Objective:to study the absorption and absorption characteristics of isomer of propranolol hydrochloride in Caco-2cell monolayers model,which have taken as the most representative model to investigate the absorption mechanism of oral drug in recent years. Methods:Caco-2 cell monolayers model was set up to study transport of isomer of propranolol hydrochloride. RP-HPLC method was applied to analyze isomer of propranolol hydrochloride through precolumn derivatization. Results: Propranolol hydrochloride was absorbed completely,and was a passive diffusion mechanism. There was no chiral selectivity of transport and absorption of them across Caco-2 cell monolayers. Conclusion: Caco-2 cell model was established and the cell integrity was evaluated. The integrity of Caco-2 cell was in good condition,which could be used to study the absorption and transport. RP-HPLC method was established to separated isomer of propranolol hydrochloride within 20 min by precolumn derivatization. The method is convenient, sensitive,accurate and suitable for the analysis of telbivudine.

ObjectiveTo investigate the effect of heme oxygenase-1 (HO-1) on cyclin-dependent kinase 5 (CDK5)-ataxia telangiectasia mutated (ATM)-P53 signal transduction pathway in rat hippocampal neurons subjected to oxygen-glucose deprivation (OGD) injury.MethodsHippocampal neurons of newborn Wistar rats ( ＜ 48 h) were cultured for 7 days in vitro.The primary cultured neurons were randomly divided into 4 groups with 10 wells in each group:control group (group C),OGD (group D),OGD + hemin (HO-1 inducer) group (group D + H ) and OGD + hemin + zinc protoporphyrin ( HO-1 inhibitor) group ( group D + H + T).For OGD experiments,cultures were washed three times in a glucose-free balanced salt solution (BSS).They were then placed in deoxygenated glucose-free medium and sealed under 95％ N2-5％ CO2 in an anaerobic chamber equilibrated to 37°C and 100％ humidity for 45 min.OGD was terminated by replacement of stored medium and by returning the cultures to a standard incubator maintained at 37 ℃ in 95％ air-5％ CO2.The OGD model was established after the neurons were preconditioned with hemin 10 μmol/L for 24 h in group D + H.The OGD model was established after the neurons were preconditioned with hemin 10 μmol/L and zinc protoporphyrin 10 μmol/L for 24 h in group D + H + T.After 24 h of culture,the neuronal viability,apoptosis rate,and expression of HO-1 mRNA and protein,and CDK5,ATM and P53 protein were detected.ResultsCompared with group C,the expression of HO-1 mRNA,and HO-1,CDK5,ATM and P53 protein was up-regulated,the neuronal viability was significantly decreased,and the apoptosis rate was significantly increased in group D (P ＜ 0.01 ).Compared with group D,the expression of HO-1 mRNA and protein was up-regulated,the expression of CDK5,ATM and P53 protein was down-regulated,the neuronal viability was significantly increased,and the apoptosis rate was significanlly decreased in group D + H ( P ＜ 0.01 ).Compared with group D + H,the expression of HO-1 mRNA and protein was down-regulated,the expression of CDK5,ATM and P53 protein was up-regulated,the neuronal viability was significantly decreased,and the apoptosis rate was significantly increased in group D + H + T ( P ＜ 0.01 ).ConclusionHO-1 can inhibit neuronal apoptosis through blocking CDK5-ATM-P53 signal transduction pathway in rat hippocampal neurons subjected to OGD injury.

Objective To investigate the clinical characteristics,pathogenic causes and treatment outcomes of acute kidney injury (AKI) in very old patients in order to improving the diagnosis and treatment.Methods 39 AKI patients aged ≥80 years in the department of geriatric medicine of our hospital were enrolled and followed up for 3 months.Clinical and laboratory data were analyzed and the pathogenic causes as well as the treatment outcomes were summarized.Results Among the 39 very old patients,31(79.5％) were male,8(20.5％) were female,and the mean age was (93.5±4.6) years.33 (84.6％)patients had chronic kidney diseases.The pathogenic causes of AKI were mainly as follows:urological infections (71.8％),blood volume deficiency (48.7％),cardiac dysfunction (23.1％) and hypotension (15.4％).2 to 4 pathogenic causes were co present in 64.1％ patients.Renal function was improved and recovered in 69.2 ％ patients and the death rate was 25.6％ after treatment.The main causes of death were septic shock (30.0％),multiple organ failure (20.0％),massive gastrointestinal hemorrhage (20.0％) et al.Conclusions Most of the very old patients may suffer from AKI on the basis of chronic kidney disease.AKI is often induced by multiple pathogenic causes.The main factors leading to AKI are urological infections,followed by blood volume deficiency and cardiac dysfunction.Most patients with AKI can recover after the precipitating factors are removed and supportive treatments are administered in time.Septic shock is the main cause of death.

