Comparison of Foaming Properties Between the Shirasu Porous Glass Membrane Device and Tessari’s Three-way Stopcock Technique for Polidocanol and Ethanolamine Oleate Foam Production: A Benchtop Study

PurposeTo compare the characteristics of polidocanol (POL) and ethanolamine oleate (EO) sclerosing foams produced by a Shirasu porous glass membrane (SPGM) device with those made using a 3-way stopcock (3WSC).Materials and MethodsFoam half-life times were measured in an ex-vivo benchtop study. Computed tomography (CT) images of each foam were obtained over the time course, and a CT texture analysis was conducted. The bubble size in each foam was measured by an optical microscope.ResultsMedian foam half-life times were longer in the SPGM group than in the 3WSC group (POL: 198 vs 166 s, P = .02; EO: 640 vs 391 s, P < .01). In the CT texture analysis, median standard deviation (SD) and entropy (randomness) were lower, and median energy (uniformity) and gray-level cooccurrence matrix (GLCM) homogeneity were higher in the SPGM group than in the 3WSC group (POL SD: at 30 s and 50–300 s; POL entropy: at 0–60 s; EO SD: at 0–600 s; EO entropy: at 0–460 s; POL energy: at 0–40 s; POL GLCM homogeneity: at 0–250 s; EO energy: at 0–360 s; EO GLCM homogeneity: at 0–480 s; all P < .05). Median bubble diameters in the SPGM group and in the 3WSC group were 69 and 83 μm (P < .01), respectively, in the POL foam; and 36 and 36 μm (P = .45), respectively, in the EO foam.ConclusionsPOL and EO foams had greater uniformity and longer foam half-life time when prepared with an SPGM device than with a 3WSC.     

亚砷酸钠联合粉防己碱对乳腺癌MDA-MB-231细胞的增殖抑制作用及机制研究

目的:探讨亚砷酸钠联合粉防己碱对乳腺癌MDA-MB-231细胞的增殖抑制作用。方法:MTT法检测细胞活力，Annexin V-FITC/PI双染法检测细胞凋亡，Hoechst33258染色观察细胞染色质固缩情况，碘化丙啶PI单染法检测细胞周期，Western blot检测p-GSK3β、GSK3β及凋亡相关蛋白 PARP、bcl-2的表达。结果:不同浓度的亚砷酸钠或粉防己碱单用均可抑制MDA-MB-231细胞增殖（P＜0.01）；与单独用药相比，两药联合使用可显著增强细胞增殖抑制效果（P＜0.000 1）。两药联用可显著诱导MDA-MB-231细胞凋亡（P＜0.01），细胞凋亡率呈现浓度依赖性递增，并出现细胞核染色质固缩。联合用药浓度为亚砷酸钠10 μmol/L+粉防己碱4 μg/ml时，S期细胞所占百分比显著增高（P＜0.05）；联合用药浓度为亚砷酸钠15 μmol/L+粉防己碱4.5 μg/ml时，G2/M期细胞所占百分比显著增高（P＜0.001）。联合用药后，凋亡相关蛋白PARP的表达显著上调（P＜0.000 1）；bcl-2的表达显著下调（P＜0.05）；p-GSK3β、GSK3β蛋白表达均显著上调（P＜0.000 1）。 结论:亚砷酸钠联合粉防己碱对乳腺癌MDA-MB-231细胞具有增殖抑制作用，其机制与诱导细胞周期 S期、G2/M期阻滞、GSK3β蛋白水平上调及促进细胞凋亡有关，促凋亡作用与bcl-2蛋白水平下调、PARP蛋白水平上调有关。     

Proteases and their inhibitors as prognostic factors for high-grade serous ovarian cancer

