3D打印制备不同重量比例的n-HA/PLA/PVA复合膜性能比较

目的:通过3D打印的方法制备的不同重量比例的纳米羟基磷灰石/聚乳酸/聚乙烯醇(n-HA/PLA/PVA)复合膜,并对其相关性能检测。方法:采用3D打印技术制备不同重量比例的n-HA/PLA/PVA复合膜,分别为PLA/PVA复合膜、15%n-HA/PLA/PVA复合膜、50%n-HA/PLA/PVA复合膜、75%n-HA/PLA/PVA复合膜。扫描电镜下观察各组膜形态,对其力学性能、细胞毒性及动物实验相应指标进行检测。结果:扫描电镜下观察,n-HA/PLA/PVA复合膜呈现三维网状结构,各材料间相互结合,孔隙分布不均,大小不一。随着n-HA质量浓度的提高,电镜下见各材料间孔隙逐渐减小,形成结构均匀的复合膜。力学性能及吸水率检测中,随着nHA含量的增加,n-HA/PLA/PVA复合膜的拉伸强度及吸水率呈下降趋势;细胞毒性检测,不同比例复合膜的细胞增殖率无明显差别,无细胞毒性。动物实验测量牙周菌斑指数及龈沟出血指数未发现不同比例n-HA/PLA/PVA复合膜有统计学差异。结论:3D打印不同比例的n-HA/PLA/PVA复合膜具有良好的物理性能和细胞生物相容性,n-HA比例更高的复合膜可能具有更好的物理性能及良好的生物相容性。     

Arachidonic acid-stimulated platelet tests: Identification of patients less sensitive to aspirin treatment

Serum thromboxane-B2 (TxB2), together with arachidonic acid (AA)-induced platelet aggregation, are, at the moment, the most used tests to identify patients displaying high on-aspirin treatment platelet reactivity (HAPR). Both tests are specific for aspirin action on cyclooxygenase-1. While the correlation between serum TxB2 assay and clinical outcome is established, data are conflicting with regard to aspirin treatment and a possible association with AA-stimulated platelet markers and clinical outcome. To understand such discrepancy, we performed a retrospective study to compare both assays. We collected data from 132 patients receiving a daily dose of aspirin (100?mg/day) and data from 48 patients receiving aspirin on alternate days. All Patients who received a daily dose of aspirin were studied for AA-induced platelet aggregation together with serum TxB2 levels and AA-induced TxB2 formation was also studied in 71 patients out of entire population. Consistent with recommendations in the literature, we defined HAPR by setting a cut-off point at 3.1?ng/ml for serum levels of thromboxane B2 and 20% for AA-induced platelet aggregation. According to this cut-off point, we divided our overall population into two groups: (1) TxB2?<?3.1?ng/ml and (2) TxB2?>?3.1?ng/ml. We found low agreement between such tests to identify patients displaying HAPR. Our results show that AA-induced platelet aggregation >20% identify a smaller number of HAPR patients in comparison with TxB2. A good correlation between serum TxB2 and arachidonic acid-induced TxB2 production was found (r?=?0.76619).     

Poly(ortho ester) nanoparticles targeted for chronic intraocular diseases: ocular safety and localization after intravitreal injection

Treatment of posterior eye diseases is more challenging than the anterior segment ailments due to a series of anatomical barriers and physiological constraints confronted by drug delivery to the back of the eye. In recent years, concerted efforts in drug delivery have been made to prolong the residence time of drugs injected in the vitreous humor of the eye. Our previous studies demonstrated that poly(ortho ester) (POE) nanoparticles were biodegradable/biocompatible and were capable of long-term sustained release. The objective of the present study was to investigate the safety and localization of POE nanoparticles in New Zealand white rabbits and C57BL/6 mice after intravitreal administration for the treatment of chronic posterior ocular diseases. Two concentration levels of POE nanoparticles solution were chosen for intravitreal injection: 1.5?mg/ml and 10?mg/ml. Our results demonstrate that POE nanoparticles were distributed throughout the vitreous cavity by optical coherence tomography (OCT) examination 14 days post-intravitreal injection. Intraocular pressure was not changed from baseline. Inflammatory or adverse effects were undetectable by slit lamp biomicroscopy. Furthermore, we demonstrate that POE nanoparticles have negligible toxicity assessed at the cellular level evidenced by a lack of glia activation or apoptosis estimation after intravitreal injection. Collectively, POE nanoparticles are a novel and nontoxic as an ocular drug delivery system for the treatment of posterior ocular diseases.     

Factors associated with clinically significant hypoglycemia in patients with type 1 diabetes using sensor-augmented pump therapy with predictive low-glucose management: A multicentric study on iberoamerica

Background and aimsDespite using sensor-augmented pump therapy (SAPT) with predictive low-glucose management (PLGM), hypoglycemia is still an issue in patients with type 1 Diabetes (T1D). Our aim was to determine factors associated with clinically significant hypoglycemia (<54 mg/dl) in persons with T1D treated with PLGM-SAPT.Methodology: This is a multicentric prospective real-life study performed in Colombia, Chile and Spain. Patients with T1D treated with PLGM-SAPT, using sensor ≥70% of time, were included. Data regarding pump and sensor use patterns and carbohydrate intake from 28 consecutive days were collected. A bivariate and multivariate Poisson regression analysis was carried out, to evaluate the association between the number of events of <54 mg/dl with the clinical variables and patterns of sensor and pump use.Results188 subjects were included (41 ± 13.8 years-old, 23 ± 12 years disease duration, A1c 7.2% ± 0.9). The median of events <54 mg/dl was four events/patient/month (IQR 1–10), 77% of these events occurred during day time. Multivariate analysis showed that the number of events of hypoglycemia were higher in patients with previous severe hypoglycemia (IRR1.38; 95% CI 1.19–1.61; p < 0.001), high glycemic variability defined as Coefficient of Variation (CV%) > 36% (IRR 2.09; 95%CI 1.79–2.45; p < 0.001) and hypoglycemia unawareness. A protector effect was identified for adequate sensor calibration (IRR 0.77; 95%CI 0.66–0.90; p:0.001), and the use of bolus wizard >60% (IRR 0.74; 95%CI 0.58–0.95; p:0.017).ConclusionIn spite of using advanced SAPT, clinically significant hypoglycemia is still a non-negligible risk. Only the identification and intervention of modifiable factors could help to prevent and reduce hypoglycemia in clinical practice.     

