ABSTRACT OBJECTIVE To explore the pharmacological mechanism of trace elements in preterm low birth weight infants through network pharmacology. METHODS Targets associated with trace elements were obtained from Drugbank database and TTD database. Genes related to preterm low birth weight infants were collected from GeneCards database and DisGeNET database. Two groups of data were intersected to get mapping targets. Protein-protein interaction network of mapping targets were constructed by STRING database. Candidate targets were screened by Cytoscape 3.6.1 and ranked to obtain key targets. The major trace elements were defined by establishing network of “trace elements-candidate targets”. Kyoto Encyclopedia of Genes and Genomes(KEGG) and Gene Ontology(GO) term enrichment analysis was performed via g:Profiler software to predict the molecular mechanisms and related pathways of trace elements on preterm low birth weight infants. RESULTS A sum of 211 targets of trace elements in preterm low birth weight infants were screened, including 26 candidate targets and three key targets: albumin(ALB), glyceraldehyde-3-phosphate dehydrogenase(GAPDH) and fibronectin 1(FN1). The major trace elements were copper(Cu) and zinc(Zn), regulating 22 and 19 targets respectively. KEGG pathway enrichment analysis predicted that three major pathways were complement and coagulation cascades, cholesterol metabolism as well as lipid and atherosclerosis. CONCLUSION The major trace elements Cu and Zn may cause neuronal damage and reduce the risk of oxidative stress-related diseases in premature infants through the regulation of GAPDH, ceruloplasmin(CP), superoxide dismutase 1(SOD1), etc. The appropriate levels of Cu and Zn for preterm infants may regulate cholesterol metabolism and other signaling pathways and therefore reduce the risk of cardiovascular diseases in premature infants and adult. Further investigation of the pharmacological mechanism of trace elements in preterm infants is necessary to provide a more sufficient theoretical basis for the good growth and development of preterm infants.

BACKGROUND:The mechanism underlying Wal erian degeneration fol owing peripheral nerve injury is complex. Immune regulation on Wal erian degeneration is beneficial for early repair of perpheral nerve injury.
OBJECTIVE:To investigate the effects of Tol-like receptor 4 (TLR4) antagonist on Wal erian degeneration and axonal regeneration after early peripheral nerve injury in rats.
METHODS:Fifty male Wistar rats were recruited and randomly divided into treatment group (n=20), model group (n=20) and sham group (n=10). The right sciatic nerves of rats in treatment and model groups were cut and sutured end-to-end, while the sciatic nerves of rats in sham group were only exposed. In the treatment group rats were intravenously injected with 0.15 mg/kg TAK-242 via tail vein 1 hour preoperatively and 7 days postoperatively, and the rats in the other two groups were given intravenous injection of the same volume of normal saline. The sciatic nerves were removed at 24 hours, 3, 4 and 7 days after surgery.
RESULTS AND CONCLUSION:Real-time PCR indicated that the mRNA expressions of interleukin-1βand monocyte chemoattractant-1 were significantly increased in the model group compared with the sham group at 24 hours after surgery (both P<0.001), while the expressions were significantly decreased after TAK-242 injection (both P<0.001). Immunofluorescence showed that compared with the model group, down-regulated expression of CD68+and iba1+cel s appeared in the treatment group at 3 days after surgery (P<0.01, P<0.05). Luxol fast blue staining revealed that demyelination at the sciatic nerve stump appeared in both model and treatment groups at postoperative 7 days, but myelin debris clearance in the treatment group was significantly reduced compared with the model group (P<0.05). Hematoxylin-eosin staining showed that a lot of inflammatory cel s, Schwann cells and regenerated nerve fibers at the sciatic nerve stump were found in the model group, while there were few inflammatory cells, Schwann cel s and regenerated nerve fibers in the treatment group at 7 days after surgery. Immunohistochemistry found that the expression of growth-associated protein-43 in the treatment group was significantly lower than that in the model group at 4 days postoperatively (P<0.05). Besides, compared with the model group, a significantly decreased sciatic functional index was found in the treatment group at 20, 30 and 40 days after surgery (P<0.05). These results show that TLR4 antagonists delay early nerve regeneration in rats after sciatic nerve injury probably by inhibiting the TLR4 signaling pathway.

