Retraction notice to: The optimality principle decreases hemodynamic stresses for aneurysm initiation at anterior cerebral artery bifurcations [WNEU 121 (2019) e379-e388/10317].

This article has been retracted: please see Elsevier Policy on Article Withdrawal (http://www.elsevier.com/locate/withdrawalpolicy). This article has been retracted at the request of the Editor-in-Chief.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.

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This article has been retracted: please see Elsevier Policy on Article Withdrawal (http://www.elsevier.com/locate/withdrawalpolicy). This article has been retracted at the request of the Editor-in-Chief.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.

Adaptation insights from comparative transcriptome analysis of two Opisthopappus species in the Taihang mountains.

Opisthopappus is a major wild source of Asteraceae with resistance to cold and drought. Two species of this genus (Opisthopappus taihangensis and O. longilobus) have been employed as model systems to address the evolutionary history of perennial herb biomes in the Taihang Mountains of China. However, further studies on the adaptive divergence processes of these two species are currently impeded by the lack of genomic resources. To elucidate the molecular mechanisms involved, a comparative analysis of these two species was conducted. Among the identified transcription factors, the bHLH members were most prevalent, which exhibited significantly different expression levels in the terpenoid metabolic pathway. O. longilobus showed higher level of expression than did O. taihangensis in terms of terpenes biosynthesis and metabolism, particularly monoterpenoids and diterpenoids. Analyses of the positive selection genes (PSGs) identified from O. taihangensis and O. longilobus revealed that 1203 genes were related to adaptative divergence, which were under rapid evolution and/or have signs of positive selection. Differential expressions of PSG occurred primarily in the mitochondrial electron transport, starch degradation, secondary metabolism, as well as nucleotide synthesis and S-metabolism pathway processes. Several PSGs were obviously differentially expressed in terpenes biosynthesis that might result in the fragrances divergence between O. longilobus and O. taihangensis, which would provide insights into adaptation of the two species to different environments that characterized by sub-humid warm temperate and temperate continental monsoon climates. The comparative analysis for these two species in Opisthopappus not only revealed how the divergence occurred from molecular perspective, but also provided novel insights into how differential adaptations occurred in Taihang Mountains.

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.

Current status of thromboembolism risk assessment in patients hospitalized with non-valvular atrial fibrillation in tertiary hospitals in China / 中华心血管病杂志

Objective: To analyze the current status, trend and predictors of thromboembolism risk assessment in patients hospitalized with non-valvular atrial fibrillation (NVAF) in tertiary hospitals in China. Methods: The study was based on data from the Improving Care for Cardiovascular disease in China (CCC)-Atrial Fibrillation (AF) project. About 10% of the tertiary hospitals in each geographic-economic stratum were recruited. Participating hospitals reported the first 10 to 20 patients with a discharge diagnosis of atrial fibrillation monthly. From February 2015 to December 2019, a total of 49 104 NVAF patients from 151 tertiary hospitals in 30 provinces, municipalities and autonomous regions were enrolled. Clinical data of the patients was collected. The proportion of NVAF patients receiving thromboembolism risk assessment, variations in the proportion between different hospitals, the time trend of the application of thromboembolism risk assessment, and the predictors of the application of thromboembolism risk assessment were analyzed. Results: The age of the NVAF patients was (68.7±12.1) years, 27 709 patients (56.4%) were male. Only 17 251 patients (35.1%) received thromboembolism risk assessment. The proportion varied substantially between hospitals with the lowest value of 0 and the highest value of 100%. Among the hospitals, which enrolled more than 30 patients, no patients received thromboembolism risk assessment in 18.4% (26/141) of the hospitals, more than 50% of the patients received thromboembolism risk assessment in 21.3% (30/141) of the hospitals, and all the patients received thromboembolism risk assessment in only 1 hospital. The proportion of NVAF patients receiving thromboembolism risk assessment was 16.2% (220/1 362) in the first quarter of 2015, and significantly increased to 67.1% (1 054/1 572) in the last quarter of 2019 (P<0.001). Patients' characteristics were associated with the application of thromboembolism risk assessment. The odds of receiving thromboembolism risk assessment was lower in male patients compared to female patients(OR=0.94,95%CI 0.89-0.99), lower in patients with acute coronary syndrome or other cardiovascular diseases compared to those with AF as the primary admission reason (OR=0.59, 95%CI 0.55-0.63, OR=0.52, 95%CI 0.45-0.61, respectively), and lower in patients with paroxysmal, persistent and long-standing/permanent AF compared to those with first detected AF (OR=0.62, 95%CI 0.57-0.67, OR=0.72, 95%CI 0.66-0.79, OR=0.57, 95%CI 0.52-0.64, respectively). The odds was higher in patients with a history of hypertension, heart failure, stroke/TIA, and previous anticoagulant therapy compared to those without the above conditions (OR=1.17, 95%CI 1.11-1.23, OR=1.18, 95%CI 1.07-1.30, OR=1.17, 95%CI 1.08-1.27, OR=1.28, 95%CI 1.19-1.37, respectively) (P all<0.05). Conclusion: Thromboembolism risk assessment was underused in patients hospitalized with NVAF in tertiary hospitals in China, and there were substantial variations between hospitals in the application of thromboembolism risk assessment. The application of thromboembolism risk assessment in tertiary hospitals has been improved in recent years, but there is still plenty of room for future improvement. Patients' characteristics could affect the application of thromboembolism risk assessment in China.

