Lung cancer is the leading cause of cancer deaths in the world. Brain metastasis (BM) can affect about 25% of non-small cell lung cancer (NSCLC) patients during their lifetime. Efforts to characterize patients that will develop BM have been disappointing. MicroRNAs (miRNAs) play a role in regulating a variety of targets and, consequently, multiple pathways, which make them a powerful tool for early detection of disease, risk assessment and prognosis. In this study, using RT-PCR and further northern blot validation, we confirmed that miR-378 was significantly differentially expressed in the matched NSCLC from 8 patients with BM and 21 without BM. Our study showed evidences that miR-378 is associated with non-small cell lung cancer brain metastasis by promoting cell migration, invasion and tumor angiogenesis. MiR-378 may be a potential biomarker for characterizing non-small cell lung cancer brain metastasis and assisting clinicians in stratifying the high-risk patients on a clinical trial for either prophylactic cranial irradiation or a new intervention that may mitigate BM development, ultimately leading to a new standard of care for NSCLC patients.

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Ischemic stroke not only induces neuron death in the infarct area but also structural and functional damage of the surviving neurons in the surrounding peri-infarct area. In the present study, we first identified cofilin rod, a pathological rod-like aggregation, formed in neurons of in vivo ischemic stroke animal model and induced neuronal impairment. Cofilin rods formed only on the ipsilateral side of the middle cerebral artery occlusion and reperfusion (MCAO-R) rat brain and showed the highest density in peri-infarct area. Our real-time live cell imaging, immunostaining and patch clamp studies showed that cofilin rod formation in neurons led to dendritic mitochondrial transportation failure, as well as impairment of synaptic structure and functions. Overexpression of LIM kinase or activation of its upstream regulator Rho, suppressed ischemia-induced cofilin rod formation and showed protective effect on synaptic function and structure impairment in both cultured neurons and MCAO-R rat model. In summary, our results demonstrate a novel mechanism of ischemic stroke-induced neuron injury in peri-infarct area and provide a potential target for the protection of neuronal structure and function against brain ischemia insult.

The authors Jing Liang and Xiao-quan Xu contributed equally to this article.Objective: To differentiate pre-invasive lesion from invasive pulmonary adenocarcinoma (IPA) appearing as ground-glass nodules (GGNs) using CT features. Methods: 149 GGNs were enrolled in this study, with 74 pure GGNs (p-GGNs) and 75 mixed GGNs (m-GGNs). Firstly, univariate analysis was used to analyse the difference of CT features between pre-invasive lesion and IPA. Then, multivariate analysis was conducted to identify variables that could independently differentiate pre-invasive lesion from IPA. Receiver operating characteristic curve analysis was performed to evaluate the differentiating value of identified variables. Results: In the p-GGNs, multivariate analysis showed that the amount of blood vessels was an independent risk factor. Using the amount of blood vessels "$1" as the diagnostic criterion, we could diagnose IPA with a sensitivity of 100%. Using the amount of blood vessels "50" as the diagnostic criterion, we could diagnose pre-invasive lesions with a specificity of 100%. In the m-GGNs, multivariate analysis showed that the volume of solid portion (V Solid ) and pleural indentation were two independent risk factors. One further model was constructed using these two variables: model 5 2.508 3 (V Solid 1 1.407) 3 (pleural indentation 2 1.016). Using the new model, improved diagnostic ability was achieved compared with using V Solid or pleural indentation alone. Conclusion: The amount of blood vessels through the p-GGNs would be an important criterion during clinical management, while V Solid and pleural indentation seemed important for m-GGNs. Moreover, the new model could further improve the differentiating value for m-GGNs. Advances in knowledge: CT features are useful in differentiating pre-invasive lesion from IPA appearing as GGNs. INTRODUCTIONAccording to the new pathological classification constituted in 2011, lung adenocarcinoma was divided into the preinvasive lesion group and the invasive pulmonary adenocarcinoma (IPA) group.1,2 Significant difference existed between these two groups regarding the surgical method and the scope of lymph node dissection.2-5 Sublobar resection could be acceptable for pre-invasive lesion, while the standard surgical treatment for IPA should be lobectomy.2-5 Skip metastases involving mediastinal lymph nodes, without hilar lymph nodes appeared mostly in the IPA group, thus the scope of lymph node dissection for the IPA group should be larger than for the pre-invasive lesion group.2-5 Therefore, accurate differentiation between preinvasive and IPA lesions before surgery was crucial, particularly for surgery planning, prognosis assessment and doctor-patient communication.