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Objective: Circular RNAs (circRNAs) have been identified as potential biomarkers and therapeutic targets for various types of cancer, including Oral squamous cell carcinoma (OSCC). Hsa_circRNA_101036 was found to function as a cancer suppressor gene in OSCC; however, the underlying regulatory mechanism remains unclear. We investigated the role of hsa_circRNA_101036 in OSCC development and progression and explored its potential as a therapeutic target. Methods: We performed a bioinformatics analysis and used experimental approaches to investigate the regulatory mechanism of hsa_circRNA_101036. The database StarBase v.2.0 was used to predict potential target-miRNAs of hsa_circRNA_101036. The levels of hsa_circRNA_101036, miR-21-3p, and TMTC2 expression in samples of OSCC cancer tissue (n = 15) and adjacent tissue (n = 15) were determined. We also examined the effects of hsa_circRNA_101036 overexpression on OSCC cell lines by using cell viability, migration, and invasion assays. The proportions of apoptotic cells and the reactive oxygen species (ROS) levels were analyzed by flow cytometry. We also investigated how hsa_circRNA_101036 overexpression affected the levels of miR-21-3p and TMTC2, and endoplasmic reticulum (ER) stress in OSCC cells. Results: The levels of hsa_circRNA_101036 and TMTC2 expression were significantly lower, while miR-21-3p expression was higher in tumor tissues and OSCC cells when compared to adjacent tissues and normal oral fibroblasts, respectively. The levels of HIF-1α and miR-21-3p expression were significantly increased under conditions of hypoxia, while the levels of hsa_circRNA_101036 and TMTC2 were decreased. The expression levels of proteins associated with ER stress, the proportions of apoptotic cells, and the levels of ROS were all increased by hypoxia stimulation. In addition, overexpression of hsa_circRNA_101036, but not mutant hsa_circRNA_101036, was found to enhance the effect of hypoxia on HSC3 and OECM-1 cells. Hsa_circRNA_101036 overexpression suppressed tumor growth and induced ER stress. Finally, knockdown of miR-21-3p had the same effect as overexpression of hsa_circRNA_101036. Conclusion: Our findings suggest that hsa_circRNA_101036 plays a critical role in the development and progression of OSCC. Overexpression of hsa_circRNA_101036 aggravated ER stress, and increased cell apoptosis and ROS production in OSCC under hypoxic conditions. Hsa_circRNA_101036 up-regulated TMTC2 expression by sponging miR-21-3p in OSCC.
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Background: The Pilot Plan of National Centralized Volume-Based Procurement (NCVBP) was adopted to cope with the rapid increase in drug expenditures. This research aimed to quantitatively evaluate the impact of the NCVBP on antiviral medications for the hepatitis B virus. Methods: Data on nucleoside analogs (NAs) medications of hepatitis B virus monthly procurement records in the pilot cities from January 2018 to December 2019 were extracted from the China Drug Supply Information Platform (CDSIP). The impacts of the NCVBP on purchased volumes, expenditures, and pre-defined daily dose costs were evaluated by interrupted time-series (ITS) analysis using Stata 16.0. We constructed two segments with one interruptive point (March 2019). Results: Compared to the same period between pre-and post-intervention, the purchased volume of NAs medications were increased by 92.85%, and selected medications were increased by 119.09%. Analysis of changes in the level of NAs medication followed a decrease in purchased expenditure (coefficient: 5364.88, p < 0.001), meanwhile, the purchased volume was increased with statistical significance (coefficient:605.49, p < 0.001). The Defined Daily Dose cost (DDDc) of NAs medication followed a decrease (coefficient: 8.90, p < 0.001). The NCVBP reform was followed by an increase of 618.41 ten thousand Defined Daily Dose (DDD) (p < 0.001) in purchased volume and a reduction of 5273.84 ten thousand Chinese Yuan (CNY) (p < 0.001) in the purchased expenditure of selected medications in the level. The DDDc of selected medications decreased in the level (coefficient: 9.87, p < 0.001), while the DDDc of alternative medications increased in the slope (coefficient:0.07, p = 0.030). The purchased volume and expenditure of bid-winning products increased by 964.08 ten thousand DDD and 637.36 ten thousand CNY in the level (p < 0.001). An increase of 633.46 ten thousand DDD (p < 0.001) in purchased volume and a reduction of 4285.32 ten thousand CNY (p < 0.001) in the purchased expenditure of generic drugs in the level was observed. Conclusion: The NCVBP reduced the DDDc of NAs medication, improved the utilization of the selected medications, and promoted the usage of generic products.
