Terpenoids constitute a chemically diverse family of naturally occuring compounds with pharmaceutical significance, such as artemisinin and taxin. They are synthesized in many kinds of microorganisms and plants with very low yield. Metabolic engineering, modifying metabolic pathways of terpenoids-synthesized cells by recombinant DNA techniques, has been developed and applied to improve the production of terpenoids, as well as create a novel biosynthesis pathway of terpenoids in terpenoid-free organisms. The biosynthetic pathway of terpenoids was sumed up, and recent progress of metabolic engineering aiming at raising content of terpenoids in microorganisms and plants was described.

In order to improve the production of agro-antibiotic 2-16,the producing strain(Streptomyces ahygroscopicus var.huangshanensis) was treated by protoplast regeneration,ultraviolet radiation,NTG mutagenesis and low energy C~(+) ion implantation.At last,a high-yield strain No.515 was obtained.The production of ~()No.515 was increased by 223.10%.By using Plackett-Burman design and Response Surface Analysis provided by SAS software,the cultivation condition of No.515 was optimized.The amount of agro-antibiotic 2-16 was increased by 38.53% when the strain No.515 was cultivated in the optimum medium instead of the initial one.

Adolescent ; Adult ; China ; epidemiology ; Female ; Helicobacter Infections ; epidemiology ; Humans ; Male ; Rural Population ; Transients and Migrants ; Young Adult

Appropriate selection and measurement of lead biomarkers of exposure are critically important for health care management purposes, public health decision making, and primary prevention synthesis. Lead is one of the neurotoxicants that seems to be involved in the etiology of psychologies. Biomarkers are generally classified into three groups: biomarkers of exposure, effect, and susceptibility.The main body compartments that store lead are the blood, soft tissues, and bone; the half-life of lead in these tissues is measured in weeks for blood, months for soft tissues, and years for bone. Within the brain, lead-induced damage in the prefrontal cerebral cortex, hippocampus, and cerebellum can lead to a variety of neurological disorders, such as brain damage, mental retardation, behavioral problems, nerve damage, and possibly Alzheimer's disease, Parkinsons disease, and schizophrenia. This paper presents an overview of biomarkers of lead exposure and discusses the neurotoxic effects of lead with regard to children and adults.
Alzheimer Disease ; chemically induced ; metabolism ; pathology ; physiopathology ; psychology ; Animals ; Behavior ; drug effects ; Biomarkers ; metabolism ; Brain ; metabolism ; pathology ; physiopathology ; Brain Diseases ; chemically induced ; pathology ; physiopathology ; Environmental Exposure ; adverse effects ; Humans ; Lead ; pharmacokinetics ; toxicity ; Lead Poisoning ; etiology ; metabolism ; pathology ; physiopathology ; psychology ; Neurotoxicity Syndromes ; etiology ; metabolism ; pathology ; physiopathology ; psychology ; Parkinson Disease, Secondary ; chemically induced ; metabolism ; pathology ; physiopathology ; psychology ; Schizophrenia ; chemically induced ; metabolism ; pathology ; physiopathology

A sensitive, rapid, simple and economical ultra-performance liquid chromatography–tandem mass spectro-metric method (UPLC–MS/MS) was developed and validated for simultaneous determination of imatinib, dasatinib and nilotinib in human plasma using gliquidone as internal standard (IS). Liquid-liquid extraction method with ethyl acetate was used for sample pre-treatment. The separation was performed on an Xtimate Phenyl column using isocratic mobile phase consisting of A (aqueous phase: 0.15% formic acid and 0.05% ammonium acetate)and B(organic phase:acetonitrile)(A:B=40:60,v/v).The flow rate was 0.25 mL/min and the total run time was 6 min. The multiple reaction monitoring (MRM) transitions, m/z 494.5→394.5 for imatinib, 488.7→401.5 for dasatinib, 530.7→289.5 for nilotinib and 528.5→403.4 for IS, were chosen to achieve high selectivity in the simultaneous analyses. The method exhibited great improvement in sensitivity and good linearity over the concentration range of 2.6–5250.0 ng/mL for imatinib, 2.0–490.0 ng/mL for dasatinib,and 2.4–4700.0 ng/mL for nilotinib.The method showed acceptable results on sensitivity,specificity, recovery, precision, accuracy and stability tests. This UPLC–MS/MS assay was successfully used for human plasma samples analysis and no significant differences were found in imatinib steady-state trough concentra-tions among the SLC22A5?1889T>C or SLCO1B3 699G>A genotypes(P>0.05).This validated method can provide support for clinical therapeutic drug monitoring and pharmacokinetic investigations of these three tyrosine kinase inhibitors(TKIs).

Objective To discuss whether the separating block of sensory nerve with acupoint-injection and epidural analgesia by ropivacaine during labour.Methods Ninty full term primigravidae with ASAⅠ～Ⅱwere randomly divided into 3 groups:group E(n = 30),group C(n = 30)and group A(n = 30).When the external cervi- cal os was dilated to 3cm,group A:acupiont-injection to Ci Liao;group E:epidural analgesia with 0.075% ropiva- caine and fentanyel 2?g/ml;group C:combining group A and group E except fentanyel 2?g/ml.Level of pain(VAS scores),degree of sensory and motor block,the mode of delivery,the progress of labour and side effects were recorded and compared.Results The level of pain(VAS scores)in group A was higher than that of group C and group E,and there were no significant differences in group C and group E,Bur there were some side effects discovered in group E. There was no significant differences of the mode of delivery in the groups.Conclusion The method that acupoint- rejection combined with epidural analgesia by 0.075% ropivacaine is effective and has no side effects for labour.

