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Solriamfetol is developed for the treatment of excessive sleepiness in adult patients with narcolepsy and obstructive sleep apnea (OSA). No systematic review of existing literature has been investigated before. Therefore, the meta-analysis is conducted to assess the efficacy and safety of solriamfetol for excessive sleepiness in narcolepsy and OSA.PubMed, Embase and Cochrane Library databases were searched from earliest date to July 2020 for randomized controlled trials (RCTs) and the primary outcomes were change from baseline in mean sleep latency and Epworth Sleepiness Scale (ESS).We pooled 1177 patients from five RCTs and found solriamfetol led to a significant increment in mean sleep latency (MD = 9.52, 95% CI: 7.60 to 11.44, P 0.00001) and a reduction in ESS score (MD = -3.74, 95% CI: -4.38 to -3.09, P 0.00001) compared with placebo. The proportion of patients with at least one adverse event was significantly increased in solriamfetol group (RR = 1.42, 95% CI: 1.24 to 1.64, P 0.00001), while no statistical differences existed in the risk of at least one serious adverse event between solriamfetol and controlled group (RR = 0.95, 95% CI: 0.24 to 3.77, P = 0.39).A dose of 150 mg solriamfetol is proved to be the appropriate and stable dose for excessive sleepiness. In addition, solriamfetol showed good efficacy for excessive sleepiness in narcolepsy and OSA but also significantly increases the risk of adverse events.

Intracerebral hemorrhage (ICH), the most lethal type of stroke, often leads to poor outcomes in the clinic. Due to the complex mechanisms and cell-cell crosstalk during ICH, the neurovascular unit (NVU) was proposed to serve as a promising therapeutic target for ICH research. This review aims to summarize the development of pathophysiological shifts in the NVU and neural-glia networks after ICH. In addition, potential targets for ICH therapy are discussed in this review. Beyond cerebral blood flow, the NVU also plays an important role in protecting neurons, maintaining central nervous system (CNS) homeostasis, coordinating neuronal activity among supporting cells, forming and maintaining the blood-brain barrier (BBB), and regulating neuroimmune responses. During ICH, NVU dysfunction is induced, along with neuronal cell death, microglia and astrocyte activation, endothelial cell (EC) and tight junction (TJ) protein damage, and BBB disruption. In addition, it has been shown that certain targets and candidates can improve ICH-induced secondary brain injury based on an NVU and neural-glia framework. Moreover, therapeutic approaches and strategies for ICH are discussed.

Intracerebral hemorrhage (ICH) is a devastating disease with high rates of mortality and morbidity. Galactose lectin-9 (Gal-9) belongs to the family of β-galactoside-binding lectins, which has been shown to play a vital role in immune tolerance and inflammation. However, the function of Gal-9 in ICH has not been fully studied in details. Several experiments were carried out to explore the role of Gal-9 in the late period of ICH. Primarily, ICH models were established in male adult Sprague Dawley (SD) rats. Next, the relative protein levels of Gal-9 at different time points after ICH were examined and the result showed that the level of Gal-9 increased and peaked at the 7th day after ICH. Then we found that when the content of Gal-9 increased, both the number of M2-type microglia and the corresponding anti-inflammatory factors also increased. Through co-immunoprecipitation (CO-IP) analysis, it was found that Gal-9 combines with Toll-like receptor-4 (TLR-4) during the period of the recovery after ICH. TUNEL staining and Fluoro-Jade B staining (FJB) proved that the amount of cell death decreased with the increase of Gal-9 content. Additionally, several behavioral experiments also demonstrated that when the level of Gal-9 increased, the motor, sensory, learning, and memory abilities of the rats recovered better compared to the ICH group. In short, this study illustrated that Gal-9 takes a crucial role after ICH. Enhancing Gal-9 could alleviate brain injury and promote the recovery of ICH-induced injury, so that Gal-9 may exploit a new pathway for clinical treatment of ICH.

Objectives To identify clinical characteristics of severe patients with COVID-19. Methods The WHO database of publications on COVID-19 and PubMed were searched from inception to March 20, 2020 and all valuable studies were analyzed using Stata 15.0. Results We selected forty-four studies with 13,497 patients. In the comparison of severe and non-severe groups, age over 50 (OR = 4.090; 95% CI = 2.422–6.907, P = 0.000) and underlying disease (OR = 3.992; 95% CI = 2.631–6.507, P = 0.000) are risk factors. Female gender (OR = 0.740; 95% CI = 0.622–0.881, P = 0.001) is a protective factor. Characteristics like dyspnea (OR = 4.914; 95% CI = 3.069–7.867, P = 0.000), lymphopenia (OR = 5.528; 95% CI = 3.484–8.772, P = 0.000), thrombocytopenia (OR = 3.623; 95% CI = 1.034–12.691, P = 0.044), elevated C-reactive protein (OR = 5.217; 95% CI = 2.459–11.070, P = 0.000) and D-dimer (OR = 3.780; 95% CI = 1.481–9.648, P = 0.005) were more frequently in severe cases. Diffuse lesions and consolidation (OR = 4.680; 95% CI = 3.183–6.881, P = 0.000) in imaging was considered reliable. Conclusions Men older than 50 with underlying disease are susceptible to develop severe pneumonia while female gender is protective. The typical symptom of severe pneumonia was dyspnea, but high fever, headache and diarrhea were not significantly different among patients with varying degrees of severity. Lymphopenia, thrombocytopenia, elevated C-reactive protein and D-dimer occurred more frequently in severe patients and yet leukopenia is not a characteristic laboratory indicator. Diffuse lesions and consolidation are important imaging features to distinguish severe pneumonia.

