Antigens ; chemistry ; Fixatives ; chemistry ; Humans ; Hydrogen-Ion Concentration ; Immunohistochemistry ; methods ; Microwaves ; Staining and Labeling ; methods

OBJECTIVETo study and evaluate the curative effect and mechanism of Qiangxin Granule (QXG) in intervening chronic heart failure (CHF) rats with Xin-qi deficiency complicated blood stasis and edema syndrome (XQD-BS-ES).

METHODSTotally 72 SD rats of clean grade were randomly divided to the normal control group (n =10) and the model group (n = 62). The XQD-BS-ES rat model was established by adriamycin plus propylthiouracil method. Survived modeled rats were then randomly divided to 5 groups i.e., the model group (n = 11, administered with normal saline by gastrogavage), the Western medicine (WM) group (n =11 , administered with perindopril and hydrochlorothiazide by gastrogavage), the low dose QXG (QXG(L)) group (n = 11, administered with 9.26 g/kg QXG by gastrogavage), the middle dose QXG (QXG(M)) group (n = 11, administered with 18.52 g/kg QXG by gastrogavage), the high dose QXG (QXG(H)) group (n = 11, administered with 37.04 g/kg QXG by gastrogavage). After 4 weeks of treatment, left ventricular ejection fraction (LVEF), left ventricular fraction shortening (LVFS), brain natriuretic peptide (BNP), heart rate (HR), respiratory rate (RR), urine output, ear temperature, exhaustive swimming test (EST), tri-iodothyronine (T3), tetra-iodothyronine (T4), thyroid stimulating hormone (TSH), as well as heart, lung, liver weight index and their pathological sections, and high sensitivity C-reactive protein (HS-CRP), angiotensin II (Ang II), carbohydrate antigen 125 (CA125) were detected and compared.

RESULTSCompared with the normal control group, LVEF, LVFS, BNP, HR, RR, urine output, ear temperature, EST, T3, T4, TSH, HS-CRP, Ang II, and CA125 changed significantly in the model group (P < 0.01). Compared with the model group after treatment, LVEF, LVFS, BNP, urine output, EST, T4, heart and liver weight index, HS-CRP, Ang II, CA125 were significantly improved in each QXG group (P < 0.05, P < 0.01). Moreover, TSH was improved in the QXGL and QXG(M) groups (P < 0.05); ear temperature and T3 in the QXG(M) were also improved (P < 0.05); the lung weight index decreased in the QXG(M) and QXG(H) groups (P < 0.01). Compared with the WM group, T4 and CA125 were obviously improved in all QXG groups (P < 0.01); BNP and ear temperature were obviously improved in QXG(L) and QXG(M) groups (P < 0.05, P < 0.01); LVEF, LVFS and TSH were obviously improved in the QXG(M) group (P < 0.05, P < 0.01). And as far as each treatment group, LVEF, LVFS, urine output increased significantly after treatment (P < 0.01); EST obviously increased in QXG(M) and QXG(H) groups (P < 0.01); ear temperature increased in all QXG groups (P < 0.05, P < 0.01). Moreover, compared with the model group, pathological changes of heart, lung, and liver were improved to some degree in each treatment group, especially in the QXG(M) group.

CONCLUSIONSGood curative effect was shown in each QXG group. QXG could improve LVEF, LVFS and BNP of CHF rats of XQD-BS-ES, as well as T3, T4, TSH, EST, urine output, and ear temperature. Moreover, QXG showed superiority than WM group in this respect.

Angiotensin II ; Animals ; C-Reactive Protein ; Chronic Disease ; drug therapy ; Drugs, Chinese Herbal ; pharmacology ; therapeutic use ; Edema ; Heart ; Heart Failure ; drug therapy ; Heart Ventricles ; Medicine, Chinese Traditional ; Natriuretic Peptide, Brain ; Qi ; Rats ; Rats, Sprague-Dawley ; Syndrome ; Thyrotropin ; Ventricular Function, Left

OBJECTIVETo establish and evaluate chronic heart failure (CHF) rat model of Xin-qi deficiency complicated blood stasis and edema syndrome (XQD-BSES).

