Vagal sensory neurons mediate the Bezold-Jarisch reflex and induce syncope.

Visceral sensory pathways mediate homeostatic reflexes, the dysfunction of which leads to many neurological disorders1. The Bezold-Jarisch reflex (BJR), first described2,3 in 1867, is a cardioinhibitory reflex that is speculated to be mediated by vagal sensory neurons (VSNs) that also triggers syncope. However, the molecular identity, anatomical organization, physiological characteristics and behavioural influence of cardiac VSNs remain mostly unknown. Here we leveraged single-cell RNA-sequencing data and HYBRiD tissue clearing4 to show that VSNs that express neuropeptide Y receptor Y2 (NPY2R) predominately connect the heart ventricular wall to the area postrema. Optogenetic activation of NPY2R VSNs elicits the classic triad of BJR responses-hypotension, bradycardia and suppressed respiration-and causes an animal to faint. Photostimulation during high-resolution echocardiography and laser Doppler flowmetry with behavioural observation revealed a range of phenotypes reflected in clinical syncope, including reduced cardiac output, cerebral hypoperfusion, pupil dilation and eye-roll. Large-scale Neuropixels brain recordings and machine-learning-based modelling showed that this manipulation causes the suppression of activity across a large distributed neuronal population that is not explained by changes in spontaneous behavioural movements. Additionally, bidirectional manipulation of the periventricular zone had a push-pull effect, with inhibition leading to longer syncope periods and activation inducing arousal. Finally, ablating NPY2R VSNs specifically abolished the BJR. Combined, these results demonstrate a genetically defined cardiac reflex that recapitulates characteristics of human syncope at physiological, behavioural and neural network levels.

[Expression of survivin in leukemia cells and influence on it by GM-CSF].

This study was aimed to explore the expression of survivin in leukemia cells and to investigate the effect of GM-CSF on survivin expression. The survivin expressions in 37 previously untreated leukemia patients and 10 normal persons as well as in three kinds of leukemia cell lines (K562, HL-60, U937) were analyzed by RT-PCR. The HL-60 cells were treated by the proper concentration of GM-CSF, and the changes of survivin mRNA and protein expression levels were detected by using RT-PCR and Western blot respectively. The results indicated that the positive rate of survivin gene in 37 leukemia patients was 67.6% (25/37) and significantly higher than that in normal control (20.0%). The expression level was higher in ALL cells than that in AML cells (73.3% vs 63.6%). Moreover, three kinds of leukemia cell lines all expressed survivin. After treating with the proper concentration of GM-CSF for 2 days, the expression of survivin obviously increased and the expression level of survivin mRNA was up-regulated by 26%, the expression level of survivin protein was up-regulated by 49%. It is concluded that the survivin gene extensively express in leukemia and its cell lines, and its expression can be obviously increased by GM-CSF.