The salt-inducible kinase(SIK)family includes three isoforms,SIK1,SIK2 and SIK3,which are the main regulators of physiological and patho-logical processes and participate in the regulation of glucose and lipid metabolism,tumor,inflamma-tion,depression,sleep-wake and circadian rhythm.SIK inhibitor has become a candidate drug for the treatment of a variety of diseases,and is especially expected to become a potential new drug for the treatment of nervous system diseases,such as sleep disorders,circadian rhythm disorders,and de-pression.This review summarizes the regulation and mechanism of three isoforms of SIK and their upstream and downstream signaling pathways in the above physiological and pathological processes.It also reviews the recentstudies of SIK inhibitors.

Vigilance is a sensitive ability to respond to small changes in the environment and it is a ma-jor component of various cognitive performance tasks.Professionals in a variety of fields require high physical and vigilance performance during the working process to ensure productivity,workplace safety,and their own safety.This article reviews the research progress in vigilance in terms of the examination methods,influencing factors,and drug treatment in recent years,aiming to improve the understanding of vigilance and provide support for the research on vigilance and clinical treatment of vigilance-related dysfunctions.

The salt-inducible kinase(SIK)family includes three isoforms,SIK1,SIK2 and SIK3,which are the main regulators of physiological and patho-logical processes and participate in the regulation of glucose and lipid metabolism,tumor,inflamma-tion,depression,sleep-wake and circadian rhythm.SIK inhibitor has become a candidate drug for the treatment of a variety of diseases,and is especially expected to become a potential new drug for the treatment of nervous system diseases,such as sleep disorders,circadian rhythm disorders,and de-pression.This review summarizes the regulation and mechanism of three isoforms of SIK and their upstream and downstream signaling pathways in the above physiological and pathological processes.It also reviews the recentstudies of SIK inhibitors.

Objective:To compare the sedative and anti-anxiety effects of levo-tetrahydropalmatine (L-THP) and diazepam on conditioned fear model rats.Methods:According to the random number table method, 32 adult male rats were divided into blank group, model group, diazepam group and L-THP group(with 8 rats in each group). The conditioned fear model was reproduced by the plantar electric shock method. Four days after the modeling, the rats in diazepam group and L-THP group were given diazepam (3.6 mg/kg) and L-THP (25 mg/kg) were respectively gavaged once a day for 10 days, the rats in blank group and model group were given the same volume of saline. After the administration, the elevated plus maze test and the open field test were used to measure the anxiety behavior of the rats, and the sleep energy monitoring system was used to detect changes in sleep and energy-related indicators. SPSS 23.0 and Graphpad Prism 7.0 softwares were used for data analysis, multiple samples between groups were compared by one-way ANOVA, and LSD test was used for pairwise comparison.Results:The results of the elevated plus maze experiment showed that compared with the model group, the percentage of open-arm entry times ((11.27±8.78)%, (30.11±14.59)%, P<0.05) and the percentage of open-arm residence time ((1.94±1.48)%, (17.53±8.21)%, P<0.05) in diazepam group were all significantly increased. Compared with the model group, the open arm residence time, the percentage of open arm residence time and the percentage of open arm entry times in L-THP group showed an upward trend, but there was no statistical significance (all P>0.05). The results of the open field experiment showed that compared with the model group, the time of entering the central grid ((2.99±1.83) s, (6.94±3.52) s, P<0.05) and the time of entering the peripheral field ((297.01±1.83) s, (293.30±3.52) s, P<0.05) in diazepam group both increased. Compared with the model group, there was no significant difference in the changes of various indexes in L-THP group (all P>0.05). The results of locomotor activities showed that the autonomic activity times of model group in nighttime was significantly lower than that of blank group((758.79±375.37)times/h, (1 101.93±525.96)times/h, P<0.05). Compared with the model group, the number of autonomous activities of rats in L-THP group in daytime ((820.57±364.60) times/min, (502.40±228.54)times/min, P<0.05) decreased, and the number of autonomous activities in the nighttime ((758.79±375.37) times/min, (1 146.85±309.69)times/min, P<0.05) increased, but there was no significant change in the number of autonomous activities in the whole day. Correlation analysis of energy metabolism related indexes and sleep time of rats in each group were analyzed. The experimental results showed that the daytime sleep time were negatively correlated with heat value ( r=-0.335, P<0.05), and the night sleep time was positively correlated with daytime heat value ( r=0.352, P<0.05). Conclusion:L-tetrahydropalmatine has no significant anti-anxiety effect in the concentration range used in this study, but its sedative and improving sleep activity rhythm are better than diazepam.

Aim To investigate the effect that catalpol intervenes macrophage polarization mediated by mouse mesangial cells(MMCs) stimulated by advanced glycation end products(AGEs).Methods RAW264.7 macrophages and MMCs were co-cultured in vitro and divided into model group(100 mg·L-1 AGEs), control group(100 mg·L-1 BSA), catalpol(0.1, 1.0, 10.0 μmol·L-1) group, and aminoguanidine(1.0 μmol·L-1) group which was set as positive control.After being incubated with catalpol for 1 h, MMCs were stimulated by AGEs for 23 h.The proliferation-inhibition rate of MMCs was measured by MTT assay.MCP-1 in supernatant liquid of MMCs was detected by ELISA method.The expression of iNOS, CD16/32, TNF-α, COX-2, CD206 and Arg-1 was detected by Western blot.Simultaneously, the percentage of iNOS and CD206 was also measured by flow cytometry.Results AGEs could increase the level of MCP-1 secreted by MMCs.The expression of iNOS, TNF-α, CD16/32 and COX-2 protein of macrophage was up-regulated after MMCs stimulated by AGEs, while the expression of CD206 and Arg-1 was down-regulated.After being intervened by catalpol, these effects could be reversed.All the changes were concentration-related.Conclusions Catalpol can inhibit macrophages M1-type polarization process and promote M2-type polarization, which may be mediated through MCP-1 secreted by MMCs after AGEs stimulation.Catalpol can ameliorate inflammation and relieve diabetic kidney injury.