[Retracted] Hedgehog signaling is involved in the BMP9­induced osteogenic differentiation of mesenchymal stem cells.

Subsequently to the publication of the above paper, a concerned reader drew to the authors' attention that there were a number of overlapping data panels featured in the cellular images shown in Fig. 2C on p. 1644, and Figs. 3D and 4 on p. 1645, such that data that were allegedly obtained under different experimental conditions appeared to have been derived from some of the same original sources. Given the number of errors that had been made during the compilation of the figures in this article, the Editor of International Journal of Molecular Medicine has decided that this article should be retracted from the publication owing to a lack of overall confidence in the presented data. The authors were asked for an explanation to account for these concerns, but the Editorial Office did not receive a reply. The Editor apologizes to the readership for any inconvenience that might result from the retraction of this article. [International Journal of Molecular Medicine 35: 1641­1650, 2015; DOI: 10.3892/ijmm.2015.2172].

Improved performance of soy protein adhesive with melamine-urea-formaldehyde prepolymer.

In recent years, soy protein adhesive, as an environmentally friendly bio-based adhesive, has attracted extensive attention. In this study, in order to ameliorate the bonding quality of soy protein isolate (SPI) adhesive, the melamine-urea-formaldehyde prepolymer (MUFP) was synthesized, and different amounts of it were introduced into the SPI adhesive as a cross-linking agent. Fourier transform infrared (FT-IR) spectroscopy, gel permeation chromatography (GPC), thermogravimetric analyze (TGA), and scanning electron microscopy (SEM) were used to analysis the mechanism of modification. The results of plywood test indicated that the wet bonding strength of the adhesives was first increased and then decreased with an increase in the amount of MUFP additive. FT-IR, TGA, and SEM tests suggested that the introduction of MUFP could promote the establishment of a cross-linking structure in the cured adhesive layer to improve the bonding quality of adhesives, but presence of excessive MUFP could introduce hydrophilic groups and adversely affect water resistance.

Minimally invasive perventricular versus open surgical ventricular septal defect closure in infants and children: a randomised clinical trial.

BACKGROUND: Robust evidence is lacking regarding the clinical efficacy, safety and cardiopulmonary performance of perventricular closure. This study investigated the perioperative efficacy, safety and cardiorespiratory performance of perventricular closure of perimembranous ventricular septal defects (pmVSDs). METHODS: Operation-naïve infants and young children aged 5-60 months with isolated pmVSDs were randomised to receive either standard open surgical or minimally invasive perventricular closure via direct entry into the ventricle with a catheter from a subxiphoid incision. The primary outcomes included complete closure at discharge, major and minor adverse events and the changes in perioperative cardiorespiratory performance from baseline. Complete closure was mainly analysed in the modified intention-to-treat (mITT) population, with sensitivity analyses for the ITT, per-protocol (PP) and as-treated (AT) populations (non-inferiority margin -5.0%). RESULTS: We recruited 200 patients with pmVSDs for this study (mean age 24.38 months, range 7-58 months, 104 girls), of whom 100 were randomly allocated to one of the study groups. The non-inferiority of perventricular to surgical closure regarding complete closure at discharge was not shown in the ITT (absolute difference -0.010 (95% CI -0.078 to 0.058)) and mITT populations (-0.010 (95% CI -0.069 to 0.048)), but was shown in the PP (0.010 (95% CI -0.043 to 0.062)) and AT populations (0.048 (95% CI -0.009 to 0.106)). Perventricular closure reduced the rate of compromising cardiac haemodynamics, electrophysiological responses, cardiomyocyte viability, respiratory mechanics, ventilatory and gas exchange function and oxygenation and tissue perfusion compared with surgical closure (all between-group P<0.05). CONCLUSIONS: For infants and young children with pmVSD, perventricular closure reduced the rate of postoperative cardiorespiratory compromise compared with surgical closure, but the non-inferiority regarding complete closure should be interpreted in the context of the specific population. TRIAL REGISTRATION NUMBER: NCT02794584 ;Results.

RUNX3 plays an important role in mediating the BMP9-induced osteogenic differentiation of mesenchymal stem cells.

Although bone morphogenetic protein 9 (BMP9) is highly capable of promoting the osteogenic differentiation of mesenchymal stem cells (MSCs) both in vitro and in vivo, the molecular mechanisms involved remain to be fully elucidated. Runt-related transcription factor (RUNX)3 is an essential regulator of osteoblast/chondrocyte maturation. However, the exact role of RUNX3 in BMP9 osteoinductive activity is unknown. In this study, we sought to investigate the functional role of RUNX3 in the BMP9-induced osteogenic differentiation of MSCs. We found that BMP9 upregulated the endogenous expression of RUNX3 in MSCs. The overexpression or/and knockdown of RUNX3 both increased the levels of alkaline phosphatase (ALP) a marker of BMP9-induced early osteogenic differentiation. Nevertheless, matrix mineralization, a marker of BMP9-induced late osteogenic differentiation was enhanced by the overexpression of RUNX3, whereas it was inhibited by the knockdown of RUNX3. The BMP9-induced expression of osteogenic pivotal transcription factors [inhibitor of differentiation (Id)3, distal-less homeobox 5 (DLX5) and RUNX2)] was further increased by the overexpression of RUNX3; however, it was reduced by the knockdown of RUNX3. However, the expression levels of Id1 and Id2 were both enhanced by the overexpression or/and knockdown of RUNX3. The BMP9-induced phosphorylation of Smad1/5/8 was increased with the overexpression of RUNX3, and yet was decreased with the knockdown of RUNX3. Collectively, our findings suggest that RUNX3 is an essential modulator of the BMP9-induced osteoblast lineage differentiation of MSCs.

