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.

To date, the treatment of peripheral T-cell lymphomas (PTCL) has lagged behind B-cell malignancies. Traditionally, para-digms for diffuse large B-cell lymphoma were applied to patients with PTCL, but the outcomes were poor. Recently, the FDA has ap-proved four drugs for patients with relapsed/refractory PTCL, and the Japanese government has approved of anti-CCR4 monoclonal an-tibody for patients with adult T-cell leukemia/lymphoma. Clinical studies are exploring the combination of these new agents into stan-dard CHOP-based regimens for patients with newly diagnosed PTCL. Recent studies have revealed that PTCL may be associated with epigenetic dysregulation and is thus sensitive to histone deacetylase inhibitors. These advances provide a new understanding of PTCL, whose therapeutic options will be presented in this review.

Objective One of the characteristics of rheumatoid arthritis was multiple joints involved symmetrically. The purpose was to study the method of early diagnosis and treatment for the atypical rheumatoid arthritis involving solitary joint. Methods From April 1997 to December 2002, 5 cases which were 1 male and 4 female patients with an average age of 36.8 years (range, 23 to 47 years), suffered from the swelling and pain of knee joint, and were diagnosed as early rheumatoid arthritis. The interval of the onset to surgical treatment ranged from 2 months to 3 years with a mean of 16.2 months. The patients were evaluated with serum test, joint fluids examination and radiological imaging. They were treated by the synovectomy under the arthroscopy, while the appearances of the joint under arthroscopy were recorded, and the synovial tissue was sent to the pathological examination. The improvements of the joints symptoms and the range of motion were assessed at final follow up. Results During the operation, the light green and little muddy joint fluids were found in all patients. ESR of the patients ranged from 29 to 51 mm/1h with an average of 32.2 mm/1h, all of which were higher than normal value, whereas, 3 cases had positive rheumatoid factor and 4 cases showed significant higher ?2-MG. The radiographic findings were osteoporosis in 3 cases, soft tissue swelling in 4 cases and narrowed joint space in 1 case. The synovium were proliferated and enlarged in dark violet, there were creeping pannus and necrosis fibrin deposition in the cartilage. All of the patients were diagnosed as rheumatoid arthritis confirmed by pathological changes of the synovium. The patients were followed up from 4 months to 5 years (mean, 18.7 months). Pain released in 5 cases, swelling reduced in 3 cases, the range of motion improved by 19 degrees. Unfortunately, all of the patients developed later into typical rheumatoid arthritis after the mean interval of 10.9 months (range, 3 to 25 months), the symptoms were consistent with the criteria of American Rheumatoid Association . Conclusion Solitary joint with rheumatoid arthritis is rare and may be the early status of rheumatoid arthritis. The specific appearance under the arthroscopy prompt the early diagnosis of the knee rheumatoid arthritis, and synovectomy by arthroscopy may be benificial to release the symptoms of rheumatoid arthritis.

The 2 arylpropionic acid derivatives, or "profens", are an important group of nonsteroidal antiinflammatory drugs (NSAIDs). Widely used members of this group include ibuprofen, naproxen, flurbiprofen, and etodolac. Most of these drugs were marketed as racemates, however the individual enantiomers differ in their pharmacological activity, mechanism and toxicity. This drug class is widely focused because of its various biologic properties that affect their clinical use. This review will demonstrate enantioselective pharmacodynamics and pharmacokinetics of "profens".

Objective: To construct an angiopoietin-like protein 2(ANGPTL2) expression vector and obtain ANGPTL2 over-expression endothelial cell strains.Methods: Plasmid phrGFP-C was used to amplify hrGFP protein coding sequence by polymerase chain reaction.The amplified sequence was cloned into the A multiple cloning sites of pIRES to construct plasmid pIRES-hrGFP.Complementary oligonucleotides containing the recognition sequence of BamH I,Sal I,Xba I and SSe8387 I were synthesized,annealed and cloned into a BamH I site on the backbone of plasmid pIRES-hrGFP to obtain vector pIRES-hrGFP-MS.ANGPTL2 cDNA was cloned by RT-PCR while human renal RNA was used as the templet and then inserted into the B multiple cloning sites of the vector pIRES-hrGFP-MS.The newly constructed ANGPTL2 expression vector pIRES-hrGFP-MS-ANGPTL2 was linearized by Xba I and introduced into human umbilical vein endothelial cells.ANGPTL2 over-expressed endothelial clones were screened out by G418 selection and identified by the expression levels of both hrGFP and ANGPTL2 genes in these cell clones.Results: The ANGPTL2 expression vector pIRES-hrGFP-MS-ANGPTL2 was constructed successfully and two ANGPTL2 over-expression endothelial strains were obtained.The cells displayed a significantly extended appearance quite different from that of the control cells.Conclusion: The successful construction of the ANGPTL2 expression vector pIRES-hrGFP-MS-ANGPTL2 and the obtainment of two ANGPTL2 over-expression HUVEC strains have paved the way for further investigation into the function of ANGPTL2 and its possible role in diabetic nephropathy.

