C1Q labels a highly aggressive macrophage-like leukemia population indicating extramedullary infiltration and relapse.

Extramedullary infiltration (EMI) is a concomitant manifestation that may indicate poor outcome of acute myeloid leukemia (AML). The underlying mechanism remains poorly understood and therapeutic options are limited. Here, we employed single-cell RNA sequencing on bone marrow (BM) and EMI samples from a patient with AML presenting pervasive leukemia cutis. A complement C1Q+ macrophage-like leukemia subset, which was enriched within cutis and existed in BM before EMI manifestations, was identified and further verified in multiple patients with AML. Genomic and transcriptional profiling disclosed mutation and gene expression signatures of patients with EMI that expressed high levels of C1Q. RNA sequencing and quantitative proteomic analysis revealed expression dynamics of C1Q from primary to relapse. Univariate and multivariate analysis demonstrated adverse prognosis significance of C1Q expression. Mechanistically, C1Q expression, which was modulated by transcription factor MAF BZIP transcription factor B, endowed leukemia cells with tissue infiltration ability, which could establish prominent cutaneous or gastrointestinal EMI nodules in patient-derived xenograft and cell line-derived xenograft models. Fibroblasts attracted migration of the C1Q+ leukemia cells through C1Q-globular C1Q receptor recognition and subsequent stimulation of transforming growth factor ß1. This cell-to-cell communication also contributed to survival of C1Q+ leukemia cells under chemotherapy stress. Thus, C1Q served as a marker for AML with adverse prognosis, orchestrating cancer infiltration pathways through communicating with fibroblasts and represents a compelling therapeutic target for EMI.

Scalable Fabrication of Structurally Stable Polymer Film with Excellent UV-Shielding, Fluorescent, and Antibacterial Capabilities.

This research presents a new approach to facilely fabricating a multifunctional film using polyvinyl alcohol (PVA) as the base material. The film is modified chemically to incorporate various desirable properties such as high transparency, UV-shielding, antibacterial activity, and fluorescence. The fabrication process of this film is straightforward and efficient. The modified film showed exceptional UV-blocking capability, effectively blocking 100% of UV radiation. It also exhibits strong antibacterial properties. Additionally, the film emitted bright blue fluorescence, which can be useful in various optical and sensing applications. Despite the chemical modification, the film retained the excellent properties of PVA, including high transparency (90%) at 550 nm and good mechanical strength. Furthermore, it demonstrated remarkable stability even under harsh conditions such as exposure to long-term UV radiation, extreme temperatures (-40 or 120 °C), or immersion in different solvents. Overall, this work showcases a promising strategy to develop versatile, structurally stable, transparent, and flexible polymer films with multiple functionalities. These films have potential applications in various fields that require protection, such as packaging materials, biomedical devices, and optical components.

Cone-beam computed tomographic characteristics in degenerative temporomandibular joint disease patients with chewing side preference.

OBJECTIVES: This study is aimed at assessing the Cone-beam computed tomographic (CBCT) characteristics of temporomandibular joints (TMJ) in degenerative temporomandibular joint disease (DJD) patients with chewing side preference (CSP). MATERIALS AND METHODS: CBCT images of 98 patients with DJD (67 with CSP and 31 without CSP) and 22 asymptomatic participants without DJD were measured retrospectively to compare the osteoarthritic changes and the morphology of TMJ. Quantitative analysis of the TMJ radiographic images was performed to present a comparison between the three inter-group groups and between the two sides of the joints. RESULTS: The frequencies of the articular flattening and surface erosion occur more often in the preferred side joints of DJD patients with CSP than the contralateral side. In addition, the horizontal angle of condyle, the depth of glenoid fossa (DGF), and the inclination of articular eminence (IAE) were larger in DJD patients with CSP than that in asymptomatic participants (p<0.05). Also, the condylar anteroposterior dimension of preferred side joints was significantly less than that of non-preferred side (p=0.026), while the width of condyles (p=0.041) and IAE (p=0.045) was greater. CONCLUSIONS: DJD patients with CSP appear to have a higher prevalence of osteoarthritic changes, with the morphological changes such as flat condyle, deep glenoid fossa, and steep articular eminence, which might be considered the characteristic imaging features. CLINICAL RELEVANCE: This study found that CSP is a predisposing factor for the development of DJD, and attention should be paid to the existence of CSP in DJD patients during the clinical practice.

