Genome-scale metabolic network model (GSMM) is an extremely important guiding tool in the targeted modification of industrial microbial strains, which helps researchers to quickly obtain industrial microbes with specific traits and has attracted increasing attention. Here we reviewe the development history of GSMM and summarized the construction method of GSMM. Furthermore, the development and application of GSMM in industrial microorganisms are elaborated by using four typical industrial microorganisms (Bacillus subtilis, Escherichia coli, Corynebacterium glutamicum, and Saccharomyces cerevisiae) as examples. In addition, prospects in the development trend of GSMM are proposed.
Corynebacterium glutamicum/genetics* ; Escherichia coli/genetics* ; Metabolic Engineering ; Metabolic Networks and Pathways/genetics*

As a typical food safety industrial model strain, Bacillus subtilis has been widely used in the field of metabolic engineering due to its non-pathogenicity, strong ability of extracellular protein secretion and no obvious codon preference. In recent years, with the rapid development of molecular biology and genetic engineering technology, a variety of research strategies and tools have been used to construct B. subtilis chassis cells for efficient synthesis of biological products. This review introduces the research progress of B. subtilis from the aspects of promoter engineering, gene editing, genetic circuit, cofactor engineering and pathway enzyme assembly. Then, we also summarized the application of B. subtilis in the production of biological products. Finally, the future research directions of B. subtilis are prospected.
Bacillus subtilis/genetics* ; Bacterial Proteins/genetics* ; Gene Editing ; Metabolic Engineering ; Promoter Regions, Genetic

Objective To study the pharmacokinetics of raltitrexed using different ways of drug delivery, including femoral venous infusion, hepatic artery perfusion, hepatic artery injection of lipiodol suspension, hepatic artery perfusion followed by embolization with Gelfoam. Methods According to the administration way of raltitrexed, a total of 40 New Zealand rabbit models with VX2 liver tumor were randomly divided into group A (femoral venous perfusion), group B (hepatic arterial perfusion), group C (hepatic artery injection of lipiodol suspension), and group D(hepatic artery perfusion followed by embolization with Gelfoam). Drug concentration in plasma were determined by using LC-MS/MS method and the pharmacokinetic parameters were calculated. Results After administration of raltitrexed, the Tmax was 5 minutes in all 4 groups. In group A, B, C and D, the values were (5.88±1.39), (7.31±2.60), (9.86±5.10) and (7.19±2.27) respectively, with group C having the longest t1/2 value, which was significantly different with that of group A (P＜0.05); the (ng·ml-1·h-1) values were (2 056.40± 139.17), (1 389.21±180.28), (911.84±105.62) and (1 133.41±181.42)respectively, with the value of group A being obviously higher than that of group B, C and D (P＜0.05) and the value of group C being the lowest; the AUC0-t(ng· ml-1·h-1) values were (5 482.72±1 007.07), (4 156.99±1 475.77), (2 785.13±1 107.36) and (3 903.64±947.25) respectively, with the value of group A being remarkably higher than that of group B, C and D (P＜0.05) and the value of group C being the lowest. Conclusion Compared with the femoral vein infusion way, the ways of hepatic artery infusion, hepatic artery lipiodol suspension injection and hepatic artery perfusion followed by embolization with Gelfoam may promote more raltitrexed to deposit in the tumor area, thus, the curative effect is enhanced, the drug concentration in plasma is lowered and the side effects are alleviated.

Objective This study aims to investigate the clinical value of percutaneous vertebroplasty (PVP)combined with strontium-89 (89 Sr)on patients with spinal malignant tumor.Methods Seventy four patients who were diagnosed as spinal malig-nant tumor were divided into two groups randomly.37 patients of the control group were treated by PVP only,and 37 patients of joint group were treated by PVP and 89 Sr together.Then the clinical effect of the joint group and control group was compared after treatment.Results After treatment,the quality of life,ratio of pain relief,clinical effect and survival time in joint group were dis-tinctly better than control group (P <0.05).Conclusion PVP combined with 89 Sr can be an effective and safe treatment for pa-tients with spinal malignant tumor.

Obgective To investigate the impact of different ways and doses of recombinant human interferon o1b(rhIFN-α1b) on antiviral effect on respiratory syncytial virus(RSV)-effected mice and signal pathway of JAK/ STAT.Methods Forty-eight mice were divided randomly into 6 groups,negative control group,RSV-infection model group,12.5,25.0,50.0 μg rhIFN-α1 b atomization inhalation of intervention group,and 12.5 μg rhIFN-α 1 b injection of intervention group.After continuous drug therapy for 5 days,the left lung tissues of mice were aseptically dissected in the sixth day.Then it were observed lung tissue pathology changes by optical microscope,and expression of STAT1 and STAT2 protein with laser scanning confocal microscopy.Results It was observed that RSV-infection model mice's lungs had significant inflammatory injury under light microscope.After treatments of rhIFN-α 1b,it showed that the mice lung tissue had recovery of inflammation on different degrees.The group of inhaled rhIFN-o1b 50.0 μg was damaged on lightest degree.There were statistically significant differences between each group (all P ＜ 0.05).The expression of STAT1 and STAT2 protein in RSV-infection model mice's lungs decreased remarkably under fluorescene microscopy.Treatments of rhIFN-α 1b increased the expression of STAT1 and STAT2 inhibited by RSV-infection.The expression of STAT1 and STAT2 protein of the inhaled rhIFN-α1b 50.0 μg group increased significantly.The differences between groups were statistically significant(all P ＜ 0.05).Conclusions rhIFN-α 1 b played an important role in anti-RSV effects,simultaneously,it could improve the activity of JAK/STAT signal pathway inhibited by RSV-infection.The treatment effect of rhIFN-α 1b deliveried by atomization inhalation was better than that of intraperitoneal injection.And curative effect is proportional to the atomization inhalation dose within a certain range.

