Ziheng Wu

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.

Induction of autophagy by salidroside through the AMPK-mTOR pathway protects vascular endothelial cells from oxidative stress-induced apoptosis

Vascular endothelial cells are highly sensitive to oxidative stress, and this is one of the mechanisms by which widespread endothelial dysfunction is induced in most cardiovascular diseases and disorders. However, how these cells can survive in oxidative stress environments remains unclear. Salidroside, a traditional Chinese medicine, has been shown to confer vascular protective effects. We aimed to understand the role of autophagy and its regulatory mechanisms by treating human umbilical vein endothelial cells (HUVECs) with salidroside under oxidative stress. HUVECs were treated with salidroside and exposed to hydrogen peroxide (H2O2). The results indicated that salidroside exerted cytoprotective effects in an H2O2-induced HUVEC injury model and suppressed H2O2-induced apoptosis of HUVECs. Pretreatment with 3-methyladenine (3-MA), an autophagy inhibitor, increased oxidative stress-induced HUVEC apoptosis, while the autophagy activator rapamycin induced anti-apoptosis effects in HUVECs. Salidroside increased autophagy and decreased apoptosis of HUVECs in a dose-dependent manner under oxidative stress. Moreover, 3-MA attenuated salidroside-induced HUVEC autophagy and promoted apoptosis, whereas rapamycin had no additional effects compared with salidroside alone. Salidroside upregulated AMPK phosphorylation but downregulated mTOR phosphorylation under oxidative stress; however, administration of compound C, an AMPK inhibitor, abrogated AMPK phosphorylation and increased mTOR phosphorylation and apoptosis compared with salidroside alone. These results suggest that autophagy is a protective mechanism in HUVECs under oxidative stress and that salidroside might promote autophagy through activation of the AMPK pathway and downregulation of mTOR pathway.

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.

The Use of the Angiosome Concept for Treating Infrapopliteal Critical Limb Ischemia through Interventional Therapy and Determining the Clinical Significance of Collateral Vessels

BACKGROUND The purpose of this study was to evaluate the clinical significance of the involvement of collateral vessels in interventional therapy based on the angiosome concept for infrapopliteal critical limb ischemia (CLI). METHODS We enrolled 486 patients with unilateral infrapopliteal CLI (Rutherford Stage 5 or 6) treated at 2 hospitals from January 2005 to December 2014. Using the angiosome concept, the patients were categorized into 3 groups: the direct revascularization (DR) group, the indirect revascularization through collaterals (IR-tc) group, and the indirect revascularization without collaterals (IR-wc) group. The data from 1 year of follow-up after the initial surgery were analyzed for all 3 groups. RESULTS During the 1-year follow-up, the unhealed ulcer rate of the IR-wc group was significantly higher than that of the DR group (83.4% vs. 31.7%, P < 0.001) and the IR-tc group (83.4% vs. 34.8%, P < 0.001). Furthermore, the limb salvage rate of the IR-wc group was significantly lower than that of the DR group (70.4% vs. 89.2%, P < 0.001) and the IR-tc group (70.4% vs. 85.4%, P = 0.0013). However, there were no differences in the unhealed ulcer rate or the limb salvage rate between the DR group and the IR-tc group (31.7% vs. 34.8%, P = 0.096 and 89.2% vs. 85.4%, P = 0.2834, respectively). In addition, within the IR-wc group, the unhealed ulcer rate of diabetic patients was higher than that of patients without diabetes (90.0% vs. 74.6%, P = 0.0116), but there was no difference in the limb salvage rate between diabetic and nondiabetic patients. No differences in the unhealed ulcer rate or the limb salvage rate were found between diabetic and nondiabetic patients in the other 2 groups. CONCLUSIONS Following the angiosome model of perfusion for endovascular therapy, directly revascularizing the feeding artery and indirectly achieving revascularization through collaterals can effectively prompt the healing of ulcers and decrease the amputation rate in patients with infrapopliteal CLI. Collateral vessels play a crucial role in the treatment of ischemic foot.

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.

Favourable Outcomes of Endovascular Total Aortic Arch Repair Via Needle Based In Situ Fenestration at a Mean Follow-Up of 5.4 Months

Objectives: Endovascular repair of aortic arch pathologies remains challenging. Recently, needle based in situ fenestration (ISF) has shown great potential in endovascular total aortic arch repair (ETAAR). This study aimed to evaluate the feasibility, effectiveness, and safety of ETAAR via needle based ISF, and to present initial experience with this technique. Design and methods: Patients who met the inclusion criteria were enrolled in this prospective study. The supra-arch branches were manually punctured in a retrograde manner using liver biopsy needles (18 gauge/30 cm) in the left common carotid artery (LCCA) and brachiocephalic trunk (BCT), and endo-puncture system or aspiration biopsy needles (21-gauge) in the left subclavian artery (LSA). All the branches were revascularised with bridge stents. Routine follow-up occurred at 1, 3, 6, and 12 months post surgery. Results: Ten patients with arch pathologies underwent ETAAR. Revascularisation of three branches was successfully performed in eight patients, but attempts to create ISF in LSA were unsuccessful in two patients because of tortuosity and sharp angle. The time taken to establish ISF in LCCA and BCT was 100.4s and 489.6s, respectively. Bilateral regional cerebral oxygen saturation (RCOS) decreased after the arch endograft deployment (both, p < .001) and recovered to the pre-operative level once both carotid arteries were reconstructed (left, p = .0856; right, p = .6). The right RCOS was higher with the beneficial effect of extracorporeal circulation (after cTAGs deployment, p < .001; after LCCA revascularised, p = .0148) during the ischaemic period. In one case, the left iliac artery ruptured, but no ISF related or neurological complications occurred. An early follow-up (mean 5.44 months) CTA and ultrasound confirmed patency of all the branch grafts without any endoleak or migration. Conclusions: This study demonstrated that ETAAR via needle based ISF, making full use of off the shelf devices and techniques, can be successfully performed in aortic arch pathologies with a favourable early outcome.