Yangyan He

Nutcracker Syndrome—How Well Do We Know It?

Nutcracker syndrome (NCS), which is caused by compression of the left renal vein between the abdominal aorta and the superior mesenteric artery, leads to a series of clinical symptoms including hematuria, proteinuria, flank pain, and varicocele. The diagnosis of NCS is difficult due to variations in normal anatomy. Treatment, which ranges from observation to nephrectomy, remains controversial. We conducted a review based on the related literature and our experience with hundreds of cases. We summarize the characteristics of NCS, the different measurements used in diagnosis, and the current treatment options. We present our diagnostic criteria and recommend endovascular stenting as the primary option for NCS.

Morphologic findings and management strategy of spontaneous isolated dissection of the celiac artery

OBJECTIVE We report the morphologic findings and treatment of spontaneous isolated dissection of the celiac artery (SIDCA). METHODS Twenty-three patients with SIDCA presenting between January 2009 and December 2014 were enrolled in this retrospective study. The demographic data, clinical features, morphologic findings, treatment modalities, and follow-up results of these patients were reviewed. We proposed a morphologic classification for SIDCA similar to that of spontaneous isolated dissection of the superior mesenteric artery. RESULTS Initially, 11 patients were treated endovascularly, and 12 were treated medically. Four patients treated medically had an aggravation of the dissection and needed endovascular salvage. All patients recovered successfully. None of the patients developed abdominal pain, required reintervention, or died. In the medically treated group, the false lumen was completely thrombosed and absorbed in 4 patients, partially thrombosed in 2, and patent in 2. All stents were patent with the false lumen completely thrombosed and absorbed in the endovascular group. CONCLUSIONS SIDCA can be treated medically in stable patients but requires intensive follow-up. Endovascular therapy can be applied in high-risk patients with recurrent symptoms, visceral malperfusion, or aneurysm. Open surgery should be considered if endovascular repair is not suitable or has failed. The short-term results of endovascular management are encouraging but further evaluation with long-term follow-up is necessary.

Stent migration after endovascular stenting in patients with nutcracker syndrome

OBJECTIVE In this study, we sought to investigate the incidence of stent migration after endovascular stenting (EVS) in patients with nutcracker syndrome (NCS) and to discuss the related factors. METHODS We retrospectively evaluated the data of all patients with NCS who were treated by EVS at our single center between January 2004 and October 2014. Data collection included details on clinical findings, radiologic evaluation, laboratory values, EVS procedure, stent size, and morbidity of stent migration. Sex, size of stents, interval (between EVS and stent migration), and preoperative parameters of the left renal vein (LRV) on duplex ultrasound (anteroposterior diameter in aortomesenteric portion and renal hilum of LRV, peak velocity in aortomesenteric portion and renal hilum of LRV) were analyzed. RESULTS A total of 75 patients (49 men) with a median age of 27 years (range, 16-43 years) underwent EVS for NCS. During a mean 55 months (range, 6-126 months) of follow-up, stent migration occurred in five patients (6.7%), and all of them were male. The stent migrated into the right ventricle in one patient, right atrium in one patient, inferior vena cava in two patients, and left side of the LRV in one patient. There were no significant differences in preoperative anteroposterior diameter and peak velocity of the aortomesenteric portion and renal hilum of the LRV on duplex ultrasound between patients with and without stent migration. There were also no significant differences in these parameters between patients with deployment of 12-mm and 14-mm-diameter stents. CONCLUSIONS Stent migration after EVS in patients with NCS is not as rare as we originally thought. Preoperative anatomic parameters of the LRV need to be more accurately measured. Stent choice for the individual patient and accurate stent deployment are important to avoid stent migration. Closer follow-up and early detection and treatment can reduce the number of stent migrations into the heart.

α-Tocopherol, especially α-tocopherol phosphate, exerts antiapoptotic and angiogenic effects on rat bone marrow-derived endothelial progenitor cells under high-glucose and hypoxia conditions

