Internal carotid artery bifurcation aneurysms are probably formed to decrease the abnormally-enhanced hemodynamic stresses caused by direct flow impaction

Introduction

Saccular cerebral aneurysms are local dilatation of cerebral arterial wall and closely associated with hemodynamic stresses such as dynamic and total pressure, wall shear stress (WSS), vorticity, and strain rate during all the phases of aneurysm development, including aneurysm initiation, evolution, and final rupture as the most dreaded complication (1-5). Bifurcation apexes of cerebral arteries are the most common site of aneurysm presence because of the maximal hemodynamic stresses at the bifurcation wall caused by direct blood flow impingement (1,3,6-8). Significantly increased hemodynamic stresses have been reported to be associated with aneurysm formation at the internal carotid artery (ICA) bends (2), anterior cerebral artery (ACA) bifurcation (1), anterior communicating artery (1), and major cerebral arterial bifurcations (3). It has been reported that the area circled by the aneurysm neck is the initiating location of aneurysms (1-3,9). Nonetheless, the hemodynamic stresses within this region have not been clearly specified to start an aneurysm at the ICA bifurcation. A clear understanding of the relationship between hemodynamic stresses and aneurysm formation at the ICA bifurcation is critical to the development of novel therapeutic and preventive strategies. The ICA bifurcation aneurysms have been numerically simulated using fluid-structure interaction (10) and computational fluid dynamics (CFD) (11,12) in a few models or patient-specific three-dimensional (3D) datasets. In a study evaluating the influence of postural changes on hemodynamics in ICA bifurcation aneurysm using numerical fluid-structure interaction methods (10), it was found that during the head-down position, significant changes in flow and high arterial blood pressure were observed in the ICA bifurcation aneurysm model, with significant increases in the flow velocity, WSS, and pressure. In a study assessing the pulsatile flow rate and shunt ratio on hemodynamic characteristics involved in two patient-specific ICA sidewall aneurysms (11), larger pulsatile flow rates caused higher WSS in some local regions of the aneurysmal dome, low WSS and relatively high oscillatory shear index (OSI) appeared under a smaller pulsatile flow rate, a higher pulsatile flow rate contributed more to the pressure increase in the ICA aneurysm dome, variances of shunt ratios in bifurcated distal arteries had rare impacts on the hemodynamic characteristics in the sacs, and vortex location played a major role in the temporal and spatial distribution of the WSS on the luminal wall. In a study evaluating the WSS in intracranial aneurysms and adjacent arteries (12), after formation of the anterior communicating artery aneurysm, the WSS at the dome of the ICA aneurysm increased significantly, and the WSS in the upstream arteries also changed significantly. These studies did not exactly assess the hemodynamic parameters of the ICA bifurcation aneurysms, and the aneurysms investigated were only on the ICA, namely, side wall aneurysms of the ICA (10-12). Moreover, the hemodynamic parameters only included WSS, high OSI, flow rate, or changes caused by postural changes in a few models. No specific studies have been performed on the relationship of hemodynamic stresses with aneurysm formation or presence at the ICA bifurcation before and after virtual aneurysm removal. Therefore, it was hypothesized that greater hemodynamic stresses were associated with aneurysm formation at the ICA bifurcation, and this study was conducted to investigate the hemodynamic parameters at the ICA bifurcation with aneurysms using the CFD method to compare the hemodynamic parameters before and after virtual aneurysm removal in a relatively larger cohort of patients with the patient-specific 3D imaging datasets. We present this article in accordance with the STROBE reporting checklist (available at https://qims.amegroups.com/article/view/10.21037/qims-2025-389/rc).

Methods

Participants

The study was conducted in accordance with the Declaration of Helsinki and its subsequent amendments. The study was approved by the institutional ethics board of Shijiazhuang People’s Hospital (No. 20220128) and informed consent was taken from all the patients. Participants consented to have the images published. All methods were conducted in accordance with the relevant guidelines and regulations. Between January 2018 and December 2022, 3D imaging data of consecutive patients with ICA bifurcation aneurysms were retrospectively collected. The inclusion criteria were patients with angiography-confirmed ICA bifurcation aneurysms and clear 3D angiographic imaging datasets for CFD and morphological analysis. Imaging datasets without any cerebral aneurysms, without clear 3D angiographic imaging datasets, or with aneurysm aneurysms at other cerebral arteries were excluded.

