Microbial interactions played crucial roles in influencing the assembly, stability, and function of the microbial community. The metabolites of pit mud microbiota are the key to flavor formation of Chinese strong-flavor baijiu.

Hepatoma-derived growth factor (HDGF) expression is associated with poor prognosis in non-small cell lung cancer (NSCLC); however, whether HDGF affects gefitinib resistance in NSCLC remains unknown. This study aimed to explore the role of HDGF in gefitinib resistance in NSCLC and to discover the underlying mechanisms. Stable HDGF knockout or overexpression cell lines were generated to perform experiments in vitro and in vivo. HDGF concentrations were determined using an ELISA kit. HDGF overexpression exacerbated the malignant phenotype of NSCLC cells, while HDGF knockdown exerted the opposite effects. Furthermore, PC-9 cells, which were initially gefitinib-sensitive, became resistant to gefitinib treatment after HDGF overexpression, whereas HDGF knockdown enhanced gefitinib sensitivity in H1975 cells, which were initially gefitinib-resistant. Higher levels of HDGF in plasma or tumor tissue also indicated gefitinib resistance. The effects of HDGF on promoting the gefitinib resistance were largely attenuated by MK2206 (Akt inhibitor) or U0126 (ERK inhibitor). Mechanistically, gefitinib treatment provoked HDGF expression and activated the Akt and ERK pathways, which were independent of EGFR phosphorylation. In summary, HDGF contributes to gefitinib resistance by activating the Akt and ERK signaling pathways. The higher HDGF levels may predict poor efficacy for TKI treatment, thus it has the potential to serve as a new target for overcoming tyrosine kinase inhibitor resistance in combating NSCLC.

Background. To evaluate the associations between long-term oral Chinese herbal medicines (CHMs) and recurrence and metastasis (R&M) in patients with stage II and III colorectal cancer (CRC). Furthermore, we aimed to determine the correlation between different syndrome patterns and prognosis and summarized the regularities among CHMs prescriptions, providing reference for clinical practice. Methods. An ambispective cohort study was conducted. All CRC patients who sought evaluation and treatment at Xiyuan Hospital and Beijing Cancer Hospital from August 2014 to August 2016 were included. In this study, “whether patients voluntarily take CHMs” was taken as the exposure factor, and the exposure degree was “the duration of CHM use.” Stratification was performed according to the duration of TCM use to determine the relationship with R&M of CRC. The primary outcome was disease-free survival. Patients who had R&M of CRC after taking CHMs for ≥6 months were defined as “worst patients.” R software was used for statistical analysis. The Kaplan–Meier method and Cox regression analysis were used to determine the prognosis. IBM SPSS was used to model a priori association rules; drug use rules were analyzed on this basis. Results. A total of 186 patients with stage II and III CRC after radical resection were enrolled. All patients reached the study endpoint by August 2021. The difference in disease-free survival between the two groups was most significant when the cutoff value for CHMs was 18 months ( ). Multivariate analysis showed that 18 CHMs were independent protective factors for R&M of CRC ( , HR = 0.20, 95% CI = 0.08–0.53). The ratio of Pi (spleen) and Shen (kidney) deficiency in the worst cases was higher than patients without R&M ( ). Sijunzi and Liuwei Dihuang decoctions were the most frequently used prescriptions in the anti-R&M phase. Conclusion. CHMs complying with the “Jianpi Bushen” principle may attenuate the risk of R&M in patients with stage II and III CRC. Pi (spleen) and Shen (kidney) deficiency in patients receiving TCM intervention for the first time within 6 months of radical resection may be associated with a higher CRC R&M rate. Further research is warranted to validate these findings and elucidate underlying biological mechanisms.