Lycium barbarum polysaccharides attenuate nonylphenol and octylphenol-induced oxidative stress and neurotransmitter disorders in PC-12 cells.

Nonylphenol (NP) and octylphenol (OP) are environmental contaminants with potential endocrine disrupting effects. However, there is limited research on the mechanisms and intervention of combined NP and OP exposure-induced neurotoxicity. This study aims to explore the cytotoxicity of combined NP and OP exposure and evaluate the potential of Lycium barbarum polysaccharides (LBP) in mitigating the aforementioned toxicity. In present study, LBP (62.5, 125 and 250 µg/mL) were applied to intervene rat adrenal pheochromocytoma (PC-12) cells treated with combined NP and OP (NP: OP = 4:1, w/w; 1, 2, 4 and 8 µg/mL). The results showed that NP and OP induced oxidative stress, disrupted the 5-hydroxytryptamine (5-HT) and cholinergic systems in PC-12 cells. Additionally, they activated the p38 protein kinase (p38) and suppressed the expression of silent information regulation type 1 (SIRT1), monoamine oxidase A (MAOA), phosphorylated cyclic-AMP response binding protein (p-CREB), brain-derived neurotrophic factor (BDNF) and phosphorylated tropomyosin-related kinase receptor type B (p-TrkB). However, N-acetyl-L-cysteine (NAC) treatment counteracted the changes of signalling molecule p38, SIRT1/MAOA and CREB/BDNF/TrkB pathways-related proteins induced by NP and OP. LBP pretreatment ameliorated combined NP and OP exposure-induced oxidative stress and neurotransmitter imbalances. Furthermore, the application of LBP and administration of a p38 inhibitor both reversed the alterations in the signaling molecule p38, as well as the proteins associated to the SIRT1/MAOA and CREB/BDNF/TrkB pathways. These results implied that LBP may have neuroprotective effects via p38-mediated SIRT1/MAOA and CREB/BDNF/TrkB pathways.

Lycium barbarum polysaccharides attenuate oxidative stress and mitochondrial toxicity induced by mixed plasticizers in HepG2 cells through activation of Nrf2.

AIMS: In daily life, it is common for humans to be exposed to multiple phthalate esters (PAEs). However, there is limited research on the mechanisms and intervention of combined PAEs toxicity. This study aims to explore the cytotoxicity of combined PAEs and evaluate the potential of Lycium barbarum polysaccharides (LBP) in mitigating the aforementioned toxicity. MAIN METHODS: LBP (62.5, 125 and 250 µg/mL) were applied to intervene HepG2 cells treated with DEHP and DBP mixtures (50, 100, 200, 400 and 800 µg/mL). Western Blot and different kits were mainly performed in our study. KEY FINDINGS: DEHP and DBP mixtures suppressed the expression of nuclear factor E2-related factor 2 (Nrf2), heme oxygenase-1 (HO-1) and activated MAPK pathway by increasing ROS. Combined DEHP and DBP exposure reduced ATP content and inhibited the mitochondrial biogenesis pathway in HepG2 cells through oxidative stress, which in turn caused cytotoxicity. LBP reduced oxidative stress and cell death induced by mixed plasticizers, upregulated Nrf2 levels and mitochondrial biogenesis pathway levels and inhibited MAPK pathway activation. Notably, after treating HepG2 cells with Nrf2-specific inhibitor (ML385, 0.5 µM), we found that the activation of Nrf2 played a crucial role on LBP intervention of DEHP and DBP induced HepG2 cytotoxicity. SIGNIFICANCE: This study not only enhances our understanding of the toxicological effects caused by combined PAEs exposure, but also has significant implications in devising strategies to mitigate the toxicological consequences of combined exposure to exogenous chemicals through the investigation of the role of LBP.

Anoikis-related genes signature development for clear cell renal cell carcinoma prognosis and tumor microenvironment.

