Bioinformatics analysis of C3 and CXCR4 demonstrates their potential as prognostic biomarkers in clear cell renal cell carcinoma (ccRCC).

BACKGROUND: The molecular prognostic biomarkers of clear cell renal cell carcinoma (ccRCC) are still unknown. We aimed at researching the candidate biomarkers and potential therapeutic targets of ccRCC. METHODS: Three ccRCC expression microarray datasets (include GSE14762, GSE66270 and GSE53757) were downloaded from the gene expression omnibus (GEO) database. The differentially expressed genes (DEGs) between ccRCC and normal tissues were explored. The potential functions of identified DEGs were analyzed by Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG). And then the protein - protein interaction network (PPI) was established to screen the hub genes. After that, the expressions of hub genes were identified by the oncomine database. The hub genes' prognostic values of patients with ccRCC were analyzed by GEPIA database. RESULTS: A total of 137 DEGs were identified by utilizing the limma package and RRA method, including 63 upregulated genes and 74 downregulated genes. It is found that 137 DEGs were mainly enriched in 82 functional terms and 24 pathways in accordance with the research results. Thirteen highest-scoring genes were screened as hub genes (include 10 upregulated genes and 3 downregulated candidate genes) by utilizing the PPI network and module analysis. Through integrating the oncoming database and GEPIA database, the author found that C3 and CXCR4 are not only overexpressed in ccRCC, but also associated with the prognosis of ccRCC. Further results could reveal that patients with high C3 expression had a poor overall survival (OS), while patients with high CTSS and TLR3 expressions had a good OS; patients with high C3 and CXCR4 expressions had a poor disease-free survival (DFS), while ccRCC patients with high TLR3 expression had a good DFS. CONCLUSION: These findings suggested that C3 and CXCR4 were the candidate biomarkers and potential therapeutic targets of ccRCC patients.

[Domestic artificial cervical disc interface pressure distribution and effect of bone-implant interface pressure on osseointegration].

Objective: To analyze the distribution of stress in the upper and lower plates of the prosthesis-bone interface, and the effect of interface pressure on osseointegration. Methods: CT scanning was performed on goats at 1 week after artificial cervical disc replacement to establish the finite element model of C 3, 4. The stress distribution of the upper and lower plates of the interface was observed. At 6 and 12 months after replacement, Micro-CT scan and three dimensional reconstruction were performed to measure the bone volume fraction (BVF), trabecular number (Tb. N), trabecular thickness (Tb. Th), trabecular separation (Tb. Sp), bone mineral density (BMD), bone surface/bone volume (BS/BV), and trabecular pattern factor (Tb. Pf). The C 3 lower plate and C 4 upper plate of 4 normal goat were chosen to made the cylinder of the diameter of 2 mm. The gene expressions of receptor activator for nuclear factor κB ligand (RANKL), osteoprotegerin (OPG), transforming growth factor ß (TGF-ß), and macrophage colony-stimulating factor (M-CSF) were detected by real time fluorescent quantitative PCR at immediate after cutting and at 24 and 48 hours after culture. The samples of appropriate culture time were selected to made mechanical loading, and the gene expressions of RANKL, OPG, M-CSF, and TGF-ß were detected by real time fluorescent quantitative PCR; no mechanical loading samples were used as normal controls. Results: Under 25 N axial loading, the stress of the upper plate of C 3, 4 was concentrated to post median region, and the stress of the lower plate to middle-front region and two orbits. According to stress, the plate was divided into 5 regions. The Micro-CT scan showed that BMD, Tb.Th, BVF, and Tb.N significantly increased, and BS/BV, Tb.Sp, and Tb.Pf significantly decreased at 12 months after replacement when compared with ones at 6 months ( P<0.05). At 24 and 48 hours after culture, the gene expressions of RANKL, OPG, and TGF-ß were signifi-cantly higher than those at immediate ( P<0.05), but no significant difference was found between at 24 and 48 hours after culture ( P>0.05). The mechanical loading test results at 24 hours after culture showed that the RANKL and OPG gene expressions and OPG/RANKL ratio in C 3 lower plate and C 4 upper plate were significantly up-regulated when compared with controls ( P<0.05), but no significant difference was shown in TGF-ß and M-CSF gene expressions ( P>0.05). Conclusion: Domestic artificial cervical disc endplate has different pressure distribution, the stress of lower plate is higher than that of upper plate. Pressure has important effect on local osseointegration; the higher pressure area is, the osseointegration is better. Under the maximum pressure in interface, the osteoblast proliferation will increase, which is advantageous to the local osseointegration.

Comparison of anterior cervical discectomy and fusion with the zero-profile device versus plate and cage in treating cervical degenerative disc disease: A meta-analysis.