Transparent Cellulose-Based Film with High UV-Blocking Performance Fabricated by Surface Modification using Biginelli Reaction.

Efficient and sustainable ultraviolet (UV)-blocking materials are of great interest in many fields. Herein, novel cellulose-based UV-blocking films are developed via surface modification using the Biginelli reaction. The resulting films exhibited excellent visible transparency (80%) at 550 nm and superhigh UV-blocking performance, which can shield almost 100% UVA and UVB. These features are very stable even the materials are being subjected to solvents, UV irradiation, and thermal treatment. This work provides a novel and facile strategy to fabricate functional cellulose-based films with superhigh anti-ultraviolet performance.

A comparative study of condyle position in temporomandibular disorder patients with chewing side preference using cone-beam computed tomography.

BACKGROUND: Chewing side preference (CSP) could cause structural and morphological changes of temporomandibular joint (TMJ) and has been suggested as one aetiology of temporomandibular disorders (TMDs), but the condylar position in TMD patients with CSP is unknown. OBJECTIVE: To compare the condylar position in the TMD patients with and without CSP. METHODS: Ninety TMD patients with unilateral symptom (69 with CSP and 21 without CSP) and 20 asymptomatic participants received cone-beam computed tomography. The condylar position was determined based on the measurements of sagittal joint spaces. Intergroup and intra-group comparisons of the condylar position were performed. RESULTS: The condyles in asymptomatic participants located nearly randomly in anterior, centric and posterior positions. Patients without CSP had significantly more posterior condyles than asymptomatic participants (57.1% vs 30.0%, p < 0.05). In patients with CSP, 50.7% of the condyles on the preferred chewing side and 42.0% on the unpreferred side located posteriorly, reaching no significant level compared with the asymptomatic participants and patients without CSP (p > 0.05). The symptomatic joints and asymptomatic joints in patients with CSP and without CSP showed no significant differences in condylar position. While patients without CSP had significantly more posterior condyles in symptomatic joints than asymptomatic participants (p < 0.05), patients with CSP showed a trend towards more posterior condyles in symptomatic joints compared with the asymptomatic participants (53.6% vs 30.0%, p = 0.054). CONCLUSION: Condylar position is not a strong indicator to differentiate CSP-related TMDs from non-CSP-related TMDs. Posterior condyle could not be viewed as one indicator of TMD.

Memory impairment of chewing-side preference mice is associated with 5-HT-BDNF signal pathway.

Although tooth loss is a known risk factor of cognitive function, whether and how the chewing-side preference (CSP) affects memory impairment still remains unclear. This study evaluates the behavior changes in mice after the loss of teeth on one side and explores the role of serotonin (5-HT) and brain-derived neurotrophic factor (BDNF) signal pathway within these changes. To this end, CSP mouse models with either the removal of left unilateral molars (CSP-L) or right unilateral molars (CSP-R) were established. Morris water maze test and passive avoidance test were performed to evaluate the mice's learning and memory capacity in the 4th and 8th weeks. The correlation between CSP and brain function changes was validated with changes in 5-HT and BDNF levels. CSP mice's cognitive function was found to be decreased, along with a significant decline in 5-HT1A level, especially in CSP-R mice. BDNF and TrkB levels in CSP-R mice were also significantly lowered. These findings suggest that CSP results in memory impairment, which is associated with the 5-HT-BDNF signaling pathway.

Freely Moldable Modified Starch as a Sustainable and Recyclable Plastic.