Measurement

A sphere was used to measure the hemodynamic parameters on the aneurysm dome (Figure 1A,1B) and ICA bifurcation apex after virtual aneurysm removal (Figure 1C). One longitudinal line was used to sample the hemodynamic parameters across the aneurysm dome (Figure 1D). A longitudinal line across the direct flow impinging center (DFIC) (Figure 1E) and five short lines (Figure 1F) on the bifurcation apex were used to sample the hemodynamic parameters after virtual aneurysm removal. Lines 2–4 were located within the aneurysm scope before virtual aneurysm removal, whereas lines 1 and 5 were located outside the aneurysm scope. On the aneurysm dome, one part was red with strong hemodynamic parameters and the other part was green and yellow with weaker hemodynamic parameters (Figure 1G,1H), which was measured with a sphere. A scale was used to express the magnitude of the hemodynamic parameters, with red indicating strong and blue weaker hemodynamic parameters (Figure 1I).

Figure 1 Measurement of an aneurysm on an ICA bifurcation. (A) An ICA bifurcation aneurysm is shown. (B) A sphere was used to sample the hemodynamic parameters on the ICA bifurcation aneurysm dome. (C) After the aneurysm was virtually removed, a sphere was used to sample the hemodynamic parameters on the bifurcation apex where the aneurysm was formed. (D) A line was used to sample the hemodynamic parameters on the aneurysm dome, and the shape of the line sampling on the aneurysm dome and on the adjacent bifurcation apex. (E,F) A longitudinal line across the DFIC (E) and five short lines (F) were used to sample the hemodynamic parameters on the bifurcation apex after virtual aneurysm removal. (F) Line 3 is located at the DFIC, line 3 at one peak, line 4 on the other peak of hemodynamic stresses, line 1 on the ACA, and line 5 on the MCA. (G) A sphere was used to sample the aneurysm dome where strong hemodynamic stresses were present to possibly cause further expansion. (H) A sphere was used to sample the hemodynamic parameters on the aneurysm dome with weak hemodynamic stresses. (I) A scale was shown to indicate the magnitude of hemodynamic stresses: red indicates greater magnitude. ACA, anterior cerebral artery; DFIC, direct flow impinging center; ICA, internal carotid artery; MCA, middle cerebral artery.

CFD analysis

CFD analysis was conducted using the 3D angiographic datasets of patients after reconstruction of the datasets for surface rendering with the Amira software (5.2.2, Visual Computing Laboratory, San Diego, CA, USA). Virtual aneurysm removal, surface reconstruction, and smoothing were conducted with the MeshLab software (V 1.3.2, Visual Computing Laboratory) using the Laplacian Smooth function in the Smoothing, Fairing and Deformation under Filters in the top menu, with the nearest vertex being calculated for each vertex needed to be smoothed. Polyhedral meshes with high resolution were produced using the Harpoon software (V. 4.3, Sharc, Manchester, England) at approximately 1 million cells. In producing the mesh, the 3D arterial data in the STL format was imported, the holes in the STL arterial mesh were filled automatically before using the mesh function in the top menu for mesh production with the surface cell size at level 2 or 3, and then the mesh was exported in the format of fluent (surface + volume) for further processing. The Fluent software (V 12.0.16, Ansys, Lebanon, NH, USA) was used to calculate the finite-volume solution, with the assumption of non-slip rigid arterial wall, blood density 1,070 kg/m³, and blood viscosity 3.5 cp (13). The boundary conditions were velocity inlet (0.1 m/second) and pressure outlet (0 Pa) in all cases. Postprocessing of the CFD data was performed with the Ensight software (V 9.0, Ansys).

