To cope with the increasing healthcare costs brought about by the universal health insurance programme, national volume-based procurement (NVBP) was implemented in China to reduce drug prices. However, the impact of NVBP remains unknown. We reported the effects of the NVBP pilot programme on medication affordability and discussed the challenges and recommendations for further reforms. A total of 25 molecules won the bidding in the NVBP pilot programme, and price cuts ranged from 25% to 96%. Medication affordability was measured as the number of days’ wages needed to pay for a course of treatment, and the medication was identified as affordable if the cost of a treatment course was less than the average daily wage. After the NVBP, the proportion of affordable drugs increased from 33% to 67%, and the mean affordability improved from 8.2 days’ wages to 2.8 days’ wages. Specifically, for rural residents, the proportion of affordable drugs increased from 13% to 58%, and the mean affordability improved from 15.7 days’ wages to 5.3 days’ wages. For urban residents, the proportion of affordable drugs increased from 54% to 71%, and the mean affordability improved from 5.9 days’ wages to 2.0 days’ wages. Implementing the NVBP substantially improved medication affordability. In future reforms, a multifaceted approach addressing all issues in the health system is needed to enhance medicine access.

Ovarian cancer is a gynecological malignancy with the highest recurrence and mortality rates. Although niraparib can effectively affect its progression, the challenge of drug resistance remains. Herein, niraparib-resistant ovarian cancer cell lines were constructed to identify the abnormally activated enhancers and associated target genes via RNA in situ conformation sequencing. Notably, the target gene RAD23A was markedly upregulated in niraparib-resistant cells, and inhibiting RAD23A restored their sensitivity. Additionally, abnormal activation of glycolysis in niraparib-resistant cells induced lactate accumulation, which promoted the lactylation of histone H4K12 lysine residues. Correlation analysis showed that key glycolysis enzymes such as pyruvate kinase M and lactate dehydrogenase A were significantly positively correlated with RAD23A expression in ovarian cancer. Additionally, H4K12la activated the super-enhancer (SE) of niraparib and RAD23A expression via MYC transcription factor, thereby enhancing the DNA damage repair ability and promoting the drug resistance of ovarian cancer cells. Overall, the findings of this study indicate that lactic acid accumulation leads to lactylation of histone H4K12la, thereby upregulating SE-mediated abnormal RAD23A expression and promoting niraparib resistance in ovarian cancer cells, suggesting RAD23A as a potential therapeutic target for niraparib-resistant ovarian cancer.

Introduction: Azithromycin and levofloxacin have been shown to be efficacious in treating infections. The adverse drug events associated with azithromycin and levofloxacin were considered rare. How...

An increasing number of myocarditis/pericarditis incidences has been reported after coronavirus disease-19 (COVID-19) vaccination in adolescents and young adults. This study was designed to investigate the incidence rate of—and risk for—myocarditis and pericarditis following COVID-19 vaccination in the United States according to age and vaccine type. This study used the Vaccine Adverse Events Reporting System (VAERS) from 11 December 2020 to 13 August 2021. A population-based data mining approach was performed based on the reporting odds ratio (ROR). Adverse events of myocarditis and pericarditis following COVID-19 vaccination were rare, with an incidence rate of 5.98 (95% CI = 5.73–6.24) cases per million doses administered. The incidence rate was higher in adolescents and after the administration of the second dose of messenger RNA (mRNA) vaccines. Overall, two mRNA vaccines were significantly associated with increased risks for myocarditis/pericarditis (mRNA-1273 (Moderna): ROR = 2.91, 95% CI = 2.21–3.83; BNT162b2 (Pfizer–BioNTech): ROR = 5.37, 95% CI = 4.10–7.04) compared to all other vaccines from VAERS. The viral vector vaccine of Ad26.COV2.S (Janssen) was not associated with signals of myocarditis/pericarditis (ROR = 1.39; 95% CI = 0.99–1.97). This study found increased risks for myocarditis/pericarditis following mRNA COVID-19 vaccines. For patients at high risk for myocarditis/pericarditis or with myocardial injuries, the viral vector vaccine may be an alternative for consideration.

Background: The emergency use authorization for coronavirus disease 2019 (COVID-19) vaccines brought both hopes and concerns to the Americans and others. We aimed to estimate the mortality rate of COVID-19 vaccination and presented characteristics of deaths following COVID-19 vaccination.Methods: Data on deaths following COVID-19 vaccination were obtained from the Vaccine Adverse Event Reporting System (VAERS) from December 11, 2020 through January 8, 2021. The Centers for Disease Control and Prevention (CDC) COVID Data Tracker was used to identify the total number of people receiving COVID-19 vaccines during the same period to estimate the mortality rate. Stratified analysis was conducted by the location of vaccination.Results: As of January 8, 2021, 55 deaths were reported, and the mortality rate of COVID-19 vaccination was 8.2 per million population. A total of 37 deaths were reported among long-term care facility residents, and the mortality rate was 53.4 per million population. Top reported comorbidities associated with deaths included hypertension, dementia, chronic obstructive pulmonary disease (COPD), diabetes, and heart failure. In addition, dementia was more likely to be associated with deaths vaccinated at long-term care facilities than at other locations.Conclusion: The benefits of COVID-19 vaccines outweigh the potential risks in older frail populations, and our findings do not support actions to exclude older adults from being vaccinated. However, continued monitoring of COVID-19 vaccination is still warranted.