Silver/hydroxyapatite composite coatings on porous titanium surfaces by sol-gel method

Hydroxyapatite (HA) coatings loaded with nanosilver particles is an attractive method to impart the HA coating with antibacterial properties. Producing Ag/HA coatings on porous Ti substrates have been an arduous job since commonly used line-of-sight techniques are not able to deposit uniform coatings on the inner pore surfaces of the porous Ti. In this study, porous Ti scaffolds with high porosity and interconnected structures were prepared by polymer impregnating method. A sol-gel process was used to produce uniform Ag/HA composite coatings on the surfaces of porous Ti substrates. Ca(NO(3) )(2) ·4H(2) O and P(2) O(5) in an ethyl alcohol based system was selected to prepare the sol, which ensured the homogeneous distribution of Ag in the sol. The characterization revealed that silver particles uniformly distributed in the coatings without agglomeration. High antibacterial ratio (>95%), against E. coli and S. albus was expressed by the silver-containing coatings (Ag/HA 0.8 and 1.6 wt %). The biocompatibility of the Ag/HA 0.8 surfaces was as good as that of pure HA surface, as revealed by culturing osteoblasts on them. The results indicated that Ag/HA 0.8 had the good balance between the biocompatibility and antibacterial properties of the coatings.     

Neural correlates of near-misses effect in gambling

The present study investigated the cognitive and neural mechanisms underlying the gambling near-miss effect by measuring event-related-potentials. Using a simple gambling task, we measured behavioral response and electrophysiological activity of gambling outcomes. Self-rating results showed that when compared to full-miss outcome, near-miss outcome were rated as less pleasant, but yielded higher motivation to play. Whereas the feedback-related negativity (FRN) amplitude did not reflect the motivation rating differences between near-miss and full-miss, the P300 amplitude mirrored the motivation rating differences between near-miss and full-miss, with larger amplitudes for near-miss outcomes. Dipole source analysis of the difference wave (near-miss minus full-miss) indicated that two generators of the P300, localized in the putamen and orbitofrontal cortex, might be involved in motivational evaluation and regret, respectively. Our findings indicated that the near-miss effect stems from sources: higher levels of motivation and the presence of regret, caused by counterfactual thinking.     

LMP1 antagonizes WNT/β-catenin signalling through inhibition of WTX and promotes nasopharyngeal dysplasia but not tumourigenesis in LMP1(B95-8) transgenic mice

Latent membrane protein 1 (LMP1) of Epstein-Barr virus (EBV) can induce cell transformation and tumourigenesis, but the mechanism is not understood. Previous studies have suggested that LMP1 acts through up-regulation of cellular proliferation pathways including the Wnt/β-catenin pathway, in which β-catenin is the central effector. Increased levels of β-catenin coupled with a decrease in E-cadherin lead to reduced cell adhesion. This pathway is antagonized by WTX (Wilms' tumour gene on the X chromosome), which can promote the ubiquitination and degradation of β-catenin. In the present study, we established L2/LMP1B(95 - 8) /EGFP transgenic mice to investigate the in vivo role of LMP1. Down-regulation of WTX and E-cadherin was accompanied by increased expression of β-catenin in these mice. Even though invasive tumours did not develop, dysplasia was seen in the nasopharynx and oropharynx epithelium of these transgenic mice. Analysis of LMP1(+) , WTX(+) , and LMP1 siRNA silenced HNE-1 cell lines demonstrated that WTX could exert a dominant role in LMP1-mediated WNT/β-catenin pathway regulation. This study indicates that LMP1 antagonizes the WNT/β-catenin pathway by inhibiting WTX, and this reduction in WTX is associated with epithelial dysplasia via regulation of the WNT/β-catenin pathway molecules E-cadherin and β-catenin. Further studies are required for a better understanding of the relationship between LMP1-mediated antagonization of the WNT/β-catenin pathway and tumourigenesis.     

The use of polyethylenimine-grafted graphene nanoribbon for cellular delivery of locked nucleic acid modified molecular beacon for recognition of microRNA

A simple nanocarrier of polyethylenimine-grafted graphene nanoribbon (PEI-g-GNR) was proposed as an effective gene vector. The GNR was formed by longitudinally unzipping multiwalled carbon nanotubes (MWCNTs), and treated with strong acids and sonication to obtain surface carboxylic acid groups for graft of PEI via electrostatic assembly. The PEI-g-GNR appeared to protect locked nucleic acid modified molecular beacon (LNA-m-MB) probes from nuclease digestion or single-strand binding protein interaction, thus could be used as a nanocarrier of the probes for more efficient transfection of cells than PEI or PEI-g-MWCNTs due to the large surface area of the GNR and high charge density of PEI. The cytotoxicity and apoptosis induced by the PEI-g-GNR were negligible under optimal transfection conditions. Combining with the remarkable affinity and specificity of LNA to microRNA (miRNA), a delivery system by the LNA-m-MB/PEI-g-GNR was proposed for effectively transferring LNA-m-MB into the cells to recognize the target miRNA. Using HeLa cells as model, a method for detection of miRNA in single cell was developed. These results suggested that PEI-g-GNR would be a promising nonviral vector for in situ detection of gene in cytoplasm and gene therapy in clinical application.     

