Silicone rubber membrane with specific pore size enhances wound regeneration

A porous structure is critically important for wound dressing or tissue engineering scaffolds. However, the influence of the pore sizes on cell proliferation, tissue regeneration and the underlying mechanism remains unclear. In this study, silicone rubber membranes with different pore sizes were prepared using certain constituents of liquid silicone rubber precursor/liquid paraffin/hexane based on our previous studies. It was found that pore size had a significant impact on cell proliferation and wound healing. The CCK8 analysis revealed that the membrane with a certain pore size (110.47 μm, middle pore membrane, MPM) was suitable for cell proliferation compared with the membranes with other pore sizes (218.03 μm, large pore membrane, LPM; 5.27 μm, small pore membrane, SPM; non‐porous membrane, NPM). Further studies demonstrated that the MPM promoted cell proliferation via activating the Wnt/β‐catenin signalling pathway. More importantly, wound healing experiments showed that 7 days post‐wounding, the rate of wound healing was 89.25% with the MPM, which was significantly higher than with LPM, SPM or NPM. The in vivo data indicated that wound healing was accelerated by treatment with a silicone rubber membrane with a pore size of 110.47 μm. Our results strongly suggest that different pore structures might affect cell proliferation and wound healing and that a silicone rubber membrane with a specific pore size could potentially be used as a promising wound dressing. Copyright © 2017 John Wiley & Sons, Ltd.     

Combined spectroscopy methods and molecular simulations for the binding properties of trametinib to human serum albumin

Trametinib is a novel anticancer drug for treating metastatic cutaneous melanoma. The present study probed into the binding of trametinib to human serum albumin (HSA) through spectroscopy methods and molecular simulations. Trametinib could quench the fluorescence of HSA through static quenching which could be probed via fluorescence spectroscopy and time-resolved fluorescence. Thermodynamic parameters and docking results indicated that hydrogen bonds and van der Waals forces play crucial roles in this binding process, which exerts almost no effect on the HSA conformation under synchronous fluorescence, three-dimensional fluorescence, circular dichroism spectra, and molecular dynamics simulations. Site marker displacement experiments and molecular docking reveal that trametinib primarily binds to Sudlow site I of HSA. In addition, the trametinib–HSA interaction was hardly influenced by varying amino acid (glutamine, alanine, glycine, and valine) concentrations. This study can provide useful information for the pharmacokinetic properties of trametinib.

Probing the binding properties of trametinib to human serum albumin.     

Right ventricular septomarginal trabeculation hypertrophy is associated with disease severity in patients with pulmonary arterial hypertension

To characterize the morphological change in the right ventricle (RV) of patients with pulmonary artery hypertension (PAH) and further explore the correlation between septomarginal trabeculation (SMT) and right ventricular (RV) function, myocardial fibrosis, and exercise capacity in patients with PAH. Sixty untreated PAH patients were prospectively included from May 2016 to April 2017. All patients underwent comprehensive clinical evaluation and cardiac magnetic resonance (CMR). The area and diameter of the basal segment of SMT, and the mass of SMT were measured on cine SSFP images. Relationship between parameters of SMT and RV ejection fraction (RVEF), 6 min walking distance (6MWD), myocardial fibrosis and pulmonary vascular resistance (PVR) were evaluated by Pearson’s correlation and logistic regression. Predictive performance of SMT parameters for reduced RVEF or impaired 6MWD was evaluated by receiver operating characteristics (ROC) analysis. Compared with SMT diameter index and mass index, SMT area index (SMT Ai) in basal segment was the best parameter to show correlation with RVEF (r?=???0.496, P?<?0.001), 6MWD (r?=???0.619, P?<?0.001), and inferior insertion point (I IP) extracelluar volume (ECV) (r?=?0.365, P?=?0.008). ROC showed that SMT Ai had the strongest predictive value for reduced RVEF (AUC?=?0.756), and impaired 6MWD (AUC?=?0.813). SMT parameters were closely correlated with RV systolic function and 6MWD in patients with PAH. SMT Ai is a simple imaging indicator for the severity of PAH.     

