AIM: To investigate the role of nitric oxide synthase (NOS), soluble guanylyl cyclase (sGC) and protein kinase C (PKC) signaling in tumor necrosis factor-? (TNF-?)-induced cardioprotection against hypoxia/reoxygenation (H/R) injury. METHODS: Neonatal rat ventricular myocytes were pretreated with TNF-? or sodium nitroprusside (SNP) or L-arginine (L-Arg), respectively, for 12 h and then subjected to continuous hypoxia for 12 h, followed by reoxygenation for 6 h. The manganese superoxide dismutase (Mn-SOD) activity of the cells was measured after H/R. Myocyte injury was determined by the release of lactic dehydrogenase (LDH). RESULTS: TNF-? (10~5 (U/L)) significantly increased the Mn-SOD activity and decreased release of LDH from ventricular myocytes. The cardioprotection against H/R injury was induced by the pretreatment with SNP (5 ?mol/L) or L-Arg (5 mmol/L), which was blocked by ODQ (10 ?mol/L), the specific sGC inhibitor, and Chel (5 ?mol/L), the specific PKC inhibitor. Pretreatment with L-NAME (100 ?mol/L), ODQ, Chel, antoxidant 2-MPG (400 ?mol/L) or tyrosine kinase inhibitor genistein (50 ?mol/L) attenuated the increased Mn-SOD activity and reduced LDH level induced by TNF-?. CONCLUSION: The results suggest that NO may play a role in TNF-?-induced cardioprotection, which is mediated by sGC and PKC. [

An RP-HPLC method for the simultaneous determination of and Amlodipine (AL)Ramipril (RP) in tablets was developed and validated by Chinese Pharmacopoeia 2010. The linearity of the proposed method was investigated in the range of 0.01-0.25 mg/mL (r2 ? 0.9998) for RP and 0.014-0.36 mg/mL (r2 ? 0.9997) for AL. The limits of detection (LOD) were 0.06μg/mL and 0.02μg/mL for RP and AL, and the limits of quantitation (LOQ) were 0.2μg/mL and 0.07μg/mL, respectively. Some major impurities and degradation products did not disturb the detection of RP and AL and the assay can thus be considered stability-indicating.

BACKGROUND: Rejection is the main cause of the failure in small bowel transplant. Chemotatic factor RANTES and receptor mediated cellular immunity are very important in acute rejection.OBJECTIVE: To explore the immunosuppressive effect of early adopting chemokine receptor antagonist, Met-RANTES after small bowel transplant on acute allograft rejection and its coordinative effect with Tacrolimus (FK506).DESIGN: Randomized complete-block design, controlled animal experiment.SETTING: Department of General Surgery, the 451 Hospital of Chinese PLA; Laboratory of Department of Gastrointestinal Surgery, Xijing Hospital, Fourth Military Medical University of Chinese PLA; Electronic Microscope Center, School of Basic Medicine, Fourth Military Medical University of Chinese PLA.MATERIALS: This study was carried out in the Laboratory of Department of Gastrointestinal Surgery, Xijing Hospital,Fourth Military Medical University of Chinese PLA from September 2003 to March 2005. Totally 192 animals including 96 SD rats (donors) and 96 Wistar rats (recipients) were involved in this study. Heterotopic segmental small bowel transplantation was performed.METHODS: The transplant rats were divided into 4 groups averagely by the randomized complete block design: control group (allogeneic small bowel transplant untreated group), Met-RANTES group(200 μg/d, 0-7 days, i.p.), FK506 group [0.5 mg/(kg·d) ,0-7 days,i.p.], Met-RANTES + FK506 group [Met-RANTES, 200 μg/d,0-7 days,i.p.+ FK506 0.5 mg/(kg ·d),0-7 days, i.p.]. Rats in the latter 3 groups were intraperitoneally administrated after transplant within 7 days successively.Rats in the control group were not given any treatments before and after transplant. Postoperatively, gross status,survival time and immunocyte infiltration were observed. Pathological examination was conducted in 6 rats of each group on postoperative days 3, 5 and 7. Fluorescent staining and successive quantitative measurement were conducted to detect the expressions of intragraft RANTES, CD4+, CD8+ and CD25+ T lymphocyte. Survival duration of the rest 6 rats of each group was observed for 5 weeks.MAIN OUTCOME MEASURES: ① Survival time of rats in each group following transplant. ② Pathological changes of small bowel intragraft of rats in each group. ③ RANTES and T lymphocyte expressions of rats in each group.RESULTS: Following transplantation, 96 Wistar rats (recipient) were all involved in the final analysis. ①Compared with control group, the survival time of rats in Met-RANTES group, FK506 group, Met-RANTES + FK506 group was significantly longer (P ＜ 0.01). In addition, rats in Met-RANTES + FK506 group survived the longest. There were significant differences in survival rate as compared with Met-RANTES group and FK506 group (P ＜ 0.01). ②All rats in the control group died of acute rejection and infection. Histopathologic examination showed mild, moderate and severe rejection on the postoperative days 3,5 and 7, respectively. No obvious rejection was found in the rats in the Met-RANTES group, FK56 group and Met-RANTES+FK506 group on the postoperative days 3,5 and 7. ③Postoperatively, intragraft RANTES expression of rats was significantly higher in each time period in control group than in the other 3 groups (P ＜ 0.01), and its dynamic change was positively correlated with the process of acute rejection; The expression of intragraft RANTES, CD4+, CD8+ and CD25+ T lymphocytes of rats was significantly lower, respectively, in the Met-RANTES group and Met-RANTES+FK56 group than in the control group (P ＜ 0.01).CONCLUSION: Met-RANTES may obviously suppress acute allograft rejection in small bowel transplant, effectively protect the function of grafts, and significantly prolong the survival time of the recipients. In addition, Met-RANTES may enhance the immunosuppressive function of small dose of FK506[0.5 mg/(kg · d)].

