[Predictive value of SYNTAX-â ¡ score on prognosis of patients with chronic total occlusion undergoing percutaneous coronary intervention].

Objective: To investigate the predictive value of SYNTAX-Ⅱ score on long term prognosis of patients diagnosed with chronic total occlusion (CTO) and received percutaneous coronary intervention (PCI). Methods: Patients undergoing CTO-PCI in Fuwai hospital from January 2010 to December 2013 were enrolled in this retrospective analysis. The SYNTAX-Ⅱ score of the patients was calculated. According to SYNTAX-Ⅱ score tertiles, patients were stratified as follows: SYNTAX-Ⅱ≤20, 2027. Primary endpoint was major adverse cardiac events (MACCE), including all-cause death, myocardial infarction, stroke and any revascularization. Secondary endpoints included stent thrombosis, heart failure and target lesion failure (TLF). Patients were followed up by outpatient visit or telephone call at 1 month, 6 months and 1 year after PCI, and annually up to 5 years. Multivariate Cox regression model was used to analyze the independent risk factors of all-cause death in patients undergoing CTO-PCI. The predictive value of SYNTAX score with SYNTAX-Ⅱ score for all-cause death was evaluated by the receiver operating characteristic (ROC) curve and the area under the curve (AUC). Results: A total of 2 391 patients with CTO and received PCI were enrolled in this study. The mean age was (57.0±10.5) years, 1 994 (83.40%) patients were male. There were 802 patients in lower tertile group (SYNTAX-Ⅱ≤20), 798 patients in intermediate group (2027). At the end of 5-year follow-up, the loss to follow-up rate of the three groups was 9.10%(73/802), 10.78%(86/798)and 8.85%(70/791), respectively. The rate of all-cause mortality (1.78% (13/729) vs. 3.65% (26/712) vs. 9.02% (65/721), P<0.001), cardiac death (1.37% (10/729) vs. 2.11% (15/712) vs. 4.85% (35/721), P<0.001), target vessel myocardial infarctions (4.25% (31/729) vs. 4.49% (32/712) vs. 7.07% (51/721), P=0.03), probable stent thrombosis (1.51% (11/729) vs. 2.81% (20/712) vs. 3.61% (26/721), P=0.04) and heart failure (1.78% (13/729) vs. 1.97% (14/712) vs. 5.41% (39/721), P<0.001) increased in proportion to increasing SYNTAX-Ⅱ score (all P<0.05). Multivariable Cox regression analysis indicated that female (HR=2.05, 95%CI 1.12-3.73, P=0.01), left ventricular ejection fraction (HR=0.97, 95%CI 0.95-1.00, P=0.05) and SYNTAX-Ⅱ score (HR=1.07, 95%CI 1.02-1.11,P=0.01) were independent predictors for all-cause mortality in patients undergoing CTO-PCI. The predicted value of the SYNTAX-Ⅱ score for all-cause death was significantly higher than the SYNTAX score (AUC 0.71 vs. 0.60, P=0.003). Conclusion: For CTO patients who underwent percutaneous coronary intervention, SYNTAX-Ⅱ score is an independent predictor for 5-year all-cause death, and SYNTAX-Ⅱ serves as an important predictor for all-cause death in these patients.

NSPc1 promotes cancer stem cell self-renewal by repressing the synthesis of all-trans retinoic acid via targeting RDH16 in malignant glioma.

Polycomb group (PcG) proteins play an important role in development and stem cell maintenance, and their dysregulation have been closely linked to oncogenesis and cancer stem cell phenotypes. Here, we found that nervous system polycomb 1 (NSPc1) was highly expressed in stem cell-like glioma cells (SLCs). Knockdown of NSPc1 in SLCs resulted in impaired neurosphere formation and self-renewal abilities, down-regulated expression of stemness markers such as NESTIN, CD133 and SOX2, and decreased capacity to propagate subcutaneous xenografts. In contrast, glioma cells overexpressing NSPc1 exhibited a stem cell-like phenotype, up-regulated expression of stemness markers NESTIN, CD133 and SOX2, and an enhanced capacity to propagate subcutaneous xenografts. Furthermore, we identified that NSPc1 epigenetically repressed the expression of retinol dehydrogenase 16 (RDH16) by directly binding to a region upstream (-1073 to -823) of the RDH16 promoter. Next, we confirmed that RDH16 is a stemness suppressor that partially rescues SLCs from the NSPc1-induced increase in neurosphere formation. Finally, we showed that ATRA partly reversed the NSPc1-induced stemness enhancement in SLCs, through mechanisms correlated with an ATRA-dependent decrease in the expression of NSPc1. Thus, our results demonstrate that NSPc1 promotes cancer stem cell self-renewal by repressing the synthesis of ATRA via targeting RDH16 and may provide novel targets for glioma treatment in the future.