Cerebral arterial infundibula are preaneurysmal lesions caused by direct flow impact.

PURPOSE: To investigate whether arterial infundibular widening is a preaneurysmal lesion or not. METHODS: Two hundred and nine patients with cerebral angiography were enrolled. The morphology, size and location of infundibula and cerebral aneurysms were studied in two-dimensional angiography and three-dimensional software space. Computational fluid dynamics (CFD) analysis was performed. RESULTS: 234 infundibula and 129 infundibulum-like aneurysms (IFAs) were detected. In two-dimensional space, the typical morphology of an infundibulum was a symmetric dilatation at the arterial branch origin with a small vessel branch emanating from the tip and a wide base connecting the parent artery. In three-dimensional space, the infundibulum was dissymmetric with always one side longer than the other side. Furthermore, the infundibulum tilted upstream rather than downstream, with the longer side located downstream and the shorter side upstream in all cases. All the 129 IFAs occurred on the distal wall of the vessel branch origin, and no IFAs grew from the proximal wall of the branch origin. The possible development process of an infundibulum to an IFA was described in four development stages. The CFD analysis revealed that these lesions were associated with direct flow impingement in all cases. All the hemodynamic parameters on the distal wall of infundibula and IFAs were significantly (P<0.0001 or P<0.05) decreased compared with on the distal wall after virtual lesion removal. CONCLUSION: The infundibulum is a preaneurysmal lesion associated with high total pressure and high wall shear stress resulted from direct flow impingement and will progress to an aneurysm with time.

Asymmetrical than symmetrical cerebral arterial bifurcations are more vulnerable to aneurysm presence.

In order to investigate the role of lateral angle ratio (LA ratio) and daughter artery ratio (DA ratio) for predicting aneurysmal presence in main cerebral arterial bifurcations, three-dimensional cerebral angiographic data of major cerebral artery bifurcations were used for measurement of artery diameters and bifurcation angles including 115 middle cerebral arteries (MCAs), 59 basilar arteries (BAs), 35 internal carotid arteries (ICAs) and 115 anterior cerebral arteries (ACAs) with bifurcation aneurysms and control subjects of 1921 bifurcations with no aneurysms. The LA ratio (larger lateral angle/smaller lateral angle) and DA ratio (larger branch diameter/smaller branch diameter) were calculated, and ROC curve analysis of LA and DA ratios between normal and aneurysmal cases was performed. The LA and DA ratios of MCA bifurcations and the LA ratios of BA and ICA bifurcations with aneurysms were all significantly larger than normal bifurcations (P < 0.05), and the DA ratio of ACA bifurcations with aneurysms was significantly smaller than normal cases (P < 0.01). Moreover, the LA ratio or DA ratio between the normal and aneurysm cases in MCA, BA and ACA bifurcations demonstrated significant differences by ROC analysis (P < 0.01) except in the ICA bifurcations. No significant difference was observed (P > 0.05) between ruptured and unruptured aneurysms in MCA, BA, ICA and ACA bifurcations. In summary, normal MCA, BA and ICA bifurcations show symmetrical morphology in the lateral angles and daughter branches, whereas aneurysmal bifurcations show asymmetrical morphology. Normal ACA bifurcations have asymmetrical bilateral daughter branches while symmetrical branches are associated with ACA bifurcation aneurysm presence.

