Finite element analysis of new headless compression supporting screw for the treatment of unstable femoral neck fracture.

BACKGROUND: Femoral neck fracture is an unsolved challenge in orthopedics. The complication rate in particular is high. There remains a lack of consensus on the optimal choice of internal fixation for unstable femoral neck fracture. OBJECTIVE: The study aimed to develop a new headless compression supporting screw (HCSS) for the treatment of unstable foemoral neck fracture. METHODS: We designed a new HCSS and used a femoral neck fracture (Pauwels III fracture) model (left, fourth-generation composite, Sawbones) and three-dimensional finite element analysis to compare the biomechanical performance of HCSSs with that of cannulated compression screws (CCSs) for treatment of unstable femoral neck fracture. RESULTS: Maximum displacement, peak von Mises stress, peak strain, and rotation for the HCSS were smaller than those for the CCS. The stress was more widely distributed for the HCSS, whereas the stress was concentrated for the CCS. CONCLUSIONS: The HCSS resulted in better biomechanical stability than that from the CCS. For Pauwels III fractures the HCSS exhibits better resistance to shear forces and better support, providing a new clinical treatment.

Regio/Stereoselective Glycosylation of Diol and Polyol Acceptors in Efficient Synthesis of Neu5Ac-α-2,3-LacNPhth Trisaccharide.

A concise approach to a Neu5Ac-α-2,3-LacNPhth trisaccharide derivative was developed. First, the regio/stereoselective glycosylation between glycoside donors and glucoNPhth diol acceptors was investigated. It was found that the regioselectivity depends not only on the steric hindrance of the C2-NPhth group and the C6-OH protecting group of the glucosamine acceptors, but also on the leaving group and protecting group of the glycoside donors. Under optimized conditions, LacNPhth derivatives were synthesized in up to 92 % yield through a regio/stereoselective glycosylation between peracetylated-α-galactopyranosyl trichloroacetimidate and p-methoxyphenyl 6-O-tert-butyldiphenylsilyl-2-deoxy-2-phthalimido-ß-d-glucopyranoside, avoiding the formation of glycosylated orthoesters and anomeric aglycon transfer. Then, the LacNPhth derivative was deacylated and then protected on the primary position by TBDPS to form a LacNPhth polyol acceptor. Finally, the Neu5Ac-α-2,3-LacNPhth derivative was synthesized in 48 % yield through the regio/stereoselective glycosylation between the LacNPhth polyol acceptor and a sialyl phosphite donor. Starting from d-glucosamine hydrochloride, the target Neu5Ac-α-2,3-LacNPhth derivative was synthesized in a total yield of 18.5 % over only 10 steps.

Straightforward S-S Bond Formation via the Oxidation of S-Acetyl by Iodine in the Presence of N-Iodosuccinimide.

Straightforward S-S bond formation via the oxidation of S-acetyl group by iodine was reported here. The reaction was further applied in the synthesis of per-O-acetylated glycosyl disulfides. These studies demonstrated great improvement in reaction rate, yield, and general convenience in the presence of N-iodosuccinimide. Furthermore, selectively deacetylated glycosyl thiols were obtained in high yields when these per-O-acetylated glycosyl disulfides were reduced with tris(2-carboxyethyl)-phosphine (TCEP). Our method supplied an efficient way to obtain both per-O-acetylated glycosyl disulfides and per-O-acetylated glycosyl thiols in which the sulfur group was located at any position.

Serum microRNA-195 is down-regulated in breast cancer: a potential marker for the diagnosis of breast cancer.

MicroRNA-195 (miR-195) is a tumor suppressor that plays an important role in tumorigenesis. There are few studies on miR-195 expression in breast cancer patients and the results have been inconsistent; therefore, this study examined miR-195 expression in the serum of BC patients. Samples from 102 normal subjects and 210 subjects with BC who had detailed clinical follow-up information available were selected. An internal reference (miR-16) and serum miR-195 were amplified and quantitatively detected by SYBR green-based real-time RT-PCR. We analyzed the differences in miR-195 levels between BC and healthy cases and the relationships between the miR-195 level and TNM stage and other clinicopathological parameters. In addition, changes in miR-195 levels were examined for 21 BC cases using paired samples before and after neoadjuvant chemotherapy. miR-195 was downregulated in BC compared with control samples (P = 0.000, Mann-Whitney U test). The sensitivity and specificity of miR-195 in the diagnosis of BC were 69.0 and 89.2 %, respectively; whereas, the sensitivities of carcinoembryonic antigen (CEA) and carbohydrate antigen 153 (CA153) were only 15.08 and 21.1 %, respectively. Remarkably, serum miR-195 had higher sensitivity, 73.97 % (108/146), as a tumor marker in the diagnosis of early stage BC [ductal carcinoma in situ, tumor-node-metastasis (TNM) I, II] compared with the conventional tumor markers CA153 and CEA (12.41 and 7.59 %). Moreover, compared with CEA and CA153, miR-195 had a higher sensitivity for detecting the response to neoadjuvant chemotherapy and significantly increased, more than twofold, after neoadjuvant chemotherapy (P = 0.025, paired t test) in 52.381 % (11/21) of BC cases. However, there were no significant relationships between miR-195 expression and other clinicopathological parameters (TNM stage/pathotype/ER/PR/lymph node status). Our data indicate serum miR-195 is a promising tumor marker for BC diagnosis and general screening, especially for early stage BC. The high sensitivity of miR-195 to neoadjuvant chemotherapy may lay the foundation for future studies on the use of miRNA-based methods for monitoring BC treatment and therapy.

