Retraction notice to: Enlarged anterior cerebral artery bifurcation angles may induce abnormally enhanced hemodynamic stresses to initiate aneurysms [WNEU 120 (2018) e783-e791/9025].

This article has been retracted: please see Elsevier Policy on Article Withdrawal (http://www.elsevier.com/locate/withdrawalpolicy). This article has been retracted at the request of the Editor-in-Chief. It includes data and figures from patients that were cared for by Dr. Malek at the Cerebrovascular Hemodynamics laboratory in the Department of Neurosurgery at Tufts Medical Center. The Editor-in-Chief has been informed by Tufts Medical Center that the authors of the paper did not have clinical privileges for these patients and played no clinical role in their care.

Safety and effects of endovascular treatment of basilar tip aneurysms in patients with moyamoya diseases.

The effect and safety of endovascular treatment of basilar tip aneurysms associated with moyamoya disease are unknown. This study was to investigate the safety and effect of endovascular treatment of basilar tip aneurysms associated with moyamoya disease. Patients with moyamoya disease concurrent with basilar tip aneurysms were retrospectively enrolled and treated with endovascular embolization. The clinical and angiographic data were analyzed. Thirty patients with a basilar tip aneurysm were enrolled, including 8 (26.67%) male and 22 (73.33%) female patients aged 38 to 72 years (mean 54.4 ± 8.15). Endovascular treatment was successfully performed in 29 (96.67%) patients but failed in 1 (3.33%). Immediately after embolization, aneurysm occlusion degree was Raymond-Roy grade I in 26 (89.66%), grade II in 2 (6.90%), and grade III in 1 (3.45%). Intraprocedural complications occurred in 2 (10%) patients, including aneurysm rupture in 1 (3.33%), leading to death of the patient, and stent thrombosis in 2 (6.67%) which was successfully treated with thrombolysis. At discharge, good clinical outcome (modified Rankin Scale 0-2) was achieved in 29 (96.67%) and death in 1 (3.03%). Follow-up was performed 6 to 26 months (median 15) in 27 (93.1%) patients. Aneurysm occlusion degree was Raymond-Roy grade I in 21 (77.78%) patients, grade II in 4 (14.81%), and grade III in 2 (7.41%), not significantly (P = .67) different from those immediately after embolization. Aneurysm recurrence was found in 4 patients (14.81%). The clinical outcome was modified Rankin Scale 0 to 2 in all 27 patients, not significantly different from that at discharge. Endovascular embolization can be performed safely and effectively for basilar tip aneurysms associated with moyamoya disease even though more advanced embolization techniques are necessary.

Risk factors for repeated recurrence of cerebral aneurysms treated with endovascular embolization.

Purpose: To explore the risk factors of recurrence after second endovascular embolization of recurrent aneurysms and the characteristics of recurrent refractory aneurysms to help clinical decision-making. Materials and methods: Forty-nine patients with recurrent aneurysms who underwent repeated embolization were retrospectively enrolled and divided into the recurrent and non-recurrent group. The risk factors of recurrence, complications and follow-up results of repeated embolization, and characteristics of recurrent refractory aneurysms were analyzed. Results: Among the 49 patients with the second embolization, 5 were lost to follow-up, 9 recurred, and 35 did not. Univariate analysis showed that aneurysm size (P = 0.022), aneurysm classification (P = 0.014), and Raymond-Roy grade after the second embolization (P = 0.001) were statistically different between the two groups. Multivariate analysis demonstrated the Raymond-Roy grade as an independent risk factor for the recurrence of aneurysms after the second embolization (P = 0.042). The complication rate after the second embolization was 4%. There were five recurrent refractory aneurysms with an average aneurysm size of 23.17 ± 10.45 mm, including three giant aneurysms and two large aneurysms. To achieve complete or near-complete embolization of the recurrent refractory aneurysms, multiple treatment approaches were needed with multiple stents or flow diverting devices. Conclusion: Aneurysm occlusion status after the second embolization is an independent risk factor for the recurrence of intracranial aneurysms. Compared with near-complete occlusion, complete occlusion can significantly reduce the risk of recurrence after second embolization. In order to achieve complete or near-complete occlusion, recurrent refractory aneurysms need multiple treatments with the use of multiple stents or flow diverting devices.

