Objective To observe the sequence of fat deposit and its relationship with insulin resistance in SD rats fed by high fat diet.Methods Normal 8-week-old male SD rats were randomly divided into normal chow (NC,n=40)and high fat diet(HF,n=40)groups.Triglyceride(TG)in serum,liver and muscle were measured;glucose infusion rate(GIR)and the mRNA level of genes related to lipid metabolism in liver and muscle were determined in different stages.GIR was detected by eugiyeemic-hyperinsulinemic clamp for evaluating the insulin sensitivity.Gene expression was determined by real-time PCR.Results(1)As compared with NC group,serum TG was not increased after high fat feeding for4 and 8 weeks,it began to increase after 12 weeks [0.52(0.15-1.00) mmol/L vs O.31(0.09-0.53)retool/L, P0.05)in skeletal muscle.After 8 weeks,the expression of ACC1 in liver in HF group was increased by 20.6%,CPT-1 was decreased by 27.1%(P

OBJECTIVETo construct a eukaryotic expression vector containing aldehyde dehydrogenase-2 (ALDH2) gene and investigate the effects and its possible mechanisms of ALDH2 gene on cell proliferation and anti-oxidative damage in the K562 cells.

METHODSAn eukaryotic expression vector containing the ALDH2 gene cloned from human hepatocytes was constructed and transfected into K562 cells by liposome. RT-PCR and Western blot were used to evaluate the expression of ALDH2. MTT assay was used to check the cell proliferation and trypan blue exclusion to check K562 cells damage induced by hydrogen peroxide (H2O2). RT-PCR and fluorescence spectrophotometry were used to determine the expression of heme oxygenase-1 (HO-1) and the generation of intracellular reactive oxygen species (ROS) respectively.

RESULTSRT-PCR and Western blot analysis showed distinct higher ALDH2 protein expression in gene transfected group. The latter group had a higher cell proliferation (P < 0.05) and survival rate against H2O2 induced-oxidative damage, being increased by 7.8 times (IC(50) was 12.3 µmol/L and 1.4 µmol/L for K562-pcDNA3.1-ALDH2 and control cells, respectively, P < 0.01). The HO-1 mRNA expression and the generation of intracellular ROS were downregulated at a specific concentration of H2O2 in the ALDH2 gene transfected group.

CONCLUSIONALDH2 gene transfection can protect K562 cells against oxidative damage, and the downregulation of HO-1 expression and intracellular ROS may be involved in this process.

Aldehyde Dehydrogenase ; Apoptosis ; drug effects ; Cell Proliferation ; drug effects ; Humans ; Hydrogen Peroxide ; K562 Cells ; RNA, Messenger ; genetics ; Transfection

OBJECTIVETo investigate the effect of beta cell lipoapoptosis after long term high-fat feeding in rats, and to investigate the relationship between oxidative stress, gene expression and beta cell lipoapoptosis.

METHODSForty-one SD male rats were randomly divided into 2 groups: high-fat diet group (HF group) and control group (NC group). At the end of 28 weeks, the levels of malondialdehyde (MDA) and glutamylcysteinylglycine (GSH) in plasma and pancreatic tissue,the early-phase insulin secretion in beta cells, the beta cell apoptosis (TUNEL technology) and the uncoupling protein 2 (UCP2) gene expression in islets were measured.

RESULTThe concentrations of MDA both in plasma and pancreatic tissue were higher in HF group than those in NC group.In contrast, The contents of GSH both in plasma and pancreatic tissue were lower in HF group. Insulin secretion response to glucose load was significantly decreased in HF group (3.0 fold Compared with 5.7 fold, P<0.01). Blood glucose levels at 3 min, 5 min and 10 min during IVGTT were significantly higher in HF group than those in NC group (P<0.05). The frequency of beta cell apoptosis was increased by 40.0% in HF group (P<0.01). The gene expression of UCP2 in islets was increased by 22.4% in HF group (P<0.01).

CONCLUSIONThe frequency of beta cell apoptosis in high-fat feeding rats is affected by oxidative stress, which results in increasing UCP2 gene expression.

