Background. Thymic carcinoma is a rare, indolent, and invasive cancer. This study investigated the treatment results of thymic carcinoma and clinical prognostic factors.Methods. From June 1988 to January 2002, 38 patients were enrolled in this study with the diagnosis of thymic carcinoma in the Cheng-Kung University Hospital based on Rosai's and Muller-Hermelink's classification. Clinical and pathologic data were retrospectively reviewed. Survival analysis was performed using the KaplanMeier, log rank, and Wilcoxon tests. Statistical significance was defined as p < 0.05.Results. Pathology revealed 14 poorly differentiated, 6 moderately differentiated, and 8 well-differentiated squamous cell carcinomas; 8 lymphoepithelioma-like carcinomas; and 2 other carcinomas. Pathologic staging using the Masaoka system included 6 stage II, 23 stage III, and 9 stage IV patients. Six biopsies, five debulkings,

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miR-23b is a multifunctional microRNA that contributes to the regulation of multiple signaling pathways. It has been reported that miR-23b prevents multiple autoimmune diseases through the regulation of inflammatory cytokine pathways. In addition, the function and underlying mechanisms of miR-23b on sepsis are currently being investigated. In the present study, miR-23b inhibitor and mimics sequences were transfected into human vascular endothelial cells to inhibit and upregulate the expression of miR-23b, respectively. In addition, respective negative control (NC) sequences were transfected. The expression of miR-23b was found to be downregulated in the cells transfected with the mimics NC or inhibitor NC sequences following stimulation with lipopolysaccharide (LPS; P<0.01); however, higher expression levels were maintained in the cells transfected with the mimics sequence and very low levels were observed in the cells transfected with the inhibitor sequence. In addition, the expression levels of nuclear factor (NF)-κB, tumor necrosis factor (TNF)-α, interleukin (IL)-6, intercellular adhesion molecule (ICAM)-1, E-selectin and vascular cell adhesion molecule (VCAM)-1 were shown to increase following induction by LPS in the cells transfected with inhibitor/mimics NC sequences (P<0.05). However, the expression levels of these inflammatory factors decreased in the cells transfected with the mimics sequence, and increased to a greater degree in the cells transfected with the inhibitor sequence, as compared with the inhibitor NC sequences (P<0.05). Therefore, miR-23b may play a significant role in the pathogenesis and progression of sepsis by inhibiting the expression of inflammatory factors, including NF-κB, TNF-α, IL-6, ICAM-1, E-selectin and VCAM-1.

Small cell lung cancer (SCLC) has a high degree of plasticity and is characterized by a remarkable response to chemotherapy followed by the development of resistance. Here, we use a mouse SCLC model to show that intratumoral heterogeneity of SCLC is progressively established during SCLC tumorigenesis. YAP/TAZ and Notch are required for the generation of non-neuroendocrine (Non-NE) SCLC tumor cells, but not for the initiation of SCLC. YAP signals through Notch-dependent and Notch-independent pathways to promote the fate conversion of SCLC from NE to Non-NE tumor cells by inducing Rest expression. In addition, YAP activation enhances the chemoresistance in NE SCLC tumor cells, while the inactivation of YAP in Non-NE SCLC tumor cells switches cell death induced by chemotherapy drugs from apoptosis to pyroptosis. Our study demonstrates that YAP plays critical roles in the establishment of intratumoral heterogeneity and highlights the potential of targeting YAP for chemoresistant SCLC.

Edited by Laszlo NagyKeywords: miR-344 GSK3b Adipogenesis Wnt/b-catenin signaling a b s t r a c t Differentiation of 3T3-L1 cells into adipocytes involves a highly orchestrated series of complex events in which microRNAs might play an essential role. In this study, we found that the overexpression of microRNA-344 (miR-344) inhibits 3T3-L1 cell differentiation and decreases triglyceride accumulation after MDI stimulation. We demonstrated that miR-344 directly targets the 3 0 UTR of GSK3b (Glycogen synthase kinase 3 beta). Knockdown of GSK3b with siRNA results in inhibiting 3T3-L1 differentiation, while its overexpression restores the effect of miR-344. In addition, miR-344 elevates the level of active b-catenin, which is the downstream effector of GSK3b in the Wnt/b-catenin signaling pathway. These data indicate that miR-344 inhibits adipocyte differentiation via targeting GSK3b and subsequently activating the Wnt/b-catenin signaling pathway. Crown

Our study sought to review our experience from biportal to uniportal video-assisted thoracoscopic surgery (VATS) major lung resection. Lessons we learned from the evolution regarding technical aspects were also discussed.We retrospectively reviewed patients who underwent VATS lobectomy or segmentectomies in Ditmanson Medical Foundation Chia-Yi Christian Hospital, Chia-Yi, Taiwan, during January 2012 and December 2014. Patient clinical profiles, surgical indications and procedures, postoperative course, and oncological parameters were analyzed and compared between the biportal and uniportal groups.A total of 121 patients were enrolled in this study with median follow-up of 19.5 ± 11.6 months for all patients and 22.5 ± 11.5 months for primary lung cancer patients. Operation time (146.1 ± 31.9–158.7 ± 40.5 minutes; P = 0.077), chest drainage time (3.8 ± 3.3–4.4 ± 2.4 days; P = 0.309), conversion to thoracotomy rate (2.2%–2.6%; P = 0.889), and complication rate (15.6%–19.7%; P = 0.564) were equal between the groups, whereas blood loss (96.7 ± 193.2–263.6 ± 367; P = 0.006) was lower in the uniportal group. For lung cancer cases, there were no statistical differences in the histology, cancer staging, mediastinal lymph node dissection stations, numbers of dissected N1, N2, and overall lymph nodes between uniportal and biportal groups.Our preliminary data showed that uniportal VATS anatomical lung resection is as feasible, equally safe, and of comparative oncological clearance efficacy to biportal VATS.

Nicotinamide phosphoribosyltransferase (NAMPT) is the key enzyme of the salvage pathway of nicotinamide adenine dinucleotide synthesis. NAMPT can also be secreted and functions as a cytokine. We have previously shown that in the brain, NAMPT expression and secretion can be induced in microglia upon neuroinflammation and injury. Yet the mechanism for NAMPT secretion remains unclear. Here we show that NAMPT can be actively secreted from microglia upon the treatment of ischemia‐like injury – oxygen‐glucose deprivation and recovery (OGD/R). We confirmed that classical ER‐Golgi pathway is not involved in NAMPT secretion. NAMPT secretion was further enhanced by ATP, and the secretion was mediated by P2X7 receptor and by intracellular Ca2+. Importantly, we found that phospholipase D inhibitor, n‐butanol, phospholipase D siRNA, and wortmannin significantly decreased OGD/R‐induced and ATP‐enhanced release of NAMPT in microglia. After excluding the mechanisms of involving secretory autophagy, endosomes, and secretory lysosome, we have concluded that microglial NAMPT is secreted mainly via exosome. Immune‐electron microscopy identifies NAMPT in extracellular vesicles with the size and morphology characteristic of exosome. With the vesicles harvested by ultra‐centrifugation, exosomal NAMPT is further confirmed by Western blotting analysis. Intriguingly, the amount of NAMPT relative to exosomal protein markers remains unchanged upon the treatment of OGD/R, suggesting a constant load of exosomal NAMPT in microglia. Taken together, we have identified NAMPT is actively secreted via exosome from microglia during neuroinflammation of ischemic injury.

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