Glycyrrhizic acid inhibits DNA damage repair and enhances cisplatin-induced apoptosis of melanoma cells.

This research was designed to prospect the mechanism and impact of glycyrrhizic acid (GA) on DNA damage repair and cisplatin (CP)-induced apoptosis of melanoma cells. First, human melanoma cell SK-MEL-28 was stimulated using GA for 24, 48, and 72 h. Then, the optimal treatment time and dosage were selected. After that, cell counting kit-8 (CCK-8) was employed for testing the cell viability, flow cytometry for the apoptosis, comet assay for the DNA damage of cells, and western blot for the cleaved-Caspase3, Caspase3, Bcl-2, and γH2AX protein expression levels. The experimental outcomes exhibited that as the GA concentration climbed up, the SK-MEL-28 cell viability dropped largely, while the apoptosis level raised significantly, especially at the concentration of 100 µm. In addition, compared with GA or CPtreatment only, CP combined with GA notably suppressed the viability of melanoma cells and promoted cell apoptosis at the cytological level. At the protein level, the combined treatment notably downregulated the Bcl-2 and Caspase3 expression levels, while significantly upregulated the cleaved-Caspase3 and γH2AX expression levels. Besides, CP + GA treatment promoted DNA damage at the DNA molecular level. Collectively, both GA and CP can inhibit DNA damage repair and enhance the apoptosis of SK-MEL-28 cells, and the synergistic treatment of both exhibits better efficacy.

Evaluation of marketing authorization and labels of medicines in 2021 WHO Model List of Essential Medicines for Children in China, the Russian Federation and Brazil.

OBJECTIVE: This work compares the marketing authorization, labels and dosage forms of medicines in the WHO Model List of Essential Medicines for Children (EMLc) in China, the Russian Federation and Brazil to urge policymakers to pay more attention to paediatric medication. METHODS: Medicines were selected from the 8th EMLc. By searching relevant databases, which include different types of medical information in China, the Russian Federation and Brazil, the marketing authorization, labels and dosage forms of paediatric medicines in the three countries were evaluated. RESULTS: A total of 485 drug products containing 312 active pharmaceutical ingredients listed in the WHO EMLc were evaluated. Among them, 344 products were approved for use in China, 286 in the Russian Federation and 264 in Brazil. Out of the 344 approved medicines, 317 (92.15%) were authorized for paediatric use in China, 224 (78.32%) in the Russian Federation and 218 (82.58%) in Brazil. In terms of guidance information labelling on drug labels, 75.08%, 83.04% and 88.07% of paediatric drugs approved in China, the Russian Federation and Brazil, respectively, clearly indicated the usage and dosage for paediatric use. Additionally, injections and tablets were the most prevalent dosage forms in these three countries. CONCLUSION: There is still scope for enhancing the marketing authorization and development of dosage forms for paediatric medicines in the three countries. Furthermore, additional measures are being implemented to enhance the information provided on drug labels for children, particularly in China.

Preferences and Willingness to Pay for Medication in Patients with Renal Cell Carcinoma in China: A Discrete-Choice Experiment.

OBJECTIVE: We aimed to assess the relative importance of attributes and the willingness to pay for pharmacological therapies among patients with renal cell carcinoma in China. METHODS: Patients with renal cell carcinoma completed a D-efficient-designed, discrete-choice experiment online survey that presented a series of ten trade-off questions and one examining scenario. Based on the literature review and consultations with patients with renal cell carcinoma and clinicians, each question included a pair of hypothetical renal cell carcinoma medication profiles characterized by seven attributes including progression-free survival, objective response rate, medication regimen, fatigue, gastrointestinal reaction, hand-foot syndrome, and monthly out-of-pocket costs. Relative importance and willingness to pay were calculated using coefficients estimated by mixed logit regression in the main analysis. Subgroup analyses were conducted considering the heterogeneity of the participants, based on sex, education level, and income level, using conditional logit regression. RESULTS: The analysis incorporated responses from 182 Chinese respondents. Except for the medication regimen, all attributes were statistically significant. Progression-free survival was the most important attribute, followed by objective response rate, monthly out-of-pocket costs, fatigue, gastrointestinal reaction, and hand-foot syndrome. Patients were willing to pay ï¿¥2010.51 ($298.30), ï¿¥494.93 ($73.43) for 1 unit improvement of progression-free survival, and objective response rate, andï¿¥7558.93 ($1121.50), ï¿¥6927.24 ($1027.78) to avoid experiencing fatigue and gastrointestinal reaction, respectively. Differences in preferences and willingness to pay were found according to patients' gender, income, and education level. CONCLUSIONS: In China, patients with renal cell carcinoma preferred medications with better efficacy (objective response rate and progression-free survival) and lower out-of-pocket costs. Heterogeneity can be found in preferences and willingness to pay based on patients' gender, income, and education levels.

