Microbial secondary metabolites are one of the major sources of anti-bacterial, anti-fungal, antitumor, anti-virus and immunosuppressive agents for clinical use. Present challenges in microbial pharmaceutical development are the discovery of novel secondary metabolites with significant biological activities, improving the fermentation titers of industrial microbial strains, and production of natural product drugs by re-establishing their biosynthetic pathways in suitable microbial hosts. Synthetic biology, which is developed from systematic biology and metabolic engineering, provides a significant driving force for microbial pharmaceutical development. The review describes the major applications of synthetic biology in novel microbial secondary metabolite discovery, improved production of known secondary metabolites and the production of some natural drugs in genetically modified or reconstructed model microorganisms.

Hyperuricemia mice model was established with uricase inhibitor (potassium oxonate) and uric acids in serum were observed. Polydatin (5, 10, 20 mg · kg(-1)) and benzbromarone (16.7 mg · kg(-1)) were given ig for 7 d in mice. Kidney tissues were used to detect gene contents ofurate anion transporter 1 (URAT1), organic anion transporter 1 (OAT1) and organic anion transporter 3 (OAT3) by real-time-PCR. The results showed that polydatin and benzbromarone can significantly reduce uric acid in blood of hyperuricemia mice (P < 0.05), compared with the model group. URAT1, OAT1 and OAT3 contents of the kidney in hyperuricemia mice changed significantly (P < 0.05), compared with the blank group. Polydatin can significantly inhibit the changing trends in these genes induced by potassium oxonate in a dose-dependent manner, the difference was significant (P < 0.05), compared with the model group. Those indicated that polysatin could reduce the level of the serum uric acid through promoting uric acid excretion.
Animals ; Disease Models, Animal ; Glucosides ; pharmacology ; Hyperuricemia ; drug therapy ; Kidney ; drug effects ; metabolism ; Mice ; Stilbenes ; pharmacology ; Uric Acid ; blood

Animals ; Animals, Newborn ; Disease Models, Animal ; Enterocolitis, Necrotizing ; chemically induced ; Female ; Male ; Platelet Activating Factor ; toxicity ; Rats ; Rats, Sprague-Dawley ; Sulfalene ; toxicity ; Tumor Necrosis Factor-alpha ; toxicity

Objectives:To study the enzymatic changes and protective effects of ciliary neurotrophic factor (CNTF) on neurons in spinal cord injury (SCI).Methods:SD rats were subjected to incomplete SCI with modified Allen methods.Activities of acetylcholinesterase (AChE) and acid phosphatase (ACP) in spinal cord were quantitatively measured preoperatively,and 3,7,14 days after SCI.Results:AChE activity decreased gradually after injury.ACP activity increased 3 days after injury,and reached peak on the 7th day,then recovered gradually.The rats treated with CNTF showed relatively smooth change of the 2 kinds of enzymes.Conclusions:CNTF plays a role in protecting the spinal cord neurons against injury.

Objective To investigate the role of Twist and vascular endothelial growth factor (VEGF)in the development of epithelial ovarian cancer and their relationship with clinical pathological features.Methods The expressions of Twist and VEGF were detected by immunohistochemical staining (SP)method in 80 cases of epithelial ovarian cancer and 10 paired cases of normal ovarian tissue.Results In the 80 cases of ovarian cancer tissues,the positive expression rate of Twist and VEGF in epithelial ovarian cancer was 85% and 86.25%,respectively,which were remarkably higher than those in normal ovarian tissues (P <0.01).The expressions of Twist and VEGF were closely associated with clinical stages,pathological grades and lymph node metastasis,but not correlated with age or pathological patterns (P >0.05).There was a significant correlation between the expressions of Twist and VEGF in epithelial ovarian cancer (r =0.646,P <0.01).Conclusion The high expressions of Twist and VEGF may play a potential role in the occurrence,development and invasion process of epithelial ovarian cancer.

