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The successful treatment of limb ischemia requires that promote angiogenesis along with microenvironment improvement. Zinc ions have been reported to stimulate angiogenesis, but application was limited to the toxicity concerns. We hypothesized that zinc based metal-EGCG capsule (EGCG/Zn Ps) can achieve sustained release Zn 2+ resulting in reduced toxicity and improve angiogenesis as well as the improvement of microenvironment by ROS scavenging of EGCG. The surface morphology, zeta potential, infrared absorbance peaks and zinc ion release profile of the EGCG/Zn Ps were measured. In vitro, EGCG/Zn showed significantly antioxidant, anti-inflammatory and induced cell migration effect. In addition, EGCG/Zn Ps enabled the sustained release of zinc ions, which reduced cytotoxicity and enhanced the secretion of vascular endothelial growth factor (VEGF) in vitro and in vivo. In mouse models of limb ischemia, EGCG/Zn Ps promoted angiogenesis and cell proliferation in ischemic tissues. Moreover, EGCG/Zn Ps group exhibited the most significant recovery of limb ischemic score, limb temperature and blood flow than other groups. In conclusion, EGCG/Zn Ps is a safe and promising approach to combine the merit of Zn 2+ and EGCG, thus enabling the direct application to limb ischemia.

Background We discuss the presentation and management of extracranial carotid artery aneurysms (ECAAs) and to develop a new type of classification. Material/Methods A retrospective review of 35 ECAAs patients who were admitted in our institution from January 2010 to June 2016 was conducted. The mean follow-up period was 25.58±22.13 months. Results During the study period, 35 aneurysms were diagnosed and treated (mean age, 50.8±15.6 years; 15 men). There were 28 true aneurysms, 5 false aneurysms, and 2 dissecting aneurysms. A total of 16 patients with true aneurysms underwent open surgical treatment (group 1), whereas 15 received endovascular management, including all false and dissecting aneurysms (group 2). The remaining 4 true aneurysms were treated with hybrid operation (group 3). The patency rates of groups 1, 2, and 3 were 100%, 93.3%, and 100%, respectively. According to the Peking Union Medical College Hospital (PUMCH) Classification, all 24 cases of type Ia aneurysms were treated by either open surgery and/or endovascular treatment, whereas all 3 type Ib cases were treated solely by open surgery. All 5 type IIa patients were treated by endovascular treatment, with the exception of 1 failure that was transferred to hybrid operation. All 3 type IIb patients were treated by hybrid operation. Conclusions Open surgery was more frequently feasible in true aneurysms, and endovascular surgery was the first choice for false and dissecting aneurysms. Hybrid operation was available for complicated cases. The PUMCH classification may be helpful for selection of management strategies for ECAAs.

Background:Therapeutic angiogenesis has been shown to promote blood vessel growth and improve tissue perfusion. Nerve growth factor (NGF) has been reported to play an important role in both physiological and pathological angiogenesis. This study aimed to investigate the effects of NGF on angiogenesis and skeletal muscle fiber remodeling in a murine model of hindlimb ischemia and study the relationship between NGF and vascular endothelial growth factor (VEGF) in angiogenesis.Methods:Twenty-four mice were randomly allocated to normal control group (n = 6), blank control group (n = 6), VEGF gene transfection group (n = 6), and NGF gene transfection group (n = 6). The model of left hindlimb ischemia model was established by ligating the femoral artery. VEGF165 plasmid (125 μg) and NGF plasmid (125 μg) was injected into the ischemic gastrocnemius of mice from VEGF group and NGF group, respectively. Left hindlimb function and ischemic damage were assessed with terminal points at 21th day postischemia induction. The gastrocnemius of four groups was tested by hematoxylin-eosin staining, proliferating cell nuclear antigen and CD34 immunohistochemistry staining, and myosin ATPase staining. NGF and VEGF protein expression was detected by enzyme-linked immunosorbent assay.Results:On the 21th day after surgery, the functional assessment score and skeletal muscle atrophy degree of VEGF group and NGF group were significantly lower than those of normal control group and blank control group. The endothelial cell proliferation index and the capillary density of VEGF group and NGF group were significantly increased compared with normal control group and blank control group (P < 0.05). The NGF and VEGF protein expression of NGF group showed a significant rise when compared with blank control group (P < 0.05). Similarly, the VEGF protein expression of VEGF group was significantly higher than that of blank control group (P < 0.05), but there was no significant difference of the NGF protein expression between VEGF group and blank control group (P > 0.05). The type I skeletal muscle fiber proportion in gastrocnemius of NGF group and VEGF group was significantly higher than that of blank control group (P < 0.05).Conclusions:NGF transfection can promote NGF and VEGF protein expression which not only can induce angiogenesis but also induce type I muscle fiber expression in ischemic limbs.

