Background: Hand, foot and mouth disease (HFMD) and herpangina (HA), two of the most common childhood infectious diseases, are associated with enteroviruses (EVs) infection. The aim of this study was to identify the molecular epidemiology of enterovirus causing HFMD/HA in Zunyi, China, during 2019, and to describe the clinical features of the cases.Methods: We collected the information on demographic and clinical characteristics, laboratory data of laboratory-confirmed EVs associated HFMD/HA cases in Zunyi Medical University Third Affiliated Hospital between March 1 and July 31, 2019. EV types were determined by either one-step real time RT-PCR or partial VP1 gene sequencing and sequence alignment. Phylogenetic analysis of CVA6, CVA2, and CVA5 were established based on the partial VP1 gene sequences by neighbor-joining method. Differences in clinical characteristics and laboratory results of the cases were compared among patients infected with the most prevalent EV types.Results: From 1 March to 31 July 2019, 1,377 EVs associated HFMD/HA inpatients were confirmed. Of them, 4 (0.3%, 4/1,377) were EV-A71-associated cases, 84 (6.1%, 84/1,377) were CVA16-associated cases, and 1,289 (93.6%, 1,289/1,377) were non-EV-A71/CVA16-associated cases. Of the randomly selected 372 non-EV-A71/CVA16 cases, EV types have been successfully determined in 273 cases including 166 HFMD and 107 HA cases. For HFMD cases, the three most common types were CVA6 (80.7%, 134/166), CVA2 (5.4%, 9/166) and CVA5 (3.0%, 5/166); similarly, for HA cases, the three most prevalent serotypes were CVA6 (36.5%, 39/107), CVA2 (21.5%, 23/107) and CVA5 (18.7%, 20/107). Phylogenetic analysis showed that subclade D of CVA5, and subclade E of CVA6 and CVA2 were predominant in Zunyi during the outbreak in 2019. Compared with the cases caused by CVA16, the incidence of high fever and severe infection associated with CVA2, CVA5, and CVA6 was higher.Conclusions: The recent HFMD/HA outbreak in Zunyi is due to a larger incidence of CVA6, CVA2, and CVA5. Novel diagnostic reagents and vaccines against these types would be important to monitor and control EV infections.

Purpose: Drug resistance is the main cause of chemotherapy failure in hepatocellular carcinoma. Kaempferol (KAE) is a natural flavonoid compound, which has a certain chemo-sensitivity enhancement effect. However, the potential molecular mechanism of KAE reversing drug resistance in hepatocellular carcinoma remains unclear. Methods: RT-qPCR was used to evaluate the interference effect of siDNA-PKcs. RT-qPCR and WB assays were used to detect the mRNA and protein expression of DNA damage repair related genes (γ-H2AX, DNA-PKcs, Artemis) and drug delivery pump gene (P-gp). Flow cytometry was used to detect cell cycle and apoptosis. Results: In this study, we found that KAE significantly increased the mRNA and protein levels of γ-H2AX, and down-regulated the mRNA and protein levels of DNA-PKcs and Artemis, on the other hand, it also down-regulated the mRNA and protein levels of P-gp, and ultimately jointly promoted the DNA damage, cell apoptosis, and cell cycle arresting in the G2/M phase of drug-resistant Bel-7402/5-Fu cells. Mechanically, KAE mainly promoted the degradation of DNA-PKcs through ubiquitin proteasome pathway, down-regulated the protein level of DNA-PKcs, inhibited the DNA-PKcs/Artemis pathway, promoted DNA damage, induced cell apoptosis and cell cycle arresting. Conclusions: KAE may be used as a sensitizer for clinical treatment of chemotherapy resistance of HCC, and inhibition of DNA-PKcs may also become a new strategy and target for the treatment of HCC.