Efficacy and safety of glibenclamide therapy after intracerebral haemorrhage (GATE-ICH): A multicentre, prospective, randomised, controlled, open-label, blinded-endpoint, phase 2 clinical trial.

Background: Glibenclamide is a promising agent for treating brain oedema, but whether it improves clinical outcomes in patients with intracerebral haemorrhage (ICH) remains unclear. In this study, we aimed to explore the efficacy and safety of glibenclamide treatment in patients with acute ICH. Methods: The Glibenclamide Advantage in Treating Oedema after Intracerebral Haemorrhage (GATE-ICH) study was a randomised controlled phase 2 clinical trial conducted in 26 hospitals in the northwest of China, recruiting patients with acute ganglia ICH no more than 72 h after onset from Dec 12, 2018 to Sept 23, 2020. During the first 7 days after enrolment, patients randomly assigned to the glibenclamide group were given glibenclamide orally (1.25 mg, 3/day) and standard care, while patients randomly assigned to the control group were given standard care alone. The computer-generated randomisation sequence was prepared by a statistician not involved in the rest of the study. Randomisation was computer-generated with a block size of four. The allocation results were unblinded to participants and investigators. The primary outcome was the percentage of patients with poor outcome (defined as modified Rankin Scale [mRS] score of ≥3) at day 90. The trial was registered at ClinicalTrials.gov (NCT03741530). Findings: 220 participants were randomised and 200 participants (mean [standard deviation] age, 56 [11] years; sex, 128 [64.0%] male and 72 [36.0%] female) were included in the final analysis, with 101 participants randomly assigned to the control group and 99 to the glibenclamide group. The incidence of poor outcome at day 90 was 20/99 (20.2%) in glibenclamide group and 30/101 (29.7%) in control group (absolute difference, 9.5%; 95% confidence interval [CI], -3.2%-21.8%; P = 0.121) with adjusted odds ratios of 0.54 (95% CI, 0.24-1.20; P = 0.129). No significant difference was found in the overall rates of adverse events or serious adverse events between groups. However, the incidence of asymptomatic hypoglycaemia was significantly higher in glibenclamide group than control group (15/99 [15.2%] vs 0/101 [0.0%]; absolute difference, 15.2%; 95% CI, 7.5%-24.1%; P < 0.001). Interpretation: Our study provides no evidence that glibenclamide (1.25 mg, 3/day) significantly reduces the proportion of poor outcome at day 90 after ICH. In addition, glibenclamide could result in higher incidence of hypoglycaemia. Larger trials of glibenclamide with optimised medication regimen are warranted. Funding: Shaanxi Province Key Research and Development Project (2017DCXL-SF-02-02) and Shaanxi Province Special Support Program for Leading Talents in Scientific and Technological Innovation (tzjhjw).

Alcohol dehydrogenase 5 of Helicoverpa armigera interacts with the CYP6B6 promoter in response to 2-tridecanone.

Alcohol dehydrogenase 5 (ADH5) is a member of medium-chain dehydrogenase/reductase family and takes part in cellular formaldehyde and S-nitrosoglutathione metabolic network. 2-tridecanone (2-TD) is a toxic compound in many Solanaceae crops to defend against a variety of herbivory insects. In the broader context of insect development and pest control strategies, this study investigates how a new ADH5 from Helicoverpa armigera (HaADH5) regulates the expression of CYP6B6, a gene involved in molting and metamorphosis, in response to 2-TD treatment. Cloning of the HaADH5 complementary DNA sequence revealed that its 1002 bp open reading frame encodes 334 amino acids with a predicted molecular weight of 36.5 kD. HaADH5 protein was purified in the Escherichia coli Transetta (pET32a-HaADH5) strain using a prokaryotic expression system. The ability of HaADH5 protein to interact with the 2-TD responsive region within the promoter of CYP6B6 was confirmed by an in vitro electrophoretic mobility shift assay and transcription activity validation in yeast. Finally, the expression levels of both HaADH5 and CYP6B6 were found to be significantly decreased in the midgut of 6th instar larvae after 48 h of treatment with 10 mg/g 2-TD artificial diet. These results indicate that upon 2-TD treatment of cotton bollworm, HaADH5 regulates the expression of CYP6B6 by interacting with its promoter. As HaADH5 regulation of CYP6B6 expression may contribute to the larval xenobiotic detoxification, molting and metamorphosis, HaADH5 is a candidate target for controlling the growth and development of cotton bollworm.

