Animals ; Cardiovascular System ; chemistry ; Female ; Group II Phospholipases A2 ; blood ; Group IV Phospholipases A2 ; blood ; Group V Phospholipases A2 ; blood ; Group X Phospholipases A2 ; blood ; Male ; RNA, Messenger ; genetics ; Rats ; Rats, Wistar

Objective To study whether suprachiasmatic nucleus (SCN) slices are able to induce the molecular oscillations in NIH/3T3 fibroblast. Methods SCN slices from 10-day-old SD rat and NIH/3T3 cells were co-cultured in a serum-free condition. 24h mRNA profiles of Per1 and Rev-Erbα were measured in NIH/3T3 cells using real-time PCR. Results After co-cultured for 6 days, ten SCN slices can induce the significant daily oscillation of Per1 and Rev-Erba mRNA expression in NIH/3T3 cells (P<0.01). The peak time Rev-erbα and Per1 were at CT5 and CT11 respectively. Rev-Erbα oscillations were significant even with two SCN slices and 2 days co-culture (P<0.05). In contrast, Per1 expression fluctuation was not observed until more than 6 days of co-culture and with six SCN slices (P=0.031). Conclusion Diffusible signals release from SCN slices can regulate molecular rhythms in cultured fibroblasts. Rev-Erbα and Per1 don't start to oscillate at the same time, and Rev-Erbα is more sensitive to SCN signal.

Objective To evaluate the efficacy and prognostic factors of combined medical thera-py with amitriptyline, cimetidine and intravesical resiniferatoxin post-hydrodistention for patients with painful bladder syndrome/interstitial cystitis (PBS/IC). Methods Twenty-nine patients with PBS/ IC according to NIDDK criteria were enrolled. There were 6 males and 23 females with average age of 52±14 years and average duration of symptoms of 3.7±1.9 years before diagnosis. The patients were divided into 2 groups. Non-concomitant disease group included 10 cases without concomitant disease and 7 cases with unrelated diseases such as hypertension and diabetes mellitus. Concomitant disease group included 5 cases with history of bladder neck incision, 3 cases with history of transurethral re-section of the prostate, 2 cases with history of gynecologic disease and 2 cases with history of gyneco-logic operation. Patients of concomitant disease group still had the painful bladder syndrome after 3 months when the primary disease had been cured. All patients were treated with amitriptyline (25 mg twice a day), cimetidine (800 mg per day) and intravesical resiniferatoxin (1-2 times) post-hydrodis-tention. The primary assessment index was O'Leary-Sant score. The secondary assessment index was pelvic pain score, mean voiding times per day and mean volume of each micturating. The data of pa-tients before treatment and after follow-up≥9 months were collected to evaluate the efficacy and prog-nostic factors of the combined treatment. Results The mean follow-up for all patients was 9.2±6.0 months. Patients were followed up at month 1 and month 6 after discharge. Then, patients would be followed up at each 6 months interval. The overall remission rate was 65.5% (19/29). Complete re-mission rate was 41.4% (12/29). Partial remission was 24. 1% (7/29). Non-remission rate was 34.5% (10/29). For all patients, the pre-treatment mean voiding times per day were 29±15, voiding volume each time was 64±36 ml, average O'Leary Sant score was 23. 8±4.8, and they were signifi-cantly improved post-treatment (17±12 times, 172±108 ml, 13. 3±10.4, respectively, P<0.001). O' Leary-Sant score of concomitant disease group was lower than that of non-concomitant disease group (21.5±4.7 vs 25.4±4.3, P=0.030). However, complete remission (8.3%, 1/12) of con-comitant disease group was lower than that(64. 7%, 11/17) of non-concomitant disease group (P= 0. 003). In independent variables of patients age, sex, duration of symptom, O'Leary Sant score pre-treatment, and whether or not with concomitant disease, according to the results of Logistic Regres-sion, patients with concomitant disease would have poor prognosis (P-0.008, partial regression coef-ficient was -3. 899, OR was 0. 020). Conclusions Treating PBS/IC patients with amitriptyline, ci-metidine and intravesical resiniferatoxin post-hydrodistention is effective. However, concomitant dis-eases such as gynecologic disease or urethra operation history can impair the effectiveness of these treatment.

Apoptosis ; drug effects ; Cell Line, Tumor ; Drugs, Chinese Herbal ; pharmacology ; Humans ; Polysaccharides ; pharmacology

