Design, synthesis, and evaluation of cyclic C7-bridged monocarbonyl curcumin analogs containing an o-methoxy phenyl group as potential agents against gastric cancer.

The structure-activity relationship (SAR) between toxicity and the types of linking ketones of C7 bridged monocarbonyl curcumin analogs (MCAs) was not clear yet. In the pursuit of effective and less cytotoxic chemotherapeutics, we conducted a SAR analysis using various diketene skeletons of C7-bridged MCAs, synthesized cyclic C7-bridged MCAs containing the identified low-toxicity cyclopentanone scaffold and an o-methoxy phenyl group, and assessed their anti-gastric cancer activity and safety profile. Most compounds exhibited potent cytotoxic activities against gastric cancer cells. We developed a quantitative structure-activity relationship model (R2 > 0.82) by random Forest method, providing important information for optimizing structure. An optimized compound 2 exhibited in vitro and in vivo anti-gastric cancer activity partly through inhibiting the AKT and STAT3 pathways, and displayed a favorable in vivo safety profile. In summary, this paper provided a promising class of MCAs and a potential compound for the development of chemotherapeutic drugs.

Cryopreserved platelets washed with a dialysis machine for dimethyl sulphoxide removal.

BACKGROUND AND OBJECTIVES: Cryopreserved platelets (cPLTs) can be stored for years and are mainly used in military settings. However, the commonly used cryoprotectant dimethyl sulphoxide (DMSO) has toxic side effects when utilized in high quantities. We developed a novel method to aseptically remove DMSO from thawed cPLTs by dialysis. MATERIALS AND METHODS: One unit of platelets (N = 6) was mixed with 75 mL of 27% DMSO within 4 days after collection and stored at -80°C for 1 week. The platelet counts, platelet distribution width, mean platelet volume (MPV), platelet activity, platelet release, platelet aggregation, platelet metabolism indicators and platelet ultrastructural features (determined by electron microscopy) of the samples at the pre-freeze, post-thaw wash (post-TW) and 24 h post-thaw wash (24-PTW) stages were determined and compared. RESULTS: The DMSO clearance rate from the post-TW platelets was 95.56 ± 1.3%, and the platelet recovery rate after washing was 74.66 ± 6.34%. The total count, activity, release factors, aggregation and thrombolytic ability of the post-TW platelets were lower, whereas the MPV and apoptosis rates were higher compared with those of the pre-freeze platelets. The lactic acid, glucose and potassium ions released from the platelets during washing were filtered away by the dialyser, which significantly reduced their concentration. However, 24-PTW platelets were metabolically active, resulting in a decrease in pH and glucose content and an increase in lactic acid content. The level of potassium ions remained low after 24 h of storage and washing. The pre-freeze platelets maintained their normal disc shape and exhibited an open canalicular system (OCS) and a dense tubular system. The cPLTs appeared irregular after washing, with protruding pseudopodia and an extensive OCS, which increased the release of their contents. CONCLUSION: We developed a novel dialysis method to effectively remove DMSO from cPLTs under aseptic conditions and maintain platelet quality. The clinical efficacy of our method remains to be determined. However, the function of the platelets declined 24 h after washing, making them unsuitable for transfusion.

Education reduces cognitive dysfunction in Alzheimer's disease by changing regional cerebral perfusion: An in-vivo arterial spin labeling study.

OBJECTIVE: Formal education and other cognitive challenges influence brain structure and improve function. It is believed that cognitive activities create a cognitive reserve (CR) that can slow the decline due to aging and neurodegenerative diseases. This study investigated alterations of regional cerebral blood flow (rCBF) associated with high and low CR in different stages of Alzheimer's disease (AD) and examined whether rCBF alteration mediates the relationship between education and cognitive performance. METHODS: Patients with AD or amnestic mild cognitive impairment (aMCI) and healthy controls were divided into low cognitive reserve (LCR) and high cognitive reserve (HCR) subgroups according to median of education years (≤ 9 vs. > 9 years). The final study population included 89 AD patients (67 LCR, 22 HCR), 74 aMCI patients (44 LCR, 30 HCR), and 66 healthy controls (29 LCR, 37 HCR). All subjects were examined by arterial spin labeling magnetic resonance imaging and a neurocognitive test battery. rCBF was compared among groups by two-way analysis of variance. Mediation analyses were used to explore the relationships among education, rCBF, and cognitive test scores. RESULTS: There were significant interaction effects of disease state (AD, aMCI, HC) and education level (LCR, HCR) on CBF in right hippocampus, posterior cingulate cortex, and right inferior parietal cortex (R_IPC). Education regulated episodic memory score by influencing right hippocampal CBF in HC_HCR and aMCI_HCR subgroups. CONCLUSION: Our results indicate that the protective effect of education against cognitive dysfunction in early-stage AD is mediated at least partially by altered CBF in right hippocampus.