Ovarian carcinoma is one of the most lethal malignancies, but only very few prognostic biomarkers are known. The degradome, comprising proteases, protease non-proteolytic homologues and inhibitors, have been involved in the prognosis of many cancer types, including ovarian carcinoma. The prognostic significance of the whole degradome family has not been specifically studied in high-grade serous ovarian cancer. A targeted DNA microarray known as the CLIP-CHIP microarray was used to identify potential prognostic factors in ten high-grade serous ovarian cancer women who had early recurrence (<1.6 years) or late/no recurrence after first line surgery and chemotherapy. In women with early recurrence, we identified seven upregulated genes (TMPRSS4, MASP1/3, SPC18, PSMB1, IGFBP2, CFI – encoding Complement Factor I – and MMP9) and one down-regulated gene (ADAM-10). Using immunohistochemistry, we evaluated the prognostic effect of these 8 candidate genes in an independent cohort of 112 high-grade serous ovarian cancer women. Outcomes were progression, defined according to CA-125 criteria, and death. Multivariate Cox proportional hazard regression models were done to estimate the associations between each protein and each outcome. High ADAM-10 expression (intensity of 2–3) was associated with a lower risk of progression (adjusted hazard ratio (HR): 0.51; 95% confidence interval (CI): 0.29-0.87). High complement factor I expression (intensity 2–3) was associated with a higher risk of progression (adjusted HR: 2.30, 95% CI: 1.17–4.53) and death (adjusted HR: 3.42; 95% CI: 1.72–6.79). Overall, we identified the prognostic value of two proteases, ADAM-10 and complement factor I, for high-grade serous ovarian cancer which could have clinical significance.     

绝经后妇女骨关节炎合并骨质疏松三联治疗的临床观察

目的探讨绝经后妇女骨关节炎合并骨质疏松三联治疗的临床效果。方法选取2017年4月至2018年3月在我院治疗的64例绝经后骨关节炎合并骨质疏松患者进行研究,按照简单随机法将患者分为对照组、观察组,对照组予以非甾体类药物(NSAID)+玻璃酸钠治疗,观察组予以NSAID+玻璃酸钠+依降钙素治疗。比较两组患者的治疗效果及治疗前后VAS评分、Lysholm膝关节评分、WOMAC评分、腰骨密度值变化。结果对照组患者治疗有效率为78.13%,观察组治疗有效率为93.75%,观察组患者治疗有效率高于对照组(P0.05)。两组患者治疗后骨密度高于治疗前(P0.05);而在治疗后3个月、6个月,观察组患者骨密度高于对照组(P0.05)。两组患者治疗后VAS评分、Lysholm膝关节评分、WOMAC评分低于治疗前(P0.05);而在治疗后3个月、6个月,观察组患者VAS评分、Lysholm膝关节评分、WOMAC评分均低于对照组(P0.05)。结论 NSAID、玻璃酸钠、依降钙素联合应用于绝经后妇女骨关节炎合并骨质疏松治疗,不仅可提高治疗效果,改善膝关节功能,还能提高活动度及患者生活质量,应用于临床可起到积极作用。     

Modification of the vaccine manufacturing process improves the pyrogenicity profile of inactivated influenza vaccines in young children

Background

There were increased reports of fevers and febrile reactions in young children (particularly children aged <5?years) receiving the Seqirus/CSL Southern Hemisphere 2010 trivalent inactivated influenza vaccine (IIV3). Modifying the vaccine manufacturing process by increasing the minimum concentration of splitting agent (sodium taurodeoxycholate [TDOC]) from 0.5% w/v to 1.5% w/v for all strains resolved this issue. The current analysis compared fever rates in three pediatric studies of Seqirus IIV3 (S-IIV3) or quadrivalent inactivated influenza vaccine (S-IIV4), prepared using the modified manufacturing process, with fever rates in three pediatric studies of historical (pre-2010) IIV3 formulations. The historical IIV3 formulations, S-IIV3, and S-IIV4 had 0/3, 2/3, and 4/4 vaccine strains split at 1.5% TDOC, respectively.