Objective To explore the teaching effect ofOrgan-system-based curriculum in-tegrated model on clinical graduation field work. Method 150 clinical medical undergraduates of Grade 2009 from Shenyang Medical College selected, were randomly divided into the experimental group (75 persons) and the control group (75 persons). The experimental group adopted the means of the Organ-system-based curriculum integrated model, namely practicing according to human organ-system and the control group accepted the traditional pattern of discipline centered practice during the clinical graduation internship. The two groups of students carried out questionnaire survey and comprehend examinations when the practice ended, and then statistics analysis (the chi square test, t test) was done by the SPSS 19.0 software between the two groups in order to explore the teaching effect. Result The students' satisfaction degree from six aspects of the questionnaire survey showed in the experimental group was significantly higher than that in the control group (the degree of recognition of practicing pattern: χ2=11.437, P=0.003; the architectonic integrality: χ2=9.881, P=0.007; the im-provement of the autonomic learning ability χ2=9.643, P=0.008; the teaching method and means: χ2=11.006, P=0.004; motivating learning interest: χ2=13.550, P=0.001; increasing the ability of clinical thinking: χ2=13.309, P=0.001), and the average test scores of students from three parts of examination results showed by comprehend examinations (speculative knowledge examination: t=2.768, P=0.006;technical skill examination: t=2.212, P=0.029; clinical capability examination: t=5.015, P=0.000) in the experimental group was obviously higher than that in the control group and the difference was sig-nificant. Conclusion Organ-system-based curriculum integrated model on clinical graduation in-ternship is generally approved by the students, which has significantly improved the students' clinical thinking ability, and the quality of graduation internship teaching.

Objective To investigate the effects of thymoquinone (TQ) on the levels of proteins involved in oxidative stress and cytokine in the brain of rats with type 2 diabetes mellitus.Methods Wistar rats (n=48) were randomly divided into 3 groups:normal control group,model group and TQ treatment group (n =16).The normal control group was fed with clean grade ordinary feed.The model group and TQ treatment group rats were fed with high-glucose and high-fat diet.After 6 weeks' feeding,model group and TQ treatment group rats were administered streptozocin (STZ) (35 mg/kg) to establish type 2 diabetic model by intraperitoneal injection.Then,the model group and TQ treatment group rats were fed with high-glucose and high-fat diet for another 6 weeks.After that,TQ treatment group rats were administered TQ (5 mg/kg) by intraperitoneal injection every other day.The model group rats were injected with an equal dose of ethanol.Six weeks later,all the rats were sacrificed to obtain the hippocampal tissue for the protein extract.The protein levels of nuclear factor erythroid 2-related factor 2 (Nrf2),heme oxygenase-1 (HO-1) and cyclo-oxygenase 2 (COX-2) in the hippocampal tissue were measured by Western blot.Superoxide dismutase (SOD) activity was determined by SOD kit.Blood-glucose meter was used to assess the blood glucose before the rats were sacrificed and after the model was successfully established.All the measurement data was described by the x ± s,measurement data were compared among groups using One Way ANOVA.Results The results by Western blots showed that the levels of the Nrf2 and HO-1 protein were significantly decreased in the model group compared with the normal control group,the levels of the Nrf2 and HO-1 proteins were increased in the TQ treatment group in comparison with the model group (P＜ 0.05).Meanwhile,compared with the normal control group,the SOD activity of the hippocampus in model group was significantly lower (P＜ 0.05);by contrast with the model group,the SOD activity in the TQ treatment group was considerably increased (P＜0.05).By contrast,the COX-2 level in the model group was substantially higher than that in the normal control (P＜0.05),and the COX-2 level in the TQ treatment group was lower than that in the model group (P＜0.05).Conclusions TQ might inhibit inflammation and improve oxidative stress of the brain tissue in the rats with type 2 diabetes mellitus.

Aim This study examined the uptake and transport of ecdysterone(EDS) using Caco-2 cell monolayers as a model of human intestinal mucosa.Methods Two kinds of Caco-2 cell monolayer model(Caco-2 cell monolayers;CYP3A4 expressing Caco-2 cell monolayers) were set up to study the uptake and transport of EDS.Results Compared bi-directional charaterizaton of Caco-2 cell,the apparent permeability coefficients(Papp) values of EDS were between 0.1?10-6 cm?s-1 and 1?10-6 cm?s-1.EDS absorption was 1%~10% for two kinds of Caco-2 models.The RPapp values were all less than 1.5 for 4 h.Conclusions The uptake and transport of EDS was a passive transcellular diffusion mechanism.Ecdysterone was not influenced by CYP3A4 mediate mechanism.