Clear cell renal cell carcinoma (ccRCC) is one of the most common primary malignancies of the urinary tract, highly heterogeneous, and increasing in incidence worldwide. Anoikis is a specific type of programmed cell death in which solid tumor cells or normal epithelial cells that do not have metastatic properties lose adhesion to the extracellular matrix or undergo inappropriate cell adhesion-induced apoptosis. Anoikis is thought to play a critical role in tumorigenesis, maintenance, and treatment, according to an increasing amount of research. However, there is still some uncertainty regarding the general impact of anoikis-related genes (ARGs) on the prognostic importance, tumor microenvironment characteristics, and treatment reaction of ccRCC patients. For this study, we used The Cancer Genome Atlas (TCGA) and Gene Expression Omnibus datasets to access the RNA sequencing results and clinical information from ccRCC patients. 29 ARGs related to survival were found using differential analysis and univariate Cox regression analysis. The samples were then divided into two clusters that had different immune traits via unsupervised cluster analysis using 29 prognosis-associated differently expressed ARGs. Then, to build an ARGs signature, 7 genes (PLAU, EDA2R, AFP, PLG, TUBB3, APOBEC3G, and MALAT1) were found using Least Absolute Shrinkage and Selection Operator regression analysis. The new ARGs signature demonstrated outstanding prognostic capability for ccRCC patients' overall survival. In conclusion, for ccRCC patients, we created an ARGs signature that strongly connects to immunological traits and therapy response. Clinicians may find this ARGs signature helpful in developing more individualized and detailed treatment strategies for ccRCC patients.

Analysis of cuproptosis-related genes in Ulcerative colitis and immunological characterization based on machine learning.

Cuproptosis is a novel form of cell death, mediated by protein lipid acylation and highly associated with mitochondrial metabolism, which is regulated in the cell. Ulcerative colitis (UC) is a chronic inflammatory bowel disease that recurs frequently, and its incidence is increasing worldwide every year. Currently, a growing number of studies have shown that cuproptosis-related genes (CRGs) play a crucial role in the development and progression of a variety of tumors. However, the regulatory role of CRGs in UC has not been fully elucidated. Firstly, we identified differentially expressed genes in UC, Likewise, CRGs expression profiles and immunological profiles were evaluated. Using 75 UC samples, we typed UC based on the expression profiles of CRGs, followed by correlative immune cell infiltration analysis. Using the weighted gene co-expression network analysis (WGCNA) methodology, the cluster's differentially expressed genes (DEGs) were produced. Then, the performances of extreme gradient boosting models (XGB), support vector machine models (SVM), random forest models (RF), and generalized linear models (GLM) were constructed and predicted. Finally, the effectiveness of the best machine learning model was evaluated using five external datasets, receiver operating characteristic curve (ROC), the area under the curve of ROC (AUC), a calibration curve, a nomogram, and a decision curve analysis (DCA). A total of 13 CRGs were identified as significantly different in UC and control samples. Two subtypes were identified in UC based on CRGs expression profiles. Immune cell infiltration analysis of subtypes showed significant differences between immune cells of different subtypes. WGCNA results showed a total of 8 modules with significant differences between subtypes, with the turquoise module being the most specific. The machine learning results showed satisfactory performance of the XGB model (AUC = 0.981). Finally, the construction of the final 5-gene-based XGB model, validated by the calibration curve, nomogram, decision curve analysis, and five external datasets (GSE11223: AUC = 0.987; GSE38713: AUC = 0.815; GSE53306: AUC = 0.946; GSE94648: AUC = 0.809; GSE87466: AUC = 0.981), also proved to predict subtypes of UC with accuracy. Our research presents a trustworthy model that can predict the likelihood of developing UC and methodically outlines the complex relationship between CRGs and UC.

Study on the Mechanical Properties of Perforated Steel Plate Reinforced Concrete.

In this paper, the mechanical properties of perforated steel plate reinforced concrete were studied. Through the compression test of the specimen, the failure mode, the compressive ultimate bearing capacity, and the stress−strain curve of the specimen were obtained. The results show that the compressive strength of perforated steel plate reinforced concrete is twice that of the same grade of plain concrete; through the pull-out test of the specimen, the failure mode and the ultimate uplift bearing capacity were obtained. The finite element software ANSYS was used to simulate the perforated steel plate reinforced concrete specimen, and the results show that the model is reliable. Through the range analysis method, the influence degree of the three factors of the thickness of the perforated steel plate, the hole diameter, and the hole spacing on the compressive strength and the ultimate bearing capacity of the pull-out was studied, and the optimal solution was obtained. The analysis results show that the order of the three factors on the compression and pull-out tests is: the plate thickness of the perforated steel plate > the hole diameter > the hole spacing; the optimal combination of the compressive strength of the perforated steel plate reinforced concrete specimen is that the thickness of the perforated steel plate is 0.75 mm, the diameter of the perforated steel plate is 15 mm, and the spacing of the perforated steel plate is 5 mm; the optimal combination of the ultimate bearing capacity of the pull-out is that the thickness of the steel plate with holes is 1.0 mm, the diameter of the steel plate with holes is 15 mm, and the spacing of the steel plate with holes is 15 mm.

