MicroRNA-27b exerts an oncogenic function by targeting Fbxw7 in human hepatocellular carcinoma.

Aberrant expression of microRNAs (miRNAs) plays fundamental effect on the pathogenesis of hepatocellular carcinoma (HCC). MiR-27b was previously found to play important roles in human cancers. However, its expression status, clinical significance, and biological functions in HCC remain largely unclear. The expression status of miR-27b in HCC specimens and cells were determined with qRT-PCR. MTT, 5-bromodeoxyuridine (BrdU) proliferation assays, and flow cytometry analysis were carried out to assay proliferation, cell cycle, and apoptosis. A subcutaneous model was used to evaluated the HCC tumor growth in vivo. The putative target gene of miR-27b was disclosed by TargetScan and a luciferase reporter assay. The levels of miR-27b were overexpressed in HCC. Overexpression of miR-27b was correlated with adverse prognostic features and reduced survival rate. Inhibition of miR-27b in SMMC-7721 cells remarkably suppressed proliferative ability and cell-cycle progression while enhanced apoptosis. In contrast, miR-27b overexpression resulted in prominent increased proliferation and process of cell cycle and reduced apoptosis of Hep3B cells. In vivo studies showed that knockdown of miR-27b inhibited the in vivo growth of SMMC-7721 cells in mouse xenograft model. Furthermore, we confirmed that Fbxw7 was directly regulated by miR-27b and mediated the roles of miR-27b in HCC. We suggest that miR-27b serves as an oncogenic miRNA in HCC by modulating proliferation, cell-cycle progression, and apoptosis, and its oncogenic effect is mediated by its downstream target gene, Fbxw7.

Differentiation of lipid-poor adenoma from pheochromocytoma on biphasic contrast-enhanced CT.

PURPOSE: To evaluate the diagnostic performance of biphasic contrast-enhanced CT in differentiation of lipid-poor adenomas from pheochromocytomas. METHODS: 129 patients with 132 lipid-poor adenomas and 93 patients with 97 pheochromocytomas confirmed by pathology were included in this retrospective study. Patients underwent unenhanced abdominal CT scan followed by arterial and venous phase. Quantitative and qualitative imaging features were compared between the two groups using univariate analysis. Risk factors for pheochromocytomas were evaluated by multivariate logistic regression analysis and a diagnostic scoring model was established based on odd ratio (OR) of the risk factors. RESULTS: Pheochromocytomas were larger and showed cystic degeneration more frequently compared with lipid-poor adenomas (p < 0.01). No significant difference was found in peak enhancement phase between the two groups (p = 0.348). Attenuation values on unenhanced phase (CTU), arterial phase (CTA), and venous phase (CTV) of pheochromocytomas were significantly higher than that of lipid-poor adenomas while enhancement ratio on arterial and venous phase (ERA, ERV) of pheochromocytomas was significantly lower than that of lipid-poor adenomas (all p < 0.05). Multivariate analysis revealed lesion size > 29 mm (OR: 5.74; 95% CI 2.51-13.16; p < 0.001), CTA > 81 HU (OR: 2.54; 95% CI 1.04-6.17; p = 0.04), CTV > 97 HU (OR: 11.19; 95% CI 3.21-38.97; p < 0.001), ERV ≤ 1.5 (OR: 20.23; 95% CI 6.30-64.87; p < 0.001), and the presence of cystic degeneration (OR: 6.22, 95% CI 1.74-22.25; p = 0.005) were risk factors for pheochromocytomas. The diagnostic scoring model yielded an area under the curve (AUC) of 0.911. CONCLUSIONS: Biphasic contrast-enhanced CT showed good diagnostic performance in differentiation of lipid-poor adenomas from pheochromocytomas.

Brain connectomic associations with traditional Chinese medicine diagnostic classification of major depressive disorder: a diffusion tensor imaging study.