Objective To investigate the homology of methicillin-resistant Stphylococcusaureus(MRSA)from the neonatal intensive care unit(NICU)of a children's hospital,and evaluate routes and preventive strategies of MRSA healthcare-associated infection(HAI). Methods MRSA strains from neonates and environment of NICU between October and December 2014 were collected,and strains were identified by VITEK-2 microbial analysis system and cefoxitin Kirby-Bauer method,homology of MRSA was analyzed by pulsed-field gel electrophoresis (PFGE ). Results A total of 6 MRSA strains were isolated from NICU between October and December 2014,3 of which (bed-58,70,and 100)were detected MRSA from specimens,MRSA were isolated from neonatal incubator and nurse (nasal swabs and hands)who cared for neonate at bed 58. 5 of 6 MRSA strains were homology,antimicrobial susceptibility testing result showed that No. 1-5 strains were resistant to clindamycin and amoxicillin/clavulanic acid,No. 6 strain was slightly different from No. 1-5 strains,No. 6 strain was susceptible to both clindamycin and amoxicillin/clavulanic acid. PFGE results showed that No. 1-5 strains were of the same type,No. 6 strain was a different type. Conclusion The main route of this MRSA transmission is contact transmission,especially through the hands of health care workers,identification and analysis of epidemic strains by PFGE technique is an effective measures to prevent HAI outbreak and perform epidemiological study.

BACKGROUND: AIIograft rejection is the greatest obstacle that influences graft function and survival, and the diagnosis and treatment of small intestine transplantation rejection are particularly difficult.OBJECTIVE: To explore the significance of chemokine receptor antagonist, Met-RANTES, in small intestine transplantation rejection, and the effects of tacrolimus (FK506) on RANTES expression.DESIGN, TIME AND SETTING: Randomized, controlled animal experiment was performed at the Department of General Surgery, the 451 Hospital of Chinese PLA; Laboratory of Department of Gastrointestinal Surgery, Xijing Hospital, Fourth Military Medical University of Chinese PLA; and Electronic Microscope Center, School of Basic Medicine, Fourth Military Medical University of Chinese PLA between September 2003 and March 2005.MATERIALS: A total of 72 healthy adult male SD rats (donor) and 72 healthy adult male Wistar rats (recipient) were included for heterotopic small intestine transplantation.METHODS: Heterotopic small intestine transplantation was performed. All recipients were divided into four groups (n=18): intact control group: Wistar rats as controls with no surgery; isotransplantation group: Wistar--,Wistar; allotransplantation untreated group: SD→Wistar, with no immunosuppressive agent; allograft allotransplantation and FK-506 group: SD→Wistar + FK-506 (1 mg/kg per day, i.m. for 7 days). The grafts were sampled on postoperative days 3, 5 and 7 and were examined pathologically. Successive quantitative measurement was conducted to detect the expression of graft RANTES with immunofluorescence staining and laser scanning confocal microscope technique.MAIN OUTCOME MEASURES: The pathological changes of grafts in each group; RANTES expressions in small intestine grafts of rats in each group at different time points; inhibition of FK-506 on RANTE expression.RESULTS: Postoperatively, 72 Wistar rats (recipient) were involved in the final analysis. The pathological changes of the allotransplantation untreated group rats were consistent with the criteria of mild, moderate and severe rejection on postoperative days 3, 5 and 7, respectively. No obvious rejection was found in the rats of FK506 group and isotransplantation group on the postoperative days 3, 5 and 7. Expression of intragraft RANTES of allotransplantation untreated group rats was significantly greater than the other three groups (P<0.01). The dynamic change and the process of acute rejection showed positive correlation. Expression of intragraft RANTES in FK-506 treated group was significantly less than other three groups without FK-506 (P<0.01).CONCLUSION: RANTES positive cells play an important role in small intestine allograft rejection. Dynamic observation on expression of intragraft RANTES may act as a predicator for diagnosing acute allograft rejection.