Study on Mechanical Properties of Multi-Cavity Steel-Concrete Composite Beam.

This paper proposes a new form of composite beam: a multi-cavity steel-concrete composite beam. This composite beam uses internal perforated steel plate to connect the concrete with the steel structure, and shear connectors are no longer required, which is more suitable for industrial production. The mechanical properties of a multi-cavity steel-concrete composite beam in industrial applications are studied to avoid failures. In this paper, two multi-cavity steel-concrete composite beams with a size of 2500 mm × 200 mm × 300 mm were prepared, in which the angle of internal porous steel plate was set as 60° and 75°, respectively. A full-scale static load test was conducted on the beams to research its deformation and failure modes. The finite element software ANSYS was used to perform finite element modeling of multi-cavity steel-concrete composite beams and to analyze the influence of concrete strength, steel strength, porosity, and the angle of internal porous steel plate on the mechanical properties of composite beams. The results are as follows: before the composite beam reaches its serviceability limit state, its deformation basically shows a linear change; with the increase of load, the plastic deformation is gradually obvious, which can still provide a certain bearing capacity in the failure stage; the bearing capacity of the composite beam is positively correlated with the strength of concrete and steel, while negatively correlated with the porosity and the angle of internal porous steel plate; composite beams have large bearing capacity, good ductility and integrity.

Functional Macromolecular Adhesives for Bone Fracture Healing.

Compared with traditional internal fixation devices, bone adhesives are expected to exhibit remarkable advantages, such as improved fixation of comminuted fractures and maintained spatial location of fractured scattered bone pieces in treating bone injuries. In this review, different bone adhesives are summarized from the aspects of bone tissue engineering, and the applications of bone adhesives are emphasized. The concepts of "liquid scaffold" and "liquid plate" are proposed to summarize two different research directions of bone adhesives. Furthermore, significant advances of bone adhesives in recent years in mechanical strength, osseointegration, osteoconductivity, and osteoinductivity are discussed. We conclude this topic by providing perspectives on the state-of-the-art research progress and future development trends of bone adhesives. We hope this review will provide a comprehensive summary of bone adhesives and inspire more extensive and in-depth research on this subject.

[Effects of oral propranolol on urine bFGF, MMP-2, MMP-9 expression in children with proliferative infantile hemangioma].

PURPOSE: To investigate the effect of propranolol on urine bFGF, MMP-2, MMP-9 expression of children with proliferative infantile hemangioma(IH), so as to clarify the mechanism of propranolol in treating IH. METHODS: From June 2018 to June 2019, thirty-four children with proliferative IH were treated with oral propranolol. In addition, twenty-one normal children (age <12 months) were chosen as the control group. 10 mL of sterile morning urine were collected before and 2 months after oral administration of propranolol in infants with IH. All blood samples were placed in ordinary disinfection test tubes, centrifuged at 1 000 r/min for 10 min, the supernatant of urine was collected and stored separately. The urine samples of normal control group were processed in the same way. The expression levels of bFGF in the urine of children with proliferative IH before and 2 months after oral administration of propranolol and in the normal control group were detected by enzyme-linked immunosorbent assay (ELISA). The expression levels of MMP-2 and MMP-9 in the urine of children with proliferative IH before and 2 months after treatment and in the control group were detected by gelatin zymography. SPSS 22.0 software package was used to analyze the data. RESULTS: Two months after oral propranolol treatment, the concentration of bFGF in urine was significantly lower than that before treatment (P<0.01), but still significantly higher than that in the control group (P<0.05). The expression levels of MMP-2 and MMP-9 were significantly lower than those before treatment(P<0.01), but still higher than those in the control group (P<0.05). CONCLUSIONS: One of the mechanisms of propranolol in the treatment of children with proliferative IH may be through inhibiting the expression levels of bFGF, MMP-2 and MMP-9, and then inhibiting the proliferation and angiogenesis of vascular endothelial cells in IH, so as to achieve the effect of treating hemangioma. The detection of the expression levels of bFGF, MMP-2 and MMP-9 in urine can be used as the index for oral propranolol treatment of children with proliferative IH.

microRNA-454-mediated NEDD4-2/TrkA/cAMP axis in heart failure: Mechanisms and cardioprotective implications.

