Objective: To apply PS-T in di?erent phases of carcinoma formation and development, and research the mechanism of anti-carcinoma of PS-T in the cytological level. Methods: N-nitrosodiethylamine ...Objective: To apply PS-T in di?erent phases of carcinoma formation and development, and research the mechanism of anti-carcinoma of PS-T in the cytological level. Methods: N-nitrosodiethylamine (DENA) and CCl4 were applied jointly to duplicate the rat hepatocirrhosis and hepatic cancer model. The rats were divided into 7 groups and were administrated via nasal-stomach tube with PS-T in di?erent phases to interfere the cancer genesis and development. All the rats were killed in 20 weeks for pathological observation. Results: The loss of body weight of rats slowed down in the PS-T-treated group, and the carcinogenesis rate was signi?cantly decreased correspondingly. PS-T could also inhibit the carcinogenesis by supressing the hepatocirrhosis, which showed the positive correlation between the curative e?ect and the curative period. Conclusion: Application of PS-T during cancer induction showed a signi?cant e?ect on preventing and supressing cancer. PS-T might be an ideal drug for clinical anti-cancer therapy. And it will be a main drug in both combined and single treatments for tumor.展开更多
Aim To investigate the anti-atherosclerotic mechanisms of the novel compoundpivanampeta in the early and later stages of atherosclerosis evolution. Methods Rats or rabbits wererandomly assigned to the control, the mod...Aim To investigate the anti-atherosclerotic mechanisms of the novel compoundpivanampeta in the early and later stages of atherosclerosis evolution. Methods Rats or rabbits wererandomly assigned to the control, the model and the pivanampeta-treated groups. The rats or rabbitsin the model group and the pivanampeta-treated group were fed with hypercholesterol diet. Thecarotids of rabbits were cut into pieces and stained with HE. The rat or rabbit serum levels of TC,LDL-CHO, HDL-CHO, IL-8, ET-1, PGI_2, TXA_2, and NO were assayed. The expressions of MCP-1 and IL-8mRNA on rabbit carotid were determined by semi-quantitative RT-PCR. Results Pivanampeta exerted aninhibitory effect on TXA_2 formation without PGI_2 production in the early and later stages ofatherosclerosis. The significantly increased release of NO and the decreased release of IL-8 in theanimals in pivanampeta-treated group were both detected in the rat atherosclerosis model. In therabbit atherosclerosis model the expressions of IL-8 and MCP-1 mRNA in pivanampeta-treated groupwere decreased significantly. However, the treatment with pivanampeta had no effect on the levels ofplasma cholesterol, MDA and SOD. Conclusion The increase of serum NO contents and the decrease ofplasma TXA_2 level, as well as its inhibition of expression of IL-8 and MCP-1 are probably involvedin the mechanisms underlying the anti-atherosclerotic effects of pivanampeta.展开更多
A useful helicobacter pylori-induced gastritis model using BALB/c mice was established for mimicking of human gastritis induced by Helicobacter pylori (H. pylori). The H. pylori isolates were obtained freshly from a...A useful helicobacter pylori-induced gastritis model using BALB/c mice was established for mimicking of human gastritis induced by Helicobacter pylori (H. pylori). The H. pylori isolates were obtained freshly from a human complex ulcer patient. BALB/c mice were fasted for 24 h and then 0.25 mL of 0.2 mol·L -1 NaHCO 3 was administered after by gavage to each mouse and 0.5 mL of 10 9 colonies formation unit per milliliter (CFU/mL) of H. pylori was administered 15 min. On the 3 rd day and 5 th day, the H. pylori inoculations were repeated. The inoculated mice were sacrificed in batch on the 5 th day, in the 2 nd week, 3 rd week and 4 th week. The gastric mucous membrane near pyloric portion was removed, treated and then cultured under microaerobic condition for detection of H.pylori. The remainders of the gastric membrane were fixed by 10% formaldehyde solution for pathological detection. The results showed that the H. pylori could be separated from the gastric membranes of inoculated mice. Obvious invasion of inflammatory cells in the gastric membranes of inoculated mice could be observed from pathological sections. It can be concluded that the inoculating fresh human H. pylori isolates can produce mouse gastritis. This model of BALB/c mice can be used for evaluating the therapeutic agents for the treatment of gastritis induced by H. pylori.展开更多
The retroviral vector (RCAS) has been widely used in avian system to study development and diseases, but is not suitable for mammals which do not produce the retrovirus receptor TVA. In this review, we trace the cur...The retroviral vector (RCAS) has been widely used in avian system to study development and diseases, but is not suitable for mammals which do not produce the retrovirus receptor TVA. In this review, we trace the current uses of RCAS-TVA approach in mammalian system with improved strategies, including generation of tv-a transgenic mice, use of soluble TVA receptor and retroviral receptor-ligand fusion proteins, improvement of RCAS vectors, and compare a series of mammalian models in variant studies of gene function, development, oncogenesis and gene therapy. All those studies demonstrate that the RCAS-TVA based mammalian models are powerful tools for understanding the mechanisms and target treating of human diseases.展开更多
The Mg-Ni hydride was prepared by hydriding combustion synthesis under a high magnetic field. The dehydriding kinetics of the hydrides was measured under the isothermal and non-isothermal conditions. A model was appli...The Mg-Ni hydride was prepared by hydriding combustion synthesis under a high magnetic field. The dehydriding kinetics of the hydrides was measured under the isothermal and non-isothermal conditions. A model was applied to analyzing the kinetics behavior of Mg-Ni hydride. The calculation results show that the theoretical value and the experimental data can reach a good agreement, especially in the case of non-isothermal dehydriding. The rate-controlling step is the diffusion of hydrogen atoms in the solid solution. The sample prepared under magnetic field of 6 T under the isothermal condition can reach the best performance. The similar tendency was observed under the non-isothermal condition and the reason was discussed.展开更多
Objective: To survey the effects of inhaled heparin on airway inflammation inguinea pigs with asthma and investigate the possible mechanism of inhaled heparin in the treatmentof asthma. Methods: The asthma in guinea p...Objective: To survey the effects of inhaled heparin on airway inflammation inguinea pigs with asthma and investigate the possible mechanism of inhaled heparin in the treatmentof asthma. Methods: The asthma in guinea pigs induced by ovalbumin was treated with inhaled heparin.The changes of cellularities in bronchoalveolar lavage (BAL) fluid and the airway walls wereexamined. Histologic examinations were also done in the guinea pig controls. Results: The number ofeosinophils, lymphocytes, and ciliated epithelial cells in the BAL fluid from the group treated withheparin was significantly lower than that of the group of asthma controls (P<0.01). Within theairway watts of the heparin treated group, the eosinophil infiltration was less prominent than thatof the group of asthma controls (P<0.001) and the number of mast cell was significantly higher thanthat of the group of asthma controls (P<0.01). Histologic examination showed that airway damages inthe heparin treated group were mild. Conclusion: Heparin can inhibit airway inflammation andalleviate airway damage in guinea pigs with asthma.展开更多
