Docetaxel-loaded nanoparticles based on star-shaped mannitol-core PLGA-TPGS diblock copolymer for breast cancer therapy

A star-shaped biodegradable polymer, mannitol-core poly(d,l-lactide-co-glycolide)-d-α-tocopheryl polyethylene glycol 1000 succinate (M-PLGA-TPGS), was synthesized in order to provide a novel nanoformulation for breast cancer chemotherapy. This novel copolymer was prepared by a core-first approach via three stages of chemical reaction, and was characterized by nuclear magnetic resonance, gel permeation chromatography and thermogravimetric analysis. The docetaxel-loaded M-PLGA-TPGS nanoparticles (NPs), prepared by a modified nanoprecipitation method, were observed to be near-spherical shape with narrow size distribution. Confocal laser scanning microscopy showed that the uptake level of M-PLGA-TPGS NPs was higher than that of PLGA NPs and PLGA-TPGS NPs in MCF-7 cells. A significantly higher level of cytotoxicity was achieved with docetaxel-loaded M-PLGA-TPGS NPs than with commercial Taxotere®, docetaxel-loaded PLGA-TPGS and PLGA NPs. Examination of the drug loading and encapsulation efficiency proved that star-shaped M-PLGA-TPGS could carry higher levels of drug than linear polymer. The in vivo experiment showed docetaxel-loaded M-PLGA-TPGS NPs to have the highest anti-tumor efficacy. In conclusion, the star-like M-PLGA-TPGS copolymer shows potential as a promising drug-loaded biomaterial that can be applied in developing novel nanoformulations for breast cancer therapy.     

血浆氮末端-前体脑钠肽水平预测心脏再同步化治疗的近期临床疗效

目的:探讨血浆氮末端-前体脑钠肽(NT-proBNP)水平对心脏再同步化治疗(CRT)近期临床疗效的预测价值。方法:入选成功施行CRT的心力衰竭(心衰)患者42例,ELISA法测定血浆NT-proBNP水平。随访6个月,记录心功能分级、左室射血分数(LVEF)、左室舒张末期内径(LVEDd)、QRS间期及心血管事件(心衰再入院、恶性心律失常、心脏性猝死)。结果:入选患者中,CRT有反应者34例,无反应者8例,有效率达81%。CRT术前反应组血浆NT-proBNP水平低于无反应组(P<0.05)。CRT术后6个月反应组LVEF、LVEDd、QRS间期与无反应组比较,均差异有统计学意义(均P<0.01)。Logistic回归分析显示术前NT-proBNP能独立预测CRT临床疗效。术前NT-proBNP对CRT近期临床疗效判定的ROC曲线下面积为0.770,灵敏度为87.5%,特异度为55.9%。结论:血浆NT-proBNP水平可作为评价CRT近期临床疗效的指标。     

75岁以上急性心肌梗死患者的临床特征

目的:了解执行《心肌梗死全球统一定义》后,75岁以上高龄急性心肌梗死(acute myocar-dial infarction,AMI)患者的临床特征。方法:入选2009年7月至2011年8月在我院心内科冠心病监护病房住院的老年AMI患者563例,年龄≥75岁的患者作为高龄组,65～74岁的患者作为对照组(非高龄老年组)。回顾性分析两组患者的一般情况、吸烟、心脑血管疾病史、主要症状与体征、生化、心电图、超声心动图结果、主要治疗、合并疾病、并发症、院内不良事件等临床资料和随访情况,并进行比较。结果:与对照组比较,高龄组女性、既往有心绞痛和心肌梗死及脑血管病史、无典型胸痛症状、非ST段抬高心肌梗死(NSTEMI)的比例较高(P<0.05);院前延误时间较长(P<0.01);而舒张压、低密度脂蛋白胆固醇、肌酸激酶同工酶(CK-MB)峰值、左心室射血分数较低;接受血运重建、RAS抑制剂治疗的比例较低(P<0.05),合并疾病、并发症、院内不良事件发生率和病死率更高(P<0.05)。在高龄组中,男性比女性吸烟率较高(P<0.05),接受血运重建率也有增高的趋势(P=0.0682)。随访发现两组患者院外坚持服用阿司匹林、β受体阻滞剂、β受体阻滞剂、肾素血管紧张素抑制剂(RAS)、他汀类调脂药物的百分率均较住院时显著下降(P<0.05),而高龄组比对照组坚持服药率更低(P<0.05);高龄组较对照组院外病死率、再住院率更高(P<0.05)。结论:与非高龄老年组比较,高龄组AMI患者一般情况较差,合并疾病和并发症较多;女性、NSTEMI的比例较高;症状不典型、就诊较晚;较少接受充分治疗,预后较差。     

Positive effects of concomitant heavy metals and their reduzates on hexavalent chromium removal in microbial fuel cells

Cr(vi) laden wastewaters generally comprise a range of multiple heavy metals such as Au(iii) and Cu(ii) with great toxicity. In the present study, cooperative cathode modification by biogenic Au nanoparticles (BioAu) reduced from aqueous Au(iii) and in situ Cu(ii) co-reduction were investigated for the first time to enhance Cr(vi) removal in microbial fuel cells (MFCs). With the co-existence of Cu(ii) in the catholyte, the MFC with carbon cloth modified with nanocomposites of multi-walled carbon nanotubes blended with BioAu (BioAu/MWCNT) obtained the highest Cr(vi) removal rate (4.07 ± 0.01 mg L⁻¹ h⁻¹) and power density (309.34 ± 17.65 mW m⁻²), which were 2.73 and 3.30 times as high as those for the control, respectively. The enhancements were caused by BioAu/MWCNT composites and deposited reduzates of Cu(ii) on the cathode surface, which increased the adsorption capacity, electronic conductivity and electrocatalytic activity of the cathode. This study provides an alternative approach for efficiently remediating co-contamination of multiple heavy metals and simultaneous bioenergy recovery.