Inhibition of LZIP-mediated transcription through direct interaction with a novel host cell factor-like protein.

Host cell factor 1 (HCF-1) is a cellular transcriptional coactivator which coordinates the assembly of enhancer complex through direct interactions with viral and cellular trans-activators such as VP16, Oct-1, LZIP, and GA-binding protein. These interactions are mediated by the beta-propeller domain comprising the first 380 residues of HCF-1 with six kelch repeats. Here we describe the identification and characterization of a novel HCF-like kelch repeat protein, designated HCLP-1. HCLP-1 is a ubiquitously expressed nuclear protein which is composed almost entirely of a six-bladed beta-propeller. HCLP-1 selectively interacts with LZIP but not with VP16. The physical interaction between HCLP-1 and LZIP leads to the repression of the LZIP-dependent transcription. The HCLP-1-binding domain of LZIP maps to residues 109-315, which contain the bZIP DNA-binding motif. Electrophoretic mobility shift assay demonstrates that HCLP-1 indeed interferes with the binding of LZIP to its DNA target. Thus, HCLP-1 serves a transcriptional co-repressor function mediated through its inhibitory interaction with the LZIP transcription factor. Our findings suggest a new mechanism for transcriptional regulation by HCF-like proteins.

The effect of nonporous PTFE-covered stents on intimal hyperplasia following balloon arterial injury in minipigs.

PURPOSE: To report an experimental study investigating the ability of nonporous polytetrafluoroethylene (PTFE) covering on a metallic stent to retard the development of neointimal hyperplasia (NIH). METHODS: Three groups of Hanford miniature swine underwent standardized balloon injury to both external iliac arteries. Group I animals (control) received balloon injuries only. Group II had the site of balloon injury supported by a properly sized, balloon-expandable Palmaz stent placed directly over the injury site. Group III animals received a Palmaz stent covered with PTFE graft. All animals underwent arteriography immediately after intervention and again prior to sacrifice and specimen harvest at 4 weeks. The specimens were examined grossly and histologically at the proximal, middle, and distal segments for NIH development. RESULTS: Uncovered stents developed significantly more NIH (p < 0.0001) and greater luminal narrowing (p < 0.001) than the controls. PTFE-covered stents (group III) exhibited less NIH (p < 0.001) and luminal reduction (p < 0.01) than bare stents (group II) at the middle portion of the stent-graft, but the PTFE cover had no effect on NIH and lumen reduction at the proximal or distal ends of the prosthesis. CONCLUSIONS: PTFE-covered stents retarded NIH at 4 weeks, but only at the midportion of the devices; the covering did not prevent neointimal pannus ingrowth at the proximal and distal ends.

Ex vivo human carotid artery bifurcation stenting: correlation of lesion characteristics with embolic potential.

PURPOSE: To develop an ex vivo human carotid artery stenting model that can be used for the quantitative analysis of risk for embolization associated with balloon angioplasty and stenting and to correlate this risk with lesion characteristics to define lesions suitable for balloon angioplasty and stenting. METHODS: Specimens of carotid plaque (n = 24) were obtained circumferentially intact from patients undergoing standard carotid endarterectomy. Carotid lesions were prospectively characterized on the basis of angiographic and duplex findings before endarterectomy and clinical findings. Specimens were encased in a polytetrafluoroethylene wrap and mounted in a flow chamber that allowed access for endovascular procedures and observations. Balloon angioplasty and stenting were performed under fluoroscopic guidance with either a Palmaz stent or a Wallstent endoprosthesis. Ex vivo angiograms were obtained before and after intervention. Effluent from each specimen was filtered for released embolic particles, which were microscopically examined, counted, and correlated with various plaque characteristics by means of multivariate analysis. RESULTS: Balloon angioplasty and stenting produced embolic particles that consisted of atherosclerotic debris, organized thrombus, and calcified material. The number of embolic particles detected after balloon angioplasty and stenting was not related to preoperative symptoms, sex, plaque ulceration or calcification, or artery size. However, echolucent plaques generated a higher number of particles compared with echogenic plaques (p < 0.01). In addition, increased lesion stenosis also significantly correlated with the total number of particles produced by balloon angioplasty and stenting (r = 0.55). Multivariate analysis revealed that these two characteristics were independent risk factors. CONCLUSIONS: Echolucent plaques and plaques with stenosis > or = 90% produced a higher number of embolic particles and therefore may be less suitable for balloon angioplasty and stenting. This ex vivo model can be used to identify high-risk lesions for balloon angioplasty and stenting and can aid in the evaluation of new devices being considered for carotid balloon angioplasty and stenting.