Neuroprotective effects of donepezil against Aß25-35-induced neurotoxicity.

PURPOSE: The purpose of this study was to investigate the neuroprotective effect of donepezil against ß-amyloid25-35 (Aß25-35)-induced neurotoxicity and the possible mechanism. METHODS: PC12 cells were conventionally cultured. Serial concentrations of Aß25-35 and donepezil (0, 0.5, 1, 5, 10, 20 and 50 µmol/L) were added to the PC12 cells, and 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl-2H-tetrazolium bromide (MTT) staining was performed to detect the effects of these treatments on PC 12 viability. The PC 12 cells were pretreated with 1, 5, 10, 20 or 50 µmol/L donepezil two hours before 20 µmol/L Aß25-35 was added to pretreatment groups A, B, C, D and E. Normal control group I and the 20 µmol/L Aß25-35-treated group were selected. An MTT assay was used to detect PC12 cell viability, and the level of lactate dehydrogenase (LDH) was determined. PC12 cells were pretreated with 10 µmol/L GF109203X (a protein kinase C [PKC] antagonist) 30 min before 10 µmol/L donepezil was added to pretreatment group F, and normal control group II, the 10 µmol/L GF109203X-treated group and the 10 µmol/L donepezil-treated group were chosen. The expression of phosphorylation-PKC (P-PKC) and its major substrate phosphorylated myristoylated alanine-rich protein C kinase substrate (P-MARCKS) was measured by Western blotting. The effects of donepezil on the subcellular distribution of the PKCα and PKCε isoforms were detected by immunofluorescence staining. RESULTS: Treatment with Aß25-35 (5, 10, 20 or 50 µmol/L) for 24 h significantly (P < 0.05) decreased PC 12 cell viability in a dose-dependent manner. Compared with the PC12 cells in the control group, those in the 20 µmol/L Aß25-35-treated group exhibited lower viability but higher LDH release. Compared with the 20 µmol/L Aß25-35-treated group, pretreatment groups B, C, D and E exhibited significantly (P < 0.05) increased cell viability but significantly (P < 0.05) decreased LDH release. Western blotting demonstrated that compared with control, 10 µmol/L donepezil promoted PKC and MARCKS phosphorylation and that the expression of P-PKC and P-MARCKS in pretreatment group F was significantly (P < 0.05) lower than that in the donepezil-treated group. Immunofluorescence staining revealed that the PKCα and PKCε isoforms were located mainly in the cytoplasm of PC12 control cells, whereas donepezil increased the expression of the PKCα and PKCε isoforms in the membrane fraction. The Western blot results showed that donepezil altered the subcellular distribution of the PKCα and PKCε isoforms by decreasing their expression in the cytosolic fraction but increasing their expression in the membrane fraction. CONCLUSION: Donepezil can antagonize Aß25-350-induced neurotoxicity in PC 12 cells, and PKC activation may account for the neuroprotective effect of donepezil.

Associations Between Posterior Communicating Artery Aneurysms and Morphological Characteristics of Surrounding Arteries.