Objective To explore the diagnostic value of three-dimensional ultrasound parameters-vascularity index (VI) and the volume of kidney in chronic kidney disease (CKD). Methods A total of 80 CKD patients at different stages and 30 healthy adults were enrolled in the study. VI and the renal volume were calculated with three-dimensional ultrasound, while resistance index (RI), cortical thickness (CT) and the volume of kidney were calculated with two-dimensional ultrasound, and the correlation of those parameters were analyzed statistically. Results VI of CKD2 patients reduced significantly compared with the control group, and RI of CKD3 patients increased significantly, CT of CKD3 patients reduced significantly. The diagnostic sensitivity, specificity and diagnostic value of VI in patients with early and late CKD were all higher than thpse of RI. Compared with the control group, three-dimensional ultrasound of renal volume and two-dimensional ultrasound volume of CKD 1 patients increased significantly, three-dimensional ultrasound volume of CKD2 patients reduced significantly, and two-dimensional ultrasound volume of CKD4 patients reduced significantly. There was significant negative correlation among VI, three-dimensional ultrasound volume, CT, two-dimensional ultrasound volume and pathological change scoring (r=-0.67, -0.52, -0.43, -0.52). Conclusion VI and three-dimensional ultrasound volume can detect renal function damage more earlier and sensitively than RI and two-dimensional ultrasound volume.

To obtain the P8 protein of Rice gall dwarf virus (RGDV) with biological activity, its outer coat protein gene S8 was expressed in Spodoptera frugiperda (Sf9) insect cells using the baculovirus expression system. The S8 gene was subcloned into the pFastBacTM1 vector, to produce the recombinant baculovirus transfer vector pFB-S8. After transformation, pFB-S8 was introduced into the competent cells (E. coli DH10Bac) containing a shuttle vector, Bacmid, generating the recombinant bacmid rbpFB-S8. After being infected by recombinant baculovirus rvpFB-S8 at different multiplicities of infection, Sf9 cells were collected at different times and analyzed by SDS-PAGE, Western blotting and immunofluorescence microscopy. The expression level of the P8 protein was highest between 48-72 h after transfection of Sf9 cells. Immunofluorescence microscopy showed that P8 protein of RGDV formed punctate structures in the cytoplasm of Sf9 cells.

ObjectiveTo study the effect of tetramethylpyrazine cooperated with autogenous periosteum graft on fibrous scar formation in the epidural space after laminectomy. Methods48 SD rats were divided randomly into 4 groups. Laminectomy was performed in lumbar 2 segment, and the exposed duras were covered with saline solution (group A), tetramethylpyrazine (group B), autogenous periosteum (group C), and tetramethylpyrazine and autogenous periosteum (group D) respectively. 12 weeks postoperatively, they were evaluated with the gross and histopathological observation, biochemistry examination. ResultsThe assessment of Rydell-Balazs and Nussbaum's Criterion of group B, C, D were obviously better than that of group A (P<0.01), and that of group D was superior to group B and C (P<0.05), no significant difference between group B and C (P>0.05). ConclusionTetramethylpyrazine cooperated with autogenous periosteum graft has a better effect on prevention peridural adhesion after laminectomy.

OBJECTIVE:To investigate the distribution and drug resistance of High-level Aminoglycoside Resistance Enterococcus spp (HLAR) in hospital infection. METHODS:The clinical specimens collected from 2004 to 2007 in our hospital were isolated by routine method. Identification of the bacteria and Antimicrobial susceptibility test were performed using automatic microbiology analysis system. RESULTS:Of the total 292 strains of Enterococcus which induced HLAR in hospital infection,Enterococcus faecalis (E.faecalis) represented 49.3% (144/292) and Enterococcus faecium (E.faecium) 41.4% (121/292). 27.4% (80/292) were from intensive care unit,17.5% (51/292) the department of nephrology and 8.9% (26/292) the neurosurgery department. The urinary system infection represented 29.8% (87/292) in hospital infection. The antimicrobial resistance of E.faecium was significantly higher than that of E.faecalis against quinolones and ?-lactamase antibiotics,but the antimicrobial resistance of E. faecalis was higher than that of E,faecium(P

OBJECTIVE: To establish a new pattern of ward round record for clinical pharmacist and rational use of drug. METHODS: The new pattern of ward round record was established according to domestic and foreign history pattern, The Principle and Proposed Pattern of Clinical Medication History in China, disease course record. This new pattern focused on patients’ disease and medication changes. A case of cardiovascular department was taken as example. RESULTS: Established ward around record contained two parts, i.e. first page and record chart. CONCLUSION: Established pattern is concise and practical and covers essential medical information. It makes communication more easily between pharmacist and doctors and meets the needs of clinical pharmacy practice.