Altered resting-state cerebellar-cerebral functional connectivity in patients with end-stage renal disease.

BACKGROUND: End-stage renal disease (ESRD) patients have functional and structural brain abnormalities. The cerebellum also showed varying degrees of damage. However, no studies on cerebellar-cerebral functional connectivity (FC) have been conducted in ESRD patients. This study aimed to investigate the changes in cerebellar-cerebral FC in ESRD patients and its relationship with neuropsychological and clinical indexes. METHODS: Resting-state functional magnetic resonance imaging and neuropsychological assessment were performed on 37 ESRD patients and 35 control subjects. Seed-based FC analysis was performed to investigate inter-group differences in cerebellar-cerebral FC. In addition, the relations of altered FC with the neuropsychological function and clinical indicators were analyzed in ERSD patients. RESULTS: ESRD patients exhibited alterations in cerebellar-cerebral FC involving the executive control network, default mode network, and affective-limbic network compared to control subjects (False discovery rate-corrected, p < 0.05). The altered cerebellar-cerebral FC was associated with the Montreal Cognitive Assessment Scale score (p < 0.05), and correlated with serum creatinine and uric acid levels within the ESRD group (p < 0.05). CONCLUSIONS: The study indicates that cerebellar-cerebral FC is involved in the neural substrates of cognitive impairment in ESRD patients. The findings may provide clinically relevant new neuroimaging biomarkers for the neuropathological mechanisms underlying cognitive impairment of ESRD.

The protective impact of education on brain structure and function in Alzheimer's disease.

BACKGROUND: The Cognitive Reserve (CR) theory posits that brains with higher reserve can cope with more cerebral damage to minimize clinical manifestations. The aim of this study was to examine the effect of education (CR proxy) on brain structure and function in Alzheimer's disease (AD) and amnestic mild cognitive impairment (aMCI) patients and in cognitively healthy elderly (HC) individuals. METHODS: Fifty-seven AD patients, 57 aMCI patients and 48 HCs were included to investigate the relationships between education years and gray matter volume (GMV), regional homogeneity (ReHo) and functional connectivity (FC) in brain regions to show associations with both structure and function. Taking the severity of the disease into account, we further assessed the relationships in AD stratified analyses. RESULTS: In AD group, the GMV of the dorsal anterior cingulate cortex (dACC) and ReHo in the left inferior temporal cortex (ITC) were inversely associated with education years, after adjustment for age, sex, Mini-Mental State Examination (MMSE), and total intracranial volume or head motion parameters. Seed-based FC analyses revealed that education years were negatively correlated with the FC between the left anterior ITC and left mid frontal cortex as well as right superior frontal cortex and right angular gyrus. Stratified analyses results indicated that this negative relation between education and GMV, ReHo, FC was mainly present in mild AD, which was attenuated in moderate AD and aMCI groups. CONCLUSIONS: Our results support the CR theory, and suggest that CR may be protective against AD related brain pathology at the early stage of clinical dementia. These findings could provide the locus of CR-related functional brain mechanisms and a specific time-window for therapeutic interventions to help AD patients to cope better with the brain pathological damage by increasing CR.

Identification and the potential roles of long non-coding RNAs in regulating acetyl-CoA carboxylase ACC transcription in spirotetramat-resistant Aphis gossypii.

Long non-coding RNAs (lncRNAs) represent the largest class of non-coding transcripts. They act a pivotal part in various insect developmental processes and stress responses. However, the investigation of lncRNA functions in insecticide resistant remains at an early phase. Herein, we conducted whole-transcriptome RNA sequencing for two cotton aphid (Aphis gossypii Glover) strains, i.e., insecticide-susceptible (SS) and spirotetramat-resistant (SR). We discovered 6059 lncRNAs in the RNA-Seq data, and 874 lncRNAs showed differential expression. In addition, 5 lncRNAs among 874 lncRNAs were predicted as targets of acetyl-CoA carboxylase (ACC). Reverse transcription real-time quantitative PCR (RT-qPCR) combined with RNA interference (RNAi) confirmed that selected ACC lncRNA was related to the expression of ACC. Moreover, we also identified two transcription factors, i.e., C/EBP and C/EBPzeta, that regulate the transcription level of ACC lncRNA. These results provide a good basis for the study of cotton aphid lncRNA functions in insecticide resistance development.

