Case Report: Two Patients With EGFR Exon 20 Insertion Mutanted Non-Small Cell Lung Cancer Precision Treatment Using Patient-Derived Xenografts in Zebrafish Embryos.

Background: Epidermal growth factor receptor (EGFR) exon 20 insertion mutations are uncommon EGFR mutations and generally resistant to first- and second-generation EGFR-tyrosine kinase inhibitors (TKIs). In precision oncology, treatment regimens are tested for improving the clinical outcomes. Zebrafish embryo tumor transplant models are used in cancer research. Methods: We report two Chinese females who were diagnosed with stage IV lung adenocarcinoma and shown to harbor EGFR exon 20 insertion mutations by next-generation sequencing (NGS). Then, we established lung cancer patient-derived xenografts using a zebrafish model. The tumor cells were isolated from the patient. For case one, tumor cells were collected from lymph node biopsy, while the tumor cells were obtained from the pleural effusion. Zebrafish were inoculated with tumor cells and placed in the culture medium containing the third-generation EGFR-TKI, osimertinib. Fluorescence microscope photographs were used to record the red fluorescence area, which represented the proliferation and migration of tumor cells in the zebrafish. Results: Case one was diagnosed with lung adenocarcinoma (cT4N3M1b, stage IVB) and had an EGFR exon 20 mutation (p. N771delinsHH [abundance 14.08%]). Tumor cell proliferation and migration were significantly reduced in the osimertinib group compared with the control group. The patient received first-line osimertinib (160 mg). According to RECIST v1.1, she achieved a partial response. Case two had stage IVA lung adenocarcinoma with a pleural effusion. The pleural effusion sample was selected to obtain tumor cells for injection, and the zebrafish lung cancer model was established. The proliferation of tumor cells in the osimertinib group was significantly reduced compared to the control group. The migration of tumor cells was not significantly reduced compared to the control group. The patient also received first-line osimertinib (160 mg). The lung lesions were stable, but the pleural effusion was poorly controlled. Conclusion: Our study demonstrates the applicability of a zebrafish embryos model as an innovative platform to targeted drug testing. More precise methods are needed to select treatment options in the future.

Changes in aerobic fermentation and microbial community structure in food waste derived from different dietary regimes.

This study aimed to analyze the relationship between food components and food waste aerobic fermentation efficiency. Different food wastes were designed to be reflective of different dietary regimes, including formulated (R1), high oil/fat and salt (R2), high oil/fat and sugar (R3), and vegetarian (R4) diets, after which the physicochemical properties, enzyme activity, and structural characteristics of food waste microbial communities were examined to explore the potential mechanisms of food waste degradation under different dietary regimes. The main results of this study demonstrated that the physicochemical properties and hydrolase activity of different food waste were significantly different. The species richness in R2 and R3 food waste was higher than that of R1 and R4, whereas the community diversity of R1 and R4 food waste was higher than that of R2 and R3. At the genus level, the dominant bacteria in the four food waste types were Bacillus, Thermoactinomyces, Paenibacillus, and Cohnella.

Characteristics of gut microbiota and its response to a Chinese Herbal Formula in elder patients with metabolic syndrome.

Alterations in gut microbiota have been known to play a critical role in metabolic syndrome. However, the microbial features in elderly patients with metabolic syndrome remain unclear. A traditional Chinese Herbal Formula, Yangyin Tiluo Decoction (YTD), can alleviate metabolic syndrome and cardiovascular disease. To characterize gut microbiota in elder patients and effects of YTD on gut microbiota during treatment of metabolic syndrome, 11 healthy elderly persons and 12 elderly persons (aged 60-90 years) with metabolic syndrome were enrolled. The patients were randomly assigned to receive YTD for 4 weeks (200 mL of the decoction two times daily). The microbial composition in healthy control, pre- and post- YTD treatment group were analyzed by 16S rRNA sequencing of fecal DNAs. Biochemical measurements were conducted for elderly patients. The results showed a high inter-individual variation of gut microbiota in elderly persons. The gut microbiota was dominated by phylum Firmicutes and Actinobacteria, which was distinct from the previously defined microbiota in Irish elderly persons. The elderly patients with metabolic syndrome had higher proportions of Lactobacillus and Bifidobacterium, and lower proportions of Anaerostipes, Coprococcus, Ruminococcus than healthy controls. YTD treatment reduced the abundance of genus Bacteroidales Incertae Sedis and species Enterobacteriaceae Incertae Sedis. The concentration of plasma lipoprotein (a) was also reduced, which was negatively correlated with the abundance of an Acinetobacter species. These results reveal a remarkable dominance of Firmicutes and Actinobacteria, and highlight the distinct gut microbiota in elderly patients with metabolic syndrome, which may be involved in pathogenesis. Furthermore, the benefits of YTD treatment were observed, providing an approach to improve metabolic syndrome in elderly patients.