AMPK promotes osteogenesis and inhibits adipogenesis through AMPK-Gfi1-OPN axis.

Several metabolic, genetic and oncogenic bone diseases share the common pathological phenotype of defective bone marrow stromal cell (BMSC) differentiation. Many reports in bone science in the past several years have suggested that the skeleton also has an endocrine role. The role of AMP-activated protein kinase (AMPK) as an energy metabolism sensor and how it regulates BMSC differentiation is largely unknown. In the current study, we used AMPK agonists to activate AMPK in MC3T3-E1 cells to investigate the functional roles of AMPK in osteogenesis. However, metformin and AICAR failed to activate AMPK consistently. Therefore, we established MC3T3-E1 and 3T3-L1 cell models of AMPK α subunit overexpression through lentivirus vector, in which AMPK was overactivated. AMPK hyperactivation stimulated MC3T3-E1 cell osteogenesis and inhibited 3T3-L1 cell adipogenesis. Osteopontin (OPN) mediated AMPK regulation of osteogenesis and adipogenesis. Furthermore, we provided evidence that the transcriptional repressor growth factor independence-1 (Gfi1) was downregulated and disassociated from the OPN promoter in response to AMPK activation, resulting in the upregulation of OPN. Overexpression of wild-type and dominant-negative Gfi1 modulated MC3T3-E1 osteogenesis and 3T3-L1 adipogenesis. Further evidence suggested that AMPK enhanced ectopic bone formation of MC3T3-E1 cells through the AMPK-Gfi1-OPN axis. In conclusion, AMPK was sufficient to stimulate osteogenesis of MC3T3-E1 cells and inhibit adipogenesis of 3T3-L1 cells through the AMPK-Gfi1-OPN axis. These findings helped elucidate the molecular mechanisms underlying AMPK regulation of osteogenesis and adipogenesis.

Treatment of kaposiform hemangioendothelioma and tufted angioma.

This meta-analysis was to evaluate the efficacy of current treatment modalities for kaposiform hemangioendothelioma and tufted angioma. A systematic review was performed using PubMed (Medline), Web of Science and Embase for clinical studies. The outcome was measured by pooled response rate with 95% confidence intervals (CIs), together with heterogeneity, subgroup analysis, sensitivity analysis and publication bias. Fifteen studies with 244 participants were included in this analysis. Vincristine therapy exhibited a relatively higher response rate (0.72; 95%CI, 0.64-0.79) compared with other therapies including systemic corticosteroid (0.27; 95%CI, 0.17-0.36), interferon (0.36; 95%CI, 0.24-0.48), radiotherapy (0.49; 95%CI, 0.26-0.73), embolization (0.66; 95%CI, 0.48-0.83), aspirin/ticlopidine (0.42; 95%CI, 0.06-0.78) and sirolimus (0.57; 95%CI, 0.00-0.10), in treating KHE/TA. Subgroup analysis indicated that the efficacy of systemic corticosteroids therapy was age-related. The pooled response rate was 0.15 (95%CI, 0.08-0.23) for participants 3.5 months of age and older compared with 0.35 (95% CI, 0.26-0.44) for participants less than 3.5 months. Regarding side effects, systemic corticosteroids treatment was 0.32 (95%CI, 0.15-0.50), vincristine modality was 0.16 (95%CI, 0.08-0.24) and interferon therapy was 0.28 (95%CI, 0.13-0.43). In conclusion, as one of the first reviews evaluating the effect of common therapies in the treatment of KHE/TA, our meta-analysis displayed that vincristine was more effective. Thus, vincristine was the most effective, providing evidence supporting the use of vincristine as a first-line therapy for KHE/TA.

Fabrication, characterization, and biocompatibility of ethyl cellulose/carbonated hydroxyapatite composite coatings on Ti6Al4V.

In order to improve the biocompatibility of metallic implants, bioactive components are often used as coatings so that a real bond with the surrounding bone tissue can be formed. We prepared ethyl cellulose/carbonated hydroxyapatite composite coatings (ECHCs) on Ti6Al4V substrates with carbonated hydroxyapatite coatings (CHACs) without ethyl cellulose as controls. The inorganic constituent on the CHACs and ECHCs is calcium-deficient carbonated hydroxyapatite with a flaky texture and a low degree of crystallinity. The flaky carbonated hydroxyapatite plates aggregate to form macropores with an aperture size of around 0.5-2.0 µm. The presence of ethyl cellulose provides superior morphology, contact angle, and biocompatibility characteristics. In comparison to CHACs, ECHCs exhibit a smoother, crack-free surface because the cracks are filled by ethyl cellulose. Moreover, the contact angle of ECHCs is 37.3°, greater than that of CHACs (13.0°). Surface biocompatibility was investigated by using human bone mesenchymal stem cells (hBMSCs). The attachment, spreadability, viability and proliferation of hBMSCs on ECHCs are superior to those on CHACs. Thus, the crack-free ECHCs have excellent biocompatibility and are appropriate for use as biological implants.

