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No consensus has been achieved on the benefit of radiotherapy for resected stage IIIA NSCLC patients. The division of stage IIIA has changed significantly in 2017. This study aims to explore the effects of radiotherapy on the survival of patients with resectable stage IIIA NSCLC in the new era.Patients diagnosed with NSCLC between 2010 and 2018 were identified in the 8th edition TNM classification from the Surveillance, Epidemiology, and End Results database. A nomogram was developed by integrating all independent predictors for lung cancer-specific survival (LCSS). The Propensity Score Matching (PSM) and subgroup analysis were applied to mitigate potential bias. Survival analyses were conducted using the Kaplan Meier curves and Cox proportional hazards regression.A total of 2632 stage IIIA NSCLC patients were enrolled. The C-index of the nomogram for the prediction of LCSS was 0.636 (95% CI, 0.616-0.656). In the group of patients with N2 stage who featured more than 5 positive regional lymph nodes, compared with non-PORT, PORT did prolong postoperative survival time (50 vs. 31 months; P= .005). N2 patients with visceral pleural invasion (VPI), older (age65), or had a larger tumor (size3 cm) could also benefit from adjuvant radiotherapy.Treatment protocol for stage IIIA NSCLC patients should be individualized. Based on our findings, N2 patients with more than 5 positive regional lymph nodes, VPI, larger tumor size (greater than 3 cm), and older (age above 65) could benefit from adjuvant radiotherapy. Further well-designed randomized trials are warranted.

Cancer has been the leading cause of death due mainly to tumor metastasis. The tumor microenvironment plays a key role in tumor metastasis. As the main stromal cells in tumor microenvironment originated from activated fibroblast, cancer-associated fibroblasts (CAFs) play a major role in promoting tumor metastasis. A promising therapeutic avenue is reprogramming of CAFs into tumor-restraining quiescence state. In this study, we observed that CAF-like active pancreatic stellate cells (PSCs) interact with each other via N-cadherin, a force-sensitive transmembrane receptor. Since N-cadherin ligation mediated mechanotransduction has been reported to restrict integrin mediated signalling, we thus hypothesized that the reprogramming of activated PSCs by mechanical modulation of N-cadherin ligation might be possible. To test this hypothesis, we grafted N-cadherin ligand (HAVDI peptide) onto soft polyethylene glycol hydrogel substrate prior to cell adhesion to mimic cell-cell interaction via N-cadherin ligation. We found that the activated PSCs could be reprogrammed to their original quiescent state when transferred onto the substrate with immobilized HAVDI peptide. These results reveal a key role of mechanosensing by intercellular transmembrane receptor in reprogramming of activated PSCs, and provide a potential way for designing novel therapeutic strategies for cancer treatment.

R mRNA in the mPFC was significantly decreased to 5-Hydroxytryptamine7 (5-HT7) receptors in the medial prefrontal cortex (mPFC) play a critical role in complex cognitive impairment in schizophrenia. The mouse model of schizophrenia was established through the neonatal administration of phencyclidine (nPCP). Recombinant adeno-associated virus-mediated gene knockdown was used to investigate the role of mPFC 5-HT7 receptor in the schizophrenia-like symptoms in mice. Under baseline conditions in the 5-choice serial reaction time task (5-CSRTT), nPCP produced a significant attentional impairment that was exacerbated when mice were tested under LITI. Premature and perseverative responding in nPCP mice were both increased, thus suggesting deficits in inhibitory response control. The deficits in attentional performance and premature responding of nPCP mice were improved or fully rescued by 5-HT7 receptor downregulation under heavy perceptual load. Downregulation of the 5-HT7 receptor in the mPFC ameliorated spatial working memory and had no effects on nPCP-induced impairments in recognition memory and MA-induced hyperlocomotion. These results suggest that 5-HT7 receptor is involved in the cognitive outcomes of schizophrenia-like symptoms similar to humans. Downregulation of the 5-HT7 receptor in the mPFC exert complex effects in a mouse model of schizophrenia and may be of benefit in treating schizophrenia-related impulsive actions.