by flow cytometry. To evaluate the anti-tumor effect of 9b in vivo, mouse model bearing inoculated S180 and B16 tumor were established. RESULTS: MTT assay revealed that 9b obviously suppressed SK-OV3 and 143B cells growth and proliferation in a dose-dependent manner within the concentration ranging from 3.7 to 300 Limol·L-1 and in a time-dependent manner from 24 to 72 h. The IC50 value of 9b was (71.27±1.08) μmol·L-1 for SK-OV3 cells, and (98.50±0.82) μmol·L-1 for 143B cells respectively when incubation for 48 h. The results of flow cytometry indicated that after treated for 48 h with different concentration of 9b, the ratios of 143 B cells in the G0/G1 phase and SK-OV3 cells in the G0/G1 phase and G2/M phase were significantly increased compared with control group (P<0.05, P<0.01), the apoptosis rate had significantly increased (P<0.05, P<0.01). 9b (3, 10 and 30 mg·kg-1·d-1) could significantly reduce tumor weight in the S180 and B16 solid tumor mouse model in vivo. CONCLUSION: 9b showed significantly anti-tumor activity both in vivo and in vitro, of which the mechanism might be associated with the change of cell cycle distribution and induction of tumor cell apoptosis.

Child ; Child Welfare ; Education, Medical, Continuing ; Humans ; Pediatrics ; education

OBJECTIVETo assess the efficacy of nasal intermittent positive pressure ventilation (NIPPV) in treatment of respiratory distress syndrome (RDS) in premature infants.

METHODSAccording to the requirements of Cochrane systematic review, a thorough literature search was performed among PubMed (1977-2008), Embase (1989-2008), OVID, Cochrane (2008), Chinese Digital Hospital Library (www.chkd.cnki.net) and Chinese Biomedical Literature Disk Database (CBMdisc). Quality assessments of clinical trials were carried out. Randomized controlled trials (RCTs) with NIPPV and RDS were enrolled, and Revman 4.2 software was used for meta-analysis. The trials were analyzed using relative risk (RR) for dichotomous data, weighted mean difference (WMD) were used for continuous data, both kind of data were expressed by 95% confidence intervals (95% CI). For homogenous data (P> or =0.10), fixed effects model was calculated, for heterogeneity data (P<0.10), random effects model was calculated.

RESULTSFive RCTs involving 284 premature infants diagnosed as respiratory distress syndrome (RDS) were included. Three studies comparing NIPPV with nasal continuous positive airway pressure (NCPAP) in the postextubation period, the extubation failure rate was 8.34% vs 40.79% in NIPPV group and NCPAP group, the NIPPV group had significantly lower extubation failure rates [RR 0.21 (95% CI: 0.10-0.45; P<0.001)]. Two of the above-mentioned three studies analyzed bronchopulmonary dysplasia (BPD) rates, the incidence of BPD was 39.34% vs 54.39% in NIPPV group and NCPAP group, the NIPPV group had a trend towards lower BPD rates, but this did not reach statistical significance [RR 0.73 (95% CI: 0.49-1.07; P=0.11)]. NIPPV was used as primary mode in two studies, one compared with conventional ventilation (CV), which detected that the NIPPV group had significantly lower BPD rates (10% vs. 33.33%, P=0.04); the other compared with NCPAP, which also showed that NIPPV group had significantly lower BPD rates (2.33% vs. 17.07%, P=0.03).

CONCLUSIONThe primary mode NIPPV was found to be feasible as a method of ventilation in preterm infants with RDS, and was associated with a decreased incidence of BPD. In the postextubation period, NIPPV is more effective in preventing failure of extubation than NCPAP.

Humans ; Infant, Newborn ; Infant, Premature ; Intermittent Positive-Pressure Ventilation ; Respiratory Distress Syndrome, Newborn ; therapy

Atrial Flutter ; diagnosis ; drug therapy ; physiopathology ; Female ; Humans ; Infant, Newborn ; Male

OBJECTIVETo evaluate the clinical features of respiratory diseases of late preterm neonates.