Efficiently preparing a starch-based plastic with moisture insensitivity and toughness is a challenge to improve the high-value utilization of polysaccharide resources. Herein, a sustainable, recyclable starch-based plastic was prepared in a facile and eco-friendly way. First, starch acetoacetate (SAA) with different degrees of substitution (DSs) was synthesized by transesterification. Then, the SAA film was obtained through a solvent-free hot-pressing method. Notably, SAA with different DSs exhibited various glass transition temperatures (109-140 °C), and SAA with high DS (>0.84) was insoluble even after boiling in water for 1 h. Also, the maximum fracture strength of SAA film up to 15.5 MPa and a maximum elongation at break up to 30% were reached . In addition, the starch-based plastic film retained the original mechanical properties after three cycles of hot processing. In consideration of the facile preparation process, this protocol provided a new avenue for developing sustainable and recyclable starch-based plastics.

Biosynthesis and metabolic engineering of 1-hydroxyphenazine in Pseudomonas chlororaphis H18.

BACKGROUND: 1-Hydroxyphenazine (1-OH-PHZ) is a phenazine microbial metabolite with broad-spectrum antibacterial activities against a lot of plant pathogens. However, its use is hampered by the low yield all along. Metabolic engineering of microorganisms is an increasingly powerful method for the production of valuable organisms at high levels. Pseudomonas chlororaphis is recognized as a safe and effective plant rhizosphere growth-promoting bacterium, and faster growth rate using glycerol or glucose as a renewable carbon source. Therefore, Pseudomonas chlororaphis is particularly suitable as the chassis cell for the modification and engineering of phenazines. RESULTS: In this study, enzyme PhzS (monooxygenase) was heterologously expressed in a phenazine-1-carboxylic acid (PCA) generating strain Pseudomonas chlororaphis H18, and 1-hydroxyphenazine was isolated, characterized in the genetically modified strain. Next, the yield of 1-hydroxyphenazine was systematically engineered by the strategies including (1) semi-rational design remodeling of crucial protein PhzS, (2) blocking intermediate PCA consumption branch pathway, (3) enhancing the precursor pool, (4) engineering regulatory genes, etc. Finally, the titer of 1-hydroxyphenazine reached 3.6 g/L in 5 L fermenter in 54 h. CONCLUSIONS: The 1-OH-PHZ production of Pseudomonas chlororaphis H18 was greatly improved through systematically engineering strategies, which is the highest, reported to date. This work provides a promising platform for 1-hydroxyphenazine engineering and production.

Cone-beam computed tomographic assessment of the inclination of the articular eminence in patients with temporomandibular disorders and chewing side preference.

BACKGROUND: Chewing side preference (CSP) has been proposed as one etiology of temporomandibular disorders (TMDs) as it can induce the structural changes of the temporomandibular joint. But its association with the inclination of the articular eminence (IAE) is unknown. This study aimed to compare IAE between patients with CSP and without CSP. METHODS: Cone-beam computed tomography images of 90 patients with TMD (mean age of 45.6 years, 69 with CSP, 21 without CSP) and 20 participants without TMD and CSP (mean age of 41.3 years) were measured to compare IAE and depth of the glenoid fossa (DGF) RESULTS: IAE and DGF showed a positive correlation among all the participants. Compared with the participants without TMD and CSP, the TMD patients without CSP presented a similar IAE but with a significantly higher value of DGF (p < 0.05); in contrast, the TMD patients with CSP presented a significantly greater IAE and DGF (p < 0.05). No bilateral differences in IAE and DGF were observed in all the participants. Except the male patients with CSP had a deeper fossa than did the female, no differences in IAE and DGF according to gender were observed. CONCLUSIONS: TMD patients with CSP seem to have a deep glenoid fossa with steep eminence which might be considered one characteristic imaging feature.

Low Frequency Vibration Visual Monitoring System Based on Multi-Modal 3DCNN-ConvLSTM.

