Development and validation of the osteoporosis scale among the system of quality of life instruments for chronic diseases QLICD-OS (V2.0).

BACKGROUND: Quality of life of osteoporosis patients had caused widespread concern, due to high incidence and difficulty to cure. Scale specifics for osteoporosis and suitable for Chinese cultural background lacked. This study aimed to develop an osteoporosis scale in Quality of Life Instruments for Chronic Diseases system, namely QLICD-OS (V2.0). METHODS: Procedural decision-making approach of nominal group, focus group and modular approach were adopted. Our scale was developed based on experience of establishing scales at home and abroad. In this study, Quality of life measurements were performed on 127 osteoporosis patients before and after treatment to evaluate the psychometric properties. Validity was evaluated by qualitative analysis, item-domain correlation analysis, multi-scaling analysis and factor analysis; the SF-36 scale was used as criterion to carry out correlation analysis for criterion-related validity. The reliability was evaluated by the internal consistency coefficients Cronbach's α, test-retest reliability Pearson correlation r. Paired t-tests were performed on data of ​​the scale before and after treatment, with Standardized Response Mean (SRM) being calculated to evaluate the responsiveness. RESULTS: The QLICD-OS, composed of a general module (28 items) and an osteoporosis-specific module (14 items), had good content validity. Correlation analysis and factor analysis confirmed the construct, with the item having a strong correlation (most > 0.40) with its own domains/principle components, and a weak correlation (< 0.40) with other domains/principle components. Correlation coefficient between the similar domains of QLICD-OS and SF-36 showed reasonable criterion-related validity, with all coefficients r being greater than 0.40 exception of physical function of SF-36 and physical domain of QLICD-OS (0.24). Internal consistency reliability of QLICD-OS in all domains was greater than 0.7 except the specific module. The test-retest reliability coefficients (Pearson r) in all domains and overall score are higher than 0.80. Score changes after treatment were statistically significant, with SRM ranging from 0.35 to 0.79, indicating that QLICD-OS could be rated as medium responsiveness. CONCLUSION: As the first osteoporosis-specific quality of life scale developed by the modular approach in China, the QLICD-OS showed good reliability, validity and medium responsiveness, and could be used to measure quality of life in osteoporosis patients.

[Trametenolic acid inhibits migration and invasion of hepatocellular carcinoma HepG2.2.15 cells via RhoC/ROCK1 pathway].

This study investigated the effect of trametenolic acid(TA) on the migration and invasion of human hepatocellular carcinoma HepG2.2.15 cells by using Ras homolog gene family member C(RhoC) as the target and probed into the mechanism, aiming to provide a basis for the utilization of TA. The methyl thiazolyl tetrazolium(MTT) assay was employed to examine the proliferation of HepG2.2.15 cells exposed to TA, and scratch and Transwell assays to examine the cell migration and invasion. The pull down assay was employed to determine the impact of TA on RhoC GTPase activity. Western blot was employed to measure the effect of TA on the transport of RhoC from cytoplasm to cell membrane and the expression of RhoC/Rho-associated kinase 1(ROCK1)/myosin light chain(MLC)/matrix metalloprotease 2(MMP2)/MMP9 pathway-related proteins. RhoC was over-expressed by transient transfection of pcDNA3.1-RhoC. The changes of F-actin in the cytoskeleton were detected by Laser confocal microscopy. In addition, the changes of cell migration and invasion, expression of proteins in the RhoC/ROCK1/MLC/MMP2/MMP9 pathway, and RhoC GTPase activity were detected. The subcutaneously transplanted tumor model of BALB/c nude mice and the low-, medium-, and high-dose(40, 80, and 120 mg·kg~(-1), respectively) TA groups were established and sorafenib(20 mg·kg~(-1)) was used as the positive control. The tumor volume and weight in each group were measured, and the expression of related proteins in the tumor tissue was determined by Western blot. The results showed that TA inhibited the proliferation of HepG2.2.15 cells in a concentration-dependent manner, with the IC_(50) of 66.65 and 23.09 µmol·L~(-1) at the time points of 24 and 48 h, respectively. The drug administration groups had small tumors with low mass. The tumor inhibition rates of sorafenib and low-, medium-and high-dose TA were 62.23%, 26.48%, 55.45%, and 62.36%, respectively. TA reduced migrating and invading cells and inhibited RhoC protein expression and RhoC GTPase activity in a concentration-dependent manner, dramatically reducing RhoC and membrane-bound RhoC GTPase. The expression of ROCK1, MLC, p-MLC, MMP2, and MMP9 downstream of RhoC can be significantly inhibited by TA, as confirmed in both in vitro and in vivo experiments. After HepG2.2.15 cells were transfected with pcDNA3.1-RhoC to overexpress RhoC, TA down-regulated the protein levels of RhoC, ROCK1, MLC, p-MLC, MMP2, and MMP9 and decreased the activity of RhoC GTPase, with the inhibition level comparable to that before overexpression. In summary, TA can inhibit the migration and invasion of HepG2.2.15 cells. It can inhibit the RhoC/ROCK1/MLC/MMP2/MMP9 signaling pathway by suppressing RhoC GTPase activity and down-regulating RhoC expression. This study provides a new idea for the development of autophagy modulators targeting HSP90α to block the proliferation and inhibit the invasion and migration of hepatocellular carcinoma cells via multiple targets of active components in traditional Chinese medicines.