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ObjectiveTo establish a neuroinflammation-based obesity and depression comorbidity （COM） model in mice and explore the pharmacodynamics and preliminary pharmacological mechanism of tripterine on COM mice. MethodC57BL/6J mice were randomly divided into a normal group （Chow）， a diet-induced obesity group （DIO）， and a COM group. The mice in the COM group were fed on a high-fat diet and chronically stressed with moist litter for 12 weeks to establish the COM model. C57BL/6J mice were randomly divided into a Chow group， a COM group， and a tumor necrosis factor-α（TNF-α） knock-down group. In the TNF-α knock-down group， TNF-α shRNA adeno-associated virus was injected into the amygdala through brain stereotaxis， and the expression of TNF-α in the amygdala was down-regulated. C57BL/6J mice were randomly divided into a Chow group， a DIO group， a DIO + low-dose tripterine group （0.5 mg·kg-1）， a DIO + high-dose tripterine group （1.0 mg·kg-1）， a COM group， a COM + low-dose tripterine group （0.5 mg·kg-1）， and a COM + high-dose tripterine group （1.0 mg·kg-1）. The body weight， food intake， glucose tolerance， white/brown fat ratio， serum total cholesterol （TC）， triglyceride （TG）， and high-/low-density lipoprotein cholesterol （HDL-C and LDL-C） content were recorded， and obesity of mice in each group was evaluated. Forced swimming test （FST）， tail suspension test （TST）， and open field test were used to evaluate the degree of depression of mice in each group. Immunofluorescence staining was used to detect the protein expression levels of neuropeptide Y， tryptophan hydroxylase 2 （TPH2）， and brain-derived neurotrophic factor （BDNF） in various brain nuclei of mice. Correlation analysis was used to detect the correlation of obesity and depression indexes. ResultThe comparison of the Chow group and the DIO group indicated that COM mice showed obesity and depression. To be specific， obesity was manifested as increased body weight and food intake （P<0.05， P<0.01）， as well as increased NPY expression in the central amygdala， and depression was manifested as prolonged immobility time in FST and TST （P<0.01）， and reduced TPH2-positive 5-hydroxytryptamine neurons in the dorsal raphe nucleus （DRN） and basolateral nucleus of the amygdala （BLA）. The down-regulation of TNF-α protein in BLA of COM mice shortened the immobility time in FST and TST （P<0.05， P<0.01）， increased TPH2/BDNF-positive neurons in BLA， and showed no significant changes in obesity. In DIO mice， the administration of 0.5 mg·kg-1 tripterine for 9 days significantly decreased the 60 min blood glucose in glucose tolerance （P<0.01） and food intake （P<0.05）. In COM mice， 1.0 mg·kg-1 tripterine was administered for 14 days to significantly decrease 30 min blood glucose in glucose tolerance （P<0.01）， and food intake （P<0.05）， and immobility time in TST （P<0.01）， increase TPH2-BDNF double-labeled cells in BLA and DRN， and reduce the area of TMEM119-stained cells. ConclusionThe model of obesity and depression comorbidity can be properly induced in mice under the condition of dual stress of energy environment. Tripterine can effectively interfere with obesity-depression comorbidity， and its mechanism may be related to the inhibition of central nervous system inflammation.
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OBJECTIVE：To prepare GGPFV-modified Daunorubicin/dioscin liposomes ，and to optimize their formulation and to preliminarily evaluate their cytotoxicity to breast cancer cells in vitro . METHODS ：Daunorubicin and diosgenin were wrapped by thin film dispersion method and ammonium sulfate hydration method ；the surface was modified with DSPE-PEG2000-GGPFV to prepare GGPFV-modified Daunorubicin/dioscin liposomes. Taking encapsulation rate as index ，Box-Behnken response surface methodology was used to optimize the film hydration volume ，cholesterol amount and daunorubicin amount in the formulation. The entrapment efficiency of 3 batches of liposomes prepared according to the optimal formulation was determined. The effects of Daunorubicin/dioscin liposomes ，GGPFV-modified Daunorubicin/dioscin liposomes and blank liposomes on the survival rate of human breast cancer MDA-MB- 435S cells were compared. RESULTS ：The optimal formulation was as film hydration volume of 5 mL，cholesterol of 4 mg，yolk lecithin of 22 mg，daunorubicin of 0.55 mg，dioscin of 0.85 mg，DSPE-PEG2000 of 3.5 mg， DSPE-PEG2000-GGPFV of 2 mg. The encapsulation rate of daunorubicin was （96.21±1.54）％ and that of dioscin was （95.39± 2.48）％ in the 3 batches of liposomes prepared. The in vitro cytotoxicity tests showed that the inhibition effect of GGPFV-modified Daunorubicin/dioscin liposome on MDA-MB-435S cells was significantly stronger than that of Daunorubicin/dioscin liposome （P＜ 0.05）. There was no cytotoxicity in the membrane. CONCLUSIONS ：GGPFV-modified Daunorubicin/dioscin liposomes are successfully prepared ，and its inhibitory effect on human breast cancer MDA-MB- 435S cells in vitro was significantly enhanced.
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ObjectiveTo analyze Rome Ⅱ and Rome Ⅲ criteria in clinical characteristics of functional dyspepsia (FD) diagnosis and the differences in subtypes of FD,and to assess the psychosocial status of FD patients.Methods From June 2008 to December 2008,1600 random outpatients who underwent upper gastrointestinal endoscopy in department of gastroenterology fulfilled the inquiry questionnaire.The subtype was diagnosed according to Rome Ⅲ and the Rome Ⅱ criteria and the results were analyzed.ResultsA total of 215 patients (13.44％) were in accordance with Rome Ⅱ criteria and 249 patients (15.56 ％) were in accordance with Rome Ⅲ criteria,there was no difference in FD detection rate between these two criteria (x2=2.176,P＞0.05).About 71.16％(153/215) of the FD patients diagnosed according to Rome Ⅱ criteria were also in accordance with Rome Ⅲ criteria,and 23.26％ (50/215) who had bothersome postprandial fullness,early satiation,epigastic pain or epigastric burning did not meet Rome Ⅲ criteria.About 61.45 ％ (153/249) of the FD patients diagnosed according to Rome Ⅲ criteria were also in accordance with Rome Ⅱ criteria,and the courses of disease of 28.92％(72/249) patients didn't met Rome Ⅱ criteria.According to RomeⅡ,51 (23.72％) patients were ulcer-like type,103 (47.91％)patients were dysmotility-like type,and 61 (28.37％) patients were non-idiotype.According to Rome Ⅲ criteria,76.31％ (190/249) patients were consistent with postprandial distress syndrome (PDS),52.61％ (131/249) patients were consistent with epigastric pain syndrome (EPS),and 28.92％ (72/249) patients met both PDS and EPS.The percentage of the FD patients with anxiety and depression was 16.83％ and 47.52％respectively.Of the FD patients in accordance with Rome Ⅲ criteria who were with both anxiety and depression,the total symptom scores of bothersome postprandial fullness,early satiation,epigastic pain or epigastic burning were the highest (x2 =49.637,P＜0.05).ConclusionsRome Ⅲ criteria is easier to understand and more practical.FD patients always have psychosocial disorders,which may worsen the clinical symptoms.