ObejectiveTo establish the lenvatinib-resistant model of hepatocellular carcinoma (HCC) in vitro in order to study the effect of disulfiram combined with copper ions on the proliferation and apoptosis of lenvatinib-resistant Huh7 cells.MethodsThe half-inhibitory concentration (IC50) of Huh7 cells treated with lenvatinib was detected by the CCK8 method, and the resistance of Huh7 cells to lenvatinib was induced by increasing concentration method. The cell treatment of each group: The Huh7 cells cultured with common culture medium and with 10 μmol/L lenvatinb in the control group and lenvatinib sensitive group, respectively; The lenvatinib-resistant Huh7 cells cultured with 10 μmol/L lenvatinb, with 10 μmol/L lenvatinib+1 μmol/L disulfiram+0.5 μmol/L copper ions, and with 10 μmol/L lenvatinib+10 μmol/L Akt inhibitor MK2206 in the lenvatinib-resistant group, combined drugs group, and inhibitor group, respectively. The cell survival and apoptosis rates were detected by the CCK8 and flow cytometry, respectively. The Western blot method was used to detect the expressions of phospho-protein kinase B (p-Akt), cysteine aspartic acid specific protease (caspase-9), and B-cell lymphoma-2 (Bcl-2) proteins. The Transwell assay was used to detect the cell invasiveness.ResultsThe lenvatinib-resistant cell line was successfully established. The concentrations of 10, 20, 40, 60, 80 and 160 μmol/L leventinib were applied to the Huh7 cells for 48 h, and the IC50 was calculated to be 12.35 μmol/L. The cell survival rate of the lenvatinib-resistant group was significantly higher than that of the lenvatinib sensitive group (P<0.01), which in the combined drugs group was significantly lower than that of the lenvatinib-resistant group (P<0.01), which in the inhibitor group was significantly lower than that of the lenvatinib-resistant group (P<0.05). The apoptosis rate of the combined drugs group was significantly higher than that of the lenvatinib-resistant group (P<0.01). Compared with the lenvatinib-resistant group, the expression of p-Akt protein was significantly decreased (P<0.01) and caspase-9 expression was significantly increased (P<0.01) in the combined drugs group, while the difference of Bcl-2 protein between the lenvatinib-resistant group and the combined drugs group was not statistically significant (P>0.05). The invasive cells were more in the combined drugs group as compared with the lenvatinib-resistant group (P<0.01). ConclusionThe combination of disulfiram and copper ion could increase the sensitivity of lenvatinib to lenvatinib-resistant Huh7 cells, the cell inhibition rate is significantly increased, it’s mechanism might be related to the inhibiting p-Akt expression and promoting caspase-9 expression.
ObjectiveTo investigate the role of non-coding RNA (ncRNA) in the proliferation, migration and metastasis of hepatocellular carcinoma (HCC) and the mechanism of HCC resistance to sorafenib.MethodThe literatures of ncRNA studies related to the incidence of HCC in recent years were reviewed, and the relationship between different ncRNAs and the proliferation, migration and metastasis of HCC was summarized, and the mechanism of sorafenib resistance in the HCC was analyzed from the perspective of ncRNA.ResultsThere were many kinds of ncRNAs, which were classified into the long ncRNA and short ncRNA according to their length. Currently, microRNA, which was widely studied, belonged to the short ncRNA. The regulation of the expressions of different microRNAs and long ncRNA could enhance or inhibit the signaling pathway of the producing HCC and played an important guiding role in the diagnosis and treatment of HCC. Meanwhile, the targeted regulation of this ncRNA could reverse the sorafenib resistance in the HCC.ConclusionsncRNA plays an important role in the pathogenesis of HCC and has become a potential target for the treatment of HCC. Targeted regulation of specific ncRNA expression could reverse sorafenib resistance in HCC.
In medical research, pilot and feasibility studies are conducted to reduce the uncertainty of future main trial and enhance its overall quality and probability of successful completion. The objective of a pilot and feasibility study is to answer whether the main trial can be performed, should be performed, and if so, how. Due to the tremendous resources, time, and funding required for a phase Ⅲ clinical trial, conducting a pilot and feasibility study is generally a pivotal step. While pilot and feasibility studies are gaining increasing attention in clinical research, efforts are largely required to promote the dissemination in China. Therefore, in this article, we briefly introduce the concepts of a pilot and feasibility study, its importance to the main trial, and current practice. Examples are also provided to help illustrate the introduction.
Objective To evaluate the disease burden of acne vulgaris in China from 1990 to 2019 and to provide references for the prevention and control of acne vulgaris in China. MethodsThe quantity of incidences/illnesses, age-standardized incidence/prevalence rates, disability-adjusted life years (DALYs), and DALY rate of acne vulgaris in China from 1990 to 2019 which were derived from the Global Burden of Disease (GBD) 2019 were evaluated. The epidemiological trends, age-birth-cohort trends, and the relationship between the incidence and sociodemographic index (SDI) were also analyzed. Results In 2019, the prevalence and incidence of acne vulgaris in China were higher than the global average. The quantity of patients was slightly higher in 2019 than that in 1990 (3.91%), and the prevalence, incidence, and DALY rate showed a continuous growth trend. The incidence of acne vulgaris peaked at 10 to 14 years old. Acne vulgaris mostly affected young males, and its prevalence peaked at approximately 15 to 19 years old. With these two age groups as the boundary, there was a trend of the prevalence of acne vulgaris increasing initially and then decreasing. Obvious gender differences existed for acne vulgaris diagnoses, and most of the above indicators were shown at a higher level in females than in males. The age period cohort analysis showed that the incidence rate of acne vulgaris in China from 1990 to 2019 was significantly different from the net drift, age effect, period effect and cohort effect. As the SDI value increased, the incidence of acne vulgaris showed a linear growth trend. Conclusions From 1990 to 2019, the burden of acne disease in China increases significantly.