The effect of IL-10 genetic variation and interleukin 10 serum levels on Crohn's disease susceptibility in a New Zealand population

Interleukin (IL)-10 has important effects in immunoregulation and inflammation, and previous studies have provided evidence for the involvement of IL-10 in the pathogenesis of Crohn's disease (CD). In this study, we investigated whether genetic variants of the IL-10 gene were associated with CD in a New Zealand population. Three single nucleotide polymorphisms (SNPs) in the promoter region of IL-10 (rs1800871, rs1800872, and rs1800896) and a flanking SNP, rs3024505, were genotyped in a well-characterized New Zealand dataset consisting of 342 CD cases and 610 controls. Furthermore, we measured serum IL-10 levels in a number of the CD patients and controls and examined whether a relationship existed between these polymorphisms and serum IL-10 levels. We demonstrated an association with CD for SNPs rs3024505 and rs1800896, and phenotypic analysis indicated an association of rs3024505 with an early age at first diagnosis, stricturing CD behavior, and requirement for bowel resection. We also observed that IL-10 concentration was significantly higher in CD patients than in the controls and that the T allele of rs1800896, the A allele of rs1800871, and the T allele of rs1800872 were associated with increased serum IL-10 levels.     

MCCC2基因变异致3-甲基巴豆酰辅酶A羧化酶缺乏症患儿的家系分析

目的对1例临床疑诊3-甲基巴豆酰辅酶A羧化酶缺乏症(3-methylcrotonyl-coenzyme A carboxylase deficiency,MCCD)患儿及其父母进行基因变异分析,寻找该家系的致病变异,为临床诊断提供分子遗传学依据。方法抽提先证者及其父母的外周血基因组DNA,应用全外显子组基因测序技术对疑似为MCCD疾病的先证者进行致病基因筛查。根据高通量测序结果,对先证者及其父母进行变异位点的Sanger测序验证分析。应用计算机软件预测变异位点氨基酸进化保守性和变异可能导致的蛋白质结构和功能变化,分析变异位点的性质。结果Sanger测序结果显示先证者为MCCC2基因c.1342G>A(p.Gly448Ala)纯合错义变异,为未报道过的新变异。先证者母亲为c.1342G>A(p.Gly448Ala)杂合变异携带者,父亲未检测到该变异。用PolyPhen-2和Mutation Taster软件预测该变异为致病性,变异区域序列在不同物种间高度保守。根据美国医学遗传学与基因组学学会遗传变异分类标准与指南,MCCC2基因c.1342G>A(p.Gly448Ala)变异判定为可能致病性变异(PM2+PP2~PP5)。结论先证者MCCC2基因c.1342G>A(p.Gly448Ala)纯合错义变异是其分子发病机制,基因变异分析有助于明确临床诊断。     

七例Alström综合征的 ALMS1基因变异分析

目的:对7例Alstr?m综合征患者的 ALMS1基因进行变异分析,明确其致病原因,为临床诊断提供依据。 方法:提取7例患儿及其父母外周血DNA,对患儿进行全外显子组基因测序,应用Sanger测序对患儿及父母进行变异位点验证及致病性分析。结果:基因测序结果显示在7例患儿中检出12个 ...     

Risk factors for severe and critically ill COVID-19 patients: A review

The pandemic of coronavirus disease 2019 (COVID-19), caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), has caused an unprecedented global social and economic impact, and high numbers of deaths. Many risk factors have been identified in the progression of COVID-19 into a severe and critical stage, including old age, male gender, underlying comorbidities such as hypertension, diabetes, obesity, chronic lung diseases, heart, liver and kidney diseases, tumors, clinically apparent immunodeficiencies, local immunodeficiencies, such as early type I interferon secretion capacity, and pregnancy. Possible complications include acute kidney injury, coagulation disorders, thoromboembolism. The development of lymphopenia and eosinopenia are laboratory indicators of COVID-19. Laboratory parameters to monitor disease progression include lactate dehydrogenase, procalcitonin, high-sensitivity C-reactive protein, proinflammatory cytokines such as interleukin (IL)-6, IL-1β, Krebs von den Lungen-6 (KL-6), and ferritin. The development of a cytokine storm and extensive chest computed tomography imaging patterns are indicators of a severe disease. In addition, socioeconomic status, diet, lifestyle, geographical differences, ethnicity, exposed viral load, day of initiation of treatment, and quality of health care have been reported to influence individual outcomes. In this review, we highlight the scientific evidence on the risk factors of severity of COVID-19.     

椎弓根钉内固定加植骨融合术治疗峡部不连性腰椎滑脱

目的 :评价椎弓根内固定结合椎间及后外侧植骨治疗峡部不连性腰椎滑脱的临床疗效。方法 :本组 38例 ,均行椎弓根内固定结合椎管减压、椎间植骨及后外侧植骨融合术治疗。椎弓根内固定技术包括 :Steffee 2 0例 ,RF 8例 ,TSRH 5例 ,Socon 5例 ;固定融合范围 :1个节段 2 4例 ,2个节段 14例。结果 :36例病人获随访 ,平均时间 4±2 .6a年。滑脱椎体复位率 80 .6 %～ 93.4 % ,平均 87.37% ;腰痛改善率 94 .3% ;下肢疼痛、麻木改善率 94 .5 % ;间歇性跛行改善率 97.3%。并发症共 6例 ,其中术中并发症 2例 ,发生率 5 .5 % ;术后并发症 4例 ,发生率 11.1%。结论 :椎弓根内固定可满足腰椎滑脱的短节段固定和复位要求 ,临床疗效满意 ,复位、融合率高。并发症的预防与掌握椎弓根内固定技术的熟练程度有关