With the advent of the cancer stem cell hypothesis,the field of cancer research has experienced a revolution in how we think of and approach cancer. The discovery of "tumor-initiating cell" has offered an explanation for several long-standing conundrums on why tumors behave the way they do to treatment. Despite the great amount of research that has been done in order to understand the molecular aspects of tumors,the prognosis of tumors remains dismal. The slow progress in extending the survival of patients with malignant tumors is very likely due to poor understanding of the cell of origin in these tumors.This review article discusses the progress in our understanding of tumor-initiating cell as the cell of origin in cancers. We review the different proposed mechanisms of how tumor-initiating cell may originate,the molecular mechanisms of cancer initiation and progression, and finally the clinical implications of this research.

ObjectiveTo determine optimal positive end expiratory pressure (PEEP) in mechanical ventilation in children with severe asthmatoid disease based on the quasistatic pressure-volume (P-V) curve.MethodsA serf-control study was done on 23 children with severe asthmatoid disease in the pediatric intensive care unit( PICU ).Quasistatic lung P-V curve of these patients was analyzed and the lower inflection point (LIP) from P-V curve was determined.Three different PEEP (0 cm H2O,LIP,LIP+2 cm H2O,1 mm H2O =0.098 kPa) were given to the patients.The effects of PEEP at different levels on gas exchange,hemodynamic and airway pressure were observed.ResultsThe quasistatic LIP were (2.70 ±2.00)cm H2O.When PEEP was increased to the level of LIP + 2 cm H2O,PaO2 / FiO2 and lung compliance improved significantly (P ＜ 0.01 ) and dynamic lung compliance was the highest,peak inspiratory pressure was (22.30 ± 3.00) cm H2O and mean airway pressure was( 14.11 ± 1.01 ) cm H2O,without obvious adverse effects on mean arterial blood pressure and heart rate.There was no difference in PaCO2,when compared PEEP =0 cmH2O to PEEP =LIP + 2 cmH2O.ConclusionThe application of PEEP is safe.LIP + 2 cm H2O from quasistatic P-V curve could be set as the optimal PEEP under which mechanical ventilation has the best efficacy and do not aggravate CO2 retention and abnormality of hemodynamics in children with severe asthmatoid disease.

OBJECTIVE:To explore the effect of nifedipine combined with losartan on the blood pressure and renal function of hypertension complicated with coronary heart disease. METHODS:150 patients with hypertension complicated with coronary heart disease were randomly divided into observation group and control group. Control group was orally treated with Nifedipine sustained release tablet 30 mg,once a day;observation group was additionally treated with Losartan potassium capsules 50 mg,once a day. The treatment course for both groups was 1 month. Systolic blood pressure,diastolic blood pressure,renal function indicators be-fore and after treatment,and incidence of adverse reactions in 2 groups were observed. RESULTS:After treatment,systolic blood pressure and diastolic blood pressure after 3 months was lower than 1 month and lower than before treatment in same group,renal function indicators were significantly lower than before treatment,and observation group was lower than control group,the differ-ences were statistically significant(P<0.05);the incidence of adverse reactions in observation group was significantly lower than control group,the difference was statistically significant(P<0.05). CONCLUSIONS:Nifedipine combined with losartan can well control the blood pressure of hypertension complicated with coronary heart disease,protect renal functions,with good safety.

Objective To explore differences of drug resistance of temozolomide(TMZ) on different CD133 immune prototype of glioma cells and study on the changes of their sensitivity to TMZ through increased PUMA. Methods CD133+-U87MG cells sorted by CD133 magnetic beads were cultured in serum-free stem cell medium respectively. The cells were infected with recombinant adenovirus, Ad-PUMA, diluted in cell culture medium with or without TMZ intervention.The inhibitory rate of cell proliferation was detected by MTT assay and 50 ％ inhibition concentration of TMZ was calculated. Apoptosis rates of CD133+-U87MG cells were assessed by flow cytometry (FCM) before and after intervention of exogenous PUMA and TMZ.Results The TMZ IC50 values of CD133+glioma cells were higher than that of CD133- glioma cells. There were significant differences in apoptosis rate between CD133+ glioma cell and CD133- glioma cell (all P＜0.05).Conclusion AdPUMA joint TMZ can promote glioma stem cells apoptosis, thus improve the sensitivity to chemotherapy of glioma.