Activation of PKA/CREB Signaling is Involved in BMP9-Induced Osteogenic Differentiation of Mesenchymal Stem Cells.

BACKGROUND/AIMS: BMP9 is highly capable of promoting osteogenic differentiation of mesenchymal stem cells (MSCs) although the molecular mechanism involved is largely unknown. Here, we explored the detail role of PKA/CREB signaling in BMP9-induced osteogenic differentiation. METHODS: Activation status of PKA/CREB signaling is assessed by nonradioactive assay and Western blot. Using PKA inhibitors and a dominant negative protein of CREB (A-CREB), we investigated the effect of PKA/CREB signaling on BMP9-induced osteogenic differentiation. RESULTS: We found that BMP9 promotes PKA activity and enhances CREB phosphorylation in MSCs. BMP9 is shown to down-regulate protein kinase A inhibitor γ (PKIγ) expression. We demonstrated that PKA inhibitors suppress BMP9-induced early osteogenic marker alkaline phosphatase (ALP) activity in MSCs as well as late osteogenic markers osteopontin (OPN), osteocalcin (OCN) and matrix mineralization. We found that PKA inhibitor reduces BMP9-induced Runx2 activation and p38 phosphorylation in MSCs. Lastly, interference of CREB function by A-CREB decreased BMP9-induced osteogenic differentiation as well. CONCLUSION: Our results revealed that BMP9 may activate PKA/CREB signaling in MSCs through suppression of PKIγ expression. It is noteworthy that inhibition of PKA/CREB signaling may impair BMP9-induced osteogenic differentiation of MSCs, implying that activation of PKA/CREB signaling is required for BMP9 osteoinductive activity.

Hedgehog signaling is involved in the BMP9-induced osteogenic differentiation of mesenchymal stem cells.

Nonunion is a serious complication of a bone fracture that may occur in any bone of the skeletal system. It occurs when a broken bone fails to heal. Mesenchymal stem cell (MSC)-based tissue engineering technology has been considered an efficient method to improve the healing rate of nonunions. Although previous studies have demonstrated that bone morphogenetic protein 9 (BMP9) is highly capable of promoting the osteogenic differentiation of MSCs, the mechanisms involved remain largely unclear. In the present study, we investigated the possible involvement and the detailed role of Hedgehog (Hh) signaling in the BMP9-induced osteogenic differentiation of MSCs. It was found that BMP9 exerts an effect on Hh signaling in MSCs. The expression levels of early markers of BMP9-induced osteogenic differentiation, such as alkaline phosphatase (ALP) activity, and late markers of osteogenic differentiation, such as matrix mineralization, as well as the expression levels of osteopontin (OPN) and osteocalcin (OCN) were decreased by the Hh signaling inhibitor, cyclopamine, whereas these levels were increased by the Hh signaling agonist, purmorphamine. Furthermore, the BMP9-induced transcriptional activity of Smad1/5/8 and the expression of pivotal osteogenic transcription factors were reduced by cyclopamine, and were increased by purmorphamine. Taken together, our results demonstrate that BMP9 exerts an effect on Hh signaling in MSCs. What is most noteworthy, however, is that the inhibition or enhancement of Hh signaling resulted in the reduction and augmentation of the BMP9-induced osteogenic differentiation of MSCs, respectively, suggesting that Hh signaling is involved and plays a regulatory role in the osteogenic differentiation of MSCs induced by BMP9.

Fetal echocardiography for congenital heart disease diagnosis: a meta-analysis, power analysis and missing data analysis.

BACKGROUND: Prenatal ultrasonography is the most widely available diagnostic test for fetal congenital heart disease (CHD), but the factors influencing its diagnostic accuracy remain uncertain despite extensive research. The aim of the present study was to evaluate the potential role of demographic, clinical and ultrasonographic characteristics on diagnostic yields for detecting CHD. METHODS: A systematic search of PubMed, ISI Web of Science, SinoMed, and the Cochrane Library was performed to identify studies assessing the accuracy of prenatal ultrasound in the detection of CHD. A random effects model was used to generate pooled sensitivity and specificity in addition to summary receiver operating characteristic (SROC) curves. RESULTS: Overall, prenatal ultrasound in the detection of CHD had a moderate sensitivity of 68.1% (95% CI 59.6-75.5) and a favorable specificity of 99.9% (99.7-99.9). Risk level and gestation age were independent predictors of diagnostic performance for detecting CHD (p = 0.004 vs. p = 0.002, respectively). The pooled sensitivities significantly increased to varying extents with the following echocardiographic views: 48.7% (34.8-67.2) for four-chamber view (4CV); 58.0% (40.3-73.9) for a combination of 4CV and outflow tract views (OTV); 73.5% (59.2-84.1) for combination of 4CV, OTV and three vessels and trachea view (3VTV); 77.1% (62.0-87.5) for extensive cardiac echocardiography examination (ECEE); and 89.6% (81.0-94.6) for spatiotemporal image correlation (STIC). CONCLUSIONS: Prenatal ultrasound is a powerful tool for the diagnosis of CHD; however, a single ultrasonographic regime is not definitive on its own and must be interpreted in the context of demographic and clinical characteristics.