Statistical analysis

The statistical analysis of this study was performed with the software SPSS (version 20.0, IBM Corp., Chicago, IL, USA). Measurement data were presented as a mean ± standard deviation (SD) and tested with the t-test if confirming to a normal distribution or as a median and interquartile range (IQR; lower and upper quartile) and tested with the Mann-Whitney U test if it was not normally distributed. Categorical data were presented as frequency and percentage and tested with the chi square test or Fisher’s exact test. The level of significance was set at P<0.05.

Results

The 3D angiographic imaging datasets of 20 patients with ICA bifurcation aneurysms were collected for CFD analysis, including 15 (75%) female and 5 (25%) male patients aged 26–76 (50.0±13.4) years. The ICA bifurcation aneurysm was on the right side in 12 (60%) patients and left side in 8 (40%).

Compared with the hemodynamic parameters on the aneurysm dome (Table 1 and Figure 2), all the hemodynamic parameters (dynamic and total pressure, vorticity, cell and turbulence Reynolds numbers, turbulence kinetic energy, intensity, dissipation rate, WSS, and strain rate) on the ICA bifurcation apex after virtual aneurysm removal were significantly (P<0.0001) increased.

Figure 2 Demonstration of the hemodynamic parameters on an ICA bifurcation aneurysm and on the bifurcation apex after virtual aneurysm removal. (A1,A2) Hemodynamic parameters with different magnitudes were shown on the ICA bifurcation aneurysm dome and adjacent arteries. (B1,B2) After the ICA bifurcation aneurysm was virtually removed, hemodynamic parameters were shown on the bifurcation apex. Double arrows indicate the part of aneurysm dome with lower hemodynamic stresses while the single arrow indicates the part of aneurysm dome with significantly higher hemodynamic stresses. Color significance: blue indicates lower magnitude, red indicates higher magnitude, and from blue to red, the magnitude of hemodynamic parameters increases gradually. ICA, internal carotid artery; Turb, indicates turbulence.

On the plane of blood flow simulation, blood flow entered the bifurcation aneurysm close to the middle cerebral artery (MCA) branch which formed an obtuse angle with the ICA, and the strong part of the aneurysm dome was at strong direct flow impact (Figure 3). After virtual aneurysm removal, blood flow directly impinged the DFIC on the bifurcation apex close to the ACA branch which formed an acute angle with the ICA.

Figure 3 Hemodynamic parameters related to the blood flow near an ICA bifurcation with an aneurysm and with virtual aneurysm removal. (A1,A2) Blood flow was shown to enter the ICA bifurcation aneurysm mainly through the side formed a large angle (93.57°) with the middle cerebral artery. (B1,B2) Blood flow directly impinged the bifurcation apex after virtual aneurysm removal, with the major blood flow impacting the bifurcation wall (DFIC) towards the side of anterior cerebral artery forming an acute angle (34.88°) with the ICA. Double arrows indicate the part of aneurysm with direct strong flow impact and the single arrow shows the part of aneurysm with weaker flow impact. Color significance: blue indicates lower magnitude, red indicates higher magnitude, and from blue to red, the magnitude of hemodynamic parameters increases gradually. DFIC, direct flow impinging center on the bifurcation apex after virtual aneurysm removal; ICA, internal carotid artery; Turb, turbulence.

On the line for sampling hemodynamic parameters across the aneurysm dome and bifurcation apex after aneurysm removal, the hemodynamic parameters on the aneurysm were significantly decreased (P<0.0001) compared with those on the bifurcation apex after aneurysm removal (Table 2 and Figures 4,5). The hemodynamic profiles on the line showed typical features. On the line across the bifurcation apex after aneurysm removal, the WSS, dynamic pressure, vorticity, strain rate, and cell Reynolds number were very low at the DFIC, and two peaks of hemodynamic parameters appeared when flow moved towards the ACA and MCA branches (Figure 4). On the line across the aneurysm dome, the hemodynamic parameters remained very low except for the aneurysm part with strong hemodynamic parameters (Figures 4,5). For the turbulence parameters (Figure 5), the turbulence Reynolds number, kinetic energy, intensity, and dissipation rate fluctuated greatly on the line after aneurysm removal but remained relatively stable on the line across the aneurysm dome except for the aneurysm part with strong hemodynamic parameters.