Cardiac function in patients with polymyositis or dermatomyositis: a three-dimensional speckle-tracking echocardiography study

Cardiac event is a major cause of death in patients with idiopathic inflammatory myopathies (IIM). The most frequent IIMs are polymyositis (PM) and dermatomyositis (DM). The purpose of this study was to analyze cardiac involvement by three-dimensional speckle-tracking echocardiography (3D STE) in patients with PM or DM, and to identify the relationship of cardiac injury with clinical characteristics and disease-specific parameters. 60 PM/DM patients with preserved left ventricular ejection fraction and 30 matched healthy controls were assessed by conventional echocardiography, 3D STE with biventricular strain analysis and electrocardiogram. Compared to controls, patients with PM/DM had significantly diminished left ventricular global longitudinal systolic strain and right ventricular longitudinal systolic strain (LVGLS, ? 20.3?±?2.5 vs. ? 23.4?±?1.7%; RVLS, ? 19.4?±?4.2 vs ? 24.8?±?2.0%; both P?<?0.001), and longer QTc intervals(421.0?±?38.4 vs 400.6?±?14.5 ms, P?=?0.001). Multiple regression analysis showed that Myositis Damage Index (MDI) was independently associated with LVGLS (R²?=?0.44, P?=?0.002) and RVLS (R²?=?0.56, P?<?0.001) in PM/DM patients with established disease course more than 1 year. In multivariate analysis of pooled data for all the PM/DM patients, when MDI was excluded due to missing observations, disease duration correlated with worse LVGLS (R²?=?0.24, P?=?0.002), while concomitant interstitial lung disease correlated with worse RVLS (R²?=?0.30, P?<?0.001). Disease activity scores (Myositis Intention to Treat Activities Index) had a weak positive correlation with QTc intervals (r_sp = 0.31, P?=?0.02). Our results suggest that cardiac injury in PM/DM is a long-term process and its severity depends on patients’ heterogeneous clinical features and systemic disease burden.     

In vitro and in vivo assessment of nanostructured porous biphasic calcium phosphate ceramics for promoting osteogenesis in an osteoporotic environment

Treatment of bone defects in osteoporotic patients with bone substitutes is difficult, due to insufficient osseointegration. The development of appropriate biomaterials to solve the problem requires the assessment of the material performance in an osteoporotic environment, which is rarely investigated. Herein, nanostructured biphasic calcium phosphate (nBCP) ceramics were prepared via the incorporation of hydroxyapatite nanoparticles (HANPs) into porous biphasic CaP (BCP) substrates, leading to an increase of over 500% in the specific surface area. Primary osteoblasts harvested from osteoporotic rats were cultured on the nBCP ceramics, and it was found that the osteoblast functions, including proliferation, alkaline phosphatase activity, osteocalcin secretion and expression of osteogenic genes, were significantly enhanced compared with osteoblasts grown on non-nanostructured BCP ceramics. To further assess the osteoinduction ability, the ceramics were implanted in the femur of osteoporotic rats. Compared to the rats implanted with non-nanostructured BCP ceramics, a higher amount of mechanically matured bone was newly formed in the rats with nBCP ceramics after 6 weeks of implantation. Such enhanced osteoinduction ability of the nBCP ceramics may be due to the incorporated HANPs, as well as the nanostructured topography induced by the HANPs. These results indicate good in vitro and in vivo osteoinductivity of the nBCP ceramics in an osteoporotic environment and offer potential benefits for treating bone defects in osteoporotic patients.

Nanostructured porous biphasic calcium phosphate ceramics are able to significantly promote bone defect healing in an osteoporotic environment.     