The cooperative cathode modification by BioAu from Au(iii) and in situ Cu(ii) co-reduction enhanced Cr(vi) removal and bioelectricity generation in MFCs.     

Recent advances in the chemistry and biology of azaphilones

Azaphilones have continuously aroused considerable attention owing to their structural diversity and significant biological activities recently. This review attempts to give a comprehensive summary of recent progress on the isolation, identification, and biological activity, along with synthetic and biosynthetic studies of azaphilones reported from October 2012 to December 2019. Herein, a total of 252 compounds predominantly originated from 32 genera of fungi, such as Penicillium (20%) and Talaromyces (11%), were included in this research with citations of 105 references. Among these azaphilones, approximately half of them were found with various biological activities, of which over 40% displayed cytotoxic/anti-tumor effects. This review would shed light on the future development and research of azaphilones.

Recent advances in the chemistry and biology of structurally diverse azaphilones from 2012 to 2019.     

中晚期宫颈癌伴绝经患者综合治疗的临床观察

目的 本研究通过应用三维适形放疗加热疗及抗骨质疏松药物的综合治疗100例宫颈癌伴绝经患者,探讨综合治疗的可行性和优越性,以改进临床工作,提高肿瘤患者的生活质量和疗效。预防和延迟 骨质疏松的发生。方法 将100例宫颈癌患者分为三维适形放疗加热疗及抗骨质疏松药物组50例（R＋H＋OP）和单纯三维适形放疗组50例（R）。治疗过程中观察不良反应,治疗结束后一个月评价疗效。结果 宫颈癌伴绝经患者与对照组相比BGP、BMD均明显降低,P<0.01、P <0.001;AKP升高,两者比较有明显差异,P <0.05; 血 Ca、P无明显变化,P >0.05。结论 对中晚期宫颈癌伴绝经患者用三维适形放疗加热疗及抗骨质疏松药物综合治疗的同时,测定BGP、BMD、AKP等具有临床价值。为进一步提高患者的生活质量必须采取适当的治疗和预防措施,以降低恶性肿瘤的骨转移及其引起的骨破坏,有针对性的选择适形放疗热疗及抗骨质疏松药物等同时对肿瘤引起的骨破坏或继发病症进行治疗和预防,以减轻症状和防止严重并发症的发生。     

Umbrella-shaped, memory alloy femoral head support device for treatment of avascular osteonecrosis of the femoral head

Purpose

Avascular necrosis (AVN) of the femoral head is a common orthopaedic disease that is difficult to treat. The purpose of this study was to explore the preliminary efficacy of a self-designed umbrella-shaped memory alloy femoral head support device in the treatment of adult patients with avascular osteonecrosis of the femoral head.

Methods

The minimally-invasive approach involved curettage of the necrotic tissue of the femoral head, and a self-designed umbrella-shaped, memory alloy femoral head support device was implanted into the collapsed necrotic area to support the collapsed femoral head. Autologous iliac bone and artificial bone were implanted into the support device for the treatment of adult patients with avascular osteonecrosis of the femoral head.

Results

The clinical device was used in ten patients and 18 hip joints. The support device failed in one hip joint, which subsequently underwent joint replacement surgery, and the remaining 17 implanted devices were followed up for four to 19 months. The 17 postoperative hip joints were evaluated using the percent-efficacy evaluation method for avascular osteonecrosis of the femoral head in adult patients, and the efficacy rate was 82.35 %.

Conclusion

The umbrella-shaped femoral head support device can be used in Ficat stage I, stage II, and stage III adult patients with avascular osteonecrosis of the femoral head.     

Local Immune Response Predicts Survival in Patients with Thick (T4) Melanomas

Background

Tumor infiltrating lymphocytes (TIL) and histological regression in primary melanoma are generally considered indicators of the local immune response but their roles as prognostic factors have been variably reported. We examined the prognostic role of these variables in patients with high risk (T4) primary melanomas in a large series of patients with long-term follow-up.

Methods

From a prospectively maintained cohort of patients diagnosed between 1971 and 2004, 161 patients were retrospectively identified with primary thick melanomas (>4 mm), no clinical evidence of regional nodal disease (RND) at diagnosis and complete histopathologic data. Univariate and multivariate Cox regression models were performed to identify clinical and histopathologic predictors of disease-specific survival (DSS) and to identify subgroups with differential survival.

Results

Factors significantly associated with decreased DSS by univariate analysis included male gender, age ≥ 60 years, axial anatomic location, presence of ulceration, RND, absence of TIL, and presence of regression. In the final multivariate model, TIL and regression, as interacting variables, and RND status remained significantly associated with DSS. In the presence of TIL, concomitant regression was associated with significantly worse survival (p ≤ 0.0001). In the absence of TIL, there was no effect of regression on survival (p = 0.324).

Conclusions

Primary TIL and regression status and RND status are independently associated with melanoma-specific survival in patients with T4 melanomas; presence of TIL in the primary melanoma with concomitant radial growth phase regression is associated with a poor prognosis and may reflect an ineffective local regional immune response.