OBJECTIVETo examine the temporal and spatial expression of vascular endothelial growth factor (VEGF) and angiopoietins (Ang) in rat brain after cerebral ischemia, and to elucidate the roles they played in angiogenesis and vascular permeability.

METHODSRats were subjected to either middle cerebral artery occlusion (MCAO) or sham operation. Reverse transcriptase-polymerase chain reaction, Western blotting, and immunohistochemistry were used to detect the expression of VEGF, Ang-1 and Ang-2 at different time points after ischemia. CD31 was used to label endothelial cells after MCAO. Vascular permeability was determined by Evans blue.

RESULTSVEGF was markedly increased at 2 h, had an initial peak at 12 h (0.7249 ± 0.1933, P < 0.01), and a second peak at 7 days (0.5264 ± 0.1519, P < 0.01). Ang-2 mRNA and protein significantly increased after MCAO, both of them peaked at 12 h (0.6747 ± 0.2416, P < 0.01; 1.1197 ± 0.1780, P < 0.01). In contrast, Ang-1 mRNA and protein gradually decreased after MCAO, respectively reaching a minimum at 3 d (0.3220 ± 0.1427, P < 0.01) and 1 d (0.1298 ± 0.0293, P < 0.01). Changes in the expression of these factors correlated with the progress of angiogenesis and vascular permeability. Evans blue test revealed that the vascular permeability gradually increased, and peaked at day 1 after ischemia [(6.219 ± 0.887) µg/g, P < 0.01].

CONCLUSIONDynamic temporal changes in VEGF, Ang-1 and Ang-2 expression stimulate the cerebral angiogenesis after focal cerebral ischemia.

Angiopoietin-1 ; genetics ; metabolism ; Angiopoietin-2 ; genetics ; metabolism ; Animals ; Blotting, Western ; Capillary Permeability ; Immunohistochemistry ; Infarction, Middle Cerebral Artery ; metabolism ; pathology ; physiopathology ; Male ; Neovascularization, Physiologic ; RNA, Messenger ; metabolism ; Random Allocation ; Rats ; Rats, Sprague-Dawley ; Reverse Transcriptase Polymerase Chain Reaction ; Vascular Endothelial Growth Factor A ; genetics ; metabolism

Objective To explore risk factors of congenital malformations (CMs) and to evaluate its impacts on adverse pregnancy outcomes (APOs). Methods A prospective cohort study was conducted among pregnant women who received the first antenatal care from March 2013 to February 2016 in the reproductive center, obstetrics clinics, infertility clinics and ultrasound department of Hunan Provincial Maternal and Child Health Hospital. Corresponding information from pregnant women and their spouses were collected. Univariate and multivariate Logistic regression were used to screen possible risk factors of CMs and evaluate the impacts of CMs on other APOs. Results The study showed that women had history of non-standard BMI, smoking, hepatitis, pregnancy-related complications, gestational diabetes mellitus, infertility and using assisted reproductive technology before pregnancy; had no folic acid taking, active and passive smoking, drinking, uneven diet, high intensity physical activity during pregnancy increased the risk of CMs in offspring. Furthermore, the history of spouse smoking and eating betel nut also increased the risk of CMs in offspring. CMs might increase the risk of preterm birth, very preterm birth, low birth weight, very low birth weight, and perinatal mortality. Conclusions There are many risk factors of CMs. Knowing these risk factors, and giving them optimal prevention strategies and effective intervention measures are important measures in preventing the occurrence of CMs and other APOs.

AIM:To investigate the effect of proline-spirooxindole on the viability and apoptosis of human nonsmall-cell lung cancer A549 cells.METHODS:The effect of proline-spirooxindole on the viability of A549 cells was determined by CCK-8 assay.The apoptosis was analyzed by flow cytometry.The effects of proline-spirooxindole on the expression of PARP and p53 and the phosphorylation of m TOR were determined by Western blot.RESULTS:After A549 cells were treated with proline-spirooxindole (25, 50 and 100 mg/L) , the cell viability was decreased (P<0.01) compared with DMSO control group.The apoptotic rate was increased compared with DMSO control group (P<0.01).The protein expression of p53 was up-regulated, the increased apoptotic protein cleaved PARP was observed, and the phosphorylation of m TOR was inhibited (P<0.01).CONCLUSION:Proline-spirooxindole inhibits the viability of A549 cells and induces apoptosis, which may be related to the phosphorylation of m TOR.

Objective To investigate the effect of matrine on Fas expression in C6 glima in a tumor-bearing rat model. Methods Cultured cerebral glioma C6 cells wgre injected stereotactically into the lef tcaudate nucleus of the rats.The ratswere randomized into untreated group,bomeol-treated group,low-dose matrine group,high-dose maaine group,low-dose matrine+bomeol group,and high-dose matrine+borneol group.The effect of matrine on the quality of life of the rats and the glioma volume was evaluated according to the survival state of the rats and by gross observation,magnetic resonance imaging(MRJ)and HE smining of the brain tissue.Immunohistochemistry was performed to detect Fas expression in the glioma cells. Results The survival state ofthe rats,gross observation of the brain specimen. and results of MRI and HE staining all showed that matrine significantly improved the quality oflife of the glioma-bearing rats and inhibited the glioma cell proliferation.Fas expression Was significantly higher in low-dose matrine+bomeol group(98.16±11.82) and high-dose matrine+bomeol group(112.80±12.12)than in untreated group(39.09±7.79),bomeol group(46.87±7.43),low-dose matrinc group(42.41±7.83),and high-dose matrine group(44.20±7.47)(P＜0.05).Fas expression Was obviously upregulated in the high-dose matrine+bomeol group aS compared with the low-dose matrine+bomeol group(P＜0.05).Conclusion Matrine Can significantly upregulate Fas expression in glioma and inhibit glioma cell proliferation in the glioma-bearing rat model.