Objectives: To explore the associations between posterior communicating artery (PComA) aneurysms and morphological characteristics of arteries upstream of and around the PComA bifurcation site. Methods: In this study, fifty-seven patients with PComA aneurysms and sixty-two control subjects without aneurysms were enrolled. The centerlines of the internal carotid artery (ICA) and important branches were generated for the measurement and analysis of morphological parameters, such as carotid siphon types, diameters of two fitting circles, and the angle formed by them (D1, D2, and ϕ), length (L) and tortuosity (TL) of ICA segment between an ophthalmic artery and PComA bifurcations, bifurcation angle (θ), tortuosity (TICA and TPComA), and flow direction changes (θICA and θPComA) around the PComA bifurcation site. Results: No significant difference (p > 0.05) was found in the siphon types (p = 0.467) or L (p = 0.114). Significant differences (p < 0.05) were detected in D1 (p = 0.036), TL (p < 0.001), D2 (p = 0.004), ϕ (p = 0.008), θ (p = 0.001), TICA (p < 0.001), TPComA (p = 0.012), θICA (p < 0.001), and θPComA (p < 0.001) between the two groups. TICA had the largest area under the curve (AUC) (0.843) in the receiver operating characteristic (ROC) analysis in diagnosing the probability of PComA aneurysms presence and was identified as the only potent morphological parameter (OR = 11.909) associated with PComA aneurysms presence. Conclusions: The high tortuosity of the ICA segment around the PComA bifurcation is associated with PComA aneurysm presence.

Efficacy and long-term results of endovascular embolization and surgical clipping for posterior communicating artery unruptured aneurysms complicated with oculomotor nerve palsy.

THIS STUDY AIMED: to investigate the efficacy and long-term outcomes of endovascular embolization and surgical clipping for patients with posterior communicating artery unruptured aneurysms (PcomAs) concomitant with oculomotor nerve palsy (ONP). No significant (P > .05) difference existed in the age, gender, proportion of complete ONP, and size of eye fissure and pupil before treatment between 2 groups. After compared with before treatment, the eye fissure was widened significantly (P < .05) and the pupil narrowed significantly (P < .05), but no significant (P > .05) differences existed between the 2 groups. Complete ONP recovery was observed in 32 (80%) patients in the embolization group and 31 (77.5%) in the microsurgical group, partial ONP recovery occurred in 6 (15%) in the embolization group and 8 (20%) in the microsurgical group. The recovery rate was 95% in the embolization group and 97.5% in the microsurgical group, with no significant (P > .05) difference between 2 groups. The recovery rate of the ONP was significantly (P < .01) greater in the microsurgical group than that in the embolization group at follow-up of 1 month, 3 months, six and 12 months, respectively. At 18 months, the ONP recovery rate was not significantly different between 2 groups (95% vs 97.5%) Surgical clipping may have a faster effect on the recovery of oculomotor nerve palsy than endovascular embolization for patients with posterior communicating artery unruptured aneurysms complicated with oculomotor nerve palsy, but both approaches may result in a similar effect on the nerve recovery in the long run.Eighty patients treated with endovascular embolization or surgical clipping were retrospectively enrolled into the endovascular embolization group or surgical clipping and analyzed.

Cerebral aneurysms at major arterial bifurcations are associated with the arterial branch forming a smaller angle with the parent artery.

Currently, the relationship of bifurcation morphology and aneurysm presence at the major cerebral bifurcations is not clear. This study was to investigate cerebral arterial bifurcation morphology and accompanied hemodynamic stresses associated with cerebral aneurysm presence at major cerebral arterial bifurcations. Cerebral angiographic data of major cerebral artery bifurcations of 554 anterior cerebral arteries, 582 internal carotid arteries, 793 middle cerebral arteries and 195 basilar arteries were used for measurement of arterial diameter, lateral and bifurcation angles and aneurysm deviation. Hemodynamic stresses were analyzed using computational fluid dynamic simulation. Significantly (P < 0.001) more aneurysms deviated toward the smaller branch and the smaller lateral angle than towards the larger branch and larger lateral angle at all four major bifurcations. At the flow direct impinging center, the total pressure was the greatest while the dynamic pressure, wall shear stress (WSS), vorticity and strain rate were the least. Peak 1 and Peak 2 were located on the branch forming a smaller and larger angle with the parent artery, respectively. The dynamic pressure (175.4 ± 18.6 vs. 89.9 ± 7.6 Pa), WSS (28.9 ± 7.4 vs. 15.7 ± 5.3 Pa), vorticity (9874.6 ± 973.4 vs. 7237.8 ± 372.7 1/S), strain rate (9873.1 ± 625.6 vs. 7648.3 ± 472.5 1/S) and distance (1.9 ± 0.8 vs. 1.3 ± 0.3 mm) between the peak site and direct flow impinging center were significantly greater at Peak 1 than at Peak 2 (P < 0.05 or P < 0.01). Moreover, aneurysms deviation and Peak 1 were always on the same side. In conclusion, the branch forming a smaller angle with the parent artery is associated with abnormally enhanced hemodynamic stresses to initiate an aneurysm at the bifurcation apex.

