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Background This study aims to report the experience of a single center using thoracic endovascular aortic repair (TEVAR) to treat retrograde type A intramural hematoma (IMH) with focal intimal disruption (FID) in descending aorta. Methods A total of 24 consecutive patients with retrograde type A IMH and complicated with FID in descending aorta underwent TEVAR in our center from 2015 to 2020. Their clinical data, imaging manifestation and follow-up results were retrospectively reviewed and analyzed. Results The median age of patients was 57.9 years (range, 42-80 years) and 18 were men (75%). As the preoperative CT angiography showed, the 24 patients developed IMH complicated with different kinds of FIDs in descending aorta [5 had intramural blood pool (IBP), 15 had ulcer-like projection (ULP), 2 had penetrating atherosclerotic ulcer (PAU), and 5 had localized dissection]. Successful deployment of aortic stent graft was achieved in all patients. There was no endoleak, stent graft migration, spinal cord ischemia, stroke, or 30-day mortality observed after TEVAR. The median duration of follow-up was 30.0 months (range, 3-60 months). As the last follow-up CT angiography showed, most of the patients (23 in 24, 96%) had favorable aortic remodeling. The maximum hematoma thicknesses and maximum diameters of both ascending and descending aorta were significantly decreased. During follow-up, 1 patient developed retrograde type A aortic dissection (RAAD) and underwent open surgery 3 months after TEVAR. 1 patient died of lung cancer 2 years later. There was no aorta-related death observed. Conclusions TEVAR provides a safe and effective treatment strategy for selected patients with retrograde type A IMH, and FID developed in descending aorta could be the possible treatment target. However, RAAD remains one of the most serious postoperative complications of concern.

ObjectiveThis study aimed to summarize the long-term experience of using the chimney technique in thoracic endovascular aortic repair (TEVAR) for aortic arch diseases.MethodsFrom November 2007 to June 2021, a total of 345 consecutive patients (mean age 56 ± 11.3 years, range 28–83, 302 men) with aortic arch pathologies underwent TEVAR combined with chimney technique (cTEVAR). Their medical data and follow-up results were retrospectively reviewed and analyzed.ResultsAmong the 345 patients, 278 (80.6%) received single chimneys, 53 (15.4%) received double chimneys, 7 (2%) received triple chimneys, and 7 (2%) underwent cTEVAR accompanied by other techniques (two with extra-anatomical bypass, two with in situ fenestration, and three with physician modified fenestration). A total of 412 chimney stents were used, including 27 in the innominate artery (IA), 113 in the left common carotid artery, 270 in the left subclavian artery, and two in the aberrant right subclavian artery. Early type IA endoleaks were found in 38 (11%) patients, including 12 with the double or triple chimney technique. Early type II endoleak was found in nine (2.6%) patients. Early re-intervention occurred in two patients with double chimney technique, one for chimney stent migration and the other for compression of chimney stent. The 30-day mortality was 1.2% (4 in 345). During a mean follow-up of 42 ± 22 months (range 1–108 months), major stroke occurred in nine (2.6%) patients, chimney occlusion or stenosis occurred in six (1.7%), and retrograde type A aortic dissection occurred in four (1.2%). Fourteen (4.1%) patients received the secondary intervention. The all-cause mortality was 6.7% (23 in 345). Additionally, the total adverse event rate after cTEVAR was 13.9% (48 in 345).ConclusionTEVAR with chimney technique provides a minimally invasive alternative with good chimney graft patency and low postoperative mortality during follow-up. However, the double and triple chimney techniques should be used cautiously as they seem to have a higher risk for type IA endoleak and adverse events after the operation.

PurposeTo report the technology and preliminary result of gutter-free design stent-grafted in in situ fenestration thoracic endovascular aortic repair (TEVAR).DescriptionThe gutter-free stent-graft has a nickel-titanium self-expanding skeleton, double polytetrafluoroethylene coating, and an outer-skirt fabric structure (named C-skirt endograft). The outer skirt fabric prevents endoleak from the gutter around the stent graft fenestration. Further, the skirt structure right under the fenestration in the aortic stent graft can function as a fixation of the side-branch artery endograft. These designs have the following advantages, such as: 1) prevention of endoleak; and 2) fixation tightly between the branch and aorta endograft pieces.EvaluationA patient who was diagnosed with an aortic arch aneurysm, combined with localized dissection, has successfully implanted the aortic stent graft and C-skirt endograft for the left subclavian artery. The 6-month follow-up result of the C-skirt in situ fenestration TEVAR is satisfactory without obvious endoleak.ConclusionsThe new gutter-free C-skirt stent graft is being safely and effectively used for aortic arch TEVAR. Long-term evaluation of safety, effectivity, and durability needs to be proven by future multi-center studies.

