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.

Adult ; Aged ; Aged, 80 and over ; Combined Modality Therapy ; Female ; Humans ; Male ; Manipulation, Orthopedic ; methods ; Middle Aged ; Radius Fractures ; surgery ; Splints ; Traction ; methods

Artemisinin is a sesquiterpene lactone compounds,their derivatives include mainly dihydroartemisinin,artesunate,artemether and Artemisia ether. These drugs are now mainly used for clinical treatment of malaria. With the pharmacological action of artemisinin and its derivatives have been further studied,except antimalarial effects,researchers have found their anti-inflammatory,anti-sepsis,antitumor,radiosensitization,antimicrobial sensitivity,anti-fibrosis effects in recent years. Here,we collect and review the most newly pharmacological effects of artemisinin and its derivatives all over the world in past years.

Objective:To observe cardiovascular events and risk of tumor in aged patients with diabetes mellitus (DM) .Methods :A total of 2743 DM patients ,who visited to our department of endocrinology from 2004 to 2010 , were enrolled as DM group ,another 2642 people without glucose metabolic disorder ,who visited to our hospital dur‐ing the same period with the same age ,were regarded as normal control group .Incidence rates of cardiovascular dis‐eases and morbidity of malignant tumor ,levels of tumor markers were compared between two groups (both groups were followed up for 2~7 years) .Results:Follow‐up found that cardiovascular disease rate in DM group was signif‐icantly higher than that of normal control group (21.47% vs .6.43% , P<0.05 );tumor marker CA19‐9 level in DM group was significantly higher than that of normal control group [ (17.89 ± 3.61) kU/L vs .(9.78 ± 2.64) kU/L ,P=0.001] ,and incidence rate of malignant tumor was significantly higher than that of normal control group (18.34% vs .8.18% , P=0.001) .Conclusion:Incidence rate of cardiovascular events and tumor in aged patients with diabetes mellitus is significantly higher than that of people without glucose metabolic disorder of same age .

0.05) except IP between T_4 and T_(16)(P0.05).the dynamic and static RBI showed the same change tendency.[Conclusion]The intraosseous and intramedullary blood circulation is severely damaged after blocking of the proximal and middle FMC with bone cement,it induces a long time high IP and a series of changes of blood flow at distal femur.

[Objective]To explore the effects on the distal femoral joint by high intraosseous pressure after blocking of proximal and middle femoral medullary cavity with bone cement.[Method]The rabbit model was established whose proximal and middle femoral medullary cavity of left side was infused with PMMA while the right side served as the control.Twenty-six rabbits were cavided randomly into 4 groups,8 for normal control group,the remained modeled rabbits were grouped according to the observing time-point into following groups:4th(T4),8th(T8) and 16th week(T16).The rabbits was killed to obtain the samples of distal femoral articular synovium,cartilage and the bone under cartilage.Then the structural changes of these tissues were observed by HE staining,toluidine blue staining,immunohistochemistry and transmission electron microscope.[Result](1)HE staining:the damage to articular cartilage,synovial tissue and the bone under cartilage aggravated with time.At the 16th week,it showed the articular cartilage was destructed,the bone structure was severely damaged with the synovial tissue proliferation and swelling.(2)Toluidine blue staining(16th week):all the layers of articular cartilage appeared loss of stain while the superficial layers were slightly loss of stain in control group.(3)Immunohistochemistry(16th week):①CollagenⅡ:the chondrocytes were positively stainned.②TGF-?1:chondrocytes stain was positive;the staining of articular synoviocytes appeared positive.(4)Transmission electron microscope:The lesions to articular chondrocytes and bone cells aggravated with time,part of which presented with necrosis and collapse at the 16th week.[Conclusion]The distal femoral intraosseous and intramedullary blood circulation is severely damaged after blocking of the proximal and middle femoral medullary cavity with bone cement,leading to continuous high intraosseous pressure.It makes the bone metabolism disordered in distal femur,which results degeneration and necrosis in distal femur,cartilage and synovial tissue.

