Functional polymorphisms in Linc-ROR may change its ability of regulation by regulating Linc-ROR expression. However, these functional polymorphisms in Linc-ROR and their associations with breast cancer (BC) susceptibility were scarcely reported. In this molecular epidemiological study, four SNPs (rs6420545, rs4801078, rs1942348 and rs9636089) were selected in Linc-ROR by bioinformatics method. Unconditional logistic regression model was performed to analyze the associations between four SNPs and BC susceptibility adjusted for reproductive factors. Quantitative real-time (qRT) PCR was used to evaluate relative expression of Linc-ROR in plasma. The interactions of gene reproductive factors were assessed by Multifactor Dimensionality Reduction (MDR) method. A novel finding showed TT (OR: 1.79; 95%CI: 1.20-2.68) genotype of rs4801078 in Linc-ROR had a significant association with the higher risk of BC and the expression of Linc-ROR mRNA was closely related with the alleles of rs4801078. In addition, we found the interaction of rs4801078, number of pregnancy and menopausal status might increase BC risk (OR: 2.78; 95%CI: 2.74-3.61). Our results suggest that interactions of SNPs in Linc-ROR and reproductive factors might contribute to BC risk, and alleles of rs4801078 might affect Linc-ROR expression level.

Osteosarcoma (OS) is the most common malignant bone tumor in children and young adults. Despite that high-risk factors have been identified, no test for early detection is available. This study aimed to identify circulating nucleic acid sequences associated with serum extracellular vesicle (EV) preparations at the time of OS diagnosis, as a step towards an OS early detection assay. Sequencing of small nucleic acids extracted from serum EV preparations revealed increased representation of diverse repetitive element sequences in OS patient versus control sera. Analysis of a validation cohort using qPCR of PEG-precipitated EV preparations revealed the over-representation of HSATI, HSATII, LINE1-P1, and Charlie 3 at the DNA but not RNA level, with receiver operating characteristic (ROC) area under the curve (AUC) ≥ 0.90. HSATI and HSATII DNAs co-purified with EVs prepared by precipitation and size exclusion chromatography but not by exosome immunocapture, indicative of packaging in a non-exosomal complex. The consistent over-representation of EV-associated repetitive element DNA sequences suggests their potential utility as biomarkers for OS and perhaps other cancers.

The associations of physical activity (PA) intensity and types with CVD (cardiovascular diseases) in different population are inconsistent and remains not very clear. A total of 7854 males and 10,876 females over 15 years were selected by multistage random sampling methods. In males, moderate-intensity physical activity (MPA) had no effect, while vigorous-intensity physical activity (VPA) played a significant protective role (OR = 1.319 and 0.615). However, in females, both MPA and VPA had significant protective effects (OR = 0.593 and 0.537). VPA presented as a significant protective factor in stroke patients and combined CVDs for males in all age groups; however, in females, the results suggested that, for those aged over 60-74 years, MPA was a protective factor. Furthermore, for the middle-aged or younger participants, the area under the curves (AUCs) of work, housework, and leisure activity were generally higher than that of other types, while for patients aged over 60 years, the AUCs of sedentary time and sleep activity seemed much higher. VPA had a better protective effect for preventing cardiovascular events, while the young and female population could benefit from MPA as well. Regardless of the types of PA, leisure activities were strongly recommended, and young people were much more likely to benefit from exercise than older people.

Glioblastoma (GB) remains the most aggressive primary brain malignancy. Adoptive transfer of chimeric antigen receptor (CAR)-modified immune cells has emerged as a promising anti-cancer approach, yet the potential utility of CAR-engineered natural killer (NK) cells to treat GB has not been explored. Tumors from approximately 50% of GB patients express wild-type EGFR (wtEGFR) and in fewer cases express both wtEGFR and the mutant form EGFRvIII; however, previously reported CAR T cell studies only focus on targeting EGFRvIII. Here we explore whether both wtEGFR and EGFRvIII can be effectively targeted by CAR-redirected NK cells to treat GB. We transduced human NK cell lines NK-92 and NKL, and primary NK cells with a lentiviral construct harboring a second generation CAR targeting both wtEGFR and EGFRvIII and evaluated the anti-GB efficacy of EGFR-CAR-modified NK cells. EGFR-CAR-engineered NK cells displayed enhanced cytolytic capability and IFN-γ production when co-cultured with GB cells or patient-derived GB stem cells in an EGFR-dependent manner. In two orthotopic GB xenograft mouse models, intracranial administration of NK-92-EGFR-CAR cells resulted in efficient suppression of tumor growth and significantly prolonged the tumor-bearing mice survival. These findings support intracranial administration of NK-92-EGFR-CAR cells represents a promising clinical strategy to treat GB.