Low frequency vibration monitoring has significant implications on environmental safety and engineering practices. Vibration expressed by visual information should contain sufficient spatial information. RGB-D camera could record diverse spatial information of vibration in frame images. Deep learning can adaptively transform frame images into deep abstract features through nonlinear mapping, which is an effective method to improve the intelligence of vibration monitoring. In this paper, a multi-modal low frequency visual vibration monitoring system based on Kinect v2 and 3DCNN-ConvLSTM is proposed. Microsoft Kinect v2 collects RGB and depth video information of vibrating objects in unstable ambient light. The 3DCNN-ConvLSTM architecture can effectively learn the spatial-temporal characteristics of muti-frequency vibration. The short-term spatiotemporal feature of the collected vibration information is learned through 3D convolution networks and the long-term spatiotemporal feature is learned through convolutional LSTM. Multi-modal fusion of RGB and depth mode is used to further improve the monitoring accuracy to 93% in the low frequency vibration range of 0-10 Hz. The results show that the system can monitor low frequency vibration and meet the basic measurement requirements.

A D-Shaped Photonic Crystal Fiber Refractive Index Sensor Coated with Graphene and Zinc Oxide.

A surface plasmon resonance (SPR) sensor based on a D-shaped photonic crystal fiber (PCF) with an uncomplicated structure is proposed to detect the change of refractive index of liquid analytes, and numerical simulation is carried out by the finite element method (FEM). Using silver as the plasmonic metal, the performances of the SPR-PCF sensor coated with a graphene layer and zinc oxide (ZnO) layer were assessed. The sensor designed is only coated with material on the polished surface, which makes the sensor production uncomplicated and solves the problems of filling material in the hole and coating on the hole wall. The effects of structural parameters such as graphene layer thickness, silver layer thickness, ZnO thickness, lattice spacing and manufacturing tolerance of blowhole diameter on the sensor performance were numerically simulated. The numerical results show that the sensitivity of the SPR-PCF sensor coated with 25 nm ZnO is highest in the ZnO thickness range from 10 to 25 nm. In the refractive index range of 1.37-1.41 for liquid analyte, the maximum sensitivity and corresponding resolution reach 6000 nm/RIU and 1.667 × 10-5, respectively. In addition, the sensor has good stability and high structural tolerance under the tolerance of ±5% of blowhole diameter. This work has wide application value in the detection of biochemical analytes, water pollution monitoring, food quality, and medical diagnosis.

Role of TiO2 Nanotubes on the Surface of Implants in Osseointegration in Animal Models: A Systematic Review and Meta-Analysis.

PURPOSE: This systematic review and meta-analysis aims to synthesize evidence relating to the effects of TiO2 nanotubes on osseointegration in animal models. MATERIALS AND METHODS: The focused question was "Does the preparation of TiO2 nanotubes on the surface of implants enhance osseointegration?" Searches were performed for relevant manuscripts up to September 2019 using the PubMed, Embase, Scopus and Google Scholar databases with terms such as "TiO2 nanotubes" in combination with "osseointegration", "osteogenic", "osteogenesis", and "bone regeneration". The titles, abstracts and full texts of the manuscripts were reviewed in accordance with the eligibility criteria. The meta-analysis were then performed to analyze the effects of TiO2 nanotubes in bone-implant contact (BIC) and biomechanical tests. RESULTS: Fourteen manuscripts were included for the systematic review and meta-analysis. Eleven studies showed that the results of a histological analysis, micro-CT evaluation and biomechanical tests were significantly higher near TiO2 than titanium. The meta-analysis demonstrating similar results in the BIC and biomechanical tests were obtained. The selected studies also showed the preferable nanotube diameter (70, 80, or 100 nm) to enhance osseointegration in BIC and/or bone area (BA). CONCLUSION: TiO2 nanotubes, especially those with large diameters, enhanced osseointegration near titanium implants. Compared to bare nanotubes, TiO2 nanotube composite coatings resulted in higher osteogenic ability.

The molecular mechanism study of insulin in promoting wound healing under high-glucose conditions.