Arsenic trioxide inhibits Ewing's sarcoma cell invasiveness by targeting p38(MAPK) and c-Jun N-terminal kinase.

Ewing's sarcoma is the second most frequent primary malignant bone tumor, mainly affecting children and young adults. The notorious metastatic capability of this tumor aggravates patient mortality and remains a problem to be overcome. We investigated the effect of arsenic trioxide (As2O3) on the metastasis capability of Ewing's sarcoma cells. We performed 3-(4,5-dimethylthiazol-2-yl)-2, 5-diphenyl-2H-tetrazolium bromide assays to choose appropriate concentrations of As2O3 for the experiments. Migration, invasion, and adhesion assays were performed to assess the effect of As2O3 on the metastasis of Ewing's sarcoma. Immunofluorescent staining was used to observe cytoskeleton reorganization in Ewing's sarcoma cells treated with As2O3. Changes in matrix metalloproteinase-9 expression and the mitogen-activated protein kinase (MAPK) pathway were investigated using western blot. Inhibitors of p38(MAPK) (sb202190) and c-Jun NH2-terminal kinase (JNK, sp600125) were used in invasion assays to determine the effect of p38(MAPK) and JNK. We found that As2O3 may markedly inhibit the migration and invasion capacity of Ewing's sarcoma cells with structural rearrangements of the actin cytoskeleton. The expressions of matrix metalloproteinase-9, phosphor-p38(MAPK), and phosphor-JNK were suppressed by As2O3 treatment in a dose-dependent manner. The inhibitors of p38(MAPK) (sb202190) and JNK (sp600125) enhanced the inhibition induced by As2O3, which was counteracted by anisomycin, an activating agent of p38(MAPK) and JNK. Taken together, our results demonstrate that As2O3 can inhibit the metastasis capability of RD-ES and A-673 cells and may have new therapeutic value for Ewing's sarcoma.

Expression of stromal derived factor-1 (SDF-1) and chemokine receptor (CXCR4) in bone metastasis of renal carcinoma.

Renal cancer is a relatively common malignant carcinoma that metastasizes to bone. The chemokine stromal derived factor-1 (SDF-1) and its corresponding receptor CXCR4 have been shown to regulate organ-specific metastasis in other cancer types. Based on this observation, we predicted that the expressions of SDF-1 and CXCR4 play a role in renal carcinoma metastasis to bone. To investigate the expressions of SDF-1 and CXCR4, and to assess the correlation between SDF-1 and CXCR4 immunoreactivity in bone metastasis of renal carcinoma, we collected 10 in situ renal carcinoma samples and 30 bone metastasis samples. We analyzed SDF-1 and CXCR4 expression with immunohistochemical analysis on paraffin-embedded sections. Compared with primary renal carcinomas, the SDF-1 expression in bone metastases was significantly higher [80% (24/30) vs. 30% (3/10), P = 0.006]; the expression of CXCR4 was also higher [83.3% (25/30) vs. 40% (4/10), P = 0.014]. Pearson correlation analysis supports a positive correlation between SDF-1 and CXCR4 in bone metastasis of renal carcinoma. In addition, RT-PCR demonstrated that, as compared with in situ renal carcinoma tissues, SDF-1 expression was predominant in the bone metastasis samples (P = 0.001), while CXCR4 was overexpressed in the bone metastasis tissues (P = 0.028). Western blot analysis confirmed these trends. Our data suggest that the expression of SDF-1/CXCR4 is high in bone metastases and over-expression of SDF-1/CXCR4 may play important roles in the bone metastasis of renal carcinoma.

(-)-Epigallocatechin-3-gallate induces apoptosis and suppresses proliferation by inhibiting the human Indian Hedgehog pathway in human chondrosarcoma cells.

PURPOSE: Chondrosarcoma is a soft tissue sarcoma with a poor prognosis that is unresponsive to conventional chemotherapy. The regulatory mechanisms for the rapid proliferation of chondrosarcoma cells and the particular aggressiveness of this sarcoma remain poorly understood. In this study, we investigate the effect of epigallocatechin-3-gallate (EGCG) on growth and apoptosis of chondrosarcoma cells. METHODS: The chondrosarcoma cell lines, SW1353 and CRL-7891, were cultured with and without EGCG. The MTT assay was used to test the cytotoxicity of EGCG. Flow cytometry and DAPI staining were used to observe cell apoptosis caused by EGCG. To explore the effect of EGCG on the Indian Hedgehog signaling pathway and apoptosis-related proteins, RT-PCR and Western blotting were used to detect the expression of PTCH and Gli-1 in the Indian Hedgehog signaling pathway. Meanwhile, expression of Bcl-2, Bax, and caspase-3 were also evaluated by Western blot analysis. RESULTS: EGCG effectively inhibited cellular proliferation and induced apoptosis of SW1353 and CRL-7891. EGCG inhibited the human Indian Hedgehog pathway, down-regulated PTCH and Gli-1 levels, and induced apoptosis as confirmed by DAPI staining followed by flow cytometry. Protein expression levels of caspase-3 were unchanged in response to EGCG treatment in chondrosarcoma cells; however, the expression levels of Bcl-2 were significantly decreased and the levels of Bax were significantly increased. CONCLUSIONS: Our findings demonstrate that EGCG is effective for growth inhibition of a chondrosarcoma cell lines in vitro, and suggest that EGCG may be a new therapeutic option for patients with chondrosarcoma.