The cytokines of acute leukemia (AL) patients have certain expression patterns, forming a complex network involved in diagnosis, progression, and prognosis. We collected the serum of different AL patients before and after complete remission (CR) for detection of cytokines by using an antibody chip. The expression patterns of cytokines were determined by using bioinformatics computational analysis. The results showed that there were significant differences in the cytokine expression patterns between AL patients and normal controls, as well as between acute myeloid leukemia (AML) and acute lymphoblastic leukemia (ALL). In confirmatory test, ELISA revealed the expression of uPAR in AL. Moreover, the bioinformatic analysis showed that the differentially expressed cytokines among the AL groups were involved in different biological behaviors and were closely related with the development of the disease. It was concluded that the cytokine expression pattern of AL patients is significantly different from that of healthy volunteers. Also, differences of cytokine expression patterns exist between AML and ALL, and between before and after CR in the same subtype of AL, which holds important clinical significance for revealing disease progression.

Objective To explore the clinical applicating and efficacy of free fibula osteomyocutane- ous flap in mandible defect reconstruction in osteoradionecrosis patients.Methods The mandible defects were reconstructed by free fibula flaps with or without muscle cuff.The soft tissue defects were repaired by skin paddles.Status of osteotomy in fibula and flap survival was recorded.The complication in recipient site and donor site,as well as mouth opening and occlusion were reviewed.Facial contour and chewing function after reconstruction were evaluated.Results Patients were followed up 3-16 months.4 free fibula flaps with muscle cuff and 5 without muscle cuff survived well.The size of mandible defects covered from 6cm to 17cm. And the harvested fibula flaps with length of 8.6-17cm were cut into 3 segments in 2 cases,and 2 segments in 5 cases.Fibula flap was divided into 2 segments and overlapped in 2 cases.No serious complication was oh- served in recipient site and donor site.Satisfying esthetic result and normal occlusiong of heath mandible were obtained in all cases.The degree of mouth opening was 2.5-3.3cm.Fair chewing function was revealed in re- constructive region after prosthesia repaired.Conclusion Free fibula osteomyocutaneous flap is relatively ideal reconstruction material of mandible defect in osteoradionecrosis patients for its high survival rate and well esthetic results.

Objective To compare mobilization effects of endogeneous MSCs in the treatment of ulcerative colitis rats by Shenling Baizhu Powder and Tongxie Yaofang Decoction. Methods Twenty SD male rats were randomly divided into blank group, model group, Shenling Baizhu Powder group and Tongxie Yaofang Decoction group. TNBS/ethanol method was used to build the ulcerative colitis model. Administration groups were given Shenling Baizhu Powder and Tongxie Yaofang Decoction for gavage and model group and blank group were given normal saline for gavage. After gavage, MSCs from peripheral blood and bone marrow were extracted for primary culture. MSCs of bone marrow and peripheral blood were detected by flow cytometry. Results MSCs from bone marrow showed: Compared with the blank group, the percentage of positive cells in the model group decreased (P<0.05); Compared with the model group, the percentage of positive cells in Shenling Baizhu Powder group and Tongxie Yaofang Decoction group increased, and the expression of Shenling Baizhu Powder group was more obvious (P<0.05). MSCs from peripheral blood showed: Compared with the blank group, the percentage of positive cells in the model group increased (P<0.05); Compared with the model group, the percentage of positive cells in Shenling Baizhu Powder group and Tongxie Yaofang Decoction group decreased, and the expression of Shenling Baizhu Powder group was more obvious (P<0.05). Conclusion Shenling Baizhu Powder and Tongxie Yaofang Decoction have the function of promoting the increase of bone marrow-derived MSCs and the reduction of peripheral blood source of MSCs in model rats, and Shenling Baizhu Powder is better than Tongxie Yaofang Decoction.

Objective To investigate the imaging manifestations of lung neoplasms in pre- and post- treatment with CT-guided Argon-Helium cryoablation.Methods All the lung neoplasms in 96 patients have been treated with CT-guided percutaneous Argon-Helium targeted cryoablation.All patients have pre- and post-treatment CT scanning in measurement of lesion size and CT value.The CT scanning has been rerpeated afterl,3,6,12 months of treatment.Results Among total 96 cases,there are 82 cases of lung cancer and 14 cases of metastasis with 110 lesions(89 cases with single lesion,7 cases with multiple lesions).The Ar-He cryoablation has been given 103 times in total.The size of each lesion ranged from 1.2 cm to 15.0 cm in diameter with mean value of(4.0?2.5)cm,including 12 lesions less than 2 cm,51 lesions between 2— 4 cm,24 lesions between 4—6 cm,23 lesions over 6 cm.There are 25 patients whose lesions covered by iceball with 1 cm of overloaping it's margin.There are 63 lesions with diameter less than 4 cm gained 100% ablation rate,24 lesions with 4—6 cm diameter gained 95.8% ablation rate,and 23 lesions with over 6 cm diameter gained 69.6% ablation rate.The post-treatment CT show a progressively enlarged round,low density refrigerant area which clearly demarked with non- refrigerant area.The center of each refrigerant area has negative CT value,the mean decreased CT value of lesion instantly after the treatment are about 30— 50 HU with P