Pharmacological inhibition of fatty acid-binding protein 4 (FABP4) protects against renal ischemia-reperfusion injury

Fatty acid-binding protein 4 (FABP4) is a key mediator of endoplasmic reticulum (ER) stress and apoptosis in diabetes and atherosclerosis. Studies also confirmed that circulating FABP4 depended on renal function in chronic kidney disease (CKD) and acute kidney injury (AKI) patients. However, the function of FABP4 in AKI remains poorly understood and the aim of this study was to investigate the role of FABP4 in ischemia-reperfusion (I/R)-induced AKI. In the present study, renal I/R injury triggered the high expression of the FABP4 gene and protein in the nucleus and cytoplasm of tubular cells of mouse kidney tissue compared to that of Sham. Pretreatment with BMS309403, a highly selective inhibitor of FABP4 at a dose of 20 mg kg⁻¹ d⁻¹ for 4 d, significantly reduced serum creatinine levels to improve acute renal dysfunction and attenuated renal tubular damage in injured kidneys. Pharmacological inhibition of FABP4 also decreased the number of TdT-mediated dUTP nick-end labeling (TUNEL) positive apoptotic tubular cells, accompanied by the down-regulation of cleaved-caspase-3 expression. Furthermore, oral administration of FABP4 inhibitor resulted in a significant attenuation of ER stress indicated by its maker proteins expression of glucose-regulated protein 78 (GRP78), C/EBP homologous protein (CHOP), and caspase-12 in I/R injured kidneys. In vitro, the increased expression of FABP4 in the human renal proximal tubule cell line (HK-2 cell) was induced by hypoxia followed by reoxygenation (HR) and the FABP4 inhibitor resulted in a significant attenuation of cell apoptosis and ER stress in HR-induced HK-2 cells. In summary, these findings indicated that FABP4 contributed to the pathogenesis of I/R-induced AKI and suggested that the inhibition of FABP4 might be a promising therapeutic strategy for AKI treatment.

FABP4 inhibition might attenuate I/R-induced AKI through reducing ER stress and apoptosis.     

孕前健康体检的现状分析及孕前保健的模式探讨

目的:分析成都某三甲医院孕前健康体检的现状,探讨孕前保健的服务模式,为提高孕前保健质量提供依据。方法:采用计算机分层随机抽取2008年9月~2013年8月首次于该三甲医院行孕前检查的16 038名妇女中的375名妇女的相关体检数据资料,重点调查血、尿常规及肝肾功、血脂、血糖、血型、地贫筛查、妇科超声、乙肝、梅毒和HIV筛查等国家孕前优生健康检查项目,进而采用SPSS 17.0完成统计分析。结果:受检率排在前五位的依次为TORCH 66.13%、妇科超声56.53%、宫颈癌细胞筛查44.00%、白带常规41.33%和甲状腺功能20.53%,尿常规、地贫筛查、75 g口服葡萄糖耐量试验、心电图和胸片的受检率均低于5.00%;血及白带常规、妇科超声、75 g口服葡萄糖耐量试验、血脂、甲状腺功能、宫颈癌细胞筛查和HPV病毒分型以及乙肝、梅毒筛查因就诊科室不同而受检率明显不同,差异有统计学意义(P<0.05)。但白带常规、TORCH感染和宫颈癌细胞筛查的阳性率分别为22.31%、16.20%和10.74%,而乙肝、梅毒和HIV的阳性率分别为4.54%、3.70%和0.00%,不同就诊科室间相关检查的阳性率差异均无统计学意义(P>0.05)。结论:通过加强干预、加强优生健康教育的宣传、设置规范的孕前保健门诊服务模式、婚检与孕前检查相结合、建立孕前保健信息化服务平台等手段可提高孕前保健服务质量。     

四川省农村地区高血压患病率及相关因素分析

目的 了解四川省农村地区高血压流行及诊疗状况。方法 利用中英合作项目“中国慢性病前瞻性研究”项目四川省基线调查人群数据,分析彭州市不同特征人群高血压患病情况和知晓、治疗及控制情况。结果 四川省农村地区30～79岁人群高血压患病率为25.2%,高血压知晓率、治疗率和控制率低,分别为24.7%、14.7%和3.7%。高血压患病率、知晓率、治疗率和控制率与社会人口学相关;冬季高血压患病率比夏季高70%～80%,“三率”明显低于夏季。高血压人群吸烟、饮酒比例较高,饮食习惯较差,体力活动不足,肥胖比例较高;知晓自己患病的人群生活方式有适当改善,但体力活动更差和肥胖比例较高。结论 四川省农村地区高血压患病率高,知晓率、治疗率和控制率低。应加强年轻人群健康教育,重视老年人群高血压的治疗和控制,规范高血压患者的管理。