Ocular dysfunctions and toxicities induced by antiepileptic medications: Types,pathogenic mechanisms,and treatment strategies

Introduction: Ocular dysfunctions and toxicities induced by antiepileptic drugs (AEDs) are rarely reviewed and not frequently received attention by treating physicians compared to other adverse effects (e.g. endocrinologic, cognitive and metabolic). However, some are frequent and progressive even in therapeutic concentrations or result in permanent blindness. Although some adverse effects are non-specific, others are related to the specific pharmacodynamics of the drug.

Areas covered: This review was written after detailed search in PubMed, EMBASE, ISI web, SciELO, Scopus, and Cochrane Central Register databases (from 1970 to 2019). It summarized the reported ophthalmologic adverse effects of the currently available AEDs; their risks and possible pathogenic mechanisms. They include ocular motility dysfunctions, retinopathy, maculopathy, glaucoma, myopia, optic neuropathy, and impaired retinal vascular autoregulation. In general, ophthalmo-neuro- or retino-toxic adverse effects of AEDs are classified as type A (dose-dependent), type B (host-dependent or idiosyncratic) or type C which is due to the cumulative effect from long-term use.

Expert opinion: Ocular adverse effects of AEDs are rarely reviewed although some are frequent or may result in permanent blindness. Increasing knowledge of their incidence and improving understanding of their risks and pathogenic mechanisms are crucial for monitoring, prevention, and management of patients’ at risk.     

Antisense oligonucleotide eluforsen improves CFTR function in F508del cystic fibrosis

BackgroundCystic fibrosis (CF) is caused by mutations in the CF transmembrane conductance regulator (CFTR) gene. In this study we assessed the effect of antisense oligonucleotide eluforsen on CFTR biological activity measured by Nasal Potential Difference (NPD) in patients with the most common mutation, F508del-CFTR.MethodsThis multi-centre, exploratory, open-label study recruited adults with CF homozygous or compound heterozygous for the F508del-CFTR mutation. Subjects received intranasal eluforsen three times weekly for 4 weeks. The primary endpoint was the within-subject change from baseline in total chloride transport (Cl-free+iso), as assessed by NPD. Secondary endpoints included within-subject change from baseline in sodium transport.ResultsIn the homozygous cohort (n = 7; per-protocol population), mean change (90% confidence interval) in Cl-free+iso was ?3.0 mV (?6.6; 0.6) at day 15, ?4.1 mV (?7.8; ?0.4, p = .04) at day 26 (end of treatment) and ? 3.7 mV (?8.0; 0.6) at day 47. This was supported by improved sodium transport as assessed by an increase in average basal potential difference at day 26 of +9.4 mV (1.1; 17.7, p = .04). The compound heterozygous cohort (n = 7) did not show improved chloride or sodium transport NPD values. Eluforsen was well tolerated with a favourable safety profile.ConclusionsIn F508del-CFTR homozygous subjects, repeated intranasal administration of eluforsen improved CFTR activity as measured by NPD, an encouraging indicator of biological activity.     

Evaluation of the effectiveness of Er: YAG laser and calcium sodium phosphosilicate (Novamine) prophylaxis paste on remineralization of incipient enamel lesions in primary teeth: An in-vitro study

AimThe aim of this study was to evaluate the potential remineralization effect of Novamine and Er:YAG laser on artificial enamel lesions in primary teeth.Materials and methodsIn this in vitro study, 30 sound buccal and lingual surfaces of human primary canines were randomly divided (6 per group) into 5 groups (Novamine, Laser, Novamine+ Laser, Positive control, and a negative control). Remineralization agents were applied for 1 min to teeth using a rubber cup after creating artificially demineralised lesions. EDX analysis was performed to evaluate the Ca/P ratio and take Scanning electron microscope images.ResultsData were analyzed using Kruskal Wallis analysis. Ca/P ratio was higher in all 4 groups than the negative control group, and higher in Novamine+ Laser group than the positive control group with a statistically significant difference between groups. Overall Ca/P ratio was found to be highest in the Novamine group followed by the laser then positive control group. There were no significant differences between groups regard to Ca/P Ratios.ConclusionBased on these result Er:YAG laser combined with Novamine was provided the greatest contribution to remineralization process of primary teeth.