BackgroundAbdominopelvic arteriovenous malformation is an uncommon congenital vascular lesion, for which the diagnosis and treatment are usually difficult. Though embolization and sclerotherapy are the primary treatment strategies, traditional surgical resection remains a valuable option.Case PresentationHerein, we present a 32-year-old female diagnosed with a massive abdominopelvic arteriovenous malformation that originates from the splenic artery and drains into the portal vein. The vascular lesion was evaluated with multiple imaging modalities and then surgically resected successfully. The patient was discharged post-operatively on day 6 and free of symptoms during the 12-month follow-up.ConclusionTo our knowledge, the presented abdominopelvic arteriovenous malformation is the first to be reported in the literature, with such a rare condition originating from the splenic artery and draining into the portal vein.

To report the technology and preliminary result of gutter-free design stent-grafted inThe gutter-free stent-graft has a nickel-titanium self-expanding skeleton, double polytetrafluoroethylene coating, and an outer-skirt fabric structure (named C-skirt endograft). The outer skirt fabric prevents endoleak from the gutter around the stent graft fenestration. Further, the skirt structure right under the fenestration in the aortic stent graft can function as a fixation of the side-branch artery endograft. These designs have the following advantages, such as: 1) prevention of endoleak; and 2) fixation tightly between the branch and aorta endograft pieces.A patient who was diagnosed with an aortic arch aneurysm, combined with localized dissection, has successfully implanted the aortic stent graft and C-skirt endograft for the left subclavian artery. The 6-month follow-up result of the C-skirt in situ fenestration TEVAR is satisfactory without obvious endoleak.The new gutter-free C-skirt stent graft is being safely and effectively used for aortic arch TEVAR. Long-term evaluation of safety, effectivity, and durability needs to be proven by future multi-center studies.

BackgroundThe Ankura II Thoracic Stent Graft System (Lifetech, Shenzhen, China) is an evolution of the Ankura stent graft. This study reports one-year outcomes of the Ankura II Thoracic Stent Graft System for endovascular treatment of Stanford type B aortic dissections.MethodsThe Ankura II Thoracic Aortic Endovascular Trial was a randomized, single-blinded, clinical trial conducted at 12 Chinese institutes. The enrolled patients diagnosed with Stanford type B aortic dissections (TBADs) were randomly assigned to the Ankura group or Ankura II group. Standard follow-up examinations were performed at 1, 6, and 12 months. Safety and efficacy data were analyzed.Results132 patients with TBADs were enrolled. The outcomes for the primary safety end points revealed that the Ankura II stent graft was statistically non-inferior compared to the Ankura stent graft. The 1-month device-related major adverse events (1.6 vs. 0%; p = 0.48), 1-month all-cause mortality (1.7 vs. 4.5%; p = 0.621), 12-month survival rate (95.2 ± 2.7% vs. 94.1 ± 2.9%; p = 0.769), and major adverse event (MAE) rate (5.1 vs. 4.7% at 1 month; p = 0.73 and 5.8 vs. 8.9% at 12 months; p = 0.718) of Ankura II group are all comparable to Ankura group. The two groups showed similar primary effectiveness and true lumen expansion effect, and false lumen remodeling was improved in Ankura II group (−100.0 vs. −48.5%; p = 0.08).ConclusionsThe one-year outcomes from this prospective, randomized, multicenter study demonstrate that Ankura II stent graft shows comparable results to Ankura for treating TBADs, resulting in low mortality rates, MAEs and reintervention rates.Clinical Trial RegistrationChiCTR-TRC-12002844.

