Summary The nature of fluid dynamics within the brain parenchyma is a focus of intensive research. Of particular relevance is its participation in diseases associated with protein accumulation and aggregation in the brain, such as Alzheimer’s disease (AD). The meningeal lymphatic vessels of the central nervous system have recently been recognized as an important player in the complex circulation and exchange of soluble contents between the cerebrospinal fluid (CSF) and the interstitial fluid (ISF). In aging mammals, for example, impaired functioning of the meningeal lymphatic vessels can lead to accelerated accumulation of toxic amyloid beta protein in the brain parenchyma, thus aggravating AD-related pathology. Given that meningeal lymphatic vessels are functionally linked to paravascular influx/efflux of the CSF/ISF, and in light of recent findings that certain cytokines, classically perceived as immune molecules, exert neuromodulatory effects, it is reasonable to suggest that the activity of meningeal lymphatics could alter the accessibility of CSF-borne immune neuromodulators to the brain parenchyma, thereby altering their effects on the brain. Accordingly, in this Perspective we discuss the suggestion that the meningeal lymphatic system can be viewed as a novel player in neurophysiology.

Background: The third fatal coronavirus is the novel coronavirus (SARS-CoV-2) that causes novel coronavirus pneumonia (COVID-19) which first broke out in December 2019. Patients will develop rapidly if there is no any intervention, so the risk identification of severe patients is critical. The aim of this study was to investigate the characteristics and rules of hematology changes in patients with COVID-19, and to explore the possibility differentiating moderate and severe patients using conventional hematology parameters or combined parameters. Methods:The clinical data of 45 moderate and severe type patients with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infections in Jingzhou Central Hospital from January 23 to February 13, 2020 were collected. The epidemiological indexes, clinical symptoms, and laboratory test results of the patients were retrospectively analyzed. Those parameters with significant differences between moderate and severe cases were analyzed, and the combination parameters with the best diagnostic performance were selected using the linear discriminant analysis (LDA) method.Results: Of the 45 patients with the novel 2019 corona virus (COVID-19) (35 moderate and 10 severe cases), 23 were male and 22 were female, with ages ranging from 16 to 62 years. The most common clinical symptoms were fever (89%) and dry cough (60%). As the disease progressed, white blood cell count (WBC), neutrophil count, neutrophil-to-lymphocyte ratio (NLR), platelet-to-lymphocyte ratio (PLR), red blood cell distribution width-coefficient of variation (RDW-CV), and red cell volume distribution width-standard deviation (RDW-SD) parameters in the severe group were significantly higher than those in the moderate group (P<0.05); meanwhile, lymphocyte count (Lym#), eosinophil count (Eos#), high fluorescent cell percentage (HFC%), red blood cell count (RBC), hemoglobin (HGB), and hematocrit (HCT) parameters in the severe group were significantly lower than those in the moderate group (P<0.05). For NLR parameter, it's area under the curve (AUC), cutoff, sensitivity and specificity were 0.890, 13.39, 83.3% and 82.4% respectively; meanwhile, for PLR parameter, it's AUC, cutoff, sensitivity and specificity were 0.842, 267.03, 83.3% and 74.0% respectively. The combined parameters of NLR and RDW-SD had the best diagnostic efficiency (AUC =0.938), and when the cutoff value was 1.046, the sensitivity and the specificity were 90.0% and 84.7% respectively, followed by the combined parameter NLR&RDW-CV (AUC =0.923). When the cut-off value was 0.62, the sensitivity and the specificity for distinguishing severe type from moderate cases

Background: The global mortality rate for coronavirus disease 2019 (COVID-19) is 3.68%, but the mortality rate for critically ill patients is as high as 50%. Therefore, the exploration of prognostic predictors for patients with COVID-19 is vital for prompt clinical intervention. Our study aims to explore the predictive value of hematological parameters in the prognosis of patients with severe COVID-19.Methods: Ninety-eight patients who were diagnosed with COVID-19 at Jingzhou Central Hospital and Central Hospital of Wuhan, Hubei Province, were included in this study. Results:The median age of the patients was 59 years; the median age of patients with a good prognosis was 56 [28-79] years, and the median age of patients with a poor outcome was 67 years.The patients in the poor outcome group were older than the patients in the good outcome group (P<0.05).The comparison of hematological parameters showed that lymphocyte count (Lym#), red blood cells (RBCs), hemoglobin (HGB), hematocrit (HCT), mean corpuscular volume (MCV), and mean corpuscular hemoglobin (MCH) were significantly lower in the poor outcome group than in the good outcome group (P<0.05). Further, the red cell volume distribution width-CV (RDW-CV) and red cell volume distribution width-SD (RDW-SD) were significantly higher in the poor outcome group than in the good outcome group (P<0.0001). Receiver operating characteristic (ROC) curves showed RDW-SD, with an area under the ROC curve (AUC) of 0.870 [95% confidence interval (CI) 0.796-0.943], was the most significant single parameter for predicting the prognosis of severe patients. When the cut-off value was 42.15, the sensitivity and specificity of RDW-SD for predicting the prognosis of severe patients were 73.1% and 80.2%, respectively. Reticulocyte (RET) channel results showed the RET level was significantly higher in critical patients than in moderate patients and severe patients (P<0.05), which may be one cause of the elevated RDW in patients with a poor outcome. Conclusions:In this study, the hematological parameters of COVID-19 patients were statistically analyzed. RDW was found to be a prognostic predictor for patients with severe COVID-19, and the increase in RET may contribute to elevated RDW.

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Excessive glutamate release causes overactivation of N-methyl D-aspartate receptors (NMDARs), leading to excitatory neuronal damage in cerebral ischemia. Hydroxysafflor yellow A (HSYA), a compound extracted from Carthamus tinctorius L., has been reported to exert a neuroprotective effect in many pathological conditions, including brain ischemia. However, the underlying mechanism of HSYA's effect on neurons remains elusive. In the present study, we conducted experiments using patch-clamp recording of mouse hippocampal slices. In addition, we performed Ca 2þ imaging, Western blots, as well as mitochondrial-targeted circularly permuted yellow fluorescent protein transfection into cultured hippocampal neurons in order to decipher the physiological mechanism underlying HSYA's neuroprotective effect. Through the electrophysiology experiments, we found that HSYA inhibited NMDAR-mediated excitatory postsynaptic currents without affecting a-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptor and g-aminobutyric acid A-type receptor-mediated currents. This inhibitory effect of HSYA on NMDARs was concentration dependent. HSYA did not show any preferential inhibition of either N-methyl D-aspartate receptor subtype 2A-or N-methyl D-aspartate receptor subtype 2B-subunit-containing NMDARs. Additionally, HSYA exhibits a facilitatory effect on paired NMDAR-mediated excitatory postsynaptic currents. Furthermore, HSYA reduced the magnitude of NMDAR-mediated membrane depolarization currents evoked by oxygen-glucose deprivation, and suppressed oxygen-glucose deprivation-induced and NMDARdependent ischemic long-term potentiation, which is believed to cause severe reperfusion damage after ischemia. Through the molecular biology experiments, we found that HSYA inhibited the NMDA-induced and NMDAR-mediated intracellular Ca 2þ concentration increase in hippocampal cultures, reduced apoptotic and necrotic cell deaths, and prevented mitochondrial damage. Together, our data demonstrate for the first time that HSYA protects hippocampal neurons from excitotoxic damage through the inhibition of NMDARs. This novel finding indicates that HSYA may be a promising pharmacological candidate for the treatment of brain ischemia.