The current study aimed to investigate the mechanism by which miR-454 influences the progression of heart failure (HF) in relation to the neural precursor cell expressed, developmentally downregulated 4-2 (NEDD4-2)/tropomyosin receptor kinase A (TrkA)/cyclic adenosine 3',5'-monophosphate (cAMP) axis. Sprague-Dawley rats were used to establish a HF animal model via ligation of the left anterior descending branch of the coronary artery. The cardiomyocyte H9c2 cells were treated with H2 O2 to stimulate oxidative stress injury in vitro. RT-qPCR and Western blot assay were subsequently performed to determine the expression patterns of miR-454, NEDD4-2, TrkA, apoptosis-related proteins and cAMP pathway markers. Dual-luciferase reporter gene assay coupled with co-immunoprecipitation was performed to elucidate the relationship between miR-454, NEDD4-2 and TrkA. Gain- or loss-of-function experiments as well as rescue experiments were conducted via transient transfection (in vitro) and adenovirus infection (in vivo) to examine their respective functions on H9c2 cell apoptosis and myocardial damage. Our results suggested that miR-454 was aberrantly downregulated in the context of HF, while evidence was obtained suggesting that it targeted NEDD4-2 to downregulate NEDD4-2 in cardiomyocytes. miR-454 exerted anti-apoptotic and protective effects on cardiomyocytes through inhibition of NEDD4-2, while NEDD4-2 stimulated ubiquitination and degradation of TrkA protein. Furthermore, miR-454 activated the cAMP pathway via the NEDD4-2/TrkA axis, which ultimately suppressed cardiomyocyte apoptosis and attenuated myocardial damage. Taken together, the key findings of the current study highlight the cardioprotective role of miR-454, which is achieved through activation of the cAMP pathway by impairing NEDD4-2-induced TrkA ubiquitination.

Propranolol Participates in the Treatment of Infantile Hemangioma by Inhibiting HUVECs Proliferation, Migration, Invasion, and Tube Formation.

OBJECTIVE: Infantile hemangiomas (IHs) are the most common benign tumors in infancy. The purpose of this study was to study the effects of propranolol on the function of human umbilical vein endothelial cells (HUVECs), in order to preliminarily elucidate the mechanism of propranolol in the treatment of IHs. METHODS: HUVECs were treated with different concentrations of propranolol (30 µM, 60 µM, 90 µM, and 120 µM) with or without VEGF. Their proliferation, migration, invasion, adhesion, and tube formation ability were tested by using CCK-8, wound healing assay, transwell, cell adhesion assay, and tube formation assay. The expressions of HUVECs angiogenesis signaling molecules pERK/ERK, pAKT/AKT, p-mTOR/mTOR, and pFAK/FAK were detected by Western blot. RESULTS: Compared with the control group, propranolol could significantly inhibit the proliferation, migration, invasion, adhesion, and tube formation of HUVECs. Further studies showed that it could not only inhibit the migration, invasion, and tube formation ability of HUVECs after VEGF induction but also inhibit the phosphorylated protein expressions of angiogenesis-related signaling molecules like AKT, mTOR, ERK, and FAK in HUVECs, with a concentration-dependent inhibitory effect. CONCLUSION: Propranolol can inhibit the proliferation, migration, invasion, adhesion, and tube formation of hemangioma endothelial cells; block VEGF-mediated angiogenesis signaling pathway; suppress the expressions of downstream angiogenesis-related signaling molecules; and ultimately achieve the effect of treatment of IHs.

Synthesis and Evaluation of BMMSC-seeded BMP-6/nHAG/GMS Scaffolds for Bone Regeneration.

