[ ABSTRACT] AIM:To investigate the cardiac AMP-activated protein kinase ( AMPK) activity and the effects of AMPK activator on cardiac structure and function in the mice with different β-adrenoceptor (β-AR) stimulation patterns . METHODS:Male BALB/c mice were subcutaneously injected with AMPK activator ( AICAR, 250 mg· kg -1 · d-1 ) or saline, and infused with β-AR agonist isoproterenol (ISO, 5 mg· kg-1· d-1) for 14 d.The cardiac functions were evalu-ated by echocardiography or hemodynamic method , and the hearts were harvested after infusion cessation immediately or 3 d later.Phosphorylated AMPK ( p-AMPK) was measured by Western blot .RESULTS:Sustained ISO infusion increased p-AMPK level.AICAR did not further increase p-AMPK but attenuated ISO-induced increase in heart weight .Sustained ISO infusion increased cardiac systolic function as indicated by left ventricular fractional shortening ( FS) and maximum rate of pressure rise (+dp/dtmax).The cardiac systolic function was not further increased by AICAR .The cardiac diastolic func-tion as indicated by left ventricular end-diastolic pressure (LVEDP) was not different in each group .In contrast, cardiac p-AMPK level was similar between the control mice and the mice with sustained ISO infusion and ceased infusion for 3 d. In this model, AICAR improved the cardiac systolic and diastolic functions , which were impaired by ISO.Moreover, the increased pattern of p-AMPK level was similar with that of heart rate upon ISO stimulation .CONCLUSION: Sustained ISO infusion increases p-AMPK.After ISO infusion cessation for 3 d, p-AMPK is decreased to the basal level .β-AR-in-duced inotropic effects should be avoided to investigate the cardioprotective role of AMPK activation in the β-AR stimulation models.

Objective To investigate the distribution and incidence of hyperuricemia for the Zhoushan island residents in Zhe-jiang province and provide scientific advice for health management.Methods The uric acid reports of island residents were analyzed by a retrospective statistical analysis in the Physical Examination Center of the 413 Hospital from October 2013 to October 2015.The patients with metabolic diseases (such as diabetes,chronic renal failure and other people,etc.)were ex-cluded.According to the different gender and different age groups,the average level of uric acid,hyperuricemia occurrence rate and the difference among the groups were performed statistical analyses.The single factor analysis of variance was used by Microsoft 2003 Excel software.Results The average serum uric acid level of 7 310 island residents was 283±82μmol/L and the incidence of hyperuricemia was 21.2%.The incidence of hyperuricemia was 33.6% in 31~40 years group,and the average level of uric acid was 343±86μmol/L and significantly higher than≤30 years group,significant statistic difference were observed.The incidence of hyperuricemia was more than 15% in≥41 years group,significantly higher than≤30 years group.The population of physical examination was concentrated in the 31~40 years group.The hyperuricemia incidence was 27.9% in 5 214 male residents,and the average serum uric acid level was 368±74μmol/L and higher than the female group (P<0.001).The hyperuricemia incidence was as high as 43.1% in 31~40 years group.But the level of average serum uric acid showed no significant difference with≤30 years group(P>0.05).The level of average serum uric acid level was less in≥61 and 41~50 years group than in ≤30 years group (P<0.05),but the hyperuricemia incidence were higher than ≤30 years group.The incidence of hyperuricemia was 4.6% in 2 096 female residents.The level of average serum uric acid was 257±57μmol/L and lower than the male group in all age groups (P<0.001).The incidence of hyperuricemia was 18.6% in≥60 years old and lower than 10% in the other groups.The incidence of hyperuricemia increased gradually with age.Conclu-sion The hyperuricemia incidence in island residents was higher,and higher in male than in female.The occurrence of hype-ruricemia was significantly younger.Therefore,health education,reasonable diet adj ustment,improvement of lifestyle and eating habits etc.Should be conducted for a long time to prevent the occurrence of hyperuricemia and related diseases.

Objective: To investigate the effect of fluid flow shear stress (FFSS) on the fluid mechanic threshold of high-mobility group box 1 (HMGB1) release by synovial cells and chondrocytes. Moreover, the mechanism of chondrocyte and synovial cell damage induced by abnormal mechanical force was investigated to provide an experimental basis for exploring the pathogenesis and pathology of temporomandibular joint osteoarthritis. Methods: With the approval of the Ethics Committee for Animal Experiments of the hospital, synovial tissue and cartilage tissue blocks were obtained from the knee joints of Sprague-Dawley (SD) rats, and synovial cells and chondrocytes were cultured and digested for subsequent experiments. Synovial cells and chondrocytes of 3-4 generations were acquired, and FFSS was applied to synovial and cartilage cells using a fluid shear mechanical device. The cells were divided according to the FFSS values of different sizes. Synovial cells were stimulated for 1 h with 1, 3, 5, or 10 dyn/cm2 of FFSS, and chondrocytes were stimulated for 1 h with 4, 8, 12, or 16 dyn/cm2 of FFSS. Resting cultures (0 dyn/cm2) were used as the control group. Changes in the morphology of the cells were observed. The expression and distribution of HMGB1 and interleukin-1β (IL-1β) were observed by immunohistochemistry. The expression of HMGB1 and IL-1β in the supernatant was analyzed by ELISA. The protein expression levels of intracellular HMGB1 and IL-1β were detected by Western blot. Results: With increasing FFSS, the synovial cells and chondrocytes gradually swelled and ruptured, and the number of cells decreased. With increasing FFSS, the localizationof HMGB1 and IL-1β gradually shifted from the nucleus to the cytoplasm. In synovial cells, compared with those in the control group, the expression levels of HMGB1 and IL-1β were increased both in the supernatant and cells in the 1, 3, 5 and 10 dyn/cm2 intervention groups (P<0.01). In chondrocytes, compared with those in the control group, the expression levels of HMGB1 in the supernatant were increased in the 4, 12 and 16 dyn/cm2 intervention groups (P<0.05), and the protein expression levels of HMGB1 were significantly increased (P<0.01). The expression levels of HMGB1 in the supernatant were significantly increased in the 8 dyn/cm2 intervention groups (P<0.01); however, the protein expression levels of HMGB1 were significantly decreased. Compared with those in the control group, the expression levels of IL-1β in the supernatant gradually increased in the 4, 8, 12 and 16 dyn/cm2 intervention groups (P<0.01). With the exception of those in the 4 dyn/cm2 group, the protein expression levels of IL-1β gradually increased with increasing FFSS (P<0.05). Conclusion With increasing FFSS, synovial cells and chondrocytes gradually swelled and burst, and the hydromechanical thresholds of HMGB1 release were 1 dyn/cm2 and 8 dyn/cm2, respectively. Therefore, upon stimulation with a mechanical force, synovial damage was damaged before chondrocytes.