GPBAR1 is associated with asynchronous bone metastasis and poor prognosis of hepatocellular carcinoma.

Background: Hepatocellular carcinoma (HCC) is the second leading cause of cancer-related death in China. Asynchronous metastasis is the main reason for HCC recurrence, but the current assessment of HCC metastasis and prognosis is far from clinically satisfactory. Materials: In our study, we investigated the expression of G-protein-coupled bile acid receptor (GPBAR1) in HCC tissues and tumor-adjacent tissues by qRT-PCR and immunohistochemistry. The associations between GPBAR1 expression, clinicopathological factors, and asynchronous metastases were assessed by the Chi-square test. The overall survival curves of different variables were plotted with the Kaplan-Meier method, and the statistical significance between different subgroups was analyzed with the log-rank test. The independent prognostic factors were identified by the Cox regression hazard model. Results: GPBAR1 was more highly expressed in HCC tissues than in tumor-adjacent tissues. GPBAR1 expression in HCC was significantly higher than that in liver cirrhosis, followed by normal liver tissues. GPBAR1 was significantly associated with poor prognosis in HCC and can be regarded as an independent prognostic biomarker. Interestingly, GPBAR1 expression in HCC was significantly correlated with asynchronous metastasis to the bone but not to the liver or lung. Conclusions: GPBAR1 was found to be an independent, unfavorable prognostic factor of HCC, as well as an indicator of asynchronous bone metastasis but not liver or lung metastases. Our results could provide a new aspect for HCC metastasis studies and help identify high-risk HCC patients, which helps ameliorate the prognostic assessment of HCC.

Multiplex analysis of serum hormone and cytokine in patients with cervical cOPLL: towards understanding the potential pathogenic mechanisms.

Cervical ossification of the posterior longitudinal ligament (cOPLL) is one of the major causes of myelopathy. However, the mechanism underlying remains elusive. In the present study, using MILLIPLEX magnetic bead panel, we investigated four serum hormones and six serum cytokines in cOPLL patients and healthy subjects. The results showed that tumor necrosis factore-α (TNF-α) were significantly increased, and DDK-1 was significantly decreased in the serum from male and female cOPLL patients compared with those from healthy controls, respectively. Osteopontin (OPN) and fibroblast growth factor-23 (FGF-23) were significantly increased in male cOPLL patients compared with that in healthy male controls. Further analysis showed that FGF-23 and OPN significantly increased, dickkopf-1 (DKK-1) decreased in the extensive cOPLL group. In addition, a significant positive correlation between the OPN and FGF-23 was observed in male cOPLL patients. The results are useful for understanding the mechanism underlying cOPLL.

Bioinformatics analyses of pathways and gene predictions in IL-1α and IL-1ß knockout mice with spinal cord injury.

PURPOSE: This study aimed to explore the potential genes and pathways regulated in spinal cord injury (SCI) model mice with IL-1α and IL-1ß knockout (KO). METHODS: Gene expression profile GSE70302, which includes data from injured spinal cord of 4 IL-1α-KO mice, 4 IL-1ß-KO mice and 4 C57BL with 6 mice as controls was downloaded from the Gene Expression Omnibus database. The differentially expressed genes (DEGs) of the IL-1α-KO or IL-1ß-KO vs. control, and IL-1α-KO vs. IL-1ß-KO groups were screened, followed by function enrichment and protein-protein interaction (PPI) analyses. Finally, miRNAs associated with SCI that may target the DEGs were predicted. RESULTS: A total of 579 and 992 DEGs were selected from the IL-1α-KO vs. control group and the IL-1ß-KO vs. control group, respectively, and 208 genes common between the 2 comparison groups were identified. Additionally, 526 DEGs were identified from the IL-1α-KO vs. IL-1ß-KO groups. These DEGs were significantly enriched in functions and pathways associated with ion transport, neuron apoptotic processes and inflammatory responses. The common genes were enriched in the pathways for cytokine-cytokine receptor interaction. DEGs of IL-1α-KO vs. IL-1ß-KO were significantly enriched in the immune system, hematopoietic cell lineage and PI3K-Akt signalling pathway-associated biological processes and pathways. The PPI network consisted of 76 nodes, such as Saa2, Kcna1, Scn8a, Ccl5, Ccl28 and Pink1. A total of 94 miRNAs, including mir-17-5P and mir-30a-5p were predicted that could target the DEGs. CONCLUSION: IL-1α and IL-1ß may play important roles in SCI by regulating ion transport, inflammation and neuron apoptotic processes and their associated genes or miRNAs. Compared with IL-1ß-KO, IL-1α-KO may improve the outcome of SCI via the alteration of hematopoietic cell lineage and PI3K-Akt signalling pathways.

Intra-discal vancomycin-loaded PLGA microsphere injection for MRSA discitis: an experimental study.