An Analysis of Accessibility of Representative Psychotropic Medicine From the World Health Organization Model List of Essential Medicines in Developing Countries With Different Income Levels.

OBJECTIVES: The objective of this study was to analyze the accessibility of psychotropic medicine in developing countries based on the availability, price, and affordability indicators to create international evidence to guide the development of policies on the accessibility of medicines. METHODS: This study included 5 types of psychotropic medicines listed in the 22nd edition of the World Health Organization Model List of Essential Medicines published by the World Health Organization in 2021. Derived from 84 surveys in 59 countries, this study summarizes the availability, price, and affordability of originator branded drugs (OBs) and lowest-price generic drugs (LPGs) in the public and private sectors and compares them based on income levels in different countries. RESULTS: The average availability of psychotropic medicine was 45% in low- and lower-middle-income countries (LLMICs) compared with 49% in high- and upper-middle-income countries (HUMICs) whereas the availability of LPGs was higher than that of OBs in all country groups. The average patient price for OBs and LPGs was 94.0 and 23.2, respectively, and the overall patient price of psychotropic medicine in LLMICs was higher than that in HUMICs. The affordability of psychotropic medicine in LLMICs was lower than that in HUMICs. CONCLUSIONS: Psychotropic medicines in lower-middle-income countries have lower availability, a higher average patient price, and lower average affordability than in HUMICs, which requires lower-middle-income countries to take effective and various measures to improve the accessibility of psychotropic medicine.

Degarelix vs. leuprorelin for the treatment of prostate cancer in China: A cost-utility analysis.

Objective: To explore the cost-effectiveness of degarelix acetate for injection (degarelix) compared to leuprorelin in prostate cancer (Pca) castration treatment from Chinese healthcare system perspective. Methods: A Markov model, adapted from the one established in Finland was conducted for the cost-effectiveness analysis of degarelix and leuprorelin for Pca treatment. The main data were derived from global phase III clinical trials of degarelix (CS21), published study and expert surveys. Outcomes, utility and costs of prostate cancer patients were calculated on a 30-year time horizon. The CS21 study based population of intention-to-treat (ITT) population and three scenarios were modeled. Taking three times of the Gross domestic product (GDP) per capita (242,928 yuan, 2021) as the acceptable threshold for cost-effectiveness. One-way and probabilistic sensitivity analyses were performed on key parameters, including transition probabilities, costs, utility, and discount rate to test the robustness of the model. Results: Base case analysis for ITT population revealed that total costs of degarelix and leuprorelin were 566,226 yuan and 489,693 yuan, while the total quality-adjusted life years (QALYs) were 5.19 and 4.51 during the 30-year time horizon, resulting an incremental cost effectiveness ratio (ICER) of 112,674 yuan/QALY which was 1.39 times the GDP per capita, lower than willingness-to-pay level of three times the GDP per capita. The results for scenario analyses revealed that compared to leuprorelin, degarelix for Pca treatment in China was cost-effective. One-way sensitivity analysis showed that the model was most sensitive to price of 80 mg degarelix, utility of 1st-line therapy, hazard ratio of PSA recurrence, price of 3.75 mg leuprorelin, response rate of docetaxel per cycle, and discount rate of cost. In probabilistic sensitivity analysis, compared to leuprorelin, the probability of degarelix to be cost-effective was 53 and 81% for willingness-to-pay threshold of one and three times the GDP per capita. Conclusion: Compared to leuprorelin, degarelix for prostate cancer treatment is cost-effective. Moreover, scenario, one-way, and probabilistic sensitivity analyses revealed that the model was robust.

