Development and validation of a nomogram to predict overall survival for patients with metastatic renal cell carcinoma.

BACKGROUND: Heterogeneity of metastatic renal cell carcinoma (RCC) constraints accurate prognosis prediction of the tumor. We therefore aimed at developing a novel nomogram for accurate prediction of overall survival (OS) of patients with metastatic RCC. METHODS: We extracted 2010 to 2016 data for metastatic RCC patients in the Surveillance, Epidemiology, and End Results (SEER) database, and randomly stratified them equally into training and validation sets. Prognostic factors for OS were analyzed using Cox regression models, and thereafter integrated into a 1, 3 and 5-year OS predictive nomogram. The nomogram was validated using the training and validation sets. The performance of this model was evaluated by the Harrell's concordance index (C-index), calibration curve, integrated discrimination improvement (IDI), category-free net reclassification improvement (NRI), index of prediction accuracy (IPA), and decision curve analysis (DCA). RESULTS: Overall, 2315 metastatic RCC patients in the SEER database who fulfilled our inclusion criteria were utilized in constructing a nomogram for predicting OS of newly diagnosed metastatic RCC patients. The nomogram incorporated eight clinical factors: Fuhrman grade, lymph node status, sarcomatoid feature, cancer-directed surgery and bone, brain, liver, and lung metastases, all significantly associated with OS. The model was superior to the American Joint Committee on Cancer (AJCC) staging system (7th edition) both in training (C-indices, 0.701 vs. 0.612, P < 0.001) and validation sets (C-indices, 0.676 vs. 0.600, P < 0.001). The calibration plots of the nomogram corresponded well between predicted and observed values. NRI, IDI, and IPA further validated the superior predictive capability of the nomogram relative to the AJCC staging system. The DCA plots revealed reliable clinical application of our model in prognosis prediction of metastatic RCC patients. CONCLUSIONS: We developed and validated an accurate nomogram for individual OS prediction of metastatic RCC patients. This nomogram can be applied in design of clinical trials, patient counseling, and rationalizing therapeutic modalities.

Evaluation of Effectiveness of Atorvastatin in Treating Chronic Subdural Hematoma not Requiring Surgery: A Meta-Analysis of Randomized Controlled Trials.

Chronic subdural hematoma (CSDH) is a chronic space-occupying lesion formed by blood accumulation between the arachnoid membrane and the dura mater. Atorvastatin is of increasing clinical interest for CSDH. We performed a meta-analysis of published randomized controlled trials (RCTs) and used objective data as the primary outcomes to provide an evidence-based analysis of the efficacy of atorvastatin for CSDH treatment. Databases of MEDLINE (via PubMed), EMBASE, the Cochrane Library, Scopus, Web of Science, ScienceDirect, Chinese National Knowledge Infrastructure (CNKI), Cqvip database (CQVIP), and Wanfang database were systematically searched for RCTs reporting the use of atorvastatin for CSDH treatment. Odds ratio (OR), standard mean difference (SMD), and 95% confidence intervals (CIs) were used as summary statistics. I-square (I2) test was performed to assess the impact of study heterogeneity on the results of the meta-analysis. Nine relevant RCTs with 611 patients were identified for inclusion in this meta-analysis. Compared to controls, atorvastatin treatment had a significantly higher effectiveness (OR: 7.41, 95% CI: 3.32-16.52, P < 0.00001, I2 = 0%), lower hematoma volume (SMD: -0.46. 95% CI: -0.71 to -0.20, P = 0.0005, I2 = 0%), higher activities of daily living-Barthel Index (ADL-BI) (SMD: 2.07, 95% CI: 1.06-3.09, P < 0.0001, I2 = 92%), and smaller Chinese stroke scale (CSS) (SMD: -1.10, 95% CI: -1.72 to -0.48, P = 0.0005, I2 = 57%). In view of these findings, we conclude that the outcomes of experimental group are superior to the control group with respect to effectiveness, hematoma volume, ADL-BI, and CSS based on nine RCTs with 611 patients. Atorvastatin is beneficial to CSDH patients without surgery.

Nomogram prediction of overall survival based on log odds of positive lymph nodes for patients with penile squamous cell carcinoma.

PURPOSE: This study aimed to establish a nomogram to predict the long-term overall survival (OS) for patients with penile squamous cell carcinoma (PSCC). METHOD: The PSCC patients receiving regional lymph node dissection (RLND) were enrolled from the Surveillance, Epidemiology, and End Results (SEER) database between 2004 and 2015. The dataset of all eligible patients were used to develop the predictive model. The significant independent predictors were identified through Cox regression modeling based on the Bayesian information criterion and then incorporated into a nomogram to predicted 1-, 3-, and 5-year OS. Internal validation was performed using the bootstrap resampling method. The model performance was evaluated using Harrell's concordance index (C-index), calibration plots, integrated discrimination improvement (IDI), net reclassification improvement (NRI), and decision curve analysis (DCA). RESULTS: Totally, 384 eligible PSCC patients were enrolled from the SEER database. A nomogram for OS prediction was developed, in which three clinical variables significantly associated with OS were integrated, including age, N classification, and log odds of positive lymph nodes (LODDS). The C-index of the nomogram (0.746, 95% CI: 0.702-0.790) was significantly higher than that of the American Joint Committee on Cancer (AJCC) staging system (0.692, 95% CI: 0.646-0.738, P = .020). The bootstrap optimism-corrected C-index for the nomogram was 0.739 (95% CI: 0.690-0.784). The bias-corrected calibration plots showed the predicted risks were in good accordance with the actual risks. The results of NRI, IDI, and DCA exhibited superior predictive capability and higher clinical use of the nomogram compared with the AJCC staging system. CONCLUSION: We successfully constructed a simple and reliable nomogram for OS prediction among PSCC patients receiving RLND, which would be beneficial to clinical trial design, patient counseling, and therapeutic modality selection.