Ke Lei, 1 Bing Ma, 2 Ping Shi, 2 Che Jin, 3 Tan Ling, 1 Longjiang Li, 4 Xiangyi He, 5 Lunchang Wang 1 1Department of Stomatology, Central Hospital of Guangyuan, Guangyuan 628000, People’s Republic of China; 2Department of Respiratory, Central Hospital of Guangyuan, Guangyuan 628000, People’s Republic of China; 3Endodontics Department, Dental Hospital of Lanzhou, Lanzhou 730000, People’s Republic of China; 4State Key Laboratory of Oral Diseases, Sichuan University, Chengdu 610041, People’s Republic of China; 5Department of Prosthodontics, School of Stomatology, Lanzhou University, Lanzhou 730000, People’s Republic of ChinaCorrespondence: Ping ShiDepartment of Respiratory, Central Hospital of Guangyuan, Guangyuan 628000, People’s Republic of ChinaTel/Fax +86 839-3222256Email shi0036369692@163.comBackground: Oral squamous cell carcinoma (OSCC) is an aggressive malignancy worldwide. Icariin (ICA), an active ingredient of flavonoids, has been demonstrated to possess antitumor activity in diverse cancers. Whereas, the role of ICAin OSCC is still unclear.Methods: Herein, we investigated the anti-tumor effects of ICA in vitro and in vivo. CCK-8, colony formation and trans-well assay were used to examined viability, proliferation and invasion in SCC-9 and SCC-15 cell lines, respectively. Next, we tested the expression of toll-like receptor 4 (TLR4) and NF-κB P65 by western blot or immunofluorescence staining. Finally, we constructed a xenograft mice model to investigate the effect of ICA in vivo.Results: In vitro, ICA decreased the human oral squamous cells viability, proliferation and invasion in a concentration-dependent manner. Besides, ICA decreased the phosphorylation level of P65 and down-regulated TLR4 protein. In vivo, compared with control, ICA significantly suppressed the tumor size and weight. In addition, ICA downregulated the levels of Ki67 and VEGF markedly. Dramatically, ICA decreased the phosphorylation level of P65 in tumor tissues.Conclusion: Taken together, ICA could act as a anticancer drug against OSCC to mitigate the growth and invasion ability, the underlying mechanism may due to the down-regulation of TLR4/NF-κB signaling.Keywords: icariin, toll-like receptor 4, oral squamous cell carcinomas, NF-κB

The present study aimed to analyze the experience of a single center and assess the efficacy and durability of endovascular aortic repair (EVAR) in patients with tuberculous infected native aortic aneurysms (INAAs).All patients who underwent EVAR for INAAs between September 2014 and August 2021 were reviewed retrospectively. The primary end points were 30-day and overall mortality rates; the secondary outcomes included major complications, endoleak, recurrence, reintervention rate, and thrombosis of the pseudoaneurysmal sac.A total of 18 patients (average age, 61.3 years; 10 female [55.6%]) were identified. Fifteen patients (83.3%) had adjunctive procedures. Both the in-hospital and 30-day mortality rates were 0%. The overall cumulative survival rates estimated by Kaplan-Meier were 100% at 1 and 6 months, and 92.3% at 12 and 24 months, and 80.8% at 36 and 48 months. Type Ib and II endoleaks each occurred in 1 patient (5.6%) and resolved without treatment after 1 month. No graft infections, strokes, paraplegia, ischemic abdominal complications, or other major complications occurred. The overall rates of cumulative freedom from recurrence of aneurysm and reintervention were 83.9% and 81.8%, respectively, during the median follow-up period of 28.5 months (range, 1-72 months). The median time of administering antituberculosis drugs was 10.5 months (range, 2-44 months).EVAR combined with oral antituberculosis medication is effective and may be an appealing treatment option for patients with high-risk INAAs. Adjunctive procedures, including targeted drug delivery to the site of infection, could be a solution to further controlling the infection, but still needs further evaluation.

Backgrounds and Objectives: Thoracic endovascular aortic repair (TEVAR) has currently become the “first-line choice” for descending aortic pathologies. For pathologies located at the aortic arch, TEVAR with physician-modified fenestration (PMF) has been gained popularity as an alternative choice. However, stent fenestration is an experience-dependent technique and comes with possible adverse events such as misalignment. This study aims to introduce the self-radiopaque PMF (SF), which uses the radiopaque marker as a guiding indicator.Methods: This is a single-center retrospective study of 125 patients who underwent the SF-TEVAR in Second Xiangya Hospital from December 2015 to December 2020. Data include basic clinical information and technique records of SF-TEVAR with follow-up results.Results: According to the SF-TEVAR protocol, we have performed the procedures on 125 patients and obtained an instant success rate of 98.4%. A total of 140 aortic stent-grafts and 44 bridging stents have been implanted in this study. The operation time is 64.6 ± 19.3 min, X-ray exposure time (from first digital subtraction angiography (DSA) to last DSA) is 25.6 ± 14.3 min, and contrast volume is 82.2 ± 22.6 ml. The success rate of PMF alignment is 98.4%. One bailout stent-graft was implanted into the left subclavian artery (LSA) by the chimney technique (0.8%). One fenestration was successfully and immediately corrected after misalignment (0.8%). Large simultaneous fenestration was performed in six patients (4.8%) for the left common carotid artery (LCCA) and LSA and in two patients (1.6%) for IA, LCCA, and LSA. One hundred twenty-two out of 125 patients' LSAs have been kept patent by the technique during the follow-up. The bridging stent group consists of 44 patients who received LSA stents, while the non-bridging stent group includes the other 81 patients. Type I endoleak has occurred in seven patients (5.6%) 1 week after the procedure. During follow-up (23 ± 18 months), survival rate is 95.7% and branch artery patent rate is 97.4%.Conclusions: The SF-TEVAR technique, which utilizes the radiopaque marker in stent-graft as an indication for PMF in TEVAR, seems a likely safe, effective, and efficient procedure that brings acceptable survival rate and branch artery patency rate. SF-TEVAR serves as a progressive alternative method to keep the branch artery patent in aortic arch endovascular reconstruction.