OBJECTIVE: To prepare the vancomycin hydrochloride (VA)-loaded poly lactic acid-glycolic acid (PLGA) copolymer microsphere by the multiple emulsion method and evaluate its therapeutic effects on infective discitis. METHODS: Firstly, the particle diameter distribution, shape, encapsulation efficiency, drug-loaded dosage and release curve of VA-PLGA microspheres were evaluated in vitro. Rabbits with methicillin-resistant Staphylococcus aureus infective discitis were treated with VA-PLGA intra-discal injection. Meanwhile, VA intravenous injection, blank PLGA microspheres intra-discal injection served as controls. Thirty days later, therapeutic effects were evaluated through X-ray radiophotography, histopathological and bacteriological examination. RESULTS: Mean particle diameter was between 61.57 ± 4.37 and 67.45 ± 8.13 µm, and mean encapsulation efficiency was between 60.20 ± 1.61 and 75.27 ± 1.60 %m/m. In vitro release experiment showed that the release time was over 30 days. The result of in vivo experiment showed that inflammatory reaction in the VA-PLGA intra-discal injection group was milder than the intravenous injection group (P < 0.05), also with less inflammation. The bacterial count was also significantly lower (1.02 × 10(3) ± 1.22 × 10(3) CFU/g) than the intravenous injection group (7.51 × 10(4) ± 7.16 × 10(4) CFU/g) (P < 0.05). Besides these data, the amount used in VA-PLGA intra-discal injection group is about 20 mg, and that used in the intravenous injection group is about 2.4 g. So, we just use 1/120 of VA i.v. to obtain the better results with our microparticles. CONCLUSION: Intra-discal injection with VA-PLGA sustained-release microspheres can use much less dosage, and effectively control and reduce infective discitis, and the therapeutic effect is superior to that of intravenous injection. A need for the clinical trials will be carried out in the near future.

Simultaneous ossification of the posterior longitudinal ligament and ossification of the ligamentum flavum causing upper thoracic myelopathy in DISH: case report and literature review.

A rare case of a 44-year-old Chinese male with diffuse idiopathic skeletal hyperostosis (DISH) and simultaneous ossification of the posterior longitudinal ligament (OPLL) and ossification of the ligamentum flavum (OLF) at T1-2 causing thoracic myelopathy is reported herein. Posterior decompression without extirpating the OPLL was performed at T1-2. Postoperatively, symptoms were greatly improved, with remaining hyperreflexia and Grade 4/5 muscle strength in the lower extremities. The Japanese Orthopedic Association score improved from 5 preoperatively to 9 at final follow-up. The presence of a cyst due to leakage of cerebrospinal fluid was confirmed by MRI at day 27, but it resolved after conservative management. The clinical manifestation of DISH, the relationship among DISH, OPLL, and OLF, and management of thoracic myelopathy due to OPLL and OLF were reviewed.

C2 translaminar screw as the optimal choice for atlantoaxial dislocation with C2-C3 congenital fusion.

OBJECTIVE AND IMPORTANCE: The entry point and trajectory are very important for transarticular screw (TAS) and C2 pedicle screw (PDS) plantation. When the physical size is not large enough for the screw passing through, an accurate entry point is the most important point for successful screw insertion without vertebral artery (VA) injury and spinal cord injury. Once the laminas of C2 and C3 are fused, the normal anatomic mark might disappear and the insertion point would be hard to find. As a result, the complication of TAS or PDS implantation increases rapidly. We used C2 translaminar screws (TLSs) with C1 lateral mass screws as the optimal fixation for atlantoaxial dislocation in order to reduce the risk of VA injury and spinal cord injury. CLINICAL PRESENTATION: A 37-year-old woman with atlantoaxial dislocation due to obsolete odontoid fracture complained of neck pain and myelopathy. Preoperative CT reconstruction showed C2-C3 fusion and small size of C2 isthmus. TECHNIQUE: The patient underwent posterior atlantoaxial fusion using C1 lateral mass screws and C2 TLSs. The posterior arch of atlas was removed for decompression and fusion was done at C1-C2 joints by grafting bone fragments from the posterior iliac crest. CONCLUSION: TLSs combined with C1 lateral mass screws might be a useful technique for patients with atlantoaxial dislocation and C2-C3 fusion, especially with small size of C2 isthmus. Also, the fusion of posterior elements between C2 and C3 might be a relative contraindication for TAS fixation.

NgR expression in macrophages promotes nerve regeneration after spinal cord injury in rats.

OBJECTIVE: This study aimed to investigate the expression of Nogo-66 receptor (NgR) in macrophages after SCI and clarify its role in neuron regeneration. METHODS: Macrophages harvested from injured spine cord of rats were stained by double immunofluorescence labeling technique to observe the expression of NgR at histological and cellular levels. Macrophages which expressed NgR were constructed in vitro, and then the effects of NgR on macrophage phagocytosis and neuraxon regeneration in three groups (NgR-macrophages group, mock group and normal macrophages group) were studied using Western blot, micro-MTT colorimetry, and LDH assay separately. RESULTS: The results showed that CD68-positive macrophages in injured tissue of spine cord expressed NgR after double immunofluorescence staining on day 7 after SCI, and so did macrophages isolated and cultured from the injured spine cord. The results of Western blot showed that phagocytosis of macrophages in NgR-macrophages group was much better than that in mock group and normal macrophage group (p < 0.05). And the results of Micro-MTT colorimetry and LDH assay indicated that the capacity of neuraxon regeneration in NgR-macrophages group was significantly higher than that in the other two groups (p < 0.05). CONCLUSIONS: The results suggested that there was NgR expressing in the infiltrated macrophages following SCI, which increased phagocytosis of the macrophages, and promoted post-SCI CNS regeneration in vitro.