OBJECTIVE To compare the acute toxicity characteristics and differences of water extracts from unprocessed and different processed products of Psoraleae Fructus in mice. METHODS Kunming mice were divided into 36 groups, including Psoraleae Fructus raw product group, stir-fried group, salt-baked group, Leigong group, and wine soaked group, as well as control group. Each group of mice was given a single intragastric administration of 0.04 mL·g-1 and observed for 14 d. The body weight, serum biochemical indices, and mortality of the mice were detected, and the LD50 value was calculated to study the toxicity differences of Psoraleae Fructus raw product and different processed products. RESULTS There was no statistically significant difference in the body weight of mice before administration in different groups. On the first day of administration, some mice in the administration group showed a certain decrease in body weight. The LD50 values of the Psoraleae Fructus raw product group, stir-fried group, salt-baked group, Leigong group, and wine soaked group were 63.20, 56.92, 51.95, 88.61, 59.02 g·kg-1, respectively. Compared with the control group, the serum ALT and TBA levels in the male mice in the Psoraleae Fructus raw product group were significantly increased; the serum ALT, AST, and TBA levels in the stir-fried group were significantly increased, but the ALP level was not statistically significant; the serum ALP, ALT, AST, and TBA levels in the salt-baked group, Leigong group, and wine soaked group were significantly increased. Compared with the control group, the serum ALP, ALT, AST, and TBA levels in female mice in the Psoraleae Fructus raw product group, salt-baked group, Leigong group, and wine soaked group were significantly increased; the serum ALT, AST, and TBA levels in the stir-fried group were significantly increased; all groups had significantly decreased TP levels. Pathological results showed that there was no abnormality in the liver of mice in the control group; the liver of mice in the Psoraleae Fructus raw product group, stir-fried group, salt-baked group, Leigong group, and wine soaked group had pathological changes such as vacuolar degeneration of liver cells, glycogen degeneration of liver cells, loose cytoplasm of liver cells, and partial central hepatocellular hypertrophy; the degree of liver damage in mice caused by different processed products compared with the raw product group: raw product group > wine soaked group > stir-fried group > salt-baked group > Leigong group. Among them, the wine soaking method caused the highest degree of liver damage, while the Leigong method caused the least. CONCLUSION Psoraleae Fructus has different toxicities after being processed by different methods. According to LD50, the toxicity of Leigong method processed products is significantly reduced.

OBJECTIVE To stud y the regulation mechanism of miRNA- 18a and miRNA-4802 on drug resistance of lymphoma cells via autophagy. METHODS Using human burkitt ’s lymphoma cell Daudi and human mantle cell lymphoma cell JeKo- 1 as the research objects ，adriamycin（ADR）and vincristine （VCR）as experimental drugs. After treatment of ADR and VCR ，relative cell viability was detected with CCK- 8 kit；the expression of apoptosis marker protein activated cleaved caspase- 9 and cleaved caspase-6 were detected by Western blot assay. The drug resistances of the two cells to ADR and VCR were investigated. The difference of autophagy activity between the two kinds of cells by expression detection of autophagy related proteins LC 3-Ⅱ and p62，autophagy flow experiment and transmission electron microscope observation. Fluorescence quantitative polymerase chain reaction was used to investigate the expression differences of miRNA- 18a and miRNA- 4802，ULK1 and ATG 7 mRNA in the two cells，and to detect the expression differences of ULK 1 and ATG 7 proteins. Taking JeKo- 1 cells as the research object ，the changes of autophagy activity and drug resistance were investigated after treatment with endogenous miRNAs （miRNA-18a mimics ， miRNA-4802 mimics）of two simulated organisms. RESULTS After ADR and VCR treatment ，compared with Daudi cells ，JeKo-1 cells had stronger drug resistance and autophagy activity. The expression of miRNA- 18a and miRNA- 4802 in JeKo- 1 cells were significantly lower than Daudi cells ，mRNA and protein expression of ULK 1 and ATG 7 were significantly higher than those of Daudi cells （P＜0.001）. After treatment of miRNA- 18a mimics and miRNA- 4802 mimics，the autophagy activities and drug resistances of JeKo- 1 cells were decreased significantly. CONCLUSIONS miRNA-18a and miRNA- 4802 can decrease drug resistances of lymphoma cells to ADR and VCR by reducing 2 the expression of autophagy-initiating genes ULK1 and ATG7， and inhibiting the autophagy activity of lymphoma cells.