Objective To evaluate three different tracer-kinetic models used for dynamic contrast-enhanced MRI (DCE-MRI) data processing in the prediction of the histopathologic grade of cerebral gliomas.Methods Forty-one patients with histopathologically graded gliomas (grade Ⅱ 13,grade Ⅲ 14,grade Ⅳ 14)were imaged with DCE-MRI from March,2013 to November,2014.The values of Ktrans of gliomas were obtained by three tracer-kinetic models,which were Patlak model,Tofts model and Extended Tofts Linear model.All data were analyzed statistically by a Graphpad 6.0 statistical software.Comparison of the differences of Ktrans among different grades of gliomas was conducted using the Kruskal-Wallis test and Dunn's multiple comparisons test for the data not conform to normal distribution.Correlations of Ktrans values among those three models were analyzed using linear regression analysis,The differences of Ktrans between low grades and high grades of gliomas was conducted using the Mann-Whitney U test.Receiver operating characteristic (ROC) curve analyses were performed to determine the cut-off values for Ktrans to distinguish different low grades and high grades of gliomas.Results The Ktrans values obtained by Patlak model was 0.008(0.004-0.043) min-1for grade Ⅱ,0.021(0.005-0.088) min-1 for grade Ⅲ,and 0.035(0.017-0.061) min-1 for grade Ⅳ.The Ktrans values obtained by Tofts model was 0.085 (0.041-0.158)min 1for grade Ⅱ,0.140 (0.063-0.315) min-1for grade Ⅲ,0.229 (0.126-0.419)min 1 for grade Ⅳ.The Ktrans values obtained by Extended Tofts Linear model was 0.012 (0.004-0.092) min 1 for grade Ⅱ,0.048 (0.010-0.188) min-t for grade Ⅲ,0.094 (0.036-0.215)min 1 for grade Ⅳ.All the Ktrans values obtained by three models increased when the histological grades increased,with statistical significance between grade Ⅱ and Ⅲ (H=18.31,18.09,20.18,P＜0.05).Ktrans values among the three models had good linear correlations.The Ktrans obtained by Extended Tofts Linear model had good linear correlations with both Patlak model and Tofts model (r=0.933,0.893,P＜0.05),and the Ktrans obtained by Patlak model had less linear correlation with Tofts model (r=0.822,P＜0.05).The K values were statistically different between LGG and HGG (P＜0.01).The cut-off value of K provided good combination of sensitivity and specificity in the differentiation between LGG and HGG,and the K obtained by Extended Tofts Linear model had the best sensitivity and specificity among the three models (sensitivity 92.3％,specificity 85.7％).Conclusions K from DCE-MRI has a high performance in predicting the histopathologic grade of brain glioma,and the Extended Tofts Linear model is more suitable for the evaluation of cerebral glioma.

Objective To evaluate the efficiency and safety of esophageal stents combined with radiotherapy compared with esophageal stents alone in the treatment of advanced esophageal cancer.Methods CBM,VIP,CNKI,Cochrane Library,Pubmed and Embase etc were searched by computer begining from the establishment of these datebases to December 2012.The related references as well as communicated with other researchers were also traced to obtain certain informations.Randomized and quasi-randomized controlled trials compared esophageal stents plus radiotherapy with esophageal stents alone in the treatment of advanced esophageal cancer were included.The statistical software RevMan 5.0 was used.Results Seven published articals were included (443 patients),and all trails methodological quality were grade C.The results of Metaanalysis showed that compared with esophageal stents along,esophageal stents combined with radiotherapy improve 1-year survival rates and reduce the local recurrence rates.Gastrointestinal bleeding rates,chest pain rates,gastro-esophageal reflux rates remained similarily.Conclusion Compared with esophageal stents along,esophageal stents combined with radiotherapy can improve 1-year survival rates and reduce the local recurrence rates.

Objective To study the effect of the petroleum ether fraction of ethanol extracts of Polyrhachisvicina Roger with antigout activity on liver microsomal cytochrome P450 in rats.Methods Healthy male SD rats were randomly divided into six groups (3 rats of each group):three groups of the petroleum ether fraction of ethanol extracts of Polyrhachisvi-cina Roger ( test groups, the low dose group, the middle dose group and the high dose group with equivalent to 1, 2, 4 g? kg -1, respectively), two positive control groups and one blank control group.The rats in the low dose, the middle dose and the high dose test groups were adminis-tered daily by gavage at corresponding dose of the petroleum ether frac-tion of ethanol extracts of Polyrhachisvicina Roger for 10 consecutive days.The rats in positive control groups were treated by dexamethasone ( 100 mg? kg-1? d-1 , ip, daily for 4 days ) or phenobarbital ( 80 mg? kg-1? d-1 , ip, daily for 3 days ) .Blank control rats received equivalent volume of sterile normal saline daily by gavage for 10 consecu-tive days.The levels of CYP450 activity, mRNA, protein in rat liver mi-crosome were analyzed by LC/MS/MS or RP-HPLC-FLD, RT-PCR, Western blot, respectively.Results CYP1A2 activity, protein expression and mRNA levels were increased signifi-cantly in a dose-dependent manner with the petroleum ether fraction of ethanol extracts of Polyrhachisvicina Roger at low, middle and high dose, respectively.Conclusion The petroleum ether fraction of ethanol extracts of Polyrhachis-vicina Roger can induce CYP1A2 in rats, suggesting the potential of drug-drug interactions between the petroleum ether fraction of ethanol extracts of Polyrhachisvicina Roger and the inducers, inhibitors, or substrates of CYP1A2.