Asymmetrical middle cerebral artery bifurcations are more vulnerable to aneurysm formation.

The objective of this study was to elucidate possible relationship between middle cerebral artery (MCA) bifurcation aneurysms and bifurcation morphology. In the present study, 799 patients with three-dimensional angiography were enrolled, including 115 patients with MCA bifurcation aneurysms and 684 subjects without aneurysms. The MCA bifurcation geometry, including angles formed between two M2 segments (φ1) and between M1 and M2 segments, vessel diameters and aneurysm sizes were measured. DA ratio (larger/smaller M2 in diameter) and LA ratio (larger/smaller lateral angle) were also analyzed. The LA and DA ratios and angle φ1 were significantly (P < 0.0001) greater in patients harboring MCA bifurcation aneurysms than in the control, whereas lateral angles and bifurcation branch diameters were significantly smaller (P < 0.01) in patients with than without bifurcation aneurysms. Angle φ1 was significantly increased (P < 0.0001) while both lateral angles significantly decreased (P < 0.0001 and P = 0.0005, respectively) with increase of patients' age. The size of MCA bifurcation aneurysms was significantly (P < 0.05) positively correlated with the bifurcation vascular diameter and aneurysm neck at the MCA bifurcation. A significantly positive correlation existed between aneurysm neck and DA ratio (P = 0.0075), whereas an inverse correlation between aneurysm neck and LA ratio (P = 0.0219). MCA bifurcation aneurysms were mostly deviated toward the smaller lateral angles and smaller M2 branch. In conclusion, aneurysmal MCA bifurcations have asymmetrical bifurcation structures with widened bifurcation angles, narrowed lateral angles, decreased M1 diameter, imbalanced lateral angles and M2 segments, with the cutoff bifurcation angle of 125.0° and cutoff lateral angle ratio of 1.57 for predicting MCA bifurcation aneurysms, whereas normal MCA bifurcations show close to symmetrical structures in the lateral angles and M2 branches.

[Slit/Robo pathway participates in luteal cells apoptosis].

This study was aimed to examine the expression and function of Slit/Robo family members in mouse ovary. Real-time PCR was used to assess the mRNA expression levels of Slit/Robo family members, and immunohistochemistry was used to examine the location of Slit2 and Robo1 in the ovary. The mRNA and protein expression levels of Slit2 and Robo1 in early-, middle- and late-phase corpus luteum (CL) were examined by real-time PCR and immunohistochemistry, respectively. Blocking agent ROBO1/Fc chimera was used in the luteal cells in vitro to examine the function of Slit/Robo signaling pathway in mouse CL. The results showed that, among the Slit/Robo family members, the expression levels of ligand Slit2 and receptor Robo1 were the highest in mouse ovarian tissue. Moreover, both of them were specifically expressed in mouse luteal cells. Compared with proestrus ovaries, the expression levels of Slit2 and Robo1 mRNA in the ovaries during diestrus were significantly up-regulated (P < 0.01, P < 0.001). The mRNA expression levels of Slit2 and Robo1 in late-phase CL were significantly increased when compared with pregnant CL. Furthermore, blocking Slit/Robo signaling pathway with ROBO1/Fc chimera in the luteal cells in vitro significantly decreased the apoptotic rate of late luteal cells. These results suggest that Slit/Robo family members are mainly expressed in the late-phase CL of ovary and participate in luteal cells apoptosis.

The Optimality Principle Decreases Hemodynamic Stresses for Aneurysm Initiation at Anterior Cerebral Artery Bifurcations.