AIM: To evaluate and analyze the morphological property and physiological activity of cartilaginous loose bodies in the knee joint, to research the changeable mechanism of histological morphous and physiological function. METHODS: The experiment was conducted at the Department of Pathology of the First Affiliated Hospital of Anhui Medical University, the Physical Testing & Chemical Analysis Center of Anhui Medical University, and the Electron Microscope Center of Anhui Provincial Hospital Affiliated to Anhui Medical University from January 2005 to January 2006. ①Experimental samples were 30 cartilaginous loose bodies all through arthroscopy as experimental group in which Group A (less than 6 months) had 14 samples and group B (between 6 and 12 months) 10, group C (more than 12 months) 6. Another 30 control samples were originated from non-weight loading side of articular cartilage through special equipment by arthroscopy. ②All samples were carried out the morphological measurement, light and transmission electron microscope exam, Ⅱ-collagen immunohistochemical stain, the measurement of collagen, calcium and fosforus. RESULTS: ①To compare the samples in the group A and control group, they had the identical or similar morphosis, microscopic structure of chondrocyte and distribution of extracellular matrix, the statistical treatments of the content of calcium, fosforus and collagen showed that the differences of scores between two groups were not statistically significant [calcium:(3.120?0.224),(3.090?0.231) mg/g;fosforus:(0.432?0.045),(0.455?0.067) mg/g;collagen:(462.43?17.12)(466.71?14.59) mg/g]. General speaking, comparing with the control articular cartilage, the loose bodies in group A had the normal histological property and physiological activity. ②Compared with control group, the samples in group B and C had the tendency of fibrous degeneration: necrotic or degenerative chondrocytes increasing, the contents of proteoglycan and Ⅱ-collagen decreasing, the tendency in group C more than group B, but the cartilaginous loose bodies in group B and C had many active chondrocytes mainly. Total content of collagen [(441.20?16.49),(417.33?8.38) mg/g] and Ⅱ-collagen decreased, while the contents of calcium and fosforus increased [calcium: (3.696?0.442),( 6.469?0.555) mg/g;fosforus:(0.523?0.068),(0.683?0.056) mg/g]. Generally, compared with the control articular cartilage, the histological property and physiological activity of the loose bodies in groups B and C had changed. CONCLUSION: The cartilaginous loose bodies can remain its histological property and physiological activity in the knee articular cavity for a long time, but it has the tendency of disorganization and physiological activity descending as time prolongs.

Objective: To observe the changes of mu-opioid receptors (MOR) expression in acute inflamed knee joint synovium tissue of dogs, so as to discuss the feasibility of using peripheral local opioid for analgesia in acute inflammation. Methods: Knee joint synovium tissues were taken from 9 dogs with acute arthritis and 8 dogs with normal knee joints. The expression of MOR protein and mRNA was examined by immunohistochemistry and real-time quantitative PCR. Results: The expression of MOR mRNA in the acute inflamed group was significantly higher than that in the normal control group ([34.40±5.48] % vs [16.54±8.03] %, P<0.05). Immunohistochemical result showed more positive staining of MOR particles and stronger signal in the acute arthritis group than in normal control group. The immunohistochemical index of MOR positive cells in the acute arthritis was significantly higher than that in normal control group ([323 175.00±92 614.94] vs [175 444.10±75 149.06], P< 0.05). Conclusion: MOR exists in the knee joint synovium tissue of dogs, and acute inflammation can enhance the expression of MOR.

This study is to establish the gastric cold model of rats. After gastric feeding with cold water for 5 weeks and extra iced water bath in the last 2 weeks, model group show distinct physical sign of gastric cold syndrome. The pathology of gastrics reveals gastricism of model group, while treatment group(treated with Fanzuojin Wan) show mild lesion. Elisa detection of model group show that the solution of interleukin-2 (IL-2) is higher than blank group. The difference with significance among model group, treatment group and blank group reveals the success of the establishment of gastric cold syndrome.
Animals ; Cold Temperature ; Disease Models, Animal ; Female ; Humans ; Male ; Rats ; Rats, Wistar ; Stomach ; chemistry ; metabolism ; pathology ; physiopathology ; Stomach Diseases ; metabolism ; pathology ; physiopathology

Animals ; Avoidance Learning ; physiology ; Cues ; Extinction, Psychological ; physiology ; Fear ; physiology ; Male ; Mental Recall ; physiology ; Rats ; Sleep Deprivation ; physiopathology ; Sleep, REM ; physiology