Perineural invasion (PNI) as the fourth way for solid tumors metastasis and invasion has attracted a lot of attention, recent research reported a new point that PNI starts to include axon growth and possible nerve “invasion” to tumors as the component. More and more tumor–nerve crosstalk has been explored to explain the internal mechanism for tumor microenvironment (TME) of some types of tumors tends to observe nerve infiltration. As is well known, the interaction of tumor cells, peripheral blood vessels, extracellular matrix, other non-malignant cells, and signal molecules in TME plays a key role in the occurrence, development, and metastasis of cancer, as to the occurrence and development of PNI. We aim to summarize the current theories on the molecular mediators and pathogenesis of PNI, add the latest scientific research progress, and explore the use of single-cell spatial transcriptomics in this invasion way. A better understanding of PNI may help to understand tumor metastasis and recurrence and will be beneficial for improving staging strategies, new treatment methods, and even paradigm shifts in our treatment of patients.

The prediction of the impact of olfactory impairment on cognitive decline in older adults has been different among different age groups. This meta-analysis sought to estimate the predictive power of olfactory impairment on cognitive decline during follow-up in older adults of different ages. A medical literature search was carried out using these databases for eligible studies: MEDLINE, COCHRANE and EMBASE. Studies recording olfaction and cognition detection at the beginning and end of the follow-up were included in the preliminary screening. The medical records of older adults without cognitive impairment at the beginning of the follow-up were taken into account in this analysis. Raw data was extracted in order to estimate the relative risk and the corresponding 95% confidence interval (95% CI). Subgroup analysis of age was performed to eliminate the effect of age on the results. Statistical heterogeneity was measured using the I² index and Cochran's Q test. Eight studies were enrolled in this analysis (3237 events and 13165 participants), and the pooled relative risk for the 70–80 years old subgroup was 2.00 (95% CI = 1.79–2.23). Relatively, there is a higher risk of cognitive impairment at the end of follow-up in younger adults with olfactory impairment at the beginning of follow-up. The length of follow-up has a little effect on the relative risk.

Cyclooxygenase-2 (COX-2) directs the synthesis of prostaglandins important for mitogenic signaling. Here we report that COX-2 is a transcriptional target of the CREB co-activator CRTC1. In addition, we detected a correlation between the LKB1-null status and presence of 72/74 kDa glycosylated COX-2, but not inactive hypoglycosylated COX-2 in fresh lung adenocarcinoma samples. Since CRTC1 is suppressed by cytoplasmic shuttling following LKB1/AMPK/SIK phosphorylation, we developed an LKB1 signature in lung cancer to search the Connectivity-MAP drug response database. Remarkably, all high-ranking drugs positively associated with the LKB1-null signature were known CRTC1 activators. Somatic LKB1 mutations are present in 20% of lung adenocarcinomas and we observed growth and cell motility inhibition with COX-2 inhibitors in LKB1-null lung cancer cells with activated CRTC1, but negligible inhibition in LKB1-wildtype cells. In summary, the CREB co-activator CRTC family directly links LKB1 with COX-2 activation and provides a new framework for selecting patients for COX-2 inhibition.