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The regeneration and repair of damaged load-bearing segmental bones require considerable mechanical strength for the artificial implants. The ideal biomaterials should also facilitate the production of porous implants with high bioactivity desirable for stimulating new bone growth. Here we developed a new mechanically strong, highly bioactive dilute magnesium-doped wollastonite (CaSiO3–Mg; CSi–Mg) porous scaffold by the robocasting technique. The sintered scaffolds had interconnected pores 350 µm in size and over 50% porosity with appreciable compressive strength (>110 MPa), 5–10 times higher than those of pure CSi and β-TCP porous ceramics. Extensive in vitro and in vivo investigations revealed that such Ca–silicate bioceramic scaffolds were particularly beneficial for osteogenic cell activity and osteogenic capacity in critical size femoral bone defects. The CSi–Mg porous constructs were accompanied by an accelerated new bone growth (6–18 weeks) and a mechanically outstanding elastoplastic response to finally match the strength (10–15 MPa) of the rabbit femur host bone after 18 weeks, and the material itself experienced mild resorption and apatite-like phase transformation. In contrast, the new bone regeneration in the β-TCP scaffolds was substantially retarded after 6–12 weeks of implantation, and exhibited a low level of mechanical strength (

Osteoarthritis (OA) is the most prevalent joint disease and uncontrolled inflammation is now recognized to play vital roles in OA development. Targeting the endogenous counterpart of inflammation may develop new therapeutic approaches in resolving inflammation persistence and treating inflammatory disease including OA. The orphan nuclear receptor 4A1 (NR4A1) is a key negative regulator of inflammatory responses but its role in osteoarthritis remains unclear. In the present study, we found that the NR4A1 expression was elevated in human osteoarthritis cartilage and in vitro OA model, which could be blocked by NF-κB signal inhibitor JSH23. The overexpression of NR4A1 inhibited, whereas knockdown of NR4A1 enhanced IL-1β induced COX-2, iNOS, MMP3, MMP9 and MMP13 expression, and luciferase reporter activity of NF-κB response element. Though NR4A1 was upregulated in inflammatory stimulation and creates a negative feedback loop, persistent inflammatory stimulation inhibited NR4A1 expression and activation. The expression of NR4A1 declined rapidly after an initial peak in conditions of chronic IL-1β stimulation, which could be partially restored by HDACs inhibitor SAHA. The phosphorylation of NR4A1 was increased in human osteoarthritis cartilage, and p38 inhibitor SB203580, JNK inhibitor SP600125 and ERK inhibitor FR180204 could significantly inhibited IL-1β induced NR4A1 phosphorylation. Reactivation of NR4A1 by its agonist cytosporone B could inhibit IL-1β induced chondrocyte inflammation and expression of COX-2, iNOS, MMP3, MMP9, and MMP13. In rat OA model, intra-articular injection of cytosporone B protected cartilage damage and ameliorated osteoarthritis. Thus, our study demonstrated that the NR4A1 is a key endogenous inhibitor of chondrocyte inflammation, which was relatively inactivated under chronic inflammatory stimulation through HDACs mediated transcriptional suppression and MAKP dependent phosphorylation in osteoarthritis. NR4A1 agonist cytosporone B could reactivate and restore the inhibitory regulatory ability of NR4A1, prevent excessive inflammation, and ameliorates osteoarthritis.

Objective This article determines which of the one-and-a-half nostril, mononostril, and binostril endoscopic endonasal transsphenoidal approaches provide a superior manipulation during surgery. Methods The three approaches were orderly performed on 10 silicon-injected cadaveric heads to quantitatively assess surgical freedom and attack angle for sella. Measurements were determined with a standardized method under neuronavigation system using data of computed tomography. Results The one-and-a-half nostril endoscopic transsphenoidal approach (OETA) offered superior exposed area than that of the mononostril approach (META), and similar to that of the binostril approach (BETA). For surgical freedom at anatomic targets, the OETA showed greater surgical flexibility at pituitary center, the right medial optic carotid recess (R-mOCR), the left mOCR, the medial intersection of the right cavernous internal carotid artery, and extension line of upper margin of the clivus (R-mICC) than those of the META, and similar to those of the BETA.For sagittal angle of attack to the R-mOCR, R-mICC, and L-mOCR, the OETA can provide better angular freedom for surgeon than that of the META, and similar to that of the BETA. The OETA had the same axial attack to the pituitary center with the BETA. The OETA and the META had limited surgical freedom at L-mICC, and both inferior to the BETA. Conclusion The OETA has similar exposed area, surgical freedom, and attack angle for most anatomic targets to the BETA without resecting contralateral nasal septal mucosa, and obviously superior to the META.

Additional file 1. SPIRIT 2013 Checklist: Recommended items to address in a clinical trial protocol and related documents.

Glioblastoma (GBM, WHO grade 4) is a highly heterogeneous and aggressive primary malignant brain tumor. BTB domain and CNC homology 1 (BACH1) is a transcription factor, and it plays an essential role in regulating tumor metastasis, tumor metabolism, and tumor stem cell self-renewal. However, its role in glioma is still unclear. In this research, we confirmed that BACH1 as an independent prognostic indicator was enriched in GBMs. BACH1 was strongly correlated with immune responses in GBMs, especially the M0 and M2 tumor-associated macrophage (TAM) mediated immune responses. GBMs with high expression of BACH1 express high levels of immune checkpoints (ICs), glioma cell-derived TAM chemokines, and M2 TAM markers. Interestingly, single cell RNA-seq analysis showed that the expression level of BACH1 in TAMs was higher than that in the other cell types in GBM. Transcriptome analysis of U87-MG cells showed that compared with the BACH1-vector U87-MG group, glioma cell-derived TAM chemokines (including monocyte chemotactic protein-1 (MCP-1), granulocyte-macrophage colony-stimulating factor (GM-CSF), and EGF) and ICs (including CD276, TIM-3, LAG3, TIGIT and LGALS9) were enriched in the BACH1-overexpressing U87-MG group. In addition, we constructed a polygenic risk scoring model and compound nomogram model based on BACH1, which might provide a reliable prognosis assessment tool for clinicians and aid in treatment decision-making in the clinic. In conclusion, this research identified that BACH1 might be a potential molecular signature for survival and immunotherapy response. GBMs with high expression of BACH1 have a stronger immunosuppressive tumor microenvironment (TME). Overexpression of BACH1 can upregulate the expression of glioma cell-derived TAM chemokines and ICs in vitro. Moreover, the risk model and nomogram model based on BACH1 can provide a reliable prognosis assessment tool. Therefore, BACH1 is a promising therapeutic target for GBMs.

