To study the effect of Fuzheng Huayu recipe (FZHY) on five types of isozymes of cytochrome P450 (CYP450) of normal and liver fibrosis rats by using the cocktail probe method. Dimethylnitrosamine ( DMN) was injected to induce the liver fibrosis model. After the tail vein injection with Cocktail probe solutions prepared with five CYP450s probe substrates (phenacetin-CYP1A2, omeprazole-CYP2C9, tolbutamide-CYP2C19, dextromethorphan-CYP2D6, midazolam-CYP3A4), the plasma concentrations of the five probe substrates were determined by LC-MS/MS, and the pharmacokinetic parameters were calculated by PK solutions 2. After the oral administration with FZHY, normal rats given phenacetin, omeprazole, tolbutamide and dextromethorphan showed increase in AUC(0-t) and decrease in CL to varying degrees, indicating that FZHY obviously inhibited the activities of CYP1A2, CYP2C9, CYP2C19 and CYP2D6 in normal rats, but with no obvious effect on the activity of CYP3A4. After the oral administration with FZHY, liver fibrosis rats treated with CYP2C9 showed the significant increase in AUC(0-t) and significant decrease in Vd, hut with no obvious changes in the pharmacokinetic parameters of other four types of prove substances, suggesting that FZHY could significantly inhibit the activity of CYP2C9 in rats but had no effect on the activities of CYP1A2, CYP2C19, CYP2D6 and CYP3A4. The changes in the activity of CYP450 isozymes in liver fibrosis rats may be the reason for FZHY's different effects on CYP450 isozymes in normal and liver fibrosis rats.
Animals ; Cytochrome P-450 Enzyme System ; genetics ; metabolism ; Disease Models, Animal ; Drugs, Chinese Herbal ; administration & dosage ; chemistry ; pharmacokinetics ; Humans ; Isoenzymes ; genetics ; metabolism ; Liver Cirrhosis ; drug therapy ; enzymology ; genetics ; Male ; Mass Spectrometry ; Rats ; Rats, Wistar

Acyl carrier protein is an essential component involved in the biosynthesis of DHA(Docosahexaenoic Acid) via PKS(Polyketide synthase) pathway,which takes the growing acyl chain from one enzyme to another.One cDNA clone,with high homology of ACP,was isolated from Schizochytrium sp.FJU-512 cDNA library.The deduced amino acid sequence contained 142 residues with isoelectric point of 5.04 and had the 4'-phosphopantetheine prosthetic(4'-PP) binding site.The target fragment was digested with BamHⅠ/HindⅢand inserted into the expression vector pET-30a resulting in the plasmid pET-30a/acp.The recombinant vector was transformed into E.coli BL21(DE3) and induced by IPTG.SDS-PAGE analysis demonstrated that ACP was effectively expressed.

Objective To observe the effect of artificial nose in the artificial airway humidity among the elderly patients with artificial airway. Methods Sixty-eight patients undergoing artificial airway at department of respiratory were randomly divided into 2 groups, 34 of them in the artificial nose airway humidity group, and 34 in the regular humidity group. The quantity of sputum secretion, times of sputum absorption, degree of airway humidity and acute reaction of respiratory tract were observed. Results The artificial nose airway humidity group was better than the regular humidity group in view of reducing the quantity of sputum secretion, times of sputum absorption, degree of airway humidity and acute reaction of respiratory tract, with significant meanings by the analysis of Chi square test and T test (P<0.01). Conclusions Artificial nose is superior to the method of regular humidity in respect of reducing the quantity of sputum secretion and times of sputum absorption, keeping well effect of airway humidification, and reducing the complications of artificial airway.

OBJECTIVETo investigate whether myocardial bridging (MB) is independently associated with coronary atherosclerosis proximal to MB in the left anterior descending coronary artery (LAD) identified by computed tomographic coronary angiography (CCTA).

METHODSFrom March 2011 to December 2012, patients (n=9 862) with suspected coronary disease underwent CCTA using dual-source CT scanner. The baseline clinical characteristics (age, gender, smoking history, presence of hypertension, dyslipidemia, diabetes mellitus, family history of heart attack, and body mass index) and the results of CCTA were reviewed. Two radiologists evaluated the coronary artery for MB and coronary atherosclerosis stenosis (CAS) in LAD and made a diagnosis by consensus. Significant independent risk factors for CAS were investigated by multivariate logistic regression analysis.