The accuracy of ultrasonography in the preoperative diagnosis of cervical lymph node metastasis in patients with papillary thyroid carcinoma: A meta-analysis.

BACKGROUND: Ultrasonography has been proposed to enhance preoperative assessment of cervical lymph node status in patients with papillary thyroid carcinoma (PTC). Management is most controversial for patients with a clinically negative (cN0) neck. We aimed to evaluate the diagnostic properties of ultrasonography in the detection of cervical lymph node metastasis in patients with PTC. MATERIALS AND METHODS: Studies evaluating the diagnostic accuracy of Ultrasonography in the diagnosis of cervical lymph node metastasis in patients with PTC were systematically searched for in the MEDLINE, EMBASE, Cancerlit and Cochrane Library and other database from January 1995 to November 2010. Two reviewers independently abstracted data including research design, sample size, imaging technique and technical characteristics, method of image interpretation. By patient-based and region- or node-based data analyses, we determined pooled sensitivities and specificities across studies, and constructed summary receiver operating characteristic curves, and area under summary receiver operating characteristic curves were calculated. RESULTS: The pooled patient-based sensitivity for ultrasonography was 0.72 (95% CI, 0.46-0.88), specificity was 0.98 (95% CI, 0.84-1.00), and the area under the curve (AUC) was 0.94 (95% CI, 0.92-0.0.96). The pooled region- or node-based sensitivity for ultrasonography was 0.63 (95% CI, 0.47-0.76), specificity was 0.93 (95% CI, 0.73-0.99), and the AUC was 0.81 (95% CI, 0.77-0.84). For lesion-based analysis, the subgroup of lateral compartment lymph node involvement was found to have the highest sensitivity (0.72, 95% CI 0.68-0.75) and specificity (0.97, 95% CI 0.93-0.99) among the studies (p<0.05). Study sensitivity was not correlated with the prevalence of cervical lymph node metastasis (patient-based: R(2)=0.0196, p=0.7915; region- or node-based: R(2)=0.3835, p=0.1381). CONCLUSIONS: We conclude that preoperative ultrasonography is a good technique for the preoperative lymph node staging of PTC and is helpful for detecting metastatic cervical lymph nodes at the lateral group. High-quality prospective studies regarding ultrasonography in the evaluation of cervical lymph node status in patients with PTC are still needed to be conducted.

Usefulness of CT angiography in diagnosing acute gastrointestinal bleeding: a meta-analysis.

AIM: To analyze the accuracy of computed tomography (CT) angiography in the diagnosis of acute gastrointestinal (GI) bleeding. METHODS: The MEDLINE, EMBASE, Cancerlit, Cochrane Library database, Sciencedirect, Springerlink and Scopus, from January 1995 to December 2009, were searched for studies evaluating the accuracy of CT angiography in diagnosing acute GI bleeding. Studies were included if they compared CT angiography to a reference standard of upper GI endoscopy, colonoscopy, angiography or surgery in the diagnosis of acute GI bleeding. Meta-analysis methods were used to pool sensitivity and specificity and to construct summary receiver-operating characteristic. RESULTS: A total of 9 studies with 198 patients were included in this meta-analysis. Data were used to form 2 x 2 tables. CT angiography showed pooled sensitivity of 89% (95% CI: 82%-94%) and specificity of 85% (95% CI: 74%-92%), without showing significant heterogeneity (chi(2) = 12.5, P = 0.13) and (chi(2) = 22.95, P = 0.003), respectively. Summary receiver operating characteristic analysis showed an area under the curve of 0.9297. CONCLUSION: CT angiography is an accurate, cost-effective tool in the diagnosis of acute GI bleeding and can show the precise location of bleeding, thereby directing further management.

Does Helicobacter pylori infection play a role in iron deficiency anemia? A meta-analysis.

AIM: To perform a meta-analysis of observational studies and randomized controlled trials (RCTs) on the association between Helicobacter pylori (H. pylori) and iron deficiency anemia (IDA). METHODS: A defined search strategy was used to search Medline, Embase, the Cochrane Library, Clinical Trials, Cochrane Central Register of Controlled Trials, Premedline and Healthstar. Odds ratio (OR) was used to evaluate observational epidemiology studies, and weighted mean difference (WMD) was used to demonstrate the difference between control and intervention groups. RESULTS: Fifteen observational studies and 5 RCTs were identified and used for calculation. The pooled OR for observational studies was 2.22 (95% CI: 1.52-3.24, P < 0.0001). The WMD for hemoglobin (HB) was 4.06 g/L (95% CI: -2.57-10.69, P = 0.01), and the WMD for serum ferritin (SF) was 9.47 mug/L (95% CI: -0.50-19.43, P < 0.0001). Results were heterogeneous for all comparisons. CONCLUSION: This meta-analysis on observational studies suggests an association between H. pylori and IDA. In RCTs, eradication of H. pylori can improve HB and SF levels but not significantly.