Objective To explore the expression of P -glycoprotein ( P-gp) in rat liver during acute inflammation ( AI ) and the possible mechanism involved.Methods Twenty rats were randomly divided into two groups:model group (n=10) and control group (n=10).The rats in model group were treated by a single 5 mg? kg -1 intraperitoneal injec-tion of lipopolysaccharide ( LPS).Control rats received equivalent injec-tion of sterile normal saline.The levels of P-gp, ubiquitinated P-gp and 26 S proteasome activity in both groups were analyzed by Western blot, immunoprecipitation and fluorescence detection, respectively. Results Compared to the control groups, ubiquitination levels of liver P-gp and 26S proteasome activity in model groups were significantly in-creased ( P<0.01 ) , accompanied by an decrease of liver P-gp protein expression level. Conclusion The participation of the ubiquitin -proteasome system in down-regulation of liver P-gp expression levels under AI conditions.

OBJECTIVEOver the last few decades, diabetic cardiomyopathy has been identified as a significant contributor in cardiac morbidity. However, the mechanisms of diabetic cardiomyopathy have not been clarified.

METHODSIn the present study, a diabetic rat model was induced by the intraperitoneal injection of streptozotocin. The myocardial CD147 expression and extent of glycosylation, as well as thematrixmetalloproteinases(MMPs) expression and activity, were observed in the diabetic and synchronous rats.

RESULTSThe results showed that CD147 located on sarcolemma of cardiomyocytes. The myocardial CD147 expression and glycosylation were significantly increased in the diabetic rats as compared with the control. Expression of MMP-2 protein, MMP-2 and MMP-9 activity were also increased in left ventricular myocardium in the diabetic rats. Tamoxifen only inhibited the enhanced expression of myocardial CD147 in the diabetic rats, but not in synchronous control rats. Tamoxifen inhibited glycosylation of myocardial CD147 in both diabetic and control rats. The inhibition of tamoxifen on CD147 glycosylation was stronger than on the expression in the myocardium. The extent of myocardial CD147glycosylation was positively related toMMP-2 and MMP-9 activity. Tamoxifen induced an inhibition of myocardial MMP-2 and MMP-9 activity in the control and diabetic rats.

CONCLUSIONThese results indicate that myocardial CD147 expression, especially the extent of glycosylation, regulates MMP-2 and MMP-9 activity, then accelerates cardiac pathological remodeling inducing diabetic cardiomyopathy. Tamoxifen inhibits myocardial CD147 glycosylation and further depress the activity of MMPs. Therefore, tamoxifen may protect the diabetic rats against diabetic myocardium.

Animals ; Basigin ; metabolism ; Diabetes Mellitus, Experimental ; complications ; Diabetic Cardiomyopathies ; drug therapy ; Glycosylation ; Heart ; drug effects ; Matrix Metalloproteinase 2 ; metabolism ; Matrix Metalloproteinase 9 ; metabolism ; Myocardium ; metabolism ; Myocytes, Cardiac ; cytology ; Rats ; Sarcolemma ; metabolism ; Tamoxifen ; pharmacology

OBJECTIVETo explore the in vitro anti-tumor effect and mechanism of dendritic cell (DC) tumor vaccine induced by astragalus polysacharin (APS).

METHODSPeripheral blood mononuclear cells (PBMCs) isolated from human peripheral blood. DCs obtained from human peripheral blood were cultivated and added with culture solution for in vitro inducing them to immature DCs. On the 5th day of culture, 100 microg/mL (as the final concentration) APS was added to cells in the APS group. DCs were induced to mature in the cytokine groups by adding 20 ng/mL rhTNF-alpha (as the final concentration). Changes of morphology and phenotype of DCs were observed. Mature DCs were sensitized with tumor antigen SGC-7901 and co-cultured with allogeneic T cells. The proliferative function of T lymphocytes was detected by MTT assay. Levels of IL-12 and IFN-gamma in co-cultured supernatant were detected by ELISA. Cytotoxic lymphocytes (CTL) activated by DC were co-cultured with tumor cell SGC-7901. The specific killing capacity of CTL to target cells was detected by LDH release assay.

RESULTSThe morphological observation and phenotypic identification of APS induced DCs were in accordance with the characteristics of mature DCs. APS induced mature DCs could stimulate the proliferation of allogeneic T lymphocytes. The proliferation index of T cells increased with increased ratio of stimulator cells to effector cells (P < 0.05). Levels of IL-12 and IFN-gamma in co-culture supernatant significantly increased in a time-dependent manner (P < 0.05). CTL cells activated by sensitization of DCs could significantly kill tumor cells, and the killing effect increased along with increased effector-to-target ratio.

CONCLUSIONAPS could in vitro induce DCs to mature, promote its antigen-presenting capacity, effectively activate CTLs, and enhance anti-tumor function of the organism.

Antigen-Presenting Cells ; cytology ; drug effects ; immunology ; Cancer Vaccines ; immunology ; Cell Line ; Cell Proliferation ; drug effects ; Coculture Techniques ; Dendritic Cells ; cytology ; drug effects ; immunology ; Drugs, Chinese Herbal ; pharmacology ; Humans ; Interferon-gamma ; immunology ; Interleukin-12 ; immunology ; Leukocytes, Mononuclear ; cytology ; immunology ; Lymphocyte Activation ; T-Lymphocytes, Cytotoxic ; cytology ; drug effects