Backgrounds: The prognosis of thoracic aortic pseudoaneurysm (TAP) after thoracic endovascular aortic repair (TEVAR) remains unclear. This study investigates the early and midterm clinical outcome as well as relevant risk factors of TAP patients following TEVAR therapy.Methods: From July 2010 to July 2020, 37 eligible TAP patients who underwent TEVAR were selected into our research. We retrospectively explored their baseline, perioperative and follow-up data. Fisher exact test and Kaplan-Meier method were applied for comparing difference between groups. Risk factors of late survival were discerned using Cox regression analysis.Results: There were 29 men and 12 women, with the mean age as 59.5±13.0 years (range, 30-82). The mean follow-up time was 30.7±28.3 months (range, 1-89). For early result, early mortality (≦30days) happened in 3(8.1%) zone 3 TAP patients versus 0 in zone 4 (p= 0.028); acute arterial embolism of lower extremity and type II endoleak respectively occurred in 1(2.7%) case. For midterm result, survival at 3 months, 1 year and 5 years was 88.8±5.3%, 75.9±7.5% and 68.3±9.9%, which showed significant difference between zone 2/3 versus zone 4 group (56.3±14.8% versus 72.9±13.2%, p= 0.013) and emergent versus elective TEVAR groups (0.0±0.0% versus 80.1±8.0%, p= 0.049). On multivariate Cox regression, lesions at zone 2/3 (HR 4.605, 95%CI 1.095-19.359), concomitant cardiac disease (HR 4.932, 95%CI 1.086-22.403) and emergent TEVAR (HR 4.196, 95%CI 1.042-16.891) were significant independent risk factors for worse late clinical outcome. Conclusions: TEVAR therapy is effective and safe with satisfactory early and midterm clinical outcome for TAP patients. Lesions at zone 2/3, concomitant cardiac disease and emergent TEVAR were independent risk factors for midterm survival outcome.

We aimed to establish an animal model of abdominal aortic vascular replacement in mongrel dogs to investigate the effect of extracorporeal radiotherapy on the intima. Twenty healthy mongrel dogs were randomly divided into four groups: 5-week control group, 5-week radiotherapy group, 10-week control group and 10-week radiotherapy group. We first performed an artificial vascular replacement of the abdominal aortic segment. The radiotherapy group received external radiotherapy with a dose of 7 Gy for 4 days. The thickness of neointimal hyperplasia, immunoreactivity and expression of proliferation-related factors were detected by hematoxylin and eosin (HE) staining, immunohistochemistry, quantitative real-time polymerase chain reaction (qRT-PCR )and western blotting at 5 and 10 weeks after the reconstruction. The results showed that the intimal thickness of the artificial blood vessel in the 5- and 10-week radiotherapy groups was thinner than that in the control groups by HE staining. The immunoreactivity and expression levels of Skp2, c-Myc and CyclinE1 were significantly decreased in the radiotherapy groups than those in control groups by immunohistochemistry, qRT-PCR and western blotting. On the contrary, immunoreactivity and expression levels of P27kip1 were increased. In conclusion, we discovered that postoperative external radiotherapy significantly decreases the intimal hyperplasia of artificial blood vessels by regulating c-Myc-Skp2-P27-CyclinE1 network.

Endovascular repair including percutaneous transluminal angioplasty (PTA) and stent implantation has become the standard approach for the treatment of peripheral arterial disease; however, restenosis is still the main limited complication for the long-term success of the endovascular repair. Endothelial denudation and regeneration, inflammatory response, and neointimal hyperplasia are major pathological processes occurring during in-stent restenosis (ISR). MicroRNAs exhibit great potential in regulating several vascular biological events in different cell types and have been identified as novel therapeutic targets as well as biomarkers for ISR prevention. This review summarized recent experimental and clinical studies on the role of miRNAs in ISR modification, with the aim of unraveling the underlying mechanism and potential therapeutic strategy of ISR.