BACKGROUND: Wound healing is a complex process in bone development. The aim of this study was to explore the molecular mechanism study of insulin in promoting wound healing. METHODS: Firstly, the acute human monocyte leukemia cell lines were induced to differentiate into macrophages. Secondly, the porphyromonas gingivalis was applied to mix with the differentiated macrophages. Thirdly, the effect of different concentrations of insulin (0 ng/mL, 5 ng/mL, 50 ng/mL, 100 ng/mL, 200 ng/mL, 500 ng/mL, and 1,000 ng/mL) on the phagocytosis of macrophages and production of reactive oxygen species was investigated. Depending on these experiments, the optimal insulin concentration was used to treat the macrophages at different time points (0 hours and 0.5 hours) to identify the differentially expressed mRNAs. Finally, functional analysis including gene ontology (GO) and the Kyoto Encyclopedia of Genes and Genomes (KEGG) and protein-protein interaction (PPI) analysis was carried out to explore the biological function of these differentially expressed mRNAs. RESULTS: The test of phagocytosis function and production of reactive oxygen species showed that 200 ng/mL insulin treatment had a significant influence on antibacterial and production of reactive oxygen species. In RNA sequencing, a total of 415 (245 upregulated and 170 downregulated) differentially expressed mRNAs were identified between different time points. Two important signaling pathways including endocytosis and systemic lupus erythematosus were found in the KEGG enrichment analysis. In the PPI network, several hub proteins encoded by differentially expressed mRNA including ALB, HIP1R, RAB5A, HIST1H2BJ, HIST1H3G, and HIST1H2BO were identified. CONCLUSION: Our work demonstrated that several differentially expressed mRNAs, such as EGR1, RAB34, ALB, HIP1R, RAB5A, HIST1H2BJ, HIST1H3G, and HIST1H2BO and two important signaling pathways including endocytosis and systemic lupus erythematosus may play important roles in the bone wound healing.

Multi-responsive, self-healing and adhesive PVA based hydrogels induced by the ultrafast complexation of Fe3+ ions.

Herein, a PVA (polyvinyl alcohol)-based multi-responsive hydrogel was prepared by introducing the dynamic and reversible supramolecular complexation between polyvinyl alcohol acetoacetate (PVAA) and Fe3+ ions within 20 s at room temperature. PVAA-Fe hydrogels could be achieved by the simple mixing process of a PVAA aqueous solution with FeCl3 aqueous solution. The soluble PVAA was synthesized by the reaction of PVA with tert-butyl acetoacetate (t-BAA) via transesterification in dimethyl sulfoxide (DMSO). The chemical structure of PVAA was systematically characterized by FT-IR and 1H NMR spectroscopy. The resulting hydrogel showed excellent self-healing behavior without other external stimuli. It was also demonstrated that the PVAA-Fe hydrogel exhibited multi-responsive properties, such as responsiveness to pH, redox, light irradiation and temperature. In addition, the presence of Fe3+ ions and Cl- ions in the gel imparted the PVAA-Fe hydrogel with favorable conductivity. Therefore, the strategy for the facile preparation of the hydrogel in this work could provide a benign and versatile method for achieving multi-functional soft materials for various applications such as smart devices, logic gates, and sensors.

Tantalum-incorporated hydroxyapatite coating on titanium implants: its mechanical and in vitro osteogenic properties.

OBJECTIVE: The fabrication of bioactive coatings on metallic implants to enhance osseointegration has become a topic of general interest in orthopedics and dentistry. Hydroxyapatite (HA) coating has been shown to induce bone formation and promote bone-implant integration. Unfortunately, poor mechanical performance has hindered this from becoming a favorable coating material. The majority of present studies have focused in incorporating different elements into HA coatings to improve mechanical properties. In recent years, tantalum (Ta) has received increasing attention due to its excellent biocompatibility and corrosion resistance. The aim of on the present study was to investigate the fabrication and biological performance of Ta-incorporated HA coatings. METHODS: Ta-incorporated HA coatings were fabricated using the plasma spray technique on a titanium substrate, and the surface characteristics and mechanical properties were examined. In addition, the effects of Ta-incorporated HA coatings on the biological behavior of mesenchymal stem cells (BMSCs) were investigated. RESULTS: Ta-incorporated HA coatings with microporous structure had higher roughness and wettability. In addition, the bonding strength of Ta/HA coatings with the substrate was substantially superior to HA coatings. Furthermore, Ta-incorporated HA coatings not only facilitated initial cell adhesion and faster proliferation, but also promoted the osteogenic differentiation of BMSCs. CONCLUSION: These results indicate that the incorporation of Ta could improve mechanical performance and increase the osteogenic activity of HA coatings. The Ta-incorporated HA coating fabricated by plasma spraying is expected to be a promising bio-coating material for metallic implants.