Accuracy of duplex ultrasound in evaluating carotid artery anatomy before endarterectomy.

PURPOSE: Anatomic features, such as a high carotid bifurcation (< 1.5 cm from the angle of the mandible), excessive distal extent of plaque (> 2.0 cm above the carotid bifurcation), or a small diameter (< or = 0.5 cm) redundant or kinked internal carotid artery can complicate carotid endarterectomy. In the past, arteriography was the only preoperative study capable of imaging these features. This study assessed the ability of duplex ultrasound to evaluate their presence before surgery. METHODS: A consecutive series of 20 patients who underwent 21 carotid endarterectomies had preoperative duplex ultrasound evaluations of these anatomic features. These evaluations were correlated with operative measurements from an observer blinded to the duplex findings. RESULTS: The mean difference between duplex and operative measurements for the distance between the carotid bifurcation and the angle of the mandible, the distal extent of plaque, and the internal carotid artery diameter was 0.9 cm, 0.3 cm, and 0.8 mm, respectively. The correlation coefficient between the two methods was 0.86, 0.75, and 0.59, respectively. Duplex ultrasound predicted a high carotid bifurcation, excessive distal extent of plaque, or a redundant or kinked internal carotid artery with 100% sensitivity (p < 0.05, p < 0.01, and p < 0.001, respectively). The sensitivity of duplex ultrasound in predicting a small internal carotid artery diameter was 80%. The specificity of duplex ultrasound for predicting excessive distal extent of plaque, small internal carotid artery diameter, high carotid bifurcation, and a coiled or kinked carotid artery was 92%, 56%, 100%, and 100%, respectively. CONCLUSION: Duplex ultrasound can predict the presence of anatomic features that may complicate carotid endarterectomy. Preoperative duplex imaging of these features may be helpful in patients who undergo carotid endarterectomy without preoperative arteriography.

Endoleaks after endovascular graft treatment of aortic aneurysms: classification, risk factors, and outcome.

PURPOSE: Incomplete endovascular graft exclusion of an abdominal aortic aneurysm results in an endoleak. To better understand the pathogenesis, significance, and fate of endoleaks, we analyzed our experience with endovascular aneurysm repair. METHODS: Between November 1992 and May 1997, 47 aneurysms were treated. In a phase I study, patients received either an endovascular aortoaortic graft (11) or an aortoiliac, femorofemoral graft (8). In phase II, procedures and grafts were modified to include aortofemoral, femorofemoral grafts (28) that were inserted with juxtarenal proximal stents, sutured endovascular distal anastomoses within the femoral artery, and hypogastric artery coil embolization. Endoleaks were detected by arteriogram, computed tomographic scan, or duplex ultrasound. Classification systems to describe anatomic, chronologic, and physiologic endoleak features were developed, and aortic characteristics were correlated with endoleak incidence. RESULTS: Endoleaks were discovered in 11 phase I patients (58%) and only six phase II patients (21%; p < 0.05). Aneurysm neck lengths 2 cm or less increased the incidence of endoleaks (p < 0.05). Although not significant, aneurysms with patent side branches or severe neck calcification had a higher rate of endoleaks than those without these features (47% vs 29% and 57% vs 33%, respectively), and patients with iliac artery occlusive disease had a lower rate of endoleaks than those without occlusive disease (18% vs 42%). Endoleak classifications revealed that most endoleaks were immediate, without outflow, and persistent (71% each), proximal (59%), and had aortic inflow (88%). One patient with a persistent endoleak had aneurysm rupture and died. CONCLUSIONS: Endoleaks complicate a significant number of endovascular abdominal aortic aneurysm repairs and may permit aneurysm growth and rupture. The type of graft used, the technique of graft insertion, and aortic anatomic features all affect the rate of endoleaks. Anatomic, chronologic, and physiologic classifications can facilitate endoleak reporting and improve understanding of their pathogenesis, significance, and fate.

Endovascular grafts for noninfected aortoiliac anastomotic aneurysms.