Bioactive scaffolding materials and efficient osteoinductive factors are key factors for bone tissue engineering. The present study aimed to mimic the natural bone repair process using an osteoinductive bone morphogenetic protein (BMP)-6-loaded nano-hydroxyapatite (nHA)/gelatin (Gel)/gelatin microsphere (GMS) scaffold pre-seeded with bone marrow mesenchymal stem cells (BMMSCs). BMP-6-loaded GMSs were prepared by cross-linking and BMP-6/nHAG/GMS scaffolds were fabricated by a combination of blending and freeze-drying techniques. Scanning electron microscopy, confocal laser scanning microscopy, and CCK-8 assays were carried out to determine the biocompatibility of the composite scaffolds in vitro. Alkaline phosphatase (ALP) activity was measured to evaluate the osteoinductivity of the composite scaffolds. For in vivo examination, critical-sized calvarial bone defects in Sprague-Dawley rats were randomly implanted with BMMSC/nHAG/GMS and BMMSC/BMP-6/nHAG/GMS scaffolds, and compared with a control group with untreated empty defects. The BMP-6-loaded scaffolds showed cytocompatibility by favoring BMMSC attachment, proliferation, and osteogenic differentiation. In radiological and histological analyses, the BMMSC-seeded scaffolds, especially the BMMSC-seeded BMP-6/nHAG/GMS scaffolds, significantly accelerated new bone formation. It is concluded that the BMP-6/nHAG/GMS scaffold possesses excellent biocompatibility and good osteogenic induction activity in vitro and in vivo, and could be an ideal bioactive substitute for bone tissue engineering.

The Ex Vivo Time of Fresh Autologous Cartilage Before Transplantation and Cartilage Absorption Degree.

OBJECTIVE: This study aims to determine the relationship between the time of autogenous cartilage in vitro and the degree of absorption in animal experiments. METHODS: New Zealand white rabbits were randomly divided into 3 groups according to the time of cartilage in vitro: 1-hour group, 2-hour group, and 3-hour group. A volume of ear cartilage was taken and transplanted into the back, according to the group. After 1 month, the volume was taken out and remeasured. Then, these were compared by scanning electron microscopy and hematoxylin and eosin staining. RESULTS: The cartilage bulk absorption level of different groups is different (P < 0.05). There was statistical significance when the 3-hour group was compared with the other 2 groups (P < 0.05). This shows that cartilage volume absorption level becomes higher after 3 hours. Scanning electron microscopy revealed that before and after transplantation, the arrangement of collagen fibers and the gap between these fibers changed. Hematoxylin and eosin staining revealed that there were some morphological changes in chondrocytes, and the degree of chondrocyte apoptosis increased with time, which was accompanied by granulation tissue formation. In addition, the cartilage tissue survived after transplantation. CONCLUSION: The change in cartilage volume was more obvious after 3 hours of autogenous fresh cartilage transplantation, when compared with that of the first 2 hours. The longer the time of light microscopy was, the longer the apoptosis of cartilage cells, the more serious the destruction of collagen fibers and the cartilage matrix, and the greater the absorption of cartilage and the new chondrocytes.

Improvement of Aesthetic and Nasal Airway in Patients With Cleft Lip Nasal Deformities: Rhinoplasty With Septal Cartilage Graft and Septoplasty.

OBJECTIVE: To assess the improvement of nasal morphologies and ventilation after septal cartilage graft and septoplasty of patients with unilateral cleft lip and palate (UCLP). DESIGN: Retrospective case-control study. SETTING: Tertiary stomatology hospital. PATIENTS: In total, 118 patients with UCLP who had been diagnosed with a secondary nasal deformity and had reconstructive rhinoplasty and/or septoplasty between 2010 and 2015. MAIN OUTCOME MEASURES: Nasal Obstruction Symptoms Evaluation (NOSE) questionnaire, septum deviated angle, rhinoplasty satisfaction questionnaire, and 3-dimensional photographs. RESULTS: Average follow-up period was approximately 12 months for both groups. NOSE and 3-dimensional computed tomography (3DCT) analysis demonstrated postoperative improvement in nasal airway function of those patients who underwent rhinoplasty and septoplasty simultaneously ( P < .05). Subjective assessment by patients' visual analog scale (VAS) and objective assessment by 3-dimensional stereophotography demonstrated postoperative improvement in nasal morphologies, particularly the columella deviation angle and nasal depth (representing nasal tip height), which are crucial parameters of nasal aesthetics ( P < .05). CONCLUSIONS: In patients who underwent simultaneous rhinoplasty and septoplasty, nasal symmetry and ventilation function were significantly improved compared to the control group. Septum grafts could provide nasal tip support for patients with cleft lip. Three-dimensional stereophotogrammetry helped us to better visualize the surgical results. Although the septal cartilage of Asian patients is sometimes insufficient for simultaneous use for multiple grafts, septum grafts in rhinoplasty of patients with cleft lip nasal deformities could give support for nasal tips.