Long non-coding RNA OIP5-AS1 suppresses multiple myeloma progression by sponging miR-27a-3p to activate TSC1 expression.

BACKGROUND: Multiple myeloma (MM) is a prevalent hematological malignancy. Long noncoding RNAs are correlated with the development of MM. In this project, the function of lncRNA opa interacting protein 5-antisense 1 (OIP5-AS1) in MM and the potential mechanistic pathway were explored. METHODS: The expression of OIP5-AS1, microRNA (miR)-27a-3p and tuberous sclerosis 1 (TSC1) was analyzed by quantitative real-time polymerase chain reaction (qRT-PCR) assay. Cell proliferation was assessed by Cell Counting Kit-8 (CCK-8) assay, colony formation assay and Bromodeoxyuridine (BrdU) staining. And cell apoptosis was evaluated by flow cytometry assay. Cell metastasis was assessed utilizing transwell assay. Western blot analysis was employed to detect protein level. The target relation between miR-27a-3p and OIP5-AS1 or TSC1 was confirmed via dual-luciferase reporter assay and RNA immunoprecipitation assay. Tumor xenograft assay was conducted to measure the function of OIP5-AS1 in vivo. RESULTS: The expression levels of OIP5-AS1 and TSC1 were decreased in MM, whereas miR-27a-3p was upregulated. High level of OIP5-AS1 could predict favourable prognosis of MM patients. Overexpression of OIP5-AS1 inhibited cell viability, colony formation ability, migration and invasion, induced cell cycle arrest in G1 phase and apoptosis of MM cells in vitro as well as repressed tumorigenesis in vivo. MiR-27a-3p was a target of OIP5-AS1, and reversed the impact of OIP5-AS1 on MM cells. MiR-27a-3p directly targeted TSC1. Silencing of miR-27a-3p repressed MM progression by elevating TSC1 expression. OIP5-AS1 upregulated TSC1 by sponging miR-27a-3p. CONCLUSION: OIP5-AS1 repressed multiple myeloma progression by regulating miR-27a-3p/TSC1 axis.

The top-down regulation from the prefrontal cortex to insula via hypnotic aversion suggestions reduces smoking craving.

Hypnosis has been shown to have treatment effects on nicotine addiction. However, the neural basis of these effects is poorly understood. This preliminary study investigated the neural mechanisms of hypnosis-based treatment on cigarette smoking, specifically, whether the hypnosis involves a top-down or bottom-up mechanism. Two groups of 45 smokers underwent a smoking aversion suggestion and viewed smoking-related pictures and neutral pictures. One group underwent functional magnetic resonance imaging scanning twice (control and hypnotic states), whereas the other group underwent two electroencephalograph sessions. Our study found that self-reported smoking craving decreased in both groups following hypnosis. Smoking cue-elicited activations in the right dorsal lateral prefrontal cortex (rDLPFC) and left insula (lI) and the functional connectivity between the rDLPFC and lI were increased in the hypnotic state compared with the control state. The delta band source waveforms indicated the activation from 390 to 862 ms at the rDLPFC and from 490 to 900 ms at the lI was significantly different between the smoking and neutral conditions in the hypnotic state, suggesting the activation in the rDLPFC preceded that in the lI. These results suggest that the decreased smoking craving via hypnotic aversion suggestions may arise from the top-down regulation of the rDLPFC to the lI. Our findings provide novel neurobiological evidence for understanding the therapeutic effects of hypnosis on nicotine addiction, and the prefrontal-insula circuit may serve as an imaging biomarker to monitor the treatment efficacy noninvasively.

Selective micro-structural integrity impairment of the isthmus subregion of the corpus callosum in alcohol-dependent males.

