The cell cycle regulator p16 is known as a biomarker and an effector of aging. However, its function in intervertebral disc degeneration (IVDD) is unclear. In this study, p16 expression levels were found to be positively correlated with the severity of human IVDD. In a mouse tail suspension (TS)-induced IVDD model, lumbar intervertebral disc height index and matrix protein expression levels were reduced significantly were largely rescued by p16 deletion. In TS mouse discs, reactive oxygen species levels, proportions of senescent cells, and the senescence-associated secretory phenotype (SASP) were all increased, cell cycling was delayed, and expression was downregulated for Sirt1, superoxide dismutase 1/2, cyclin-dependent kinases 4/6, phosphorylated retinoblastoma protein, and transcription factor E2F1/2. However, these effects were rescued by p16 deletion. Our results demonstrate that p16 plays an important role in IVDD pathogenesis and that its deletion attenuates IVDD by promoting cell cycle and inhibiting SASP, cell senescence, and oxidative stress.
Long noncoding RNAs (lncRNAs) play a critical role in the initiation and progression of colorectal cancer (CRC), but little is known about the function of lncRNAs in the colorectal liver metastasis (CLM). This study was designed to identify specific lncRNAs correlating to liver metastasis of CRC, and to further assess their clinical value.Seventeen patients with primary CRC lesions, adjacent normal mucosa, and synchronous liver metastases lesions were divided into discovery set (six patients) and test set (11 patients). Transcriptome sequencing (RNAseq) was used to screen differential expression of lncRNAs in the discovery set. Based on bioinformatics data, quantitative reverse-transcription polymerase chain reaction (qRT-PCR) was used to verify the target lncRNA in test set. The relationships between target lncRNA and clinical values were analysed in an expanded validation set of additional 91 patients. 23 upregulated and 14 downregulated lncRNAs were detected for distinguishing synchronous liver metastases, primary CRC lesions from adjacent normal mucosa in the RNAseq set. The expression levels of four lncRNAs in the 37 lncRNA signature were verified by qRT-PCR in the test set. Compared with the paired normal mucosa, high expression levels of lnc-small-nucleolar RNA host gene 15 (SNHG15) were detected not only in primary CRC lesions but also in liver metastases lesions in the test set.Furthermore, in the expanded validation set, high expression of lnc-SNHG15 was significantly associated with lymph-node metastasis and liver metastasis (p < 0.05), and patients displaying high lncRNA-SNHG15 expression exhibited a shorter median overall survival duration than those displaying low expression (30.7 vs. 35.2 months; p = 0.003).Multivariate analyses demonstrated that lncRNA-SNHG15 overexpression may serve as a poor prognostic biomarker for CRC patients (p = 0.049; Cox's regression: 2.731). Lnc-SNHG15 overexpression was significantly associated with CLM and high-expression of lnc-SNHG15 in CRC was an independent predictor of poor survival. K E Y W O R D S colorectal liver metastasis, lncRNA-SHNG15, long noncoding RNA J Cell Physiol. 2019;234:7032-7039. wileyonlinelibrary.com/journal/jcp 7032 |
Background: Complicated acetabular fractures comprise the most challenging field for orthopedists. The purpose of this study was to develop three-dimensional printed patient-specific (3DPPS) Ti-6Al-4 V plates to treat complicated acetabular fractures involving quadrilateral plate (QLP) disruption and to evaluate their efficacy. Methods: Fifty patients with acetabular fractures involving QLP disruption were selected between January 2016 and June 2017. Patients were divided into a control group (Group A, 35 patients) and an experimental group (Group B, 15 patients), and were treated by the conventional method of shaping reconstruction plates or with 3DPPS Ti-6AL-4 V plates, respectively. The efficacy of Ti-6AL-4 V plates was evaluated by blood loss, operative time, reduction quality, postoperative residual displacement, and complications. Results: The operative time and blood loss in Group B were reduced compared to Group A, and the difference was statistically significant (P < 0.05). There was no significant difference in reduction quality between the two groups (P > 0.05). Reduction quality in Group B was anatomic in 10 (66.7%), satisfactory in four (26.7%), and poor in one (6.7%). In Group A, they were anatomic in 18 (51.4%), satisfactory in 13 (37.1%), and poor in four (11.4%). Residual displacement in Group B was less than that in Group A, and the difference was statistically significant (P < 0.05). In Group B, one case exhibited loosening of the pubic screw postoperatively. In Group A, there was one case of wound infection, one of deep vein thrombosis (DVT) in the ipsilateral lower limb, one case of traumatic arthritis and two obturator nerve injuries.
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