BackgroundP21-activated kinase 4 (PAK4), an effector of the Rho family protein Cdc42, is an important oncogene whose expression is increased in many human cancers and is generally positively correlated with advanced disease and decreased survival. However, little is known about the expression and biological function of PAK4 in human non-small cell lung cancer (NSCLC).MethodsPAK4 expression in NSCLC tissues and adjacent non-tumor tissues were assessed by immunohistochemistry, real-time PCR, and western blotting. Prognostic value of PAK4 expression was evaluated by Kaplan-Meier analysis and Cox regression. siRNA-mediated gene silencing and protein kinase assay was applied to demonstrate the role and the mechanism of PAK4 in lung cancer cell migration, invasion.ResultsThe results showed that PAK4 was overexpressed in NSCLC cell lines and human NSCLC tissues. PAK4 expression was detected both in the membranes and cytoplasm of NSCLC cancer cells in vivo. Moreover, increased expression of PAK4 was associated with metastasis, shorter overall survival, advanced stage of NSCLC. Furthermore, PAK4 expression was positively correlated with phosphorylation of LIMK1 expression levels. Knockdown of PAK4 in NSCLC cell lines led to reduce the phosphorylation of LIMK1, which resulted in decrease of the cell migration and invasion. In addition, PAK4 bound to LIMK1 directly and activated it via phosphorylation.ConclusionsThese data demonstrate that PAK4 mediated LIMK1 phosphorylation regulates the migration and invasion in NSCLC. Therefore, PAK4 might be a significant prognostic marker and potential therapeutic molecular target in NSCLC.

Purpose Pneumonia is one of the common complications of hip fracture. This study aimed to evaluate the risk factors and apply a nomogram to predict postoperative pneumonia in elderly hip fracture patients. Materials and Methods From August 2014 to October 2019, 1113 hip fracture patients who were older than 65 years and underwent surgical treatment in our hospital were subjects of this study. Univariate and multivariate Cox analyses were used to identify independent risk factors. A predictive nomogram model was built, and the discrimination and calibration were determined by receiver operating characteristic and calibration plot. Results A total of 166 patients developed pneumonia after operation (14.91%, pneumonia group) while the remaining 947 patients did not (85.09%, non-pneumonia group). According to the results, body mass index (OR, 0.76, 95% CI, 0.70 to 0.84, P<0.001), serum albumin (OR, 0.86, 95% CI, 0.79 to 0.93, P<0.001), c-reactive protein (OR, 1.01, 95% CI, 1.00 to 1.92, P=0.011), functional status (OR, 2.94, 95% CI, 1.69 to 5.10, P<0.001) and time to surgery (OR, 4.56, 95% CI, 2.64 to 7.88, P<0.001) were identified as independent risk factors of pneumonia. The area under the curve value for postoperative pneumonia risk was 0.905, and the P-value of the Hosmer-Lemeshow calibration test was 0.529. Conclusion Our nomogram model can be used to predict the risk of pneumonia in elderly hip fractures after surgery and provide clinicians with guidance for better perioperative intervention to improve prognosis and reduce mortality.

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The apoptotic mechanism dysfunction plays a critical role in cancer cell growth and escaping from cancer therapies; the underlying mechanisms are to be further elucidated. This study aims to investigate the role of phospholipase C epsilon 1 (PLCE1) in modulating the apoptosis mechanism in esophageal cancer (Eca) cells. The results showed that Eca cell lines, OE33 and CP-C cells expressed high levels of PLCE1. Knockdown of PLCE1 markedly increased 9.26 folds of the expression of p53 and 13.8 folds of the frequency of apoptotic CP-C cells via modulating the p53 promoter methylation.

Purpose. Due to the rarity, it is difficult to predict the survival of patients with fibrosarcoma. This study aimed to apply a nomogram to predict survival outcomes in patients with fibrosarcoma. Methods. A total of 2235 patients with diagnoses of fibrosarcoma were registered in the Surveillance, Epidemiology, and End Results database, of whom 663 patients were eventually enrolled. Univariate and multivariate Cox analyses were used to identify independent prognostic factors. Nomograms were constructed to predict 3-year and 5‐year overall survival and cancer‐specific survival of patients with fibrosarcoma. Results. In univariate and multivariate analyses of OS, age, sex, race, tumor stage, pathologic grade, use of surgery, and tumor size were identified as independent prognostic factors. Age, sex, tumor stage, pathologic grade, use of surgery, and tumor size were significantly associated with CSS. These characteristics were further included to establish the nomogram for predicting 3-year and 5-year OS and CSS. For the internal validation of the nomogram predictions of OS and CSS, the C-indices were 0.784 and 0.801. Conclusion. We developed the nomograms that estimated 3-year and 5-year OS and CSS. These nomograms not only have good discrimination performance and calibration but also provide patients with better clinical benefits.

Non-small cell lung cancer (NSCLC) is a major type of human lung cancer and the primary cause of cancer-associated cases of mortality worldwide. Phosphatase and tensin homolog (PTEN) is a potent tumor suppressor gene in various human cancer types. The aim of the current study was to explore the role of PTEN and its associated regulatory mechanisms in NSCLC. Firstly, the expression of PTEN was detected using western blotting in a variety of NSCLC cell lines. The results revealed that compared with normal control cells, PTEN levels were significantly decreased in NSCLC cell lines (P<0.01). Short hairpin (sh)RNAs specific to PTEN were also used to knockdown endogenous PTEN in NSCLC cells. The results indicated that cell viability was significantly increased in PTEN-knockdown cells compared with those transfected with negative control shRNA (P<0.01). Conversely, overexpression of PTEN in A549 and SK-MES-1 cells significantly decreased the optical density of NSCLC cells (P<0.01). Flow cytometry was used to investigate the cell cycle; the results revealed that PTEN knockdown significantly increased the percentage of cells at G 0 /G 1 phase (P<0.01) and decreased the number of cells at S phase (P<0.01). The molecular mechanism was further explored using western blotting and the results demonstrated that PTEN overexpression increased the levels of cleaved caspase-3 (P<0.01). These results suggest that PTEN may be a potential target gene for gene therapy in patients with NSCLCs.

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Extramedullary hematopoiesis (EMH) is a rare disease, where hematological disorder drives extramedullary hematopoietic tumor formation in multiple regions of the body. The present study reports a case of EMH presenting as multiple tumor-like lesions of mediastinum in a 61-year-old male with α-thalassemia, which was subjected to a video-assisted thoracoscopic surgery tissue biopsy to differentiate it from other mediastinal tumors. To date, only three cases of EMH in patients with α-thalassemia have been described in the literature. Patients with EMH typically exhibit no hematological disorder preoperatively and therefore EMH is frequently misdiagnosed. In the present study, along with a literature review of the clinicopathological features of EMH, the diagnosis and treatment of this rare case was discussed, in order to differentiate diagnosis, and particularly to distinguish EHM from extramedullary myeloid sarcoma.