Objective To explore the relationship between vitamin D and depression and the effects of chronic unpredictable mild stress (CUMS) plus sertraline on vitamin D metabolism in rat brain.Methods Male SD rats were randomly divided into normal control group,normal control + sertraline group,CUMS group and CUMS+sertraline group.CUMS was used to build the animal model of depression.After chronic exposure to CUMS or sertraline (8 mg·kg-1·d-1) for 6 weeks,behavioral response (sucrose preference test) and vitamin D metabolism in the prefrontal cortex were analyzed.Results Compared with normal control group,6 weeks of CUMS procedure induced the rats to a depression-like state,decreased weight and sucrose preference,and increased the expression of enzymes involved in vitamin D activation and catabolism (CYP27B1 and CYP24A1,respectively) and vitamin D receptor (VDR) in rat prefrontal cortex.As compared with CUMS group,CYP27B1,CYP24A1 and VDR were significantly decreased in CUMS+sertraline group (P<0.01 or P<0.05).Conclusion CUMS activates vitamin D signaling in the brain of the animal models of depression,while sertraline alleviates depressive behavior and relieves stress-induced activation of vitamin D signaling,indicating that vitamin D signaling may be involved in the stress-induced depression.

Objective To investigate the effects of lipopolysaccharide(LPS) on the tryptophan-kynurenine(TRP) metabolic pathway in rat brains and provide new evidence for the relationship between inflammation and depression.Methods Rats in LPS group were given a single dose of 3.5 mg/kg LPS.while the rats in control group were given the same dosage of saline.The dialysis in ventro-hippocampus were collected by microdialysis within 8 hours and then the TRP,KYN and KA were detected by LC-MS/MS.And the expression of indoleamine 2,3-dioxygenase was detected by Western-blot.Results The level of TRP((550.15± 107.96) pmol/L) and KYN ((337.95±62.73) pmol/L) showed a time-dependent increase after administration LPS 4 h compared with the control group(TRP (368.38±59.31) pmol/L,KYN (172.80±43.96) pmol/L),while KA level in the circulation exhibited a trend to decrease,especially at 7 h ((3.47±0.62) pmol/L,P＜0.05).The ratio of KYN/TRP significantly increased at about 5 h (0.69±0.11,P＜ 0.05),and an ratio of KA/KYN (0.02±0.00) was dramatically decreased after administering LPS 4 h compared with the control group (0.05±0.01)(P＜0.05).Most of the analytes showed more dramatic changes around 4 h to 8 h.LPS group(1.48±0.37) increased the protein expression of indoleamine 2,3-dioxygenase compared with the control group(1.00±0.24) (P＜0.01).Conclusions LPS may cause tryptophan metabolic abnormalities and accelerate the way of kynurenine metabolism,leading to decreased the kynurenic acid status.

A sensitive, rapid, simple and economical ultra-performance liquid chromatography–tandem mass spectro-metric method (UPLC–MS/MS) was developed and validated for simultaneous determination of imatinib, dasatinib and nilotinib in human plasma using gliquidone as internal standard (IS). Liquid-liquid extraction method with ethyl acetate was used for sample pre-treatment. The separation was performed on an Xtimate Phenyl column using isocratic mobile phase consisting of A (aqueous phase: 0.15% formic acid and 0.05% ammonium acetate)and B(organic phase:acetonitrile)(A:B=40:60,v/v).The flow rate was 0.25 mL/min and the total run time was 6 min. The multiple reaction monitoring (MRM) transitions, m/z 494.5→394.5 for imatinib, 488.7→401.5 for dasatinib, 530.7→289.5 for nilotinib and 528.5→403.4 for IS, were chosen to achieve high selectivity in the simultaneous analyses. The method exhibited great improvement in sensitivity and good linearity over the concentration range of 2.6–5250.0 ng/mL for imatinib, 2.0–490.0 ng/mL for dasatinib,and 2.4–4700.0 ng/mL for nilotinib.The method showed acceptable results on sensitivity,specificity, recovery, precision, accuracy and stability tests. This UPLC–MS/MS assay was successfully used for human plasma samples analysis and no significant differences were found in imatinib steady-state trough concentra-tions among the SLC22A5?1889T>C or SLCO1B3 699G>A genotypes(P>0.05).This validated method can provide support for clinical therapeutic drug monitoring and pharmacokinetic investigations of these three tyrosine kinase inhibitors(TKIs).