【Objective】 To study the effect and mechanism of lncRNA XIST targeting miR-150 on LPS-induced apoptosis and secretion of inflammatory factors in MLE-12 cells. 【Methods】 Mouse lung epithelial MLE-12 cells were divided into control, LPS (LPS treatment), sh-NC+LPS (shRNA control transfection, LPS treatment), and sh-XIST+LPS (XIST shRNA transfection, LPS treatment) groups. We used qRT-PCR method to analyze and detect XIST expression level, Annexin V-FITC/PI double staining method to detect cell apoptosis, Western blotting method to analyze and detect the protein expressions of Bax and Bcl-2 in cells, TBA method to detect MDA content, Xanthine oxidation method to detect SOD activity, DCFH-DA method to detect ROS level, and ELISA method to analyze the levels of IL-1β and TNF-α in the culture supernatant. We used the bioinformatics software Starbase to analyze the possible target genes of XIST (miR-150), and then the luciferase reporter system to identify the target relationship between the two. In MLE-12 cells, XIST shRNA and miR-150 inhibitor were co-transfected, and then treated with LPS. We also measured apoptosis, oxidative damage indicators, and inflammatory factor secretion changes. 【Results】 Compared with control group, XIST level in MLE-12 cells of LPS group increased, apoptosis rate and Bax protein expression level increased, Bcl-2 protein expression level decreased, ROS and MDA level increased, SOD level decreased, and the secretion of IL-1β and TNF-α increased. Compared with the sh-NC+LPS group, the sh-XIST+LPSMLE-12 group had decreased XIST level, decreased apoptosis rate and Bax protein expression level, and increased Bcl-2 protein expression level, decreased ROS and MDA levels, increased SOD levels, and decreased IL-1β and TNF-α secreted by cells. Down-regulating XIST targeting promoted miR-150 expression. miR-150 inhibitor could reverse the effects of XIST shRNA on LPS-induced MLE-12 cell apoptosis, oxidative damage indicators, and inflammatory factor secretion. 【Conclusion】 Down-regulation of lncRNA XIST targeting miR-150 inhibits LPS-induced apoptosis and secretion of inflammatory factors in mouse lung epithelial MLE-12 cells.

Objective To observe changes of hippocampal levels of pro-inflammatory cytokines in rats with neuropathic pain-induced depression, and to explore the relationship between hippocampal levels of pro-inflammatory cytokines and severity of depression.Methods Twenty-eight adult male rats were randomly divided into two groups: group sham (n=14) and spared nerve injury (group SNI) (n=14).Mechanical withdrawal thresholds (MWT) were measured 1 day before and 7, 14 and 21 days after operation.Sucrose preference test and forced swim test were tested 1-3 days before and 21-23 days after operation.After test, hippocampus was collected.The hippocampal levels of interleukin (IL)-1β, IL-6 and tumor necrosis factor-α (TNF-α) were measured by ELISA.Correlational relationships between hippocampal levels of pro-inflammatory cytokines and sucrose preference were evaluated.Results Compared with group sham, MWT was decreased 7, 14, 21 days after operation (P<0.001).Group SNI displayed decreased sucrose preference 21 days after operation (P<0.01) and increased immobility time in FST 23 days after operation (P<0.05).The levels of IL-6 and TNF-α were increased in hippocampus (P<0.05 or P<0.01).No significant difference was observed in IL-1β.The hippocampal levels of IL-1β (r2=0.60,P<0.01), IL-6 (r2=0.55,P<0.01) and TNF-α(r2=0.60,P<0.01) were negatively correlated with sucrose preference.Conclusion The hippocampal levels of pro-inflammatory cytokines IL-6 and TNF-α are increased in rats with depression induced by neuropathic pain, and the levels of hippocampal pro-inflammatory cytokines are negatively correlated with the severity of depression.

During the Peace Friendship-2015and Harmony Misson-2015, the medical personnel aboard the hospital ship performed extensive medical exchanges , medical service shows ,and skill training many times and visited some local medical institutions .The exchanges involved war wound , seawater-immersion wound, drill wound, common disease, infectious disease .This paper gave an account of characteristics of and specific methods used in oversea medical exchanges . The experience from these visits and afterthoughts were presented in order to contribute to medical exchanges of this kind in the future.

On Sept 7, 2015, Chinese hospital ship Ark Peace left its home-port in Zhoushan, Zhejiang Province, forHarmony Mission-2015, the fifth in a series of annual international humanitarian and free medical assistance endeavors by the PLA Navy.This mission lasted 142 days, involving a visit to Malaysia and participation in Peace Friendship-2015 exercise,before she was dispatched to seven countries (regions) including Australia, Polynesia, USA, Mexico, Barbados, Grenada, Peru and provided a wide range of medical , humanitarian assistance to the last four countries .A total of 12 589 patients were treated on the main platform , 4852 patients by the 29 fore-lying medical corps , 59 surgeries performed , 46 patients hospitalized ,and 7130 CT and DR et al auxiliary examinations conducted during four mission stops .We organized academic exchanges , visits and interviews , get-togethers , dynamic and static exhibitions in each country .The experience from Harmony mission-2015is of great significance for such tasks in the future .