BACKGROUND: Previous studies have provided evidence that alcohol-dependent patients have abnormality in corpus callosum (CC); however, it is unclear whether micro-structural integrity of the CC subregions is differentially affected in this disorder. METHODS: In this study, a total of 39 male individuals, including 19 alcohol-dependent patients and 20 age-matched healthy controls, underwent diffusion tensor imaging (DTI). CC was reconstructed by DTI tractography and was divided into seven subregions. Multiple diffusion metrics of each subregion were compared between two groups. RESULTS: Compared to healthy controls, patients exhibited increased axial diffusivity (P = 0.007), radial diffusivity (P = 0.009) and mean diffusivity (P = 0.005) in the isthmus. In addition, we observed that daily alcohol intake was correlated positively with radial diffusivity and mean diffusivity and negatively with fractional anisotropy, while abstinence time of hospitalization was negatively correlated with mean diffusivity in the patients. CONCLUSION: These findings suggest a selective micro-structural integrity impairment of the corpus callosum subregions in alcohol dependence, characterized by axon and myelin alterations in the isthmus.

Patterns of brain structural alteration in COPD with different levels of pulmonary function impairment and its association with cognitive deficits.

BACKGROUND: To explore patterns of brain structural alteration in chronic obstructive pulmonary disease (COPD) patients with different levels of lung function impairment and the associations of those patterns with cognitive functional deficits using voxel-based morphometry (VBM) and tract-based spatial statistics (TBSS) analyses based on high-resolution structural MRI and diffusion tensor imaging (DTI). METHODS: A total of 115 right-handed participants (26 severe, 29 moderate, and 29 mild COPD patients and a comparison group of 31 individuals without COPD) completed tests of cognitive (Montreal Cognitive Assessment [MoCA]) and pulmonary function (forced expiratory volume in 1 s [FEV1]) and underwent MRI scanning. VBM and TBSS analyses were used to identify changes in grey matter density (GMD) and white matter (WM) integrity in COPD patients. In addition, correlation analyses between these imaging parameter changes and cognitive and pulmonary functional impairments were performed. RESULTS: There was no significant difference in brain structure between the comparison groups and the mild COPD patients. Patients with moderate COPD had atrophy of the left middle frontal gyrus and right opercular part/triangular part of the inferior frontal gyrus, and WM changes were present mainly in the superior and posterior corona radiata, corpus callosum and cingulum. Patients with severe COPD exhibited the most extensive changes in GMD and WM. Some grey matter (GM) and WM changes were correlated with MoCA scores and FEV1. CONCLUSIONS: These findings suggest that patients with COPD exhibit progressive structural impairments in both the GM and the WM, along with impaired levels of lung function, highlighting the importance of early clinical interventions.

Differential impairment patterns of the corticospinal tract segments in alcohol dependence.

Background: Previous studies have reported inconsistent findings regarding corticospinal tract (CST) changes in alcohol dependence. Here, we aimed to clarify this issue by examining the micro-structural integrity differences of distinct CST segments between alcohol-dependent patients and healthy controls. Methods: Diffusion tensor imaging was performed in a total of 39 male individuals, including 19 alcohol-dependent patients and 20 age-matched healthy controls. CST was reconstructed using tractography and was divided into inferior and superior segments at the level of the lateral sulcus. Multiple diffusion measures of each segment were compared between two groups. Results: For the bilateral whole CSTs, no diffusion measures showed significant between-group differences. However, compared to healthy controls, alcohol-dependent patients exhibited decreased FA and increased RD in the left-superior segment, increased FA and decreased RD/MD in the left-inferior segment, increased AD/MD in the right-superior segment, decreased RD/MD in the right-inferior segment. Conclusions: These findings suggest that CST impairments may vary with the fibre arrangement patterns of its segments in alcohol dependence. Keypoints We reconstructed the CST using tractography based on DTI data and divided the CST into different segments in order to explore more detailed micro-structural integrity changes in alcoholisms. Alcohol-dependent patients showed decreased RD and MD for the bilateral inferior segments of the CSTs. The left-superior segment exhibited decreased FA and increased RD while the right one exhibited increased AD and MD. These findings suggest that CST impairments may vary with the fiber arrangement patterns of its segments in alcohol dependence. In future work, more elaborate segmentation schemes and lager samples should be used to test the reproducibility of our findings.

Interplay Between Long Noncoding RNA ZEB1-AS1 and miR-200s Regulates Osteosarcoma Cell Proliferation and Migration.