Objective: To study the pharmacokinetics of native r SAK in rabbit's femoral artery thrombosis model, the “lytic circle' method was used to determine plasma levels of r SAK. Methods: Thirty New Zealand rabb...Objective: To study the pharmacokinetics of native r SAK in rabbit's femoral artery thrombosis model, the “lytic circle' method was used to determine plasma levels of r SAK. Methods: Thirty New Zealand rabbits were randomly assigned to the control (saline 10 ml, 30 min), r SAK low dose (0.25 mg/kg, 30 min), medial dose (0.50 mg/kg, 30 min), high dose (1.00 mg/kg, 30 min), single bolus (0.50 mg/kg, 2 min) and conjunctive therapy (initiated with heparin 200 U/kg, followed by infusion of r SAK 0.50 mg/kg for 30 min, and subsequently infused heparin 50 U/(kg·h) to endpoint) groups. The right femoral artery thrombosis model in rabbit was made by balloon injury, then the thrombolytic agents were infused through parallel ear vein and the blood samples were collected pre thrombolysis and at different time post thrombolysis to determine the plasma levels of r SAK by “lytic circle' method, the plasma levels of r SAK were processed by pharmacokinetic computing procedure to fit the model. Results: The plasma levels of r SAK and the diameters of lytic circles showed a pretty good linear correlation under the scope of 2.0×10 4 2.0×10 6 U/L, and the averaged recycle rate was (96.05±11.35)%(RSD =±11.82%).All peak concentration time in each infusion group was 30 min, and the peak concentrations positively correlated with the doses administrated in infusion groups(r=0.999 98, P <0.000 1). In single bolus group, Peak concentration time was 2 min, and the peak concentration reached (5.16±1.02) mg/L, which was significant higher than that in the same dose r SAK infusion group ( P <0.01). In conjunctive therapy group, the peak concentration showed no significant difference from that in the same dose r SAK infusion group ( P >0.05). The plasma levels of r SAK fit in two compartment model as processed by pharmacokinetic computing procedure in each group. Conclusion: The “lytic circle' method is a simple, practical and reliable method to determine the plasma level of r SAK, and the pharmacokinetics of native r SAK infusion fits in two compartment model in rabbit's femoral artery thrombosis model.展开更多
Aim To investigate the effects of FDP on different liver injury models to explore the possibility of FDP used as an oral liver protective agent. Methods Chronic liver injury model in rats was induced by carbon tetrach...Aim To investigate the effects of FDP on different liver injury models to explore the possibility of FDP used as an oral liver protective agent. Methods Chronic liver injury model in rats was induced by carbon tetrachloride ( CCl4 ) ; Acute liver injury model in mice was induced by aminogalactose (GAIN) or lipopolysaccharide (LPS). Results In CCl4-induced chronic liver injury model, FDP (1 , 4 g·kg^-1·d^-1, q.d., for 10 weeks) significantly lowered ALT, AST,γ-glutamyl transpeptidase (γ-GT), alkaline phosphatase (ALP), and total bilirubin (T-BIL) in serum compared with vehicle; simultaneously it evidently elevated abnormal total protein (TP), albumin (ALB) and total cholesterol ( T-CHO ) levels in serum; it also dose-dependently reduced hydroxyproline contents in hepatic tissue. 4 g·kg^-1·d^-1 of FDP apparently decreased incidence of hepatic cirrhosis, and alleviated pathological changes of liver tissue. In GaiN-induced model, 1.0 - 4. 0 g·kg^-1·d^-1 of FDP ( bid, for 3 d ) significantly lowered alanine aminotransferase ( ALT ) and aspartate aminotransferase ( AST ) levels in serum ; it also decreased liver coefficient. 4. 0 g·kg^-1·d^-1 of FDP significantly alleviated pathological changes of cell ultra-structures. In LPS-induced model, only high dose of FDP (4. 0 g·kg^-1·d^-1, bid, for 12 d) significantly decreased ALT level in serum. Conclusion This study first demonstrated the protective effect of oral FDP on chronic liver injury caused by CCl4, and confirmed its effect on acute liver injury at the same time, suggesting that Long-term oral FDP is efficacious against liver injury induced by different factors and can be used as an oral liver protective agent in clinic.展开更多
Objective: To observe human to mouse one way mixed lymphocyte(MLC); And to set up the xeno-grats verse host disease Xeno-graft host disease(XGVHD) model,probing its immunologic mechamism.Methods: Mouse splenic lympho...Objective: To observe human to mouse one way mixed lymphocyte(MLC); And to set up the xeno-grats verse host disease Xeno-graft host disease(XGVHD) model,probing its immunologic mechamism.Methods: Mouse splenic lymphocyte were collected in asepsis and treated by mitomycin as activating cell. Human Peripheral blood lymphocytes (hPBL)were separated and gathered as reacting cell; Mouse splenic lymphocyte and hPBL were mixed to incubate for a week. Destroying recipient (mouse) immune system by total body irradiation (TBI) and intraperitoneal injecting CTX、MTX; Separating and collecting hPBL; Injecting hPBL to mouse by caudal vein. Results; ①HPBL in the experiment groups(mixed mouse lymphocyte) proliferated obviously, the amount of 3H-TdR in corporation increased evidently(P<0.05); The mean percentage of CD 4、CD 8、IgG 、IgM positive cells rose markedly. ②Experiment groups,the hPBL were found in the spleen and kidney tissue, fas protein expressing, we occasionally discovered and apoptosis cells.Conclusion: The human to mouse one-way MLC has obvious lymphocyte proliferation. By these means,we succeed in inducing XGVHD and setting up a XGVHD model.展开更多
Methacrylic acid was used together with a molecular imprinting technique to modify chitosan. In addition, the adsorption kinetics and adsorption isotherms were recorded and the results were analyzed to investigate rep...Methacrylic acid was used together with a molecular imprinting technique to modify chitosan. In addition, the adsorption kinetics and adsorption isotherms were recorded and the results were analyzed to investigate reparative adsorption for Cr(VI) from the polluted Xiangjiang River water. A comparative X-ray analysis shows that the degree of crystallization in the imprinted polymer was significantly weakened, the area of the non-crystalline region was larger. There were more adsorption sites in the imprinted polymer, and the adsorption capacity towards Cr(VI) was increased. The adsorption capacity of the imprinted polymer towards Cr(VI) increased with time and reaches saturation after 8 h. The optimal adsorption time was 4-8 h after the adsorption starting and the optimal pH value for the solution was in the range of 4.5-7.5. When the chitosan reaches saturation, the adsorption capacity achieves a state of equilibrium, and the maximum Cr(VI) extraction rate reaches 33.7%. Moreover, the adsorption capacity of the imprinted polymer towards Cr(VI) increases with increasing chitosan concentration. In this situation, the Cr(VI) extraction rate shows little variation, and the maximum removal rate can reach 98.3%. Furthermore, the Cr(VI) extraction rate increases with an increase in the degree of deacetylation in the chatoyant and chitosan, with the best adsorption effect corresponding to 90% deacetylation. Fitting the adsorption data to the quasi first- and second-order kinetic models yields correlation coefficients of 0.9013 and 0.9875, respectively. The corresponding rate constants for the two models are 0.0091 min-1 and 7.129 g/(mg.min), respectively. Hence, the adsorption using Cr(VI)-imprinted chitosan is more consistent with the second-order kinetics. Comparing the data to Freundlich and Langrnuir adsorption isotherms shows that the latter has a better linear fit and a maximum adsorption capacity of 15.784 mg/g.展开更多