In vitro evaluation of a bone morphogenetic protein­2 nanometer hydroxyapatite collagen scaffold for bone regeneration.

Scaffold fabrication and biocompatibility are crucial for successful bone tissue engineering. Nanometer hydroxyapatite (nHAP) combined with collagen (COL) is frequently utilized as a suitable osseous scaffold material. Furthermore, growth factors, including bone morphogenetic protein­2 (BMP­2), are used to enhance the scaffold properties. The present study used blending and freeze­drying methods to develop a BMP­2­nHAP­COL scaffold. An ELISA was performed to determine the BMP­2 release rate from the scaffold. Flow cytometry was used to identify rat bone marrow­derived mesenchymal stem cells (BMSCs) prior to their combination with the scaffold. Scanning electron microscopy was used to observe the scaffold structure and BMSC morphology following seeding onto the scaffold. BMSCs were also used to assess the biological compatibility of the scaffold in vitro. BMP­2­nHAP­COL and nHAP­COL scaffolds were assessed alongside the appropriate control groups. Cells were counted to determine early cell adhesion. Cell Counting kit­8 and alkaline phosphatase assays were used to detect cell proliferation and differentiation, respectively. Gross morphology confirmed that the BMP­2­nHAP­COL scaffold microstructure conformed to the optimal characteristics of a bone tissue engineering scaffold. Furthermore, the BMP­2­nHAP­COL scaffold exhibited no biological toxicity and was demonstrated to promote BMSC adhesion, proliferation and differentiation. The BMP­2­nHAP­COL scaffold had good biocompatibility in vitro, and may therefore be modified further to construct an optimized scaffold for future bone tissue engineering.

Fibroblast growth factor 23 (FGF23) gene polymorphisms are associated with essential hypertension risk and blood pressure levels in Chinese Han population.

In this case-control study, 246 EH patients and 157 healthy controls were selected from Chinese Han population to explore the associations between the fibroblast growth factor 23 (FGF23) gene polymorphisms and essential hypertension (EH).The SequenomMassarray system was used for the genotyping of three FGF23 gene Tag single-nucleotide polymorphisms, namely rs7955866, rs13312756, and rs3812822. The primers were designed by Assay Designer 3.1 software, and then the samples were added to a 384-well plate for the polymerase chain reaction amplification, shrimp alkaline phosphatase reaction, and desalting after extension. The distributions of the alleles, genotypes, and haplotypes were compared between the two groups. Confounding factors (sex, age, BMI, smoking, and drinking) were adjusted in the non-logistic regression, and the results showed that rs7955866 and rs3812822 polymorphisms were independently associated with the risk of developing EH (P < 0.05). The statistical analysis of the haplotype of rs7955866-rs13312756-rs3812822 showed that haplotype ACC could increase the risk of developing EH (P = 0.046; OR = 1.513, 95%CI: 1.005-2.278). The analysis of the control group showed that carrying rs7955866 A allele (P = 0.031) and rs3812822 C allele (P = 0.025) was associated with the increase of systolic blood pressure (SBP). The insulin (INS) level in the peripheral blood was significantly different between the case and control groups (P = 0.014). After confounding factors were excluded, the results showed that the serum INS level was also an independent risk factor of developing EH (P = 0.044; OR = 1.604, 95%CI: 1.014-2.539). In summary, our results suggest that FGF23 gene polymorphisms are associated with the risk of developing EH in Chinese Han population.

Follow-up assessment of problem-based learning in dental alveolar surgery education: a pilot trial.