The Clinical Performance of Narrow Diameter Implants Versus Regular Diameter Implants: A Meta-Analysis.

The purpose of this study is to analyze 1- and 3-year clinical performances of narrow diameter implants (NDIs) versus regular diameter implants (RDIs). A search of electronic databases and a manual search was performed for the time period January 2000 to April 2018. A meta-regression was used to evaluate the effects of the "fixed effects" model on the implant survival rates, prosthesis success rates and marginal bone loss (MBL) with follow-up time of 1 year and 3 years. Of the 11 studies included, the overall combined 1-year implant survival rates were 98.14% for NDIs and 98.20% for RDIs. The overall combined 3-year implant survival rates were 98.71% for NDIs and 98.84% for RDIs. The corresponding values for 1-year prosthesis success rates were 96.94% for NDIs and 99.25% for RDIs. The corresponding values for 3-year prosthesis success rates were 89.25% for NDIs and 96.55% for RDIs. The meta-regression showed no significant differences between NDIs and RDIs regarding implant survival rates, prosthesis success rates, and MBL in 1-year and 3-year follow-up (P > .05). The results of this meta-analysis concluded that the implant diameter did not affect its survival rates, prosthesis success rates, and MBL in 1 and 3 years. The use of NDIs instead of bone augmentation procedures with RDIs did not affect its survival rates, prosthesis success rates, and MBL in the short-term and middle-term. However, more high-quality randomized controlled trials and long follow-up studies are needed on this topic.

Zoledronate and high glucose levels influence osteoclast differentiation and bone absorption via the AMPK pathway.

Bisphosphonates, the main drugs to treat osteoporosis, have been shown to protect against bone loss in diabetic osteoporosis. However, the effects of the bisphosphonate zoledronate (ZOL) on osteoclast differentiation and function in a high glucose environment as well as the involvement of the adenosine activated protein kinase (AMPK) pathway remain unclear. In the current study, RAW264.7 cells were induced into osteoclasts, divided into low glucose, high glucose, low glucose + ZOL, and high glucose + ZOL groups, which were tested for cell proliferation, cell migration, integrity of the osteoclast sealing zone, osteoclast differentiation, bone absorption, and protein and mRNA expression of genes in the AMPK pathway. We demonstrated that high glucose promoted the expression of AMPK, p-AMPK, while inhibited nuclear factor of activated T cells 1 (NFATc1), spleen tyrosine kinase (SYK), cathepsin K (CTSK), and tartrate-resistant acid phosphatase (TRAP), which influenced osteoclast differentiation and bone absorption. Upon addition of ZOL to high glucose, the expression of AMPK, p-AMPK increased and the expression of NFATc1, SYK, CTSK, TRAP decreased, while osteoclast differentiation and bone absorption were further inhibited. Further more, when added Compound C (AMPK antagonist), we found the expression of AMPK, p-AMPK, decreased, whereas NFATc1, SYK, and TRAP increased. In contrast, AMPK and p-AMPK increased and NFATc1, SYK, CTSK and TRAP decreased upon addition of AICAR, an AMPK agonist. In conclusion, the results suggest AMPK has potential as a new target for the treatment of osteoporosis, the high glucose environment promoted RAW264.7 cell migration, but suppressed osteoclast differentiation and bone absorption, and ZOL suppressed osteoclast migration, differentiation, and bone absorption via the AMPK pathway.

microRNA-188 is downregulated in oral squamous cell carcinoma and inhibits proliferation and invasion by targeting SIX1.

