sarcopenia has been defined as the aging-related disease with the declined mass, strength, and function of skeletal muscle, which is a major cause of morbidity and mortality in elders. Current diagnostic criteria of sarcopenia have not been agreed internationally, and the clinical diagnostic biomarkers for sarcopenia have not been identified. Circulating miRNAs (miRNAs, miRs) have recently been characterized as novel biomarkers for sarcopenia. However, the change of circulating miRNAs in response to sarcopenia are still not fully understood. Here, we enrolled a total of 93 elderly patients clinically diagnosed with sarcopenia and matching 93 non-sarcopenia elderly in this study. Specifically, levels of candidate circulating miRNAs which were involved in angiogenesis, inflammation and enriched in muscle and/or cardiac tissues were detected in these two groups. In small-sample screening experiments, plasma miR-155, miR-208b, miR-222, miR-210, miR-328, and miR-499 levels were significantly downregulated in sarcopenia compared to those who non-sarcopenia. In contrast, miR-1, mir-133a, miR-133b, miR-21, miR-146a, miR-126, miR-221, and miR-20a were not changed significantly. Subsequently, we expanded the sample size to further detection and verification, and found that plasma miR-155, miR-208b, miR-222, miR-210, miR-328, and miR-499 levels in the sarcopenia group were significantly reduced compared to the non-sarcoma group, which is consistent with the results of the small-sample screening experiment. In addition, we showed that ASM/Height2, handgrip strength, knee extension and 4-meter velocity in sarcopenia group were significantly lower than those in non-sarcopenia group. Here we correlated the decrease of miR-208b, miR-499, miR-155, miR-222, miR-328, and miR-210 in sarcopenia group and non-sarcopenia group with diagnostic indexes of sarcopenia (ASM/Height2, Handgrip strength and 4meter velocity) after adjusting sex. The results showed that miR-208b and miR-155 changes were significantly correlated with handgrip strength in woman, miR-208b, miR-499, and miR-222 changes were significantly correlated with ASM/Height2 in man, while other miRNAs changes did not show a strong correlation with these diagnostic indexes. In conclusion, plasma miR-208b, miR-499, miR-155, miR-222, miR-328, and miR-210
Objective: This study aimed to evaluate the efficacy and safety of doxorubicin-loaded drug-eluting beads transarterial chemoembolization (DEB-TACE) with CalliSpheres microspheres (CSM) in treating unresectable intrahepatic cholangiocarcinoma (ICC). Methods: 88 unresectable ICC patients who received DEB-TACE treatment with CSM were retrospectively enrolled in this study. Information about treatment response, survival and adverse events were collected. The Kaplan-Meier curve was used to evaluate progression-free survival (PFS) and overall survival (OS), and factors affecting OS were determined by Cox's proportional hazards regression model. Results: Tumor response of the whole sample of 88 patients was partial response (PR) in 58 (65.9%) patients, stable disease (SD) in 19 (21.6%) and progressive disease (PD) in 11 (12.5%) at one month after therapy, with no complete responses (CR). The median PFS and OS were 3.0 months and 9.0 months respectively. Cox's proportional hazards regression analysis disclosed that subsequent treatment was an independent favorable prognostic factor, while cholangiectasis, extensive intrahepatic tumor burden and extrahepatic metastasis were the three prognostic factors associated with poor survival in ICC patients. Besides, common adverse events included nausea/vomiting, abdominal pain and transient elevation of liver transaminase in patients treated by DEB-TACE with CSM. Conclusion: DEB-TACE with CSM is safe and well-tolerated for unresectable ICC patients, with a low complication rate and a relative benefit in terms of survival. Subsequent treatments including systemic/loco-regional treatments is an independent favorable prognostic factor, but cholangiectasis, extensive intrahepatic tumor burden and extrahepatic metastases are the three prognostic factors associated with poor survival.
Experiments were designed to determine the cause of the selective dysfunction of G i proteins, characterized by a reduced endothelium-dependent relaxation to serotonin (5-hydroxytryptamine), in coronary arteries lined with regenerated endothelial cells. Part of the endothelium of the left anterior descending coronary artery of female pigs was removed in vivo to induce regeneration. The animals were treated chronically with vehicle (control), apocynin (antioxidant), or BMS309403 (A-FABP inhibitor) for 28 days before functional examination and histological analysis of segments of coronary arteries with native or regenerated endothelium of the same hearts. Isometric tension was recorded in organ chambers and cumulative concentrationrelaxation curves obtained in response to endothelium-dependent [serotonin (G i protein mediated activation of eNOS) and bradykinin (G q protein mediated activation of eNOS)] and independent [detaNONOate (cGMP-mediated), isoproterenol (cAMP-mediated)] vasodilators. The two inhibitors tested did not acutely affect relaxations of preparations with either native or regenerated endothelium. In the chronically treated groups, however, both apocynin and BMS309403 abolished the reduction in relaxation to serotonin in segments covered with regenerated endothelium and prevented the intima-medial thickening caused by endothelial regeneration, without affecting responses to bradykinin or endothelium-independent agonists (detaNONOate and isoproterenol). Thus, inhibition of either oxidative stress or A-FABP likely prevents both the selective dysfunction of G i protein mediated relaxation to serotonin and the neointimal thickening resulting from endothelial regeneration.
In the porcine coronary artery, regenerated endothelium is dysfunctional as regards the responses to endothelium-dependent agonists. The current study aimed to determine the possible involvement of histamine in such dysfunction. Pigs were treated chronically with pyrilamine (H1 receptor inhibitor, 2 mg·kg(-1)·day(-1)) with part of their coronary endothelium and allowed to regenerate for 28 days after balloon denudation. The results showed a reduction in relaxation to bradykinin (Gq protein dependent) only in the pyrilamine-treated group (area under the curve, 269.7 ± 13.4 vs. 142.0 ± 31.0, native endothelium vs. regenerated endothelium) but not in the control group (253.0 ± 22.1 vs. 231.9 ± 29.5, native endothelium vs. regenerated endothelium). The differences in the relaxation to serotonin (Gi protein dependent) between native and regenerated endothelium were not affected by the pyrilamine treatment (control group, 106.3 ± 17.0 vs. 55.61 ± 12.7; and pyrilamine group, 106.0 ± 8.20 vs. 49.30 ± 6.31, native endothelium vs. regenerated endothelium). These findings indicate that during regeneration of the endothelium, the activation of H1 receptors by endogenous histamine may be required to maintain the endothelium-dependent Gq protein-mediated relaxation to bradykinin, suggesting a beneficial role of the monoamine in the process of endothelial regeneration.
To get the typical ship structures’ longitudinal bend stress in hogging condition, standard method and finite element method, two kinds of longitudinal strength calculating methods are studied and compared in this paper, the section elements of typical ship structures are calculated, the cabin’s finite model are established by ABAQUS, the stress distribution moiré topography are obtained, and the two methods are compared, get the following conclusion: for the section which has a regular shape, such as bottom plate, strength deck, the calculation results from the two methods are consistent; for the section which has a complex shape, such as bilge board, the results of finite method is more accurate than standard method; in standard method, for the section which has a large vertical height, such as side plate, dividing it into some plate units can enhance the calculating accuracy.
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