Animals ; Apoptosis ; physiology ; Dietary Fats ; administration & dosage ; Insulin-Secreting Cells ; metabolism ; pathology ; Ion Channels ; genetics ; metabolism ; Male ; Malondialdehyde ; metabolism ; Mitochondrial Proteins ; genetics ; metabolism ; Oxidative Stress ; physiology ; RNA, Messenger ; genetics ; metabolism ; Rats ; Rats, Sprague-Dawley ; Uncoupling Protein 2

BACKGROUNDCurrently it is unclear whether lipid accumulation occurs in a particular sequence and its relationship with whole body insulin resistance (IR). This study aimed to answer this question.

METHODSMale Sprague-Dawley (SD) rats were fed on a normal or a high-fat diet for 20 weeks. Serum triglycerides (TG), serum free fatty acids (FFA), fasting plasma glucose (FPG), and liver and skeletal muscle TG were measured. The glucose infusion rate (GIR) and mRNA levels of acetyl-CoA carboxylase (ACC) and carnitine palmitoyltransferase-1 (CPT-1) in the liver and skeletal muscle were determined at different stages.

RESULTSCompared with rats fed on the normal diet, serum FFA was not significantly increased in rats fed on the high-fat diet until 20 weeks. In contrast, liver TG was significantly increased by the high-fat diet by four weeks (20-fold; P < 0.01), and remained elevated until the end of the study. However, skeletal muscle TG was not significantly increased by the high-fat diet until 20 weeks (10.6-fold; P < 0.01), and neither was the FPG. The GIR was significantly reduced (1.6-fold; P < 0.01) by the high-fat diet after 8 weeks. The mRNA levels of ACC gradually increased over time and CPT-1 decreased over time, in both the liver and skeletal muscle in rats fed the high-fat diet.

CONCLUSIONSLipid accumulation in the liver occurs earlier than lipid accumulation in the skeletal muscle. Fatty liver may be one of the early markers of whole body IR. Changes in the gene expression levels of ACC and CPT-1 may have important roles in the process of IR development.

Acetyl-CoA Carboxylase ; genetics ; Animals ; Blood Glucose ; analysis ; Carnitine O-Palmitoyltransferase ; genetics ; Fatty Acids, Nonesterified ; blood ; Fatty Liver ; etiology ; Insulin Resistance ; Lipid Metabolism ; Liver ; metabolism ; Male ; Muscle, Skeletal ; metabolism ; RNA, Messenger ; analysis ; Rats ; Rats, Sprague-Dawley ; Triglycerides ; metabolism

To explore the clinical features, risk factors an d treatment of retinoic acid syndrome (RAS) in patients with acute promyelocytic leukemia (APL) treated with retinoic acid, the clinical and laboratory data of 11 APL patients with RAS were retrospectively analysed. The results showed that earlier and more common symptoms of RAS were successively dyspnea (11/11), fever (10/11) and hydrothorax (6/11). Higher WBC count (> or = 15.0 x 10(9)/L) in the course of treatment of all-trans retinoic acid susceptible to develop RAS (9/11). The RAS patients were treated with dexamethasone without discontinuing the treatment of retinoic acid, complete remission was achieved in 10 cases and one patient died from disseminated intravascular coagulation. It is concluded that the identification and dexamethasone treatment of RAS in earlier period are extremely important for obtaining better clinical curative effect, and it does not influence therapeutic effect of continuing application of retinoic acid.
Adolescent ; Adult ; Child ; Dyspnea ; etiology ; Female ; Fever ; etiology ; Humans ; Hydrothorax ; etiology ; Leukemia, Promyelocytic, Acute ; drug therapy ; Male ; Middle Aged ; Syndrome ; Tretinoin ; adverse effects

OBJECTIVETo compare the bidirectional effect of rhubarb total anthraquinone (TA) and total tannins (TT) on rats' liver.

METHODSOne hundred rats were randomly divided into 10 groups, i.e., the blank group, the model group, the blank + high dose TA group, the blank +low dose TA group, the blank + high dose TT group, the blank + low dose TT group, the model + high dose TA group, the model + low dose TA group, the model +high dose TT group, and the model + low dose TT group, 10 in each group. The carbon tetrachloride (CCI4) was used to prepare the acute liver injury rat model. TA and TT of rhubarb (at 5.40 g crude drugs/kg and 14.69 g crude drugs/kg) were intragastrically administrated to rats in all groups except the blank group and the model group, once daily for 6 successive days.The general state of rats, biochemical indices such as alanine aminotransferase (ALT), aspartate aminotransferase (AST), alkaline phosphatase (ALP), laminin (LN), hyaluronic acid (HA), transforming growth factor beta1 (TGF-beta1), as well pathological results of rat liver tissues. Finally the protection laws of TA and TT for rats' liver were analyzed using factor analysis.

