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ObjectiveTo explore the effect and mechanism of the classic famous prescription Anmeidan （AMD） developed in the Qing Dynasty in regulating the hepatic neurotransmitters and circadian rhythm in the rat model of insomnia via the orexin-1 receptor （OX1R）/phosphatidylinositol-specific phospholipase Cβ-1 （PLCβ-1）/protein kinase Cα （PKCα）/extracellular signal-regulated kinase 1/2 （ERK1/2） signaling pathway. MethodSixty SPF-grade SD rats were randomized into blank， model， suvorexant （30 mg·kg-1·d-1）， and low-， medium-， and high-dose （4.55， 9.09， 18.09 g·kg-1·d-1， respectively） AMD groups， with 10 rats in each group. The rats in other groups except the blank group were modeled by intraperitoneal injection of p-chlorophenylalanine （PCPA） and administrated with corresponding drugs by gavage， and the blank group received an equal volume of normal saline. The general condition， body mass， and 24 h autonomic activity of each group were observed. The pathological changes of the liver tissue were observed by hematoxylin-eosin（HE）staining and Masson staining. The expression of gamma-aminobutyric acid （GABA）， 5-hydroxytryptamine （5-HT）， epinephrine （EPI）， norepinephrine （NE）， and acetylcholine （ACh） in the liver tissue was detected by enzyme-linked immunosorbent assay. The glutamate （Glu） expression in the liver tissue was detected by the biochemical method. The mRNA levels of biological clock genes Per1， Per2， Cry1， Cry2， Bmal1， and Bmal2 in the liver were determined by Real-time fluorescence quantitative polymerase chain reaction（Real-time PCR）. The protein and mRNA levels of factors in the OX1R/PLCβ-1/PKCα/ERK1/2 signaling pathway in the liver were determined by Western blot and Real-time PCR， respectively. ResultCompared with the blank group， the modeling decreased the body mass （P<0.05， P<0.01） and caused mania and disturbed resting rhythms （P<0.01）， hepatic muscle fiber fracture， and edema with inflammatory cell infiltration. In addition， the modeling decreased the GABA， 5-HT， EPI， NE， and ACh content， increased Glu content （P<0.01）， down-regulated the mRNA levels of Per1， Per2， Cry1， and Cry2 （P<0.01）， up-regulated the mRNA levels of Bmal1 and Bmal2 （P<0.01）， and promoted the expression of OX1R， PLCβ-1， PKCα， and ERK1/2 at both protein and mRNA levels （P<0.01）. Compared with the model group， suvorexant and AMD increased the body mass （P<0.05， P<0.01）， alleviated the mania， and increased the resting time and frequency （P<0.05， P<0.01）. Moreover， the medications elevated the levels of GABA， 5-HT， EPI， NE， and ACh， lowered the Glu level， up-regulated the mRNA levels of Per1， Per2， Cry1， and Cry2 （P<0.05， P<0.01）， down-regulated the mRNA levels of Bmal1 and Bmal2， and inhibited the expression of OX1R， PLCβ-1， PKCα， and ERK1/2 at both mRNA and protein levels （P<0.05， P<0.01）. ConclusionAMD can regulate hepatic neurotransmitters and improve circadian rhythm in insomniac rats by inhibiting the OX1R/PLCβ-1/PKCα/ERK1/2 signaling pathway， and high-dose AMD demonstrated the strongest effect.
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Objective@#To analyze the status and related factors of adverse pregnancy outcomes in pregnant women with syphilis infection in Guangxi Zhuang Autonomous Region.@*Methods@#A total of 9378 pregnant women with syphilis infection who were diagnosed by Guangxi medical and health care institutions at all levels and were registered in the national "Management information system for mother-to-child transmission of AIDS, syphilis and hepatitis B" . The delivery date of these pregnant women were from 1 January 2014 to 31 December 2018, and their demographic characteristics, treatment, non-treponema pallidum titer, and pregnancy outcomes were collected. Multivariate logistic regression model was used to analyze the related factors of adverse pregnancy outcome.@*Results@#The age of the pregnant women with syphilitic infection was (30.05±6.07) years old. There were 1 184 cases with an adverse pregnancy outcome. The incidence of adverse pregnancy outcome was 12.63%, and 83.30% (7 812 cases) of patients received syphilis treatment, of which 50.32% (3 931 cases) were treated with standard treatment. The results of multivariate analysis showed that, the probability of an adverse pregnancy outcome for a 35-year-old was higher than those of the <25 year old [OR (95%CI)=1.37(1.13-1.67)]. The possibility of the occurrence of an adverse pregnancy outcome in 1-2 times of delivery was lower than that of 0 times of delivery in the past, with the OR (95%CI) value was 0.81 (0.70-0.94). Compared with those who tested for syphilis in the early stages of pregnancy, patients with gestational weeks ≥ 28 weeks of initial examination were more likely to have adverse pregnancy outcomes, with the OR (95%CI) value was 1.54 (1.26-1.88). Compared with the first test titer level was <1:8, the probability of an adverse pregnancy outcome was higher in the titer of ≥1:8, with the OR (95%CI) value was 1.33 (1.12-1.57). There was a higher probability of an adverse pregnancy outcome in the untreated patients compared to the treatment of the syphilitic, with the OR (95%CI) value was 1.41(1.19-1.68). Patients with unregulated treatment were more likely to have adverse pregnancy outcomes than those with standardized treatment, with the OR (95%CI) value was 1.27 (1.09-1.47).@*Conclusion@#Gestational weeks of first examination in pregnant women with syphilis infection, the first test titer, and the treatment condition were closely related to the occurrence of the adverse pregnancy outcome. Pregnant women with syphilis infection without treatment and unstandardized treatment were more likely to have adverse pregnancy outcomes than those of treatment and standardized treatment.