Minimally invasive endoscopic staging for mediastinal lymphadenopathy in lung cancer: a systematic review protocol.

INTRODUCTION: Minimally invasive endoscopic biopsy techniques have been widely available as potential alternatives for mediastinal lesions staging in patients with known or suspected lung cancer. Previous efforts have been made to evaluate the diagnostic performance of specific endoscopic modality alone at the level of the mediastinum for staging lung cancer, however, few studies focus on the accuracy of comparisons between different endoscopic modalities, especially at the level of any individual lymph node station. The objective of our study is to determine the diagnostic yields of different endoscopic modalities for staging mediastinal lymphadenopathy in lung cancer, especially concerning the individual lymph node station. METHODS/DESIGN: A systematic electronic search of MEDLINE, EMBASE, SinoMed and ISI Web of Science were performed to identify studies evaluating endoscopic modalities accuracy with restriction of English and Chinese languages from inception to an update until May 2014. Data were extracted with the patient as the unit of analysis with regards to the abilities of different endoscopic modalities at the level of mediastinum and particular lymph node station. The methodological quality was assessed independently according to the Quality Assessment of Diagnostic Accuracy Study (QADAS) criteria. An exact binomial rendition of bivariate mixed-effects regression model was used to estimate the pooled sensitivity and specificity. Also, pre-post probability analysis, publication bias analysis and sensitivity analysis were performed for a synthesis of knowledge of this context. DISSEMINATION: The findings will advance our better available knowledge of optimal clinical decision-making when dealing with staging of mediastinal metastasis in lung cancer. TRIAL REGISTRATION NUMBER: PROSPERO-NIHR Prospective Register of Systematic Reviews (CRD42014009792).

[Evaluation of digital subtraction angiography rabbit VX2 hepatic carcinoma model with modified hepatic artery catheterization].

OBJECTIVE: To modify the success rate of establishing VX2 transplanted tumor model with different methods in rabbits, and access new typed modification and improved technique in catheterization. METHODS: In the study, 30 rabbits were randomly divided into 2 groups. In prophase, tumor cell suspension was implanted in group I, while tumor tissue particles were implanted into liver under direct vision, to establish VX2 transplanted tumor model. The rabbits were catheterized from femoral artery to selective hepatic artery under DSA, by using conventional modification with Seldinger technique in group I and by using new typed modification with improved technique in group II. The imaging and histological features of VX2 tumor were evaluated by combining pathology and DSA, then the success rate, operation time and postoperative complications were compared and evaluated. RESULTS: The success rates of the liver tumor model were 60.0% and 93.3%; the disposable success rates of catheterization were 66.7% and 92.8%; the operation time of catheterization were (35.6±5.8) min and (27.4±5.3) min; the incidence rates of adverse reaction were 22.5% and 18.0%; the differences between the two groups in the experimental rabbits were significant (P<0.05) statistically. CONCLUSION: The efficiency of tumor tissue particles implanted is better than that of tumor cell suspension implanted in establishing VX2 transplanted tumor model under direct vision. The cathetenzation quality and outcomes of new typed modification by improved technique, from femoral artery to selective hepatic artery, is superior to those of conventional modification with Seldinger technique.

[Research on detecting concentration of serum protein based on resonance Rayleigh scattering].

The resonance Rayleigh scattering spectral detection system was designed based on the 2, 9, 16, 23-tetracarboxylate-phthalocyanine zinc and protein system. In the system, excitation light source is 405 nm wide band gap semiconductor lasers, and monochromator is 475 nm narrow-band band-pass filter, and the detector is low-noise and high-gain photoelectric amplifier based on blue-ray enhanced photodiode. Experiment shows that, the solution's strong absorption wavelength is near 420 nm. Under the action of incentive light, resonance Rayleigh scattering is generated at the resonant wavelength, and the scattering intensity is proportional to the protein content. The system uses 2, 9, 16, 23-tetracarboxylate as the spectrum probe to determine the concentration of serum proteins by resonance Rayleigh scattering method. Its linear detection range is 10 - 50 mg.mL-1, and its detection limit is 0. 001 mg.mL-1. The newly developed device for detecting concentration of the serum protein has the advantages of small size, low cost, low power consumption, and being easy to use.