非均整模式的脑转移癌分次立体定向放射治疗的剂量学研究

目的：分析非均整模式与均整模式在脑转移癌分次立体定向放射治疗中的剂量学差异，为FFF模式的脑转移癌FSRT提供剂量学参考。方法：回顾性分析2017年7月至2018年9月间，我院收治的全部实施FSRT的脑转移癌患者，共17例。对所有患者按照临床治疗计划优化参数重新设计FF模式治疗计划。比较FFF模式和FF模式计划之间靶区剂量学参数、正常脑组织剂量参数和治疗效率参数，配对t检验其差异。结果： FFF与FF计划相比，梯度指数更低(3.31±0.97 vs. 3.45±0.87，P=0.017)，差异有统计学意义。FFF及FF计划的D5%、D50%、非均匀性指数、适形度指数差异均无统计学意义。相较于FF模式，FFF模式计划中V12GyBED-Brain及Dmean-Brain均较小[（43.55±35.72） cm3 vs.( 47.75±38.79) cm3；(648.39±411.86)Gy vs. (667.15± 418.01Gy）]，P值分别为0.003和0.006，差异有统计学意义。FFF模式计划的MU为1320.46± 354.99，高于FF模式（1220.74±267.86）， P=0.004，差异有统计学意义。结论：FFF模式靶区外剂量跌落更快，正常脑组织剂量更低，有利于更好地保护正常脑组织。FFF模式计划未提高FSRT的治疗效率。     

连续腘窝上坐骨神经联合隐神经阻滞镇痛对足踝皮瓣移植后皮瓣成活和局部血运的影响

目的：探讨连续腘窝上坐骨神经联合隐神经阻滞镇痛对足踝皮瓣移植后皮瓣成活以及局部血运的影响。方法：选择2018年3月至2019年4月在宁波市第六医院择期行股外侧皮瓣移植足踝部皮肤软组织缺损的患者60例，美国麻醉医师协会（ASA）分级为I～II级，随机分为连续腘窝上坐骨神经联合隐神经阻滞镇痛组（S组）和静脉自控镇痛组（C组），每组30例。观察2组患者足踝部游离移植皮瓣后皮瓣的血液循环及皮瓣成活的变化，记录2组患者术后6 h、12 h、24 h、2 d、3 d各个时点VAS评分及不良反应发生情况。结果：S组患者毛细血管充盈时间评分、局部皮瓣弹性评分和皮瓣存活率均高于C组，血管危象率低于C组（P＜0.05），术后6 h、12 h 、24 h、2 d、3 d的VAS评分S组更低（P＜0.05）；S组不良反应发生率低于C组（P＜0.05）。结论：连续腘窝上坐骨神经联合隐神经阻滞镇痛可提高足踝皮瓣移植术患者皮瓣局部血运，提高皮瓣成活率。     

国家免费孕前优生健康检查项目试点的措施、成效与建议

出生缺陷是导致早期流产、死胎、围产儿死亡、婴幼儿死亡和先天残疾的主要原因。实施国家免费孕前优生项目,预防出生缺陷,造福子孙后代,是坚持以人为本、贯彻落实科学发展观的具体举措。该文结合所在地区国家免费孕前优生健康检查工作的开展情况,介绍了项目试点服务对象、目的和内容,阐述了项目试点的具体措施和工作成效,提出了做好下一步工作的建议。     

Application of Trifluoroacetic Acid as a Theranostic Agent for Chemical Ablation of Solid Tissue

PurposeTo evaluate trifluoroacetic acid (TFA) as a theranostic chemical ablation agent and determine the efficacy of TFA for both noninvasive imaging and tissue destruction.Materials and MethodsFluorine-19 magnetic resonance imaging (¹⁹F-MRI) was optimized at 7 T using a custom-built volume coil. Fluorine images were acquired with both rapid acquisition with relaxation enhancement and balanced steady-state free precession (bSSFP) sequences with varying parameters to determine the optimal sequence for TFA. The theranostic efficacy of chemical ablation was examined by injecting TFA (100 μL; 0.25, 0.5, 1.0, and 2.0M) into ex vivo porcine liver. ¹⁹F and proton MRI were acquired and superimposed to visualize distribution of TFA in tissue and quantify sensitivity. Tissue damage was evaluated with gross examination, histology, and fluorescence microscopy.ResultsThe optimal ¹⁹F-MRI sequence was found to be bSSFP with a repetition time of 2.5 ms and flip angle of 70°. The minimum imageable TFA concentration was determined to be 6.7 ± 0.5 mM per minute of scan time (0.63×0.63×5.00 mm voxel), and real-time imaging (temporal resolution of at least 1 s^-1) was achieved with 2M TFA both in vitro and in ex vivo tissue. TFA successfully coagulated tissue, and damage was locally confined. In addition to hepatic cord disruption, cytoskeletal collapse and chromatin clumping were observed in severely damaged areas in tissues treated with 0.5M or higher TFA concentrations.ConclusionsTFA was determined to be a theranostic agent for chemical ablation of solid tissue. Ablation was both efficacious and imageable in ex vivo healthy tissue, even at low concentrations or with high temporal resolution.     