Purpose: To study the effect of x-ray radiotherapy on vascular smooth muscle cells (VSMCs) and elucidate the mechanisms in preventing neointimal hyperplasia of prosthetic vascular grafts. Materials and methods: In model I, twelve mongrel dogs underwent revascularization with prosthetic grafts and half the dogs underwent irradiation of the grafts at 28 Gy. In model II, human VSMCs (hVSMCs) were maintained and divided into six groups to which external radiation was applied at six different doses: 0 Gy, 2 Gy, 8 Gy, 16 Gy, 24 Gy and 30 Gy. In both models, specimens were harvested and examined by using morphological, immunological, cellular and molecular methods. Results: After irradiation, the neointima thickness was significantly lower in irradiated groups (p≤0.01). The radiotherapy could up-regulate p27kip1, and down-regulate proliferating cell nuclear antigen (PCNA) and S phase kinase associated protein 2 (Skp2). X-ray irradiation inhibits the proliferation of hVSMCs via acting on G1/S phase of cell cycle. The apoptosis of hVSMCs increased significantly with dose and time. The expression of PCNA and Skp2 were decreased after a first increasing trend with dose, but had a significant negative correlation with time. The expression of p27kip1 had a significant positive correlation with dose and time. Conclusions: Postoperative external fractionated irradiation after prosthetic vessel replacement of the abdominal aorta suppressed the development of hyperplasia in the graft neointima in the short term. There was a prominent time- and dose-dependent inhibition of VSMC proliferation by radiation when it was administered.

Background: Autologous vein grafting remains the gold standard for surgical bypass grafts. However, vein bypasses still have significant incidence of failure. Ephrin type-B receptor 4 (EphB4), the embryonic venous determinant, may modulate vein graft adaptation. Although EphB4 is expressed in venous endothelial and smooth muscle cells (SMCs), it is not known whether EphB4 is functional in human SMCs. Materials and methods: Human adult venous SMCs were obtained from the inferior vena cava of an adult human liver donor. Primary SMCs were stimulated with EphrinB2/Fc or transfected with an EphB4-expression vector (GV219-EphB4). Expression of SMC phenotype markers, migration, and proliferation were evaluated. Results: Activation of EphB4 with EphrinB2/Fc increased the mRNA and protein expression of the venous SMC contractile markers alpha actin, calponin-1, SM22, and MYH11, while decreasing the expression of the synthetic marker osteopontin. EphrinB2/Fc treatment inhibited SMC migration, but not proliferation. In addition, overexpression of EphB4 increased mRNA expression of SMC contractile markers, while decreasing expression of the apoptosis marker caspase-9. Conclusions: EphB4 was present and functional in adult human venous SMCs. Stimulation of EphB4 increased expression of contractile SMC phenotypic markers and decreased SMC migration in vitro, functioning to retain the contractile phenotype of SMCs. EphB4 activation, therefore, recapitulates changes observed during vein graft adaptation to the arterial environment in vivo. EphB4 represents a new strategy to inhibit neointimal hyperplasia during vein graft adaption.

Rationale Hereditary protein C deficiency has a high prevalence in Asian populations, being the important risk factor associated with thrombophilia. Traditionally, conservative medication is the first choice for patients with hereditary protein C deficiency. However, there are few reports on whether aggressive surgical treatment can be performed when patients continue to develop life-threatening ischemic symptoms after adequate anticoagulant and thrombolytic therapy. Patient concerns A 40-year-old male presented with right lower extremity pain for 1 week. Diagnosis Computed tomography angiography (CTA) of lower extremity indicated arterial embolization of the right superficial femoral artery. Vascular ultrasonography showed old extensive thrombus in the deep vein of the left lower extremity. Electrocardiogram reported old anterior myocardial infarction. Sequencing of the gene encoding protein C (PROC) gene revealed that a heterozygous in-frame deletion mutation (c.577-579delAAG, p.192delK). Based on these findings, the diagnosis of hereditary protein C deficiency was made. Interventions The patient was given low-molecular-weight heparin (LMWH) anticoagulation and urokinase treatment immediately. Then we performed the Fogarty catheter embolectomy with about 18.5 cm thrombus being removed and utilized the balloon catheter to dilate the anterior tibial artery. Despite given adequate anticoagulant and thrombolytic therapy postoperatively, the patient still had new thrombosis, and eventually underwent arterial embolectomy and amputation. Outcomes The patient was discharged with good wound healing and continued rivaroxaban treatment at a dose of 20 mg daily. The patient was followed-up monthly until 1 year: there was no adverse ischemic events occurred. Lessons Aggressive surgical treatment may be the effective attempt for life-saving when conservative treatment as the first choice had unsatisfactory results in hereditary protein C deficiency patients. The novel oral anticoagulants (NOACs) could be more suitable than warfarin for the treatment and prevention of recurrence in patients with hereditary protein C deficiency.