Objective: Considering the poor efficacy of local intramuscular injections with endothelial progenitor cells (EPCs) for critical limb ischemia in patients with diabetes, the study aimed to investigate the effect of &agr;‐tocopherol (&agr;‐T) and &agr;‐tocopherol phosphate (&agr;‐TP) on apoptosis and angiogenesis in a rat model under oxidative stress conditions. Methods: Primary EPCs from Sprague‐Dawley rats were harvested and treated with &agr;‐T and &agr;‐TP for 24 hours. Gene transcription and protein expression were evaluated by real‐time polymerase chain reaction and Western blot, respectively. Cell apoptosis, migration, and tube formation ability were detected by flow cytometry, Transwell assay (Chemicon International, Temecula, Calif), and Matrigel‐based angiogenesis assay (Corning Inc, Corning, NY). The in vivo experiments were carried out using 30 single hind limb ischemic models of diabetic rats that were treated with allogeneic EPCs. Capillary density was evaluated by immunohistochemistry. Results: &agr;‐T and &agr;‐TP attenuated high glucose/hypoxia‐induced cell apoptosis by promoting Bcl‐2 and Akt and inhibiting nuclear factor &kgr;B p65, JNK, Notch‐1, and p38MAPK genes. Furthermore, &agr;‐T and &agr;‐TP promoted the transcription and expression of vascular endothelial growth factor receptor 2 and decreased the transcription and expression of Tie‐2 and Notch‐1 in EPCs under high‐glucose/hypoxic conditions. Moreover, &agr;‐T and especially &agr;‐TP enhanced the migratory activity of EPCs under high‐glucose/hypoxic conditions. Capillary density of ischemic hind limbs was increased on day 14 after administration of EPCs pretreated with &agr;‐T and &agr;‐TP. Conclusions: &agr;‐T, especially &agr;‐TP, possesses therapeutic potential in the inhibition of apoptosis and increases the migratory capacity of EPCs under high‐glucose/hypoxic conditions. It promotes angiogenesis by upregulating Bcl‐2, Akt, and vascular endothelial growth factor receptor 2 and decreasing nuclear factor &kgr;B p65, p38MAPK, Notch‐1, JNK, and Tie‐2. Clinical Relevance: Considering the poor efficacy of local intramuscular injections with endothelial progenitor cells for critical limb ischemia in patients with diabetes, the study aimed to investigate the effect of &agr;‐tocopherol and &agr;‐tocopherol phosphate on apoptosis and angiogenesis in a rat model under oxidative stress conditions. &agr;‐Tocopherol, especially &agr;‐tocopherol phosphate, possesses therapeutic potential in the inhibition of apoptosis and increases the migratory capacity of endothelial progenitor cells under high‐glucose/hypoxic conditions. It promotes angiogenesis by upregulating Bcl‐2, Akt, and vascular endothelial growth factor receptor 2 and decreasing nuclear factor &kgr;B p65, p38MAPK, Notch‐1, JNK, and Tie‐2.

Endovascular Aortic Repair with the Chimney Graft Technique for Abdominal Aortic Pseudoaneurysms with Aorto–Left Renal Vein Fistula

dissecting aortic aneurysm. Our experience in the present case illustrates that embolization of the false lumen can be considered as a therapeutic alternative in patients with ruptured aortic dissection after TEVAR. There are some limitations with coil embolization of false lumens. Fortunately, in the present case, the false lumen was partially thrombosed and was not too large for coils as large as 15 mm in diameter to stabilize and induce thrombosis of the total false lumen of the descending thoracic aorta. In cases with large false lumens, innumerable coils may be needed for embolization. A special, sophisticated device dedicated to embolization of the large-diameter false lumen may be required in such a case. Another drawback of coil embolization of the false lumen together with TEVAR is that it may increase the risk of spinal cord ischemia; this should not be greater in patients with aortic dissection treated with TEVAR alone than in patients with thoracic aortic aneurysms. However, coil embolization of the false lumen together with TEVAR leads to obliteration of blood flow into the intercostal arteries. In fact, paraparesis did develop in the present patient, although it could have occurred as a result of thrombosis of the false lumen by TEVAR even without coil embolization. Alternatively, it is also well known that the risk of spinal cord ischemia after TEVAR is high in those who have a history of Y-graft replacement. Therefore, it is unclear if one, both, or neither of these factors was the cause of the spinal cord ischemia in the present patient. The present patient was successfully treated by shutting down the whole communications between the true and the false lumens in the descending thoracic aorta with the use of TEVAR and false lumen embolization. However, there potentially remains blood inflow to the false lumen supplied by the aortic branches, including the intercostal arteries coming from the false lumen in a similar manner to a type II endoleak in EVAR cases. Therefore, further study is needed to clarify the efficacy of our method.

Comprehensive analysis of differentially expressed profiles of lncRNAs and mRNAs reveals ceRNA networks in the transformation of diffuse large B‑cell lymphoma

Diffuse large B-cell lymphoma (DLBCL) is one of the malignancies with a high mortality rate. The molecular mechanisms involved in transformation of DLBCL remain unclear. Therefore, it is critically important to investigate the biological mechanisms of DLBCL. Accumulating evidence indicates that long non-coding RNAs (lncRNAs) serve key functions in tumorigenesis, cancer progression and metastasis. Compared with follicular lymphoma (FL), a total of 123 upregulated lncRNAs and 192 downregulated lncRNAs in DLBCL were identified. Subsequently, a specific DLBCL-associated competing endogenous RNA (ceRNA) network and a specific FL-associated ceRNA network was constructed. Gene Oncology and Kyoto Encyclopedia of Genes and Genomes pathway analysis revealed that differentially expressed lncRNAs served key functions in regulating signal transduction, transcription, cell adhesion, development and protein amino acid phosphorylation. Furthermore, the molecular functions of PRKCQ antisense RNA 1, HLA complex P5, OIP5 antisense RNA 1, growth arrest specific 5 and taurine upregulated 1 were investigated, and it was revealed that these lncRNAs served important functions in regulating a series of biological processes, including anti-apoptosis, cell cycle, DNA repair, response to oxidative stress and transcription. The present study may provide a potential novel therapeutic and prognostic target for the treatment of DLBCL.