Novel protease inhibitor-loaded Nanoparticle-in-Microparticle Delivery System leads to a dramatic improvement of the oral pharmacokinetics in dogs

With the advent of the Highly Active Antiretroviral Therapy, the morbidity and the mortality associated to HIV have been considerably reduced. However, 35–40 million people bear the infection worldwide. One of the main causes of therapeutic failure is the frequent administration of several antiretrovirals that results in low patient compliance and treatment cessation. In this work, we have developed an innovative Nanoparticle-in-Microparticle Delivery System (NiMDS) comprised of pure drug nanocrystals of the potent protease inhibitor indinavir free base (used as poorly water-soluble model protease inhibitor) produced by nanoprecipitation that were encapsulated within mucoadhesive polymeric microparticles. Pure drug nanoparticles and microparticles were thoroughly characterized by diverse complementary techniques. NiMDSs displayed an encapsulation efficiency of approximately 100% and a drug loading capacity of up to 43% w/w. In addition, mucoadhesiveness assays ex vivo conducted with bovine gut showed that film-coated microparticles were retained for more than 6 h. Finally, pharmacokinetics studies in mongrel dogs showed a dramatic 47- and 95-fold increase of the drug oral bioavailability and half-life, respectively, with respect to the free unprocessed drug. These results support the outstanding performance of this platform to reduce the dose and the frequency of administration of protease inhibitors, a crucial step to overcome the current patient-incompliant therapy.     

Differentiating benign from malignant cardiac tumors with cardiac magnetic resonance imaging

Background

The purpose of this analysis is to describe the differences in cardiac magnetic resonance characteristics between benign and malignant tumors, which would be helpful for surgical planning.

Assessing Retention in a Free Diabetes Clinic

The PATH Clinic in Birmingham, Alabama, is a free clinic for uninsured patients with uncontrolled diabetes. In its first 22 months, more than 25% of patients were lost to follow-up. This report shares reasons for patients becoming lost to follow-up. Investigators used patient records for quantitative analyses and phone interviews for qualitative analysis. Sociodemographic factors were not associated with patients’ likelihood of becoming lost to follow-up. Qualitative results show that these patients had uncertainty regarding appointment dates, complicated life circumstances, and transportation barriers. Results indicate that social interventions may improve patient compliance and retention and should be tested.     

Toxicity of ZnO nanoparticles (NPs) to THP-1 macrophages: interactions with saturated or unsaturated free fatty acids

In a biological microenvironment, free fatty acids (FFA) as ubiquitous biological molecules might interact with nanoparticles (NPs) and consequently change the toxicological responses. However, whether the chemical structures of FFA could influence their interactions with NPs remain unknown. This study investigated the interactions between ZnO NPs and saturated or unsaturated FFA (complexed to BSA), namely stearic acid (SA, C18:0), oleic acid (OA, C18:1), and α-linolenic acid (ALA, C18:3). It was shown that BSA, SA, OA, and ALA increased the atomic force microscope (AFM) heights as well the polydispersity index (PDI) of ZnO NPs. BSA modestly protected THP-1 macrophages from ZnO NP exposure, whereas OA and ALA led to relatively less cyto-protective effects of BSA. Moreover, only co-exposure to ZnO NPs and SA significantly promoted the release of interleukin-8. BSA, SA, OA, and ALA equally changed intracellular ROS and Zn ions associated with ZnO exposure, but co-exposure to ZnO NPs and OA/ALA particularly activated the expression of endoplasmic reticulum stress-apoptosis genes. In combination, these results showed that FFA could influence the colloidal aspects and toxicological signaling pathway of ZnO NPs, which is dependent on the number of unsaturated bonds of FFA.     

醛糖还原酶和晚期糖基化终末产物受体对糖尿病视网膜病变神经元凋亡的影响

目的　探究醛糖还原酶和晚期糖基化终末产物受体对糖尿病视网膜病变神经元凋亡的影响。方法　Wistar大鼠36只，随机分为对照组、模型组、转染组，后两组建立糖尿病大鼠模型。模型建立成功后，构建含有晚期糖基化终末产物受体siRNA的质粒并利用慢病毒转染入转染组大鼠体内。造模后4周、8周、12周，记录各组大鼠体质量及空腹血糖。造模后9周，禁食6 h，测定口服葡萄糖耐量。造模后12周，处死全部大鼠后，TUNEL法检测各组大鼠视网膜神经元凋亡情况，荧光分光光度计测定醛糖还原酶活性，Western blotting法测定晚期糖基化终末产物受体的表达，RT-PCR检测视网膜中Bcl-2和Bax mRNA相对表达量。结果　造模后4周、8周、12周，转染组和模型组的大鼠体质量均低于对照组（均为P<0.05）；造模后12周，转染组大鼠体质量高于模型组（P<0.05）。造模后4周、8周、12周，各组内大鼠空腹血糖水平均无明显变化（均为P>0.05），转染组和模型组大鼠的空腹血糖水平均高于对照组（均为P<0.05）。模型组和转染组大鼠在口服葡萄糖后30 min时，血糖水平均高于对照组（均为P<0.05）；在120 min时分别下降至最低，但仍高于对照组（均为P<0.05）。模型组和转染组的视网膜神经元凋亡指数、醛糖还原酶活性、晚期糖基化终末产物受体和Bax mRNA相对表达量均高于对照组（均为P<0.05），且转染组均高于模型组（均为P<0.05）。模型组和转染组的Bcl-2 mRNA相对表达量均低于对照组（均为P<0.05），转染组低于模型组（P<0.05）。结论　晚期糖基化终末产物结合受体后产生大量的氧自由基损伤，可能是导致糖尿病视网膜神经元凋亡，进而导致糖尿病视网膜病变发生的机制之一。