RESULTSA total of 3 182 (32.3%) cases of MB and 3 359 cases of CAS of LAD were identified. No patient with CAS in the tunneled segment was found. The mean length of bridges and the mean thickness of the overlying myocardium was (17.3±5.2) mm and (1.2±0.9) mm, respectively. There were 1658 MB cases in 3 359 cases of LAD stenosis and 1 524 MB cases in 6 503 cases of no LAD stenosis (χ(2)=681.12, P<0.05). Logistic regression analysis showed that MB in the LAD were significantly associated with CAS in the proximal LAD (OR=3.07, 95%CI=2.81-3.37, P<0.001), and after final adjustment for age, gender, body mass index, family history of heart attack, smoking, hypertension, dyslipidemia, diabetes mellitus, and resting heart rate (OR=2.86, 95% CI=2.60-3.16, P < 0.001).

CONCLUSIONMB in the LAD is independently associated with CAS in the proximal segment to MB.

Adult ; Aged ; Aged, 80 and over ; Coronary Stenosis ; complications ; diagnostic imaging ; Female ; Humans ; Logistic Models ; Male ; Middle Aged ; Myocardial Bridging ; complications ; diagnostic imaging ; Risk Factors ; Tomography, X-Ray Computed

Objective To study the onset features and axiom of children disease in Duanguan region.Methods A statistic study was carried on 1 782 cases of children disease which confirmed by pathological examinations.The sex,age and pathology(congenital malformation,inflammatory disease,tumor-like lesions,benign tumors,malignant tumors)were registered.Results The inflammatory disease occupied the first place in incidence rate(44.61%),followed by tumor-like lesions(25.03%),benign tumors(23.34%),congenital malformation(5.22%)and malignant tumors(1.80%).Among inflammatory disease,appendicitis was the most common,the next was chronic tonsillitis and tuberculosis.Among tumor-like lesions,cystic disease was the most common;the next was polyps.Among benign tumors,vasculoma was the most common,the next was pilomatricoma,osteoid and chonodroid tumors.Among congenital malformation,ear fistula was the most common,the next was diverticulosis and intestineal duplicateion.Among the malignant tumors,the sarcoma of soft tissue was the most common,the next was the malignant peripheral nerve tumors and lymphoma.Conclusion Children's disease have its own characteristics which varied in age,sex and pathological types,and differ from those of adults.

OBJECTIVETo investigate the effect of the RNAi and the chemotherapy drugs nolatrxed on the expression of thymidylate synthase(TS) and the growth of the colorectal carcinoma LOVO cells.

METHODSThe siRNA was constructed targeting the human TS gene, and then transfected into the human colorectal cancer LOVO cells. RT-PCR and Western blot technique were used to observe the TS gene and protein expression levels, and MTT was used to detect cell proliferation after silencing the TS gene. In addition, siRNA and nolatrxed were applied to the LOVO cells to observe the TS protein expression and cell growth.

RESULTSTS siRNA significantly reduced the expression of TS gene and protein in LOVO cells, and inhibited cell growth. The IC50 value of LOVO cells was (1.46±0.25) μmol/L in TS siRNA combined with nolatrexed group, (6.81±0.31) μmol/L in the negative control group, and (6.47±0.43) μmol/L in the single nolatrexed group. After treatment of TS siRNA combined with nolatrexed on LOVO cells for 36 hours, the apoptosis index was higher than that in single TS siRNA and nolatrexed[(62.12±0.89)% vs.(21.56±0.67)% and(40.51±0.83)%, both P<0.05].

CONCLUSIONTS siRNA can partly suppress the expression of TS gene in LOVO cells, inhibit cell proliferation, promote cell apoptosis and enhance cell sensitivity to apoptosis induced by nolatrexd.

