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ObjectiveThe aim of this study is to create a rank order of the comparative efficacy and acceptability (risk of all-cause discontinuation) of antidepressant treatment in poststroke depression (PSD) by integrating direct and indirect evidence.DesignMultiple-treatments meta-analysis of randomised controlled trials.ParticipantsPatients with depression following stroke.Interventions10 antidepressants and placebo in the acute treatment of PSD.Outcome measuresThe primary outcomes were the overall efficacy, defined as the mean change of the total depression score. The secondary outcome was the acceptability, defined as risk of all-cause discontinuation. These estimates as standardised mean differences or ORs with 95% CIs.ResultsWe identified 12 suitable trials, with data from 707 participants. All drugs were significantly more effective than placebo apart from sertraline, nefiracetam and fluoxetine. Most of the comparisons for acceptability revealed no significant differences except that paroxetine had significantly lower all-cause discontinuation than doxepin, citalopram and fluoxetine. Standardised mean differences compared with placebo for efficacy varied from −6.54 for the best drug (reboxetine) to 0.51 for the worst drug (nefiracetam). ORs compared with placebo for acceptability ranged from 0.09 for the best drug (paroxetine) to 3.42 for the worst drug (citalopram). For the efficacy rank, reboxetine, paroxetine, doxepin and duloxetine were among the most efficacious treatments, the cumulative probabilities of which were 100%, 85.7%, 83.2%, 62.4%, respectively. With respect to the acceptability rank, paroxetine, placebo, sertraline and nortriptyline were among the most acceptable treatments, the cumulative probabilities of which were 92.4%, 63.5%, 57.3%, 56.3%.ConclusionAfter weighing the efficacy and acceptability, we conclude that paroxetine might be the best choice when starting acute treatment for PSD, and fluoxetine might be the worst choice.Trial registration numberThis systematic review has been registered in the Prospective Register of Systematic Review Protocols (PROSPERO) public database (CRD42017054741; http://www.crd.york.ac.uk/PROSPERO).

Background: Although thrombolysis is considered to be the first-line treatment for ischemic stroke, there remains an ongoing controversy on the safety and efficacy of thrombolysis in cervical artery dissection (CAD). The aim of this meta-analysis was to assess observational data related to the safety and efficacy of thrombolysis in CAD-related ischemic stroke. Methods: We performed a systematic search of the efficacy of thrombolysis treatment in CAD-related ischemic stroke with appropriate observational studies identified for the study. The meta-analysis models in Comprehensive Meta-Analysis V2 software were applied to calculate the merged rates of favorable outcome (modified Rankin Scale, mRS 0-2), excellent outcome (mRS 0-1), intracranial hemorrhage (ICH), symptomatic ICH (SICH), mortality and recurrent stroke between thrombolysis and non-thrombolysis in CAD-related stroke. The difference of outcomes and adverse events between the 2 groups was compared by analyzing the pooled OR value and chi-square test using the software SPSS. Results: A total of 846 patients were identified from 10 studies (174 with thrombolysis; 672 with non-thrombolysis). The meta-analysis detected no significant statistical difference in the proportion of CAD-related stroke patients enjoying a favorable outcome at the 3 months' follow-up between the thrombolysis and non-thrombolysis groups (53.7 vs. 58.2%, OR 0.782, χ² = 0.594, p > 0.05); non-thrombolysis was slightly superior than thrombolysis in terms of excellent outcome (52.4 vs. 34.4%, OR 0.489, χ² = 9.143, p = 0.002). There was no significant difference in SICH, mortality and recurrent stroke rates between the 2 groups (all p > 0.05). ICH rate was higher in the thrombolysis group of CAD-related stroke patients compared to that in the non-thrombolysis group (12.3 vs. 7.4%, OR 2.647, χ² = 4.127, p = 0.042). Conclusion: Thrombolysis seems to be equally safe and will achieve an efficacy similar to the efficacy of non-thrombolysis in patients with acute ischemic stroke due to CAD. It is also as effective as thrombolysis in stroke from miscellaneous causes. Therefore, CAD patients experiencing a stroke should not be denied thrombolysis therapy. However, this will need to be confirmed in large-scale randomized studies, especially involving intravenous thrombolysis treatment.

The brain can undergo self-repair and has the ability to compensate for functions lost after a stroke. The plasticity of the ischemic brain is influenced by several factors including aging and pharmacotherapy. Fluoxetine is an antidepressant which enhances serotonergic neurotransmission through selective inhibition of neuronal reuptake of serotonin. In clinical practice, fluoxetine alleviates the symptoms of post-stroke depression (PSD), helps motor recovery in stroke patients. In animal experiments, chronic administration of fluoxetine induces increased excitability of mature granule cells (GCs), enhancing axonal and dendritic reorganization, as well as promoting neurogenesis or angiogenesis in the dentate gurus (DG), but the effect of fluoxetine in the subventricular zone (SVZ) remains controversial. Meanwhile, chronic treatment with fluoxetine did not reverse age-dependent suppression of proliferation cells in the DG. Interestingly, although fluoxetine has been found to enhance neurogenesis in the DG in stroke rats, this property is not consistent with the behavioral recovery. More studies into this issue will be required to reveal how to translate enhanced neuronal plasticity into behavioral benefits. This review provides an update of the current knowledge about the neurogenesis and the fate of the newly generated cells after the use of fluoxetine, as well as its ability to promote a behavioral recovery after stroke in clinical and experimental results and attempts to define the therapeutic properties of fluoxetine in regenerative neuroscience.

