Objective Rats with nonalcoholic fatty liver disease (NAFLD) were used to investigate the secretory state of pancreas and the expression of insulin receptor (IR). Methods NAFLD rat model was reproduced, and then the structure of pancreatic tissue, secretory states of ? and ? cells (serum, tissue) and the expression of IR were examined and determined by means of HE staining, ELISA, and immunohistochemistry. Results In all experimental groups, the structure of pancreatic tissue showed no obvious change; the blood sugar level tended to rise. The insulin level in serum began to elevate obviously at 4th week (P≤0.01), while the insulin content in tissue began to increase at 6th week (P≤0.01), and distributed mainly in the middle part of the pancreas with a tendency of elevation along with the time. The content of glucagon in pancreatic tissue began to increase at 8th week (P≤0.01), and reached the peak at 12th week. The expression of IR in tissue began to decrease at 6th week (P≤0.01), and then tended to be stable after 8th week. Conclusions In NAFLD, there was changes in secretory state of pancreas with the accompaniment of insulin resistance. There was a tendency of elevation of levels of insulin both in serum and pancreatic tissue, but the time of expression was different. The expression of glucagen shows an increase tendency, while the decrease of IR might be the crucial cause of insulin resistance in NAFLD.

Objective To study the changes in serum endotoxin level of the patients with primary biliary cirrhosis (PBC) and the relationship between endotoxin and serum biochemical parameters. Methods Clinical data of 63 cases PBC patients confirmed by liver puncture biopsy were retrospectively studied. The clinical features, results of laboratory tests, pathological findings of all the 63 patients were analyzed. Endotoxin level was determined by limulus amebocyte lysate test in the serum obtained from the 63 cases of patients with primary biliary cirrhosis, and then compared with that of 30 healthy individuals. Results The sex ratio (male to female) of PBC patients was 1 to 8, and the mean age was 43.8 years. The prevalent complaints were jaundice and fatigue. 70.3% patients showed AMA positive. The levels of ?-glutamyltransferase (r-GGT), alkaline phosphatase (ALP) and bilirubin in the serum were markedly elevated in the majority of the patients. Compared with the early stage, the levels of ALT and AST declined slightly during the advanced stage (P

In order to develop ELISA method for measuring the degradation fragment of fibronectin (MAD2),hybridoma technique was used to obtain the monoclonal antibody (McAb)IgG 1 against MAD2 without cross reaction with fibronectin.The sera from 277 patients with hepatocellular carcinoma (HCC),76 with metastatic hepatic carcinoma (HMC),98 with alimentary canal carcinoma (ACC) and 156 with chronic liver disease(CLD) and 48 healthy subjects were assayed with ELISA method using this antibody.The examination showed that the mean value of MAD2 from the patients with HCC showed obviously significant difference compared with those of CLD,HMC,ACC and normal control groups ( p

To investigate MT 1 MMP mRNA expression in the development of liver fibrosis and during the reversal of liver fibrosis ,we undertook a dynamic observation by situ hybridization. Liver fibrosis model was established by intraperitoneal injection with CCl 4 in Wistar rats, then allowed them fo recover spontaneously to observe the reversal of liver fibrosis .The results showed that MT 1 MMP mRNA was expressed mainly in mesenchymal cells(such as hepatic stellate cell), also in a part of hepatocytes.The levels of MT 1 MMP mRNA expression were increased gradually in the development of liver fibrosis and decreased gradually during reversal of liver fibrosis. These results suggest that the expression of MT 1 MMP may have an important role in the development of liver fibrosis and its reversal.

To study the mechanism of matrix degradation in alcoholic liver disease (ALD), the liver tissues from 28 patients with ALD were divided into three groups according to their fibrosis degree. The mRNA expression of matrix metalloproteinase 1 (MMP 1), matrix metalloproteinase 2 (MMP 2), membrane type metalloproteinase (MT1 MMP), and tissue inhibitors of metalloproteinase (TIMP) was detected using in situ hybridization method. The results showed that the cells with positive MMP 1, MMP 2, MT1 MMP, and TIMP mRNA staining were mainly located around the fibrotic central veins, walls of sinusoids, and portal triads. These positive cells were the cells of hepatic sinusoidal walls and a few hepatocytes, meanwhile, some cells expressed both the MMP 2 and the MT 1MMP mRNA. The positive cells of the MMP 2, MT1 MMP, and TIMP mRNA increased in parallel with the severity of fibrosis, whereas the expression of MMP 1 mRNA decreased. These changes were observed predominantly in moderate fibrosis group. There findings demonstrated that down regulation of MMP 1 expression and up regulation of TIMP expression might be involved in excessive accumulation of extracellular matrix (ECM) in ALD. MMP 2 might collaborate with MT1 MMP in degradation of ECM. thereby contributing to fibrosis of central veins.Hepatic stellate cells might be the main cellular source of MMP 1, MMP 2, MT1 MMP and TIMP in ALD.

micro), hepatocyte ballooning degeneration, mild diffuse lobular inflammation and perisinusoidal collagen deposition. Zone 3 accentuation could be detected. Mallory hyaline, vacuolated nuclei in periportal hepatocytes were common. NASH has some clinical and pathological characteristics. The authors hold that combinative consideration of clinics, pathology and laboratory can ensure the diagnosis of NASH, and liver biopsy interpretation continues to be the "gold standard " for diagnosis.