Objective: To investigate the effect of insulin-like growth factor-Ⅰon osteocalcin secretion in periodontal ligament cells. Methods: Human periodontal ligament cells were cultured by tissue explant in vitro, and the concentration of osteocalcin were determined with radio-immunological method. Results: Under the condition of L-ascorbic acid and β-glycerophosphate in culture medium, human periodontal ligament cells secreted osteocalcin time-dependently and peaked at the third week; IGF-Ⅰ3.125 ng/ml，6.250 ng/ml, 12.500 ng/ml, 25.000 ng/ml could promote the secretion of osteocalcin dose dependently. Conclusion: IGF-Ⅰ can increase the secretion of osteocalcin in human periodontal ligament cells.

Objective To study the clinical value of 64-slice spiral computed tomography(64SCT) contrast-enhanced scan and three-dimensional reconstructed techniques in the diagnosis of complex congenital heart disease(CCHD). Methods 39 patients with CCHD underwent CT angiography and transthoracic echocardiograms (TTE). Of them, the electrocardiographic-gating technique was used in 8 cases. The accurate rates in diagnosing CCHD with CT, TTE and CT with or without electrocardiographic-gating were analysed compared with that of operation and χ~2 test using SPSS13.0 tool. Results A total of 102 cardiac deformities con-firmed by operations,those included 47 intracardiac deformities,the diagnostic accuracys with CT and TTE were 85.1% and 95.7%, respectively, and there was no obvious difference among them (χ~2=2.68, P>0.05). 55 extracardiac deformities, the definite diagnos-tic rates with CT and TTE were 98.2% and 78.2%, respectively. CT was superior to TTE in the indentification of extracardiac de-formities(χ~2= 14.64 ,P<0.01). There was no obvious difference between with and without electrocardiographic-gating technique during CT scanning in diagnosis of cardiac deformities(χ~2=1.84, P>0.05). Conclusion 64SCT has significant value in diagnosis of CCHD,and there was no obvious difference in diagnosis of cardiac deformities by 64SCT between with and without electrocardio-graphic-gating technic.

Objective To evaluate the safety,biocompatibility and efficacy of transcatheter closure of atrial septal defect(ASD)with no stainless-steel-screw occluder in canine model.Methods The device was constructed from superelastic Nitinol wires tightly woven into two flat disks and sewed with polyester fibers inside,with a pliable loop on the right-atrial-disk of the device,connecting to the delivery cable.ASD was created by transcatheter puncture and balloon dilatation and then closed by occluder under fluoroscopy in the catheterization laboratory.The location and the influence of the implanted device on function of tricuspid valve and mitral valve were evaluated by echocardiography.At 1,2,3 and 6 months after the operation,the animals were killed and autopsy was conducted.Results Eight dogs with puncture-produced ASD underwent ASD closing procedure successfully.The occluder showed no influence on the function of MV and AV demonstrated by echocardiogram.The two disks of the implanted device were covered with a smooth intact neogenesis layer in all dogs.Endocardial cells fully covered the surface of the two disk without inflammating reaction 3 months later. There was no evidence of corrosion on the surface of the nitinol wire removed from the dog after 6 months.Light microscopic examination of the liver,kidney,lung and spleen showed no evidence of embolization and inflammation.Conclusion Transcatheter ASD occlusion with new-type occluder is safe,feasible,effective and good biocompatibility with a good prospective clinical application.