PURPOSE: This report describes our experience with endovascular repair of aortic and iliac anastomotic aneurysms. METHODS: Between June 1994 and March 1996, 12 noninfected aortic or iliac anastomotic aneurysms in 10 patients who had serious comorbid medical conditions that precluded or made difficult standard operative repair were treated using endovascular grafts. No patient in this study had a history of fever, leukocytosis, or computed tomographic evidence of a periprosthetic fluid collection that was suggestive of infection of the original graft. Endovascular grafts composed of polytetrafluoroethylene and balloon-expandable stents were introduced through a femoral arteriotomy and were placed using over-the-wire techniques under C-arm fluoroscopic guidance. RESULTS: Endovascular grafts were successfully inserted in all patients with aortic or iliac anastomotic aneurysms. There were no procedure-related deaths, and complications included one postprocedure wound hematoma and one perioperative myocardial infarction. Graft patency has been maintained for a mean of 16.1 months, with no computed tomographic evidence of aneurysmal enlargement or perigraft leakage. CONCLUSIONS: Endovascular grafts appear to be a safe and effective technique for excluding some noninfected aortoiliac anastomotic aneurysms in high-risk patients and may become a treatment option in all patients who have clinically significant lesions.

Anastomotic intimal hyperplasia: a comparison between conventional and endovascular stent graft techniques.

Endovascular grafts (EVGs) have been proposed as a treatment for a variety of vascular diseases; however, the impact of EVGs on graft healing has not been fully evaluated. The aim of this study is to compare anastomotic intimal hyperplasia (AIH) and endothelialization in EVGs and conventional bypass grafts (CGs). Seven mongrel dogs received an EVG in one iliac artery and a CG in the other iliac artery using a 5 mm x 4 cm polytetrafluoroethylene graft. The EVG was secured to the native vessel wall, with balloon expandable stents at either ends of the graft. CGs were anastomosed using running sutures. Intravascular ultrasound was performed at the time of sacrifice (8 weeks) to determine percentage of stenosis at the distal anastomosis. Specimens were divided longitudinally for light microscopic analysis (thickness of distal AIH) and scanning electron microscopic studies (percentage of endothelial coverage of the graft). Percentage of stenosis at the distal anastomosis was significantly higher in EVGs compared with CGs (28.2 +/- 18.2% versus 1.8 +/- 2.8%; P < 0.01) due to significantly greater mean intimal thickness in the EVGs (441.1 +/- 101.1 microns versus 82.4 +/- 41.9 microns; P < 0.01). The total percentage of area covered by endothelial cells was also significantly greater in EVGs compared with CGs (80.5 +/- 37.5% versus 30.3 +/- 37.1%; P < 0.05). Intraluminal location enhanced endothelialization of the polytetrafluoroethylene graft; however, it also resulted in greater AIH. Further device refinements including stent design may be required to maximize the potential of these endovascular procedures.

Endovascular aortounifemoral grafts and femorofemoral bypass for bilateral limb-threatening ischemia.

PURPOSE: Although axillobifemoral bypass procedures have a lower mortality rate than aortobifemoral bypass procedures, they are limited by decreased patency, moderate hemodynamic improvement, and the need for general anesthesia. This report describes an alternative approach to bilateral aortoiliac occlusive disease using unilateral endovascular aortofemoral bypass procedures in combination with standard femorofemoral reconstructions. METHODS: Seven patients who had bilateral critical ischemia and tissue necrosis in association with severe comorbid medical illnesses underwent implantation of unilateral aortofemoral endovascular grafts, which were inserted into predilated, recanalized iliac arteries. The proximal end of the endovascular graft was fixed to the distal aorta or common iliac artery with a Palmaz stent. The distal end of the graft was suture-anastomosed to the ipsilateral patent outflow vessel, and a femorofemoral bypass procedure was then performed. RESULTS: All endovascular grafts were successfully inserted through five occluded and two diffusely stenotic iliac arteries under either local (1), epidural (5), or general anesthesia (1). The mean thigh pulse volume recording amplitudes increased from 9 +/- 3 mm to 30 +/- 7 mm and from 6 +/- 2 mm to 26 +/- 4 mm ipsilateral and contralateral to the aortofemoral graft insertion, respectively. In all cases the symptoms completely resolved. Procedural complications were limited to one local wound hematoma. No graft thromboses occurred during follow-up to 28 months (mean, 17 months). CONCLUSIONS: Endovascular iliac grafts in combination with standard femorofemoral bypass grafts may be an effective alternative to axillobifemoral bypass in high-risk patients who have diffuse aortoiliac occlusive disease, particularly when bilateral axillary-subclavian disease is present.

Effect of polytetrafluoroethylene covering of Palmaz stents on the development of intimal hyperplasia in human iliac arteries.

