Surgical exposures of the distal humeral fractures: An anatomical study of the anterior, posterior, medial and lateral approaches.

PURPOSE: Exposure of the articular surface is the key to the successful treatment of intra-articular fractures of distal humerus. Anterior, posterior olecranon osteotomy as well as medial and lateral approaches are the four main approaches to the elbow. The aim of this study was to compare the exposure of distal articular surfaces of these surgical approaches. METHODS: Twelve cadavers were used in this study. Each approach was performed on six elbows according to previously published procedures. After completion of each approach, the exposed articular surfaces were marked by inserting 0.5 mm K-wires along the margins. The elbow was then disarticulated and the exposed articular surfaces were painted. The distal humeral articular surfaces were then closely wrapped using a piece of fibre-glass screen net with meshes. The exposed articular surfaces and the total articular surfaces were calculated by counting the number of meshes, respectively. RESULTS: The average percentages of the exposed articular surfaces for the anterior, posterior olecranon osteotomy, medial and lateral approaches were 45.7% ± 2.0%, 53.9% ± 7.1%, 20.6% ± 4.9% and 28.5% ± 6.3%, respectively. CONCLUSION: The anterior and posterior approaches provide greater exposures of distal humeral articular surface than the medial and lateral ones in the treatment of distal humeral fractures.

Combined Inhibition of KIF11 and KIF15 as an Effective Therapeutic Strategy for Gastric Cancer.

BACKGROUND: Novel therapeutic strategies are urgently required to improve clinical outcomes of gastric cancer (GC). KIF15 cooperates with KIF11 to promote bipolar spindle assembly and formation, which is essential for proper sister chromatid segregation. Therefore, we speculated that the combined inhibition of KIF11 and KIF15 might be an effective strategy for GC treatment. Hence, to test this hypothesis, we aimed to evaluate the combined therapeutic effect of KIF15 inhibitor KIF15- IN-1 and KIF11 inhibitor ispinesib in GC. METHODS: We validated the expression of KIF11 and KIF15 in GC tissues using immunohistochemistry and immunoblotting. Next, we determined the effects of KIF11 or KIF15 knockout on the proliferation of GC cell lines. Finally, we investigated the combined effects of the KIF11 and KIF15 inhibitors both in vitro and in vivo. RESULTS: KIF11 and KIF15 were overexpressed in GC tissues than in the adjacent normal tissues. Knockout of either KIF11 or KIF15 inhibited the proliferative and clonogenic abilities of GC cells. We found that the KIF15 knockout significantly increased ispinesib sensitivity in GC cells, while its overexpression showed the opposite effect. Further, using KIF15-IN-1 and ispinesib together had a synergistic effect on the antitumor proliferation of GC both in vitro and in vivo. CONCLUSION: This study shows that the combination therapy of inhibiting KIF11 and KIF15 might be an effective therapeutic strategy against gastric cancer.

Exosomes combined with biosynthesized cellulose conduits improve peripheral nerve regeneration.

Peripheral nerve injury is one of the more common forms of peripheral nerve disorders, and the most severe type of peripheral nerve injury is a defect with a gap. Biosynthetic cellulose membrane (BCM) is a commonly used material for repair and ligation of nerve defects with gaps. Meanwhile, exosomes from mesenchymal stem cells can promote cell growth and proliferation. We envision combining exosomes with BCMs to leverage the advantages of both to promote repair of peripheral nerve injury. Prepared exosomes were added to BCMs to form exosome-loaded BCMs (EXO-BCM) that were used for nerve repair in a rat model of sciatic nerve defects with gaps. We evaluated the repair activity using a pawprint experiment, measurement and statistical analyses of sciatica function index and thermal latency of paw withdrawal, and quantitation of the number and diameter of regenerated nerve fibers. Results indicated that EXO-BCM produced comprehensive and durable repair of peripheral nerve defects that were similar to those for autologous nerve transplantation, the gold standard for nerve defect repair. EXO-BCM is not predicted to cause donor site morbidity to the patient, in contrast to autologous nerve transplantation. Together these results indicate that an approach using EXO-BCM represents a promising alternative to autologous nerve transplantation, and could have broad applications for repair of nerve defects.