Greater hemodynamic stresses initiated the anterior communicating artery aneurysm on the vascular bifurcation apex.

OBJECTIVE: To investigate hemodynamic stresses associated with the anterior communicating artery (Acom) aneurysm formation using computational fluid dynamics (CFD) analysis. METHODS: Three-dimensional geometries of the anterior cerebral artery (ACA) bifurcations in 20 patients with Acom aneurysms and 20 control subjects were used for CFD analysis to investigate hemodynamic stresses including the total and dynamic pressure, wall shear stress (WSS), vorticity and strain rate. RESULTS: At the direct flow impinging center on the bifurcation apex, the total pressure was the maximal but decreased quickly from the impinging center to both daughter branches. The WSS, dynamic pressure, vorticity and strain rate were the minimal at the direct impinging center but increased rapidly and reached the peaks at both daughter branches. The ACA bifurcation angle was significantly (P < 0.001) greater in patients with than without Acom aneurysms (144.2° ± 4.1° vs. 105.1° ± 3.2°). Most aneurysms (70% and 85%, respectively) were deviated to the smaller daughter branch or to the daughter branch forming a smaller angle with the A1 segment of ACA, where the hemodynamic stresses were significantly (P < 0.05) greater than those on the contralateral daughter branch. After aneurysm formation, the hemodynamic stresses on the aneurysm dome were all significantly decreased compared with at the aneurysm initiation site with aneurysm virtual removal (P < 0.001). CONCLUSION: Formation of the Acom aneurysm is closely associated with and is to decrease the locally abnormally enhanced hemodynamic stresses.

Middle cerebral arterial bifurcation aneurysms are associated with bifurcation angle and high tortuosity.

PURPOSE: To investigate the association of middle cerebral artery (MCA) bifurcation aneurysms with bifurcation morphology. MATERIALS AND METHODS: 205 patients were enrolled, including 61 patients with MCA bifurcation aneurysms and 144 non-aneurysmal subjects. Aneurysmal cases were divided into types C (aneurysm neck on extension of the parent artery centerline) and D (deviating neck). The radius of the parent artery M1 (RP) and bilateral branches (RS and RL, respectively), smaller (φS) and larger (φL) lateral angles, bifurcation angle, and arterial tortuosity from parent vessel to bilateral branches (TS and TL, respectively) were analyzed. Logistic regression and receiver operator characteristic (ROC) curve analysis were performed to identify risk factors and predictive values for MCA aneurysm presence and types. RESULTS: In aneurysmal MCA bifurcations, bifurcating angle, TS, TL and RL were significantly larger (P<0.01), while φS was significantly smaller (P<0.001) than those in controls. The bifurcation angle, TS and LogitP were better morphological parameters for predicting MCA aneurysm presence with the AUC of 0.795, 0.932 and 0.951, respectively. Significant (P<0.05) differences were observed in the bifurcation angle, φL, RP, RL and TL between types C and D aneurysmal bifurcations. TL was an independent factor in discriminating types C from D aneurysms with an AUC of 0.802. CONCLUSIONS: Bifurcation angle and arterial tortuosity from the parent artery to the branch forming a smaller angle with the parent artery have a higher value in distinguishing MCA aneurysmal from non-aneurysmal ones, and the tortuosity from the parent artery to the contralateral branch is the best indicator for distinguishing types C from D aneurysmal bifurcations.