PURPOSE: The occurrence of neointimal hyperplasia within a stent may result in restenosis with recurrent symptoms of end-organ ischemia. This study evaluated the potential of a nonporous covering of a stent to function as a barrier to the formation of intrastent neointimal hyperplasia. MATERIALS AND METHODS: Twelve endovascular stent grafts were used to treat 12 high-risk patients with limb-threatening ischemia secondary to long-segment iliac artery occlusion. A 6-mm, thin-walled polytetrafluoroethylene graft was inserted and anchored to the common iliac artery with use of Palmaz stents. Each stent was covered by graft material over one-half of its length. Control angiograms obtained immediately after graft insertion were compared with follow-up angiograms obtained between 4 and 6 months after the initial procedure. On each angiogram, the region of the stent was magnified by 20x to permit computerized luminal diameter measurements. RESULTS: The mean luminal diameter within the stent was significantly greater on the covered (7.7 mm +/- 0.33 standard deviation) compared with the uncovered (6.7 mm +/- 0.85 standard deviation) portions (P < .01). CONCLUSIONS: Partially covered stents are a unique model for assessing the effects of an extrinsic stent covering on arterial healing and myointimal hyperplasia. These data suggest that a relatively nonporous covering of polytetrafluoroethylene may inhibit stent-related restenosis in iliac arteries.

Enterolithiasis, refractory anemia, and strictures of Crohn's disease.

In Crohn's disease, multiple areas of small bowel stenosis are relatively common, but there are only 11 reported cases with stenosis complicated by enterolithiasis. We describe three patients with multiple strictures, enterolithiasis, and refractory iron deficiency anemia. The chronic anemia was severe, requiring multiple transfusions in two patients. One patient developed a perforation, and a second had cancer within one of the saccular dilatations between strictures. Management of this stricture-enterolith-anemia triad requires removal of the enteroliths and correction of the strictures by strictureplasty and/or resection. If the operation of choice is strictureplasty, however, meticulous inspection and biopsy of each proposed site of enteroplasty is essential to rule out carcinoma.

Determination of the complete nucleotide sequence of HBV adr NC-1 DNA.

On the basis of sequencing the large DNA-fragments which have been inserted into M13mp8, we design a simple strategy to determine the complete nucleotide sequence of HBV adr NC-1 DNA with chain termination method. The whole genome is 3195 nucleotides long. Five reading frames are observed. The gene location and organization are shown.

Expression of lipoprotein lipase gene in combined lipase deficiency.

The expression of the gene for lipoprotein lipase (LPL) was studied in brown adipose tissue and the liver of combined lipase deficient (cld/cld) and unaffected mice. The mRNA specific for LPL was detected in both animals. Although the size of LPL mRNA in cld mice was similar to that of unaffected mice, the mRNA concentration in affected animals was higher than in unaffected animals. We also studied the LPL gene mutation in cld mice by Southern blot analysis. No restriction fragment length polymorphisms were observed after digestion with 16 endonucleases. These data indicate that there is no gene insertion or deletion, but do not exclude the possibility of point mutation in the LPL structural gene. However, the present results agree with the hypothesis that the genetic defect in cld is not due to a mutation in the LPL structural gene, but instead involves the defective post-translational processing of LPL or defective cellular function affecting transport and secretion of this enzyme group.

Joining of yeast alanine transfer ribonucleic acid half molecules to form a whole molecule by T4 RNA ligase.

Covalent joining of the two half molecules of tRNAAla by T4 RNA ligase to form a reconstituted whole molecule was investigated. The two half molecules consisting, respectively, of residues 1-35 and 36-75 were prepared by partial degradation of tRNAAla with RNAase T1. The 5'-half molecule was treated with alkaline phosphatase to remove the 3'-terminal phosphate group, and the 5'-OH group of the 3'-half molecule was phosphorylated with [gamma-32P]ATP by polynucleotide kinase. The two terminal nucletides to be joined were identified as Guo and Cyd. Prior to the covalent joining reaction, the two modified half molecules in an equimolar mixture were annealed, and the rejoined half molecules, separated by gel electrophoresis, served as the substrate for T4 RNA ligase. Optimum conditions for this ligation, such as RNA ligase concentration, pH, Mg2+ concentration, reaction temperature and time of reaction, were investigated. Under the optimum conditions a yield of about 70% joining of the reconstituted whole molecule was obtained as shown by gel electrophoresis, resistance to hydrolysis by alkaline phosphatase, nearest neighbour analysis and alanine acdeptor activity.