The Consistency Between the Chinese Essential Medicines List and Treatment Guidelines-Taking Oncology Medicines as an Example.

The concepts of "essential medicine" and "national medicine policy" were first put forward for the first time at the World Health Assembly in 1975 in an effort to alleviate the problem of medicine unavailability in developing and poor countries. The essential medicine system in China has experienced three development stages since 1979, when the concept of essential medicines was first introduced, to actively respond to the call of the World Health Organization. Currently, the essential medicines list published in China is the national essential medicines list (2018 Edition). In this study, we examined the consistency between the essential medicines for treating seven cancers (liver cancer, breast cancer, esophageal cancer, lung cancer, colorectal cancer, gastric cancer, and leukemia) and the recommended medicines by cancer treatment guidelines to determine whether the essential medicines are of high quality for clinical needs. The results indicated that the degree of similarity between oncology medicines on the essential medicines list and oncology medicines recommended by guidelines was low, with the majority falling between 30 and 60%. Therefore, to improve the quality of essential medicines, it is necessary to further improve the matching degree. In addition, to further improve the consistency between the essential medicines list and treatment guidelines, the following suggestions are put forward in this paper: (1). Formulate universal treatment guidelines; (2). When selecting essential medicines, greater consideration should be given to those recommended in the guidelines; (3). The essential medicines list and treatment guidelines should be concurrently updated; (4). The cycle for updating the essential medicines list and treatment guidelines should be shortened.

Exploring The Role of Guanxi in CSR performance and Knowledge Management of a Stakeholder Network: A Case of iStone, China.

Background: CSR performance is significantly affected by the degree of knowledge exchange. As Chinese firms have increasingly engaged in CSR activities, significant attention has been paid to how groups of stakeholders share and exchange knowledge resources strategically to increase their CSR performance. A guanxi network is an important facilitator in the mobilization of knowledge in CSR activities. This study explores how stakeholders strategically leverage their guanxi and structural holes to affect the efficacy of knowledge exchange to increase CSR performance. Methods: A mixed-methods research approach was employed to gather data from the stakeholders of a Chinese digital firm iStone. Specifically, 325 questionnaires and social network analyses were collected as well as 55 semi-structured interviews were conducted to test the hypotheses. Results: As a result, structural holes impede knowledge exchange among stakeholders in their guanxi network, but guanxi moderates this impeding effect. In addition, knowledge exchange promotes CSR performance. Conclusion: By developing a mechanism to reveal how stakeholders' structural hole filling behavior influences their CSR performance, our study places an emphasis on reciprocal resource exchange which generates several implications for CSR performance enhancement. In addition, by demonstrating how structural hole controllers' become 'structural hole fillers' under the moderating influence of guanxi, this study recognizes the cultural contingency that conditions the effect of structural holes on knowledge exchange. This study also suggests stakeholders to cultivate guanxi with their network members who own yet-to-be-filled structural holes to fill their holes and increase firms sustainable performance by giving renqing, returning renqing, earning mianzi and giving mianzi.

Treatment of solitary hepatocellular carcinoma up to 2 cm: A PRISMA-compliant systematic review and meta-analysis.

BACKGROUND: In recent years, there has been considerable uncertainty about the optimal treatment option for very early hepatocellular carcinoma (HCC) with tumor size less than 2 cm. Therefore, we performed a systematic review and meta-analysis to evaluate the outcomes of the different treatments. METHODS: This study was designed in accordance with the Preferred Reporting Items for Systematic Review and Meta-analysis (PRISMA). PubMed, EMBASE, and Cochrane library were searched for calculating the survival rates, and the "time to event" method was used to compare the outcomes of liver resection (LR) and radiofrequency ablation (RFA). All studies focusing on the treatment of solitary HCC up to 2 cm by different techniques were included in our analysis. The Hazard ratios (HR) and 95% confidence intervals (CI) derived from multivariate and univariate analysis were utilized to assess the treatment risks. RESULTS: We included 32 studies in our systematic review. The median 5-year overall survival (OS) and recurrence-free survival rate (RFS) for LR were 73% and 47%, respectively, and those for RFA were 73% and 43%, respectively. RFA was found to be associated with increased risk of mortality and recurrence compared to LR (HR = 1.61, 95% CI: 1.35-1.92, P < .0001 for OS and HR = 1.75, 95% CI: 1.56-1.96, P < .0001 for RFS). CONCLUSION: Our meta-analysis demonstrated that LR is superior to RFA in the treatment of solitary HCC up to 2 cm, with reduction in mortality and recurrence risk and improved long-term outcome.

