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Abstract: Adenosquamous carcinoma (ADSQ) is uncommon in non-small cell lung cancer (NSCLC). The frequency rate of ADSQ was 9.7% of 6990 primary lung cancers resected in our department. Many researches have analyzed genetic and molecular alterations in adenocarcinoma (AD) and squamous cell carcinoma (SQ), but few molecular studies have been conducted on heterogeneous ADSQ. The current study was to investigate gene mutations of epidermal growth factor receptor (EGFR) and Kirsten rat sarcoma viral oncogene (KRAS) and their correlation with clinical variables in Chinese patients with ADSQ. Histologic features were reviewed, and immunohistochemical (IHC) and molecular (EGFR and KRAS) studies were done in 55 Chinese patients with ADSQ. Microscopically, all the tumors demonstrated dual differentiation with varying proportions of AD and SQ. Based on morphological diagnosis, a combination of multiple IHC markers is helpful for accurately discriminating two undifferentiated histologic subtypes of ADSQ. EGFR mutations were identified in 21 (38.2%) patients: 11 mutations were in exon 19, 1 in exon 20, 7 in exon 21 and double mutations were found in two patients. We also found two new mutations, namely, L747-E749del K754A within exon 19 and H850R within exon 21. Moreover, 16 (29.1%) silent mutations Q787Q in exon 20 were found in the series, five of which coexisted with other mutations. EGFR mutations were more frequently found in patients with size of the tumors ≥3cm [19/35 (54.3%); 2/20 (10%); P =0.001] or coexistent double cancer. However, the EGFR mutation was not associated with gender, age, lymph node status, tumor stage and smoking history. KRAS mutations were present in 2 (3.64%) male patients in codon12 (G12C) and none of them showed EGFR mutation. Moreover, identical EGFR and KRAS mutations in both components of ADSQ were further confirmed by microdissection techniques. The data indicated that the incidence of EGFR and KRAS mutations in Chinese patients with ADSQ were similar to those of Asian patients with AD. Furthermore, EGFR silent mutations accounted for a large proportion in ADSQ. Additional prospective studies are needed in order to define the clinical relevance of new and silent mutation variants. [Copyright &y& Elsevier]

[Display omitted] Traumatic brain injury (TBI) is a brain injury resulting from blunt mechanical external forces, which is a crucial public health and socioeconomic problem worldwide. TBI is one of the leading causes of death or disability. The primary injury of TBI is generally irreversible. Secondary injury caused by neuroinflammation could result in exacerbation of patients, which indicated that anti-inflammation and immunomodulatory were necessary for the treatment of TBI. Accumulated evidence reveals that the transplantation of umbilical cord mesenchymal stem cells (UCMSCs) could regulate the microenvironment in vivo and keep a balance of helper T 17(Th17)/ regulatory T cell (Treg). Therefore, it is reasonable to hypothesize that the UCMSCs could repair neurological impairment by maintaining the balance of Th17/Treg after TBI. In the study, we observed the phenomenon of trans-differentiation of T lymphocytes into Th17 cells after TBI. Rats were divided into Sham, TBI, and TBI + UCMSCs groups to explore the effects of the UCMSCs. The results manifested that trans-differentiation of Th17 into Treg was facilitated by UCMSCs, which was followed by promotion of neurological recovery and improvement of learning and memory in TBI rats. Furthermore, UCMSCs decreased the phosphorylation of nuclear factor-kappa B (NF-κB) and increased the expression of mothers against decapentaplegic homolog 3 (Smad3) in vivo and vitro experiments. In conclusion, UCMSCs maintained Th17/Treg balance via the transforming growth factor-β (TGF-β)/ Smad3/ NF-κB signaling pathway. [ABSTRACT FROM AUTHOR]

To investigate the cardioprotective effects of hypothermic (25 °C) reperfusion on ischemia/reperfusion injury and the role of transient potential channel M8 (TRPM8) in this process. Western blot and real-time PCR were used to monitor the expression of TRPM8 in myocardium. Myocardial ischemia/reperfusion injury was induced by 30 min of global ischemia followed by 120 min of reperfusion in Langendorff-perfused hearts from Sprague-Dawley rats. The reperfusion was either normothermic (37 °C) or hypothermic (25 °C). Infarct size and left ventricular function were assessed, and lactate dehydrogenase (LDH), superoxide dismutase (SOD), and malondialdehyde (MDA) in the coronary effluent were measured spectrophotometrically, and cardiomyocyte apoptosis was detected by TUNEL assay. The expression of TRPM8, Bcl-2, Bax, cleaved capspase-3, RhoA, and ROCK2 was quantified. TRPM8 protein and mRNA were expressed in rat myocardium. Hypothermic reperfusion decreased the infarct size, LDH activity, MDA content, apoptosis, and expression of Bax, cleaved caspase-3, RhoA, and ROCK2 compared with normothermic reperfusion. These effects were associated with improved recovery of left ventricular contractility, and were reduced by BCTC, a TRPM8 antagonist. Ischemia/reperfusion injury and the increased expression of Bax, caspase-3, RhoA, and ROCK2 induced by normothermic reperfusion were reduced by Icilin, a TRPM8 agonist. Hypothermic reperfusion at 25 °C has cardioprotective effects against ischemia/reperfusion injury via activation of TRPM8 to inhibit the oxidative stress-related RhoA/ROCK2 signal pathway. [ABSTRACT FROM AUTHOR]