Background: Inhibitors of apoptosis proteins (IAPs) are a family of antiapoptotic proteins modulating cell cycle, signal transduction and apoptosis. Dysregulated IAPs have been reported to contribute to tumor progression and chemoresistance in various cancers. However, existing studies were sporadic and only focus on one specific cancer with one particular gene in the IAPs family. A systematic investigation on the co-expression pattern, regulation frameworks on various pathways, prognostic utility on patient outcomes, and predictive value on drug sensitivity among all the IAPs across multiple tumor types was lacking. Methods: Leveraging The Cancer Genome Atlas data with comprehensive genomic characterizations on 9714 patients across 32 tumor types and the Genomics of Drug Sensitivity in Cancer data with both genomic characterizations and drug sensitivity data on > 1000 cell lines, we investigated the co-expression pattern of IAPs, their regulations of apoptosis as well as other pathways and clinical relevance of IAPs for therapeutics development. Results: We discovered diverse expression pattern among IAPs, varied spectrum of apoptosis regulations through IAPs and extensive regulations beyond apoptosis involving immune response, cell cycle, gene expression and DNA damage repair. Importantly, IAPs were strong prognostic factors for patient survival and tumor stage in several tumor types including brain, liver, kidney, breast and lung cancer. Further, several IAPs were found to be predictive of sensitivity to BCL-2 inhibitors (BIRC3, BIRC5, BIRC6, and BIRC7) as well as RIPK1 inhibitors (BIRC3 and BIRC6). Conclusion: Together, our work revealed the landscape of regulations, prognostic utilities and therapeutic relevance of IAPs across multiple tumor types.

To study the pathogenesis of diabetes mellitus (DM) and identify new biomarkers, high‐throughput RNA sequencing provides a technical means to explore the regulatory network of MD gene expression. To better elucidate the genetic basis of DM, we analysed the circRNA and mRNA expression profiles in serum samples from diabetic patients. The circRNAs and mRNAs with abnormal expression in the DM group and non‐diabetic group (NDM) were classified by RNA sequencing and differential expression analysis. The circRNA‐miRNA‐mRNA regulatory network reveals the mechanism by which competitive endogenous RNAs (ceRNAs) regulate gene expression. The biological functions and interactions of circRNA and mRNA were analysed by gene ontology (GO) enrichment and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis. Differential expression analysis showed that 441 circRNAs (366 up‐regulated, 75 down‐regulated) and 683 mRNAs (354 up‐regulated, 329 down‐regulated) were significantly differentially expressed in the DM group compared with the NDM group. Screening of the differential genes at the nodes of the interaction network showed that a single circRNA could interact with multiple miRNAs and then jointly regulate more mRNAs. In addition, the expressions of circRNA CNOT6 and AXIN1 as well as mRNA STAT3, MYD88, and B2M were associated with the progression of diabetes. Enrichment pathway analysis indicated that differentially expressed circRNA and mRNA may participate in Nod‐like receptor signalling pathway, insulin signalling pathway, sphinolipid metabolism pathway, and ribosome pathway, and play a role in the pathogenesis of diabetes. This study provides a theoretical basis for elucidating the molecular mechanism of DM occurrence and development at circRNA and mRNA levels.

Background: Intraparenchymal cerebral cavernous malformation is difficult to localize intraoperatively with conventional frameless navigation due to the “brain shift” effect. We conducted this study to evaluate the efficacy and safety of intraoperative magnetic resonance image (iMRI)-assisted neuro-port surgery for the resection of cerebral intraparenchymal cavernous malformation. Methods: Between April 2016 and December 2017, 54 consecutive patients with intraparenchymal cerebral cavernous malformation who get surgical treatment in our hospital were enrolled into this study. Twenty-one patients were treated using iMRI-assisted neuro-port surgery (experiment group), and 33 patients underwent treatment by conventional microsurgery (control group). The iMRI was used in all cases for the compensation of the “brain shift” effect and keeping the navigation system up-to-date. The surgical resection rate, the total operation time, and the preoperative and postoperative Karnofsky Performance Status (KPS) scores were determined to evaluate the operative procedures. Results: There were no significant differences between the two groups in mean age, gender ratio, and volume of lesions (P > 0.05). For the experiment group, the average duration of the procedure was 188.8 min with total resection of the lesions achieved in all 21 cases. For the control group, the average duration of the procedure was 238.2 min with total resection of the lesions achieved in 25 of 33 cases. The differences in the average duration of the procedure and the number of totally resected lesions between the two groups were statistically significant (P < 0.05). Regarding postoperative neurological function, postoperative KPS scores for the experiment group were significantly higher than those of the control group (P = 0.018). Conclusion: Our results show that iMRI-assisted neuro-port surgery is helpful for intraparenchymal cerebral cavernous malformation surgery. The method provides high accuracy and efficiency for lesion targeting and permits excellent anatomic orientation. With the assistance of iMRI technology, we achieved a higher resection rate and a lower incidence of postoperative neurological deficits. Additionally, iMRI is helpful for the compensation of the “brain shift” effect, and it can update the navigation system.

WHO grade II-III insular glioma (InG) can displace the basal ganglia, resulting in distinct linear or curved boundary shapes. This study retrospectively explored this morphological distinction and its clinical relevance. MRI and clinical data were collected from Beijing Tiantan Hospital over the past 20 years. The boundary shape on the FLAIR sequence was characterized using the fractal dimension (FD) and curved parameters. Statistical analyses included the χ² test, Cox regression, Kaplan-Meier analysis, and correlation analysis. Regression models were constructed using the stepwise Wald method. Model performance was evaluated through internal validation, including bootstrap resampling and 5-fold cross-validation. A total of 330 patients were included. Based on the FD, patients were classified into linear ('L'; 49%) and curved ('C'; 51%) subgroups. Compared with the L subgroup, the C subgroup exhibited more favorable biological features and progression-free survival (PFS) (p < 0.001). Using routine pathological variables, regression models were constructed to identify crucial factors in different subgroups and perform disease stratification for Statistical explanation. Internal validation supported model stability. With regard to surgical responses, although the rate of gross total resection (GTR) was higher in the L subgroup, the PFS was not increased, whereas that of the C subgroup demonstrated an increase (p < 0.001). The boundary shape between WHO grade II-III InG and the basal ganglia may reflect differences in biological features, survival outcomes, and surgical responses. Thus, the boundary shape should be considered in clinical practice.