OBJECTIVE：To establish the quality standard of the Tibetan medicine Ma lus Fructus （known as the fruit of Ese ）， and to provide scientific reference for quality control and utilization of resource. METHODS ：The qualitative analysis of 20 batches of Malus Fructus with different producing areas and different origins was carried out by morphological observation ，microscopic and TLC identification. According to the method stated in 2015 edition of Chinese Pharmacopoeia ，water content ，total ash content and extract content were determined. HPLC method was used to determine the contents of 6 kinds of flavones （chlorogenic acid ， hyperin，isoquercitrin，quercitin，phloridzin，quercetin）in Malus Fructus. RESULTS ：The properties of this medicinal material were obovate ，spheroidal or oval ，its surface was reddish brown to dark red ，with slight shrinkage. Its taste was sweet ，sour and slightly astringent. The microscopic characteristics of the powder were clear ，the stone cells were scattered individually or clustered，and the pulp parenchyma cells contained calcium oxalate cube crystal and cluster crystal. The results of TLC showed that there were fluorescent spots of the same color in the chromatogram of the tested product and the corresponding position of the reference substance （ursolic acid ）. The content ranges of moisture ，total ash and extracts were 9.02％-11.39％，2.29％-3.35％， 37.12％-58.41％ respectively. The linear ranges of chlorogenic acid ，hyperin，isoquercitrin，，quercetin phlorizin and quercetin were 3.12-50，1.25-20，1.25-20，3.12-50，18.7-300，0.5-8 μg/mL（all r were not less than 0.999 7）. RSDs of prescision ，stability and reproducibility tests were all lower than 3.0％（n＝6）. The average recoveries were 97.56％，98.28％，106.14％，103.74％， 98.37％，98.76％；RSDs were 1.57％，1.62％，1.38％，1.99％，2.15％，2.31％（n＝6）. The content ranges of the above six components in 20 baches of samples were 0.001 5％-0.028 8％，0.005 9％-0.022 0％，0.008 7％-0.030 4％，0.019 4％- 0.048 5％，0.068 5％-0.199 8％ and 0.005 1％-0.081 4％. CONCLUSIONS ：Established method is accurate and stable ，and can be used for quality control of Malus Fructus. It is preliminarily Δ 基金项目：四川省科技计划项目（No.2020YFS0495）；“杏林学 proposed that moisture and total ash content should not exceed 者”学科人才科研提升计划（No.CXTD2018016） 12％ and 3.5％，and extract （by dry product ）and phlorizin ＊硕士研究生 。研究方向 ：中药品种 、质量与资源 。E-mail： content should not be less than 40％ and 0.1％ respectively. 1159020313@qq.com # 通信作者：教授。研究方向：中药品种、质量与资源。E-mail：

Recently, accumulating evidence suggests that high bilirubin level is involved in the pathophysiology of schizophrenia. High bilirubin level during early childhood may increase the risk of being suffered from schizophrenia after adulthood, and schizophrenia patients with high bilirubin level have aggravated psychiatric symptoms. As compared with other psychiatric patients and general population, schizophrenia patients usually have relatively higher bilirubin level; high bilirubin level is associated with acute psychotic states, positive symptoms, and poor prognosis in patients with schizophrenia. This article reviews the relation between bilirubin and schizophrenia and its potential pathophysiological mechanism in order to provide a new direction for the study of schizophrenia pathogenesis and auxiliary diagnosis.

Hydrogen sulfide (H