ABSTRACT
PURPOSE: The accumulation of progerin (PG) in patients is responsible for the pathogenesis of Hutchinson-Gilford Progeria Syndrome (HGPS) because it triggers accelerated aging of cells. However, there are few studies on the effects of progerin on tumor cells. Lung cancer is one of the most common malignant cancers with high global morbidity and mortality rates; non-small cell lung cancer accounts for the majority of cases. The purpose of this study was to determine the effects of progerin on A549 cell proliferation, cell cycle, invasion, migration, sensitivity to DNA damaging agents, senescence and apoptosis with a goal of exploring new ideas for lung cancer treatment. METHODS: A549 cells overexpressing progerin (A549-PG) and a corresponding blank control (A549-GFP) were constructed by lentiviral infection. A nuclear staining assay was utilized to detect abnormal nuclear morphology. The proliferation, cell cycle, colony formation, invasion and migration abilities of A549-PG were compared with those of A549-GFP via EdU assays, flow cytometry, colony formation experiments, and Matrigel invasion and migration assays, respectively. SA-ß-gal staining was used to measure senescence in cells. RESULTS: The expression of progerin was significantly higher in A549-PG than A549-GFP. About 20% of A549-PG possessed abnormal nuclei. Overexpression of progerin in A549 cells inhibited cell proliferation, migration and invasion, and associated proteins (CDK4, pRB, ANLN, MMP7 and MMP9) were downregulated. DNA damage repair was also impaired. Progerin did not cause cells to senesce, and there was no difference in apoptosis. CONCLUSION: A549-PG generated some cellular changes, including the nuclear skeleton, the cell cycle, DNA damage repair, and migration and invasion abilities. Our data indicate that progerin could cause an imbalance in the steady state in A549 cells and increase their sensitivity to chemotherapeutic drugs.
ABSTRACT
The aim of this study was to develop and validate the large intestine dampness-heat syndrome questionnaire (LIDHSQ) for patients with ulcerative colitis (UC). The domains and items of the LIDHSQ were developed according to standard procedures, namely, construct definition, item generation, language testing, content validity, pilot study, and validation study. At first, a total of 20 items in 3 domains were generated based on literature review and expert consultation. After the item selection, the LIDHSQ contains 11 items in three domains: disease-related domain (diarrhoea, abdominal pain, bloody purulent stool, and mucus stool), heat domain (fever, dry mouth, red tongue, yellow fur, and anal burning), and dampness domain (greasy fur and defecation disorder). The Cronbach's alphas of all domains were greater than 0.6. All of the intraclass correlation coefficients were greater than 0.8. The LIDHSQ and domain scores of the patients with LIDHS were higher than those of the patients with other syndromes (P < 0.001). The area under the receiver operating characteristic curve of the LIDHSQ was 0.900, with a 95% confidence interval of 0.872-0.928. When the cut-off value of the LIDHSQ was ≥ 7, the sensitivity and specificity were 0.867 and 0.854, respectively. The LIDHSQ is valid and reliable for measuring LIDHS in UC patients with good diagnostic efficacy. We recommend the use of the LIDHSQ in Chinese UC patients.
ABSTRACT
BACKGROUND: The aim was to develop and validate the quality of life scale for nasopharyngeal carcinoma (NPC) patients, the QOL-NPC (version 2), a specific instrument to measure quality of life for NPC patients. METHODS: The QOL-NPC was developed and validated according to standard procedures. The patients were assessed using the QOL-NPC, FACT-G, and FACT-H&N. Classical test theory was used to evaluate the reliability, validity, and responsiveness of the QOL-NPC. RESULTS: A total of 487 patients (97.4 %) completed the questionnaire. The QOL-NPC comprised four domains, as follows: physical function (eight items); psychological function (five items); social function (five items); and side effects (eight items). All of the items had a lower proportion of missing data. Cronbach's alpha values of the domains ranged from 0.72 to 0.84. The split-half reliability coefficients ranged from 0.77 to 0.84. All of the intra-class correlation coefficients were > 0.8. The normed fit index, non-normed fit index, and comparative fit index were >0.89. The root mean square error of approximation was 0.097, with a 90 % confidence interval (0.093, 0.100). The domain scores of the QOL-NPC were significantly correlated with the FACT-G and FACT-H&N (P < 0.05). All of the domain scores of patients using different amounts of radiotherapy were significantly different (P < 0.001). All domain scores decreased at the completion of radiotherapy, with effect sizes ranging from -0.82 to -0.22. CONCLUSIONS: The QOL-NPC is valid for measuring QOL with good reliability, validity, and responsiveness. The QOL-NPC is recommended to measure the QOL for Chinese NPC patients.
