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.     

Does Outcome/Survival of Patients With Myelodysplastic Syndromes Should Be Predicted by Reduced Levels of ADAMTS-13? Results From a Pilot Study

IntroductionVon Willebrand factor (vWF) cleaving protease ADAMTS-13 has a key role for maintaining normal size of vWF. A deficiency or dysfunction of vWF cleaving protease is associated with ultra large vWF multimers and thrombotic microangiopathy. Patients with cancers have reduced levels of vWF cleaving protease. In this pilot study, we have evaluated whether or not deficiencies of ADAMTS-13 were present in myelodysplastic syndromes (MDS). Moreover, we assessed if a reduction in basal levels of ADAMTS-13 may play a role in the prognosis of MDS.Patients and MethodsWe measured and compared the levels of vWF cleaving protease ADAMTS-13 in 100 patients with MDS and 35 healthy controls. Patients were divided into 2 groups according to the International Prognostic Scoring System: group I consisting of 44 patients with low-risk MDS and group II of 56 patients with high-risk MDS. Patients with high-risk and low-risk MDS presented significantly lower levels of ADAMTS-13 than controls (P < .001 and P = .0177, respectively). High-risk patients had significantly lower levels of ADAMTS-13 when compared with the low-risk group (P < .001).ResultsWe found that reduced levels of ADAMTS-13 have a relationship with overall survival (P < .001). Statistical analysis showed that ADAMTS-13 correlates with cytogenetics (P < .001) and a tendency of slight correlation with platelet count and basal levels of ADAMTS-13 (R, 0.35; P value, 0.001). Moreover, we found that levels of ADAMTS-13 have correlation with response to treatment (P < .001).ConclusionsADAMTS-13 in MDS might represent a surrogate marker of prognosis, response to therapy, or disease progression. Further studies are needed.     

Novel lipopeptides of ESAT-6 induce strong protective immunity against Mycobacterium tuberculosis: Routes of immunization and TLR agonists critically impact vaccine’s efficacy

Mycobacterium tuberculosis (Mtb), the bacterial cause of tuberculosis, is a leading infectious agent worldwide. The development of a new vaccine against Mtb is essential to control global spread of tuberculosis, since the current vaccine BCG is not very effective and antibiotic resistance is a serious, burgeoning problem. ESAT-6 is a secreted protein of Mtb, which is absent in BCG but has been implicated in inducing protective immunity against Mtb. Peptide based subunit vaccines are attractive due to their safety and high specificity in eliciting immune responses, but small synthetic peptides are usually not very immunogenic. We have designed a novel subunit vaccine for Mtb by using simple lipid (palmitic acid) modified derivatives of peptides from ESAT-6 protein corresponding to dominant human T cell epitopes and examined their ability to stimulate protective immunity against Mtb by intranasal and subcutaneous immunization in mice. We also investigated how individual TLR agonists as adjuvants (PolyI:C, MPL and GDQ) contribute to enhancing the induced immune responses and resulting protective efficacy of our vaccine. We observed that single C-terminal palmitoyl-lysine modified lipopeptides derived from ESAT-6 induce significant cellular immune responses on their own upon mucosal and subcutaneous immunizations. Intriguingly, a combination of immunogenic lipopeptides of ESAT-6 antigen exhibited local (pulmonary) and systemic immune responses along with efficient protective efficacy when administered intranasally or subcutaneously. Surprisingly, combination of ESAT-6 derived lipopeptides with a TLR-4 agonist (MPL) enhanced protection, whereas TLR-3 (Poly I:C) and TLR-7/8 agonists (gardiquimod, GDQ) led to reduced protection associated with specific local and systemic immune modulation. Our studies demonstrate the potential of ESAT-6 derived lipopeptides as a promising vaccine candidate against Mtb, and emphasize that selection of adjuvant is critical for the success of vaccines. These findings demonstrate the promise of synthetic lipopeptides as the basis of a subunit vaccine for TB.     

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.     

负载IL-4及BMP-2的氧化石墨烯-羧甲基壳聚糖凝胶对骨免疫和骨修复的早期影响研究

目的探讨负载 IL-4 和 BMP-2 的氧化石墨烯（graphene oxide，GO）-羧甲基壳聚糖（carboxymethyl chitosan，CMC）凝胶诱导巨噬细胞 M2 型分化及对 BMSCs 成骨分化的影响。方法取 CMC、GO 制备混合溶液后，分别添加 PBS、IL-4、BMP-2 或 IL-4+BMP-2，在交联剂作用下制备单纯或负载不同因子的 GO-CMC 凝胶支架；取单纯 GO-CMC 凝胶表征观测，包括大体、扫描电镜及傅里叶变换红外吸收光谱仪（Fourier transform infrared spectroscopy，FTIR）检测，以单纯 CMC 凝胶作为对照；取负载不同因子的 GO-CMC 凝胶行体外缓释实验。取 4～5 周龄 SPF 级 SD 雌性大鼠分离培养巨噬细胞，分别与单纯以及负载不同因子的 GO-CMC 凝胶培养，24 h 后行 CD206 免疫荧光检测巨噬细胞分化情况；取第 3 代大鼠 BMSCs 分别与单纯以及负载不同因子的 GO-CMC 凝胶成骨诱导培养，10 d 后行 ALP 染色观测早期成骨，21 d 行茜素红染色观测晚期成骨。结果大体观察 GO-CMC 凝胶呈棕色、半透明状；扫描电镜观察示，GO-CMC 凝胶孔径及孔壁厚度与单纯 CMC 凝胶相似，但内壁粗糙度增加；FTIR 检测显示 CMC 发生聚合形成凝胶。体外缓释实验示 3 种负载不同因子的 GO-CMC 凝胶缓释性能相似，均呈线性缓慢释放因子。CD206 免疫荧光检测示 GO-CMC 凝胶可诱导巨噬细胞 M2 型分化，ALP 及茜素红染色示 GO-CMC 凝胶可诱导 BMSCs 成骨分化；其中负载 IL-4+BMP-2 的 GO-CMC 凝胶作用最显著（P<0.05）。 结论负载 IL-4 和 BMP-2 的 GO-CMC 凝胶可诱导巨噬细胞 M2 型分化，增强 BMSCs 成骨分化能力，为后期骨缺损修复及骨免疫调节研究提供了新的策略。     

臀部筋膜脂肪瓣修复坐骨结节和大转子复发性窦道型压疮

目的总结臀部筋膜脂肪瓣修复坐骨结节、大转子复发性窦道型压疮的效果。方法2018 年 2 月—2019 年 6 月，收治 12 例 13 处长期截瘫伴坐骨结节、大转子复发性窦道型压疮患者。其中男 10 例 11 处，女 2 例 2 处；年龄 46～56 岁，平均 51 岁。截瘫 10～20 年，平均 13 年；所有患者均有压疮手术史，术后 3 个月～12 年复发。其中坐骨结节处压疮 11 例，坐骨结节合并大转子处压疮 1 例。创面清创、切除窦道假性滑液囊，采用单侧或双侧臀部筋膜脂肪瓣填塞窦道，术区一期缝合闭合切口。结果术后 13 处压疮切口均Ⅰ期愈合，局部无红肿、渗液，术后 14 d 拆线出院。术后局部平坦，外观理想。术后患者均获随访，随访时间 8～24 个月，平均 14 个月。随访期间压疮均无复发。结论臀部脂肪组织丰富，利用筋膜脂肪瓣修复坐骨结节、大转子复发性窦道型压疮设计、操作简便，临床效果良好。