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

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.

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 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 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.

Objective To evaluate the techniques and application of 64-slice helical CT colonography in colonic lesions. Methods Thirty-eight patients (including 12 colonic carcinomas,10 polypi, 9 colon multiple scrobiculus, 2 multiple diverticula, 2 negative, 1 congenital bowel malrotaion,1 ulcerative colitis and tunica mucosa glandular organ hyperplasy,1 colocolic anastomosis of terminal ileum and sigmoid colon) underwent volume scanning using 64-slice helical CT after cleaning colon. Six types of reconstruction including CT virtual colonoscopy(CTVC), volume rendering(VR), multiple planar reconstruction(MPR), 360?sectional view, RaySum,and navigation were gained.CTVC appearances were compared with that of conventional colonoscopy(CC).Results In 12 colonic carcinomas and 10 polypi,the lesions’ morphology,number,size, were satisfactorily shown by CTVC. The lesions’ location,range,and 1 intestinal canal obviously stenosis were also exactly shown by RaySum.The relationship between tumor and environment, 3 liver or retroperitoneal lymph node metastasis were satisfactorily shown by MPR and 2D transection image. On 360?sectional view,the distance between tumor and anus was exactly measured and the result was in conformity to that of CC. Of the CTVC appearances,1 sigmoid carcinoma and 1 transverse colon polyp was in unconformity to that of CC;1 ulcerative colitis and descending colon carcinoma was diagnosed as ulcerative colitis and tunica mucosa glandular organ hyperplasy by pathology.Conclusion 64-slice helical CT is a valuable imaging technique for detecting colon diseases. CTVC can obtain more clinical information than CC combining MPR,RaySum and VR.

Diving ; Humans ; Otitis Externa ; prevention & control