In our previous study, we found long noncoding RNA ZEB1-AS1 is upregulated and functions as an oncogene in osteosarcoma. MiR-200 family (miR-200s) functions as tumor suppressor via directly targeting ZEB1 in various cancers. In this study, we further investigate the potential interplay between ZEB1-AS1, miR-200s, and ZEB1 in osteosarcoma. Our results showed that ZEB1-AS1 functions as a molecular sponge for miR-200s and relieves the inhibition of ZEB1 caused by miR-200s. ZEB1-AS1 and miR-200s reciprocally negatively regulate each other. MiR-200s are downregulated in osteosarcoma tissues, and negatively correlated with ZEB1-AS1 and ZEB1 expression levels in osteosarcoma. Functional experiments showed that consistent with ZEB1-AS1 depletion, miR-200s overexpression and ZEB1 depletion both inhibit osteosarcoma cell proliferation and migration. Overexpression of miR-200s partially abolished the effects of ZEB1-AS1 on osteosarcoma cell proliferation and migration. Moreover, the combination of ZEB1-AS1 depletion and miR-200s overexpression significantly inhibits osteosarcoma cell proliferation and migration. In conclusion, this study revealed a novel regulatory mechanism between ZEB1-AS1, miR-200s, and ZEB1. The interplay between ZEB1-AS1 and miR-200s contributes to osteosarcoma cell proliferation and migration, and targeting this interplay could be a promising strategy for osteosarcoma treatment. J. Cell. Biochem. 118: 2250-2260, 2017. © 2017 Wiley Periodicals, Inc.

Computed Tomography and Magnetic Resonance Imaging Characteristics of Peripheral Primitive Neuroectodermal Tumor: A Retrospective Analysis of 16 Cases.

PURPOSE: The aim of this study was to analyze the radiological features of peripheral primitive neuroectodermal tumor (pPNET). MATERIALS AND METHODS: The radiological and clinical findings for 16 patients with pPNETs were retrospectively reviewed. The 16 tumors were classified into 4 groups (meninges group, n = 4; spine group, n = 3; bone group, n = 5; soft-tissue group, n = 4), and clinical data, size, and common and unique CT/MRI characteristics were assessed. RESULTS: Peripheral primitive neuroectodermal tumors presented as large solid masses with aggressive extension into the neighboring tissue. Most tumors (11/16) presented with necrosis, and 5 of the 16 cases showed signs of hemorrhage. The "dural tail sign" was observed in the meninges and spine groups. The pPNETs of bone demonstrated bony destruction with spiculated periosteal reaction, and small nourishing vessels were found in tumors in the soft-tissue group. CONCLUSIONS: Peripheral primitive neuroectodermal tumor should be suggested as an important differential diagnosis when the tumor presents as a large, ill-defined solid mass with aggressive extension and significant enhancement.

[Biomechanical and biocompatible enhancement of reinforced calcium phosphate cement via RGD peptide grafted chitosan nanofibers].

Objective: To analysis the biomechanical and biocompatible properties of calcium phosphate cement (CPC) enhanced by chitosan short nanofibers(CSNF) and Arg-Gly-Asp (RGD). Methods: Chitosan nanofibers were prepared by electrospinning, and cut into short fibers by high speed dispersion. CPC with calcium phosphorus ratio of 1.5:1 was prepared by Biocement D method. The composition and structure of CPC, CSNF, RGD modified CSNF (CSNF-RGD), CSNF enhanced CPC (CPC-CSNF), RGD modified CPC-CSNF (CPC-CSNF-RGD) were observed by infrared spectrum, X-ray diffraction (XRD) and scan electron microscopy (SEM). The mechanical properties were measured by universal mechanical testing instrument. The adhesion and proliferation of MC3T3 cells were assessed using immunofluorescence staining and MTT method. Results: The distribution of CSNF in the scaffold was homogeneous, and the porous structure between the nanofibers was observed by SEM. The infrared spectrum showed the characteristic peaks at 1633 nm and 1585 nm, indicating that RGD was successfully grafted on chitosan nanofibers. The XRD pattern showed that the bone cement had a certain curability. The stain-stress test showed that break strengths were (17.74±0.54) MPa for CPC-CSNF and (16.67±0.56) MPa for CPCP-CSNF-RGD, both were higher than that of CPC(all P<0.05). The immunofluorescence staining and MTT results indicated that MC3T3 cells grew better on CPC-CSNF-RGD after 240 min of culture(all P<0.05). Conclusion: CSNF-RGD can improve the biomechanical property and biocompatibility of CPC, indicating its potential application in bone tissue repair.