A Disposable Pneumatic Microgripper for Cell Manipulation with Image-Based Force Sensing.

A new design for a single-use disposable pneumatic microgripper is presented in this paper. It enables very cost-effective batch microfabrication in SU-8 with a single lithography mask by shifting manufacturing complexity into reusable components. An optically readable force sensor with potential to be used in a feedback loop has been integrated in order to enable gripping with a controlled force. The sensors are first examined separately from the gripper and exhibit good linearity. The gripper function utilizes the disposable gripper element together with a reusable gripper fixture. During experiments, the pneumatically actuated microgripper can vary the gripping force within a range of a few mN (up to 5.7 mN was observed). This microgripper is planned to be used in a liquid environment for gripping larger aggregates of cells in combination with the patch clamp technique. This approach will allow Langerhans islets suspended in an electrolyte solution to be grasped and held during electrophysiological measurements without cell damage.

In vitro study of FUZ as a novel potential therapeutic target in non-small-cell lung cancer.

FUZ is regarded as a planar cell polarity effector that controls multiple cellular processes during vertebrate development. However, the role of FUZ in tumor biology remains poorly studied. Our purpose of this study is to discover the physiological effects and mechanism of FUZ in non-small-cell lung cancer (NSCLC) in vitro. With the help of bioinformatics analysis, we noticed that the expression level of FUZ negatively correlates with prognosis of NSCLC patients. Exogenous FUZ expression markedly promoted cell proliferation of NSCLC cells. The phosphorylation of Erk1/2, STAT3 and related signaling molecules were induced activated after FUZ over-expression. FUZ also plays an important role in cell motility by regulating cell signaling pathways and inducing epithelial to mesenchymal transition (EMT). FUZ promotes EMT along with the up-regulation of N-cadherin, vimentin, Zeb1, Twist1 and decreased level of E-cadherin. Furthermore, we also carried out FUZ directed siRNA treatments to prove the above observations. Knockdown of FUZ resulted in delayed cell growth as well as impaired cell migration and reversed EMT phonotype. Importantly, we reported for the first time that FUZ is a BNIP3-interacting protein. Loss of FUZ resulted in decreased BNIP3 protein level, but no influence on BNIP3 mRNA level, suggesting weakened stability of BNIP3 protein. Overall, our results in vitro show that FUZ is responsible for NSCLC progression and metastasis, suggesting that FUZ can be a potential therapeutic target for NSCLC.

Comparison of anticoagulation regimens for pregnant women with prosthetic heart valves: A meta-analysis of prospective studies.

INTRODUCTION: Pregnancy is associated with a hypercoagulable state, which makes pregnant women with prosthetic heart valves at high risk of thromboembolism. The proper anticoagulation regimen should take both the maternal protection and the fetal outcomes into consideration. However, no consensus on the present anticoagulation regimen for those women has been reached yet, especially in the first trimester of pregnancy. AIMS: The present meta-analysis is conducted to compare anticoagulation efficiency and feto-maternal complications of heparin and warfarin in the first trimester. RESULTS: Databases of MEDLINE, EMBASE, and the Cochrane Library were systematically searched (all from their inception to October 2016) for cohort studies reporting the outcome of anticoagulation in pregnant women with mechanical heart valves. Seven relevant prospective studies were identified for inclusion in the present meta-analysis. The forest plots indicated that warfarin was more effective in prevention valve thrombosis in the first trimester than heparin (OR: 14.58; 95% confidence interval [CI]: 3.94-53.94; P < .0001; I2  = 0%). The spontaneous abortion between the two regimens was not statistically different (OR: 1.42; 95% CI: 0.80-2.49; P = .23; I2  = 20%), which indicated that heparin could not provide better protection to the fetus in the early stage of pregnancy than warfarin. The incidence of warfarin embryopathy was low, and it only occurred in a twin among all the included cases. CONCLUSIONS: The present meta-analysis indicated that warfarin can provide better protection for the mother and the teratogenic effects may be overestimated. Heparin does not ensure better fetal outcomes as it is associated with severe adverse maternal outcomes, including mortality.

Evaluation of the novel gene Rabl3 in the regulation of proliferation and motility in human cancer cells.

Rab is a large subfamily of small GTPases which play an important role in multiple processes relating to cellular transportation and modulation of the cytoskeleton. Novel gene Rab-like 3 (Rabl3), which we originally reported as a new member belonging to this subfamily, may participate in other processes in human cancer cell lines based on our research. In order to investigate the function of Rabl3 and the basic mechanism which regulates cancer cell survival and motility, we constructed the Rabl3-pcDNA3.1 fusion plasmid, also, the specific siRNA against Rabl3 was used. We detected cellular viability and motility changes in Rabl3 overexpressed or si-Rabl3 transfected cancer cell lines. Overexpression of Rabl3 resulted in the enhancement of cell proliferation, inhibition of apoptosis and paclitaxel resistance in human cancer cell lines. Rabl3 also promoted cell motility activity. Next, we silenced Rabl3 in order to determine its exact physiological function. We found that processes which are associated with tumor formation and metastasis were inhibited. These included an increased incidence of apoptosis, abrogated cellular proliferation and mobility. Furthermore, western blot analysis revealed that the function of Rabl3 was closely associated with focal adhesion kinase (FAK) phosphorylation, both in HeLa and MDA-MB-231 cell lines at the sites of Tyr 397/576/577. Our results suggested that Rabl3 may be a novel oncogene which regulates the oncological behavior of human cancer cells. As a consequence, Rabl3 can be considered as a novel candidate in the control of tumorigenesis and as a new target for anti-tumor treatment.