The five volumes of Annals of National Medicine in Yunnan contain more than 1040 kinds of ethnic medicines and national medicines experiene that are commonly used by 25 minority nationalities in Yunnan.Among them,there are 147 species of toxic drugs,including five with fatal toxicity,14 with strong toxicity,57 with toxicity,and 71 with mild toxicity.In order to guarantee the validity and safety of national drug use,Yunnan Institute of Materia Medica applied modern science and technology to study the safety,efficacy and pharmacognosy of 30 kinds of commonly used toxic folk drugs contained in Annals of National Medicine in Yunnan.This paper chooses five typical national medicinal herbs Stephania delavayi,Euphorbia neriifolia,Alocasia cucullata,Achillea wilsoniana and Chamaenerion angustifolium,and summarizes their national medicinal and toxicity experience.The results of acute toxicity test showed that the five national medicinal herbs are toxic.The pharmacodynamic experiments showed that S.delavayi has analgesic action,E.neriifolia has anti-inflammatory action,A.cucullata has analgesic and antitussive effects,Ach.wilsoniana has analgesic effect,and C.angustifolium has analgesic and anti-inflammatory effects.

Objective To observe the effect of Shenmai injection on hemodynamics and serum inflammatory factors in patients with septic shock. Methods One hundred and fifty patients with septic shock admitted to Tianjin Fourth Center Hospital from August 2015 to March 2017 were enrolled and they were divided into a western medicine routine treatment group and an integrated traditional Chinese and western medicine treatment group according to the random number table method, 75 patients in each group. Both groups were given symptomatic treatment of basic western medicine, and the integrated traditional Chinese and western medicine treatment group was additionally given intravenous infusion (IV) of 30 mL Shenmai injection on the basis of conventional treatment, both groups were treated for consecutive 14 days. The changes in hemodynamic parameters, serum inflammatory factors: tumor necrosis factor-α (TNF-α) and interleukin (IL-6, IL-1β) were observed before and after treatment in the two groups, and the clinical efficacies of the two groups were evaluated 14 days after treatment. Results After treatment in both groups, hemodynamic indexes were improved, heart rate (HR) was decreased, and mean arterial pressure (MAP), central venous pressure (CVP), cardiac output index (CI) and peripheral vascular resistance index (SVRI) were increased; after 14 days of treatment, HR in the integrated traditional Chinese and western medicine treatment group was significantly lower than that in the western medicine routine treatment group (bpm: 101.8±3.1 vs. 104.9±9.3), while MAP [mmHg (1 mmHg = 0.133 kPa): 71.2±4.3 vs. 67.3±3.5], CI (mL·s-1·m-2: 3.6±0.4 vs. 3.4±0.6) and SVRI (kPa·s·L-1·m-2:190.37±24.91 vs. 180.23±20.13) were significantly higher than those in the western medicine routine treatment group (all P < 0.05). TNF-α, IL-6 and IL-1β were decreased in both groups after treatment; after 14 days of treatment, the above indexes in the integrated traditional Chinese and western medicine treatment group were significantly lower than those in the western medicine routine treatment group [TNF-α (ng/L): 226.3±42.8 vs. 273.7±29.4, IL-6 (ng/L):223.7±31.2 vs. 259.3±51.3, and IL-1β (ng/L): 95.1±20.7 vs. 132.4±47.5]. The total clinical effective rate in the integrated traditional Chinese and western medicine treatment group was significantly higher than that in the western medicine routine treatment group [93.3% (70/75) vs. 54.7% (41/75), P < 0.05]. Conclusion Shenmai injection can improve hemodynamics and regulate inflammatory factors; the therapeutic effect for treatment of septic shock is significant.