OBJECTIVE: To investigate hemodynamic stresses on anterior cerebral artery bifurcation apex and possible mechanism of the optimality principle in protecting bifurcation wall from supercharged hemodynamic stresses. METHODS: Three-dimensional angiographic datasets of 122 patients with anterior communicating artery (Acom) aneurysms, 21 patients with non-Acom aneurysms, and 220 control subjects with no aneurysms were used. Radii of parent (r0) and daughter branches (r1 and r2) were measured, and bifurcations obeying the optimality principle required optimal caliber control of r0n = r1n + r2n, with the junction exponent n approximating 3. Radius ratio = r03/(r13 + r23) and n were compared between aneurysmal and control bifurcations. Blood flow was simulated for analysis of hemodynamic stresses. RESULTS: Acom bifurcations in subjects without Acom aneurysms displayed optimal caliber radius, with mean radius ratio of 0.99 and n of 3.25, whereas Acom aneurysmal bifurcations had significantly lower radius ratio, 0.62 (P < 0.05), but higher n, 4.23 (P < 0.05). Peak wall shear stress and corresponding total pressure were significantly smaller for bifurcations obeying than disobeying the optimality principle (P < 0.001 and P < 0.05, respectively). Total pressures in the direct impinging center, peak wall shear stress distance, and anterior cerebral artery bifurcation angle all were significantly smaller for bifurcations obeying than disobeying the optimality principle (P < 0.05 and P < 0.001, respectively). CONCLUSIONS: Normal anterior cerebral artery bifurcations obey the optimality principle whereas bifurcations with Acom aneurysms do not. Disobeying the optimality principle presents significantly enhanced hemodynamic stresses to possibly damage the bifurcation wall for aneurysm initiation.

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.

Association of Basilar Bifurcation Aneurysms With Age, Sex, and Bifurcation Geometry.

BACKGROUND AND PURPOSE: Basilar artery (BA) bifurcation aneurysms are common, but the correlation between BA bifurcation morphology and aneurysm formation remains to be established. Our purpose was to determine the association of BA bifurcation aneurysms with patient age, sex, bifurcation angle, and branch diameter. METHODS: Three-dimensional angiographic data of 195 patients were used, including 59 patients with BA bifurcation aneurysms and 136 control subjects. The angles formed between left and right posterior cerebral arteries (φ1) and between posterior cerebral artery and BA (the smaller angle defined as φ2 and the larger one as φ3), arterial diameters, and BA bifurcation aneurysm geometric characters were examined. RESULTS: Women of 40 to 70 years of age are more vulnerable to BA bifurcation aneurysm formation than men. The φ1 bifurcation angle significantly increased (P<0.0001), whereas both φ2 and φ3 angles significantly decreased (P<0.0001 and P=0.09, respectively) with increase of patients' age. Statistically significant (P<0.0001 and P=0.0002, respectively) positive correlations were observed between BA bifurcation branch diameter and aneurysm size. The φ1 angle was significantly (P<0.0001) wider in patients harboring BA bifurcation aneurysms than the control, whereas φ2 and φ3 angles in aneurysm group were significantly smaller than those in the control group (P<0.0001). The BA bifurcation aneurysms were mostly deviated toward the smaller φ2 angle side between φ2 and φ3 angles and deviated toward the smaller-diameter daughter posterior cerebral artery branch. CONCLUSIONS: BA bifurcation aneurysms are significantly associated with patients' age, female sex, wider bifurcation angles, and smaller vascular diameter at the BA bifurcation.

Presence of Anterior Communicating Artery Aneurysm Is Associated With Age, Bifurcation Angle, and Vessel Diameter.

BACKGROUND AND PURPOSE: The anterior communicating artery (Acom) aneurysm is the most complex in all cerebral aneurysms, and wider vascular bifurcation angles are considered to be associated with aneurysm formation. The objective of this study was to investigate association of the Acom aneurysm formation with patient age and vascular bifurcation morphology. METHODS: Three-dimensional angiographic data of 665 patients were used in this study, including 160 patients with Acom aneurysms, 66 with non-Acom aneurysms, and 439 control subjects with no aneurysms. The anterior cerebral artery bifurcation angle (Acom/A2 angle), arterial diameters, and Acom aneurysm geometric characters were examined. RESULTS: Women of 50 to 70 years were more vulnerable to Acom aneurysm formation than men. The Acom/A2 bifurcation angle was significantly increased (P<0.0001) with increase of patient age. The size of the Acom aneurysm dome and neck was statistically positively correlated with the diameter of the Acom, A1 and A2 segments (P<0.0001). The Acom/A2 bifurcation angle was significantly (P<0.0001) wider in patients with than without Acom aneurysms, whereas the A1/A2 angle was significantly smaller in patients with than without Acom aneurysms (P<0.0001). The Acom aneurysms at the bifurcation apex mostly deviated toward the smaller angle formed between the parent A1 and branches and toward the daughter artery with a smaller diameter. The Acom aneurysms were located mostly on the dominant anterior cerebral artery. CONCLUSIONS: The presence of Acom aneurysm is significantly associated with patient age, wider angles of the anterior cerebral artery bifurcation, and smaller vascular diameter of the anterior communicating complex.