METHODSSix hundred and thirty late preterm infant(gestational age: 34~36+6weeks),4401 cases of term infants and 328 early preterm infants who were born at the obstetrical department of Peking University 3rd Hospital from January 2009 to December 2010 were enrolled. Among them 84 late preterm infants, 135 term infants and 182 early preterm infants developed respiratory diseases. The incidence of respiratory diseases,clinical features and the severity of the diseases were compared among the three groups.

RESULTSThe incidence and mortality rates of respiratory diseases and the percentage of severe cases were significantly higher in the late preterm group than in the term group, but lower than in the early preterm group (P<0.01). The symptoms of respiratory disease occurred earlier in the late preterm group than in the term group, but later than in the early preterm group (P<0.01). The late preterm group had a significantly higher incidence of tachypnea and lower incidence of retraction sign when compared with the term and early preterm groups (P<0.05). The percentages requiring oxygen therapy and mechanical ventilation in the late preterm group were both significantly higher than in the term group, but lower than in the early preterm group (P<0.05). The multiple linear regression analysis showed 11 factors associated with the severity of respiratory diseases: decreased arterial partial pressure of oxygen, hematokrit, pH value and respiratory rate, arterial oxyhemoglobin saturation, systolic arterial pressure, 5 minute Apgar score and gestational age, and increased blood urea nitrogen, heart rate and respiratory rate.

CONCLUSIONSLate preterm infants are more likely to develop respiratory diseases than term infants, and to develop a more severe condition and need a more intensive respiratory support treatment. Tachypnea is a common presentation of dyspnea in late preterm infants and occurs earlier than in term infants but later than in early preterm infants. It may usually indicate a serious condition when dyspnea, abnormal heart rate and blood pressure, and multisystem damages occur in late preterm infants.

Humans ; Incidence ; Infant, Newborn ; Infant, Premature, Diseases ; epidemiology ; mortality ; Prognosis ; Respiratory Tract Diseases ; epidemiology ; mortality ; Retrospective Studies

OBJECTIVETo study the relationship between angiotensin converting enzyme (ACE) gene insertion/deletion (I/D) polymorphism and left ventricular mass (LVM) in newborns admitted to the neonatal intensive care unit (NICU).

METHODSSeventy-two newborns admitted to the NICU were enrolled. ACE genotypes were determined by genomic DNA which was isolated from heel-prick blood. Disease status of the newborns was evaluated by the Neonatal Critical Score (draft) on postnatal day 1. LVM and LVM index (LVMI) were evaluated by echocardiography on postnatal days 1-3.

RESULTSDD genotype was identified in 11 cases, ID genotype in 31 cases, and II genotype in 30 cases. There were no significant differences in clinical characteristics, critical score and body measurements in newborns with different genotypes. The DD genotype group showed significantly lower LVMI than the group with ID+II genotypes (29±4 g/m2 vs 35±8 g/m2; P<0.05).

CONCLUSIONSACE gene polymorphism is associated with the LVMI in newborns admitted to the NICU. The LVMI of DD genotype carriers is significantly lower than that of ID+II genotypes carriers, which suggests that D allele may be associated with the growth and development of left ventricular.

Echocardiography ; Female ; Gene Deletion ; Genotype ; Heart Ventricles ; diagnostic imaging ; Humans ; Intensive Care Units, Neonatal ; Male ; Mutagenesis, Insertional ; Peptidyl-Dipeptidase A ; genetics ; Polymorphism, Genetic

OBJECTIVETo investigate the status of pubertal development in children born with assisted reproductive technology (ART).

METHODSA retrospective analysis was performed on the pubertal development data of children born with ART in Peking University Third Hospital from 1994 to 2003 (ART group). The data in the cross-sectional study "Reports on the Physical Fitness and Health Research of Chinese School Students in 2010" were used as a control. The age at menarche and the age at spermarche were compared between the two groups. The status of pubertal development in the overweight and obese children in the ART group was evaluated to investigate the correlation between pubertal development and body mass index (BMI).