Aims Postmenopausal osteoporosis is a bone metabolism disease that is caused by an imbalance between bone-resorbing osteoclast and bone-forming osteoblast actions. Herein, we describe the role of troxerutin (TRX), a trihydroxyethylated derivative of rutin, in ovariectomy (OVX)-induced osteoporosis and its effects on the regulation of osteoclasts and osteoblasts. Main methods In vivo, OVX female mice were intraperitoneally injected with either saline, 50 mg/kg TRX, or 150 mg/kg TRX for 6 weeks and then sacrificed for micro-computed tomography analyses, histological analyses, and biomechanical testing. In vitro, RAW264.7 cell-derived osteoclasts and MC3T3-E1 cell-derived osteoblasts were treated with different concentrations of TRX to examine the effect of TRX on osteoclastogenesis and bone resorption, as well as on osteogenesis and mineralization. Key findings In this study, we demonstrated that TRX prevented cortical and trabecular bone loss in ovariectomized mice by reducing osteoclastogenesis and promoting osteogenesis in vivo. In vitro, TRX inhibited the formation and activity of RAW264.7-derived osteoclasts and the expression of nuclear factor of activated T-cells 1 and cathepsin K. Meanwhile, TRX improved the osteogenesis and mineralization of MC3T3-E1 by enhancing the expression of Runt-related transcription factor 2, Osterix, and collagen type 1 alpha 1. Significance Our data demonstrated that TRX could prevent OVX-induced osteoporosis and be used in a novel treatment for postmenopausal osteoporosis.

Jisheng Ran,* Chiyuan Ma,* Kai Xu,* Langhai Xu, Yuzhe He, Safwat Adel Abdo Moqbel, Pengfei Hu, Lifeng Jiang, Weiping Chen, Jiapeng Bao, Yan Xiong, Lidong Wu Department of Orthopedic Surgery, The Second Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou, China *These authors contributed equally to this work Introduction: Osteoarthritis (OA) is the most prevalent joint disorder in the elderly population, and inflammatory mediators like IL-1βwere thought to play central roles in its development. Schisandrin B, the main active component derived from Schisandra chinensis, exhibited antioxidative and antiinflammatory properties. Methods: In the present study, the protective effect and the underlying mechanism of Schisandrin B on OA was investigated in vivo and in vitro. Results: The results showed that Schisandrin B decreased IL-1β-induced upregulation of matrix metalloproteinase 3 (MMP3), MMP13, IL-6, and inducible nitric oxide synthase (iNOS) and increased IL-1β-induced downregulation of collagen II, aggrecan, and sox9 as well. Schisandrin B significantly decreased IL-1β-induced p65 phosphorylation and nuclear translocation of p65 in rat chondrocytes. Mitogen-activated protein kinase (MAPK) activation was also inhibited by Schisandrin B, as evidenced by the reduction of p38, extracellular signal-regulated kinase (Erk), and c-Jun amino-terminal kinase (Jnk) phosphorylation. In addition, Schisandrin B prevented cartilage degeneration in rat OA model with significantly lower Mankin’s score than the control group. Conclusion: Our study demonstrated that Schisandrin B ameliorated chondrocytes inflammation and OA via suppression of nuclear factor-κB (NF-κB) and MAPK signal pathways, indicating a therapeutic potential in OA treatment. Keywords: osteoarthritis, Schisandrin B, chondrocytes, MMPs, NF-κB pathway, MAPK pathway

PURPOSE: To investigate imaging features of crossed cerebellar diaschisis (CCD) in cerebral gliomas, and its underlying pathophysiological mechanisms. METHODS: Thirty-three pre-surgical patients with cerebral gliomas and 33 healthy controls underwent arterial spin-labeling, diffusion tensor imaging, and high-resolution T1-weighted imaging using MRI, in order to estimate cerebral blood flow (CBF), white matter integrity, and lesion volume, respectively. Asymmetry indices of CBF in the cerebellum were used for evaluating the level of CCD in the patients. These indices were correlated with clinical variables (lesion size and position, tumor histological grade, and CBF asymmetry) and diffusion tensor imaging parameters (fractional anisotropy and number of fibers in the cortico-ponto-cerebellar pathway and across the cerebral hemispheres), respectively. RESULTS: The patients showed decreased CBF in the cerebellar hemisphere contralateral to the supratentorial tumor, and increased CBF asymmetry in the cerebellum (both P

To investigate the inflammatory effect of Interleukin 18 (IL-18) on rat chondrocytes and the involvement of Wnt/β-catenin and Hedgehog pathways, the mRNA and protein level of matix-degrading enzymes (MMP-2, 3, 9,13 and aggrecanses) and chondrocyte-specific proteins (Collagen II and aggrecan) were evaluated by qRT-PCR and Western blot, and key protein level of Wnt/β-catenin and Hedgehog pathways including β-catenin, GSK-3β, DKK-1, IHH, SHH, and Gli-2 were evaluated by Western blot. Dickkopf-1 (DKK-1) and Cyclopamine were used as antagonist of Wnt/β-catenin and Hedgehog pathways to perform pathway inhibition tests. In addition, location and expression of β-catenin, GSK-3β, Gli-2 and Smo were assessed by Immunofluorescence microscopy. The results showed up-regulation of matix-degrading enzymes (MMP-2, 3, 9,13 and aggrecanses) and down-regulation of chondrocyte-specific proteins (Collagen II and aggrecan) at both mRNA and protein level and activation of Wnt/β-catenin and Hedgehog pathways in the inflammatory reaction on rat chondrocytes caused by IL-18 treatment was observed. As conclusion, Wnt/β-catenin and Hedgehog pathways are involved in the inflammatory effect of IL-18 in vitro.

Background Use biomechanical technique to access the strain distribution and stability of Contour anti-protrusion cage with or without the whole circumference acetabular cup fixation by the transacetabular screws. Methods Pelvic specimens from 10 male cadavers were used for the biomechanical test. The models of type C bone defect were copied according to the AAOS classification. Group 1: the contour reconstruction ring was fixed only by flange screws; Group 2: the contour reconstruction ring was fixed both by flange screws and transacetabular screws in dome. Under load in Heel Strike, Midstance, and Toe off phase, the transverse and longitudinal strains were measured in both the superior measure site near the root of the iliac wing and the inferior measure site near the root of the ischium. The relative displacement between the anterior inferior spine and the root of ischium below acetabular component was also measured. Findings Compared with Group 1, the transverse and longitudinal pressure strain of Group 2 on the superior measure site decreased, and measure sites also showed reductions on the inferior under load under three different gait phases. The result of mean relative displacement showed transacetabular screws fixation couldn't provide significant improvement of displacement prevention. Interpretation Biomechanical test showed that under the premise of a satisfied bone allograft and well-fixed flange screws in iliac and ischium, the satisfactory initial stability of the reconstruction cup can be achieved, but could not be improved by transacetabular screw technique. However, the max strain in root part of the flange will be reduced using transacetabular screws in ilium, pubis and ischium together, and the strain distribution will also be improved.

