Clinicopathological and prognostic significance of hypoxia-inducible factor-1 alpha in lung cancer: a systematic review with meta-analysis / 华中科技大学学报（医学）（英德文版）

Hypoxia-inducible factor-1 alpha (HIF-1α) plays a vital role in the initiation, evaluation and prognosis in lung cancer. The prognostic value of HIF-1α reported in diverse study remains disputable. Accordingly, a meta-analysis was implemented to further understand the prognostic role of HIF-1α in lung cancer. The relationship between HIF-1α and the clinicopathological characteristics and prognosis of lung cancer were investigated by a meta-analysis. PubMed and Embase were searched from their inception to January 2015 for observational studies. Fixed-effects or random-effects meta-analyses were used to calculate odds ratios and 95% confidence intervals of different comparisons. A total of 20 studies met the criteria. The results showed that HIF-1α expression in lung cancer tissues was significantly higher than that in normal lung tissues. Expression of HIF-1α in patients with squamous cell carcinoma was significantly higher than that of patients with adenocarcinomas. Similarly, non-small cell lung cancer (NSCLC) patients had higher HIF-1α expression than small cell lung cancer (SCLC) patients. Moreover, lymph node metastasized tissues had higher HIF-1α expression than non-lymph node metastasized tissues. A high level HIF-1α expression was well correlated with the expression of vascular endothelial growth factor and epidermal growth factor receptor in the NSCLC. Notably, NSCLC or SCLC patients with positive HIF-1α expression in tumor tissues had lower overall survival rate than patients with negative HIF-1α expression. It was suggested that HIF-1α expression may be a prognostic biomarker and a potential therapeutic target for lung cancer.

Epidemiological characteristics and temporal-spatial clustering analysis on hand-foot-mouth disease in Jiangsu province, 2009-2011 / 中华流行病学杂志

Objective To analyze the epidemic characteristics of hand-foot-mouth disease (HFMD) in Jiangsu province.Methods We downloaded the case-data of HFMD in Jiangsu province during 2009-2011 from the Chinese National Notifiable Infectious Disease Reporting System,and made a comprehensive analysis on the epidemiological features of it with descriptive epidemiological methods and retrospective space-time permutation scan statistics.Results A total of 285 414 cases were reported in Jiangsu,from 2009 to 2011,with an annual incidence of 122.66 per 100 000.There were 3686 severe cases in the 3 years accumulatively,accounting for 1.29％ of the total.Proportion of the cases being 5 years old or even younger was 93.64％.Scatteredly living children accounted for 64.08％ of the total cases and 78.65％ of the severe cases,respectively.The epidemics of HFMD were visible in each city of Jiangsu province,with a lowest annual incidence rate of 44.02 per 100 000 and a highest one up to 202.90 per 100 000.Regions as Suzhou,Nanjing,Wuxi had the highest incidence in the province,with cases in these three areas occupying almost 40％ of all.The numbers of severe cases in Suqian and in Yancheng cities increased by 339.22％ and 328.33％ in 2011 compared to in 2010,respectively,and the rates of increase in these two cities were much higher than those in the other regions.Two peaks of incidence were observed every year,with the highest occurring between April and June and the second occurring in November.The spatial-temporal distribution of HFMD was not random in Jiangsu province,from 2009 to 2011.Clusters for general cases in August and 7 clusters for severe cases were detected,respectively.12 359 cases of HFMD were laboratory confirmed in the said 3 years,including 10 414 common cases and 1945 severe cases.EV71 and CoxA16 accounted for 43.49％ and 37.07％ of common cases,respectively.In terms of the severe cases,the ratios were 80.82％ and 5.96％,respectively.Conclusion HFMD was highly endemic in Jiangsu province,and the situation of prevention and control for it is still grim.Scatteredly living children of 5 years old or younger were the major population at risk,and the epidemic in different regions and seasons was different.EV71 and CoxA16 were the major etiologic agents,but the etiologic constitute showed seasonal changes.

Therapeutic efficacy of bone marrow-derived mesenchymal stem cells infused into mice with liver injury induced by concanavalin A / 中国实验血液学杂志

The aim of this study was to evaluate the therapeutic potential of bone marrow mesenchymal stem cells (MSC) on acute liver injury induced by concanavalin A (ConA). MSCs were isolated from male C57BL/6 mice and cultured, and a ConA-induced acute liver injury model was used. MSCs were systemically infused immediately after mice were challenged with ConA, control mice received only saline infusion. 24 hours after MSC transplantation, the level of serum aminotransferases, histologic change and in situ apoptosis of cells were detected, the expression of inflammatory mediators were examined by real-time RT-PCR. The results indicated that MSC transplantation significantly reduced ConA-induced acute liver injury, including the decrease of the level of serum alanine aminotransferase (ALT), serum aspartate aminotransferase (AST) and the extenuation of liver necrosis and in situ apoptosis. Furthermore, after MSC infusion the expression of TNF-alpha, IFN-gamma in liver decreased greatly (p<0.05) with no statistical difference in the expression of iNOS, IL-2 and IL-10 (p>0.05). It is concluded that the systemic infusion of MSCs can alleviate ConA induced acute liver injury in mice.

