Meis1 Regulates Nociceptor Development and Behavioral Response to Tactile Stimuli.

Nociceptors in the dorsal root ganglia (DRG) and trigeminal ganglia (TG) are necessary for transmitting pain and itch signals. However, the molecular mechanism regulating nociceptor development remains largely unknown. This study identifies that the transcription factor Meis1 is generally expressed in two groups of sensory neurons in the developing DRG. During prenatal and neonatal stages, approximately 2/3 of Meis1+ neurons are Runx1+ nociceptors, while 1/3 of Meis1+ neurons are NF200+ myelinated neurons. At postnatal stages, Meis1 expression in nociceptors is gradually reduced. Here, we constructed a Meis1 conditional knockout mouse line to selectively delete Meis1 in Nav1.8 lineage nociceptors. Microarray analyses showed that differentially expressed genes in the Meis1 mutant DRG were enriched in pathways related to sensory perception of pain and nervous system development. In addition, Meis1 regulates the expression of some marker genes of Nppb+ neurons and C-LTMRs. Furthermore, Meis1 mutant mice exhibit behavioral deficits in response to light mechanical pain, static touch and chemical itch. Therefore, this study reveals that Meis1 is required to regulate the development of nociceptors.

Application of Kalman Filter Model in the Landslide Deformation Forecast.

Nonlinear exponential trend model is linearized into the linear model, then linearized model parameters are regarded as the state vector containing the dynamic noise to erect Kalman filter model based on exponential trend model to predict the deformation of the rock landslide. Deformation observation values of the landslide are regarded as a time series to erect AR(1) model, then model parameters of AR(1) model are regarded as the state vector containing the dynamic noise to erect Kalman filter model based on AR(1) model to predict the deformation of the rock landslide. The deformation of the landslide is regarded as the function of the time, then Taylor series is used to determine the functional relationship between the deformation of the landslide and the time, and Taylor series is spread to erect Kalman filter model based on Taylor series to predict the deformation of the earthy landslide. The deformation of landslides relates to many factors, the rainfall and the temperature influence the deformation of landslides specially, thus Kalman filter model based on multiple factors is erect to predict the deformation of the earthy landslide on the basis of Taylor series. Numerical examples show that the fitting errors and the forecast errors of the four Kalman filter models are little.

Prognostic Value of the Number of Lymph Nodes Examined in Patients with Node-Negative Gastric Cancer.

BACKGROUND: Our aim was to evaluate the prognostic value of the number of lymph nodes examined (eLNs) in patients with node-negative gastric cancer (GC) and further to adjust the American Joint Committee on Cancer (AJCC) 8th staging system based on the number of eLNs. METHODS: Node-negative GC patients diagnosed during 1988-2015 from the Surveillance, Epidemiology, and End Results (SEER) database were included. On the basis of a primary cohort of 4159 node-negative GC patients, we built the adjusted AJCC 8th staging system, which was then internally validated by a bootstrap method, and externally validated with an independent cohort of 5565 node-negative GC patients. RESULTS: The median number of eLNs was 10. For the training set, the optimal eLNs thresholds were determined to be 9 for node-negative GC patients. The adjusted AJCC 8th staging system for node-negative GC patients based on the number of eLNs had a significantly higher Harrell's concordance index than the initial AJCC 8th staging system (C-index, 0.635 versus 0.616; P < 0.001). Thus, the adjusted AJCC 8th staging system had superior prognostic stratification. Similar results were found in the validation set. CONCLUSIONS: For node-negative GC patients in the United States, the adjusted AJCC 8th staging system based on the number of eLNs predicted survival more accurately and discriminatively.

Tlx3 Function in the Dorsal Root Ganglion is Pivotal to Itch and Pain Sensations.

Itch, a sensation eliciting a desire to scratch, is distinct from but not completely independent of pain. Inspiring achievements have been made in the characterization of itch-related receptors and neurotransmitters, but the molecular mechanisms controlling the development of pruriceptors remain poorly understood. Here, our RNAseq and in situ hybridization data show that the transcription factor Tlx3 is required for the expression of a majority of itch-related molecules in the dorsal root ganglion (DRG). As a result, Tlx3F/F;Nav1.8-cre mice exhibit significantly attenuated acute and dry skin-induced chronic itch. Furthermore, our study indicates that TRPV1 plays a pivotal role in the chronic itch evoked by dry skin and allergic contact dermatitis (ACD). The mutants also display impaired response to cold and inflammatory pain and elevated response to capsaicin, whereas the responses to acute mechanical, thermal stimuli and neuropathic pain remain normal. In Tlx3F/F;Nav1.8-cre mice, TRPV1 is derepressed and expands predominantly into IB4+ non-peptidergic (NP) neurons. Collectively, our data reveal a molecular mechanism in regulating the development of pruriceptors and controlling itch and pain sensations.