Objective To research the role of hypothalamocerebellar histaminergic projections in somatic‐visceral integration of rats .Methods A total of 120 SD rats were randomly divided to 6 groups :group A - F ;which separately microinjected saline (group A) ,triprolidine(selective antagonist of H1 receptor ,group B) ,2‐PyEA(selective agonist of H1 receptor ,group C) ,ranitidine (selective antagonist of H2 receptor ,group D) ,dimaprit (selective agonist of H2 receptor ,group E) and histamine (group F) to the deep nuclei of rats .The abilities of rats somatic‐visceral integration were observed when hypothalamocerebellar histaminergic pro‐jections were obstructed or enhanced compared to group A .Results The somatic‐visceral integration of rats were obstructed obvi‐ously in group D and enhanced in group E & group F compared to group A ,while group B and group C had no differences compared to group A .Conclusion Hypothalamocerebellar histaminergic projections play a key role in somatic‐visceral integration through the way of H2 receptors .

Objective To explore the impact of ischemic stroke on intestinal barrier changes in dogs.Methods Totally 20 mongrel dogs were divided into 2 groups by random number table with 10 in each.Double silicone cylinders measuring 1.1 mm in diameter and 8 mm in length were placed into their internal carotid arteries in all dogs of group A.Group B served as a control group and received sham operation.Light microscopy was performed for morphological measurement of intestinal epithelial cell.Immunohistochemistry was used to analysis the changes of protein zonula occludens-1(ZO-1)localizing at tight junction of intestinal epithelial cells.Results Ischemic stroke was confirmed by cranial CT scanning in all dogs of group A.Compared with the test results in group B,the occludin and Zo-1 protein levels in group A were significantly lower than those in group B(occludin:0.20 ±0.01 vs 0.22 ±0.01,P =0.007; ZO-1:0.20 ±0.01 vs 0.22 ±0.02,P =0.008).The apoptotic index in group A was significantly higher than in group B(29.04 ± 3.79 vs 6.44 ± 1.24,P =0.002).There was a positive correlation between occludin and ZO-1(R =0.71,P =0.02),and the apoptotic index was negatively correlated with levels of occludin,ZO-1(R =-0.91,P =0.00; R =-0.77,P =0.01).Light microscopy showed that the dogs in group A had intestinal mucousal injuries while no obvious change was detected in group B.Conclusions Dogs with ischemic stroke tend to develop intestinal barrier dysfunction,during which the destruction of tight junction plays a key role.The up-regulated apoptosis of intestinal epithelial cell constitutes one of the cellular bases of intestine injury.

Objective To explore the effect of histamine on neurons in the hippocampal C1 area of SD rats and the behavior of depressive SD rats. Methods The effect of histamine on the discharge frequency of neurons in hippocampal C1 area was observed by in vitro extracellular recording of brain slices. The effect of endogenous histamine released to hippocampal neurons was observed through in vivo extracellular recording after the hypothalamus was electrically stimulated. In addition, the changes of motor activity and the ability of spatial memory of the rats with depression after microinjection of histamine into the hippocampal C1 area were observed by open-field test and Morris water maze test. Results The results of in vitro extracellular recording of brain slices showed that the hippocampal neurons were excited by histamine via H1 receptors rather than H receptors in a concentration dependent manner. The results of in vivo extracellular recording showed that endogenous histamine had a bidirectional effect, which means a short-term excitatory effect followed by a long-term inhibitory effect on the hippocampal neurons. After injected with histamine in the hippocampal C1 area,

The coronavirus disease 2019 (COVID-19) pandemic is caused by infection with the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), which is spread primary via respiratory droplets and infects the lungs. Currently widely used cell lines and animals are unable to accurately mimic human physiological conditions because of the abnormal status of cell lines (transformed or cancer cells) and species differences between animals and humans. Organoids are stem cell-derived self-organized three-dimensional culture in vitro and model the physiological conditions of natural organs. Here we showed that SARS-CoV-2 infected and extensively replicated in human embryonic stem cells (hESCs)-derived lung organoids, including airway and alveolar organoids which covered the complete infection and spread route for SARS-CoV-2 within lungs. The infected cells were ciliated, club, and alveolar type 2 (AT2) cells, which were sequentially located from the proximal to the distal airway and terminal alveoli, respectively. Additionally, RNA-seq revealed early cell response to virus infection including an unexpected downregulation of the metabolic processes, especially lipid metabolism, in addition to the well-known upregulation of immune response. Further, Remdesivir and a human neutralizing antibody potently inhibited SARS-CoV-2 replication in lung organoids. Therefore, human lung organoids can serve as a pathophysiological model to investigate the underlying mechanism of SARS-CoV-2 infection and to discover and test therapeutic drugs for COVID-19.
Adenosine Monophosphate/therapeutic use* ; Alanine/therapeutic use* ; Alveolar Epithelial Cells/virology* ; Antibodies, Neutralizing/therapeutic use* ; COVID-19/virology* ; Down-Regulation ; Drug Discovery ; Human Embryonic Stem Cells/metabolism* ; Humans ; Immunity ; Lipid Metabolism ; Lung/virology* ; RNA, Viral/metabolism* ; SARS-CoV-2/physiology* ; Virus Replication/drug effects*