[Preparation and identification of anti-HaCHT4 mouse polyclonal antibody].

Objective The group IV chitinase from Helicoverpa armigera (HaCHT4)was expressed in prokaryotic and its polyclonal antibody against HaCHT4 was prepared. Methods The fusion protein His-HaCHT4 was expressed in E.coli and purified the target protein by Ni-column, and immunized the mice by footpad and subcutaneous injection. The titer of polyclonal antibody against His-HaCHT4 was determined by ELISA after four immunizations. The immunological specificity of the anti His-HaCHT4 was assayed by Western blot analysis. Results Fusion protein His-HaCHT4 was purified successfully and the titer of mouse anti His-HaCHT4 polyclonal antibody was higher than 1:204 800. The results of Western blot showed that the anti His-HaCHT4 polyclonal antibody was able to bind the fusion protein His-HaCHT4, and also specifically recognize the natural HaCHT4 in Helicoverpa armigera, but not the protein in Tenebrio molitor. Conclusion His-HaCHT4 was successfully expressed in prokaryotic and purified, and its mouse anti His-HaCHT4 polyclonal antibody was prepared.

[Determination of eleven elements in water-touched material by ICP-MS].

Water-touched material include water distribution equipment, protecting materials, and water treatment material. The security of the material plays an important role in everyone's daily life. So it' s necessary to determing metal elements in the material. A method for the determination of eleven elements, including Ag, As, Ba, Cd, Cu, Sb, Sn, Mn, Ni, Pb and Hg, in the water-touched material by inductively coupled plasma-mass spectrum (ICP-MS) is described. The plasma parameters were optimized as follows: The RF input power was 1350 W; flow rate of cooling gas was 13 L x min(-1); flow rate of assistant gas was 0.70 L x min(-1); flow rate of carrying gas was 0.8 L x min(-1); flow rate of atomization gas was 1.02 L x min(-1); rate of sampling was 1.48 mL x min(-1). The detection limits of these eleven elements were 0. 003-0.170 microg x L(-1). The relative standard deviations (n=6) were 0.6%-6.3%. The correlation coefficients were 0.9990-0.9996. The recoveries of the method were 92.4%-108.2%. This method is sensitive, accurate and simple compared with other methods, and has the advantage of wide linear range. The results were satisfactory.

[Randomized control study on domestic fixed-dose combinations in the initial treatment of smears positive tuberculosis].

OBJECTIVE: To explore the feasibility of domestic fixed-dose combinations as antituberculosis therapy applied in the National Tuberculosis Program. METHODS: A randomized control trial was conducted and 422 smear-positive pulmonary tuberculosis patients were randomly distributed into 2 groups. The trial group was treated daily with rifampicin, isoniazid and pyrazinamide tablets (including 120 mg rifampicin, 80 mg isoniazid and 250 mg pyrazinamide) in the first 2 months and rifampicin and isoniazid tables (including 300 mg rifampicin, 150 mg isoniazid) in the subsequent 4 months. The control group was treated by full 6-month standard regimens (2HRZE/4H3R3). RESULTS: The demographic data and the disease status were similar between the 2 groups before treatment. The rate of conversion from positive to negative cases in the trial group after therapy was 91.6% at 2 months, 97.2% at 3 months, and 97.7% at 6 months, while that of the control group was 87.3%, 97.5%, and 98.0% respectively. The difference in the conversion rates between the two groups was not statistically significant (chi2 = 2. 05, chi2 = 0.03, chi2 = 0.04, P > 0.05). The incidence of skin rash as an adverse effect was less common in the trial group as compared to the control group (Fisher's exact P = 0.024 33) . CONCLUSIONS: Domestic fixed-dose combinations as supplementary anti-tuberculous therapy could be used in the National Tuberculosis Program, but further study is needed for widespread application.