// Guan Sun 1,* , Ying Cao 2,* , Nan Jiang 1 , Dekang Nie 1 , Zhengqiang Wan 1 , Min Li 3 , Chiyuan Ma 4 and Jun Guo 1 1 Department of Neurosurgery, The First People’s Hospital of Yancheng, Yancheng, P R China 2 Department of Ear-Nose-Throat, The Second People’s Hospital of Huai’An, Huai’An, P R China 3 Department of Neurosurgery, Jiangning Hospital Affiliated with Nanjing Medical University, Nanjing, P R China 4 Department of Neurosurgery, Jinling Hospital, School of Medicine, Nanjing University, Nanjing, P R China * These authors have contributed equally to this work Correspondence to: Jun Guo, email: // Chiyuan Ma, email: // Keywords : pituitary adenomas; bilateral nostrils; sphenoid sinus; neuroendoscopy Received : February 15, 2017 Accepted : March 16, 2017 Published : April 09, 2017 Abstract Here we review the technical aspects of our experience with the neuroendoscopic bilateral nostril (binostril) transsphenoidal approach for pituitary adenomas. A total of 42 patients were treated in our hospital from September 2013 to December 2015. Total tumor resection was completed in 31 cases, nearly full resection was achieved in 9 cases, and partial resection was achieved in 2 cases. In most cases clinical symptoms were relieved after surgery. These included 18/22 cases with visual field and vision disorders; 19/25 cases with headaches; 11/15 cases where high baseline PRL returned to normal levels; 6/7 cases where elevated blood GH returned to normal levels; and 2/3 cases where elevated blood ACTH returned to normal levels after surgery. Postoperative complications were observed in 13 patients: 8 cases of diabetes insipidus, 4 cases of cerebrospinal fluid rhinorrhea, and 1 case of subarachnoid hemorrhage. Among the key advantages of the neuroendoscopic binostril transsphenoidal approach for pituitary adenoma resection are its minimally-invasive nature, clear exposure of the operative field, high full-excision rates, improved peri-operative safety, and minor patient trauma with fewer postoperative complications.

This study aims to evaluate whether the serum Anterior Gradient-2 (AGR2) can be used as a potential biomarker screening in the diagnosis of Pituitary adenomas(PAs).The serum AGR2 protein levels were preoperatively measured in 163 PA patients, 43 patients with other sellar lesions excluding PAs, 7 patients with prostate cancer as a positive control and 20 normal people(10 female and 10 male) using Enzyme-Linked ImmunoSorbent Assay (ELISA). Differences in the serum AGR2 level between different groups were analyzed for statistical significance with a Mann-Whitney U test.The data showed that serum AGR2 level was significantly higher in the serum of PA patients (250.10±79.14ng/ml) than the patients with other sellar lesions (220.84±79.62ng/ml, P=0.017) and normal people (163.67±50.38ng/ml, P0.001). Receiver operating characteristic (ROC) curve analysis was used. The detected area under the curve (AUC) was 0.835. The calculated optimal cut-off point for AGR2 level in serum samples was 158.63ng/ml (Youden index=0.564). The sensitivity was 91.4% and the specificity was 65.0%. Despite the variety of PA clinical features, the serum level of AGR2 are definite in PAs, although there may be a difference between male or female patients.Our data suggests AGR2 as a potential biomarker for the diagnosis of PAs.

Several studies have investigated strategies to improve the clinical efficacy of radiotherapy (RT) against hepatocellular carcinoma (HCC), yet the prognosis remains poor. Human adipose tissue-derived mesenchymal stem cells (AT-MSCs), easily accessible and abundant in quantity, have represented as an attractive therapeutic tool for the stem cell-based treatment for cancer diseases. Through direct co-culture and indirect separate culture experiments, we showed that AT-MSCs could enhance inhibitory effect of RT on reducing HCC cell growth, migration and invasion in both in vitro and in vivo experiments. RNA-sequencing analysis revealed a noticeable interferon-induced transmembrane 1 (IFITM1)-induced tumor gene signature. Gain and loss of mechanistic studies indicated that mechanism was attributed to downregulated expression of signal transducer and activator of transcription 3 (STAT3) and matrix metallopeptidases (MMPs) and upregulated expression of P53 and caspases. Collectively, our findings suggest that AT-MSCs might enhance the therapeutic effects of RT on HCC, providing a rationale for AT-MSCs and RT combination therapy as a new remedy for HCC.

Simulation-based training has been considered as the most promising curriculum for neurosurgical education to finally improve surgical skills with the greatest efficiency and safety. However, most of the simulators including physical models and virtual reality systems are relatively expensive, which limits their promotion. In this study, the authors tried to develop a realistic, low-cost, and reusable simulator for endoscopic third ventriculostomy (ETV) and evaluate its validity. A 3D-printed rigid skull with the ventricular system originated from a de-identified patient with obstructive hydrocephalus was constructed. The third ventricular floor was designed as a replaceable module. Thirty-nine neurosurgeons tested the simulator and a rating system was established to assess their performance. All participants filled out questionnaires to evaluate the simulator after training. Five neurosurgical students were recruited to finish the whole training for ten times in order to explore the learning curve of ETV. We found that (1) the more experienced surgeons performed obviously better than the rather inexperienced surgeons which verified that our model could reflect the ability of the trainees; (2) as the training progressed, the scores of the post-graduates increased and the fifth training average score was obviously higher than their first training average score. The feedback questionnaires showed the average scores for value of the simulator as a training tool and global rating were 3.15 and 3.54 (on a 4-point scale). Our model was practical for ETV training. The results of our program showed that our model could precisely reflect the operators’ ability to perform ETV and could make it more efficient to master basic skills.

Mammalian oocyte restores meiosis can be stimulated by follicle-stimulating hormone (FSH) under normal physiological conditions. G-protein coupled receptor 30 (GPR30), an non-classical estrogen membrane receptor, has been widely reported in teleost oocyte maturation. However, it remains unknown whether GPR30 involves the role of FSH in mammalian cumulus expansion and oocyte maturation. Here, we used mouse cumulus-oocyte complexes (COCs) as a model to investigate how FSH affects the in vitro maturation of mouse oocytes mediated by 17β-estradiol (E

Spontaneous cerebrospinal fluid (CSF) rhinorrhea represents an important clinical entity that is being observed with increasing prevalence, ranging from 14 to 55%. Spontaneous CSF rhinorrhea is associated with elevated intracranial pressure (ICP), which is rarely stopped without surgical intervention. Endoscopic endonasal repair is typically warranted for CSF rhinorrhea. However, the recurrence rate of CSF leaks after the endoscopic endonasal repair of skull base defects due to ICP is usually high. We describe a 25-year-old man without a history of head injury, tumor, or obesity. The onset of his symptoms occurred in 1 week in the form of a persistent clear left nostril rhinorrhea. Computed tomography (CT) and magnetic resonance images (MRI) showed signs of CSF in the left sphenoidal sinus, meningocele in the left frontal sinus, empty sella, hydrocephalus, and Chiari I malformation (CIM). Cine-MRI revealed the flow of CSF was obstructed at the aqueduct and the outlet of the fourth ventricle. Endoscopic third ventriculostomy (ETV) was performed for the patient with obstructive hydrocephalus. Post-operative CSF pressure measurement demonstrated elevated ICP. The patient still had case of CSF rhinorrhea, and subsequently underwent lumboperitoneal shunt (LPS) for treatment of ICP. The patient showed a prompt resolution of CSF leak. Ten months later, the patient showed a significant improvement in terms of his herniated tonsil and cessation of CSF rhinorrhea.

