ObjectiveTo explore the effect and mechanism of directive differentiation of microglia by SN50 on hypoxia-caused neurons injury in mice.MethodsThe microglia were isolated and purified from brain tissue of new-born BALB/c mice through differential velocity adherent and vibration technique. The quantity of the microglia was identified by immunofluorescence staining of inducible nitric oxide synthetase (iNOS) and ionized calcium binding adapter molecule 1 (Iba1) and real-time fluorescence quantitative PCR (qRT-PCR) for special expression genes [iNOS, CD32, and interlenkin 10 (IL-10)]. Then the microglia were cultured with SN50, and the expressions of nuclear factor κB (NF-κB), differentiation-related genes (iNOS, CD11b, IL-10, and CD206), and apoptosis were detected by Western blot, qRT-PCR, and flow cytometry, respectively. The hypoxia model of neuron was established, and the cell apoptosis was evaluated by MTT after 0, 2, 6, 12, 24, and 48 hours of anoxic treatment. The apoptosis related markers (Bcl-2 and Caspase-3) were measured by Western blot and flow cytometry. In addition, the neurons after anoxic treatment were co-cultured with SN50 treated microglia (experimental group) and normal microglia (control group) for 24 hours. And the cell viability and apoptosis related markers (Bcl-2 and Caspase-3) were also measured.ResultsImmunofluorescence staining and qRT-PCR analysis showed that the cells expressed the specific proteins and genes of microglia. Compared with the normal microglia, the relative expressions of NF-κB protein and iNOS and CD11b mRNAs in the microglia treated with SN50 significantly decreased (P<0.05), the relative expressions of IL-10 and CD206 mRNAs significantly increased (P<0.05), and the cell apoptosis rate had no significant change (P>0.05). Compared with the normal neurons, the cell viability, the relative expressions of Bcl-2 and Caspase-3 proteins after anoxic treatment significantly decreased (P<0.05), while the relative expressions of cleaved-Caspase-3 protein and cell apoptosis rate of neurons significantly increased (P<0.05). In the co-culture system, the cell viability, the relative expressions of Bcl-2 and Caspase-3 proteins were significantly higher in experimental group than those in control group (P<0.05), while the relative expressions of cleaved-Caspase-3 protein and cell apoptosis rate were significantly lower in experimental group than those in control group (P<0.05).ConclusionSN50 can induce the microglia differentiation into M2 type through NF-κB pathway. The SN50-induced microglia can protect neurons from hypoxic injury.
Does-response meta-analysis, which has being developed for more than 30 years, is a type of regression function and can be both linear and non-linear model. It plays an important role in investigating the relationship between dependent and independent variable. With its special advantages, dose-response meta-analysis has been widely used in evidence-based practice and decision. Currently there are several models can be used to perform dose-response metaanalysis with various advantages and disadvantages. It is vital to choose best model to perform dose-response metaanalysis in evidence-based practice. In this paper, we briefly introduce and summarize the methodology of dose-response meta-analysis.
Dose-response meta-analysis is being increasingly applied in evidence production and clinical decision. The research method, synthesizing certain dose-specific effects across studies with the same target question by a certain types of weighting schedule to get a mean dose-response effect, is to reflect the dose-response relationship between certain exposure and outcome. Currently, the most popular method for dose-response meta-analysis is based on the classical "two-stage approach", with the advantage that it allows fixed- or random-effect model, according to the amount of heterogeneity in the model. There are two types of random-effect model available for dose-response meta-analysis, that is, the generally model and the coefficient-correlation-adjusted model. In this article, we briefly introduce two models and illustrate how they are applied in Stata software, which is expected to provide theoretical foundation for evidence-based practice.
ObjectiveTo investigate the effects and safety of intravitreous injection of Conbercept combined with laser photocoagulation for macular edema secondary to branch retinal vein occlusion. MethodsAll subjects were assigned randomly to 3 groups:intravitreal Conbercept combined with laser photocoagulation group (CL group), intravitreal triamcinolone combined with laser photocoagulation group (TL group), and photocoagulation group (L group). The best-corrected visual acuity (BCVA), central macular thickness (CMT), fundus oculi and fundus fluorescein angiography (FFA), intraocular pressure (IOP), slit lamp were observed before and 1 day, 1 week, 1 month, 3 months after treatment. The changes of post-treatment BCVA and CMT in pre-therapy and post-treatment were compared, and related complications were recorded. ResultsThere were significant differences of BCVA (χ2=9.754, 12.430, 17.424, 13.189) and CMT (F=10.614, 4.099, 4.927, 8.99) between 3 groups in post-treatment 1 day, 1 week, 1 month and 3 months. The numbers of subjects of improving and stabilizing BCVA in CL group were remarkably more than that in L group in every post-treatment follow-up time (P < 0.01), whereas the CMTs in CL group were significantly less than that in L group in every post-treatment follow-up time (P < 0.05). The CMTs in post-treatment 1 day, 1 week, 1 month, 3 months were thinner than that in pretreatment in CL group and TL group (P < 0.05). Meanwhile, there was no significant difference (P > 0.05)between any two CMTs in post-treatment 1 day, 1 week, 1 month and 3 months in CL group. Yet, the CMT in post-treatment 3 months was thicker than those in post-treatment 1 day, 1 week and 1 month in TL group(P < 0.05). And there was no significant difference(P > 0.05)between any two CMTs in post-treatment 1 day, 1 week and 1 month in TL group. There was no conspicuous difference in CMTs(P > 0.05)between in CL group and in TL group in every viewing time, except for that in post-treatment 3 months(P < 0.05). There was only 1 case of intraocular hypertension in post-treatment in TL group. ConclusionsIntravitreous injection of Conbercept combined with laser photocoagulation for macular edema secondary to BRVO is effective, safe, and superior to laser photocoagulation only. Also it had a longer effective duration and less complications than intravitreal triamcinolone combined with laser photocoagulation.