China's new policy for healthcare cost-control based on global budget: a survey of 110 clinicians in hospitals.

BACKGROUND: The increasing cost on healthcare exposes China's healthcare budgets and system to financial crisis. To control the excessive growth of healthcare expenditure, China's healthcare reforms emphasize the control of the global budget for healthcare, which leads to the release of relevant policy and a series of cost-control actions implemented by different hospitals. This work aims to identify the effects brought by the cost-control policy and actions via surveying and analysing feedback from clinicians. METHODS: Questionnaires on the cost-control policy and actions were designed for surveying 110 clinicians in hospitals from different regions of China. The data on the implementation of the cost-control actions and doctors' feedback on these actions were analysed using descriptive statistics. Pearson's chi-squared tests were performed to detect associations between doctors' opinions and specific cost-control actions. A value of p < 0.05 was considered statistically significant. Association relationships between doctors' opinions and cost-control actions were modelled into network models, and key factors were identified in a multi-variate framework. Last, we visualized our resultant data using a network model, and further multi-variate analysis was performed. RESULTS: There were three main findings. (1) The cost-control policy has been widely implemented in the sampled hospitals in different regions of China, with more than 80% of those surveyed acknowledging that their hospitals take actions of reducing average prescription fees for outpatients, drug costs, and in-hospitalization durations. (2) Most doctors have a negative view of some cost-control actions; this is mainly due to concerns about the effects of these actions on the doctors' own healthcare performance and patient satisfaction. (3) Cost-control actions that had a significant impact on doctors' performance included limiting average prescription fees for outpatients and limiting the use of examinations/drugs/surgeries. Decreased patient satisfaction was associated with fewer admissions of critically ill patients, reduced use of brand-name drugs, and increased total costs to patients due to increased frequencies of visits to the hospitals. CONCLUSIONS: Cost-control actions implemented in hospitals in response to the government's policy to reduce its national healthcare budget affect both doctors and patients in several ways. Moreover, the cost-control policy and actions can be improved.

Indirect comparison of the efficacy and safety of gefitinib and cetuximab-based therapy in patients with advanced non-small-cell lung cancer.

The aim of this study was to systematically evaluate the efficacy and safety of gefitinib and cetuximab-based therapies in patients with advanced non-small-cell lung cancer (NSCLC). The studies to be used for the comparisons were selected from the available literature on gefitinib and cetuximab-based therapies compared to conventional chemotherapy in patients with advanced NSCLC. The meta-analysis was performed with RevMan 5.0 software and the Bucher approach was applied to conduct the indirect comparisons. A total of 4 studies, including 935 patients, on gefitinib therapy vs. conventional chemotherapy and 4 studies, including 1,015 patients, on cetuximab-based therapy vs. conventional chemotherapy, were used for indirect comparisons. As regards efficacy, the risk ratio (RR) of objective response rate and 1-year survival rate between gefitinib and cetuximab-based therapies in patients with advanced NSCLC were 0.99 [95% confidence interval (CI): 0.75-1.32; P=0.9584] and 0.85 (95% CI: 0.71-1.01; P=0.0696), respectively, and the mean difference of progression-free survival and overall survival (OS) were -0.15 (95% CI: -0.90 to 0.60; P=0.6946) and -1.84 (95% CI: -3.53 to -0.15; P=0.0331), respectively. As regards safety, the RR of grade 3/4 adverse events (AEs) was 0.29 (95% CI: 0.19-0.44; P=0.0001). The results demonstrated that cetuximab-based therapy was superior to gefitinib therapy in terms of OS and inferior to gefitinib therapy in terms of AEs, whereas there were no significant differences in terms of efficacy and safety between the two therapies on other endpoints adopted for advanced NSCLC. However, further well-designed randomized controlled trials and continuous studies are required to confirm our findings.