As a joint disease, osteoarthritis (OA) is caused by the breakdown of subchondral bone and cartilage damage. Inflammatory factors, such as interleukin- (IL-) 1β, mediate the progression of OA. Madecassoside (MA), a triterpenoid component derived from the gotu kola herb (Centella asiatica), exhibits various pharmacological effects, including antioxidative and anti-inflammatory properties. In the present study, the protective effects and possible mechanism of MA on the treatment of OA were investigated. MA was demonstrated to significantly suppress the IL-1β-induced overexpression of matrix metalloproteinase- (MMP-) 3, MMP-13, inducible nitric oxide synthase (iNOS), and cyclooxygenase-2 (COX-2) and to decrease the IL-1β-induced degradation of type II collagen and sox9. Additionally, MA was able to reduce the IL-1β-induced phosphorylation of p65 in osteoarthritic chondrocytes. Furthermore, in a rat OA model, MA prevented cartilage degeneration and reduced the OARSI score in the MA-treated group compared with the OA group. The present study showed that MA suppresses the nuclear factor-κB signaling pathway, reducing IL-1β-induced chondrocyte inflammation, which indicates the therapeutic potential of MA in patients with OA.

Summary Objective Metabolic disorders and inflammation of chondrocytes are major pathological changes in aging cells and osteoarthritis (OA). Recent studies demonstrated age-related mitochondrial dysfunction may be a key contributing factor in the development of OA. Mitofusin 2 (MFN2) is a key regulator of mitochondrial fusion, cell metabolism, autophagy and apoptosis. This study was performed to ascertain whether MFN2 was involved in the aging of chondrocytes and OA. Methods Metabolic measurements were taken in rat chondrocytes between different ages (3-week, 5-month, 12-month). MFN2 activity was detected in both human and rat chondrocytes during aging and OA. Then, knockdown of MFN2 with small interfering RNA (siRNA) was performed to confirm whether MFN2 contributes to metabolic changes. Lentiviruses were used to establish MFN2-overexpression/knockdown OA models both in vivo and in vitro to confirm whether MFN2 contributes to OA progress. Further, regulatory mechanism of MFN2 was assessed and interaction between MFN2 and PARKIN was performed. Results A metabolic shift to mitochondrial respiration was confirmed in rat chondrocytes during aging. MFN2 expression was elevated in both human and rat chondrocytes during aging and OA. Knockdown of MFN2 with siRNA reversed the age-related metabolic changes in rat chondrocytes. Overexpression of MFN2 exacerbated inflammation and OA progress, while knockdown of MFN2 ameliorated inflammation and OA progress. Further, MFN2 could be ubiquitinated by PARKIN, declined PARKIN expression during aging and OA might result in elevated MFN2 expression. Conclusions Elevated MFN2 contributes to metabolic changes and inflammation during aging of rat chondrocytes and osteoarthritis.

Overactivation of the Gs-mediated pathway by mutations of the G-protein α subunit (Gsα), a gsp oncogene, results in increased growth hormone (GH) hypersecretion and reduced tumor volume in patients with GH-secreting pituitary tumors. However, the mechanism underlying the clinical characteristics of gsp oncogene requires further investigation. Cyclic adenosine monophosphate-responsive element binding (CREB), as a downstream target gene of gsp oncogene, is implicated in activating maternally expressed gene 3 (MEG3). The present study proposes that gsp oncogene mediates MEG3-regulating GH hypersecretion, resulting in the small tumor size of GH-secreting tumors. Therefore, the present study detected Gsα mutations by polymerase chain reaction in GH-secreting tumors, and revealed that Gsα mutations were observed in 7/25 (28%) GH-secreting tumors. Gsp-positive tumors indicated significantly increased levels of phosphorylated p-CREB (P

Dopamine agonists such as bromocriptine and cabergoline are the predominant treatment drugs for prolactinoma by inhibiting prolactin secretion and shrinking tumor size. However, the pathways of either dopamine or its agonists that lead to the death of cells are incompletely understood and some are even conflicting conclusions. The main aim of this paper is to review the different pathways of dopamine and its agonists in prolactinomas to help to gain a better understanding of their functions and drug resistance mechanisms.

Ca-silicate cements have drawn considerable attention for their potential applications in the field of bone repair due to their excellent bioactivity in vitro. Significant progress with regard to physicochemical properties and optimization of fabrication techniques of this new cement system has been achieved. However, it is unknown whether these so-called bioactive cements could efficiently repair critical-size bone defects in vivo. Herein we systematically investigated the biological performance of a β-dicalcium silicate (β-C2S)-based bone cement in comparison with the clinically used calcium phosphate cement (CPC) and Bio-Oss®. The results indicated that β-C2S-based cement with 25% gypsum exhibited appreciable Ca and Si release and weight loss (∼28%) in Tris buffer within the initial 7 d but then maintained a mild degradation rate during 1–4 weeks. Also, the β-C2S-based cement extracts readily enhanced MC3T3 proliferation at a 25 mg ml−1 level at 4 d and ALP expression at 50–100 mg ml−1 levels at 7 d. For the β-C2S-based group, increased mRNA levels of osteogenic genes, including Collagen I, osteocalcin, special protein 7, and runt-related transcription factor 2, were observed. In particular, histological staining and microCT reconstruction analyses demonstrated that this new cement could significantly enhance new bone regeneration in a critical-sized skull defect model in rabbits compared with CPC and Bio-Oss®. These findings suggest that β-C2S-based biocement is a promising bone implant for bone regeneration and repair due to its excellent biological performance in vitro and in vivo.

Osteoarthritis (OA) is a chronic joint disease involving cartilage erosion and matrix degradation. Costunolide is a sesquiterpene lactone that has been demonstrated to exert anti‑inflammatory activities in a wide variety of cells. The aim of the present study was to investigate the effect of costunolide in OA treatment, using rat chondrocytes and an OA rat model, in which animals were subjected to destabilization of the medial meniscus. The results revealed that costunolide (2‑6 µM) had no effect on chondrocyte viability or phenotype maintenance. Costunolide decreased the interleukin (IL)‑1β‑induced upregulation of matrix metalloproteinases (MMPs), inducible nitric oxide synthase, cyclooxygenase‑2 and IL‑6, and increased the expression of collagen II and transcription factor SOX‑9, which were inhibited by IL‑1β. Costunolide significantly decreased p65 phosphorylation induced by IL‑1β and the translocation of p65 into the nucleus of rat chondrocytes, as observed by western blot analysis and immunofluorescence staining. In addition, activation of the Wnt/β‑catenin signaling pathway was inhibited by costunolide, as demonstrated by the level of activation of β‑catenin and the transfer of β‑catenin into the nucleus induced by IL‑1β. In vivo, cartilage treated with costunolide exhibited attenuated degeneration and lower Mankin scores compared with the OA group. The present study investigated the anti‑osteoarthritic effects of costunolide, which exerted anti‑inflammatory activities and inhibited MMPs expression. Taken together, these results indicate that costunolide may have a potential value in the treatment of OA.

