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Objective To investigate the changes in endogenous metabolites in a rat model of depression and the modulatory effect of Baihe Zhimu decoction (BZD) on the abnormal metabolites through a metabolomic approach. Methods Forty rats were randomly divided into normal control group, depression model group, fluoxetine treatment group and BZD treatment group. In all but the control group, rat models of depression were established by keeping the rats in separate cages combined with exposure to chronic unpredictable mild stress. A metabolomic approach was used to identify the endogenous metabolites and metabolic pathways that were related to the antidepressive effects of BZD. Results BZD could significantly increase the body weight, sucrose preference and behavioral scores in the rat models of depression (P < 0.05). BZD treatment resulted in the recovery of normal levels for 23 metabolites that showed abnormal serum levels in the depressive rats, and these metabolites were associated with fatty acid amide metabolism, phenylalanine metabolism, glycine metabolism and lipid metabolism. By comparison, fluoxetine treatment only restored the normal levels for 17 abnormal metabolites, which were related with glycine metabolism and lipid metabolism. Conclusion BZD can modulate more metabolic pathways than fluoxetine for treatment of depression.

Jing Ouyang,1,2,* Fengjun Sun,1,* Dongsheng Zhou,3 Jiao Feng,3 Zhe Zhan,3 Zhijian Xiong,4 Bo Yang,1 Zhirui Liu,1 Tingbo Li,1 Yigang Tong,3 Peiyuan Xia1 1Department of Pharmacy, Southwest Hospital, The Third Military Medical University, Chongqing 400038, China; 2Department of Pharmacy, Chongqing Public Health Medical Center, Chongqing 400038, China; 3State Key Laboratory of Pathogen and Biosecurity, Beijing Institute of Microbiology and Epidemiology, Beijing 10007, China; 4Outpatient Department of August First Film Studio, Beijing 100161, China *These authors contributed equally to this work Background: Plasmid-mediated multi-drug resistance (MDR) has been widely found in Citrobacter freundii. C. freundii P10159 was isolated from a human case of postoperative urinary tract infection in a Chinese teaching hospital.Methods: The complete nucleotide sequences of five resistance plasmids pP10159-1, pP10159-2, pP10159-3, pP10159-4 and pP10159-5 from C. freundii P10159 were determined through high-throughput genome sequencing, and then compared with related plasmids sequences. Plasmid transfer, CarbaNP test of carbapenemase activity, and bacterial antimicrobial susceptibility test were performed to characterize resistance phenotypes mediated by these plasmids.Results: pP10159-1 carrying blaNDM-1 and pP10159-2 harboring blaIMP-4 plus qnrS1 were almost identical to IncX3 plasmid pNDM-HN380 and IncN1 plasmid pP378-IMP, respectively. The blaKPC-2-carrying plasmids pP10159-3, pHS062105-3 and pECN49-KPC were highly similar to each other, and constituted a novel group of plasmids belonging to an unknown incomparability group. The MDR plasmids pP10159-4 and pP10159-5 had the backbones highly similar to IncHI4 plasmid pNDM-CIT and type 2 IncC plasmid pR55, respectively, but their accessory resistance regions differed from pNDM-CIT and pR55, respectively. The five plasmids from the P10159 isolate contained a total of 24 different genes or gene loci, which contributed to resistance to 13 distinct antibiotic molecules or toxic compounds.Conclusion: This is the first report of co-occurrence of five different resistance plasmids, with determination of their complete sequences. Data presented here provide a deeper insight into co-selection and maintenance of multiple plasmids and an extremely large number of resistance genes in a single bacterial isolate. Keywords: Citrobacter freundii, multi-drug resistance, plasmids, mobile elements

Background Crush injury from debris, combined with hypoxia and water and food deprivation (combined crush injury), is common in industrial accidents and events such as earthquakes and terrorist attacks. Whether electrocardiographic changes are associated with combined crush injury is unclear. Methods Thirty-six rats underwent electrocardiography at baseline then were randomly assigned to 6 groups of 6. Bilateral hind limbs of all rats were compressed with custom-made clips (pressure 4.5 ± 0.3 kg), and the rats were put into a hypoxic compartment (oxygen concentration 10% ± 0.1%) for 72 hours without food or water. After 72 hours, the rats were moved to a normoxic environment, where the clips were removed (decompression) and food and water were freely accessible. Electrocardiography was performed in a different group at each of days 0, 1, 3, 7, 14, and 28 after decompression. Results One rat died at 0.6 days. Among the remaining 35 rats, 28 (80%) had abnormal electrocardiographic changes: ST-segment depression (n = 25), tall-peaked T waves (n = 16), arrhythmias (n = 4), abnormal Q waves (n = 2), wide QRS complexes (n = 2) and QT prolongation (n = 1). The abnormality rates among assessed rats were 100% on days 0, 1, and 3; 83% on day 7; and 50% on days 14 and 28. Conclusions The findings suggest that abnormal electrocardiographic changes were seen in rats after simulated combined crush injury and decompression and were slow to resolve.

Voltage-gated sodium channels (VGSCs) are important membrane protein carrying on the molecular basis for action potentials (AP) in neuronal firings. Even though the structure-function studies were the most pursued spots, the posttranslation modification processes, such as glycosylation, phosphorylation, and alternative splicing associating with channel functions captured less eyesights. The accumulative research suggested an interaction between the sialic acids chains and ion-permeable pores, giving rise to subtle but significant impacts on channel gating. Sodium channel-specific neurotoxic toxins, a family of long-chain polypeptides originated from venomous animals, are found to potentially share the binding sites adjacent to glycosylated region on VGSCs. Thus, an interaction between toxin and glycosylated VGSC might hopefully join the campaign to approach the role of glycosylation in modulating VGSCs-involved neuronal network activity. This paper will cover the state-of-the-art advances of researches on glycosylation-mediated VGSCs function and the possible underlying mechanisms of interactions between toxin and glycosylated VGSCs, which may therefore, fulfill the knowledge in identifying the pharmacological targets and therapeutic values of VGSCs.

In this paper, from the view of financial risk early-warning, we select the indexes which can give early-warning of financial crisis, and propose two ways from subjectivity and objectivity to get weights, where we choose factorial analysis as objective method, and Analytic Hierarchy Process as subjective method. Then we use combined means to acquire a compositive weight of each index, then it can reflect the importance of each index in financial risk early-arming. At last, we can perpetrate early-arming of the condition of financial safety via the weight of the indexes.