Objectives To characterize the clinical features, treatment, and prognosis of superior mesenteric artery aneurysms and provide evidence for clinical decision-making. Methods We retrospectively reviewed the diagnosis and treatment of 18 cases of superior mesenteric artery aneurysm admitted to our center from 2003 to 2020, including demographic data, risk factors, clinical manifestations, diagnosis, treatment strategies, and follow-up results. Results The average age of the patients was 49.1 years, and males accounted 83.3%. The development of the disease was associated with infection, hypertension, pancreatitis, and trauma, but no significant associations with atherosclerosis were noted by our results. Nine patients were diagnosed with true aneurysm, seven patients with pseudoaneurysm, and two patients with dissecting aneurysm. Rupture of aneurysm occurred in three patients (16.7%), and one of them died before surgery. The surgery success rate was 94.1%, and open surgery was performed on nine patients, endovascular surgery on three patients, and conservative treatment on three patients. The follow-up rate was 77.8% (14/18), and the average follow-up time was 48.2 months. The mortality and reintervention rate during follow-up was 0. The two-year patency rate of artificial vessels and covered stents was 50%. Conclusion The clinical manifestations and features of superior mesenteric artery aneurysms vary between patients. Careful evaluation of vascular anatomy and personalized treatment strategy are critical in the management of superior mesenteric artery aneurysms. Midterm follow-up results of superior mesenteric artery aneurysms are satisfactory.

Ectodysplasin (EDA) gene mutation is associated with hypohidrotic ectodermal dysplasia (HED). The aim of this study was to investigate the effect of ectodysplasin, transcript variant 1 (EDA-A1) on the proliferation and cell cycle of ECV304 human umbilical vein endothelial cells (HUVECs). Recombinant eukaryotic expression vectors containing mutant (M) and wild-type (W) EDA-A1 coding sequences, pcDNA3.1 (-)-EDA-A1-M and pcDNA3.1 (-)-EDA-A1-W, respectively, were transfected into ECV304 cells. The EDA-A1 gene was amplified by reverse transcription polymerase chain reaction (RT-PCR), and the protein was detected by western blotting. The EDA-A1 gene and protein were detected in ECV304 cells transfected with pcDNA3.1 (-)-EDA-A1-M and pcDNA3.1 (-)-EDA-A1-W, but not in ECV304 cells transfected with empty plasmid or cells that had not undergone transfection. Compared with the control group, the EDA-A1 gene mutant significantly decreased the proliferation of ECV304 cells and its inhibition rate was 45.70% (P 0.05). A significant increase of the fraction of cells in the G0/G1 phase of the cell cycle was observed in the ECV304 cells of the mutant group compared with wild type group, with an increase in the S phase population and a concomitant reduction in the G2/M phase population (P

This clinical report describes a relatively infrequent patient with inferior alveolar nerve damage caused by foreign material within the mandibular canal, which is one of the most severe complications of endodontic therapy. Although the circumstance is uncommon, it can have extremely unfavorable consequences for patients, such as anesthesia and paresthesia. In the present case, a patient suffered pain and severe paresthesia in the corresponding area after routine endodontic therapy. Several treatments were conducted to relieve the patient's symptoms, ranging from medication to tooth extraction, but all were of no avail. Ultimately, surgical exploration and debridement were performed with assistance of a customized surgical template. Once the foreign material was excavated, the exacerbation of condition was terminated and gradually reverted. This patient illustrates that special attention is required when undertaking intracanal procedures of lower posterior teeth so as to avoid iatrogenic damage to inferior alveolar nerve. Even more significant, when above-mentioned condition occurs, prompt surgical intervention is essential for recovery of sensation. It also demonstrates the advantages of applying surgical template and piezosurgery in removal of foreign material within the mandibular canal.