BACKGROUND: Major depressive disorder (MDD) is highly heterogeneous in pathogenesis and manifestations. Further classification may help characterize its heterogeneity. We previously have shown differential metabolomic profiles of traditional Chinese medicine (TCM) diagnostic subtypes of MDD. We further determined brain connectomic associations with TCM subtypes of MDD. METHODS: In this naturalistic study, 44 medication-free patients with a recurrent depressive episode were classified into liver qi stagnation (LQS, n = 26) and Heart and Spleen Deficiency (HSD, n = 18) subtypes according to TCM diagnosis. Healthy subjects (n = 28) were included as controls. Whole-brain white matter connectivity was analyzed on diffusion tensor imaging. RESULTS: The LQS subtype showed significant differences in multiple network metrics of the angular gyrus, middle occipital gyrus, calcarine sulcus, and Heschl's gyrus compared to the other two groups. The HSD subtype had markedly greater regional connectivity of the insula, parahippocampal gyrus, and posterior cingulate gyrus than the other two groups, and microstructural abnormalities of the frontal medial orbital gyrus and middle temporal pole. The insular betweenness centrality was strongly inversely correlated with the severity of depression and dichotomized the two subtypes at the optimal cutoff value with acceptable sensitivity and specificity. CONCLUSIONS: The LQS subtype is mainly characterized by aberrant connectivity of the audiovisual perception-related temporal-occipital network, whereas the HSD subtype is more closely associated with hyperconnectivity and microstructural abnormalities of the limbic-paralimbic network. Insular connectivity may serve a biomarker for TCM-based classification of depression.Trial registration Registered at http://www.clinicaltrials.gov (NCT02346682) on January 27, 2015.

Symptomatic adjacent segment disease after single-lever anterior cervical discectomy and fusion: Incidence and risk factors.

The purpose of this study was to determine the incidence and risk factors of symptomatic adjacent segment disease (ASD) following single-lever anterior cervical discectomy and fusion (ACDF) for cervical degenerative diseases.From January 2000 to December 2010, a total of 582 patients with cervical radiculopathy and myelopathy who had undergone single-lever ACDF surgery in the authors' institution were reviewed retrospectively. Patients who had a revision surgery for symptomatic ASD were selected for this study. The authors analyzed the incidence for ASD after single-lever ACDF. And univariate analysis and logistic regression analysis were performed to identify the risk factors of ASD.Among the 582 patients, 36 patients received subsequent surgical management for ASD after initial single-lever ACDF for an overall prevalence of 6.2%. The average onset time of ASD was 8.5 (2-15) years. The univariate analysis showed that there were no significant differences in sex, duration of disease, BMI, DM, smoking, operative levels, and follow-up period (P > .05) between the 2 groups with and without ASD. There were statistically significant differences in age at the time of operation (χ = 4.361, P = .037), and developmental canal stenosis (χ = 4.181, P = .041) between patients with and without ASD. The variables of age at the time of operation and developmental canal stenosis were included in a logistic regression model. The logistic regression analysis revealed that age at the time of operation ≤50 years (P = .045, OR = 3.015, 95% CI = 1.024-8.882) and developmental canal stenosis (P = .042, OR = 2.797, 95% CI = 1.039-7.527) were the risk factors for ASD after single-lever ACDF.In the present study, the incidence of symptomatic ASD after single-lever ACDF was 6.2%. And the age at the time of operation ≤50 years and developmental canal stenosis were the risk factors for ASD. The patients ≤50 years old at the time of operation or with developmental canal stenosis are more likely to develop ASD after surgery, and the risk of reoperation will increase.

Effect of toll-like receptor 3 agonist poly I:C on intestinal mucosa and epithelial barrier function in mouse models of acute colitis.