Objective To observe the influence of p53-upregulated modulator of apoptosis (PUMA) on the growth of human brain glioma cell lines U251 (p53 mutant) and SHG-44 (p53 wild type),and to explore its possible mechanism.Methods Construct the adenovirus PUMA (Ad-PUMA) and vector of adenovirus (AdDsRed) which were respectively transfected into glioma cell lines U251 and SHG-44.Cells proliferation rates were measured with cell counting kit-8 (CCK-8).The apoptotic ratios were detected by flow cytometry.The expression of PUMA and apoptosis associated proteins (bcl-2,Bax) were determined with Western blot analysis.Caspase-3,Caspase-8,Caspase-9 activity were measured by Caspase activity assay kit.Results Compared with vector group and blank control group,Ad-PUMA transfected group showed strong cell proliferating inhibition effects [the inhibition rates were (50.89±4.73) ％ and (44.45±5.33) ％ respectively,P ＜0.05] and pro-apoptotic effects [apoptotic rates were (44.89±5.08) ％ and (31.67±7.32) ％,P ＜ 0.05] in different p53 glioma cell lines U251 and SHG-44.Western blot analysis showed that PUMA protein expression increased after Ad-PUMA transfection,accompanied by the reduced expression of the anti-apoptotic protein bcl-2 and the increased expression of pro-apoptotic protein Bax.The activity of Caspase testing results showed that the Caspase-3,Caspase-9 activity increased significantly,while the Caspase-8 activity changed little.Conclusion No matter how p53 phenotype,PUMA can inhibit glioma proliferation,promote apoptosis,and its mechanism may be through the mitochondrial apoptotic pathways,upregulation of Bax and inhibition of bcl-2 expression,which activated Caspase-9.Ad-PUMA is expected to become a new target for gene therapy of gliomas.

Objective To investigate the correlation between Dishevelled protein expression and the proliferation and invasion of glioma cells.Methods 67 cases of brain glioma specimens were collected.The expression of Dishevelled protein was detected with immunohistochemical method.The immunoreactivity score (IRS) of Dishevelled protein,and proliferation index (PⅠ) and invasion index (Ⅱ) were measured and their correlations were analyzed.Results The positive rate of Dishevelled protein in glioma was 65.7 ％ (44/67).IRS,PⅠ and Ⅱ were 4.15±3.13,(30.93±17.92) ％,(20.38±13.36) ％,respectively.Both PⅠ and Ⅱ significantly increased with an increase in the pathological grade of brain glioma (P ＜ 0.001).Furthermore,PⅠ and Ⅱ were significantly higher in the Dishevelled protein-positive group than those in the Dishevelled protein-negative group [(38.27±17.60) ％ vs (16.02±8.92) ％ of PⅠ and (30.03±13.81) ％ vs (10.63±4.41) ％ of Ⅱ,respectively,P ＜ 0.001].PⅠ and Ⅱ of glioma cells were positively correlated with IRS of Dishevelled protein (r =0.940 between PⅠ and IRS,and r =0.953 between Ⅱ and IRS,respectively).Conclusion Dishevelled protein plays an important role in the proliferation and invasion of brain malignant glioma.

Objective To investigate the role of endoplasmic reticulum stress ( ERS) in human brain gliomas cell(SHG-44) apoptosis induced by proteasome inhibitor MG-132. Methods Human glioma cells were passage cultured. Glioma cells were treated by MG-132 with varying concentration(5, 10, 15 and 50 μmol/L) for 24 h. Compared with cells prior to the treatment (control group), cell viability was detected by MTT assay and the expression of ERS associated proteins GRP78 and apoptosis associated proteins Caspsse-12 was examined by PCR and Western-blotting. Results After MG-132 treatment for 24 h, SHG-44 cell viability was decreased significantly (39 %) (P <0.05), and continued to show a significant decline with the increasing concentration of MG-132 (P <0.05). RT-PCR results showed that the expression of ERS associated proteins GRP78 in SHG-44 cells were significantly increased after 5, 10, 15 and 50 μmol/L MG-132 treatment, and the expression of Caspase-12 was significantly increased after 5 μmol/L MG-132 treatment, slightly increased after 10 and 15 μmol/L treatment compared with that after 5 μmol/L treatment and reached the peak after 50 μmol/L treatment. Western-blotting results of GRP78 in SHG-44 cells were same as results of RT-PCR. Conclusion ERS may be involved in the apoptosis of gliomas cells induced by proteasome inhibitor MG-132.