Active shape models (ASM), consisting of a shape model and a local gray-level appearance model, can be used to locate the objects in images. In original ASM scheme, the model of object′s gray-level variations is base...Active shape models (ASM), consisting of a shape model and a local gray-level appearance model, can be used to locate the objects in images. In original ASM scheme, the model of object′s gray-level variations is based on the assumption of one-dimensional sampling and searching method. In this work a new way to model the gray-level appearance of the objects is explored, using a two-dimensional sampling and searching technique in a rectangular area around each landmark of object shape. The ASM based on this improvement is compared with the original ASM on an identical medical image set for task of spine localization. Experiments demonstrate that the method produces significantly fast, effective, accurate results for spine localization in medical images.展开更多
AIM To investigate the chemopreventive effect of sulindac, one of the nonstroidal anti inflammatory drugs (NSAIDs), on the growth of N methyl N nitrosourea (MNU) induced mouse colonic tumors.
The nonlinear mixed-effects model with stochastic differential equations (SDEs) is used to model the population pharmacokinetic (PPK) data that are extended from ordinary differential equations (ODEs) by adding ...The nonlinear mixed-effects model with stochastic differential equations (SDEs) is used to model the population pharmacokinetic (PPK) data that are extended from ordinary differential equations (ODEs) by adding a stochastic term to the state equation. Compared with the ODEs, the SDEs can model correlated residuals which are ubiquitous in actual pharmacokinetic problems. The Bayesian estimation is provided for nonlinear mixed-effects models based on stochastic differential equations. Combining the Gibbs and the Metropolis-Hastings algorithms, the population and individual parameter values are given through the parameter posterior predictive distributions. The analysis and simulation results show that the performance of the Bayesian estimation for mixed-effects SDEs model and analysis of population pharmacokinetic data is reliable. The results suggest that the proposed method is feasible for population pharmacokinetic data.展开更多
AIM:Irritable bowel syndrome(IBS)is a functional bowel disorder characterized by visceral hypersensitivity and altered bowel motility.There is increasing evidence suggesting the role of inflammation in the pathogenesi...AIM:Irritable bowel syndrome(IBS)is a functional bowel disorder characterized by visceral hypersensitivity and altered bowel motility.There is increasing evidence suggesting the role of inflammation in the pathogenesis of IBS,which addresses the possibility that formerly established rat model of colitis could be used as an IBS model after the inflammation subsided. METHODS:Colitis was induced by intracolonic instillation of 4% acetic acid in male Sprague-Dawley rats.The extent of inflammation was assessed by histological examination and myeloperoxidase(MPO)activity assay.After subsidence of colitis,the rats were subjected to rectal distension and restraint stress,then the abdominal withdrawal reflex and the number of stress-induced fecal output were measured, respectively. RESULTS:At 2 days post-induction of colitis,the colon showed characteristic inflammatory changes in histology and 8-fold increase in MPO activity.At 7 days post-induction of colitis,the histological features and MPO activity returned to normal.The rats at 7 days post-induction of colitis showed hypersensitive response to rectal distension without an accompaning change in rectal compliance,and defecated more stools than control animals when under stress.CONCLUSION: These results concur largely with the characteristic features of IBS, visceral hypersensitivity and altered defecation pattern in the absence of detectable disease, suggesting that this animal model is a methodologically convenient and useful model for studying a subset of IBS.展开更多
This review describes the woodchuck and the woodchuck hepatitis virus (WHV) as an animal model for pathogenesis and therapy of chronic hepatitis B virus (HBV) infection and disease in humans. The establishment of wood...This review describes the woodchuck and the woodchuck hepatitis virus (WHV) as an animal model for pathogenesis and therapy of chronic hepatitis B virus (HBV) infection and disease in humans. The establishment of woodchuck breeding colonies, and use of laboratory-reared woodchucks infected with defined WHV inocula, have enhanced our understanding of the virology and immunology of HBV infection and disease pathogenesis, including major sequelae like chronic hepatitis and hepatocellular carcinoma. The role of persistent WHV infection and of viral load on the natural history of infection and disease progression has been firmly established along the way. More recently, the model has shed new light on the role of host immune responses in these natural processes, and on how the immune system of the chronic carrier can be manipulated therapeutically to reduce or delay serious disease sequelae through induction of the recovery phenotype. The woodchuck is an outbred species and is not well defined immunologically due to a limitation of available host markers. However, the recent development of several key host response assays for woodchucks provides experimental opportunities for further mechanistic studies of outcome predictors in neonatal- and adult-acquired infections. Understanding the virological and immunological mechanisms responsible for resolution of self-limited infection, andfor the onset and maintenance of chronic infection, will greatly facilitate the development of successful strategies for the therapeutic eradication of established chronic HBV infection. Likewise, the results of drug efficacy and toxicity studies in the chronic carrier woodchucks are predictive for responses of patients chronically infected with HBV. Therefore, chronic WHV carrier woodchucks provide a well-characterized mammalian model for preclinical evaluation of the safety and efficacy of drug candidates, experimental therapeutic vaccines, and immunomodulators for the treatment and prevention of HBV disease sequelae.展开更多