Construction of an in vivo carotid siphon model for testing endovascular devices for neuro-interventions.

Objective The aim of this study was to construct an in vivo carotid siphon model for testing neurovascular devices for endovascular interventions. Methods A model of a human carotid siphon was pre-shaped using a glass tube from a human cadaver and used to confine a segment of one side of the common carotid artery (CCA) in canines. This segment of CCA with the glass carotid siphon on was interposed end-to-end onto the contralateral CCA so as to simulate a human carotid artery siphon in vivo. Two weeks later, the siphon model was evaluated using computed tomography angiography and digital subtraction angiography, and the covered stent specially designed for intracranial vasculature was navigated through the siphon model for a longitudinal flexibility test. Results All dogs tolerated the procedures well, and the artificial siphon model in vivo provided realistic conditions for device testing. Two weeks later, the in vivo carotid siphon model remained patent with no thrombosis. Five covered stents were navigated to pass through five siphon models successfully, with vasospasm occurring in two siphons. Conclusion Construction of an in vivo siphon model in dogs with a glass tube is feasible and useful for the test of endovascular devices for treating neurovascular diseases.

Study of reducing graft-versus-host disease by in vitro blockade of CD40-CD40 ligand co-stimulatory pathway in allogeneic bone marrow transplantation mouse model / 中华血液学杂志

<p><b>OBJECTIVE</b>To investigate the effect and its mechanism of reducing graft-versus-host disease (GVHD) by in vitro blockade of CD(40)-CD(40)L pathway in vitro, the donor T lymphocytes cultured in vitro with anti-CD(40)L mAb were transfused in bone marrow transplantation (BMT) GVHD mouse model.</p><p><b>METHODS</b>C57BL/6(H-2b) spleen T cells were isolated as responder cells, and BALB/c(H-2d) spleen cells as stimulator cells. They were cocultured with or without Anti-CD(40)L mAb as anti-CD(40)L mAb group and control group, respectively. At day 5, the mixed lymphocyte response (MLR)-culture cells mixed with bone marrow cells and transfused respectively into the TBI conditioned recipient mice. The mice were divided into two groups: group A, bone marrow cells (2 x 10(6)) and spleen T lymphocytes (2 x 10(6)) from MLR control group; group B, bone marrow cells (2 x 10(6)) and spleen T lymphocytes (2 x 10(6)) from MLR anti-CD(40)L mAb group. The GVHD incidence and hematopoietic reconstitution were observed. Peripheral blood sera and spleen cells of the recipients mice were harvested at scheduled time points for the measurement of cytokines and T cell immunophenotyping with flow cytometry.</p><p><b>RESULTS</b>The incidence of GVHD in group A was 100% (10/10), and in group B was 20% (2/10). The percentage of H-2D(b) positive cells in group B (n = 8) was (93.54 +/- 2.32)% at day 40 after transplantation. The levels of cytokines in serum from group B were significantly lower than those from group A (P < 0.05). The expressions of CD(4)(+), CD(8)(+), CD(4)(+)CD(25)(+), CD(8)(+)CD(25)(+), CD(4)(+)CD(69)(+), CD(8)(+)CD(69)(+) and CD(4)(+)CD(40)L(+) were lower in group B than in group A (P < 0.05). The expressions of CD(8)(+)CD(40)L(+) and CD(4)(+)CD(45)RA(+) were similar in the two groups (P > 0.05).</p><p><b>CONCLUSION</b>Blockade of CD(40)-CD(40)L interaction in vitro could induce immune tolerance in vivo, reduce aGVHD in aGVHD mice model and form chimerism, which was mediated by inhibiting the Th1 and Th2 cytokines production, inducing tolerance of CD(4)(+) and CD(8)(+) cells to alloantigens. The obstruction of T cells activation after tolerance happened mainly at the early and mature phase of T cells activation. These provided the experimental basis for the use of anti-CD(40)L mAb in the clinical transplantation to prevent aGVHD.</p>