Estrogen plays a critical role in the regulation of gap junctions between oocytes and granulosa cells in mammalian ovaries. G protein-coupled receptor 30 (GPR30) was identified as a membrane estrogen receptor, mediating rapid, nongenomic signaling events that might be responsible for the regulation of oocyte meiosis resumption and gap junction intercellular communications (GJICs). The present study aimed to determine the expression and localization of GPR30 and its role in oocyte meiotic progression and GJICs in goat cumulus-oocyte complexes (COCs). Immunofluorescence experiments revealed that GPR30 was primarily located in the plasma membrane of cumulus cells and oocytes in goats. 17β-estradiol could promote oocyte meiotic progression, which was blocked by G15 (a selective GPR30 antagonist) but not ICI182780 (a nuclear estrogen receptor inhibitor) in the early stage of in vitro culture. The effect of 17β-estradiol on the GJICs was quantified by lucifer yellow (LY) microinjection and calcein-AM fluorescent dye diffusion. 17β-estradiol treatment of goat COCs resulted in rapid downregulation of GJICs. The transfer of calcein from cumulus cells to oocytes could be significantly inhibited by carbenoxolone (a known gap junction blocker), 17β-estradiol or G1 (a GPR30 agonist), and this inhibition could be reversed by G15 but not ICI182780, indicating that GPR30 mediates the effect of 17β-estradiol on the rapid downregulation of GJICs. 17β-estradiol also stimulated the serine 368 phosphorylation of connexin 43 (Cx43) when COCs were in vitro cultured for 4 h, 6 h, and 8 h. More importantly, 17β-estradiol or G1 could separately promote the phosphorylation of extracellular signal-regulated kinase 1/2 (ERK 1/2) and Cx43 significantly when COCs were cultured for 4 h. Furthermore, both ERK1/2 and Cx43 phosphorylation could be inhibited by G15 and the epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor AG1478 or by the ERK1/2 inhibitor PD98059, indicating that EGFR-ERK1/2 signaling was involved in these events. These results supported the hypothesis that GPR30 mediated 17β-estradiol-stimulated meiotic resumption and GJIC reduction in goat COCs. Thus, the present study provides novel insights into elucidating the mechanisms for steroid hormone action in the regulation of oocyte maturation.

Pituitary adenoma (PA) rarely coexists with Rathke's cleft cyst (RCC). Previously, only 13 cases of patients with growth hormone (GH)-producing PA and concomitant RCC have been reported. Here, the authors report a 54-year-old female patient with a GH-secreting PA coexisting with an RCC. Acromegaly was diagnosed according to the physical examination and endocrine data. Preoperatively, the coronal magnetic resonance imaging (MRI) contained 2 different signal intensities, these unusually MRI findings for the intrasellar mass were rarely. According to our clinical experience for diagnosis of PA and RCC, besides GH-producing PA in this case, but the possibility of concomitant RCC should be considered. One-and-a-half nostril endoscopic transsphenoidal approach was performed. Intraoperatively, the adenoma was successfully removed and a large amount of grayish fluid from the cyst was released. The endocrine testing was normal soon after the operation and the patient remained well for a follow-up period of 3 months. The postoperative MRI (obtained 3 months after surgery) showed no intrasellar and suprasellar mass. The authors retrospectively analyzed the all 14 cases of concomitant GH-secreting PAs and RCCs and summarized MRI characteristics. When preoperative MRI contained 2 different signal intensities, one mass lesion showed low or isointense signal on the T1-weighted and T2-weighted images, whereas the other lesion showed low signal on the T1-weighted images and hyperintense on the T2-weighted images, the collision MRI features may be helpful for the preoperative diagnosis of concomitant PAs and RCCs.

Adipose tissue-derived stem cell (ADSC)-based therapy is promising for the treatment of intervertebral disc (IVD) degeneration, but the difficulty in inducing nucleus pulposus (NP)-like differentiation limits its clinical applications. Forkhead box (Fox)-A2 is an essential transcription factor for the formation of a normal NP. We demonstrated that type II collagen stimulates NP-like differentiation of ADSCs, partly by increasing the expression of FoxA2. We constructed FoxA2-overexpressing and -knockdown ADSCs by using lentiviral vectors. FoxA2 overexpression significantly enhanced NP-specific gene expression and the synthesis of glycosaminoglycan and collagen, whereas FoxA2 knockdown decreased NP-like differentiation and the expression of aggrecan and collagen II. The enhanced NP-like differentiation related to FoxA2 overexpression was partially rescued by an Shh signaling pathway inhibitor. In addition, FoxA2 inhibited the expression of Itg-α2 and further promoted NP-like differentiation induced by type II collagen. Furthermore, FoxA2-overexpressing ADSCs combined with type II collagen hydrogels promoted regeneration of degenerated NP in vivo. Our findings suggest that FoxA2 plays an essential role in the NP-like differentiation of ADSCs by activating the Shh signaling pathway.-Zhou, X., Ma, C., Hu, B., Tao, Y., Wang, J., Huang, X., Zhao, T., Han, B., Li, H., Liang, C., Chen, Q., Li, F. FoxA2 regulates the type II collagen-induced nucleus pulposus-like differentiation of adipose-derived stem cells by activation of the Shh signaling pathway.

As a chronic disease, osteoarthritis (OA) leads to the degradation of both cartilage and subchondral bone, its development being mediated by proinflammatory cytokines like interleukin-1β. In the present study, the anti-inflammatory effect of specnuezhenide (SPN) in OA and its underlying mechanism were studied in vitro and in vivo. The results showed that SPN decreases the expression of cartilage matrix-degrading enzymes and the activation of NF-κB and wnt/β-catenin signaling, and increases chondrocyte-specific gene expression in IL-1β-induced inflammation in chondrocytes. Furthermore, SPN treatment prevents the degeneration of both cartilage and subchondral bone in a rat model of OA. To the best of our knowledge, this study is the first to report that SPN decreases interleukin-1β-induced inflammation in rat chondrocytes by inhibiting the activation of the NF-κB and wnt/β-catenin pathways, and, thus, has therapeutic potential in the treatment of OA.

Osteoarthritis (OA) is a chronic degenerative joint disease that has been shown to be closely related to the over expression of matrix metalloproteinases (MMPs). Polygalacic acid is a triterpene isolated from the root of Polygala tenuifolia Willd. In the present study, the anti-inflammatory effect of polygalacic acid in OA was investigated as well as its in vitro and in vivo mechanism. In vitro, rat chondrocytes were induced with interleukin-1beta (IL-1β) and treated with different concentrations of polygalacic acid; real-time PCR and Western blotting were performed to evaluate the expressions of MMP-3, MMP-9, MMP-13, and COX-2. In addition, the MAPK and Wnt/β-catenin signaling pathways were analyzed via Western blotting and immunofluorescence staining. In vivo, a rat OA model was treated with polygalacic acid. Gross morphological and histological assessments were performed to evaluate the resulting cartilage damage. Polygalacic acid significantly reduced the expression of MMPs and COX-2, which could be induced by IL-1β in rat chondrocytes. Furthermore, polygalacic acid treatment prevented the degeneration of cartilage in the rat OA model. To investigate the underlying mechanism, we found that polygalacic acid suppressed both the IL-1β-induced activation of Wnt/β-catenin and the mitogen-activated protein kinase (MAPK) signal pathway in chondrocytes. These results suggest that polygalacic acid may have a therapeutic effect in OA treatment.