microRNA-188 expression is downregulated in several tumors. However, its function and mechanism in human oral squamous cell carcinoma (OSCC) remains obscure. The present study aims to identify the expression pattern, biological roles, and potential mechanism by which miR-188 dysregulation is associated with oral squamous cell carcinoma. Significant downregulation of miR-188 was observed in OSCC tissues compared with paired normal tissues. In vitro, gain-of-function, loss-of-function experiments were performed to examine the impact of miR-188 on cancer cell proliferation, invasion, and cell cycle progression. Transfection of miR-188 mimics suppressed Detroit 562 cell proliferation, cell cycle progression and invasion, with downregulation of cyclin D1, MMP9, and p-ERK. Transfection of miR-188 inhibitor in FaDu cell line with high endogenous expression exhibited the opposite effects. Using fluorescence reporter assays, we confirmed that SIX1 was a direct target of miR-188 in OSCC cells. Transfection of miR-188 mimics downregulated SIX1 expression. SIX1 siRNA treatment abrogated miR-188 inhibitor-induced cyclin D1 and MMP9 upregulation. In addition, we found that SIX1 was overexpressed in 32 of 80 OSCC tissues. In conclusion, this study indicates that miR-188 downregulation might be associated with oral squamous cell carcinoma progression. miR-188 suppresses proliferation and invasion by targeting SIX1 in oral squamous cell carcinoma cells.

High glucose microenvironments inhibit the proliferation and migration of bone mesenchymal stem cells by activating GSK3ß.

Diabetes mellitus involves metabolic changes that can impair bone repair. Bone mesenchymal stem cells (BMSCs) play an important role in bone regeneration. However, the bone regeneration ability of BMSCs is inhibited in high glucose microenvironments. It can be speculated that this effect is due to changes in BMSCs' proliferation and migration ability, because the recruitment of factors with an adequate number of MSCs and the microenvironment around the site of bone injury are required for effective bone repair. Recent genetic evidence has shown that the Cyclin D1 and the CXC receptor 4 (CXCR-4) play important roles in the proliferation and migration of BMSCs. In this study we determined the specific role of glycogen synthase kinase-3ß (GSK3ß) in the proliferation and migration of BMSCs in high glucose microenvironments. The proliferation and migration ability of BMSCs were suppressed under high glucose conditions. We showed that high glucose activates GSK3ß but suppresses CXCR-4, ß-catenin, LEF-1, and cyclin D1. Inhibition of GSK3ß by LiCl led to increased levels of ß-catenin, LEF-1, cyclin D1, and CXCR-4 expression. Our data indicate that GSK3ß plays an important role in regulating the proliferation and migration of BMSCs by inhibiting cyclin D1 and CXCR-4 under high glucose conditions.

Intrapleural Fibrinolytic Therapy for Residual Coagulated Hemothorax After Lung Surgery.

BACKGROUND: Many studies have described the use of intrapleural fibrinolytics for the treatment of complex pleural processes and traumatic hemothorax, but data are scarce regarding their use for hemothorax after lung surgery. OBJECTIVE: To evaluate the utility of intrapleural fibrinolytic therapy with urokinase for residual coagulated hemothorax (blood clot accumulation in the pleural cavity) after lung surgery. METHODS: From July 2009 to November 2013, 46 patients (33 males; mean age, 56.9 ± 10.7 years) were treated with intrapleural urokinase (250,000 IU per dose) for residual hemothorax after lung surgery. Complete response was defined as clinical improvement with complete drainage of the retained collection shown by chest X-ray, and partial response as substantial resolution with minimal residual opacity (<25 % of the thorax). Follow-up was at least 30 days. RESULTS: The procedure was successful in 42 patients (91.3 %), with complete response observed in 35/46 patients (76.1 %) and partial response in 7/46 (15.2 %). These 42 patients did not require re-intervention for fluid accumulation in the pleural cavity. Treatment failed in 4 patients (8.7 %): one developed bronchopleural fistula that later resolved spontaneously and three (6.5 %) required thoracoscopic drainage for pleural cavity fluid accumulation and lung collapse. No patient required thoracotomy for total decortication. Intrapleural urokinase administration was not associated with serious adverse events, including bleeding complications or allergic reactions. CONCLUSIONS: Intrapleural fibrinolytic agents should be considered a useful therapeutic option for the treatment of postoperative residual hemothorax. This method appears to be safe and effective in >90 % of patients with postoperative hemothorax.