Effect of KIF22 on promoting proliferation and migration of gastric cancer cells via MAPK-ERK pathways.

BACKGROUND: Gastric cancer (GC) is one of the most globally prevalent cancers in the world. The pathogenesis of GC has not been fully elucidated, and there still lacks effective targeted therapeutics. The influence of altered kinesin superfamily protein 22 (KIF22) expression in GC progression is still unclearly. The aim of this study was to investigate the KIF22 effects on GC and related mechanisms. METHODS: Gastric carcinoma tissues and matching non-cancerous tissues were collected from patients with GC who have accepted a radical gastrectomy in Lanzhou University Second Hospital from May 2013 to December 2014. The expression of KIF22 was examined in GC of 67 patients and 20 para-carcinoma tissues by immunochemical staining. The relationship between the expression of KIF22 and clinicopathologic characteristics was next investigated in the remaining 52 patients except for 15 patients who did not complete follow-up for 5 years. Cell viability was performed via 3-(4,5-dimethyl-2-thiazolyl)-2,5-diphenyl-2-H-tetrazolium bromide (MTT) test and colony formation assay in the MGC-803 and BGC-823 GC cells. Cell scratch and trans-well invasion assay was performed to assess migration ability in the MGC-803 and BGC-823 GC cells. Gene set enrichment analysis (GSEA) pathway enrichment analysis was performed to explore the potential functions. Cell cycle was detected by flow cytometry. In addition, the two GC cell lines were used to elucidate the underlying mechanism of KIF22 in GC in vitro via assessing the effects on mitogen-activated protein kinase and extracellular regulated protein kinases (MAPK/ERK) signal transduction pathway-related expressions by Western blotting assays. The differences were compared by t tests, one-way analysis of variance, and Chi-squared tests. RESULTS: The study showed that KIF22 was up-regulated in GC, and KIF22 high expression was significantly related to differentiation degree (χ = 12.842, P = 0.002) and poorly overall survivals. GSEA pathway enrichment analysis showed that KIF22 was correlated with the cell cycle. Silence of KIF22 decreased the ability of the proliferation and migration in gastric cells, induced G1/S phase cell cycle arrest via regulating the MAPK-ERK pathways. CONCLUSIONS: KIF22 protein level was negatively correlated with prognosis. KIF22 knockdown might inhibit proliferation and metastasis of GC cells via the MAPK-ERK signaling pathway.

Natural Value of Böhler's Angle in Normal Chinese Population.

OBJECTIVE: To determine the value of Böhler's angle (BA) in a group of Chinese people, analyze possible factors that influence it, and compare BA with that in previous literature. METHODS: A total of 143 cases, aged from 4 to 79 years, were enrolled in the study, including 64 males and 79 females (79 left feet and 64 right feet). Radiographs were independently measured by six observers. Age, sex, body side, subtalar joint congruity (STJC), and X-beam obliquity (TT) were recorded. The database was assessed based on intraobserver agreement, data distribution, the randomness of case selection, and the ratio equality of binomial variables. Then, the normal value of BA was established, as well as the correlation between BA and other parameters. RESULTS: In the present study, the interobserver reliability of BA, STJC, and TT was excellent. The BA data revealed a normal distribution, and the randomness of case selection was verified for age, sex, and body side. The ratio of sex and body side was equal. Homogeneity of variance was observed when comparing the value of BA between different groups. The value of BA was 31.6° ± 5.19° (range, 20.08°-47.19°), which was not related to age, sex, body side, and minor X-ray beam obliquity. BA application was not suitable for individuals younger than 10 years. The mean value of BA in this study was not identical with those in previous reports. This demonstrated that BA varies for different races. CONCLUSION: For Chinese people, 30° to 33° is recommended as the target value of BA for calcaneal fracture reduction, except in children under 10 years of age.

The Role of Shcbp1 in Signaling and Disease.