Objective To explore the effects of severe acute respiratory syndrome coronavirus (SARS-CoV) on heart and its conduction system in SARS patients. Methods Six specimens of heart tissue and one specimen of heart condunction system from patients who died from SARS were studied histologically, and by histochemical and in situ hybridization examinations. Results The pathological changes showed that a part of cardiomyocytes manifested slight vacuolar degeneration, atrophy and cytoplasmic lysis, stromal edema, mild mononuclear infiltration, and vasculitis. SARS-CoV was identified within some cardiomyocytes and specialized cardiomyocytes which belonged to the conduction system of the heart by in situ hybridization in combination with Macchiavello's viral inclusion stain. Conclusions The results showed that SARS-CoV could invade not only cardiomyocytes, but also the specialized cells of heart conduction system, thus resulting in mild viral myocarditis-like pathological changes. The results provided the evidence in explaining the clinical manifestations of cardiac dysfunction in patients with SARS.

Objective To explore the significance of cellular apoptosis induced by severe acute respiratory syndrome cronovirus (SARS-CoV) in the pathogenesis of SARS. Methods TdT-mediated biotinylated-dUTP nick end ladelling method (TUNEL), and the double immunochemical staining with cytokeratin and CD3, CD8, CD20 and CD68 monoclonal antibodies were used to study the cellular apoptosis in tissue specimens from six patients who died from SARS. Meanwhile, the expression of Fas, Fas ligand (FasL), P53 and Bcl-2 proteins was detected by immunohistochemical method. Results The number of cellular apoptosis was obviously increased in multiple organs from the six patients died from SARS. The cellular apoptosis occurred predominantly in cytokeratin-positive pneumoncytes, terminal bronchiolar epithelium, CD3 + and CD8 + lymphocytes, as well as a part of CD20 + lymphocytes and CD68 + macrophages. Fas protein was mainly expressed in the infiltrated mononuclear cells, while FasL was chiefly expressed in SARS-CoV target cells, especially in the apoptotic cells. In the lung and immune organs, down-regulation of P53 and Bcl-2 expression was found. Conclusion The occurrence of increased and rapid cell apoptosis induced by SARS-CoV might be the main cause of the injuries to the lung and immune system. That the activated lymphocytes which expressed Fas and FasL attack SARS-CoV target cells might be the underlying mechanism of cell apoptosis in SARS. Down-expression of Bcl-2 and P53 proteins might also participate in cell apoptosis induced by SARS-CoV.

Objective To explore the mechanism of Fufangbiejiaruanganpian(FFBJRGP) treating liver fibrosis. Methods Needle biopsies before and after treatment with FFBJRGP were done in 65 patients with chronic viral hepatitis B, and the liver tissues were studied with Ishak scoring system to evaluate the effects of treatment. The activation, proliferation and apoptosis of hepatic stellate cells (HSCs) in the liver specimens were determined by using the double immunohistochemical staining of in situ terminal deoxynucleotidyl transferase mediated dUTP nick end labelling method (TUNEL) and smooth muscle actin (SMA). Results Compared with the specimens before treatment, the stages of liver fibrosis and histological activity grades in liver tissues were significantly improved after treatment with FFBJRGP for 6 months (mean value: P

Objective To study the effect of the traditional Chinese medicinal herbs, Fufangbiejiaruanganpian (FFBJRGP), in an experimental model of hepatic fibrosis and its pharmacodynamics. Methods An experimental model of hepatic fibrosis induced by carbon tetrachloride in rat was reproduced, and FFBJRGP was given in high, moderate, and low dosage for 0, 1, 3 and 6 months respectively. Six months after the treatment, matrix metalloproteinase MMP-2, MMP-13, MT-MMP-1, MT-MMP-2 and their inhibitor TIMP-1 and TIMP-2, total extracellular matrix and collagen I, Ⅲ and Ⅳ, and active hepatic stellate cells in the fibrotic livers were qualitatively and quantitatively examined at the protein and/or mRNA expression levels by using immunohistochemistry, in situ hybridization, image analysis and Chevallier's scoring system. Meanwhile, enzyme-degrading activities of MMP-2 and MMP-13 were assessed with gelatin or collagen substrate zymography respectively. Results Compared with the control group, in which rats with hepatic fibrosis were not treated with FFBJRGP, the histological examination of rat livers in the treatment groups showed that the total scores of hepatic fibrosis in treatment groups with varions dosage were significantly decreased 3,6 months after the treatment and 3,6 months after the termination of treatment (P