Objective To study the expressions of IGF-Ⅰ and TGF-?1 in lung tissue of rats with pulmonary fibrosis.Methods Sixty male Wistar rats were randomly divided into two groups: control group(n=20) and experimental group(n=40),and poured respectively by saline and bleomycin solutions,and killed on the 7th,14th,21th,28th day.Immunohistochemistry method was used to analyze the expressions of IGF-Ⅰ and TGF-?1 in lung tissue.Results After 4 weeks induction by bleomycin solutions,the lung tissue was obtained and stained by HE,the pathological changes were in accordance with pulmonary fibrosis.Pulmonary interstitial fibers were found by VG staining.So lung fibrosis models induced by bleomycin were set up successfully.The expressions of IGF-Ⅰ and TGF-?1 were increased during the progression of pulmonary fibrosis.Excellent differences of percentage of positive cells and expression level of IGF-Ⅰ and TGF-?1 were found between control group and experimental group(P

We studied 22 Wilms'tumors of children immunohistochemically.We've found that the positive rate of p53 in slices was 31.8% (7),of nm23 was 50% (11),and of p16 was 86.4% (19).It suggested that mutation rate of p53 was high in tumors,expression of nm23 in favorite histology(FH)was higher than that in unfavorite histology(UFH) group,and p16 showed very high positive rate in tumors.All of the three showed no relation with sex,age,or pathological type.So each one may be useful in clinic to evaluate pathogenesis and prognosis.

OBJECTIVE:To explore the method and role of clinical pharmacists in pharmaceutical care for nephrotic syndrome complicated with Pneumocystis carinii pneumonia (PCP). METHODS:Clinical pharmacists participated in the treatment for a pa-tient with nephrotic syndrome complicated with PCP,and implemented pharmaceutical care in terms of the development of anti-in-fective therapy regimens,glucocorticoid optimization,guardianship for drug use,the medication education for patients. Clinical pharmacists provided suggestion that primary anti-infective plan of azithromycin 0.5 g,ivgtt,qd+Compound sulfalene tablet 2 tab-lets,po,q12 h;which was not effective,was adjusted plan as Compound sulfalene tablet 3 tablets,po,q6 h+clindamycin 0.6 g, ivgtt,q8 h+caspofungin 50 mg,ivgtt,qd. The dose of Methylprednisolone for injection was adjusted 4 times according to disease progression. RESULTS:Physicians adopted the suggestions of clinical pharmacists. After 30 days of treatment, lung abnormal le-sion was absorbed basically and infection control was achieved. CONCLUSIONS:Clinical pharmacists participate in anti-infective treatment and pharmaceutical care,and assist physicians to develop therapy plan to promote rational drug use in the clinic and im-prove the effectiveness and safety of clinical treatment.

Objective To investigate the effects of Xiao Yao San on intracellular Ca2 + concentration in cultured rat hippocampal neurons in the state of chronic stress and study the mechanism of chronic stress injuring and XiaoYao San protecting. Methods MK-801 acts as tool,cultured rat hippocampal neurons were divided into seven groups, those were group 1 (control), group 2 (normal serum), group 3 (normal serum + Glu), group 4 (model serum + Glu), group 5 (model serum + Glu + MK-801), group 6 (Xiaoyaosan + Glu), group 7 (Xiaoyaosan + Glu + MK-801). to detect intracellular Ca2+ concentration in cultured hippocampal neurons in the simulated micro - environment of chronic stress and after intervention with the serum treated with Xiao Yao San by confocal laser microscope at the same period of time. Results Compared with group 1 (779.97 ± 36.81), concentration of Ca2+ intracellular of group 2 (1092.38 ± 36.41), group 3 (1472.49 ± 76. 19), group 4 (1509.52 ±104.69) and group 5 (1186.97 ±41.92) all increased significantly (P＜0.01) ,group 6 (908.74 ±40.24) increased too (P ＜ 0.05), compared with group 2, concentration of Ca2 + intracellular of group 3,4 and 5 all increased significantly (P ＜ 0.01), but group 7 (721.99 ± 60.33) decreased significantly (P ＜ 0.01). Compared with group 4, concentration of Ca2+ intracellular of group 6 and 7 decreased significantly (P＜ 0.01), group 5 decreased too (P ＜ 0.05), compared with group 6, concentration of Ca2 + intracellular of group 5 increased significantly (P ＜ 0.01),when group 7 decreased significantly (P＜0.01). Conclusion Serum of chronic stress treated with Xiao Yao San has the effect of inhibiting Ca2+ overload in hippocampal neurons,it may work through a variety of signaling pathways including Glu-NR-Ca2+ to maintain the steady-state of Ca2+ concentration in hippocampal neurons, and then to protect neurons from the neurotoxic effects of excitatory.