Evodiamine-inspired dual inhibitors of histone deacetylase 1 (HDAC1) and topoisomerase 2 (TOP2) with potent antitumor activity

A great challenge in multi-targeting drug discovery is to identify drug-like lead compounds with therapeutic advantages over single target inhibitors and drug combinations. Inspired by our previous efforts in designing antitumor evodiamine derivatives, herein selective histone deacetylase 1 (HDAC1) and topoisomerase 2 (TOP2) dual inhibitors were successfully identified, which showed potent in vitro and in vivo antitumor potency. Particularly, compound 30a was orally active and possessed excellent in vivo antitumor activity in the HCT116 xenograft model (TGI = 75.2%, 150 mg/kg, p.o.) without significant toxicity, which was more potent than HDAC inhibitor vorinostat, TOP inhibitor evodiamine and their combination. Taken together, this study highlights the therapeutic advantages of evodiamine-based HDAC1/TOP2 dual inhibitors and provides valuable leads for the development of novel multi-targeting antitumor agents.     

脑脊液降钙素原及乳酸测定在早期诊断颅脑术后颅内感染的意义

目的研究降钙素原(PCT)及乳酸水平在早期诊断颅脑术后颅内感染的意义。方法颅脑术后颅内感染患者(n=20)和非颅内感染患者(n=20)的脑脊液和血液样本,检测脑脊液和血清PCT,脑脊液和血液乳酸水平等指标并进行统计分析。结果感染组脑脊液和血清PCT、乳酸水平较非感染组显著升高,差异有统计学意义(P0.05)。脑脊液PCT和乳酸水平诊断敏感性及特异性均较血清PCT和乳酸水平高。结论脑脊液PCT、乳酸在颅脑手术术后颅内感染的诊断中均有意义,其中脑脊液PCT较乳酸敏感性更高,临床应用价值更大。     

Who should do endovascular repair of complex aortic aneurysms and how should they do them?

BackgroundCure of aneurysms which involve the aorta at the level of the visceral arteries and the thoracoabdominal segment remains a considerable surgical enterprise with a relatively high mortality and morbidity despite improvements of the surgical procedure and anesthetic technique. Fenestrated and branched endovascular stent grafts are currently available offering an attractive less invasive option especially for most frail patients. These grafts are relatively recent, technically more demanding to insert than the current stent graft for infrarenal aneurysm and besides, given the relative low frequency of the disease, they are much less used by practitioners. Thus, unconditional widespread of this sophisticated technique may not necessarily benefit patients.MethodsWe reviewed our experiences and articles regarding this concern, 1) who should perform this new technique and 2) in what kind of setting.ConclusionBased on the combined complexities of 1) patients selection, 2) proper planning and manufacturing of the graft, 3) the need for outstanding imaging and operating facilities, 4) and the required endovascular skill of physicians involved in the procedure, we feel that only highly specialized centers should be allowed to perform this complex procedure.     

Residential Greenness Alters Serum 25(OH)D Concentrations: A Longitudinal Cohort of Chinese Older Adults

ObjectivesVitamin D deficiency is prevalent among older adults. We aimed to study whether residential greenness could alter serum 25(OH)D concentrations as a possible mechanism of residential greenness's positive health effects.DesignA longitudinal cohort study.Setting and ParticipantsWe included older adults aged ≥65 years from the Chinese Longitudinal Healthy Longevity Survey (CLHLS) with follow-up between 2012 and 2014.MethodsWe measured residential greenness by calculating annual average Normalized Difference Vegetation Index (NDVI) in a 500 m radius by using satellite images around each participant's residential address. Serum 25-hydroxyvitamin D (25(OH)D) concentration was dichotomized into 2 categories: nondeficiency (≥50 nmol/L) and deficiency (<50 nmol/L). We used the generalized estimating equation to examine the relationship between annual average NDVI and serum 25(OH)D.ResultsWe included 1336 participants in our analysis. The annual average NDVI was 0.49, and mean serum 25(OH)D was 43 nmol/L at baseline. Each 0.1-unit increase in annual average NDVI was associated with a 13% higher odds of vitamin D nondeficiency [95% confidence interval (CI): 1.01, 1.26]. The association was stronger among men [odds ratio (OR): 1.17, 95% CI: 1.02, 1.35] than women (OR: 1.08, 95% CI: 0.91, 1.29) and also stronger among those who were free of activities of daily living (ADL) disability at baseline (OR: 1.12, 95% CI: 1.00, 1.25). During the follow-up period, the participants who lived in greener areas were more likely to have an improved, rather than stable or deteriorated, vitamin D status (OR: 1.94, 95% CI: 1.51, 2.51).Conclusions and ImplicationsOur study suggests that higher levels of residential greenness are associated with higher serum 25(OH)D concentrations, which has implications for prevention of vitamin D deficiency among older adults.