Zero-profile device was applied to diminish the irritation of the esophagus in the treatment of cervical degenerative disc disease. However, the clinical application of the zero-profile device has not been testified with clinical evidence. The aim of the meta-analysis was to systematically compare the safety and effectiveness of anterior cervical discectomy and fusion with zero-profile device with plate and cage for the treatment of cervical degenerative disc disease. Electronic searches of PubMed and Embase were conducted up to May 2015. Relevant studies were included. Weighted mean difference (WMD) and 95% confidence intervals (CI) were assessed for continuous data. Risk ratio (RR) and 95% CI were assessed for dichotomous data. P value <0.05 was considered to be significant. Eleven studies were included in the meta-analysis. Compared with plate and cage, zero-p is associated with lower operation time of two-level surgery, less intraoperative blood loss, higher subsidence rate, higher JOA score, lower incidence of dysphagia in short-term (RR: 0.72, 95% CI [0.58, 0.90], P=0.005, I2=22%) and long-term (RR: 0.12, 95% CI [0.05, 0.30], P<0.00001, I2=0%) and lower Cobb angle of multilevel surgery (WMD: -3.16, 95% CI: [-4.35, -1.97], P<0.00001, I2=0%). No significant difference was found in one-level and two-level Cobb angle, fusion rate and operation time of one-level and three-level surgery. Both zero-p implantation and the plate and cage have respective advantages and disadvantages.

Use of a biological reactor and platelet-rich plasma for the construction of tissue-engineered bone to repair articular cartilage defects.

Articular cartilage defects are a major clinical burden worldwide. Current methods to repair bone defects include bone autografts, allografts and external fixation. In recent years, the repair of bone defects by tissue engineering has emerged as a promising approach. The present study aimed to assess a novel method using a biological reactor with platelet-rich plasma to construct tissue-engineered bone. Beagle bone marrow mesenchymal stem cells (BMSCs) were isolated and differentiated into osteoblasts and chondroblasts using platelet-rich plasma and tricalcium phosphate scaffolds cultured in a bioreactor for 3 weeks. The cell scaffold composites were examined by scanning electron microscopy (SEM) and implanted into beagles with articular cartilage defects. The expression of osteogenic markers, alkaline phosphatase and bone γ-carboxyglutamate protein (BGLAP) were assessed using polymerase chain reaction after 3 months. Articular cartilage specimens were observed histologically. Adhesion and distribution of BMSCs on the ß-tricalcium phosphate (ß-TCP) scaffold were confirmed by SEM. Histological examination revealed that in vivo bone defects were largely repaired 12 weeks following implantation. The expression levels of alkaline phosphatase (ALP) and BGLAP in the experimental groups were significantly elevated compared with the negative controls. BMSCs may be optimum seed cells for tissue engineering in bone repair. Platelet-rich plasma (PRP) provides a rich source of cytokines to promote BMSC function. The ß-TCP scaffold is advantageous for tissue engineering due to its biocompatibility and 3D structure that promotes cell adhesion, growth and differentiation. The tissue-engineered bone was constructed in a bioreactor using BMSCs, ß-TCP scaffolds and PRP and displayed appropriate morphology and biological function. The present study provides an efficient method for the generation of tissue-engineered bone for cartilage repair, compared with previously used methods.

New Dynamic Plate System Combined with Titanium Mesh Cage and Bone Graft in the Treatment of Cervical Spondylosis.

AIM: Dynamic plates have been popularized to promote cervical spine fusion. There are no studies comparing the effectiveness and complications between traditional static plates and new dynamic plates (Vectra-T, Synthes, Switzerland). MATERIAL AND METHODS: From June 2009 to October 2012, 70 patients underwent anterior cervical corpectomy and fusion (ACCF) in our hospital for the treatment of cervical spondylosis. Vectra-T plate was used in 36 patients (dynamic group) while traditional static plate was used in 34 patients (static group). Sagittal section angle, sagittal plane mobility, coronal angle of the titanium mesh cage were measured and the change of sedimentation rate was calculated at the postoperative 3 < sup > rd < /sup > , 6 < sup > th < /sup > , 12 < sup > th < /sup > months and at the end of follow-up period for each patient. The Japanese Orthopedic Association (JOA) score and local cervical angle were also measured before, immediately after surgery and at the end of follow-up period. These data were compared for both groups. RESULTS: The follow-up period was between 12 and 38 months. The clinical outcome was similar in both groups based on the JOA score, local cervical angle and regional cervical angle. All patients had good clinical outcome without fracture of the plates or screws. There were no differences between the two groups at the 3rd, 6th and 12th months after surgery regarding to fusion rate (p > 0.05). Settling of the construct and plate migration was similar between the groups at all time points. CONCLUSION: There was no statistically significant difference between dynamic plates and static plates regarding to fusion rate. The clinical outcomes and radiographic changes were also similar in both groups.