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Introduction: This study evaluated quantitatively the impact of the first batch of the catalog of Key Monitoring and Rational Use Drugs (KMRUD) in Hubei Province on policy-related drug use and expenditures. Methods: This study is aimed to provide a basis for the successful implementation of subsequent catalogs of KMRUD, which may promote the standardization of clinical application of related drugs and effectively reduce drug expenses of the patients. Data on the procurement records of policy-related drugs from January 2018 to June 2021 were obtained from the Drug Centralized Procurement Platform of the Public Resources Trading Center in Hubei Province. Interrupted time-series (ITS) analysis was used in this study. Results: After the implementation of the first batch of the catalog of KMRUD, the consumption of policy-related drugs decreased by 83.29% in 2020. The spending on policy-related drugs decreased by 83.93% in 2020. The introduction of the first batch of the catalog of KMRUD was associated with a significant decrease in the spending on policy-related drugs in the level (p = 0.001). Before the implementation of the KMRUD catalog policy, the Defined Daily Doses (DDDs) (ß1 = -32.26 p < 0.001) and spending (ß1 = -3662.19 p < 0.001) on policy-related drugs showed a downward trend. In the aggregated ITS analysis, the Defined Daily Dose cost (DDDc) of policy-related drugs decreased significantly in the trend (p < 0.001). After the implementation of the KMRUD catalog policy, the monthly procurement volume of 10 policy-related drugs have a significant downward trend (p < 0.05), and 4 policy-related drugs have a significant upward trend (p < 0.05). Conclusion: After the policy intervention, the total DDDc on policy-related drugs indicated sustained reductions. The KMRUD policy overall achieved the goal of limiting policy-related drug use and controlling cost increases. And it is recommended that the health department quantify the usage indicator of adjuvant drugs, uniform standards, and apply prescription reviews and dynamic supervision, and other measures to strengthen supervision.
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Objectives: The purpose of this study was to quantitatively evaluate the impacts of the"4 + 7" pilot policy on purchase volume, purchase expenditures, and daily cost and to find the changes in the use of SSRIs. Methods: Data was collected covering 31 months, before, during, and after the "4 + 7" pilot policy was implemented in Shenzhen. Interrupted time-series (ITS) analysis was used to examine whether there had been a significant effect with the onset of the "4 + 7" pilot policy in March 2019. Findings: The daily cost of policy-related drugs had a substantial drop of 2.93 yuan under the "4 + 7" pilot policy. The result has shown a 76.70% increase in volume and a 3.39% decrease in the expenditure on policy-related drugs. This study found that the "4 + 7" pilot policy increased the proportion of purchasing winning drugs, with an increment of 85.60 percent. After the implementation of the "4 + 7" pilot policy, policy-related drugs decreased by 443.55thousand Chinese yuan. The study indicated that volume of winning products significantly increased as shown in the regression with a level coefficient (ß 2 ) of -224.17 (p < 0.001) and trend coefficient (ß 3 ) of 15.74 (p < 0.001). The result revealed that both volume and expenditures on branded products showed a significant decrease in the regression in the post-intervention period (level coefficient of volume: ß 2 = -57.65, p < 0.01, trend coefficient of volume: ß 3 = -3.44, p < 0.01; level coefficient of expenditure: ß 2 = -712.98, p < 0.01, trend coefficient of expenditure: ß 3 = -40.10, p < 0.01). Conclusion: The volume-based procurement has successfully led to price reductions and improved the affordability of medicines, especially for those with chronic diseases. The volume-based procurement has demonstrated initial success in reshaping the composition of the Chinese pharmaceutical market in favor of generics with high quality and low prices.