METHODSTotally 40 SD rats were randomly divided into the normal control group (Control), the propylthiouracil (PTU) group, the adriamycin (ADR), and the ADR + PTU group. Normal saline was used as equivalent solvent of each group. Rats in the Control group were intragastrically and intraperitoneally injected with normal saline. Rats in the PTU group were intragastrically injected with PTU suspension and intraperitoneally injected with normal saline. Rats in the ADR group were intragastrically injected with ADR solution and intraperitoneally injected with normal saline. And rats in the ADR + PTU group were intragastrically injected with PTU suspension and intraperitoneally injected with ADR solution. The dose of PTU was 0.2% of daily forage weight, once daily. The dose of ADR was 3.5 mg/kg, once per week. The modeling lasted for 6 weeks. Left ventricular ejection fraction (LVEF), left ventricular fraction shortening (LVFS), brain natriuretic peptide (BNP), heart rate (HR), respiratory rate (RR), urine output, ear temperature, exhaustive swimming test (EST), Tri-iodothyronine (T3), tetra-iodothyronine(T4), thyroid stimulating hormone (TSH) as well as heart, lung, liver weight indices and their pathological sections were integrated and compared.

RESULTSCompared with the Control group, LVEF, LVFS, BNP, HR, RR, heart, lung, liver weight indices, urine output, ear temperature, EST, and T3, T4, and TSH changed significantly in the ADR group, the PTU group, and the ADR + PTU group with statistical significance (P < 0.05), and pathological changes of heart failure occurred in pathological sections of heart, lung, and liver. Compared with the ADR group, LVEF, LVFS, BNP, and lung, liver weight indices, urine output, ear temperature, T3, T4, and TSH changed significantly in the ADR + PTU group with statistical significance (P < 0.05), and pathological changes of heart failure were more serious in pathological sections of heart, lung, and liver. Compared with the PTU group, LVEF, LVFS, BNP, HR, RR, urine output, EST, T4, heart and lung weight indices changed significantly in the ADR + PTU group with statistical significance (P < 0.05), and pathological changes of heart failure were quite serious in pathological sections of heart, lung, and liver.

CONCLUSIONADR + PTU was an appropriate method to establish CHF rat model of XQD-BSES.

Animals ; Edema ; Heart Failure ; diagnosis ; Heart Ventricles ; Humans ; Judgment ; Models, Animal ; Qi ; Rats ; Ventricular Function, Left

In order to establish a method by which the recombinant suicide plasmids integrated on the chromosome could be recircled, A simple method of transconjugative cloning was established with the helper plasmids pMT999 or pRK2013 and fusion strains of Shigella flexneri which were obtained by screening with in vivo expression technology. And the cloning efficiency with this method is very high.

Coal ; Dust ; analysis ; Gases ; adverse effects ; Humans ; Male ; Middle Aged ; Occupational Exposure ; analysis ; Pulmonary Alveolar Proteinosis ; etiology

OBJECTIVETo study the clinicopathologic and prognostic features of neuroendocrine neoplasm of digestive system with different grades.

METHODSThe clinicopathologic features of 139 cases of neuroendocrine neoplasm occurring in digestive system were retrospectively reviewed and graded according to the 2010 World Health Organization classification of tumours of the digestive system. Immunohistochemical study for synaptophysin, chromogranin A and Ki-67 was carried out. The follow-up and survival data were analysed using Kaplan-Meier method. Prognostic factors were tested by Log-rank testing and independent risk factors were analysed using Cox regression model.

RESULTSAmongst the 139 cases studied, there were 88 cases (63.3%) of grade 1 tumors, 9 cases (6.5%) of grade 2 tumors and 42 cases (30.2%) of grade 3 tumors. There was diffusely positive staining for synaptophysin and chromogranin A in most of the grade 1 and grade 2 tumors. The staining in grade 3 tumors however was focal (P < 0.05). The differences in tumor size, depth of invasion, presence of tumor emboli, perineural permeation, nodal involvement, distant metastasis and survival rate amongst the three groups was statistically significant (P < 0.05).

CONCLUSIONSThere is significant difference in the clinicopathologic and prognostic features of neuroendocrine neoplasm of digestive system with different grades. It is considered as an independent prognostic factor and represents a useful tool for prognostic evaluation of such tumors, both in clinical practice and research.

Adult ; Aged ; Aged, 80 and over ; Chromogranin A ; metabolism ; Digestive System Neoplasms ; metabolism ; pathology ; Female ; Follow-Up Studies ; Humans ; Ki-67 Antigen ; metabolism ; Lymphatic Metastasis ; Male ; Middle Aged ; Neoplasm Grading ; Neoplasm Invasiveness ; Neoplasm Metastasis ; Neoplastic Cells, Circulating ; Neuroendocrine Tumors ; metabolism ; pathology ; Proportional Hazards Models ; Retrospective Studies ; Survival Rate ; Synaptophysin ; metabolism ; Tumor Burden ; Young Adult

OBJECTIVETo compare the effect of high frequency oscillatory ventilation (HFOV) and conventional mandatory ventilation (CMV) on the myocardial function of rabbits with inhalation injury.