Objective To study the risk factors for children with acute central nervous system(CNS)viral in-fection,so that pediatrician may identify children with poor prognosis at early stages of the disease,and provide them with a theoretical basis for clinical treatment. Methods The clinical data of a cohort patients of acute CNS viral infec-tion who were hospitalized at the First Affiliated Hospital of Fujian Medical University between January 2010 and June 2013 were retrospectively collected and analyzed. According to Glasgow outcome scale on discharge,children were di-vided into good prognosis group and poor prognosis group. Clinical data and outcomes were analyzed by using univariate analysis and binary Logistic regression multivariate analysis. Results Three hundred and one cases were enrolled,278 (92. 36% )patients were assigned to the good prognosis group,and 23(7. 64% )patients were assigned to the poor prognosis group. By univariate analysis,the patients in the poor prognosis group had longer duration of sickness before admission,longer time of fever,lower white blood cell count in cerebrospinal fluid,a relatively lower calcium level,con-scious disturbance at the early stage,multiple seizures,convulsive status epilepticus,meningeal irritation sign,muscle weakness,severe changes in electroencephalogram(EEG),and abnormal neuroimaging findings(computed tomography or magnetic resonance imaging,or both)had significant differences between the good prognosis group and the poor short - term outcome groups(all P < 0. 05). By binary Logistic regression multivariate analysis,factors indicating a poor prognosis during the early stage were conscious disturbance at the early stage(0R = 4. 885,95% CI:1. 523 - 15. 670, P = 0. 008),multiple seizures(0R = 6. 352,95% CI:1. 905 - 21. 178,P = 0. 003),severe changes in EEG( 0R =4. 269,95% CI:1. 708 - 10. 666,P = 0. 002),and abnormal neuroimaging findings( 0R = 9. 740,95% CI:2. 360 -40. 192,P = 0. 002). Conclusions Conscious disturbance at the early stage,multiple seizures,severe changes in EEG and abnormal neuroimaging findings are risk factors for acute viral infection of CNS in children.

Objective To analyze blood stream infections(BSI)in ICU patients,to explore the bacterial spectrum characteristics and time distribu?tion,so as to provide a reference for the clinical use of antibiotics. Methods A retrospective analysis was carried out. A total of 1 330 patients admit?ted in our hospital intensive care unit(ICU)from January 2012 to March 2013(15 months)were selected for the study,the occurrence rate of blood stream infections,the bacteria spectrum of it and the bacteria spectrum distribution in different period of time(admitted in ICU for the first week,sec?ond week and later)were analyzed. The subjects were divided into 2 groups(CVC cases and non?CVC cases)depended on CVC indwelling or not. Results There were 971 cases with central venous catheter(CVC),the occurrence of bloodstream infection were 96 cases,the infection rate was 9.89%,including 359 non?CVC cases and 12 blood stream infection cases. The infection rate was 3.34%,and the total blood infection rate was 8.12%. A total of 157 strains of pathogen were isolated,among which 16 strains were isolated from non?CVC cases. Infection of gram?negative bacilli, gram?positive cocci and fungi were 56.7%,32.5%and 10.8%,respectively. Staphylococcus(16.6%),Bauman acinetobacter(15.9%),Enterococ?cus(14.6%),Pseudomonasaeruginosa(10.2%)and Klebsiella(10.2%)were the most common bacteria. For the distribution of time,in non?CVC cases gram?negative bacilli were more than other bacilli in the first and second week(3 vs 1,4 vs 1)in ICU,more gram?positive cocci( 5 vs 2) were isolated after two weeks,no fungi were detected;in CVC cases,gram negative bacilli were in a dominant position all the time(the number of gram negative bacilli,gram positive bacteria and fungi were 31 cases,24 cases and 3 cases in the first week respectively,23 cases,12 cases,11 cas?es in the second week,26 cases,8 cases and 3 cases after the second week),the proportion of each species in the first week were 53.4%,41.4%and 5.2%,respectively,50%,26.1%and 23.9%in the second week,70.3%,21.6%and 8.1%after the second week . The highest fungemia was found in the second week. Conclusion For the 1st 2 weeks in ICU,the most common bacilli was gram negative bacilli with BSI. After 2 weeks admitted in the ICU,it was mainly gram negative bacilli in CVC cases,and mainly gram positive cocci in non?CVC cases. In the 2nd week,fungemia had the? highest probability in CVC cases,and it appeared low possibility in non?CVC cases. Non?CVC cases have a lower risk of blood stream infection.