Objectives: Little is known about patients with neuromyelitis optica spectrum disorders (NMOSD) as defined by onset age. This study aimed to analyze the different demographic, clinical, laboratory, and magnetic resonance imaging (MRI) characteristics in early-onset (≤50 years) NMOSD (EONMOSD) and late-onset (>50 years) NMOSD (LONMOSD). Materials and Methods: We enrolled 142 patients with NMOSD from Tianjin Medical University General Hospital, Tianjin, China, and categorized them into two groups according to the age of onset: EONMOSD and LONMOSD. Demographic, clinical, laboratory, and MRI characteristics were collected and compared between the two groups. Serum aquaporin-4 (AQP4) antibody levels were determined by cell-based assay and fluorescence immunoprecipitation assays. Results: Among the patients studied, 83 had early onset (≤50 years) and 59 had late onset (>50 years) of NMOSD. As compared with LONMOSD, EONMOSD patients had more severe visual disability according to functional scores in clinical parameters, significantly lower C3 and C4 serum levels, more frequent cervical lesions, and more lesions around the fourth ventricle, but fewer lesions in hemispheric white matter. LONMOSD patients suffered more motor and sensory disability than EONMOSD patients. Conclusions: In NMOSD, the clinical, laboratory, and MRI features differ according to age of onset, suggesting that differences in pathogenesis and treatment should be further investigated.

Up-down determination of the 90% effective dose (ED₉₀) of remimazolam besylate for anesthesia induction Zhixia Lu, Na Zhou, Yan Li, Li Yang, Wei Hao

Background: Ischemic stroke is one of the leading causes of mortality and morbidity in the world and effective neuroprotectants are yet to be developed. Recent studies have demonstrated excellent neuroprotective effects of a bivalent enkephalin opioid agonist, biphalin in multiple stroke models. Methods: The purpose of this study is to evaluate novel multifunctional enkephalin-fentanyl opioid agonists, LYS436, LYS739 and LYS416 for their neuroprotective potential using in vitro and in vivo ischemic stroke models and to compare the effect to that of biphalin. Results: In general, all non-selective opioid agonists significantly decreased neuronal cell death and levels of reactive oxygen species in primary neurons subjescted to hypoxia-aglycemia/re-oxygenation or NMDA neurotoxicity. Fluorinated enkephalin-fentanyl conjugate, LYS739 showed enhanced neuroprotection in both in vitro models compared to biphalin. Based on further in vitro screening and comparative studies to biphalin, LYS739 was selected as a lead for in vivo experimentation. A mouse middle cerebral artery occlusion (MCAO) stroke model was utilized to study biphalin and the lead analog, LYS739. Both agonists significantly decreased brain infarct and edema ratios compared to saline treated group. Neurological impairment after stroke was statistically significantly improved in terms of neurological score and locomotor activities with LYS739 and biphalin treatment. Importantly, LYS739 and biphalin demonstrated better neuroprotection compared to fentanyl, and this effect was reversed by non-selective opioid antagonist naltrexone. Conclusion: In summary, the results of this study suggest that the multifunctional fluorinated enkephalin analog, LYS739 can be considered as a potential lead for ischemic stroke research and may provide advantages given the multimeric peptide-opiate structure.