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In order to elucidate the pathogenesis and explore new biomarkers for diabetes and diabetic foot (DF), an analysis using RNA sequencing affords broader insights into gene expression regulatory networks in DF. To better explore the molecular basis of DF, we carried out an analysis of circular RNA (circRNA) and messenger RNA (mRNA) expression profiles of serum samples from DF patients and diabetes mellitus (DM) patients. The potential roles and interactions of differentially expressed circRNAs and mRNAs were classified by gene ontology enrichment and Kyoto Encyclopedia of Genes and Genomes pathway analyses. Compared with diabetes patients, 279 mRNAs were upregulated and 353 mRNAs were downregulated in the serum of DF patients, and 33 circRNAs were differently expressed. The differential genes at the nodes of the interaction network were screened, and TLR6 RUNX1 and ST2 were found to be related to the progression of diabetes and DF. The enrichment pathway analysis revealed that the lysosomal pathway played a critical role in the occurrence and development of DF. TLR6, RUNX1, and ST2 mRNA expressions and the lysosomal pathway may be involved in the pathogenesis of diabetes and DF. In addition, methane metabolism and Chagas disease pathways were observed in the occurrence and development of DF, which is a new discovery in this study. This study provides clues on the molecular mechanisms of DF at the circRNA and mRNA levels.

Background:The chimney/periscope technique has been used to address complex aortic pathologies. This study aimed to report the outcomes and experiences of chimney and/or periscope grafts (CPGs) used in the endovascular management of complex aortic pathologies.Methods:Twenty-two patients with complex aortic pathologies were retrospectively studied from January 2013 to August 2016 in two vascular centers of teaching hospitals. All patients were diagnosed using computed tomography angiography (CTA). The patients were followed up at postoperative 1, 3, 6, and 12 months and yearly thereafter with X-ray, ultrasound, and/or CTA.Results:Twenty-two cases (17 males; mean age 60.7 ± 16.3 years) with complex aortic pathologies were analyzed. Nineteen patients underwent CPGs only, and the other three cases underwent the simultaneous implantation of chimney/periscope and fenestrated/scallop grafts. Twenty-six arteries were managed with forty CPGs during the procedures. Complete angiographies revealed two Type I endoleaks, one Type III endoleak, and one Type IV endoleak. Other intraoperative complications included brachial thrombosis, external iliac artery rupture, and left renal stenosis. The 30-day mortality was 0. The mean follow-up was 26.1 ± 10.1 months with a range of 2–39 months. During the follow-up, two Type I endoleaks and one Type IV endoleak were observed. One right renal stent occlusion occurred in the 5th month and turned patent after reintervention. Three patients died during the follow-up, one due to an aneurysm rupture as a Type I endoleak, and two due to myocardial infarction. The instant technical success was 96%. The primary and secondary patencies were 92% and 96%, respectively. The overall survival rates were 95%, 84%, and 84% at 12, 24, and 36 months, respectively. Stent migration was not observed in any patient.Conclusions:Chimney/periscope techniques could be used to tackle complex aortic pathologies, but the indications must be strictly controlled, and additional experiences are required.

Objectives: Takayasu Arteritis (TA) is a highly specific vascular inflammation and poses threat to patients’ health. Although some patients have accepted medical treatment, their culprit lesions require surgical management (TARSM). This study aimed at dissecting the transcriptomes of peripheral blood mononuclear cells (PBMCs) in these patients and to explore potential clinical markers for TA development and progression.Methods: Peripheral blood were collected from four TA patients requiring surgical management and four age-sex matched healthy donors. Single cell RNA sequencing (scRNA-seq) was adopted to explore the transcriptomic diversity and function of their PBMCs. ELISA, qPCR, and FACS were conducted to validate the results of the analysis.Results: A total of 29918 qualified cells were included for downstream analysis. Nine major cell types were confirmed, including CD14+ monocytes, CD8+ T cells, NK cells, CD4+ T cells, B cells, CD16+ monocytes, megakaryocytes, dendritic cells and plasmacytoid dendritic cells. CD14+ monocytes (50.0 vs. 39.3%, p &lt; 0.05) increased in TA patients, as validated by FACS results. TXNIP, AREG, THBS1, and CD163 increased in TA patients. ILs like IL-6, IL-6STP1, IL-6ST, IL-15, and IL-15RA increased in TA group.Conclusion: Transcriptome heterogeneities of PBMCs in TA patients requiring surgical management were revealed in the present study. In the patients with TA, CD14+ monocytes and gene expressions involved in oxidative stress were increased, indicating a new treatment and research direction in this field.