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The prognosis-associated genes of urinary bladder cancer have been systematically investigated in the Pathology Atlas project based on The Cancer Genome Atlas data. However, the biological functions of most genes in bladder cancer remain unknown. The present study investigated the biological function of 12 of the most significant survival-associated genes ( ABRACL, MITD1, ZNF524, EMP1, HSPB6, CXorf38, TRIM38, ZNF182, ZNF195, SPRN, PTPN6 and LIPT1 ) in urothelial cancer reported by the Pathology Atlas project, with respect to cell proliferation and migration. In vitro , proliferation and migration analyses of T24 cells were performed following the transfection of the 12 prognostic genes. The results were validated with a small interfering (si)RNA library. Immunohistochemistry (IHC) analysis of clinical samples was performed to determine the association between gene expression and tumor metastasis. Furthermore, RNA sequencing was used to investigate the downstream signals. Among the 12 prognostic genes, MIT-domain containing protein 1 ( MITD1 ) transfection was demonstrated to inhibit T24 cell migration to a certain degree. Experiments performed with a 7-gene siRNA library demonstrated that MITD1 knockdown markedly upregulated cell migratory abilities. Mechanistically, the influence of MITD1 on cell signal transduction was assessed via RNA sequencing. Cell migration-associated genes, including KISS1, SPANXB1, SPINT1, PIWIL2, SNAI1, APLN and CTHRC1 were dysregulated. IHC analysis demonstrated that MITD1 protein expression was notably lower in metastatic lymph nodes compared with the primary tumors. Taken together, the results of the present study suggest that the prognostic gene, MITD1 may serve as a migration inhibitor, and be developed as a potential therapeutic target for improving the prognosis of bladder cancer.

Diabetes mellitus (DM) and Parkinson’s disease (PD) are both age-related diseases of global concern being among the most common chronic metabolic and neurodegenerative diseases, respectively. While both diseases can be genetically inherited, environmental factors play a vital role in their pathogenesis. Moreover, DM and PD have common underlying molecular mechanisms, such as misfolded protein aggregation, mitochondrial dysfunction, oxidative stress, chronic inflammation, and microbial dysbiosis. Recently, epidemiological and experimental studies have reported that DM affects the incidence and progression of PD. Moreover, certain antidiabetic drugs have been proven to decrease the risk of PD and delay its progression. In this review, we elucidate the epidemiological and pathophysiological association between DM and PD and summarize the antidiabetic drugs used in animal models and clinical trials of PD, which may provide reference for the clinical translation of antidiabetic drugs in PD treatment.

The aim of the present study was to compare the survival outcomes for patients with metastatic renal cell carcinoma (mRCC) who underwent laparoscopic cytoreductive nephrectomy (CN) vs. open CN vs. targeted therapy (TT) alone at our institution. A retrospective chart review was performed at our institution for patients who underwent CN prior to TT (laparoscopic, n=48; open, n=48) or who were deemed unfit for surgery and received TT alone (n=36), between January 2007 and December 2012. Kaplan-Meier estimated survival and Cox proportional hazards analyses were performed. Laparoscopic CN was associated with significantly longer survival compared with open CN or TT alone (median survival 24 vs. <12 months, respectively; P<0.01). On multivariate analysis, laparoscopic CN was an independent predictor of survival [hazard ratio (HR)=0.48, P<0.01), controlling for preoperative risk factors, while survival was similar between open CN and TT alone (HR=0.85, P=0.54). In our experience, laparoscopic CN appears to be a significant predictor of survival in mRCC. Selection bias of the surgeon for patients with improved survival may account for clinical variables that were otherwise difficult to quantify. For patients who were not candidates for laparoscopic CN, open CN did not confer a survival benefit over TT alone, while it was associated with increased morbidity.

With the continuous development of robotics and artificial intelligence, robots are being increasingly used in various applications. For traditional navigation algorithms, such as Dijkstra and A , many dynamic scenarios in life are difficult to cope with. To solve the navigation problem of complex dynamic scenes, we present an improved reinforcement-learning-based algorithm for local path planning that allows it to perform well even when more dynamic obstacles are present. The method applies the gmapping algorithm as the upper layer input and uses reinforcement learning methods as the output. The algorithm enhances the robots' ability to actively avoid obstacles while retaining the adaptability of traditional methods.

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Background. Kallikrein-related peptidase 6 (KLK6) has been substantiated as a diagnostic, prognostic, and therapeutic molecular in several cancer types. In our study, we attempt to explore the biological functions of KLK6 in bladder urothelial carcinoma (BLCA). Methods. KLK6 gene expression prognostic, gene ontology (GO), Kyoto Encyclopedia of Genes and Genomes (KEGG), gene set enrichment analysis (GSEA), and immune infiltration were analyzed using The Cancer Genome Atlas (TCGA) database. In vitro and in vivo experimental measurements, including CCK8, transwell migration, TUNEL, and nude mouse transplanted tumor model, were used to evaluate the antineoplastic activities of KLK6 loss-of-function. Results. The combination of bioinformatics analyses and experimental measurements demonstrate that KLK6 expression is aberrantly upregulated in human specimens and cell lines of BLCA. GO and GSEA enrichment analyses exhibited that KLK6 is implicated in the inflammatory response and immune infiltration, suggesting that upregulation of KLK6 may be associated with the progression of BLCA. Knockdown of KLK6 is able to inhibit the growth and migration and trigger apoptosis of RT4 and T24 cells. Moreover, the TCGA database indicates that KLK6 high expression in BLCA patients showed a poorer prognosis than those patients with KLK6 low expression. Univariate and multivariate regression analyses suggest KLK6 as an independent prognostic factor to predict unfavorable OS in patients with BLCA. Conclusion. KLK6 is an independent prognostic factor and an antitumor target of BLCA. KLK6 expression positively correlates with several immune cells infiltration, indicating that inhibition of KLK6 may contribute to immunotherapy of BLCA.

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