Apoptosis ; drug effects ; Cell Cycle ; drug effects ; Cell Line, Tumor ; Cell Proliferation ; drug effects ; Colorectal Neoplasms ; enzymology ; pathology ; Humans ; Quinazolines ; pharmacology ; RNA Interference ; Thymidylate Synthase ; genetics ; metabolism

Animals ; COS Cells ; Female ; Hepatitis B Core Antigens ; genetics ; Hepatitis B Surface Antigens ; genetics ; Hepatitis B Vaccines ; immunology ; Interleukin-12 ; genetics ; Mice ; Mice, Inbred BALB C ; Vaccines, DNA ; immunology

Triclosan(TCS)is a broad-spectrum antibacterial agent that is widely used in personal care products. Humans are exposed to these chemicals through oral intake or direct dermal absorption. The main way to eliminate TCS is through urine. Studies have shown that TCS may interfere with thyroid function and the reproductive endocrine system. In recent years, increasing epidemiological studies have focused on TCS exposure during pregnancy and the relationship between TCS exposure and birth outcomes. Compared with other countries and regions, pregnant women have lower levels of TCS exposure in China. Animal experiments suggested that high dose of TCS exposure during pregnancy may affect birth outcomes through its endocrine disruption. This review is aimed to summarize the effects of TCS exposure during pregnancy on the birth outcomes.

Background:X-linked inhibitor of apoptosis (XIAP) is a vital factor in the anti-apoptosis mechanism of tumors and is highly expressed in renal cell carcinoma (RCC).However,the mechanism through which XIAP regulates DNA damage repair is unknown.This study investigated the regulatory mechanism of XIAP in etoposide-induced apoptosis in two Caki-1 cell lines with high or low XIAP expression.Methods:The two cell lines were established using RNA interference technology.The differentially expressed proteins in the two cell lines were globally analyzed through an isobaric tags for relative and absolute quantitation-based quantitative proteomics approach.Proteomic analysis revealed 255,375,362,and 5 differentially expressed proteins after 0,0.5,3,and 12 h of drug stimulation,respectively,between the two cell lines.The identified differentially expressed proteins were involved in numerous biological processes.In addition,the expression of histone proteins (H1.4,H2AX,H3.1,H3.2,and H3.3) was drastically altered,and the effects of XIAP silencing were accompanied by the marked downregulation of H2AX.Protein-protein interactions were assessed and confirmed through immunofluorescence and Western blot analyses.Results:The results suggested that XIAP may act as a vital cell signal regulator that regulates the expression of DNA repair-related proteins,such as H2AX,and influences the DNA repair process.Conclusions:Given these functions,XIAP may be the decisive factor in determining the sensitivity of RCC cell apoptosis induction in response to chemotherapeutic agents.

Objective To observe changes of left ventricular function and the level of autophagy after treatment with trimetazine in rats with heart failure after myocardial infarction(MI). Methods Twenty healthy male Wistar rats with the ligation of the proximal part of the left descending branch were randomly and equally allocated into two groups,model group (M group) and trimetazine group (Q group). A sham group (S group) was made up by 10 sham-operated rats. Rats of trimetazine group were given trimetazine(15 mg/kg)once a day for 4 weeks.Then left ventricular function was measured by echocardiography,and hemodynamics was evaluated by Millar pressure-volume system.Serum levels of NT-proBNP and hs-TnT were tested by ELISA.Pathological changes and fibrosis of myocardium were observed by HE and Masson staining.The myocardial apoptosis level was observed by TUNEL, and expressions of autophagy related protein and gene in myocardial tissue were detected by Western blot assay and RT-PCR. Results Trimetazine treatment significantly improved left ventricular dilatation and dysfunction in rats with myocardial failure. Trimetazine treatment also significantly improved pressure overload and the compliance decrease of left ventricular in rats with heart failure after myocardial infarction. Trimetazidine reduced the edema,necrosis and myocardial fibrosis of cardiac myocytes in rats with heart failure.The results from ELISA showed that serum levels of NT-proBNP and hs-TnT were significantly lower in the trimetazine group than those of model group.Compared with model group,the cardiomyocyte apoptosis decreased significantly in the trimetazine group.The results from Western blot assay and RT-PCR showed that autophagic flow of myocardium was increased remarkably in the trimetazine group than that of model group. Conclusion Autophagy has a protective effect on myocardial cells. Trimetazine can improve cardiac function through up-regulation of autophagy in cardiomyocytes in MI rats with heart failure.