Enlarged Anterior Cerebral Artery Bifurcation Angles May Induce Abnormally Enhanced Hemodynamic Stresses to Initiate Aneurysms.

OBJECTIVE: To investigate the relationship of anterior cerebral artery (ACA) bifurcation angles with hemodynamic stresses for aneurysm initiation. METHODS: Forty patients with or without anterior communicating artery aneurysms were enrolled, and 3 patients with ACA bifurcation angles of 169.0°, 136.9°, and 73.2°, respectively, were entered into computational fluid dynamics analysis for hemodynamic stresses. RESULTS: Larger bifurcation angles had a larger direct flow impinging zone and larger peak pressure area. In the direct flow impinging center, the total pressure was the highest, whereas the other stresses were the lowest. As blood flowed distally, the total pressure decreased rapidly, whereas all other parameters increased quickly to their peaks. The hemodynamic peak distance was decreased as the bifurcation angle became narrower. The total pressure summit and the peak hemodynamic stresses all decreased with the decrease of bifurcation angles. The distance between the hemodynamic peaks was the smallest at 73.2° compared with larger angles. A significant (P < 0.01) positive linear correlation existed in the ACA bifurcation angle with the distance between hemodynamic stress peaks or in the ACA branch diameter with the distance from the direct impinging center to the ipsilateral hemodynamic stress peak. The hemodynamic stresses on the aneurysm dome were significantly (P < 0.001) smaller than at the aneurysm initiation site. CONCLUSIONS: Larger bifurcation angles may lead to abnormally enhanced hemodynamic stresses, enlarged zones of direct flow impingement, and increased distance between hemodynamic stress peaks to damage the vascular wall for aneurysm initiation on the bifurcation apex wall.

RETRACTED: Endovascular Stent Deployment in the Management of Lesions Related to Internal Carotid Artery Redundancy.

This article has been retracted: please see Elsevier Policy on Article Withdrawal (https://www.elsevier.com/about/our-business/policies/article-withdrawal). This article has been retracted at the request of of the Editor-in-Chief because this article has included both figures and data from patients that were cared for by Dr. Malek at the Cerebrovascular Hemodynamics laboratory in the Department of Neurosurgery, at Tufts Medical Center. As we understand, Dr. Gao did not have clinical privileges and played no clinical role in the care of Dr. Malek's patients while at Tufts Medical Center.

Expression of soluble programmed death-1 protein in peripheral blood regulatory T cells and its effects on rheumatoid arthritis progression.

The present study aimed to investigate the role of the soluble programmed death­1 (sPD-1) protein, which is released by peripheral blood regulatory T cells (Treg) during the progression of rheumatoid arthritis (RA). From October 2012 to May 2014, 82 RA patients (RA group) and 90 healthy volunteers (healthy controls; HC) were recruited. Cluster of differentiation (CD)4, CD25 and forkhead/winged helix transcription factor p3 (Foxp3) and expression of cytotoxic T lymphocyte associated antigen 4 (CTLA-4) and Foxp3 were detected by flow cytometry. Expression of sPD­1 in Treg was detected by western blot analysis. Immunosuppressive activity of CD4+CD25­ Treg was measured via thiazolyl blue in an MTT assay. ELISA was used to detect interleukin­10 (IL­10), transforming growth factor beta (TGF-ß), interleukin-4 (IL-4), interferon­Î³ (IFN-γ) and nuclear factor of activated T cells (NF­AT). It was observed that in peripheral blood, CD4+CD25-FOXP3+/CD4+ levels were reduced in the RA group (P<0.001), and sPD­1 levels were markedly higher (P<0.001), compared with the HC group. Additionally, it was observed that relative sPD­1 protein expression in the small interfering RNA (siRNA)-sPD-1 treated group was reduced compared with the untreated and scrambled siRNA groups (all P<0.0001). The mean fluorescence intensity of CTLA-4 and Foxp3 decreased markedly upon transfection with siRNA-sPD-1 (P<0.001). Compared with the normal CD4+CD25­ T group, optical density (OD)540 values, IFN-γ/IL-4 concentration ratio and NF­AT activity in siRNA untreated and scramble groups reduced significantly (all P<0.001). OD540 value, IFN-γ/IL-4 concentration ratio and NF­AT activity in the siRNA­sPD­1 group were significantly upregulated (all P<0.001). Therefore, sPD-1 may suppress the level of CD4+CD25­ Tregs in the peripheral blood of RA patients, and may be involved in a variety of immune processes mediated by CD4+CD25­ Tregs.