Objective To observe the mechanisms that Xiaoyao powder influences the hypothalamus-pituitary-adrenal (HPA) axis of chronic-stress rats. Methods Chronic stress rats were as researching object,and RU-38486 acted as tool drugs. The serum-GC density of rats were tested with ELISA,and the glucocortcoid(GR) in hippocampus neuron were tested with immunofluorescence,the CRH mRNA in hypothalamus were tested by in situ hybridization (ISH). Results Compared with normal group ( 1.09 ± 0.11 ;0.57 ± 0.10), the expression of GR in hippocampus of model group decreased(0.65 ± 0. 10; P ＜ 0. 01 ), and the expression of CRH mRNA in hypothalamus of model group increased ( 1.12 ±0. 11; P＜0. 0l ) ,the GR in hippocampus of RU-38486 group increased ( 1.59 ± 0. 11; P ＜ 0. 01 ), and the expression of CRH mRNA in hypothalamus of RU-38486 group reduced (0.48±0.10; P＜0.05) ,but both the expression of GR in hippocampus and the CRH mRNA in hypothalamus of Xiaoyao powder group were no change (0.62 ±0.08;0.97 ±0.13; P＞0.05). Compared with model group,both the expression of GR in hippocampus of RU-38486 and Xiaoyao powder group increased (P＜0. 01) ,and both the expression of CRH mRNA in hypothalamus of RU-38486 and Xiaoyao powder group reduced (P＜0.01). Conclusion Multi-stress can result in the expression of GR in hippocampus of rats decreasing and the expression of CRH mRNA in hypothalamus increasing, but those changes can be restrained by Xiaoyao powder, and it is the maybe mechanism of Xiaoyao Powder resisting chronic stress in HPA axis.

This study aimed to explore the impact of depression caused by chronic unpredictable mild stress (CUMS) on in vivo activity of six kinds of CYP450 isoforms in rats. According to 'Katz' method, the model of CUMS was established. Tolbutamide, chlorzoxazone, theophylline, midazolam, omeprazole and dextromethorphan were chosen as probe substrates of CYP2C6, CYP2E1, CYP1A2, CYP3A2, CYP2D1 and CYP2D2 of rats. Plasma concentration of six kinds of CYP450 in control group and model group were determined by LC-MS/MS and computed pharmacokinetic parameters. Consequently, metabolism of theophylline and chlorzoxazone accelerated significantly (P < 0.01), but tolbutamide, dextromethorphan, omeprazole and midazolam had no significant difference. The present study proved that depression caused by CUMS had strong induction to CYP1A2 and medium induction to CYP2E1.

Aim To investigate the influence of sarpog-relate hydrochloride (SH)on the pharmacokinetic pro-file of dextromethorphan (DM),the typical substrate of CYP2D1 /2,in rats when they were administered co-instantaneously.Methods A total of 1 2 SD rats were randomly divided into two groups:the control group (DM,1 0 mg·kg-1 )and the sarpogrelate group (SH, 1 0 mg·kg-1 ;DM,1 0 mg·kg-1 ),which received in-tragastric administration.Plasma samples were collected immediately before and at different time points after drug administration.A LC-MS /MS method was used to determine the concentrations of DM in rat plasma. Pharmacokinetic parameters were analyzed using Drug and Statistics (DAS 2.0).Results There were signif-icant differences in the pharmacokinetic parameters of DM,including T1 2 (2.49 h ±0.93 h vs 1 .47 h ±0.20 h,P <0.05 ),Cmax (325.7 μg·L -1 ±1 33.2 μg· L -1 vs 1 04.5μg·L -1 ±52.4 μg·L -1 ,P <0.05), AUC0 -t(785.5 μg·L -1 ·h ±451 .9 μg·L -1 ·h vs 244.8 μg·L -1 ·h ±1 68.3μg·L -1 ·h,P <0.05) and AUC0 -∞(804.7 μg·L -1 ·h ±445.6 μg·L -1 ·h vs 251 .4 μg·L -1 ·h ±1 73.4 μg·L -1 ·h,P<0.05 )between the two groups.Conclusion SH could significantly inhibit the elimination of DM,the substrate of CYP2D1 /2 in rats.