Human mesenchymal stem cells (hMSCs) can home to tumor sites and inhibit the growth of tumor cells. Little is known about the underlying molecular mechanisms that link hMSCs to the targeted inhibition of tumor cells...Human mesenchymal stem cells (hMSCs) can home to tumor sites and inhibit the growth of tumor cells. Little is known about the underlying molecular mechanisms that link hMSCs to the targeted inhibition of tumor cells. In this study, we investigated the effects of hMSCs on two human hepatoma cell lines (H7402 and HepG2) using an animal transplantation model, a co-culture system and conditioned media from hMSCs. Animal transplantation studies showed that the latent time for tumor formation was prolonged and that the tumor size was smaller when SCID mice were injected with H7402 cells and an equal number of Z3 hMSCs. When co-cultured with Z3 cells, H7402 cell proliferation decreased, apoptosis increased, and the expression of Bcl-2, c-Myc, proliferating cell nuclear antigen (PCNA) and survivin was downregulated. After treatment with conditioned media derived from Z3 hMSC cultures, H4702 cells showed decreased colony-forming ability and decreased proliferation. Immunoblot analysis showed that β-catenin, Bcl-2, c-Myc, PCNA and survivin expression was downregulated in H7402 and HepG2 cells. Taken together, our findings demonstrate that hMSCs inhibit the malignant phenotypes of the H7402 and HepG2 human liver cancer cell lines, which include proliferation, colony-forming ability and oncogene expression both in vitro and in vivo. Furthermore, our studies provide evidence that the Wnt signaling pathway may have a role in hMSC-mediated targeting and tumor cell inhibition.展开更多
AIM: To study the capacity of bone marrow mesenchymal stem cells (BM-MSCs) trans-differentiating into islet-like cells and to observe the effect of portal vein transplantation of islet-like cells in the treatment of s...AIM: To study the capacity of bone marrow mesenchymal stem cells (BM-MSCs) trans-differentiating into islet-like cells and to observe the effect of portal vein transplantation of islet-like cells in the treatment of streptozotocin-induced diabetic rat. METHODS: BM-MSCs were isolated from SD rats and induced to differentiate into islet-like cells under defined conditions. Differentiation was evaluated with electron microscopy, RT-PCR, immunofluorescence and flow cytometry. insulin release after glucose challenge was tested with ELiSA. Then allogeneic islet-like cells were transplanted into diabetic rats via portal vein. Blood glucose levels were monitored and islet hormones were detected in the liver and pancreas of the recipient by immunohistochemistry. RESULTS: BM-MSCs were spheroid adherent monolayers with high CD90, CD29 and very low CD45 expression. Typical islet-like cells clusters were formed after induction. Electron microscopy revealed that secretory granules were densely packed within the cytoplasm of the differentiated cells. The spheroid cells expressed islet related genes and hormones. The insulin-positive cells accounted for 19.8% and mean fluorescence intensity increased by 2.6 fold after induction. The cells secreted a small amount of insulin that was increased 1.5 fold after glucose challenge. After transplantation, islet-like cells could locate in the liver expressing islet hormones and lower the glucose levels of diabetic rats during d 6 to d 20.CONCLUSION: Rat BM-MSCs could be transdifferentiated into islet-like cells in vitro . Portal vein transplantation of islet-like cells could alleviate the hyperglycemia of diabetic rats.展开更多
AIM: To establish an ideal model of multiple organ injury of rats with severe acute pancreatitis (SAP).METHODS: SAP models were induced by retrograde injection of 0.1 mL/100 g 3.5% sodium taurocholate into the bil...AIM: To establish an ideal model of multiple organ injury of rats with severe acute pancreatitis (SAP).METHODS: SAP models were induced by retrograde injection of 0.1 mL/100 g 3.5% sodium taurocholate into the biliopancreatic duct of Sprague-Dawley rats. The plasma and samples of multiple organ tissues of rats were collected at 3, 6 and 12 h after modeling. The ascites volume, ascites/body weight ratio, and contents of amylase, endotoxin, endothelin-1 (ET-1), nitrogen monoxidum (NO), phospholipase A2 (PLA2), tumor necrosis factor-α (TNF-α), interleukin-6 (IL-6) in plasma were determined. The histological changes of multiple organs were observed under light microscope.RESULTS: The ascites volume, ascites/body weight ratio, and contents of various inflammatory mediators in blood were higher in the model group than in the sham operation group at all time points [2.38 (1.10), 2.58 (0.70), 2.54 (0.71) vs 0.20 (0.04), 0.30 (0.30), 0.22 (0.10) at 3, 6 and 12 h in ascites/body weight ratio; 1582 (284), 1769 (362), 1618 (302) (U/L) vs 5303 (1373), 6276 (1029), 7538 (2934) (U/L) at 3, 6 and 12 h in Amylase; 0.016 (0.005), 0.016 (0.010), 0.014 (0.015) (EU/mL) vs 0,053 (0.029), 0.059 (0.037), 0.060 (0.022) (EU/mL) at 3, 6 and 12 h in Endotoxin; 3.900 (3.200), 4.000 (1.700), 5.300 (3.000) (ng/L) vs 41.438 (37.721), 92.151 (23.119), 65.016 (26.806) (ng/L) at 3, 6 and 12 h in TNF-α, all P 〈 0.01]. Visible congestion, edema and lamellar necrosis and massive leukocytic infiltration were found in the pancreas of rats of model group. There were also pathological changes of lung, liver, kidney, ileum, lymphonode, thymus, myocardium and brain.CONCLUSION: This rat model features reliability, convenience and a high achievement ratio. Complicated with multiple organ injury, it is an ideal animal model of SAR展开更多
Nonalcoholic fatty liver disease(NAFLD) is a condition in which excess fat accumulates in the liver of a patient without a history of alcohol abuse.Nonalcoholic steatohepatitis(NASH),a severe form of NAFLD,can progres...Nonalcoholic fatty liver disease(NAFLD) is a condition in which excess fat accumulates in the liver of a patient without a history of alcohol abuse.Nonalcoholic steatohepatitis(NASH),a severe form of NAFLD,can progress to liver cirrhosis and hepatocellular carcinoma.NAFLD is regarded as a hepatic manifestation of metabolic syndrome and incidence has been increasing worldwide in line with the increased prevalence of obesity,type 2 diabetes,and hyperlipemia.Animal models of NAFLD/NASH give crucial information,not only in elucidating pathogenesis of NAFLD/NASH but also in examining therapeutic effects of various agents.An ideal model of NAFLD/NASH should correctly reflect both hepatic histopathology and pathophysiology of human NAFLD/NASH.Animal models of NAFLD/NASH are divided into genetic,dietary,and combination models.In this paper,we review commonly used animal models of NAFLD/NASH referring to their advantages and disadvantages.展开更多
文摘Objective: To apply PS-T in di?erent phases of carcinoma formation and development, and research the mechanism of anti-carcinoma of PS-T in the cytological level. Methods: N-nitrosodiethylamine (DENA) and CCl4 were applied jointly to duplicate the rat hepatocirrhosis and hepatic cancer model. The rats were divided into 7 groups and were administrated via nasal-stomach tube with PS-T in di?erent phases to interfere the cancer genesis and development. All the rats were killed in 20 weeks for pathological observation. Results: The loss of body weight of rats slowed down in the PS-T-treated group, and the carcinogenesis rate was signi?cantly decreased correspondingly. PS-T could also inhibit the carcinogenesis by supressing the hepatocirrhosis, which showed the positive correlation between the curative e?ect and the curative period. Conclusion: Application of PS-T during cancer induction showed a signi?cant e?ect on preventing and supressing cancer. PS-T might be an ideal drug for clinical anti-cancer therapy. And it will be a main drug in both combined and single treatments for tumor.