The relative position between the optic chiasm and the pituitary adenoma will affect the pattern and severity of visual field defect, which is the most common and early onset visual disability induced by this kind of tumor. In this paper we describe an interactive method to localize the optic chiasm from multi-parametric magnetic resonance imaging (MRI) data by using a combined random walk algorithm. In the optic chiasm extraction framework, the modified random walk segmentation integrates the different information of T1-weighted (T1W) and T2-weighted (T2W) three-dimension (3-D) MRI data into the energy formulation to deduce the probabilities that voxels are assigned to the foreground and background. To avoid extract the wrong region into the object, we design a threshold based region detection method to segment the optic chiasm from the probabilities map. The proposed method is tested on 16 T1W and T2W MRI data from 16 patients diagnosed with pituitary adenoma. Experimental results show that the proposed method provides clinicians with good effectiveness and accuracy in the segmentation of the optic chiasm in patients with pituitary tumors to assist diagnosis and treatment.

Postoperative cerebrospinal fluid (CSF) leaks still occur in patients without intraoperative CSF leaks after endoscopic endonasal pituitary adenoma surgery. We propose a reconstructive technique, the sellar floor flap (SFF), for universal sellar anatomical reconstruction. A total of 113 patients without intraoperative CSF leaks after endoscopic endonasal pituitary adenoma surgery from July 2013 to June 2016 were reviewed: 43 underwent sellar reconstruction with the SFF (the SFF group) and 70 underwent sellar packing only (the nonreconstruction group). No case of postoperative CSF leak was reported in the SFF group, whereas 7 cases were reported in the nonreconstruction group ( P < .05). The SFF is suitable for universal reconstruction after endoscopic endonasal pituitary adenoma surgery and may decrease postoperative CSF leak.

Metabolism of bone is regulated by the balance between osteoblast‐mediated bone formation and osteoclast‐mediated bone resorption. Activation of osteoclasts could lead to osteoporosis. Thus, inhibiting the activity of osteoclasts becomes an available strategy for the treatment of osteoporosis. Tectorigenin is an extract of Belamcanda chinensis In the present study, the anti‐osteoclastogenesis effects of tectorigenin were investigated in vitro and in vivo. The results showed preventive and therapeutic effects of tectorigenin at concentrations of 0, 10, 40, and 80 μmol/L in the maturation and activation of osteoclasts. A signalling study also indicated that tectorigenin treatment reduces activation of NF‐κB signalling in osteoclastogenesis. Animal experiment demonstrated that tectorigenin treatment (1‐10 mg/kg, abdominal injection every 3 days) significantly inhibits bone loss in ovariectomized C57BL/6. Our data suggest that tectorigenin is a potential pharmacological choice for osteoporosis.

Purpose Review the current evidence-based status of pulsed radiofrequency (PRF) treatment for patients with shoulder pain based on randomized controlled trials (RCTs) to provide a comprehensive analysis and a balanced view of the strengths and weaknesses of this treatment. Methods PubMed, EMBASE, the Cochrane Library, and ISI Web of Science were searched up to July 2014, using the Boolean operators as follows: shoulder pain OR painful shoulder AND pulsed radiofrequency). All prospective randomized controlled trials of PRF treatment for patients with shoulder pain were retrieved. No limitation of the language or publication year existed in our analysis. Results Five of 114 studies that involved PRF treatment met the inclusion criteria of this review article. These studies compared the clinical outcomes of PRF with those of other treatments such as intra-articular corticosteroid injection and conventional transcutaneous electrical nerve stimulation. All the studies reported improvements in passive range of motion (PROM), visual analog scale (VAS), and Shoulder Pain and Disability Index (SPADI) in PRF treatment that persisted for at least 12 weeks. In addition, no complications were reported in all trials. Conclusion The use of PRF treatment for patients with shoulder pain was observed to result in good clinical efficacy for at least 12 weeks with no complication reported. However, it is still unclear from the currently available publications whether PRF is superior to other treatment techniques such as intra-articular corticosteroid and conventional transcutaneous electrical nerve stimulation.

Tectonic-1, also named as TCTN1 or TECT1, which belongs to a family of signal-sequence-containing secreted and transmembrane proteins evolutionarily conserved among eukaryotes, was reported to be involved in central nervous system development and ciliogenesis. In this paper, we found that TCTN1 is extensively expressed in human glioma cell lines. To clarify the role of TCTN1 in glioma, we employed lentivirus-mediated short hairpin RNA to knock down TCTN1 expression in U251 and U87MG glioma cells. Knockdown of TCTN1 potently inhibited cell proliferation, as determined by MTT and colony formation assays. Cell cycle analysis showed depletion of TCTN1 led to both U251 and U87MG cells arrested in the G0/G1 phase. These data suggest TCTN1 is essential for glioma cell viability, and dysregulation of TCTN1 may play a key role in glioma tumorigenesis.

Purpose To quantitatively investigate the characteristics of eyes with pituitary adenoma presented by three-dimensional (3D) spectral-domain optical coherence tomography (SD-OCT) using three common indices, including thickness, optical intensity ratio, and optical intensity attenuation coefficient (OIAC). Methods The SD-OCT database of 38 patients with pituitary adenoma and 39 normal controls were included in the study. Quadrantal and average measurements of thickness, optical intensity ratio, and OIAC were calculated for macular retinal nerve fiber layer (mRNFL), ganglion cell layer (GCL) combined with inner plexiform layer (IPL) (GCIPL) and/or the collective ganglion cell complex (GCC). The parameters of patients and controls were compared by unpaired t-test and Mann-Whitney U-test. The relationships between the optical intensity ratio and the thickness of mRNFL and GCIPL were evaluated by Pearson's correlation. Diagnostic performances of these indices were assessed using receiver operating characteristic (ROC) analysis. Results Significant decreases in thickness existed in the mRNFL and nasal GCC of patients compared with controls (p-values of 0.000 to 0.039). Optical intensity ratios in the relevant retinal layers of patients were almost all lower than those of controls. In patients, optical intensities were increased in the mRNFL but decreased in the GCIPL along with an increase of retinal thicknesses. The OIAC measurements were significantly higher in the upper quadrants and global average of the mRNFL in patients. The areas under the ROC curves (AUC) obtained by global average mRNFL thickness was significantly greater than that of the global average OIAC in the mRNFL (p = 0.0265). Conclusions Thicknesses of the mRNFL and nasal GCC were significantly decreased in the retinas of patients with pituitary adenoma compared with controls. The differences of the optical intensity ratio and OIAC between patients and controls were not all statistically significant. Thickness was more sensitive than optical characteristics indices in distinguishing pituitary adenoma from controls.