MicroRNA (miR)-1 is associated with various human malignancies through repressing tumor growth, migration and angiogenesis. Recently, high-throughput transcriptional profiling confirmed that miR-1 is markedly downregulated in metastatic colorectal cancer; however, its biological functions and the specific underlying mechanisms in colorectal cancer (CRC) require further investigation. In this study, the expression of miR-1 in 111 CRC and paired normal tissue samples was measured using quantitative polymerase chain reaction analysis, and the association between miR-1 expression and clinical characteristics was evaluated. miR-1 was found to be significantly downregulated in CRC tissues compared with paired normal tissues, and in CRC cell lines compared with non-cancer cells (P<0.001), and was negatively associated with tumor size (P=0.001), differentiation (P=0.011), lymph node metastasis (P=0.001) and TNM stage (P=0.001). Further experiments revealed that miR-1 inhibited the migration and invasion of HCT116 and ClonA1 cells, and inhibited cell proliferation by affecting the cell cycle. Vascular endothelial growth factor (VEGF) was found to be a potential target of miR-1 by biological prediction, and further investigation confirmed that miR-1 significantly inhibited the expression and paracrine function of VEGF. In CRC tissues, the expression of VEGF was negatively correlated with miR-1. The low expression of miR-1 in CRC may be one of the reasons for the abnormally high expression of VEGF; the upregulation of miR-1 expression may inhibit cancer progression by downregulating VEGF. These findings indicate that treatment with miR-1 may be a novel method of tumor suppression, and provide a theoretical and experimental basis for the further targeted treatment of CRC through the regulation of miR-1 and VEGF expression.

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BackgroundThe question of which antidepressants should be preferred for the treatment of post-stroke depression is controversial, and pairwise meta-analyses cannot provide a hierarchy of these interventions. We aimed to integrate the available evidence to create hierarchies of the comparative efficacy and acceptability of treatments.Methods We did a multiple-treatments meta-analysis (which uses both direct and indirect comparisons) of randomised controlled trials to compare antidepressants and placebo in the acute treatment of post-stroke depression. Electronic databases (MEDLINE, Embase, PsycINFO, Cochrane Central Register of Controlled Trials [CENTRAL], Web of Science) were searched up to Dec 31, 2016. We included only randomised controlled trials that compared antidepressants as monotherapy in patients with post-stroke depression. The patients had to have had a stroke diagnosed clinically or by CT scan or MRI and have been subsequently diagnosed with depression. We applied no inclusion restrictions on the basis of patient and study characteristics, such as age, sex, study dates, and class of antidepressants. The primary outcome was overall efficacy, defined as the mean change of the total depression score between baseline and 6 weeks. If 6-week data were not available, we used data from between 4 and 12 weeks (the datapoint closest to 6 weeks was given preference). The secondary outcome was acceptability, defined as risk of all-cause discontinuation. We tested for inconsistency with the design-by-treatment interaction model that provides a single inference, using the χ² test. This study has been registered with PROSPERO, number CRD42017054741. FindingsWe identified 12 suitable trials, with data from 707 participants. 11 antidepressants were assessed in the trials, including placebo. All drugs were significantly more effective than placebo apart from sertraline (odds ratio [OR] -0•61, 95% CI -1•47 to 0•25), nefiracetam (OR 0•51, -0•17 to 1•19), and fluoxetine (OR 0•46, -0•35 to 1•27). For efficacy, standardised mean differences, compared with placebo, varied from -6•54 (95% CI -8•42 to -4•65) for the best drug (reboxetine) to 0•51 (-0•17 to 1•19) for the worst drug (nefiracetam). Reboxetine, paroxetine, and doxepin were the most efficacious treatments (ranked in order), the cumulative probabilities of which were 100%, 85•7%, and 83•2%, respectively. For acceptability, ORs compared with placebo ranged from 0•09 (95% CI 0•00 to 1•83) for paroxetine to 3•42 (0•73 to 15•91) for citalopram. Patients assigned to paroxetine had significantly lower all-cause discontinuation than those assigned to doxepin (OR 0•04, 95% CI 0•00 to 0•73), citalopram (OR 0•03, 0•00 to 0•78), and fluoxetine (OR 0•04, 0•00 to 0•89); all other comparisons were not significant. Paroxetine (cumulative probability 92•4%), placebo (63•5%), and sertraline (57•3%) were the most acceptable treatments. Comparison-adjusted funnel plots for efficacy and acceptability were largely symmetrical. For acceptability (all-cause discontinuation), we found no e...