Background Some studies have reported that women are at higher risk for spontaneous subarachnoid hemorrhage (SAH) compared with men, and smoking is the most important lifestyle risk factor for spontaneous SAH. However, it is still unknown whether the risk of SAH from smoking and smoking status is differential for women and men. We performed a meta-analysis to estimate the effect of smoking on SAH in women compared with men. Methods PubMed (January 1, 1966 to February 19, 2020) and EMBASE (January 1, 1980 to February 19, 2020) were systematically searched. Studies that estimated sex-specific relative risks (RRs) of SAH were selected. We pooled sex-specific RRs, comparing women with men using random-effects meta-analysis. Results Data from 20 observational studies that included 1,387,204 participants (563,898 women) and 7,838 SAHs (3,977 women) were analyzed. The combined women-to-men RRs of former smokers versus never smokers for SAH were 1.08 (95% confidence interval [CI] 0.62–1.89, p = 0.78). The pooled women-to-men RRs of current smokers versus never smokers were 1.39 (95% CI 1.05–1.83, p = 0.02). The combined women-to-men RRs of total smokers versus never smokers RRs were 1.15 (95% CI 0.88–1.52, p = 0.30). Conclusions Our study shows there is not enough evidence to suggest that women who smoke have a greater risk for SAH than men; however, women who persistently smoke have a greater risk. Smoking seems to be more susceptible in the increased SAH risk in women.

The activation of microglia and inflammatory responses is essential for the process of intracerebral hemorrhage (ICH)-induced secondary brain injury (SBI). In this study, we investigated the effects of luteolin on ICH-induced SBI and the potential mechanisms. Autologous blood was injected to establish the ICH model in vivo, and oxyhemoglobin (OxyHb) was used to mimic the ICH model in vitro. We found that the administration of luteolin significantly improved motor and sensory impairments and inhibited neuronal cell degeneration in vivo. In the in vitro study, the decrease of the neuronal cell viability induced by activated microglia was alleviated by luteolin treatment. Furthermore, by antagonizing the activation of the Toll-like receptor 4 (TLR4)/TNF receptor-associated factor 6 (TRAF6)/nuclear transcription factor-κB (NF-κB) signaling pathway, the ICH-induced elevation of cytokine release was decreased after treatment with luteolin, which was confirmed both in vivo and in vitro. Additionally, we found that luteolin engaged with TRAF6 and inhibited the ubiquitination of TRAF6. Taken together, our findings demonstrate the neuroprotective effects of luteolin after ICH and the potential mechanisms, which suggest that luteolin is a potential therapeutic candidate for ICH treatment.

Excessive daytime sleepiness is considered as the prominent symptom in narcolepsy and Obstructive Sleep Apnea (OSA). Pitolisant is a novel selective histamine H3 receptor antagonist approved for improving excessive daytime sleepiness. The meta-analysis is conducted to assess the efficacy and safety of pitolisant versus placebo for excessive daytime sleepiness in narcolepsy and OSA. PubMed, Embase and Cochrane Library databases were searched from earliest date to November 2020 for randomized controlled trials (RCTs). The primary outcomes were mean changes in Epworth Sleepiness Scale (ESS), mean sleep latency, European quality-of-life questionnaire (EQ-5D), and risk ratio of treatment-emergent adverse events (TEAEs). We pooled 678 patients from four RCTs and found pitolisant significantly decreased ESS by mean difference (MD) of − 2.86 points (95% CI: − 3.75 to − 1.96), increased mean sleep latency by MD of 3.14 min (95% CI: 2.18–4.11), and increased EQ-5D by MD of 3.32 points (95% CI: 0.26–6.39) compared with placebo. The risk ratio of TEAE was 1.37 (95% CI: 1.08–1.74). Insomnia was the only TEAE significantly associated with pitolisant treatment. In conclusion, pitolisant showed great efficacy and controllable security versus placebo for excessive daytime sleepiness in narcolepsy and OSA. Compared with narcolepsy, patients with OSA were deemed to benefit more from pitolisant especially in terms of improving mobility and quality of life of patients without continuous positive airway pressure therapy.