BACKGROUNDNo-reflow after emergency percutaneous coronary intervention (PCI) for acute ST segment elevation myocardial infarction (STEMI) is related to the severe prognosis. The aim of this study was to evaluate the efficacy of Tongxinluo, a traditional Chinese medicine, on no-reflow and the infarction area after emergency PCI for STEMI.

METHODSA total of 219 patients (female 31, 14%) undergoing emergency PCI for STEMI from nine clinical centers were consecutively enrolled in this randomized, double-blind, placebo-controlled, multicenter clinical trial from January 2007 to May 2009. All patients were randomly divided into Tongxinluo group (n = 108) and control group (n = 111), given Tongxinluo or placebo in loading dose 2.08 g respectively before emergency PCI with aspirin 300 mg and clopidogrel 300 mg together, then 1.04 g three times daily for six months after PCI. The ST segment elevation was recorded by electrocardiogram at hospitalization and 1, 2, 6, 12, 24 hours after coronary balloon dilation to evaluate the myocardial no-flow; myocardial perfusion scores of 17 segments were evaluated on day 7 and day 180 after STEMI with static single-photon emission computed tomography (SPECT) to determine the infarct area.

RESULTSThere was no statistical significance in sex, age, past history, chest pain, onset-to-reperfusion time, Killip classification, TIMI flow grade just before and after PCI, either in the medication treatment during the follow up such as statin, β-blocker, angiotensin converting enzyme inhibitor (ACEI) or angiotensin receptor blocker (ARB) between two groups. There was significant ST segment restoration in Tongxinluo group compared to the control group at 6 hours ((-0.22 ± 0.18) mV vs. (-0.18 ± 0.16) mV, P = 0.0394), 12 hours ((-0.24 ± 0.18) mV vs. (-0.18 ± 0.15) mV, P = 0.0158) and 24 hours ((-0.27 ± 0.16) mV vs. (-0.20 ± 0.16) mV, P = 0.0021) reperfusion; and the incidence of myocardial no-reflow was also reduced significantly at 24-hour reperfusion (34.3% vs. 54.1%, P = 0.0031). The myocardial perfusion scores of 17 segments evaluated by static SPECT was improved significantly on day 7 and day 180 after STEMI in Tongxinluo group compared to the control group (0.61 ± 0.40 vs. 0.76 ± 0.42, P = 0.0109 and 0.51 ± 0.42 vs. 0.66 ± 0.43, P = 0.0115, respectively). There was no significant difference in severe adverse events between two groups.

CONCLUSIONTongxinluo as a kind of traditional Chinese medicine could reduce myocardial no-reflow and infarction area significantly after emergency PCI for STEMI with conventional medicine therapy.

Acute Disease ; Aged ; Coronary Circulation ; Double-Blind Method ; Drugs, Chinese Herbal ; therapeutic use ; Electrocardiography ; Female ; Humans ; Male ; Medicine, Chinese Traditional ; Middle Aged ; Myocardial Infarction ; drug therapy ; physiopathology ; Tomography, Emission-Computed, Single-Photon

OBJECTIVETo study the association of single nucleotide polymorphisms (SNPs) of transcription factors (NKX2.5, GATA4, TBX5, and FOG2) with congenital heart disease (CHD) in the Chinese population.

METHODSPubMed, Google Scholar, CNKI, Wanfang Data, and Weipu Data were searched for articles on the association of SNPs of target genes with CHD in the Chinese population. If one locus was mentioned in at least two articles, the random or fixed effect model was used to perform a pooled analysis of study results and to calculate the pooled OR and its 95%CI. If a locus was mentioned in only one article, related data were extracted from this article to analyze the association between the SNPs of this locus and CHD.

RESULTSTwenty-three articles were included. The Meta analysis showed that there were significant differences between the CHD and control groups in the genotype and allele frequencies of GATA4 rs1139244 and rs867858 and the genotype frequency of GATA4 rs904018, while there were no significant differences in the SNPs of the other genetic loci between the two groups. The single-article analysis showed that there were significant differences between the two groups in the allele frequencies of NKX2.5 rs118026695/rs703752, GATA4 rs884662/rs12825/rs12458/rs3203358/rs4841588, and TBX5 rs6489956. There were no significant differences in the SNPs of FOG2 locus between the two groups.

CONCLUSIONSThe SNPs of some loci in NKX2.5, GATA4, and TBX5 are associated with CHD in the Chinese population, but the association between the SNPs of FOG2 locus and the development of CHD has not been found yet.

Asian Continental Ancestry Group ; genetics ; DNA-Binding Proteins ; genetics ; GATA4 Transcription Factor ; genetics ; Genetic Predisposition to Disease ; Heart Defects, Congenital ; genetics ; Homeobox Protein Nkx-2.5 ; genetics ; Humans ; Polymorphism, Single Nucleotide ; T-Box Domain Proteins ; genetics ; Transcription Factors ; genetics

Acute Disease ; Adult ; Cerebral Infarction ; diagnosis ; diagnostic imaging ; Fabry Disease ; diagnosis ; diagnostic imaging ; Humans ; Magnetic Resonance Imaging ; Male

Humans ; Vascular Stiffness ; Coal Mining ; Occupational Diseases/epidemiology* ; Risk Factors ; Coal ; Miners