[Study on the association between the HLA-DRB1 alleles and type 2 diabetes in Yi nationality of Yunnan].

OBJECTIVE: To investigate the association between the polymorphism of HLA-DRB1 alleles and type 2 diabetes mellitus in Yi nationality of Yunnan. METHODS: Polymerase chain reaction-sequence specific primers (PCR-SSP) genotyping method was conducted in 79 patients with type 2 diabetes mellitus and 47 ethnically matched controls in Yi Nationality Autonomous Prefecture, Chuxiong. RESULTS: HLA-DR7 and DR11 allele frequencies in type 2 diabetic mellitus patients were significantly higher than those in non-diabetic control subjects respectively(P is 0.009, RR is 8.329;P is 0.029, RR is 7.734). CONCLUSION: DR7 and DR11 alleles are probably susceptible genes of type 2 diabetes mellitus in Yunnan Yi nationality.

[Association between the polymorphism of HLA-DQA1 alleles and type 2 diabetes in Yi nationality of Yunnan].

OBJECTIVE: To investigate the association between the polymorphism of HLA-DQA1 alleles and type 2 diabetes in Yi nationality of Yunnan. METHODS: Polymerase chain reaction with sequence-specific primers (PCR-SSP) genotyping method was conducted in 58 ethnic Yi patients with type 2 diabetes mellitus and 82 ethnically matched controls from Chuxiong of Yunnan. Then a study was made on the association between the polymorphism of HLA-DQA1 alleles and type 2 diabetes mellitus. RESULTS: The frequency of HLA-DQA1*0301 allele in the patients with type 2 diabetes mellitus was significantly higher than that in the healthy controls (P=0.002, RR=3.097), and the frequency of HLA-DQA1*0601 in the patients was significantly lower (P=0.025, RR=0.429). CONCLUSION: In Yi nationality of Yunnan, HLA-DQA1*0301 allele may be a susceptible gene and the HLA-DQA1*0601 allele may protect individuals from the risk of diabetes mellitus.

[Study on the association between the polymorphism of HLA-DQA1 alleles and type 2 diabetes in Yunnan Han nationality].

OBJECTIVE: To investigate the association between the polymorphism of HLA-DQA1 alleles and type 2 diabetes mellitus in Yunnan Hans. METHODS: Polymerase chain reaction-sequence specific primers(PCR-SSP) genotyping method was conducted in 108 Han patients with type 2 diabetes and 56 ethnically matched controls from the same area of Yunnan Province. RESULTS: HLA-DQA1*0301(RR=3.092, P<0.01) and DQA1*0501 (RR=3.257, P<0.05) allelic frequencies in type 2 diabetic patients were significantly higher than those in non-diabetic control subjects respectively. HLA-DQA1*0401 (RR=0.371, P<0.01) allelic frequencies in patients were significantly decreased, compared with controls; HLA-DQA1*0302 (RR=3.356, P<0.01) allelic frequencies in patients with type 2 diabetic nephropathy were significantly increased. CONCLUSION: HLA-DQA1*0301 and DQA1*0501 are susceptible genes of type 2 diabetes in Yunnan Han nationality; in reverse, HLA-DQA1*0401 is a resistant gene. HLA-DQA1*0302 is a susceptible gene of type 2 diabetic nephropathy.