Objective To summarize and evaluate our surgical approach of tetralogy of Fallot with complete atrioventricular septal defect.Methods 11 patients underwent surgical correction at our institute between June 2007 and April 2012.All of the 11 patients received biventricular or partial biventricular repair through a combined right atrial and right ventricular outflow tract approach.Two-patch technique was used in all 11 children.To minimize the incision in the right ventricular outflow tract(ROVT),8 patients underwent a transatrial approach to close ventricular septal defect.A transannular patch was needed in 7 patients,and a monocuspid valve was inserted in 1 of these patients.Results One hospital death occurred during intensive care stay due to severe low cardiac output syndrome and one late death took place six months after operation because of pneumonia and heart failure.The mean follow-up time was (21.20 ± 19.08) months (range,3-60 months).The KaplanMeier curve for the survival rate was 79.5％ at 5 years.Several postoperative complications occurred during the first 3 months,including 1 mild RVOT obstruction and 1 pulmonary artery stenosis,2 tiny residual atrial septal defects and 1 slight residual ventricular septal defect.Moderate pulmonary valve regurgitation was present in all patients,whether transannular patch was used or not.All survivors remained in good condition in NYHA class Ⅰ or Ⅱ.Conclusion Outcomes of complete correction of tetralogy of Fallot with complete atrioventricular septal defect are favorable during follow-up time.It is feasible to close a ventricular septal defect with a 2-patch technique through a transatrial approach alone.Accurate suturing is the key to the success of the surgery.

Objective To explore the feasibility of differentiation into neural cells from bone marrow stromal cells(BMSCs) in vitro by breviscapine,and to offer reference for the applying of BMSCs. Methods The bone marrow stromal cells of SD rat were separated and purified by passsage culture.After phenotype characterization,the 4th passage of BMSCs was exposed to breviscapine. Differentiation was observed under phase contrast microscope every 6 hours and the cells were stained immunocytochemically with neuronspecific enolase(NSE)and glial fibrillary acidic protein(GFAP).The induced cells activity was detected by MTT. NSE and GFAP were determined by flow cytometry and RT-PCR. Results The BMSCs were CD44~+,CD54~+,CD34~-. After 18 hours of induction, cytoplasm of BMSCs partly contracted with protruding;The immunocytochemical staining was performed on cells after induction for 24 hours,the rates of NSE and GFAP staining positive were(48.7±3.4)% and(56.8±4.2)%.By using flow cytometer, expressions of NSE and GFAP showed much higher in induced group than that in control group. By using RT-PCR, expressions of NSE and GFAP were positive in induced group. Conclusion Breviscapine could induce adult rat BMSCs to differentiate into neuron and glial cells.

This study was amied to construct CXCR4 gene modified bone marrow mesenchymal stem cells (MSCs), and investigate the effect of CXCR4 expression on MSCs migration. The retrovirus vector pMSCV-CXCR4-IRES-GFP that expresses human CXCR4 gene was cloned,the MSCs were transduced by the virus, and the expression of OXCR4 was analyzed by FACS, RT-PCR and immunofluorescence staining. The migration assay was performed using Transwell method in the presence of SDF-1. FACS results showed that 46% of the transduced MSCs were CXCR4 positive, and 57% were GFP positive. The expression of CXCR4 in MSCs was also confirmed by RT-PCR and immunostaining. The migration of MSCs was induced by SDF-1 and was strongly dependent on CXCR4 expression. The concentration of SDF-1 had effect on the migration and the transmigration rate of CXCR4 modified; the amount of MSCs was 5-fold higher than that of untransduced MSCs when the optimal concentration rose to 50 ng/ml. These data indicate that SDF-1/CXCR4 plays an important role in MSCs migration ,and the CXCR4 genetic modification approach could be applied to enhance cell homing, and engraftment in MSCs therapy.
Bone Marrow Cells ; cytology ; Cell Movement ; Cells, Cultured ; Chemokine CXCL12 ; pharmacology ; Genetic Vectors ; genetics ; Humans ; Mesenchymal Stromal Cells ; cytology ; metabolism ; Receptors, CXCR4 ; biosynthesis ; genetics ; Retroviridae ; genetics ; metabolism ; Transduction, Genetic ; Transfection

OBJECTIVETo study the hormonal and metabolic responses of fetal lamb during cardiopulmonary bypass.

METHODSSix pregnant ewes underwent fetal cardiopulmonary bypasses with artificial oxygenators and roller pumps for 30 minutes, which maintained the blood gas value at the fetal physiological level. The fetal blood pressure, heart rate, pH value and blood lactate levels were monitored. The levels of catecholamine, cortisol and insulin were measured pre-bypass and then again 30 minutes later. The blood glucose and free fatty acid levels were monitored continuously during the bypass. Fetal hepatic PAS staining was also carried out.

RESULTSThere were no changes before and during the bypass in fetal blood pressure, heart rate and blood gas. However, pH values decreased and blood lactate levels increased (P < 0.05). The fetal catecholamine and cortisol levels increased significantly (P < 0.01), while the levels of insulin did not change. The blood glucose and free fatty acid levels increased at the beginning of the bypass (P < 0.01), and then gradually slowed down during the bypass. The fetal hepatic PAS staining showed that hepatic glycogen was consumed in large amounts. After 30 minutes of bypass, the fetal lamb would not survive more than 1 hour.

CONCLUSIONThe fetal lamb has a strong negative reaction to cardiopulmonary bypass.