Src homolog and collagen homolog (Shc) proteins have been identified as adapter proteins associated with cell surface receptors and have been shown to play important roles in signaling and disease. Shcbp1 acts as a Shc SH2-domain binding protein 1 and is involved in the regulation of signaling pathways, such as FGF, NF-κB, MAPK/ERK, PI3K/AKT, TGF-ß1/Smad and ß -catenin signaling. Shcbp1 participates in T cell development, the regulation of downstream signal transduction pathways, and cytokinesis during mitosis and meiosis. In addition, Shcbp1 has been demonstrated to correlate with Burkitt-like lymphoma, breast cancer, lung cancer, gliomas, synovial sarcoma, human hepatocellular carcinoma and other diseases. Shcbp1 may play an important role in tumorigenesis and progression. Accordingly, recent studies are reviewed herein to discuss and interpret the role of Shcbp1 in normal cell proliferation and differentiation, tumorigenesis and progression, as well as its interactions with proteins.

Bone marrow mesenchymal stem cell-derived exosome uptake and retrograde transport can occur at peripheral nerve endings.

We investigated the occurrence of mesenchymal stem cell (MSC)-derived exosome uptake and retrograde transport at peripheral nerve endings using bone marrow MSCs (bMSCs) transduced with recombinant CD63-green fluorescent protein (GFP) lentiviral plasmid. GFP was used to track the release of bMSC-derived exosomes and the uptake and transport at peripheral nerve terminals, the dorsal root ganglion (DRG), and the spinal cord. In vitro cell culture and injection of a CD63-GFP exosome suspension into the right gastrocnemius muscle of an in vivo rat model were also performed. Fluorescence microscopy of co-cultured CD63-GFP exosomes and SH-SY5Y or BV2 cell lines and primary cultured DRG cells in a separate experiment demonstrated exosome uptake into DRG neurons and glia. Moreover, we observed both retrograde axoplasmic transport and hematogenous transport of exosomes injected into rat models at the DRG and the ipsilateral side of the anterior horn of the spinal cord using fluorescence microscopy, immunohistochemistry, and Western blot analyses. In conclusion, we showed that exosome uptake at peripheral nerve endings and retrograde transport of exosomes to DRG neurons and spinal cord motor neurons in the anterior horn can occur. In addition, our findings propose a novel drug delivery approach for treating neuronal diseases.

[Biomechanics and imaging evaluation on stable structure of pelvis].

The treatment of difficulty and prognosis of pelvic fracture are directly related to the pelvic girdle stability. Diagnosis of pelvic fracture is mainly imaging manifestations based on biomechanics of pelvic anatomy. With the progress of biomechanics experiment technology, previousopinion has changed, such as separation of symphysis pubis 2.5 cm could not be seen as distinguishing feature of type I and II for anterior-posterior compression;displacement of sacroilliac joints less than 1 cm could cause loss of vertical stability;lateral extrusion could also cause vertical instability;part description of Young-Burgess classification is not suitable for experiment results;ligament plays an important role in restricting displacement and having proprioceptors;SPECT-CT could improve sensitivity of diagnosis, but could not evaluate stability of pelvic fractures precisely.

The protective effect and underlying mechanism of Hainan papaya water extract against neuronal apoptosis induced by Aß40.

OBJECTIVE: To investigate whether Hainan papayas has protective effects in an Aß40-induced primary neuron injury model and elucidate the underlying molecular mechanism. METHODS: Cultured primary neurons from the dorsal root ganglia (DRG) of Sprague-Dawley (SD) rats were treated with 20 µM Aß40 peptide, 100 µg/L Hainan papaya water extract, peptide plus extract, or culture medium for 24 h. Cell viability was measured by MTT assay, and neuronal apoptosis was evaluated by DAPI staining. ERK signaling pathway-associated molecule activation and changes in Bax expression were analyzed by Western blotting and immunofluorescence. RESULTS: A cell viability rate of (44.11 ± 6.59)% in the Aß40 group was rescued to (79.13 ± 6.64)% by adding different concentrations of the extract. DAPI showed pyknotic nuclei in 39.5% of Aß40-treated cells; the fraction dropped to 17.4% in the 100 µg/L extract group. ERK phosphorylation was observed in the Aß40 group but was ameliorated by pretreatment with 100 µg/L extract. Hainan papaya water extract also prevented Aß40-induced phosphorylation of MEK, RSK1 and CREB associated with ERK signaling and downregulated Bax expression in the neurons. CONCLUSION: The results suggest that Hainan papaya water extract has protective effects on neurons; the mechanism may be related to suppression of ERK signaling activation.

srGAP3 promotes neurite outgrowth of dorsal root ganglion neurons by inactivating RAC1.