Objective To explore the clinical pathological features of Wilson's disease and the pathogenesis of liver fibrosis. Methods The clinical data and liver biopsy specimens obtained from 48 children with Wilson's disease were analysed. The pathological changes were studied with light microscopy, electron microscopy, combined with rhodanine and rubeanic acid for copper staining, Gordon-Sweet's staining for reticular fibers and Masson's staining for collagen fibers. Meanwhile, immunohistochemistry was used to investigate the expression of tissue inhibitors of metalloproteinase (TIMP) -1 and TIMP-2. The apoptosis of activated hepatic stellate cells (HSC) in liver tissues was illustrated with in situ end labeling (ISEL)(TUNEL POD method) and ?-SMA double staining. Results In all the cases, the mean onset age was 10.0?3.8 years, and the positive rates of family history, Kayser-Fleischer’s ring and decreased serum ceruloplasmin level were 29.2%, 68.8% and 93.0%, respectively. The levels of serum ALT, AST, ALP and ?-Glo were 3.6, 3.0, 2.7 and 2.0 fold of normal cutoff values. The major pathological changes in childhood patients with Wilson’s disease presented various chronic inflammatory changes in hepatic acini and portal tracts, interface hepatitis, focal or diffuse vesicular/ microvesicular steatosis, with large and irregular apoptotic bodies, Mallory's bodies, glycogenated nuclei, and eosinophilc granular hepatocytes. Among all the cases, 77.0% of liver specimens were positive for rhodanine and rubeanic acid staining for copper in hepatocyts, especially in the zone I of acinus. Ultrastructural observation showed swollen and unusual giant mitochondria, increased lysosomes and vesicular inclusions in hepatocytes. The incidence of hepatic fibrosis was 100%, presenting expanded portal tracts in the early, fibrotic septa in the moderate and cirrhosis in the late stage. The extent of TIMP-1 and TIMP-2 expression and number of activated HSC were increased in various degrees in all the liver specimens, while apoptotic HSCs were obviously decreased in the majority of cases. Conclusions The clinical and pathological changes of children with Wilson’s disease are varied and relatively obscure, and liver fibrosis appears early and progressive. Excessive activation and proliferation of HSC stimulated by liver injury and inflammation due to copper deposition and the decrease in activity of matrix degradation enzymes might be the important mechanisms underlying the occurrence and progression of hepatic fibrosis in Wilson's disease.

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

Objective To explore the mechanism of fibrosis in autoimmune hepatitis(AIH). Methods By using synaptophysin (SYN) as a new marker for hepatic stellate cells (HSCs),HSCs,collagen I,collagen IV,and MT-MMP-1 were detected by immunohistochemistry,and the expressions of MT-MMP-1 and TIMP-1 mRNA were assessed by in situ hybridization in liver tissues obtained by needle biopsy from 36 AIH patients. Results The HSCs were observed in the portal tracts,fibrotic septa and lobules of AIH liver tissues where inflammation was active,especially in the interface of inflammatory and non-inflammatory areas. The number of HSCs increased in proportion to the increase in histoligical active index (HAI,Knodell),while the deposition of Col I and Col IV were increased with increase in hepatic fibrosis stages (Knodell). MT-MMP-1 and its mRNA were mainly expressed in mesenchymal cells which were distributed in the areas of interface of inflammation and borders of fibrotic septa. It was also observed in a few hepatocytes. The expression of MT-MMP-1 was parallel to collagen IV distribution,and increased with advancement of HAI and fibrosis stages,reaching the peak at S4-5 stage. In addition,the expression of TIMP-1 mRNA was similar to that of MT-MMP-1 mRNA. Conclusions The results of immunohistochemistry and in situ hybridization suggested persistant active inflammation,triggering the activation and proliferation of HSC,and the resultant deposition of extracellular matrix such as collagen IV and I might be one of pathogenetic mechnisms of hepatic fibrosis in AIH. The increased expression of MT-MMP-1 in liver tissues of AIH in parallel with the advancement fibrotic stages also suggested that the relative lower level of ECM degeneration due to metalloproteinase suppression might be another reason for fibrogenesis and development of fibrosis in AIH. In addition,it was shown that synaptophysin was another good marker for HSC.

Objective MRI was a powerful technique for evaluation of the meniscus injury.However,meniscal injuries were the most common reason for arthroscopy of the knee.The research was to reveal the relationship between the classification on MRI and the morphological changes of the meniscus injury under the arthroscopy in order to indicate the surgical procedures according to the MRI degree of meniscus in-juries.Methods From October2000to December2001,157knees of152cases with meniscus tears were analyzed retrospectively,who were classified into the osteoarthritis group and sport injury group depending on the causes of injury.There were107knees in osteoarthritis group,50knees in sport injury group.All cases were made MRI examination with T 1 and T 2 sequences,and152of them underwent arthroscopic oper-ation.According to the different signal intensity,changes of contour and edge of meniscus,juried meniscus were divided into four degrees,referring to the standard described by Stoller.The conditions of torn menis-cus were observe and recorded while performing arthroscopy in order to compare with that on MRI.Results The MRI classification in osteoarthritis group,there were gradeⅠin21knees,gradeⅡin34knees,gradeⅢin40knees,and gradeⅣin12knees;Depending on the exploration in arthroscopy,the accurate rate of diagnosis of MRI for meniscus injury was100%(21/21)for gradeⅠ,91.2%(31/34)for gradeⅡ,92.5%(37/40)for gradeⅢand100%(12/12)for gradeⅣ.The patients with gradeⅢand gradeⅣinjury of the meniscus all underwent the operation of arthroscopy.The MRI classification in sport injury group,there were gradeⅠin5knees,gradeⅡin4knees,gradeⅢin26knees,and gradeⅣin15knees.The accurate rate of diagnosis of MRI was75%(3/4)for gradeⅡ,92.3%(24/26)for gradeⅢand93.3%(14/15)for gradeⅣ.Conclusion In the meniscus tears,gradeⅠinjury on MRI is not indicated to surgical treatment,gradeⅡcan be explored in arthroscopy or observed when it is in need based on clinical symptoms.GradeⅢand gradeⅣof meniscus injury necessitate partial meniscectomy or meniscoplasty.