BACKGROUND: Limited information exists on the effects of an oral and maxillofacial surgery integrated problem-based learning (PBL) course for dental undergraduates and the performance of these students after graduation. Therefore, we designed a PBL-implemented course with integrated dental alveolar surgery to evaluate its effects on the preparedness of graduates for clinical practice, their lifelong learning habits and their ability to collaborate, compared with the results of traditional courses. METHODS: A randomised controlled trial was performed with 90 undergraduate students. The undergraduates were asked to perform a theoretical examination and to complete a clinical case analysis at the end of the course. Three years later, a follow-up survey was administered via a telephone interview and a questionnaire that measured self-perceived and supervisor-rated preparedness for clinical practice related to professional knowledge of dental alveolar surgery, lifelong learning habits, attitude and collaboration ability. All results were analysed using one-way analysis of variance (ANOVA) and a t-test. RESULTS: At the 3-year post-graduation time point, both PBL graduates and their supervisors rated their preparation for clinical practice as higher than those who received traditional lecture-based courses. In addition, the respondents in the PBL group believed that they were more likely than their counterparts in the traditional group to consult with professionals and other health-care staff members. No significant between-group differences were observed in the graduates' habits or lifelong learning attitudes. CONCLUSIONS: The PBL mode of teaching integrated dental alveolar surgery may improve preparedness for clinical practice and help undergraduates to develop the desire to collaborate.

Evaluation of the efficacy and safety of topical timolol maleate combined with oral propranolol treatment for parotid mixed infantile hemangiomas.

The aim of the present study was to assess the efficacy and safety of topical timolol maleate combined with oral propranolol for parotid infantile hemangiomas. Between October 2012 and April 2014, propranolol was administered orally at a dose of 1.0-1.5 mg/kg/day to 22 infants with proliferating hemangiomas in the Department of Oral and Maxillofacial Surgery (Hospital of Stomatology, China Medical University, Shenyang, Liaoning, China). A small amount of 0.5% timolol maleate eye drop solution was topically applied with medical cotton swabs to the area of the lesion twice a day, every 12 h. The study group consisted of 9 males and 13 females, aged 2-9 months, with a median age of 4.7 months. The lesions were all located in the parotid region, and measured between 3.5×4×0.5 and 7×8×3 cm in volume. The planned duration of therapy was 6-8 months, or the two drugs were stopped when complete regression of the lesions was obtained. The therapeutic outcomes and safety were assessed by the change in the size and color of the tumor, and the presence of adverse effects throughout the course of treatment. The mean duration of therapy was 21.1 weeks and ranged from 3 to 8 months. Of the 22 patients, 16 demonstrated an excellent response, 6 showed a good response and 2 displayed a moderate response. No major collateral effects were observed. Overall, oral propranolol combined with topical timolol maleate may be used as the first-line therapeutic choice in the treatment of infantile parotid mixed hemangioma.

[Chinese experts consensus on the use of oral propranolol for treatment of infantile hemangiomas].

Infantile hemangioma (IH) is one of the most common benign vascular tumors in children. A variety of treatment methods have been documented for the management of IH over the past years, including pharmacotherapy via oral administration or injection of corticosteroids, vincristine, alpha interferon and bleomycin; laser therapy, radionuclide therapy, cryotherapy and excisional surgery. The therapeutic efficacy of each treatment modality is variable, while adverse effects or complications are common and sometimes serious. Since the serendipitous discovery of propranolol, a nonselective beta-adrenergic receptor blocker, being very efficacious in treating IH in 2008, oral propranolol has earned a role as a first-line medical therapy for complicated IH. However, the appropriate drug dosage, dosing regimen, time for initiation, optimal duration, monitoring for side effects remains controversial. To standardize the use of propranolol in treating IH, avoid overtreatment or under-treatment, as well as minimize complications, a Chinese experts consensus on the use of oral propranolol for treatment of IH has been approved and written by a multidisciplinary experts group based on an up-to-date literature review and repeated discussion.

Synthesis of and in vitro and in vivo evaluation of a novel TGF-ß1-SF-CS three-dimensional scaffold for bone tissue engineering.