The rock pigeon (Columba livia), or Rock dove, is a member of the bird family Columbidae. We mapped the complete mitochondrial genome of the Rock pigeon. The mitochondrial genome of this species is a circular molecule of 17,229 bp in length, encoding a standard set of 13 protein-coding genes, two ribosomal RNA genes, and 22 transfer RNA genes, plus a putative control region, demonstrating a structure very similar to that of other birds. As found in other vertebrates, most of these genes are coded on the H-strand, except for NADH dehydrogenase subunit 6 (nad6) and eight tRNA genes (Gln, Ala, Asn, Cys, Tyr, Ser(UCN), Pro, Glu). The AT skew and GC skew of the whole genome, protein-coding genes, tRNA, rRNA, and the control region were calculated for the complete mitochondrial genomes of 30 avian species, representing 29 orders. All protein-coding genes initiated with ATG, except for cox1 and nad5, which began with GTG. One extra nucleotide 'C' was present in NADH dehydrogenase subunit 3 (nad3). All tRNA gene sequences have the potential to fold into typical cloverleaf secondary structures. Within the control region, conserved sequences were identified in three domains. Although the conserved blocks, such as ETAS1, ETAS2, CSB1, CSB1-like, and boxes C, D, E, and F, are readily identifiable in the C. livia control region, the typical origin of H-strand replication (O(H)), CSB2 and CSB3 could not be detected. These results provide basic information for phylogenetic analyses of birds, especially Columbiformes species.

Cardiovascular disease is the leading cause of mortality worldwide. Current surgical treatments for cardiovascular disease include vascular bypass grafting and replacement with autologous blood vessels or synthetic vascular grafts. However, there is a call for better alternative biological grafts.Tissue-engineered vascular grafts (TEVGs) are promising novel alternatives to replace diseased vessels. However, obtaining enough functional and clinically usable vascular cells for fabrication of TEVGs remains a major challenge. New findings in adult stem cells and recent advances in pluripotent stem cells have opened a new avenue for stem cell-based vascular engineering. In this review, recent advances on stem cell sourcing for TEVGs including the use of adult stem cells and pluripotent stem cells and advantages, disadvantages, and possible future implementations of different types of stem cells will be discussed. In addition, current strategies used during the fabrication of TEVGs will be highlighted.The application of patient-specific TEVGs constructed with vascular cells derived from immune-compatible stem cells possesses huge clinical potential. Advances in lineage-specific differentiation approaches and innovative vascular engineering strategies will promote the vascular regeneration field from bench to bedside.

Individuals with bicuspid aortic valves (BAV) are at a high risk to develop a thoracic aortic aneurysms (TAA) than patients with trileaflet aortic valves (TAV), most commonly involving ascending aorta and sparing the descending aorta. Smooth muscle cells (SMCs) in the ascending and descending aorta arise from neural crest and paraxial mesoderm, respectively. We hypothesize the aortopathy associated with BAVs is due to aberrant differentiation of neural crest stem cells (NCSCs) to SMCs. Induced pluripotent stem cell (iPSC) lines were established from a patient with BAV/TAA, and control patients with TAV and a normal aorta. The iPSCs pluripotency was verified by standard stem cell markers and teratoma formation in SCID mice. iPSCs were differentiated into NCSCs and paraxial mesoderm cells (PMCs) separately, and verified by specific neural crest markers and paraxial mesoderm markers. Both NCSCs and PMCs were differentiated into SMCs, NCSC-SMCs and PMC-SMCs, by treating with TGFβ1 and PDGF-bb. With differentiation, both SMCs lines expressed SMC specific markers including MYH11, CNN1, ACTA2, and TAGLN by quantitative RT-PCR and immunohistochemical staining. However, NCSC-derived SMCs from BAV/TAA patient demonstrated significantly decreased expression and protein levels of MYH11 and ACTA2 and impaired contraction by gel contraction assay compared to NCSC-SMCs derived from control. In contrast, the PMC-derived SMCs from BAV/TAAD patient had similar or higher expression and levels of contractile proteins, including MYH11, CNN1, ACTA2, and TAGLN, and contractile response to carbacol treatment when compared with control PMC-SMCs. The defective differentiation of NCSC-SMC from the BAV/TAA patient was coupled with the decreased TGFβ signaling as assessed by decreased gene expression of TGFβ1 and connective tissue growth factor (CTGF) when compared to control cells. Increasing the concentration of TGFβ1, rescued the gene expressions of TGFβ1, CTGF, MYH11 and ACTA2 in the NCSC-SMCs from the BAV/TAA. Taken together, our data demonstrate that defective TGFβ signaling and differentiation of specifically NCSC-derived SMCs contributes to aortopathy in BAV with ascending aortic aneurysm.