Animals ; Blood Gas Analysis ; Blood Glucose ; analysis ; Cardiopulmonary Bypass ; adverse effects ; Catecholamines ; blood ; Fatty Acids, Nonesterified ; blood ; Fetus ; physiology ; Hemodynamics ; physiology ; Hydrocortisone ; blood ; Lactates ; blood ; Sheep

15 mm) should be used in patients over the age of 4 and later reoperation might be avoided. For D-TGA without long segment of LVOTO, we can choose arterial switch plus pulmonary valvotomy or Konno procedure to relief the LVOTO. To prevent postoperative functional mitral regurgitation, in C-TGA-VSD-PS patients the best surgical procedure is double switch operation.

Objective: To investigate the effect of electroacupuncture (EA) on rat with diet induced obesity (DIO) and to explore the possible neurochemical mechanisms using the technique of immumohistochemisty. Methods:To establish DIO rat model by feeding the animals with high fat diet for 14 weeks. DIO rats were randomly divided into 4 groups: (1) 2Hz EA group, (2) 100Hz EA group, (3) restrain control group,(4) diet resistance (DR) group,(5) DIO group and (6) normal control group. EA treatment: (1) The acupoints used were Zusanli and Sanyinjiao on both legs. (2) The intensities of stimulation were 0.5, 1.0 and 1.5mA for 10 mins each. EA treatment was administered 3 times per week. Food intake and body weight were measured daily for 4 weeks. (3) The changes of the expression of ? melanocyte stimulating hormone (? MSH) in the hypothalamic arcuate nucleus (ARC) were measured with immunohistochemical semiquantitative analysis. Results: (1) The food intake and body weight of 2 Hz EA group and 100 Hz EA group were decreased significantly compared with the restrain control group and DIO group. (2) The number of ? MSH positive cells in hypothalamic ARC in 2 Hz EA and 100 Hz EA group was significantly higher than that in restrain control group and DIO group. The number of ? MSH positive cells in hypothalamic ARC in DIO group is significantly lower than those in DR group or normal control group. Conclusion: A decrease of ? MSH level in hypothalamus may be associated with diet induced obesity. The therapeutic effect on obesity produced by EA may be accounted for by the stimulation of pro opio melanocortin neurons in hypothalamic ARC to release ? MSH, which inhibits food intake , resulting in a decrease of body weight.

Objective To review and evaluate the effect of one stage surgical correction of congenital heart disease with tracheal stenosis in infants.Methods Between August 2001 and December 2005,six infants with congenital heart disease with tracheal steno- sis were repaired at one stage operation.The age was 24 d～3 y[mean(13.16?12.03)months]and the weight was 4.2～10.0 kg [mean(7.98?2.03)kg].There were 3 patients with tetralogy of Fallot,1 with pulmonary atresia;2 with ventricular septal defect, 1 with coarctation of aorta;and 1 with pulmonary sling.The congenital heart disease were repaired underwent low temperature and car- diopulmonary bypass,and the tracheal stenosis were corrected simultancously.Results There was one death postoperative because of right and left branch stenosis.One patient with pulmonary sling died of granulation tissue on the patch 3 months after operation.All other 4 patients recovered uneventfully.These patients were followed up from 6 month to 4 years.There were no complications.CT scan shows that the tracheal anastomosis was patent without any stenosis.Conclusion One stage repair of congenital heart disease with tracheal stenosis in infants may have a satisfactory result.To deal with the tracheal stenosis is difficult,the operative methods de- pends on the length of stenosis.The principles of surgical methods consist of using autologous material,maintaining its contour and function of respiratory epithelium,and maintaining its growth.

AIM　To investigate effect of urotensin Ⅱ (UⅡ)on proliferation of aort a smooth muscle cells （ASMC）of rat and study the signal transduction pathway o f it. METHODS　In cultured ASMC of rat, UⅡ was used to stimulate proliferation of these cells and levels of ［3H］-TdR incorporation were used to evaluate the speed of DNA synthesis, and different inhibitors were used to s tudy the action of different signal transduction pathway of mitogenic effect of UⅡ on VSMC. RESULTS　1×10-9～1×10-7 mol*L- 1 UⅡ caused marked concentration-dependent increasing of ［3H］-TdR i ncor poration of ASMC. ［3H］-TdR incorporation of 1×10-9,1×10-8 and 1×10-7 mol*L-1 UⅡ were 22%（P<0.05）, 57%（P<0.01）and 65%（P<0.01）higher than control. Nicardipine, H7, W7 and PD98059 , which are inhibitors of calcium channel, PKC, CaM-PK and MAPK respectively, inhibited the effects of UⅡ obviously, with the inhibitory rate by 55%（P< 0.01）, 27%（P<0.01）,18%（P<0.05）and 16%（P<0.05）respectively . CONCLUSION　UⅡ is a strong mitogen for VSMC and the mitogenic e ffect of UⅡ is probably mediated by Ca2+, PKC, CaM-PK and MAPK signal tr ansduction pathway.