文摘Aim To investigate the anti-atherosclerotic mechanisms of the novel compoundpivanampeta in the early and later stages of atherosclerosis evolution. Methods Rats or rabbits wererandomly assigned to the control, the model and the pivanampeta-treated groups. The rats or rabbitsin the model group and the pivanampeta-treated group were fed with hypercholesterol diet. Thecarotids of rabbits were cut into pieces and stained with HE. The rat or rabbit serum levels of TC,LDL-CHO, HDL-CHO, IL-8, ET-1, PGI_2, TXA_2, and NO were assayed. The expressions of MCP-1 and IL-8mRNA on rabbit carotid were determined by semi-quantitative RT-PCR. Results Pivanampeta exerted aninhibitory effect on TXA_2 formation without PGI_2 production in the early and later stages ofatherosclerosis. The significantly increased release of NO and the decreased release of IL-8 in theanimals in pivanampeta-treated group were both detected in the rat atherosclerosis model. In therabbit atherosclerosis model the expressions of IL-8 and MCP-1 mRNA in pivanampeta-treated groupwere decreased significantly. However, the treatment with pivanampeta had no effect on the levels ofplasma cholesterol, MDA and SOD. Conclusion The increase of serum NO contents and the decrease ofplasma TXA_2 level, as well as its inhibition of expression of IL-8 and MCP-1 are probably involvedin the mechanisms underlying the anti-atherosclerotic effects of pivanampeta.
文摘A useful helicobacter pylori-induced gastritis model using BALB/c mice was established for mimicking of human gastritis induced by Helicobacter pylori (H. pylori). The H. pylori isolates were obtained freshly from a human complex ulcer patient. BALB/c mice were fasted for 24 h and then 0.25 mL of 0.2 mol·L -1 NaHCO 3 was administered after by gavage to each mouse and 0.5 mL of 10 9 colonies formation unit per milliliter (CFU/mL) of H. pylori was administered 15 min. On the 3 rd day and 5 th day, the H. pylori inoculations were repeated. The inoculated mice were sacrificed in batch on the 5 th day, in the 2 nd week, 3 rd week and 4 th week. The gastric mucous membrane near pyloric portion was removed, treated and then cultured under microaerobic condition for detection of H.pylori. The remainders of the gastric membrane were fixed by 10% formaldehyde solution for pathological detection. The results showed that the H. pylori could be separated from the gastric membranes of inoculated mice. Obvious invasion of inflammatory cells in the gastric membranes of inoculated mice could be observed from pathological sections. It can be concluded that the inoculating fresh human H. pylori isolates can produce mouse gastritis. This model of BALB/c mice can be used for evaluating the therapeutic agents for the treatment of gastritis induced by H. pylori.
文摘The retroviral vector (RCAS) has been widely used in avian system to study development and diseases, but is not suitable for mammals which do not produce the retrovirus receptor TVA. In this review, we trace the current uses of RCAS-TVA approach in mammalian system with improved strategies, including generation of tv-a transgenic mice, use of soluble TVA receptor and retroviral receptor-ligand fusion proteins, improvement of RCAS vectors, and compare a series of mammalian models in variant studies of gene function, development, oncogenesis and gene therapy. All those studies demonstrate that the RCAS-TVA based mammalian models are powerful tools for understanding the mechanisms and target treating of human diseases.
基金Project(51464008) supported by the National Natural Science Foundation of ChinaProject(KY[2012]004) supported by the Key Laboratory Item of Education Office in Guizhou Province,China
文摘The Mg-Ni hydride was prepared by hydriding combustion synthesis under a high magnetic field. The dehydriding kinetics of the hydrides was measured under the isothermal and non-isothermal conditions. A model was applied to analyzing the kinetics behavior of Mg-Ni hydride. The calculation results show that the theoretical value and the experimental data can reach a good agreement, especially in the case of non-isothermal dehydriding. The rate-controlling step is the diffusion of hydrogen atoms in the solid solution. The sample prepared under magnetic field of 6 T under the isothermal condition can reach the best performance. The similar tendency was observed under the non-isothermal condition and the reason was discussed.