AIM:MicroRNAs ( miRNAs) were recognized to play significant roles in cardiac hypertrophy .But, it remains unknown whether cyclin/Rb pathway is modulated by miRNAs during cardiac hypertrophy .This study investigates the potential roles of microRNA-1 (miR-1) and microRNA-16 (miR-16) in modulating cyclin/Rb pathway during cardiomyocyte hypertrophy .METHODS:An animal model of hypertrophy was established in a rat with abdominal aortic constriction (AAC).In addition, a cell model of hypertrophy was also achieved based on PE-promoted neonatal rat ventricular cardiomyocyte .RESULTS:miR-1 and-16 expression were markedly de-creased in hypertrophic myocardium and hypertrophic cardiomyocytes in rats .Overexpression of miR-1 and -16 suppressed rat cardiac hypertrophy and hypertrophic phenotype of cultured cardiomyocytes .Expression of cyclins D1, D2 and E1, CDK6 and phosphorylated pRb was increased in hypertrophic myocardium and hypertrophic cardiomyocytes , but could be reversed by enforced expression of miR-1 and -16.CDK6 was validated to be modulated post-transcriptionally by miR-1, and cyclins D1, D2 and E1 were further validated to be modulated post-transcriptionally by miR-16.CONCLUSION: Attenuations of miR-1 and -16 provoke cardiomyocyte hypertrophy via derepressing the cyclins D1, D2, E1 and CDK6, and activating cyclin/Rb pathway.

AIM:To investigate the effect of miR-214 on cardiomyocyte hypertrophy and the expression of the potential target genes . METHODS:A cell model of hypertrophy was established based on angiotensin-Ⅱ( Ang-Ⅱ)-induced neonatal mouse ventricular car-diomyocytes (NMVCs).Dual luciferase reporter assay was performed to verify the interaction between miR-214 and the 3’ UTR of MEF2C.The expression of MEF2C and hypertrophy-related genes at mRNA and protein levels was determined by RT-qPCR and Wes-tern blotting, respectively.RESULTS:The expression of ANP, ACTA1,β-MHC and miR-214 was markedly increased in Ang-Ⅱ-in-duced hypertrophic cardiomyocytes .Dual luciferase reporter assay revealed that miR-214 interacted with the 3’ UTR of MEF2C, and miR-214 was verified to inhibit MEF2C expression at the transcriptional level .The protein expression of MEF2C was markedly in-creased in the hypertrophic cardiomyocytes .Moreover, miR-214 mimic, in parallel to MEF2C siRNA, inhibited the expression of hy-pertrophy-related genes in Ang-Ⅱ-induced NMVCs.CONCLUSION:MEF2C is a target gene of miR-214, which mediates the effect of miR-214 on attenuating cardiomyocyte hypertrophy .

OBJECTIVE:To explore the similarity of dissolution profiles of self-development and original preparation of Solife-nacin succinate tablet,and provide reference for the prescription and process screening of the former one and the quality similarity evaluation of the latter one. METHODS:The paddle method was adopted with rotational speed of 50 r/min,using water,pH1.2 hy-drochloric acid solution,pH4.0 acetate buffer solution and pH6.8 phosphate buffer solution as dissolution media,HPLC was used to determine the cumulative dissolution of main components of self-development and original preparation of Solifenacin succinate tablet at different time points,dissolution profile was drew,then f2 was used to evaluate its similarity. RESULTS:In the 4 dissolu-tion media,the f2 of both self-development and original preparation of Solifenacin succinate tablet was higher than 50,which indi-cated that the dissolution profiles showed similarity. CONCLUSIONS:The established HPLC is suitable for the dissolution determi-nation of Solifenacin succinate tablet;the dissolution profiles of the self-development and original preparations are basically simi-lar,which indicates the prescription and technology of self-development preparation are feasible.