To compare the clinical outcomes of double-bundle (DB) single-tibial tunnel technique and double-tunnel technique for ACL reconstruction in patients with knee hyperextension. Defined as having constitutional hyperextension of greater than 10°, 56 patients with knee hyperextension who underwent ACL reconstruction were included in this study. To exclude concomitant lesions, preoperative magnetic resonance imaging (MRI) was performed in all knees. 24 patients (Group A) were treated with the anatomic DB/single-tibial tunnel ACL reconstruction and 32 patients (Group B) were treated with DB/double-tibial tunnel ACL reconstruction, all the included patients had knee hyperextension. Clinical results were evaluated by the extension angle, ROM, IKDC 2000 subjective score, rotational stability, pivot-shift test and anterior–posterior translation test before the operation and at the end of follow-up. MRI scan of the knee positioned in full extension was performed after 6 months post-operation. Location of tibial tunnels and graft signal intensity were assessed according to the MRI. Postoperative extension deficit was detected in Group B, ROM of the injured knee in Group A was from extension angle 8.91 ± 3.16° to flexion angle 115.58 ± 10.53°. ROM of the injured knee in Group B was from extension angle − 2.13 ± 5.88° to flexion angle 119.25 ± 12.63°. Flexion angles of two groups did not show any significant difference (p = 0.24), while extension angles were quite different (p

Accurate volume measurements of pituitary adenoma are important to the diagnosis and treatment for this kind of sellar tumor. The pituitary adenomas have different pathological representations and various shapes. Particularly, in the case of infiltrating to surrounding soft tissues, they present similar intensities and indistinct boundary in T1-weighted (T1W) magnetic resonance (MR) images. Then the extraction of pituitary adenoma from MR images is still a challenging task. In this paper, we propose an interactive method to segment the pituitary adenoma from brain MR data, by combining graph cuts based active contour model (GCACM) and random walk algorithm. By using the GCACM method, the segmentation task is formulated as an energy minimization problem by a hybrid active contour model (ACM), and then the problem is solved by the graph cuts method. The region-based term in the hybrid ACM considers the local image intensities as described by Gaussian distributions with different means and variances, expressed as maximum a posteriori probability (MAP). Random walk is utilized as an initialization tool to provide initialized surface for GCACM. The proposed method is evaluated on the three-dimensional (3-D) T1W MR data of 23 patients and compared with the standard graph cuts method, the random walk method, the hybrid ACM method, a GCACM method which considers global mean intensity in region forces, and a competitive region-growing based GrowCut method planted in 3D Slicer. Based on the experimental results, the proposed method is superior to those methods.

The aim of the present study was to determine whether tumor necrosis factor (TNF)-α regulates the expression levels of excitatory amino-acid transporters (EAATs) in primary astrocytes and its roles in brain ischemia. Exogenous TNF-α was administered to pure cultured astrocytes and the expression levels of EAAT1, EAAT2 and glial fibrillary acidic protein (GFAP) were evaluated. The results showed that TNF-α at 10 ng/ml enhanced the expression of EAAT2 in a time-dependent manner, while the expression levels of EAAT1 and GFAP did not change. To determine whether the elevation in the levels of the EAAT2 protein induced by TNF-α had a beneficial effect on ischemic insult, TNF-α was applied to in vitro models of cerebral ischemia; the treatment was observed to increase neuronal viability. The present results suggest that a relatively short-term application of an optimal concentration of TNF-α may protect neurons against ischemic injury by elevating the expression of EAAT2 in astrocytes.

Some Ca–Mg-silicate ceramics have been widely investigated to be highly bioactive and biodegradable, whereas their osteogenic potential and especially biomechanical response in the early stage in vivo are scarcely demonstrated. Herein, the osteogenesis capacity and mechanical evolution of the akermanite (Ca2MgSi2O7) porous materials manufactured by ceramic ink writing three-dimensional printing technique were investigated systematically in a critical size femur defect model, in comparison with the clinically available β-tricalcium phosphate porous bioceramic. Such three-dimensional printed akermanite scaffolds possess fully interconnected pores of ∼280 × 280 µm in size and over 50% porosity with appreciable compressive strength (∼71 MPa), that is 7-fold higher than that of the β-tricalcium phosphate porous bioceramics (∼10 MPa). After 6 weeks and 12 weeks of implantation, the percentage of newly formed bone and more new bone was observed in the akermanite group as compared with the β-tricalcium phosphate group ( p

Wollastonite (CaSiO3; CSi) ceramic is a promising bioactive material for bone defect repair due to slightly fast degradation of its porous constructs in vivo. In our previous strategy some key features of CSi ceramic have been significantly improved by dilute magnesium doping for regulating mechanical properties and biodegradation. Here we demonstrate that 6 ~ 14% of Ca substituted by Mg in CSi (CSi-Mgx, x = 6, 10, 14) can enhance the mechanical strength (>40 MPa) but not compromise biological performances of the 3D printed porous scaffolds with open porosity of 60‒63%. The in vitro cell culture tests in vitro indicated that the dilute Mg doping into CSi was beneficial for ALP activity and high expression of osteogenic marker genes of MC3T3-E1 cells in the scaffolds. A good bone tissue regeneration response and elastoplastic response in mechanical strength in vivo were determined after implantation in rabbit calvarial defects for 6‒12 weeks. Particularly, the CSi-Mg10 and CSi-Mg14 scaffolds could enhance new bone regeneration with a significant increase of newly formed bone tissue (18 ~ 22%) compared to the pure CSi (~14%) at 12 weeks post-implantation. It is reasonable to consider that, therefore, such CSi-Mgx scaffolds possessing excellent strength and reasonable degradability are promising for bone reconstruction in thin-wall bone defects.

Background Binostril endoscopic transsphenoidal approach (BETA) provides sufficient manipulation space and wide endoscopic vision, although it increases the trauma of nose. Mononostril endoscopic transsphenoidal approach (META) has minimal trauma of nose, at the expense of space within the operation. We describe a one-and-a-half nostril endoscopic transsphenoidal approach (OETA) that combines the advantages of BETA and META. Methods We introduced OETA for pituitary adenomas with a detailed technical description. A retrospective analysis was also performed on 57 consecutive patients who underwent one-and-a-half nostril endoscopic transsphenoidal surgery between March 2014 and June 2015 at Jinling hospital. Results The gross total resection rate was 79%. The gross complete resection rate of Knosp grade 3 tumors were 63.6, and 27.3% in grade 4 tumors. Postoperative hormone remission was achieved in 14 out of 18 (77.8%) patients with secreting adenomas. Postoperative abnormal visual function improvement was achieved in 23 out of 32 patients (73%) with preoperative visual dysfunction. The overall intra-operative CSF leak was 17.5%, with the postoperative CSF leak decreased to 3.5% after the sellar reconstruction with the unilateral “rescue” nasoseptal flap procedure. The main sinonasal complaints 2 weeks after surgery were: loss of sense of smell (28%), decrease in sense of taste (4%), trouble breathing during the day (18%), thick nasal discharge (36%), post nasal discharge (8%), dried nasal material (6%), and headache (6%). Three months after surgery, there were no reports of decrease of taste, post nasal discharge, or dried nasal material. Other complaints were decreased significantly. Six months after surgery, the main complaints of sinonasal quality of life were negligible, and overall health status was near complete recovery to preoperative status. Conclusions The one-and-a-half nostril endoscopic transsphenoidal approach for pituitary adenomas is a simple and reliable technique. It provides not only a sufficient surgical corridor for a 2-surgeon/4 or 3-hands technique, but also ensures minimal invasion of the nasal canal.