Objective To prepare nifedipine( NF)sustained-release pellet tablets,and study of its release behavior in vitro. Methods Soluplus was selected as a carrier to prepare solid dispersion of NF by hot melt extrusion technique( HME), and the ratio of the drug to carrier was 1:1. The samples were validated as the solid dispersion by differential scanning calorimetry(DSC). Extrusion-spheronization technique was introduced to prepare NF pellets and EudragitRS 30D was used as the coating material. The NF sustained-release tablets were prepared by direct compression of the coated pellets and suitable excipients. Results The release data in vitro proved that the drug release from the tablets was steady and complete over 24 hours. Conclusion The release of NF from sustained-release tablets is slow and steady. The method is easy to operate. The in vitro drug release pattern follows first-order kinetics.

ObjectiveTo study the role of L-arginine/nitric oxide (NO) pathway in the antidepressant effects of ketamine.MethodsForty two male Wistar rats (200-250 g) were equally randomized into 7 groups ( n =6 ):control group ( C group ),L-Arginine ( a precursor of NO ) group ( LA group),L-NAME ( an non-selectivity inhibitor of NO synthase) group ( LN group),ketamine 3 mg/kg group ( K3 group),ketamine 10 mg/kg group (K10 group),L-Arginine + ketamine 10 mg/kg group(LAK10 group),L-NAME + ketamine 3 mg/kg group (LNK3 group).The forced swimming test (FST) of 15 min (pre-test session) was used to establish a rat depression model,then twenty-four hours later FST (test session) was carried out of 6 min and the immobility time in last 5 min was recorded. All the groups were pretreated with saline 1.0 ml,L-arginine 750 mg/kg or L-NAME 30 mg/kg 90 min before FST.Saline 1.0 ml,ketamine 3.0 mg/kg or ketamine 10.0 mg/kg were injected 60 min before FST.The content of hippocampal NO was detected immediately after ethology measurement.ResultsCompared with C group (immobility time:( 139.0 ± 27.6)s),the immobility time decreased significantly (( 85.5 ± 34.2),(91.3 ±31.6)s) in K10 group and LNK3 group (P＜0.05),K3 group,LA group,LAK10 group and LN group had no significant difference (P＞0.05) ;compared with C group ( (0.61 ±0.21 ) μmol/gProt),the content of NO increased in LA group ( ( 1.09 ±0.39) μmol/gProt) and decreased in K10 group and LNK3 group significantly( (0.28 ± 0.12),(0.31 ± 0.14 ) μmol/gProt) (P ＜ 0.05 ),K3 group,LAK10 group and LN group had no significant difference (P ＞ 0.05).ConclusionThe antidepressant effects of ketamine are related to the suppression of L-arginine/nitric oxide pathway.

Objective To investigate the effects of different doses of ketamine on brain-derived neurotrophic factor (BDNF) and tyrosine receptor Idnase B (TrkB) in the hippocampus in mentally depressed rats.Methods Fifty male Wistar rats weighing 180-220 g were randomly divided into 5 groups ( n = 10 each): group control (group C) and groups K1-4 ketamine 2.5, 5.0, 10.0 and 20.0 mg/kg. On the 1st day the animals were forced to swim for 15 min. On the 2nd day ketamine 2.5, 5.0, 10.0 and 20.0 mg/kg were given iniraperitoneally in groups K1-4 respectively at 30 min after administration. The immobility time of the rats during the forced swimming test was recorded. The animals were then decapitated. The hippocampus was harvested for determination of BDNF and TrkB levels. Results Ketamine significantly decreased the immobility time during forced swimming test in a dose-dependent manner. The BDNF and TrkB levels in the hippocampus were significantly increased in K, and K4 groups as compared with group C, and K1 and K2 groups. Conclusion The increased levels of BDNF and TrkB in the hippocampus are involved in the dose-dependent antidepressant effect of ketamine.

Objective:To investigate the clinical and experimental effect of Zhao's Weitiao Ⅲ decoction on colorectal cancer.Methods:Clinical study:After oral administration of Zhao's Weitiao Ⅲ decoction,main symptoms,quality of life,clinical curative effect and survival rate of the patients were observed.Experimental study:Zhao's Weitiao Ⅲ decoction was observed by the antitumor effect on transplanted sarcoma,the influence on cytokine of experimental animal and the inhibition and apoptosis of HT-29 and LOVO cells.Results:Clinical study:Zhao's Weitiao Ⅲdecoction could improve patients’ main symptoms(the total effective rate was 89.52%),improve patients’ quality of life(P