RESULTSCompared with the blank control group, all biochemical indices increased in the blank group (P < 0.05, P < 0.01). HA also increased in the blank + high dose TA group; AST, ALT, and HA also increased in the blank +high dose TT group (P < 0.05). Compared with the model group, AST, ALT, ALP, HA, and TGF-beta1 significantly decreased in the model + low dose TA group, the model + high dose TA group, the model + low dose TT group (P < 0.05, P < 0.01). Serum AST, ALT, and ALP also decreased in the model + high dose TT group (P < 0.05, P < 0.01). Pathological results showed that mild swollen liver cells in the model + high dose TA group. Fatty degeneration and fragmental necrosis around the central veins occurred in the blank + high dose TA group. The pathological injury was inproved in the model +low dose TA group. Two common factors, liver fibrosis and liver cell injury, were extracted by using factor analysis. TA showed stronger improvement of the two common factors than TT.

CONCLUSIONSRhubarb TA and TT showed protective and harmful effects on rats' liver. At an equivalent dosage, TA had better liver protection than TT. High dose TT played a role in liver injury to some extent.

Animals ; Anthraquinones ; adverse effects ; pharmacology ; Carbon Tetrachloride ; toxicity ; Chemical and Drug Induced Liver Injury ; drug therapy ; pathology ; Dose-Response Relationship, Drug ; Female ; Liver ; drug effects ; Male ; Rats ; Rats, Sprague-Dawley ; Rheum ; chemistry ; Tannins ; adverse effects ; pharmacology

To investigate the effect of flavonoid compounds on vascular endothelial cells. Vascular endothelial cells were located between plasma and vascular tissue, and can complete the metabolic exchange of plasma and interstitial fluid, synthesize and secrete a variety of biologically active substances, so as to ensure the normal contraction and relaxation of blood vessels, and maintain the tension of blood vessels. Besides, it can regulate blood pressure and the balance of blood coagulation and anticoagulation, and maintain normal blood flow and long-term patency of blood vessels. Endothelial cell damage can cause a series of cardiovascular diseases, such as hypertension and coronary heart disease. Flavonoids are widely found in nature. Because these compounds are mostly yellow or light yellow, they contain ketone groups in the molecule, which are called flavones. Flavonoids are widely distributed, mostly in higher plants and ferns. Various flavonoid compounds, such as flavonoids, flavonols, flavanones isoflavones and flavanones, can protect vascular endothelial cells. This article reviews relevant findings published in domestic and foreign journals. It is found that flavonoids have effects in resisting inflammation, reducing blood vessel fragility, improving blood vessel permeability, lowering blood lipids and cholesterol, vasodilating and resisting hemagglutinating, with the same effect as phytoestrogens. They can reduce vascular endothelial cell damage through anti-inflammatory, anti-oxidative stress, stable mitochondrial function, and regulating nitric oxide（NO）. It can be used in clinic to treat diseases, such as insufficient cerebral blood supply, sequelae caused by cerebral hemorrhage, hyperviscosity, cerebral thrombosis, coronary heart disease and angina pectoris.

OBJECTIVETo assess the feasibility, safety and outcome of anatomical laparoscopic left lateral hepatic lobectomy for benign and malignant liver tumors.

METHODSFrom April 2005 to May 2008, 11 patients (7 male, 4 female; mean age 51.7 years) underwent anatomical laparoscopic left lateral hepatic lobectomy. Four patients presented with hepatocellular carcinoma and cirrhosis, while 1 patient had metastatic liver tumors from postoperatively colon cancer, five patients had hemangioma (2 cases with gallstones underwent cholecystectomy), 1 patient had a huge symptomatic angiolipoleiomyoma. Mean tumor size was 5.8 cm (range 2.1 to 12.0 cm). All the lesions were localized in the anatomical left lateral lobe (segments II to III).

RESULTSThe mean operative time was 147 min (range 120 to 180 min). There were no intraoperative or postoperative complications, and blood transfusions were not required. The mean postoperative hospital stay was 5.9 days.