Objective To analyze the Doppler indices of uterine artery at 11-16 weeks normal gestation. Methods Two hundred and ninty-seven normal pregnant women were consecutively recruited to take routine ultrasound examination at 11-16 weeks' gestation. According to gestational week, they were divided into 6 groups (11-11+6 weeks, 12-12+6 weeks, 13-13+6 weeks, 14-14+6 weeks, 15-15+6 weeks, 16-16+6 weeks). According to the location of placenta, they were divided into 3 groups (central placenta, right placenta, left placenta). Finally, the pregnant women were divided into 5 groups (RI<0.60 group, 0.60-0.69 group, 0.70-0.79 group, 0.80-0.85 group and ≥ 0.85 group) according to resistance index (RI). Doppler indices of uterine artery were measured in each case. Results (1) The PIm, RIm, S/Dm values (the mean PI, RI, S/D values of bilateral uterine artery) were decreased with the progress of pregnancy, but the difference of the RIm, S/Dm were not significant. Only the decrease of PIm after 15 weeks was significant (P<0.05). The mean PIm of each group was:11 weeks 1.96±0.39, 12 weeks 1.94±0.45, 13 weeks 1.79±0.43, 14 weeks 1.79±0.36, 15 weeks 1.51±0.43, 16 weeks 1.50±0.30. (2) The PI, RI, S/D values of uterine artery with placenta attached were lower than the other side. In the left placenta group, bilateral RI difference was-0.04 (t=-3.095, P=0.005), bilateral PI difference was -0.24 (t=-3.232, P=0.004), bilateral S/D difference was-1.00 (t=-2.965, P=0.007);in the right placenta group, bilateral RI difference was 0.04 (t=6.159, P=0.000), bilateral PI difference was 0.43 (t=6.614, P=0.000), bilateral S/D difference was 2.05 (t=6.378, P=0.000);in the middle placenta group, bilateral RI difference was 0.02 (t=4.150, P=0.000), bilateral PI difference was 0.14 (t=4.475, P=0.000), bilateral S/D differencewas 0.54 (t=4.376, P=0.000). (3) According to the RI, incidence rates ofα-notch detected:in<0.60 group both sides were 0;in 0.60-0.69 group, left uterine artery was 0.08, right uterine artery was 0.08;in 0.70-0.79 group, left uterine artery was 0.34, right uterine artery was 0.31;in 0.80-0.85 group, left uterine artery was 0.65, right uterine artery was 0.72;in≥0.85 group, left uterine artery was 0.81, right uterine artery was 0.87. Conclusion The uterine artery Doppler indices of 11-16 weeks maybe a reliable and non-invasive method for examining uteroplacental perfusion.

Objective To investigate the effect of berberine on growth and apoptosis of human cervical cancer cell line HeLa and its possible mechanism.Methods The effect of berberine on growth of HeLa cells was studied by MTT assay.Apoptosis of HeLa cells exposed to berberine was observed by flow cytometry and DNA gel electrophoresis.The expression of Bax and Bcl-2 was studied by Western blotting analysis.Results Berberine markedly inhibited the proliferation of HeLa cells in a time-and dose-dependent manner.After incubation of HeLa cells with 20 and 40 mg/L berberine for 48 h,DNA Ladder can be observed.A typical "sub-G1 peak" was checked by flow cytometry.There was a very low rate of natural apoptosis(1.9?0.6)%,while in 5 mg/L berberine group,the apoptosis rate was(2.3?0.8)%.After exposing HeLa cells for 48 h to 20 and 40 mg/L berberine,the apoptosis rate reached(16.7?2.8)%(P

Objective To reports to anatomy and clinical application of the medialis pedis perforator flap. Methods The origin, course, distribution and out diameter of medial plantar perforators, which were located at the septums between the abductor hallucis muscle and the flexor digitorum brevis, and between the abductor hallucis muscle and the skeleton, were observed on 10 sides adult feet specimens perfused with red latex. 11 free medialis pedis perforator flaps were transferred for soft-tissue defect in hand. The areas of tissue defect ranged from 2 cm x 2 cm - 9 cmx 4 cm. Results The medial plantar artery sends 2 perforators with regular anatomy through the septum between the abductor hallucis muscle and the flexor digitomm bre-vis, and 2 perforators with regular anatomy through the septum between the abductor hallucis muscle and nav-icluar bone and the medial cuneiform bone. These perforators supply the medial plantar flap and medialis pedis flap respectively. All of the 11 cases of free medialis pedis perforator flap survived uneventfully. The flap areas ranged from 2 cm × 3 cm - 11 cm× 5 cm. The appearance and functional results were satisfactory with following up for 6 to 24 months. Conclusion The free medialis pedis perforator flap is a good method in repairing soft-tissue defect in hand.