Study of the relationship between early growth response gene 1 activity in p38 mitogen-activated protein kinase pathway and epirubicin resistance of human breast carcinoma cells / 中华病理学杂志

<p><b>OBJECTIVE</b>To investigate the relationship between activities of early growth response gene 1 (EGR-1) of p38 mitogen-activated protein kinase (MAPK) pathway and in the epirubicin resistance of breast carcinoma cells.</p><p><b>METHODS</b>Protein expression of phosphorylated p38MAPK was detected by confocal spectral microscopy. Using specific inhibitor SB203580, the effect of p38MAPK on cell apoptosis was analyzed by FITC-Annexin-V/PI double staining. The concentration of epirubicin was detected by flow cytometry (FCM). The 50% inhibition concentration (IC50) of epirubicin on MCF-7/Adr cells was determined by MTT method. Electrophoretic motility shift assay (EMSA) was performed to examine the affinity of EGR-1. EGR-1 mRNA was assessed by RT-PCR. The expression levels of p-glycoprotein, phosphorylated p53 and p38 were detected by Western blot.</p><p><b>RESULTS</b>After treatment with SB203580 (15 micromol/L) 24 h and 48 h, (1) the early and late apoptosis of MCF-7/Adr cells expressing the phosphorylated p38MAPK protein was (25.36 +/- 1.17)% and (38.21 +/- 1.25)%, respectively, P < 0.05. And the tendency was in a time-dependent manner. (2) The average fluorescence intensity of MCF-7/Adr cells expressing the phosphorylated p38MAPK protein was (32.45 +/- 2.36) and (41.66 +/- 3.12), higher than the blank group (14.17 +/- 1.45) and DMSO group (16.28 +/- 0.63), P < 0.01. The epirubicin resistance of MCF-7/Adr cells significantly decreased. (3) SB203580 demonstrated a significantly higher level of EGR-1 activity. The IC50 was (21.53 +/- 2.17) and (8.77 +/- 1.02), lower than the DMSO group (40.74 +/- 2.56). MCF-7/Adr cells treated with SB203580 down-regulated the p38MAPK pathway activity, but up-regulated the EGR-1 mRNA expression. SB203580 significantly increased the cellular phosphorylated p53 protein level, but decreased the p-glycoprotein level in MCF-7/Adr cells.</p><p><b>CONCLUSIONS</b>There is a close relationship between p38MAPK pathway activity and the epirubicin resistance of breast carcinoma cells. The activation of EGR-1 mediated by p38MAPK pathway plays a critical role in epirubicin resistance.</p>

Effect of total body irradiation on cellular senescence related indexes of bone marrow mesenchymal stem cells / 中国实验血液学杂志

The aim of this study was to explore the changes in cellular senescence related indexes of bone marrow mesenchymal stem cells (BMMSCs) after total body irradiation (TBI). At different time points after 4 Gy irradiation, BMMSCs were isolated from male C57BL/6 mice and cultured. Morphology, senescence-associated beta-galactosidase (SA-beta-gal) staining and cell cycle analysis were used to evaluate the changes in BMMSCs at cellular level while real-time RT-PCR was used to detect the alterations in senescence related gene expression including p16INK4a, p21Cip1/Waf1, p53 and TGF-beta1. The results showed that within 4 weeks after exposure to 4 Gy TBI, the morphology of BMMSCs and the expression level of SA-beta-gal were not significantly changed, the cellular senescence-related cell cycle arrest was not occurred and the senescence related gene expression level was not increased. It is concluded that at the early stage after 4 Gy TBI, the related molecular level of cellular senescence in BMMSCs is not changed.

Reduction of bone marrow mesenchymal stem/progenitor cells pool and alteration of their osteogenesis potential caused by total body irradiation / 中国实验血液学杂志

To investigate the effect of irradiation on the quantity and osteogenesis potential of BMMSCs and to explore the response of them in the irradiation stress and its contribution to long-term effects of radiation-induced bone and hematologic injury, a total body irradiation (TBI) murine model was adopted. The number of CFU-F and cell cycle profile of BMMSCs were analyzed at different time points before and after TBI. Osteogenic differentiation was evaluated by Von Kossa staining, expressions of osteogenesis-related genes and transcriptional coactivator with PDZ-binding motif (TAZ) were detected by real-time RT-PCR. The results showed that the number of CFU-F decreased greatly at day 28 after TBI. At day 3 after TBI, more cells entered cell cycle and the osteogenesis potential was greatly enhanced followed by recovery of cell cycle distribution and significant defect in osteoblast differentiation respectively, meanwhile the expression of TAZ was changed. It is concluded that TBI results in the reduction of bone marrow mesenchymal stem/progenitor cell pool and alters the osteogenesis potential of BMMSCs, which is related to the change of TAZ expression.