AIM: To investigate potential effects of poly I:C on mucosal injury and epithelial barrier disruption in dextran sulfate sodium (DSS)-induced acute colitis. METHODS: Thirty C57BL/6 mice were given either regular drinking water (control group) or 2% (w/v) DSS drinking water (model and poly I:C groups) ad libitum for 7 d. Poly I:C was administrated subcutaneously (20 µg/mouse) 2 h prior to DSS induction in mice of the poly I:C group. Severity of colitis was evaluated by disease activity index, body weight, colon length, histology and myeloperoxidase (MPO) activity, as well as the production of proinflammatory cytokines, including tumor necrosis factor-α (TNF-α), interleukin 17 (IL-17) and interferon-γ (IFN-γ). Intestinal permeability was analyzed by the fluorescein isothiocyanate labeled-dextran (FITC-D) method. Ultrastructural features of the colon tissue were observed under electron microscopy. Expressions of tight junction (TJ) proteins, including zo-1, occludin and claudin-1, were measured by immunohistochemistry/immunofluorescence, Western blot and real-time quantitative polymerase chain reaction (RT-qPCR). RESULTS: DSS caused significant damage to the colon tissue in the model group. Administration of poly I:C dramatically protected against DSS-induced colitis, as demonstrated by less body weight loss, lower disease activity index score, longer colon length, colonic MPO activity, and improved macroscopic and histological scores. It also ameliorated DSS-induced ultrastructural changes of the colon epithelium, as observed under scanning electron microscopy, as well as FITC-D permeability. The mRNA and protein expressions of TJ protein, zo-1, occludin and claudin-1 were also found to be significantly enhanced in the poly I:C group, as determined by immunohistochemistry/immunofluorescence, Western blot and RT-qPCR. By contrast, poly I:C pretreatment markedly reversed the DSS-induced up-regulated expressions of the inflammatory cytokines TNF-α, IL-17 and IFN-γ. CONCLUSION: Our study suggested that poly I:C may protect against DSS-induced colitis through maintaining integrity of the epithelial barrier and regulating innate immune responses, which may shed light on the therapeutic potential of poly I:C in human colitis.

[Subtype classification of Garden III femoral neck fractures in the elderly based on frontal Garden index and its clinical significance].

OBJECTIVE: To retrospectively study postoperative Garden III femoral neck fractures in the elderly so as to explore the different degree of displacement of Garden III femoral neck fracture, and discuss the basis and clinical significance of the subtype classification. METHODS: A total of 492 patients with complete clinical data out of the 1397 patients with femoral neck fractures treated by closed reduction and internal fixation with cannulated compression screws from September 2005 to September 2010 were included in the study. Each patient's frontal Garden Index was measured. On the basis of the frontal Garden Index, these cases were divided into three types:type A, which frontal Garden Index was more than or equal to 140°, included 53 males and 84 females with an average age of(65.3±7.2) years old ranging from 60 to 75 years old; type B, more than 120°and less than 140°, included 79 males and 172 females with an average age of (67.5±3.6) years old;and type C, less than or equal to 120°, included 38 males and 66 with an average age of(68.6±5.7) years old. Aspects were followed up including complications, consequences and hip joint function. The fracture healing and femoral head necrosis were compared among three types. RESULTS: Operative incision of 492 cases was primary healing, and no infection and other complications occurred. All patients were followed up from 2 to 10 years with an average of 6.3 years, the healing of femoral neck fracture occurred in 432 cases, and the total union rate was 87.8%. Femoral head necrosis occurred in 83 cases, and the total necrosis rate of femoral head was 16.9%. The nonunion rate of type A was 6.6%, type B was 13.5%, and type C was 16.3%, there were significant differences among three types(χ²2AB=4.377, P=0.036;χ²2AC=5.872, P=0.015;χ²2BC=0.469, PBC=0.494). The necrosis rate of femoral head of group A was 8.8%, group B was 16.7%, and group C was 27.9%, there were significant differences among three groups(χ²2AB=4.704, P=0.030;χ²2AC=15.317, P=0.000;χ²2BC=5.715, P=0.017). CONCLUSIONS: It is different for the degree of displacement of Garden III femoral neck fracture in the elderly. Based on frontal Garden Index to differentiate degree of fracture displacement, Garden III femoral neck fracture would be divided into A, B and C subtypes. The prognosis of Garden III femoral neck fracture in the elderly is negatively related to its degree of displacement, which has clinical significance to make treatment plan for Garden III femoral neck fracture in the elderly.