OBJECTIVE: To explore effect of srGAP3 promotes neurite outgrowth of dorsal root ganglion neurons. METHODS: In this study, expression of Slit1 was observed predominantly in the glia, while expression of Robo2 and srGAP3 was detected in sensory neurons of postnatal rat cultured dorsal root ganglion (DRG). Furthermore, upregulation of srGAP3 following sciatic nerve transection was detected by immunohistochemistry and Western blotting. RESULTS: It was observed that inhibition of neurite outgrowth in cultured adult DRG neurons following treatment with anti-srGAP3 or anti-Robo2 was more effectively (1.5-fold higher) than that following treatment with an anti-BDNF positive control antibody. It demonstrated that srGAP3 interacted with Robo2 and Slit1 protein to decrease Rac1-GTP activity in cultured adult rat DRG neurons and the opposite effect on Rac1-GTP activity was detected by co-immunoprecipitation and immunoblotting analyses following treatment with anti-Robo2 or anti-srGAP3. These data demonstrated a role for srGAP3 in neurite outgrowth of DRG sensory neurons. CONCLUSIONS: Our observations suggest that srGAP3 promotes neurite outgrowth and filopodial growth cones by interacting with Robo2 to inactivate Rac1 in mammalian DRG neurons.

Slit1 promotes regenerative neurite outgrowth of adult dorsal root ganglion neurons in vitro via binding to the Robo receptor.

Secreted Slit proteins have previously been shown to signal through Roundabout (Robo) receptors to negatively regulate axon guidance and cell migration. During vertebrate development, Slit proteins have also been shown to stimulate branching and elongation of sensory axons and cortical dendrites. In this study, Slit1/Robo2 mRNA and protein expressions were detected in adult rat dorsal root ganglion (DRG) and in cultured DRG neurons. Treatment of both models with recombinant, soluble Slit1 protein was found to promote neurite outgrowth and elongation. In contrast, treatment with a recombinant human Robo2/Fc chimera inhibited neurite outgrowth and elongation. When adult DRG and cultured DRG neurons were pretreated with soluble recombinant human Robo2/Fc chimera, neurite outgrowth and elongation was not induced. These findings indicate that Slit1/Robo2 signaling may have a role in regulating peripheral nerve regeneration.

[Expression of ET-3 in hippocampal CA1 of ovariectomied mice after cerebral ischemia/reperfusion].

OBJECTIVE: To detect the expression of endothelins-3 (ET-3) immunoactivity in hippocampal CA1 of ovariectomied (OVX) mice after ischemia/reperfusion (IR), and to further explore the relationship between estrogen and ET-3. METHODS: Fifty-four adult female mice were randomly divided into 3 groups. 1. IR group: the bilateral common carotid occlusion (BCCO) was carried out for 7 min on the 1st, 3rd, 5th and 14th day of reperfusion. 2. OVX/IR group: firstly the ovariectomy was performed, and after a week, BCCO was carried out for 7 min on the 1st, 3rd, 5th and 14th day of reperfusion (each time spot, n = 6). 3. sham-operated group (n = 6). RESULTS: Few ET-3 positive cells were diffusely distributed in the hippocampal CA1 region in the control group, whereas the expression of ET-3 increased in the experimental groups. The number of ET-3 positive cells significantly increased in the OVX/IR group compared with that of the IR group 1 d after the reperfusion (P < 0.01). It reached the maximum in both the OVX/IR and IR group on the 5th day of the reperfusion. CONCLUSION: Estrogen is involved in the regulation of ET-3 in the early stage of the reperfusion, and probably plays a protective role in the survival of neurons.