Objective Meta-analysis the efficacy and safety of Exenatide and insulin therapy oral hypoglycemic drugs effect of obesity with type 2 diabetes .Methods According to the research purpose to set up the screening of related literature and exclusion criteria; formulatethe searching strategy, through PubMed、the Chinese Biological Medicine Datebase(CBM)、 CNKI、Wanfang Data Knowledge Service Platform, VIP to retrieve all theliterature selection of efficacy and safety by Exenatide oral hypoglycemic drugs and insulin therapy of obese type 2 diabetes mellitus.Choose met inclusion exclusion criteria, the complete data information randomized controlled trial (RCT) as the research object; Apply to the international commonly used Jadad score method to evaluate quality included in the test; To process the relevant data in the test ; Apply the ReviewManager 5.1 software to analysis the extracted research data.Analysis the results and put forward conclusions.Results Participants included 11 RCT , meta analysis results showed that compared with the Exenatide, in terms of reducing fasting glucose ,insulin effect more apparent [MD = 0.35, 95％CI: (0.11, 0.59), P = 0.004)]. In control effect of glycosylated hemoglobin, there was no statistically significant difference[MD=-0.04 ,95％CI:(-0.20,0.11), P=0.58],between Exenatide and insulin. Compared with the insulin, Exenatide reduce BMI more apparent[MD=-2.77,(95％CI: -3.34,-2.20),P<0.00001]; Compared with the insulin, Exenatide reduce insulin resistance index, the effect is more obvious[MD=-1.67,95％CI:(-1.93,-1.41), P<0.00001]; Adverse reaction in the process of treatment, the insulin is more likely to lead to hypoglycemia, [OR = 0.32, 95％ CI: 0.19, 0.54), P<0.0001]; While Exenatide are more likely to lead to gastrointestinal adverse reaction [OR = 4.04, 95％ CI: 2.35, 6.93), P<0.00001).Conclusion According to the Meta-analysis: Exenatide can be used in the treatment of oral hypoglycemic drugs of adult obesity with type 2 diabetes, and obvious effects of treatment of insulin resistance, long-term results still needs a large number of samples of high quality RCT to verify.

OBJECTIVE: To prepare Salinomycin nanostructured lipid carriers (Sal-NLCs) and optimize its formulation. METHODS: Sal-NLCs was prepared by emulsion evaporation-low temperature solidification method. Using particle size, Zeta potential, encapsulation efficiency and drug loading as evaluation indexes, central composite design-response surface methodology was used to optimize the amount of Sal, the ratio of solid lipid glyceryl bisstearate to liquid lipid glyceryl octanoate in oil phase, ratio of surface active agent polyoxyethylene 35 castor oil (EL) to polyethylene glycol-15-hydroxy stearate (HS 15), the amount of polyoxyethylene (40) stearate (P40). The morphology, particle size, polydispersity index (PDI), Zeta potential, encapsulation efficiency, drug loading and in vitro release mechanism of Sal-NLCs were investigated. RESULTS: The optimal prescription was as follows as Sal 0. 86 mg, glyceryl bisstearate 40.70 mg, glyceryl octanoate 11.30 mg, EL 44.05 mg, HS15 7.95 mg, P40 3.8 mg. Prepared Sal-NLCs was round-like and dispersed evenly. The particle size, PDI, Zeta potential, encapsulation efficiency and drug loading of prepared Sal-NLCs were(81.81 ± 2.60) nm, 0.183 ± 0.042, (-24.9 ± 3.4) mV,(94.35 ± 1.50)％ and (1.47 ±0.04)％ (n=5), respectively.24 h accumulative release rate was (99.81 ± 3.90)％ (n=3).Drug release behavior was in line with Higuchi model, and relative error of particle size, Zeta-potential, encapsulation efficiency and drug loading to predicted value of model were all lower than 4％. CONCLUSIONS: Sal-NLCs with sustained-release effect is prepared successfully according to optimized formulation, and its quality meets the expected standard.

The possibility of reusing Escherichia coli cells from the broth for succinic acid production was investigated. Using succinic acid yield and productivity as criterion, we investigated the effects of cell concentration, initial glucose concentration, different neutralizers on the bioconversion. The results revealed that E. coli could convert glucose to succinic acid in a water solution of glucose and a neutralizer. According to the results, the optimal condition was as follows: the cell concentration was 50 (OD600), glucose concentration was 40 g/L and neutralizer was MgCO3. Under the optimum conditions, we carried out the consecutive batch bioconversion in 7 L fermenter. Succinic acid yield reached 91% with the productivity of 3.22 g/(L x h) for the first conversion. For the second conversion, succinic acid yield reached 86% with productivity of 2.04 g/(L x h). Furthermore, we achieved a high mass yield above 83% with the productivity of 1.82 g/(L x h) for the third bioconversion.
Escherichia coli ; genetics ; metabolism ; Fermentation ; Genetic Engineering ; Glucose ; metabolism ; Industrial Microbiology ; Succinic Acid ; metabolism