We aimed to present a practical three-dimensional (3D) printed simulator to comprehensively and effectively accelerate the learning curve of endoscopic endonasal transsphenoidal surgery (EETS). The 3D printed simulator consists of three parts: (1) skull frame, (2) the nasal passage and the nasal alar of the face, and (3) a modified sella turcica. We aimed to improve three basic operational skills of surgeons: drilling, curetting, and aspirating. Eighteen neurosurgeons and five post-graduates were recruited and consented for the training. For trainees, (1) as the training progressed, the scores increased gradually, (2) a significant increase in the average scores was observed in the tenth training compared to the first training, and (3) there is a significant decrease in trainee variability in the shortening of the gap. The 18 neurosurgeons were divided into three groups: experts, assistants, and observers. For all three basic operations, (1) the average score of experts was obviously higher than that of the assistants, observers, and trainees’ tenth training and (2) the average scores of assistants and observers were obviously higher than that of trainees’ first training. A significant high in the average score between the assistants and the observers was seen for aspirating, but not for drilling or curetting. For curetting and aspirating, the tenth training average score of trainees was obviously higher than that of assistants and observers. This 3D printed simulator allows different endoscopic basic operations to be simulated and improves the EETS techniques of surgeons. We believed it to be a practical, simple, and low-cost simulator.

Background Over the past several decades, the endoscopic endonasal transsphenoidal approach (EETA) has gradually become a preferred option of pituitary adenomas surgery because of its minimal invasiveness and high efficiency. However, some EETA operations were performed through one nostril (mononostril), while other EETA operations were performed through both nostrils (binostril). Therefore, we conducted this study to compare the pros and cons of these two methods in an attempted to confirm which method is more effective. Methods We executed a systematic literature search of PubMed, the Cochrane Library, and the Web of Science and Medline (1992–2015). The language is limited to English and all studies should meet the inclusion criteria. Comparisons were made for postoperative outcomes, complications, and other relevant parameters between the mononostril and the binostril group. Statistical analyses of categorical variables were undertaken by the use of Stata 12.0 and SPASS 19.0. Results Thirty studies, involving 4805 patients, were included. The two groups had similar results in GTR rate (included GTR rate of macroadenomas), hormonal remission rate, improvement in visual function, postoperative CSF leak, permanent diabetes insipidus, meningitis, and sinusitis. The binostril group had less temporary diabetes insipidus (2.9% vs. 5.3%, p = 0.022), less anterior pituitary insufficiency (2.3% vs. 6.4%, p = 0.000) and few hospitalization days (3.2 days vs. 4.4 days, p

In this paper we propose a Language-Extension-based Vectorizing Compiling Scheme (LEVCS) for a newly developed DSP. The DSP is mainly designed for Software-Defined Radio (SDR) and is called SDR-DSP. The SDR-DSP architecture mixes the styles of VLIW (Very Long Instruction Word) and SIMD (Single Instruction Multiple Data). To explore the potential of SDR-DSP and achieve high performance, vectorization is one of the must equipped critical methods. Because auto-vectorization techniques cannot satisfy the requirements of the typical application, LEVCS is used to direct the vectorization. The C-extending programming language used in LEVCS is called SDR-DSP-C. LEVCS uses flexible data reorganization to make vectorization on SDR-DSP more efficient. We use LEVCS to vectorize five benchmark kernels: Fast Fourier Transform (FFT), Finite Impulse Responsefilter (FIR) and Infinite Impulse Response filter (IIR), Dot product implementation (Dotprod), Sum of vectors (vecsum). Experiment results show that LEVCS is functional correct and can achieve 2.883–8.074 speedups comparing to TI-DSPs.

Object Sonic hedgehog (Shh) is a glycoprotein molecule that upregulates the transcription factor Gli1. The Shh protein plays a critical role in the proliferation of endogenous neural precursor cells when directly injected into the spinal cord after a spinal cord injury in adult rodents. Small-molecule agonists of the hedgehog (Hh) pathway were used in an attempt to reproduce these findings through intravenous administration. Methods The expression of Gli1 was measured in rat spinal cord after the intravenous administration of an Hh agonist. Ten adult rats received a moderate contusion and were treated with either an Hh agonist (10 mg/kg, intravenously) or vehicle (5 rodents per group) 1 hour and 4 days after injury. The rats were killed 5 days postinjury. Tissue samples were immediately placed in fixative. Samples were immunohistochemically stained for neural precursor cells, and these cells were counted. Results Systemic dosing with an Hh agonist significantly upregulated Gli1 expression in the spinal cord (p < 0.005). After spinal contusion, animals treated with the Hh agonist had significantly more nestin-positive neural precursor cells around the rim of the lesion cavity than in vehicle-treated controls (means ± SDs, 46.9 ± 12.9 vs 20.9 ± 8.3 cells/hpf, respectively, p < 0.005). There was no significant difference in the area of white matter injury between the groups. Conclusions An intravenous Hh agonist at doses that upregulate spinal cord Gli1 transcription also increases the population of neural precursor cells after spinal cord injury in adult rats. These data support previous findings based on injections of Shh protein directly into the spinal cord.

In recent years, mass mortalities of Chinese mitten crab ( Eriocheir japonica sinensis ) larvae have been reported in several crab culture regions in China and have resulted in great economic losses. The mass mortality usually occurs in seawater ponds in the afternoon of sunny days when water color suddenly changes from dark green or brown to cloudy white or light yellow, and mineral precipitate occurs. Moribund and dead larvae are typically covered with debris. A series of experiments was conducted to examine the cause of precipitation and mass mortality of crab larvae. Analysis of the precipitate from ponds with mass mortalities showed that CaCO 3 was the main component of the precipitate, accounting for 70.8% of the total weight. In an animal experiment, mortalities were observed within 48 h in all groups with CaCO 3 precipitate, and generally increased as pH and CaCO 3 saturation rates increased. Mortalities in groups with CaCO 3 precipitate were greater than those in groups without CaCO 3 precipitate ( P ≤ 0.05). All larvae in groups with CaCO 3 precipitate sank to the bottom of the beaker within 48 h. The animal experiment also showed that increased pH (up to 9.4) alone without CaCO 3 precipitate did not result in larval mortality within 48 h. Results from the present investigation indicate that mass mortalities of the crab larvae are caused by CaCO 3 supersaturation and rapid precipitation possibly triggered by increased pH as a result of intensive photosynthesis of phytoplankton in the seawater ponds. By comparing mean Ca 2+ and CO 3 2− ionic product obtained at the equilibrium with solubility product constants for various CaCO 3 crystal forms, it appears that CaCO 3 ·H 2 O is the main CaCO 3 form. Based on the CaCO 3 ·H 2 O solubility product constant and our field investigations, we suggest that CaCO 3 ·H 2 O saturation indices of 2.5 and below be considered safe and 3.4 as warning signal for CaCO 3 precipitation. Since several factors may cause CaCO 3 supersaturation and precipitation in crab larval ponds, preventive measures should be implemented to stabilize pH and reduce the CaCO 3 saturation rate.