METHODSSteam inhalation injury model was reproduced in 16 New Zealand albino rabbits. They were randomly divided into CMV group (n = 8) and HFOV group (n = 8) by drawing lots, and they received ventilation in metered volume and HFOV treatment respectively. Heart blood was drawn from rabbits before they were sacrificed 4 hours after treatment to determine the plasma activity of lactate dehydrogenase 1 (LDH1) and creatine phosphorylated kinase (CPK-MB). Myocardial tissue from left ventricle was harvested and homogenized to determine the concentration of TNF-α and IL-8, the activity of caspase-1, and the activity of myosin-light-chain kinase (MLCK) and the ATPase of myosin light chain (MLC-ATPase) by enzyme-linked immunosorbent assay, spectrophotometry, and the nuclide liquid scintillation technique respectively. Part of the myocardial tissue sample was examined pathologically. Data were processed with analysis of variance.

RESULTS(1) The activities of LDH1 and CPK-MB in plasma were obviously higher in CMV group than in HFOV group [(643 ± 108), (342 ± 48) U vs. (233 ± 92), (186 ± 36) U, with F value respectively 10.326 and 9.846, P values all below 0.01]. (2) The contents of TNF-α, IL-8 and the activity of caspase-1 in myocardial tissue homogenate were obviously higher in CMV group than in HFOV group [(181 ± 35), (89 ± 19) pg/g, and (0.56 ± 0.27) g/g protein vs. (94 ± 21), (43 ± 11) pg/g, and (0.24 ± 0.12) g/g protein, with F value respectively 8.239, 7.826, 5.716, P values all below 0.01]. (3) The activities of MLC-ATPase and MLCK were lower in CMV group than in HFOV group [(0.24 ± 0.12) µmol×mg(-1)×min(-1), (3.3 ± 1.1) mmol×mg(-1)×min(-1) vs. (0.48 ± 0.16) µmol×mg(-1)×min(-1), (7.7 ± 1.7) mmol×mg(-1)×min(-1), with F value respectively 4.125, 4.766, P values all below 0.01]. (4) No obvious necrosis, degeneration or inflammatory cell infiltration was observed in myocardial tissue of rabbits in 2 groups under light microscope; but the myocardial fiber was slightly swollen, and it was less marked in the HFOV group.

CONCLUSIONSThe influence of HFOV on myocardial myosin phosphorylation system of rabbits with inhalation injury is less than that of CMV.

Animals ; Burns, Inhalation ; metabolism ; physiopathology ; therapy ; High-Frequency Ventilation ; Myocardium ; metabolism ; Myosin-Light-Chain Kinase ; metabolism ; Rabbits ; Respiration, Artificial

OBJECTIVETo investigate the effects of high frequency oscillatory ventilation (HFOV) and its combination with administration of pulmonary surfactant (PS) on inflammatory response of lung tissue in rabbits with inhalation injury.

METHODSSevere steam inhalation injury models were reproduced in 24 New Zealand albino rabbits. They were divided into control group (n = 8), HFOV group (n = 8), and HFOV + PS group (n = 8) according to the random number table, and they received ventilation in metered volume, HFOV, and HFOV + PS treatment respectively. Lung tissue samples of rabbits were collected at 3.5 h after treatment for pathological inspection and pulmonary injury score, assay of the activity of myeloperoxidase (MPO) and cysteinyl aspartate-specific protease 1 (caspase-1), and the determination of the contents of TNF-alpha, IL-18, IL-10, IL-13 and their mRNA expression.

RESULTSPathological change in different degree of rabbit lung tissue in each group were observed, and they were most obvious in the control group, and least in the HFOV + PS group. The lung tissue injury scores of control group, HFOV group, and HFOV + PS group was 3.71 +/- 0.43, 2.87 +/- 0.26, and 2.08 +/- 0.28 respectively. The difference between either two of them were statistically significant (P < 0.01). The MPO content and caspase-1 activity of rabbits in HFOV and HFOV + PS groups were obviously lower than those in control group (P < 0.01), and MPO content and caspase-1 activity of rabbits in HFOV + PS group were obviously lower than those in HFOV group (P < 0.05). In HFOV group and HFOV + PS group, the contents of TNF-alpha, IL-18 and their mRNA expression in lung tissue homogenates were obviously lower than those in control group (P < 0.01); while the contents of IL-10, IL-13 and their mRNA expression were obviously higher than those in control group (P < 0.01). Changes in these contents and expression in HFOV + PS group were more obvious than those in HFOV group (P < 0.05).