Objective:To investigate the hierarchical management scheme of cervical adenocarcinoma in situ (AIS) based on cervical conization margin state.Methods:All medical records of 249 patients diagnosed as AIS by loop electrosurgical excision procedure (LEEP) conization from Jan. 2010 to Dec. 2015 in Obstetrics and Gynecology Hospital of Fudan University were retrospectively reviewed, to explore the relationship between the status of the resection margin and the residual lesion after LEEP, and the multivariate logistic regression method was used to analyze the related factors that affect the residual lesion after LEEP in cervical AIS patients.Results:(1) The age of 249 cervical AIS patients was (40±8) years old (range: 23-71 years old). Of the 249 patients, 19 (7.6%, 19/249) had residual lesions; 69 cases were pathologically diagnosed as AIS after LEEP, and the residual lesion rate was 13.0% (9/69), which was significantly higher than that of AIS + high-grade squamous intraepithelial lesion [5.6% (10/180); χ2=3.968, P=0.046]; 33 cases were multifocal lesions, the residual rate of lesions was 21.2% (7/33), which was significantly higher than that of single focal lesions patients [5.6% (12/216); χ2=7.858, P=0.005]; 181 patients underwent endocervical curettage (ECC) before surgery, the residual rate of lesions in ECC-positive patients was 14.0% (14/100) , significantly higher than that of ECC-negative patients [4.9% (4/81); χ2=4.103, P=0.043]. (2) Among 249 cases of AIS patients, the positive rate of resection margins after LEEP was 35.3% (88/249); the residual rate of lesions in patients with positive resection margins (14.8%, 13/88) was significantly higher than those with negative margins [3.8%(6/156); χ2=9.355, P=0.002]. The age of patients underwent total hysterectomy after LEEP was (43±7) years old, which was significantly higher than that of patients who did not undergo total hysterectomy [(37±8) years old; t=6.518, P<0.01].Among the patients underwent total hysterectomy after LEEP, 3 cases (2.0%, 3/152) had fertility requirements, while 38 cases (39.2%, 38/97) did not underwent total hysterectomy, the difference between the two groups was statistically significant ( χ2=59.579, P<0.01). Among the 152 patients who underwent total hysterectomy after LEEP, the residual rate of lesions was 11.8% (18/152); the residual rate of lesions in patients with positive resection margins was significantly higher than that of patients with negative resection margins [18.8% (12/64) vs 7.0% (6/86); χ2=4.861, P=0.028]. The median follow-up time of 97 patients who did not undergo total hysterectomy after LEEP was 32 months (range: 4-70 months). During the follow-up period, 3 cases of cervical AIS recurrence (3.1%, 3/97) and were followed by hysterectomy,no invasive adenocarcinoma were seen. (3) Multivariate logistic regression analysis showed that the positive resection margin ( OR=4.098, 95% CI: 1.235-13.595, P=0.021), multifocal lesions ( OR=5.464, 95% CI: 1.494-19.981, P=0.010) were independent risk factors that affected the residual lesions in patients with cervical AIS after LEEP. Conclusions:The cervical AIS patients after LEEP conization suggested be stratified by cone margin state as the first-line stratified index, age and fertility needs as the second-line stratified management index. The individualized management plan should be developed based on comprehensive assessment of high-risk factors of residual lesions.

Tryptophan 2,3-dioxygnease 2 (TDO2) is specific for metabolizing tryptophan to kynurenine (KYN), which plays a critical role in mediating immune escape of cancer. Although accumulating evidence demonstrates that TDO2 overexpression is implicated in the development and progression of multiple cancers, its tumor-promoting role in esophageal squamous cell carcinoma (ESCC) remains unclear. Here, we observed that TDO2 was overexpressed in ESCC tissues and correlated significantly with lymph node metastasis, advanced clinical stage, and unfavorable prognosis. Functional experiments showed that TDO2 promoted tumor cell proliferation, migration, and colony formation, which could be prevented by inhibition of TDO2 and aryl hydrocarbon receptor (AHR). Further experimentation demonstrated that TDO2 could promote the tumor growth of KYSE150 tumor-bearing model, tumor burden of C57BL/6 mice with ESCC induced by 4-NQO, enhance the expression of phosphorylated AKT, with subsequent phosphorylation of GSK3

Mutations or inactivation of parkin, an E3 ubiquitin ligase, are associated with familial form or sporadic Parkinson's disease (PD), respectively, which manifested with the selective vulnerability of neuronal cells in substantia nigra (SN) and striatum (STR) regions. However, the underlying molecular mechanism linking parkin with the etiology of PD remains elusive. Here we report that p62, a critical regulator for protein quality control, inclusion body formation, selective autophagy and diverse signaling pathways, is a new substrate of parkin. P62 levels were increased in the SN and STR regions, but not in other brain regions in parkin knockout mice. Parkin directly interacts with and ubiquitinates p62 at the K13 to promote proteasomal degradation of p62 even in the absence of ATG5. Pathogenic mutations, knockdown of parkin or mutation of p62 at K13 prevented the degradation of p62. We further showed that parkin deficiency mice have pronounced loss of tyrosine hydroxylase positive neurons and have worse performance in motor test when treated with 6-hydroxydopamine hydrochloride in aged mice. These results suggest that, in addition to their critical role in regulating autophagy, p62 are subjected to parkin mediated proteasomal degradation and implicate that the dysregulation of parkin/p62 axis may involve in the selective vulnerability of neuronal cells during the onset of PD pathogenesis.
Adaptor Proteins, Signal Transducing ; chemistry ; metabolism ; Animals ; HEK293 Cells ; Heat-Shock Proteins ; chemistry ; metabolism ; Humans ; Lysine ; metabolism ; Mice ; Neurons ; metabolism ; pathology ; Oxidopamine ; pharmacology ; Parkinson Disease ; metabolism ; pathology ; Proteasome Endopeptidase Complex ; metabolism ; Protein Stability ; Proteolysis ; drug effects ; Sequestosome-1 Protein ; Ubiquitin-Protein Ligases ; metabolism ; Ubiquitination ; drug effects