文摘Objective: To survey the effects of inhaled heparin on airway inflammation inguinea pigs with asthma and investigate the possible mechanism of inhaled heparin in the treatmentof asthma. Methods: The asthma in guinea pigs induced by ovalbumin was treated with inhaled heparin.The changes of cellularities in bronchoalveolar lavage (BAL) fluid and the airway walls wereexamined. Histologic examinations were also done in the guinea pig controls. Results: The number ofeosinophils, lymphocytes, and ciliated epithelial cells in the BAL fluid from the group treated withheparin was significantly lower than that of the group of asthma controls (P<0.01). Within theairway watts of the heparin treated group, the eosinophil infiltration was less prominent than thatof the group of asthma controls (P<0.001) and the number of mast cell was significantly higher thanthat of the group of asthma controls (P<0.01). Histologic examination showed that airway damages inthe heparin treated group were mild. Conclusion: Heparin can inhibit airway inflammation andalleviate airway damage in guinea pigs with asthma.
文摘Objective: To study the pharmacokinetics of native r SAK in rabbit's femoral artery thrombosis model, the “lytic circle' method was used to determine plasma levels of r SAK. Methods: Thirty New Zealand rabbits were randomly assigned to the control (saline 10 ml, 30 min), r SAK low dose (0.25 mg/kg, 30 min), medial dose (0.50 mg/kg, 30 min), high dose (1.00 mg/kg, 30 min), single bolus (0.50 mg/kg, 2 min) and conjunctive therapy (initiated with heparin 200 U/kg, followed by infusion of r SAK 0.50 mg/kg for 30 min, and subsequently infused heparin 50 U/(kg·h) to endpoint) groups. The right femoral artery thrombosis model in rabbit was made by balloon injury, then the thrombolytic agents were infused through parallel ear vein and the blood samples were collected pre thrombolysis and at different time post thrombolysis to determine the plasma levels of r SAK by “lytic circle' method, the plasma levels of r SAK were processed by pharmacokinetic computing procedure to fit the model. Results: The plasma levels of r SAK and the diameters of lytic circles showed a pretty good linear correlation under the scope of 2.0×10 4 2.0×10 6 U/L, and the averaged recycle rate was (96.05±11.35)%(RSD =±11.82%).All peak concentration time in each infusion group was 30 min, and the peak concentrations positively correlated with the doses administrated in infusion groups(r=0.999 98, P <0.000 1). In single bolus group, Peak concentration time was 2 min, and the peak concentration reached (5.16±1.02) mg/L, which was significant higher than that in the same dose r SAK infusion group ( P <0.01). In conjunctive therapy group, the peak concentration showed no significant difference from that in the same dose r SAK infusion group ( P >0.05). The plasma levels of r SAK fit in two compartment model as processed by pharmacokinetic computing procedure in each group. Conclusion: The “lytic circle' method is a simple, practical and reliable method to determine the plasma level of r SAK, and the pharmacokinetics of native r SAK infusion fits in two compartment model in rabbit's femoral artery thrombosis model.
文摘Aim To investigate the effects of FDP on different liver injury models to explore the possibility of FDP used as an oral liver protective agent. Methods Chronic liver injury model in rats was induced by carbon tetrachloride ( CCl4 ) ; Acute liver injury model in mice was induced by aminogalactose (GAIN) or lipopolysaccharide (LPS). Results In CCl4-induced chronic liver injury model, FDP (1 , 4 g·kg^-1·d^-1, q.d., for 10 weeks) significantly lowered ALT, AST,γ-glutamyl transpeptidase (γ-GT), alkaline phosphatase (ALP), and total bilirubin (T-BIL) in serum compared with vehicle; simultaneously it evidently elevated abnormal total protein (TP), albumin (ALB) and total cholesterol ( T-CHO ) levels in serum; it also dose-dependently reduced hydroxyproline contents in hepatic tissue. 4 g·kg^-1·d^-1 of FDP apparently decreased incidence of hepatic cirrhosis, and alleviated pathological changes of liver tissue. In GaiN-induced model, 1.0 - 4. 0 g·kg^-1·d^-1 of FDP ( bid, for 3 d ) significantly lowered alanine aminotransferase ( ALT ) and aspartate aminotransferase ( AST ) levels in serum ; it also decreased liver coefficient. 4. 0 g·kg^-1·d^-1 of FDP significantly alleviated pathological changes of cell ultra-structures. In LPS-induced model, only high dose of FDP (4. 0 g·kg^-1·d^-1, bid, for 12 d) significantly decreased ALT level in serum. Conclusion This study first demonstrated the protective effect of oral FDP on chronic liver injury caused by CCl4, and confirmed its effect on acute liver injury at the same time, suggesting that Long-term oral FDP is efficacious against liver injury induced by different factors and can be used as an oral liver protective agent in clinic.
文摘Objective: To observe human to mouse one way mixed lymphocyte(MLC); And to set up the xeno-grats verse host disease Xeno-graft host disease(XGVHD) model,probing its immunologic mechamism.Methods: Mouse splenic lymphocyte were collected in asepsis and treated by mitomycin as activating cell. Human Peripheral blood lymphocytes (hPBL)were separated and gathered as reacting cell; Mouse splenic lymphocyte and hPBL were mixed to incubate for a week. Destroying recipient (mouse) immune system by total body irradiation (TBI) and intraperitoneal injecting CTX、MTX; Separating and collecting hPBL; Injecting hPBL to mouse by caudal vein. Results; ①HPBL in the experiment groups(mixed mouse lymphocyte) proliferated obviously, the amount of 3H-TdR in corporation increased evidently(P<0.05); The mean percentage of CD 4、CD 8、IgG 、IgM positive cells rose markedly. ②Experiment groups,the hPBL were found in the spleen and kidney tissue, fas protein expressing, we occasionally discovered and apoptosis cells.Conclusion: The human to mouse one-way MLC has obvious lymphocyte proliferation. By these means,we succeed in inducing XGVHD and setting up a XGVHD model.
