Objective:To investigate the awareness and knowledge of influenza and vaccine among primary care providers in Shanghai.Methods:An online questionnaires survey was conducted by Shanghai Alliance for Respiratory Diseases in Primary Care from December 2017 to August 2018, healthcare providers in district central hospitals and community health care centers of Shanghai were invited to participate in the survey. The questionnaire contained the following items: the basic information of respondents; knowledge of influenza and its vaccine; current status of influenza vaccination; factors affecting promoting vaccination; the intention, attitude, perception of promoting vaccination and the influencing factors, and suggestions on promoting influenza vaccination.Results:A total of 1 542 valid questionnaires were collected, 88.3% (1 361/1 542) responders correctly recognized main symptoms of influenza; 58.2% (898/1 542) ignored the contact transmission of influenza; 41.6% (641/1 542) didn′t know the frequency of influenza vaccination; 82.7% (1 276/1 542) failed to recognize that pregnant women should also receive influenza vaccination. The survey showed that 31.2% (481/1 542) of responders had been vaccinated against influenza. The vaccination rate in community health care institutions was significantly higher than that in district central hospitals [39.1% (304/778) vs. 23.2% (177/764), χ 2=45.44, P<0.05]. Factors affecting vaccination for healthcare providers were: influenza antigen was variable, and vaccination had no effects [49.5% (404/816)]; the efficacy of the flu vaccine was doubt [48.8% (634/1 298)]; the vaccine wasn′t free [46.5%(604/1 298)]. The respondents believed that the main ways to improve the influenza vaccination were to formulate relevant national vaccination policies [79.7%(1 229/1 542)], to regularly publicize knowledge of influenza and influenza vaccine to residents through communities [65.8% (1 015/1 542)], and to recommend the patients by primary care medical staff [64.4% (993/1 542)]. Conclusion:Many healthcare providers have insufficient knowledge about influenza and vaccine. The vaccination rate of community health institutions is higher than that in district central hospitals in Shanghai. The willingness to promote influenza vaccination can be influenced by some factors. Increasing the willingness of healthcare providers might be helpful to improve the vaccination coverage among residents in the community.

MEK is a canonical effector of mutant KRAS; however, MEK inhibitors fail to yield satisfactory clinical outcomes in KRAS-mutant cancers. Here, we identified mitochondrial oxidative phosphorylation (OXPHOS) induction as a profound metabolic alteration to confer KRAS-mutant non-small cell lung cancer (NSCLC) resistance to the clinical MEK inhibitor trametinib. Metabolic flux analysis demonstrated that pyruvate metabolism and fatty acid oxidation were markedly enhanced and coordinately powered the OXPHOS system in resistant cells after trametinib treatment, satisfying their energy demand and protecting them from apoptosis. As molecular events in this process, the pyruvate dehydrogenase complex (PDHc) and carnitine palmitoyl transferase IA (CPTIA), two rate-limiting enzymes that control the metabolic flux of pyruvate and palmitic acid to mitochondrial respiration were activated through phosphorylation and transcriptional regulation. Importantly, the co-administration of trametinib and IACS-010759, a clinical mitochondrial complex I inhibitor that blocks OXPHOS, significantly impeded tumor growth and prolonged mouse survival. Overall, our findings reveal that MEK inhibitor therapy creates a metabolic vulnerability in the mitochondria and further develop an effective combinatorial strategy to circumvent MEK inhibitors resistance in KRAS-driven NSCLC.