CONCLUSIONSAnatomical laparoscopic left lateral hepatic lobectomy are feasible and safety.

Adult ; Aged ; Female ; Hepatectomy ; methods ; Humans ; Laparoscopy ; Liver Neoplasms ; pathology ; surgery ; Male ; Middle Aged ; Treatment Outcome

OBJECTIVETo analyze the efficacy and quality of life and safety for paclitaxel and carboplatin (TC) and TC combined with endostar in the treatment of advanced non-small cell lung cancer (NSCLC).

METHODSThis is a prospective, multicenter, randomized, double-blind, placebo-controlled clinical study. A total of 126 cases of untreated advanced NSCLC were enrolled in this study. There were 63 patients in the TC control arm and TC combined endostar arm, respectively. All enrolled patients were continuously followed-up for disease progression and death.

RESULTSThe objective response rate (ORR) of TC combined with endostar arm was 39.3%, and that of TC control arm was 23.0%, P = 0.078. The progression-free survival rates for TC combined with endostar arm and TC control arm were 78.3% and 58.8%, respectively, in 24 weeks (P = 0.017). The hazard ratio for the risk of disease progression was 0.35 (95%CI 0.13 to 0.90, P = 0.030). The median time to progression (TTP) of the TC combined with endostar arm was 7.1 months and TC arm 6.3 months (P > 0.05). The follow-up results showed that the median survival time (mOS) of the TC + Endostar arm was 17.6 months; (95%CI 13.4 to 21.7 months), and the TC + placebo arm 15.8 months (95%CI 9.4 to 22.9 months) (P > 0.05). The quality of life scores (LCSS patient scale) after treatment of the TC combined with endostar arm was improved, and that of the TC group was improved after completion of two cycles and three cycles of treatment. The quality of life scores compared with baseline after the completion of one cycle treatment was significantly improved for both the TC combined with endostar arm (P = 0.028 and), and TC arm (P = 0.036). It Indicated that TC combined with endostar treatment improved the patient's quality of life in the early treatment. The difference of adverse and serious adverse event rates between the two groups was not significant (P > 0.05).

CONCLUSIONSCompared with TC alone treatmrnt, TC combined with endostar treatment can reduce the risk of disease progression at early time (24 weeks), increase the ORR, and can be used as first-line treatment for advanced NSCLC. The TC combined with endostar treatment has good safety and tolerability, improves the quality of life, and not increases serious adverse effects and toxicity for patients with advanced NSCLC.

Antineoplastic Agents ; adverse effects ; therapeutic use ; Antineoplastic Combined Chemotherapy Protocols ; adverse effects ; therapeutic use ; Carboplatin ; administration & dosage ; Carcinoma, Non-Small-Cell Lung ; drug therapy ; pathology ; Disease Progression ; Disease-Free Survival ; Double-Blind Method ; Endostatins ; adverse effects ; therapeutic use ; Follow-Up Studies ; Humans ; Leukopenia ; chemically induced ; Lung Neoplasms ; drug therapy ; pathology ; Nausea ; chemically induced ; Neoplasm Staging ; Paclitaxel ; administration & dosage ; Prospective Studies ; Quality of Life ; Remission Induction

OBJECTIVETo identify the anti-inflammatory effects of artificial musk aqueous extract(AME)on lipopolysaccharide-stimulated cytokines secreted or released by RAW264.7 cells.

METHODSCytokines including interleukin(IL)-6,IL-10,and tumor necrosis factor Α were determined using cytokine enzyme-linked immunosorbent assay kits.

RESULTCompared with model group,the levels of major cytokines such as tumor necrosis factor Α,IL-6,and IL-10 significantly decreased in different AME groups in a dose-dependent manner.

CONCLUSIONIn lipopolysaccharide-stimulated RAW264.7 macrophages,AME can remarkably inhibit the release of inflammatory cytokines and thus exerts its anti-inflammatory effects.

Animals ; Anti-Inflammatory Agents ; pharmacology ; Cell Line, Tumor ; Cytokines ; metabolism ; Enzyme-Linked Immunosorbent Assay ; Fatty Acids, Monounsaturated ; pharmacology ; Inflammation Mediators ; metabolism ; Interleukin-6 ; metabolism ; Lipopolysaccharides ; Macrophages ; Tumor Necrosis Factor-alpha ; metabolism