基金Project(41271332)supported by the National Natural Science Foundation of ChinaProject(2010YBB186)supported by the Social Science Foundation of Hunan Province,Chian
文摘Methacrylic acid was used together with a molecular imprinting technique to modify chitosan. In addition, the adsorption kinetics and adsorption isotherms were recorded and the results were analyzed to investigate reparative adsorption for Cr(VI) from the polluted Xiangjiang River water. A comparative X-ray analysis shows that the degree of crystallization in the imprinted polymer was significantly weakened, the area of the non-crystalline region was larger. There were more adsorption sites in the imprinted polymer, and the adsorption capacity towards Cr(VI) was increased. The adsorption capacity of the imprinted polymer towards Cr(VI) increased with time and reaches saturation after 8 h. The optimal adsorption time was 4-8 h after the adsorption starting and the optimal pH value for the solution was in the range of 4.5-7.5. When the chitosan reaches saturation, the adsorption capacity achieves a state of equilibrium, and the maximum Cr(VI) extraction rate reaches 33.7%. Moreover, the adsorption capacity of the imprinted polymer towards Cr(VI) increases with increasing chitosan concentration. In this situation, the Cr(VI) extraction rate shows little variation, and the maximum removal rate can reach 98.3%. Furthermore, the Cr(VI) extraction rate increases with an increase in the degree of deacetylation in the chatoyant and chitosan, with the best adsorption effect corresponding to 90% deacetylation. Fitting the adsorption data to the quasi first- and second-order kinetic models yields correlation coefficients of 0.9013 and 0.9875, respectively. The corresponding rate constants for the two models are 0.0091 min-1 and 7.129 g/(mg.min), respectively. Hence, the adsorption using Cr(VI)-imprinted chitosan is more consistent with the second-order kinetics. Comparing the data to Freundlich and Langrnuir adsorption isotherms shows that the latter has a better linear fit and a maximum adsorption capacity of 15.784 mg/g.
文摘Active shape models (ASM), consisting of a shape model and a local gray-level appearance model, can be used to locate the objects in images. In original ASM scheme, the model of object′s gray-level variations is based on the assumption of one-dimensional sampling and searching method. In this work a new way to model the gray-level appearance of the objects is explored, using a two-dimensional sampling and searching technique in a rectangular area around each landmark of object shape. The ASM based on this improvement is compared with the original ASM on an identical medical image set for task of spine localization. Experiments demonstrate that the method produces significantly fast, effective, accurate results for spine localization in medical images.
文摘AIM To investigate the chemopreventive effect of sulindac, one of the nonstroidal anti inflammatory drugs (NSAIDs), on the growth of N methyl N nitrosourea (MNU) induced mouse colonic tumors.
基金The National Natural Science Foundation of China(No.11171065,81130068)the Natural Science Foundation of Jiangsu Province(No.BK2011058)the Fundamental Research Funds for the Central Universities(No.JKPZ2013015)
文摘The nonlinear mixed-effects model with stochastic differential equations (SDEs) is used to model the population pharmacokinetic (PPK) data that are extended from ordinary differential equations (ODEs) by adding a stochastic term to the state equation. Compared with the ODEs, the SDEs can model correlated residuals which are ubiquitous in actual pharmacokinetic problems. The Bayesian estimation is provided for nonlinear mixed-effects models based on stochastic differential equations. Combining the Gibbs and the Metropolis-Hastings algorithms, the population and individual parameter values are given through the parameter posterior predictive distributions. The analysis and simulation results show that the performance of the Bayesian estimation for mixed-effects SDEs model and analysis of population pharmacokinetic data is reliable. The results suggest that the proposed method is feasible for population pharmacokinetic data.
基金the Research Institute of Veterinary Science,College of Veterinary Medieine,Seoul National University
文摘AIM:Irritable bowel syndrome(IBS)is a functional bowel disorder characterized by visceral hypersensitivity and altered bowel motility.There is increasing evidence suggesting the role of inflammation in the pathogenesis of IBS,which addresses the possibility that formerly established rat model of colitis could be used as an IBS model after the inflammation subsided. METHODS:Colitis was induced by intracolonic instillation of 4% acetic acid in male Sprague-Dawley rats.The extent of inflammation was assessed by histological examination and myeloperoxidase(MPO)activity assay.After subsidence of colitis,the rats were subjected to rectal distension and restraint stress,then the abdominal withdrawal reflex and the number of stress-induced fecal output were measured, respectively. RESULTS:At 2 days post-induction of colitis,the colon showed characteristic inflammatory changes in histology and 8-fold increase in MPO activity.At 7 days post-induction of colitis,the histological features and MPO activity returned to normal.The rats at 7 days post-induction of colitis showed hypersensitive response to rectal distension without an accompaning change in rectal compliance,and defecated more stools than control animals when under stress.CONCLUSION: These results concur largely with the characteristic features of IBS, visceral hypersensitivity and altered defecation pattern in the absence of detectable disease, suggesting that this animal model is a methodologically convenient and useful model for studying a subset of IBS.
基金Supported by contract N01-AI-05399 to the College of Veterinary Medicine, Cornell University from the National Institute of Allergy and Infectious Diseases. PC and SM also have been supported by contract N01-AI-95390 to the Georgetown University Medical Center, Georgetown University from the National Institute of Allergy and Infectious Diseases
文摘This review describes the woodchuck and the woodchuck hepatitis virus (WHV) as an animal model for pathogenesis and therapy of chronic hepatitis B virus (HBV) infection and disease in humans. The establishment of woodchuck breeding colonies, and use of laboratory-reared woodchucks infected with defined WHV inocula, have enhanced our understanding of the virology and immunology of HBV infection and disease pathogenesis, including major sequelae like chronic hepatitis and hepatocellular carcinoma. The role of persistent WHV infection and of viral load on the natural history of infection and disease progression has been firmly established along the way. More recently, the model has shed new light on the role of host immune responses in these natural processes, and on how the immune system of the chronic carrier can be manipulated therapeutically to reduce or delay serious disease sequelae through induction of the recovery phenotype. The woodchuck is an outbred species and is not well defined immunologically due to a limitation of available host markers. However, the recent development of several key host response assays for woodchucks provides experimental opportunities for further mechanistic studies of outcome predictors in neonatal- and adult-acquired infections. Understanding the virological and immunological mechanisms responsible for resolution of self-limited infection, andfor the onset and maintenance of chronic infection, will greatly facilitate the development of successful strategies for the therapeutic eradication of established chronic HBV infection. Likewise, the results of drug efficacy and toxicity studies in the chronic carrier woodchucks are predictive for responses of patients chronically infected with HBV. Therefore, chronic WHV carrier woodchucks provide a well-characterized mammalian model for preclinical evaluation of the safety and efficacy of drug candidates, experimental therapeutic vaccines, and immunomodulators for the treatment and prevention of HBV disease sequelae.
基金This work was supported by grants from the National Basic Research Program of China (973 Program, No. 2007CB914800 to Xiaodong Zhang), National Natural Science Foundation of China (No. 30570698 to Xiaodong Zhang) and Tianjin Natural Scientific Foundation (No. 033801211 to Xiaodong Zhang).