Novel Mn3 [Co(CN)6]2@SiO2@Ag Core-Shell Nanocube: Enhanced Two-Photon Fluorescence and Magnetic Resonance Dual-Modal Imaging-Guided Photothermal and Chemo-therapy.

The versatile Mn3[Co(CN)6]2@SiO2@Ag core-shell NCs are prepared by a simple coprecipitation method. Ag nanoparticles with an average diameter of 12 nm deposited on the surface of Mn3[Co(CN)6]2@SiO2 through S-Ag bonding are fabricated in ethanol solution by reducing silver nitrate (AgNO3 ) with NaBH4 . The NCs possess T1 -T2 dual-modal magnetic resonance imaging ability. The inner Prussian blue analogs (PBAs) Mn3[Co(CN)6]2 exhibit bright two-photon fluorescence (TPF) imaging when excited at 730 nm. Moreover, the TPF imaging intensity displays 1.85-fold enhancement after loading of Ag nanoparticles. Besides, the sample also has multicolor fluorescence imaging ability under 403, 488, and 543 nm single photon excitation. The as-synthesized Mn3[Co(CN)6]2@SiO2@Ag NCs show a DOX loading capacity of 600 mg g(-1) and exhibit an excellent ability of near-infrared (NIR)-responsive drug release and photothermal therapy (PTT) which is induced from the relative high absorbance in NIR region. The combined chemotherapy and PTT against cancer cells in vitro test shows high therapeutic efficiency. The multimodal treatment and imaging could lead to this material a potential multifunctional system for biomedical diagnosis and therapy.

The effectiveness of riboflavin photochemical-mediated virus inactivation and changes in protein retention in fresh-frozen plasma treated using a flow-based treatment device.

BACKGROUND: A flow-based treatment device using riboflavin and ultraviolet (UV) light was developed to inactivate viruses in fresh-frozen plasma (FFP). The objective of this study was to evaluate the in vitro effectiveness of virus inactivation and changes in protein quality in FFP treated with this device. STUDY DESIGN AND METHODS: FFP-contaminating viruses were treated with riboflavin and UV light using a one-pass linear flow device. The infectivity of viruses was measured using established biologic assays. Real-time polymerase chain reaction (PCR) was performed to detect damage to viral nucleotides after treatment. Treated plasma was analyzed using standard coagulation assays. RESULTS: FFP treated at the UV dose of 3.6 J/cm(2) (J) exhibited a mean reduction of virus titer of more than 4 logs. The effectiveness increased significantly at higher doses. Real-time PCR showed that the cycle threshold values for both complete inactivation and virus recultivation were higher than that of the untreated sample. At doses of 3.6, 5.4, and 7.2 J, the protein recovery rates were 60.2 ± 8.6, 46.6 ± 9.4, and 28.0 ± 1.0% for fibrinogen; 67.0 ± 3.1, 57.3 ± 8.0, and 49.2 ± 3.8% for Factor VIII; 93.6 ± 2.8, 89.6 ± 6.1, and 86.5 ± 5.3% for antithrombin-III; and 72.1 ± 5.6, 59.8 ± 14.2, and 49.2 ± 8.4% for Protein C, respectively. CONCLUSION: The effectiveness of virus inactivation was enhanced, but total activity of plasma factors was reduced, in a UV dose-dependent manner.

Effect of B vitamin (folate, B6, and B12) supplementation on osteoporotic fracture and bone turnover markers: a meta-analysis.

BACKGROUND: B vitamins (including folate, B6, and B12) supplementation can effectively and easily modify high plasma homocysteine (Hcy). However, the role of Hcy in the pathogenesis of osteoporotic fracture and bone turnover is still controversial. This meta-analysis aimed to assess the impact of B vitamin supplementation on occurrence of any osteoporotic fracture and bone turnover by pooling the results of previous studies. MATERIAL AND METHODS: Relevant randomized controlled trials (RCTs) were searched in databases. Data integration and analysis were done by using Review Manager 5.3 (the Cochrane Collaboration). The risk ratio (RR) and corresponding 95% confidence intervals (CI) of fracture (intervention vs. control) were estimated. Changes in bone turnover indicators (continuous data), weighted mean difference (WMD), and corresponding 95% (CI) were pooled for estimation. RESULTS: Based on the results of 4 RCTs, this meta-analysis failed to identify a risk-reducing effect of daily supplementation of B vitamins on osteoporotic fracture in patients with vascular disease and with relatively normal plasma Hcy. In addition, we also did not find any positive effects of B vitamin supplementation on bone turnover. CONCLUSIONS: B vitamin supplementation might not be effective in preventing fracture and improving bone turnover. However, the possible benefits in selective populations, such as populations with very high plasma Hcy and from regions without B vitamin fortification should be explored in the future.