CONCLUSIONSHFOV can alleviate inflammatory response in rabbit lung tissue and pulmonary injury induced by inhalation injury, and the effect is more obvious when combined with PS.

Animals ; Burns, Inhalation ; complications ; therapy ; Disease Models, Animal ; High-Frequency Ventilation ; Inflammation ; Lung Injury ; etiology ; therapy ; Pulmonary Surfactants ; therapeutic use ; Rabbits

In order to successfully develop the effective population pharmacokinetic model to predict the concentration of propofol administrated intravenously, the data including the concentrations across both distribution and elimination phases from five hospitals were analyzed using nonlinear mixed effect model (NONMEM). Three-compartment pharmacokinetic model was applied while the exponential model was used to describe the inter-individual variability and constant coefficient model to the intra-individual variability, accordingly. Covariate effect including the body weight on the parameter CL, V1, Q2, V2, Q3 and V3 were investigated. The performance of final model was assessed by Bootstrapping, goodness-of-fit and visual predictive checking (VPC). The context-sensitive half-times and the infusion rates necessary to maintain the concentration of 1 microg x mL(-1) were simulated to six subpopulations. The results were as follows: the typical value of CL, V1, Q2, V2, Q3 and V3 were 0.965 x (1 + 0.401 x VESS) x (BW/59)(0.578) L x min(-1), 13.4 x (AGE/45)(-0.317) L, 0.659 x (1 + GENDER x 0.385) L x min(-1), 28.8 L, 0.575 x (1 + GENDER x 0.367) x (1 - 0.369 x VESS) L x min(-1) and 196 L respectively. Coefficients of the inter-individual variability of CL, V1, Q2, V2, Q3 and V3 were 29.2%, 46.9%, 35.2%, 40.4%, 67.0% and 49.9% respectively, and the coefficients of residual variability were 24.7%, 16.1% and 22.5%, the final model indicated a positive influence of a body weight on CL, and also that a negative correlation of age with V1. Q2 and Q3 in males were higher than those in females at 38.5% and 36.7%. The CL and Q3 were 40.1% increased and 36.9% decreased in arterial samples compared to those in venous samples. The determination coefficient of observations (DV)-individual predicted value (IPRED) by the final model was 0.91 which could predict the propofol concentration fairly well. The stability and the predictive performance were accepted by Bootstrapping, the goodness-of-fit and VPC. The context-sensitive half-times and infusion rates necessary to maintain the concentration of 1 microg x mL(-1) were different obviously among the 6 sub-populations obviously. The three-compartment model with first-order elimination could describe the pharmacokinetics of propofol fairly well. The involved fixed effects are age, body weight, gender and sampling site. The simulations in 6 subpopulations were available in clinical anesthesia. The propofol anesthesia monitor care could be improved by individualization of pharmacokinetic parameter estimated from the final model.
Adolescent ; Adult ; Age Factors ; Aged ; Aged, 80 and over ; Anesthetics, Intravenous ; pharmacokinetics ; Body Weight ; Female ; Humans ; Male ; Middle Aged ; Models, Biological ; Nonlinear Dynamics ; Propofol ; pharmacokinetics ; Sex Factors ; Young Adult

OBJECTIVEThis study aims to establish and evaluate the methodology of isolated rabbit eye (IRE) test.

METHODSIRE test was performed according to modifications of the in vitro toxicology (INVITTOX) Protocol No.85: Rabbit enucleated eye test by European Centre for the Validation of Alternative Methods (ECVAM), and then 26 chemicals and 26 cosmetic products were tested in both in vitro IRE and in vivo Draize tests. A statistical analysis was conducted to determine the relevance of the IRE test to the data generated in the Draize test.

RESULTSIRE test was established successfully in our laboratory. It was shown that ranking correlation and class concordance were fairly well between the IRE test and the Draize test for 26 reference chemicals (Fisher's Exact Test χ(2)=51.314, P<0.001; McNemar P=0.261; Gamma=0.960, P<0.001; Kappa=0.843, P<0.001) and 26 cosmetic products (Fisher's Exact Test χ(2)=15.522, P<0.001; McNemar P=0.311; Gamma=0.967, P<0.001; Kappa=0.611, P<0.001).

CONCLUSIONIRE test was established successfully for in vitro testing of eye irritation as an alternative to Draize test.

Animal Testing Alternatives ; Animals ; Cosmetics ; toxicity ; Eye ; drug effects ; Irritants ; toxicity ; Rabbits ; Toxicity Tests ; methods