文摘Human mesenchymal stem cells (hMSCs) can home to tumor sites and inhibit the growth of tumor cells. Little is known about the underlying molecular mechanisms that link hMSCs to the targeted inhibition of tumor cells. In this study, we investigated the effects of hMSCs on two human hepatoma cell lines (H7402 and HepG2) using an animal transplantation model, a co-culture system and conditioned media from hMSCs. Animal transplantation studies showed that the latent time for tumor formation was prolonged and that the tumor size was smaller when SCID mice were injected with H7402 cells and an equal number of Z3 hMSCs. When co-cultured with Z3 cells, H7402 cell proliferation decreased, apoptosis increased, and the expression of Bcl-2, c-Myc, proliferating cell nuclear antigen (PCNA) and survivin was downregulated. After treatment with conditioned media derived from Z3 hMSC cultures, H4702 cells showed decreased colony-forming ability and decreased proliferation. Immunoblot analysis showed that β-catenin, Bcl-2, c-Myc, PCNA and survivin expression was downregulated in H7402 and HepG2 cells. Taken together, our findings demonstrate that hMSCs inhibit the malignant phenotypes of the H7402 and HepG2 human liver cancer cell lines, which include proliferation, colony-forming ability and oncogene expression both in vitro and in vivo. Furthermore, our studies provide evidence that the Wnt signaling pathway may have a role in hMSC-mediated targeting and tumor cell inhibition.
基金Supported by Medical Key Subject grants (2001-34) from Jiangsu Province of China
文摘AIM: To study the capacity of bone marrow mesenchymal stem cells (BM-MSCs) trans-differentiating into islet-like cells and to observe the effect of portal vein transplantation of islet-like cells in the treatment of streptozotocin-induced diabetic rat. METHODS: BM-MSCs were isolated from SD rats and induced to differentiate into islet-like cells under defined conditions. Differentiation was evaluated with electron microscopy, RT-PCR, immunofluorescence and flow cytometry. insulin release after glucose challenge was tested with ELiSA. Then allogeneic islet-like cells were transplanted into diabetic rats via portal vein. Blood glucose levels were monitored and islet hormones were detected in the liver and pancreas of the recipient by immunohistochemistry. RESULTS: BM-MSCs were spheroid adherent monolayers with high CD90, CD29 and very low CD45 expression. Typical islet-like cells clusters were formed after induction. Electron microscopy revealed that secretory granules were densely packed within the cytoplasm of the differentiated cells. The spheroid cells expressed islet related genes and hormones. The insulin-positive cells accounted for 19.8% and mean fluorescence intensity increased by 2.6 fold after induction. The cells secreted a small amount of insulin that was increased 1.5 fold after glucose challenge. After transplantation, islet-like cells could locate in the liver expressing islet hormones and lower the glucose levels of diabetic rats during d 6 to d 20.CONCLUSION: Rat BM-MSCs could be transdifferentiated into islet-like cells in vitro . Portal vein transplantation of islet-like cells could alleviate the hyperglycemia of diabetic rats.
基金technological foundation project of Traditional Chinese Medicine Science of Zhejiang province, No. 2003C130 No. 2004C142+4 种基金foundation project for medical science and technology of Zhejiang provinc, No. 2003B134grave foundation project for technological and development of Hangzhou, No. 2003123B19intensive foundation project for technology of Hangzhou, No. 2004Z006foundation project for medical science and technology of Hangzhou, No. 2003A004foundation project for technology of Hangzhou, No. 2005224
文摘AIM: To establish an ideal model of multiple organ injury of rats with severe acute pancreatitis (SAP).METHODS: SAP models were induced by retrograde injection of 0.1 mL/100 g 3.5% sodium taurocholate into the biliopancreatic duct of Sprague-Dawley rats. The plasma and samples of multiple organ tissues of rats were collected at 3, 6 and 12 h after modeling. The ascites volume, ascites/body weight ratio, and contents of amylase, endotoxin, endothelin-1 (ET-1), nitrogen monoxidum (NO), phospholipase A2 (PLA2), tumor necrosis factor-α (TNF-α), interleukin-6 (IL-6) in plasma were determined. The histological changes of multiple organs were observed under light microscope.RESULTS: The ascites volume, ascites/body weight ratio, and contents of various inflammatory mediators in blood were higher in the model group than in the sham operation group at all time points [2.38 (1.10), 2.58 (0.70), 2.54 (0.71) vs 0.20 (0.04), 0.30 (0.30), 0.22 (0.10) at 3, 6 and 12 h in ascites/body weight ratio; 1582 (284), 1769 (362), 1618 (302) (U/L) vs 5303 (1373), 6276 (1029), 7538 (2934) (U/L) at 3, 6 and 12 h in Amylase; 0.016 (0.005), 0.016 (0.010), 0.014 (0.015) (EU/mL) vs 0,053 (0.029), 0.059 (0.037), 0.060 (0.022) (EU/mL) at 3, 6 and 12 h in Endotoxin; 3.900 (3.200), 4.000 (1.700), 5.300 (3.000) (ng/L) vs 41.438 (37.721), 92.151 (23.119), 65.016 (26.806) (ng/L) at 3, 6 and 12 h in TNF-α, all P 〈 0.01]. Visible congestion, edema and lamellar necrosis and massive leukocytic infiltration were found in the pancreas of rats of model group. There were also pathological changes of lung, liver, kidney, ileum, lymphonode, thymus, myocardium and brain.CONCLUSION: This rat model features reliability, convenience and a high achievement ratio. Complicated with multiple organ injury, it is an ideal animal model of SAR
文摘Nonalcoholic fatty liver disease(NAFLD) is a condition in which excess fat accumulates in the liver of a patient without a history of alcohol abuse.Nonalcoholic steatohepatitis(NASH),a severe form of NAFLD,can progress to liver cirrhosis and hepatocellular carcinoma.NAFLD is regarded as a hepatic manifestation of metabolic syndrome and incidence has been increasing worldwide in line with the increased prevalence of obesity,type 2 diabetes,and hyperlipemia.Animal models of NAFLD/NASH give crucial information,not only in elucidating pathogenesis of NAFLD/NASH but also in examining therapeutic effects of various agents.An ideal model of NAFLD/NASH should correctly reflect both hepatic histopathology and pathophysiology of human NAFLD/NASH.Animal models of NAFLD/NASH are divided into genetic,dietary,and combination models.In this paper,we review commonly used animal models of NAFLD/NASH referring to their advantages and disadvantages.