Nuclear factor-erythroid 2-related factor 2 (Nrf2) is a transcription factor that regulates antioxidant and anti-inflammatory genes, and it plays a crucial role in the pathogenesis of chronic obstructive pulmonary disease (COPD). Moreover, 15-deoxy-delta12,14-prostaglandin J2 (15d-PGJ2) plays a protective role against oxidative stress and inflammation both in vivo and in vitro. In a previous study, we found that 15d-PGJ2 increased the expression of Nrf2 in a COPD rat model. This study aims to elucidate the role of 15d-PGJ2 in COPD pathogenesis and the relationship between Nrf2 and human bronchial epithelial (HBE) cells. Normal HBE (HBE) cells were cultured. Following cigarette smoke extract (CSE) stimulation, pre-incubation with or without small interfering RNA (siRNA) Nrf2, and stimulation with or without 15d-PGJ2, the expression levels of Nrf2, NF-κBp65, and IL-8 were detected by reverse transcription-polymerase chain reaction and western blot, respectively. The expression of NF-κBp65 and IL-8 in CSE-stimulated normal HBE cells was inhibited by 15d-PGJ2 at both the mRNA level and the protein level. Moreover, the expression of Nrf2 in normal HBE cells was improved by 15d-PGJ2 at both the mRNA level and the protein level. However, the inhibitory or improving effects of 15d-PGJ2 were disengaged by siRNA Nrf2 at both the mRNA level and the protein level. 15d-PGJ2 possesses anti-inflammatory properties in the pathogenesis of COPD, and HBE cells stimulated by CSE via Nrf2 activation.

Ascending aortic aneurysm occurs in 35%-68% patients with bicuspid aortic valves (BAV), which is more frequently than it does in patients with normal trileaflet aortic valves (TAV). In contrast to recurrent aneurysms of the ascending aorta, descending aortic aneurysms is very rare in patients with BAV. Vascular Smooth Muscle Cells (SMCs) make up the media of the aortic walls, and their contractile properties help sustain vessel tone. Interestingly, ascending aorta is populated by SMCs arising from neural crest and descending aorta by SMCs from paraxial mesoderm. An intriguing hypothesis is that the distinct susceptibility of aneurysm in the ascending and descending aorta in patients with BAV is due in part to disparities in SMC embryonic origins. To prove our hypothesis, we used an induced Pluripotent Stem Cells (iPS) model system to generate SMCs from neural crest and paraxial mesoderm. Firstly, iPSCs were established from a patient with BAV and ascending thoracic aortic aneurysm (BAV/TAA) and two control patients with normal aorta and TAV. The iPSCs pluripotency was verified by standard stem cell markers and teratoma formation. Neural crest stem cells (NCSCs) were differentiated from iPSCs and expressed neural crest markers, including P75, HNK1, AP2 and Sox9. In parallel, paraxial mesoderm cells (PMCs) were differentiated from iPSCs and expressed specific markers, including TCF15, TBX6, Meox1 and Pax1. The SMCs differentiated from both lineages had expression of SMC markers including MYH11, CNN1, ACTA2, SM22α. Interestingly, SMCs derived from BAV-NCSCs had significantly decreased in MYH11 and ACTA2 gene expression and impaired contractile property by gel contraction assay compared to SMCs derived from control-NCSCs. However, SMCs from BAV-PMCs had similar level of expression of MYH11 and ACTA2, and strong contractile activity with Carbacol treatment compared to SMCs derived from control PMCs. In conclusion, the iPS model system revealed decreased expression of contractile proteins and impairment of contractility in SMCs derived from NCSCs in BAV patient, but not in the SMCs derived from paraxial mesoderm cells. The high susceptibility of aneurysm in the ascending aorta in patients with BAV might be partly due to embryonic origin of the SMCs.

Ectodysplasin (EDA) gene mutation is associated with hypohidrotic ectodermal dysplasia (HED). The aim of this study was to investigate the effect of ectodysplasin, transcript variant 1 (EDA-A1) on the proliferation and cell cycle of ECV304 human umbilical vein endothelial cells (HUVECs). Recombinant eukaryotic expression vectors containing mutant (M) and wild-type (W) EDA-A1 coding sequences, pcDNA3.1 (−)-EDA-A1-M and pcDNA3.1 (−)-EDA-A1-W, respectively, were transfected into ECV304 cells. The EDA-A1 gene was amplified by reverse transcription polymerase chain reaction (RT-PCR), and the protein was detected by western blotting. The EDA-A1 gene and protein were detected in ECV304 cells transfected with pcDNA3.1 (−)-EDA-A1-M and pcDNA3.1 (−)-EDA-A1-W, but not in ECV304 cells transfected with empty plasmid or cells that had not undergone transfection. Compared with the control group, the EDA-A1 gene mutant significantly decreased the proliferation of ECV304 cells and its inhibition rate was 45.70% (P0.05). A significant increase of the fraction of cells in the G0/G1 phase of the cell cycle was observed in the ECV304 cells of the mutant group compared with wild type group, with an increase in the S phase population and a concomitant reduction in the G2/M phase population (P