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The paradigm for the pharmacological management of advanced non-small cell lung cancer (NSCLC) has been revolutionized by the development of epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors (TKIs). Developing resistance to target therapy is unavoidable. Mostly, treatments for single molecular alteration after acquiring EGFR-TKI treatment resistance are well studied. However, there is limited evidence of treatment strategies for complex resistance mechanisms. Presented here is a case of an EGFR-mutated NSCLC patient who developed a complex resistance profile: T790M point mutation and EGFR amplification after first-line EGFR-TKI. This patient was safely treated with a combination of osimertinib and icotinib and achieved a significant clinical response and clear molecular response. Here we present the clinical evidence of the efficacy of osimertinib combined with icotinib in the treatment of EGFR classical mutation along with resistant mutation of T790M point mutation and EGFR amplification.

Histamine-forming bacteria were isolated from the 70 salted fish samples bought from the town market of Guangdong Province of South China. Also, the histamine forming ability(HFA) of HFB was analyzed. There were 31 strains of HFB isolated from 36 salted fishes pickled overnight. They were identified as 6 bacteria species, including Vibrio alginolyticus , Vibrio rumoiens, Staphylococcus saprophyticus, Staphylococcus xylosus, Lactococcus lactis , and Morganella morganii. Furthermore, the rate of confirmation of Vibrio alginolyticus was highest (71.9%), exceeding 200 mg/kg histamine. Particularly, Morganella morganii produced a histamine amount which exceeded 2,000 mg/kg, although it was only one isolate in this study. In addition, 5 bacteria species of HFB were isolated from 34 dried salted fishes. Among them, Staphylococcus saprophyticus was dominant in the dried salted fishes, but Staphylococcus saprophyticus produced histamines below 200 mg/kg. However, Enterobacter aerogenes from dried salted fishes formed a histamine amount exceeding 200 mg/kg. The study showed that the dominant strain of HFB was different in two kinds of salted fish. Both kinds of salted fish contained HFB whose histamine-forming capacity exceeded 200 mg/kg. As a result, the safety of salted fish should be of concern, especially salted fish pickled overnight.

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