ABSTRACT
Objective To design an overall unloading knee brace, and analyze the relationship between the unloading force and the position of the brace as well as the thigh bracket-thigh pressure. Methods Based on biomechanical experimental platform, the mechanical and kinematic analysis on squatting down-standing upright motion was conducted to evaluate unloading capacity of the overall unloading knee brace. Results The unloading forces supplied by the brace ranged from 0 to 200 N. The forces were larger with the brace hinges installed on the front-top of the knee, and the unloading forces increased with the pressure between the thigh and thigh bracket increasing. Conclusions The proposed overall unloading knee brace can partly reduce knee force, and its unloading forces are related to the installation site of the brace as well as the elasticity of the belts.
ABSTRACT
<p><b>OBJECTIVE</b>To explore the relevance between the promoter methylation status of Notch1 gene and the invasive ductal carcinoma and ductal hyperplastic lesions of the breast.</p><p><b>METHODS</b>Methylation status of Notch1 gene in human breast invasive ductal carcinoma (IDC, n = 89), ductal carcinoma in situ (DCIS, n = 20), atypical ductal hyperplasia (ADH, n = 11) and usual ductal hyperplasia (UDH, n = 20) were quantitatively evaluated by MALDI-TOF MS. The expression of Notch1 protein was detected by immunohistochemical stain (SP method).</p><p><b>RESULTS</b>Positive expression rates of Notch1 protein in IDC and DCIS were 91.0% (81/89) and 75.0% (15/20), respectively, which were significantly higher than those of ADH (4/11) and UDH (30.0%, 6/20;P < 0.05). Notch1 protein expression was correlated significantly with lymph node metastasis, pathological grades and TNM stages of IDC. The mean methylation levels of Notch1 gene at CpG_3, CpG_4.5 and CpG_8 significantly decreased in IDC group compared with those of DCIS, ADH and UDH groups (P < 0.0083). In breast carcinomas, the mean methylation rates of Notch1 gene at CpG_4.5, CpG_10.11, and CpG_14.15.16 loci in cases with axillary node metastasis were significantly lower than those without axillary node metastasis (P < 0.05); and the methylation rates at CpG_14.15.16 and CpG_18 loci in stage Iwere lower than that in stage II, further lower than that in stage III (P < 0.05); and that in CpG_1.2, CpG_12.13 loci in grade I (highly-differentiated group) were higher than that in grade II (moderate-differentiated group) and grade III (poorly-differentiated group) (P < 0.05); and the methylation rates at CpG_3, CpG_8 and CpG_14.15.16 loci in ER(+) PR(+) HER2(-) group were lower than that in ER(-) PR(-) HER2(+) group (P < 0.05).</p><p><b>CONCLUSIONS</b>There is an overall hypomethylation of Notch1 gene in breast invasive ductal carcinomas with corresponding over-expression of Notch1 protein. This inverse correlation show that the alteration of protein expression result from hypomethylation oncogene Notch1, and this change may have important significance in breast tumorigenesis and the development. Specific hypomethylation at CpG_3, CpG_ 4.5 and CpG_8 loci of Notch1 gene may play a role in the pathogenesis of breast carcinoma, suggesting the progression and/or malignant transformation from benign glandular lesions of the breast.</p>
Subject(s)
Adolescent , Adult , Aged , Aged, 80 and over , Female , Humans , Middle Aged , Young Adult , Breast , Pathology , Breast Neoplasms , Genetics , Metabolism , Pathology , Carcinoma, Ductal, Breast , Genetics , Metabolism , Pathology , Carcinoma, Intraductal, Noninfiltrating , Genetics , Metabolism , Pathology , CpG Islands , Genetics , DNA Methylation , DNA, Neoplasm , Genetics , Disease Progression , Hyperplasia , Lymphatic Metastasis , Neoplasm Staging , Precancerous Conditions , Genetics , Metabolism , Pathology , Promoter Regions, Genetic , Receptor, Notch1 , Genetics , MetabolismABSTRACT
<p><b>OBJECTIVE</b>To compare plasma asymmetric dimethylarginine (ADMA), an endogenous nitric oxide synthase inhibitor, and cystatin C levels in patients with or without coronary artery disease (CAD).</p><p><b>METHODS</b>We recruited 87 CAD patients (39 with acute myocardial infarction and 48 with unstable angina pectoris) and 51 non-CAD controls. Plasma ADMA was measured by HPLC, cystatin C by particle-enhanced immunonephelometric assay (N Latex cystatin C, Dade Behring) with nephelometer (BNII, Dade Behring). CAD patients were further divided into low cystatin C group (< 1.0 mg/L, 36 cases) and high cystatin C group (> 1.0 mg/L, 51 cases).</p><p><b>RESULTS</b>(1) The plasma levels of ADMA [(0.47 ± 0.15) µmol/L vs. (0.37 ± 0.15) µmol/L], SDMA [(0.39 ± 0.19) µmol/L vs. (0.28 ± 0.12) µmol/L] and cystatin C [(1.16 ± 0.32) mg/L vs. (0.73 ± 0.16) mg/L] were significantly higher in CAD patients than in controls (all P < 0.05). The plasma L-Arg was significantly lower in CAD patients than in controls [(59.4 ± 19.4) µmol/L vs. (83.7 ± 19.6) µmol/L, P < 0.05]. (2) Plasma ADMA was similar in CAD patients with low cystatin C level and controls [(0.42 ± 0.12) µmol/L vs. (0.39 ± 0.15) µmol/L, P = 0.251] and Plasma ADMA was significantly higher in CAD patients with high cystatin C level than in controls [(0.50 ± 0.17) µmol/L vs. (0.39 ± 0.15) µmol/L, P < 0.05].</p><p><b>CONCLUSION</b>ADMA levels were significantly increased only in CAD patients with elevated cystatin C levels but not in CAD patients with normal renal function. The reported relationship between coronary heart disease and ADMA may not be direct, but could be secondary due to reduced renal function.</p>