Humanin prevents high glucose-induced monocyte adhesion to endothelial cells by targeting KLF2

HighlightsHumanin increased the expression of KLF2 and regulated its target genes in HUVECs.The effects of humanin on KLF2 expression is mediated by ERK5.Humanin inhibited high glucose‐ induced VCAM‐1, E‐selectin.Humanin inhibited high glucose‐ attachment of THP‐1 cells to HUVECs mediated by KLF2. &NA; Endothelial dysfunction and vascular complications induced by hyperglycemia play an important role in the pathological development of atherosclerosis in diabetes. Humanin, a 24‐amino acid mitochondria‐derived polypeptide, has displayed its cytoprotective effects in diverse cell types and tissues. In the current study, we aimed to characterize the effects of humanin on high glucose‐induced endothelial dysfunction. Firstly, we found that humanin treatment induced the expression of Krüppel‐like factor 2 (KLF2), an essential transcriptional regulator of endothelial function, at the transcriptional level in human umbilical vein endothelial cells (HUVECs). Additionally, our results indicate that humanin treatment regulated the expression of KLF2 target genes such as endothelial nitric oxide synthase (eNOS) and endothelin‐1 (ET‐1). Evidence demonstrated that the effects of humanin on KLF2 expression was mediated by the phosphorylation of extracellular signal regulated kinase 5 (ERK5). Furthermore, humanin restored high glucose‐induced reduction of KLF2 expression. We also showed that humanin significantly reduced the expression of vascular cell adhesion molecule 1 (VCAM‐1) and E‐selectin. Notably, humanin treatment markedly prevented high glucose‐induced attachment of the monocyte THP‐1 cells to HUVECs. However, knockdown of KLF2 abolished these effects. Lastly, we report that humanin treatment inhibited high glucose‐induced secretion of tumor necrosis factor‐&agr; (TNF‐&agr;) and interleukin‐1&bgr; (IL‐1&bgr;). These findings suggest that humanin may have therapeutic potential for the treatment of hyperglycemia‐associated endothelial dysfunction.

Construction of lncRNA‑miRNA‑mRNA networks reveals functional lncRNAs in abdominal aortic aneurysm

Abdominal aortic aneurysm (AAA) is one of the most significant causes of morbidity and mortality in populations aged >65 years worldwide. However, the underlying mechanisms of AAA based on the competitive endogenous RNA (ceRNA) hypothesis have remained elusive. In the present study, differently expressed long non-coding RNA (lncRNA)-microRNA (miRNA)-mRNA networks in AAA were constructed by analyzing public datasets, including GSE7084, GSE24194 from rats and that of a previous study. A total of 1,219 mRNAs, 2,093 lncRNAs and 57 miRNAs were identified to differently express in AAA. Gene Ontology and Kyoto Encyclopedia of Genes and Genomes analyses were performed to explore the potential roles of differently expressed lncRNAs based on their regulating mRNAs. Based on the ceRNA hypothesis, lncRNA-miRNA-mRNA networks in AAA were, for the first time, constructed at a system-wide level. The present study identified 5 upregulated lncRNAs [nuclear paraspeckle assembly transcript 1, cyclin-dependent kinase inhibitor 2B antisense RNA 1, small Cajal body-specific RNA 10, AC005224.4 and SUMO1/sentrin/SMT3-specific peptidase 3-eukaryotic translation initiation factor 4A1] and the downregulated zinc ribbon domain containing 1 antisense RNA 1 as key lncRNAs in ceRNA networks. To the best of our knowledge, the present study was the first to screen ceRNA networks in AAA. In addition, key lncRNA-mRNA-biological processes analysis indicated that these key lncRNAs were involved in regulating signal transduction, protein amino acid phosphorylation, immune response, transcription, development and cell differentiation. The present study provides novel clues to explore the molecular mechanisms of AAA progression in terms of lncRNA implication.

Repeat endovascular repair for multiple intimal tears after endovascular stent grafting of Stanford type B aortic dissection.

A 59-year-old man with hypertension was found to have a Stanford type B aortic dissection with a false lumen extending to the abdominal aorta. We placed a stent graft to the thoracic aorta covering the proximal entry and planned a second endovascular repair to cover the entries in the abdominal aorta. Five years later, computed tomography angiography revealed an extensive dissection to the right common iliac artery with multiple intimal tears. We placed stent grafts in the distal end of the primary stent graft and an abdominal stent graft to the aortic bifurcation to cover the entry tears. However, 3 months later it developed into a newly formed intimal tear in the right renal artery, leading to retrograde reperfusion into the false lumen. The patient was successfully treated with a third time endovascular repair and recovered smoothly during follow-up.