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

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 retrospectively analyze bacterial time distribution of ICU?acquired infections in Shengjing Hospital of China Medical Uni?versity,so as to provide reference for the early antibiotic use for ICU?acquired infections. Methods A total of 1 330 cases in ICU from Jan. 2012 to Mar. 2013 were collected,the bacterial culture was positive in 254 cases. A total of 1 110 strains were collected from all the patients. Excluding 288 strains which were detected within 48 hours of patients′admission in ICU and 222 strains which were repeatedly detected in the same patients,600 strains were finally enrolled in the statistical analysis. Results The rate of ICU?acquired infections was 19.1%. Postoperative infections accounted for 74.3%,most of which occurred after neurosurgeries,and abdominal,orthopedic operations. Pulmonary infection ranked the first in ICU?acquired infections,accounting for 40.3%,followed by blood stream infection(25.3%),postoperative drainage infection(14.2%)and urinary tract infection (7.3%). The rate of pathogenic bacteria detection was the highest in the first week of patients′admission in ICU,and was getting lower as time went by. Strains detected in ICU mainly were Bauman Acinetobacter,Pseudomonas aeruginosa,Klebsiella pneumonia and Enterococcus faecium,most of strains resulting in infections were gram negative bacilli throughout the time. In addition,the infection rate of fungi was increased at 2 weeks of pa?tients′admission in ICU. Conclusion The treatment of ICU?acquired infections should be targeted at gram negative bacilli. The detection rate of op?portunistic pathogens gradually increased with prolonged stay in ICU,most of which are non?fermentative bacteria. Fungi infections are most likely to occur at 2 weeks of patients′admission in ICU.

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 study the value of lung window and soft tissue window in measuring colon diseases with experimental CTVC examination.Methods Twenty-four artificial polypoid diseases were placed with glue in a thoroughly cleaned porcine colon(overall length,150 era)that was distented with air and submerged in a water phantom and scanned 10 times on a 64-MSCT(GE Light speed)with identical scanning parameters.The data were reconstructed every 0.625 mm and reviewed using 2D images, navigation,MPR and 3D volume-rendered images on a GE AW 4.2 workstation.The maximum diameters of the artificial polypoids were measured by two radiologists with more than 10 years working experience in lung window(W = 1000,L =-700)and soft tissue window(W =400,L =40),respectively.The average value of maximum diameters of the artificial polypoids were measured for 10 times and were compared with the actual diameter.Results Twenty-four artificial polypoid diseases and their shape,size,loeation and relation of diseases with bowel wall were all showed excellently.The maximum diameter measured was close to the actual diameter.The average value was mostly less than actual diameter and a few of them more than the actual diameter.The maximum diameter measured in lung window was close to the actual diameter,and there was no difference between the two data sets(t =0.431,P =0.669).There was difference between the maximum diameter measured in soft tissue window and the virtual diameter(t = 2.691,P = 0.010). Conclusion In screening the colon diseases,CTVC is a good method of choice with no insult or less insult, and higher repeatability.The lung window should be chosen in measuring colon diseases in CTVC examination.

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 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.

Background and purpose:Cancer microenvironment has become a hot topic of cancer research. It is important in the initiation of colorectal cancer. This study aimed to discuss the correlation between the characteristics of tissue culturein vitro and different cell types in cancer microenvironment.Methods:Samples were collected at different distances from the colorectal cancer lesions, which were named as positions 1, 2 and 3 from distal to proximal. Tissues were cut into 1-2 mm3 forin vitro culturing. HE staining was used to observe the structure of crypts. Immunohistochemistry was used to detect the expressions of Cyclin D1 (CD1), CD133, cytokeratin18 (CK18), vimentin and α-smooth muscle actin (α-SMA).Results:Position 3 grew faster than position 2 and position 1. As getting closer to the colorectal cancer lesions, expressions of CD1, CD133, vimentin and α-SMA were increased while expression of CK18 was decreased.Conclusion:The tissue structure and the expression of different cell types in cancer microenvironment changed more seriously as get-ting closer to the colorectal cancer lesions. This indicated that the change of cancer microenvironment may contribute to the initiation of colorectal cancer.