[Research achievements on biological activities of calycosin].

Calycosin, which is a kind of typical phytoestrogen, can bind with estrogen receptor and produce estrogen-like effects. Calycosin were reported to have antioxidant, anti-osteoporosis, anti-tumor and immunomodulating activities. This review covers biological activities and its mechanism of calycosin. It will provide a useful reference for clinical research and rational utilization of monomericompound.

MicroRNA-27a promotes proliferation, migration and invasion by targeting MAP2K4 in human osteosarcoma cells.

BACKGROUND: Osteosarcoma is a high-grade malignant bone neoplasm. Although the introduction of chemotherapy has reduced its mortality, more than 50% of patients develop chemoresistance and have an extremely poor prognosis due to pulmonary metastasis. Several molecular pathways contributing to osteosarcoma development and progression have recently been discovered. Various studies have addressed the genes involved in the metastasis of osteosarcoma. However, the highly complex molecular mechanisms of metastasis are still poorly understood. Recently, the decisive role of microRNAs in the regulation of molecular pathways has been uncovered. miRNAs may function as either oncogenes or tumor suppressors, depending on their target genes. miR-27a, a member of an evolutionarily conserved miRNA family, is abnormally increased in several types of cancers. It has been shown to be upregulated in osteosarcoma and plays a pro-metastatic role in osteosarcoma cell lines. However, the effects of miR-27a on osteosarcoma have not been clearly elucidated. The present study thus addressed the miR-27a sensitive mechanisms in osteosarcoma. METHODS: In this study, three biological programs were used to predict whether MAP2K4 was a target of miR-27a. A specific miR-27a inhibitor was used to inhibit the endogenous activity of miR-27a in the human osteosarcoma cell line MG63. Cell proliferation, colony formation, migration and invasion assays were performed to assess the effects of miR-27a on the proliferation, metastasis and invasion of MG63 cells. The expression levels of several proteins evolved in the JNK/p38 signaling pathway were detected using western blot analysis. RESULTS: The luciferase activity of the wild-type pGL3-MAP2K4 3'UTR vector was significantly inhibited after the miR-27a precursor or the control precursor was transfected into the MG63 cells. However, the luciferase activity was not inhibited after transfection of the mutant pGL3-MAP2K4 3'UTR vector. The inhibition of miR-27a increased the luciferase activity of the wild-type pGL3-MAP2K4 3'UTR vector after MG63 cells were transfected with the miR-27a inhibitor or the control inhibitor. Thus, MAP2K4 is a potential target of miR-27a and can be directly regulated by miR-27a. Inhibition of miR-27a significantly suppressed cell proliferation after 72 hours compared to the negative control group. Inhibition of miR-27a significantly suppressed colony formation of the MG63 cells by 39 6%. Transwell migration and invasion assays demonstrated that the number of migratory and invasive cells transfected with the miR-27a inhibitor was reduced by 63.5% and 69.1%, respectively. After transfection of the miR-27a inhibitor into the MG63 cells, the level of phospho-JNK1 and phospho-p38 increased by 25% and 29%, respectively, along with the up-regulation of MAP2K4 protein. CONCLUSION: This is the first study showing that miR-27a can function as an oncogene by targeting MAP2K4 in the osteosarcoma MG63 cell line. Inhibition of miR-27a increases MAP2K4 expression, which in turn inhibits cell proliferation and migration through the JNK/p38 signaling pathway in MG63 cells. These findings may help us understand the molecular mechanism of miR-27a in the tumorigenesis of osteosarcoma and may provide new diagnostic and therapeutic options for the treatment of this neoplasia.

Complete L5 burst fracture treated by 270-degree decompression and reconstruction using titanium mesh cage via a single posterior vertebrectomy.

Complete burst fractures of the L5 is relatively uncommon. How to accomplish a rigid internal fixation as well as preserve motor function is an enormous challenge. We report such a case treated via a single posterior vertebrectomy with 270-degree decompression and reconstruction using titanium mesh cage. The disc between L5/S1 was preserved by placing the titanium mesh cage on the inferior endplate of the L5. We hope this method can offer a possible solution for other surgeons when they meet a similar fracture pattern.