AIM:To observe the effects of prostaglandin E2 on transforming growth factor-?1(TGF-?1)triggered human lung fetus fibroblast(HLF)transdifferentiation and connective tissue growth factor(CTGF),collagen type I(COLⅠ)expression.METHODS:HLFs were treated with TGF-?1,the cells underwent phenotypic change to myofibroblast.The marker of myofibroblast-?-smooth muscle actin(?-SMA)was detected by immunofluorescence.The ?-SMA content was measured by Western blotting.The changes in CTGF and COL Ⅰ at transcription levels were estimated by RT-PCR method.CTGF protein expression was evaluated by immunocytochemical.Cell culture medium hydroxyproline amount was measured by colormetric assay.RESULTS:PGE2 blocked TGF-?1 induced ?-SMA positive myofibroblast transformation(P

Objective To study the correlation of multi-slice CT portography (MSCTP) and digestive endoscopy in the diagnosis and evaluation of esophageal and gastric varices (EGV) caused by cirrhosis.Methods A total of 92 patients with cirrhosis were enrolled in the prospective study.All the patients were examined by endoscopy and 64-slice spiral CT scan in 4 weeks.The types,grading of EGV were observed by endoscopy and MSCTP,and Kappa conformance test was applied with the endoscopic findings as gold standard.The sensitivity,specificity,consistency,and Youden index were evaluated for the diagnosis of sophageal and gastric varices by MSCTP.Results Sixty-five patients were diagnosed to have EGV by endoscopy and 27 were negative.The positive patients included 45 patients of GOV1,19 of GOV2 and 1 patient of IGV1.MSCTP diagnosed 67 cases of EGV and 25 patients of negative results.The positive patients included 46 of GOV1,18 of GOV2 and 3 of IGV1.Two patients of IGV1 varicose veins without positive findings on endoscopy were diagnosed by using MDCTP,which revealed isolated varicose veins under the gastric mucosa.There was high consistency between MSCTP and EGV in the diagnosis of EGV (Kappa =0.732,P ＜ 0.01).The sensitivity of MSCTP was 93.8％,specificity was 77.8％,consistency was 89.1％,and Youden index 71.6％.There was high consistency between MSCTP and EGV in the classification of EGV (Kappa values were 0.743 and 0.763,P ＜ 0.01).Conclusions There is high consistency between MSCTP and digestive endoscopic in the diagnosis and classification of EGV in cirrhosis.MSCTP is superior to endoscopy in the detection of gastric varices.

Objective To investigate the effect of transduction of heme oxygenase-1 (HO-1) protein on oxygen-glucose deprivation and restoration (OGD/R)-induced injury to hippocampal neurons in rats.Methods Plasmid 11R-HO-1 was constructed using plasmid pET-21a(+)-p53-11R (plasmid 11R) and 11R-HO-1 fusion protein was identified and collected.Hippocampal neurons obtained from newborn Wistar rats (＜ 48 h) were cultured for 7 days in vitro and then the neurons were randomly divided into 5 groups (n =171 each) using a random number table:OGD/R group,normal saline group (group NS),plasmid 11R group (11R group),300 nmol/L 11R-HO-1 group (H1 group),and 1 500 nmol/L 11R-HO-1 group (H2 group).In NS,11R,H1 and H2 groups,the neurons were incubated for 2 h with 300 nmol/L normal saline,300 nmol/L plasmid 11R,300 nmol/L 11R-HO-1 fusion protein,and 1 500 nmol/L 11R-HO-1 fusion protein,respectively,and then OGD/R was performed.The neurons were incubated in deoxygenated glucose-free DMEM medium and sealed under 5 ％ CO2-95 ％ N2 in an anaerobic chamber equilibrated to 37 ℃ for 45 min.OGD was terminated by replacement of the medium with high glucose DMEM medium and by returning the cultures to a standard incubator maintained at 37 ℃ in 5 ％ CO2-95 ％ air and the neurons were then incubated for 24 h.Immediately after OGD/R was established,the cell survival rate (by MTT assay),apoptosis rate (using TUNEL),and expression of HO-1 and caspase-3 protein (by using Western blot) were measured.Results Compared with group OGD/R,the cell survival rate was significantly increased,the apoptosis rate was decreased,the caspase-3 expression was down-regulated,HO-1 protein expression was up-regulated in H1 and H2 groups (P ＜ 0.05),and no significant change was found in the parameters mentioned above in NS and 11R groups (P ＞ 0.05).Compared with group H1,the cell survival rate was significantly increased,the apoptosis rate was decreased,the caspase-3 expression was down-regulated,and HO-1 protein expression was up-regulated in group H2 (P ＜ 0.05).Conclusion Transduction of HO-1 protein can reduce OGD/R-induced injury to hippocampal neurons of rats.

This article gives a profound exploration on the theoretical origin, prohibitions and mechanisms of moxibustion for heat syndrome. Based upon the ancient and modem literature, this article also gives a classified summarization on diseases of moxibustion for heat syndrome, in order to obtain a thorough understanding about the theory and clinical application of moxibustion for heat syndrome, hence to further perfect the theory of moxibustion and guide the clinical practice.