Aim To establish a LC-MS/MS method for determination of 5-HT, NE, DA and observe the con-centration of 5-HT, NE, DA in rat plasma of CUMS. Methods Twenty-two male SD rats were divided into control group and model group. Model group was given 9 kinds chronic unpredictable mild stimulating factors every day. 21 days later, behavior and orbital blood were measured before and after modeling. Using benzo-yl chloride as a pre-column derivatization reagent, three analytes and IS were derivatized before LC-MS/MS detection. Change in three kinds of neurotransmit-ter concentration was measured in rat plasma before and after modeling. Results After modeling, com-pared with control group, the weight of rats in model group was declined significantly ( P<0. 05 ) . Horizon-tal scores, vertical scores and sugar consumption were declined significantly ( P <0. 01 ) . Calibration curves of 5-HT, NE, DA were linear between 1. 47 ~752, 1. 75 ~898 , 2. 05 ~1 053 μg · L-1 and LOQ were 1. 47, 1. 75, 2. 046μg·L-1 ,respectively. The recov-ery of 5-HT, NE, DA from plasma was over than 70%, and RSD of inter-day and intra-day assay was limited in 15%. Compared with control group, the con-centration of 5-HT, NE, DA in rat plasma of model group was declined to ( 3. 99 ± 1. 21 ) , ( 6. 24 ± 1. 94), (6. 07 ± 1. 98) μg·L-1(P <0. 01). Con-clusion After making CUMS model of depression, three kinds of neurotransmitters in rat plasma are de-creased.

Objective To investigate the effect of clopidogrel on the binding rate of ginsenosides with rat serum proteins (RSA). Methods Equilibrium dialysis and liquid chromatography-mass spectrometry were employed to quantify the concentration of ginsenoside Rg1 and Rb1. The protein-binding rates of Rg1 and Rb1 in the presence or absence of clopidogrel (1.0 mg/L) were determined. A molecular simulation model (consisting of homology modeling and molecular docking interaction) was used to reveal the target protein-compound interactions. Results The binding rates of ginsenosides Rg1 (0.4, 1.0, and 2.0 mg/L) with RSA were (30.16±2.82)%, (33.42±4.21)%, and (34.61±3.42)%, and those of and Rb1 were (50.13±2.34)%, (51.23±3.23)%, and (53.11± 3.26)%, respectively. In the presence of clopidogrel, the binding rates of Rg1 decreased to (22.13 ± 2.72)%, (21.42 ± 3.22)%, and (25.45 ± 3.52)%, and those of Rb1 to (40.13 ± 3.24)%, (41.25 ± 4.15)%, and (43.11 ± 3.31)%, receptively. The molecular docking suggested that these compounds competed to bind with RSA. Conclusion Clopidogrel can competitively bind to RSA with ginsenosides to lower the plasma protein binding rates of ginsenosides.

Objective To investigate the effect of clopidogrel on the binding rate of ginsenosides with rat serum proteins (RSA). Methods Equilibrium dialysis and liquid chromatography-mass spectrometry were employed to quantify the concentration of ginsenoside Rg1 and Rb1. The protein-binding rates of Rg1 and Rb1 in the presence or absence of clopidogrel (1.0 mg/L) were determined. A molecular simulation model (consisting of homology modeling and molecular docking interaction) was used to reveal the target protein-compound interactions. Results The binding rates of ginsenosides Rg1 (0.4, 1.0, and 2.0 mg/L) with RSA were (30.16±2.82)%, (33.42±4.21)%, and (34.61±3.42)%, and those of and Rb1 were (50.13±2.34)%, (51.23±3.23)%, and (53.11± 3.26)%, respectively. In the presence of clopidogrel, the binding rates of Rg1 decreased to (22.13 ± 2.72)%, (21.42 ± 3.22)%, and (25.45 ± 3.52)%, and those of Rb1 to (40.13 ± 3.24)%, (41.25 ± 4.15)%, and (43.11 ± 3.31)%, receptively. The molecular docking suggested that these compounds competed to bind with RSA. Conclusion Clopidogrel can competitively bind to RSA with ginsenosides to lower the plasma protein binding rates of ginsenosides.