The role of transforming growth factor-ß1 (TGF-ß1) in normal human fracture healing has been previously demonstrated. The objective of the present study was to examine the biocompatibility of TGF-ß1-silk fibroin-chitosan (TGF-ß1-SF-CS) three-dimensional (3D) scaffolds in order to construct an ideal scaffold for bone tissue engineering. We added TGF-ß1 directly to the SF-CS scaffold to construct a 3D scaffold for the first time, to the best of our knowledge, and performed evaluations to determine whether it may have potential applications as a growth factor delivery device. Bone marrow-derived mesenchymal stem cells (BMSCs) were seeded on the TGF-ß1-SF-CS scaffolds and the silk fibroin-chitosan (SF-CS) scaffolds. On the TGF-ß1­SF-CS and the SF-CS scaffolds, the cell adhesion rate increased in a time­dependent manner. Using a Cell Counting Kit-8 (CCK-8) assay and analyzing the alkaline phosphatase (ALP) expression proved that TGF-ß1 significantly enhanced the growth and proliferation of BMSCs on the SF-CS scaffolds in a time-dependent manner. To examine the in vivo biocompatibility and osteogenesis of the TGF-ß1­SF-CS scaffolds, the TGF-ß1-SF-CS scaffolds and the SF-CS scaffolds were implanted in rabbit mandibles and studied histologically and microradiographically. The 3D computed tomography (CT) scan and histological examinations of the samples showed that the TGF-ß1-SF-CS scaffolds exhibited good biocompatibility and extensive osteoconductivity with the host bone after 8 weeks. Moreover, the introduction of TGF-ß1 to the SF-CS scaffolds markedly enhanced the efficiency of new bone formation, and this was confirmed using bone mineral density (BMD) and biomechanical evaluation, particularly at 8 weeks after implantation. We demonstrated that the TGF-ß1­SF-CS scaffolds possessed as good biocompatibility and osteogenesis as the hybrid ones. Taken together, these findings indicate that the TGF-ß1-SF-CS scaffolds fulfilled the basic requirements of bone tissue engineering, and have the potential to be applied in orthopedic, reconstructive and maxillofacial surgery. Thus, TGF-ß1-SF-CS composite scaffolds represent a promising, novel type of scaffold for use in bone tissue engineering.

Association between insulin dosage and insulin usage time, and coronary artery lesions in patients with type 2 diabetes and coronary heart disease.

Insulin is used in the treatment of type 2 diabetes, with its usage reaching 30-50% in Western countries. The aim of the present study was to determine the association between insulin dosage (ID)/insulin usage time (IT) and coronary artery lesions in patients of type 2 diabetes with coronary heart disease. Based on the insulin using dosage, 353 type 2 diabetes patients were divided into the high-dose (≥0.5 IU/kg) and low-dose (<0.5 IU/kg) group. Selected coronary angiography was performed and the Gensini score was used to determine the degree of the coronary artery lesions. The homeostasis model assessment-insulin sensitivity (HOMA-IS) index was assessed by HOMA2. Data including age, gender, smoking, body mass index (BMI), systolic blood pressure (SBP), diastolic blood pressure (DBP), low-density lipoprotein cholesterol (LDL-C), high-density lipoprotein cholesterol (HDL-C), total cholesterol (TC), triglyceride (TG), glucose (Glu), hemoglobin A1c (HbA1c), C-peptide, ID, IT, diabetes duration time (DT), and IT/DT were collected. The association between insulin usage (both dose and time) and the coronary artery lesions in these patients was then determined. Statistical differences for the two groups for factors including C-peptide, HbA1c, ID, IT, DT, IT/DT and the Gensini score values (P<0.05) were identified. By contrast, no significant differences for factors such as gender, smoking history, age, BMI, TC, TG, LDL, HDL, fasting insulin, Glu, SBP and DBP were observed. The coronary artery damage Gensini score in insulin-insensitive individuals was significantly greater than that in the insulin-sensitive individuals. The Spearman analysis revealed that ID and IT, DT and IT/DT were positively correlated with the coronary artery damage Gensini score. The multivariate regression, the interquartile range method and receiver operating characteristic analyses showed that ID, ID/DT, IT had a greater effect on coronary vascular damage compared with DT. In conclusion, the degree of coronary artery lesions were correlated with ID, IT, DT, IT/DT. High doses of insulin or a high IT/DT ratio may aggravate coronary artery damage.