RESULTSA total of 200 children born with ART were enrolled in this study, and 72 of them (41 males and 31 females) completed the survey (response rate=36.0%). In the ART group, the mean age at spermarche and the mean age at menarche were 13.9 years (95%CI: 13.7-14.3 years) and 12.2 years (95%CI: 11.8-12.6 years), respectively. There were no significant differences in the age at spermarche and the age at menarche between the ART and control groups (P>0.05). In the ART group, there were no significant differences in the age at spermarche and the age at menarche between the overweight and obese children and the normal weight children (P>0.05). There were also no significant differences in overweight rate and obesity rate between the children in the ART group and the adolescents in Beijing (P>0.05). In the ART group, there was no significant correlation between the age at spermarche or menarche and BMI (P>0.05).

CONCLUSIONSNo delayed or precocious puberty is observed in children born with ART. This is consistent with the normal control data. And there is no significant correlation between pubertal development and BMI in children born with ART.

Adolescent ; Body Mass Index ; Child ; Child Development ; Cross-Sectional Studies ; Female ; Humans ; Male ; Menarche ; Obesity ; physiopathology ; Overweight ; physiopathology ; Puberty ; physiology ; Reproductive Techniques, Assisted ; Retrospective Studies

Objective To assess the efficiency of synchronized nasal intermittent positive pressure ventilation (SNIPPV) as a transitional mode in treatment of neonatal respiratory distress syndrome (RDS) after extubation.Methods In this single-center and randomized controlled trial,preterm infants (gestational age less than 35 weeks)with RDS who received mechanical ventilation were randomly assigned to receive SNIPPV(33 cases) or NCPAP(34 cases) after extubation.Blood gas analysis,prevalence of extubation failure and complications were compared between the 2 groups.Results The Pa (O2) in SNIPPV group was significantly higher but the pa (CO2) was significantly lower than those in the NCPAP group at 3 h and 12 h after extubation respectively(all P ＜ 0.05).Infants treated with SNIPPV had a decreased incidence of hypoxemia,hyperbicarbonatemia and extubation failure compared with those of patients treated with NCPAP (all P ＜ 0.05).SNIPPV group had a decreased incidence of apnea (P =0.000),shorter duration of mechanical ventilation and oxygen treatment duration than those of NCPAP group (all P ＜ 0.05).Conclusions SNIPPV is superior to NCPAP in serving as a transitional mode after extubation for preterm infants with RDS,and should be used in preference after extubation.

BACKGROUNDWhite blood cell (WBC) counts and differentials performed using an automated cell counter typically require manual microscopic review. However, this last step is time consuming and requires experienced personnel. We evaluated the clinical efficiency of using flow cytometry (FCM) employing a six-antibody/five-color reagent for verifying automated WBC differentials.

METHODSA total of 56 apparently healthy samples were assessed using a five-color flow cytometer to verify the normal reference ranges of WBC differentials. WBC differentials of 622 samples were also determined using both a cell counter and FCM. These results were then confirmed using manual microscopic methods.

RESULTSThe probabilities for all of the parameters of WBC differentials exceeded the corresponding normal reference ranges by no more than 7.5%. The resulting WBC differentials were well correlated between FCM and the cell counter (r > 0.88, P < 0.001), except in the case of basophils. Neutrophils, lymphocytes, and eosinophils were well correlated between FCM and standard microscopic cytology assessment (r > 0.80, P < 0.001). The sensitivities of FCM for identification of immature granulocytes and blast cells (72.03% and 22.22%, respectively) were higher than those of the cell counter method (44.92% and 11.11%, respectively). The specificities of FCM were all above 85%, substantially better than those of the cell counter method.

CONCLUSIONThese five-color FCM assays could be applied to accurately verify abnormal results of automated assessment of WBC differentials.

Adolescent ; Adult ; Aged ; Aged, 80 and over ; Child ; Child, Preschool ; Female ; Flow Cytometry ; methods ; Humans ; Infant ; Leukocyte Count ; methods ; Leukocytes ; cytology ; Male ; Middle Aged ; Young Adult