Figure 4 Line sampling of hemodynamic parameters across the aneurysm dome and the DFIC. The hemodynamic parameters on the aneurysm dome were significantly decreased compared with those at the bifurcation apex with aneurysm removal. The hemodynamic parameters on the aneurysm part with strong hemodynamic parameters (arrow in figures of WSS, total pressure and dynamic pressure) remained very high. The profiles on the line across the bifurcation apex with aneurysm removal are characteristic. DFIC, direct flow impinging center; WSS, wall shear stress.

Figure 5 Hemodynamic parameters on the line across the aneurysm dome and bifurcation apex after virtual aneurysm removal. Top row: the turbulence parameters (turbulence Reynolds umber, kinetic energy, intensity, and dissipation rate) on the line across the aneurysm dome were stably low for most of the part except for the aneurysm dome with strong hemodynamic parameters (arrows). Bottom row: the turbulence Reynolds number, kinetic energy, intensity, and dissipation rate fluctuated greatly on the line on the bifurcation apex after aneurysm removal. ICA, internal carotid artery; Turb, turbulence.

Five lines were used to sample the hemodynamic parameters at the bifurcation apex after aneurysm removal (Figure 1F and Table 3), with line 1 being located on the smaller ACA branch forming an acute angle with the ICA, line 2 at peak 1 of hemodynamic stresses (Figure 4), line 3 at the middle of the DFIC, line 4 at peak 2 of hemodynamic stresses (Figure 4), and line 5 on the larger MCA branch forming an obtuse angle with the ICA. On line 2 at peak 1, the dynamic and total pressure, vorticity, WSS, strain rate, and cell Reynolds number were all significantly greater (P<0.0001) than those on line 3 at the DFIC except for the total pressure on line 3 or line 1 on the smaller ACA, whereas all the turbulence parameters (kinetic energy, intensity, dissipation rate, and Reynolds number) were significantly greater (P<0.0001) than those on line 1 but smaller than those on line 3. On line 4 at peak 2, all hemodynamic parameters were significantly greater (P<0.0001) than those on line 3 except for the total pressure on line 3 or on line 5 on the larger MCA.

On the aneurysm dome, the hemodynamic stresses on the stronger part were all significantly increased (P<0.0001) compared with those on the weaker part (Figure 1G,1H and Table 4).

Discussion

In this study, we investigated the hemodynamic parameters associated with the presence of ICA bifurcation aneurysms using CFD analysis of patients’ specific 3D imaging datasets. It was found that all the hemodynamic parameters on the ICA bifurcation apex after virtual aneurysm removal were significantly increased (P<0.0001) compared with those on the aneurysm dome, and blood flow directly impinged the bifurcation apex where the bifurcation aneurysm was initiated. ICA bifurcation aneurysm formation is associated with significantly decreased hemodynamic parameters, the function of which is to decrease the abnormally-enhanced hemodynamic parameters on the bifurcation apex caused by direct flow impingement.

A saccular cerebral aneurysm is only a local pathological dilatation of a weakened arterial wall with localized elastic laminal destruction, medial smooth apoptosis, and inflammatory cell infiltration (1,13-17). It only involves a small portion of the arterial wall in pathology and is different from a fusiform aneurysm in that a fusiform aneurysm affects the whole vascular wall within a certain range like a deformed cigar (3,18,19). Thus, virtual removal of the aneurysm is reasonable to restore the arterial wall to the state before aneurysm formation, and this virtual aneurysm removal technique has been applied by many researchers in aneurysm investigation (1-3,20-24). After virtual aneurysm removal, blood flow directly impinged the ICA bifurcation apex at the DFIC which was close to the ACA branch forming an acute angle with the ICA. The hemodynamic parameters on the bifurcation apex with aneurysm removal were significantly increased compared with those on the aneurysm dome, which may indicate that aneurysm formation has the purpose of decreasing the abnormally enhanced hemodynamic stresses caused by direct flow impingement.

One longitudinal line was used to sample the hemodynamic stresses across the aneurysm dome and on the bifurcation apex after aneurysm removal. The hemodynamic parameters on the line across the aneurysm dome were all significantly decreased compared with those on the line across the bifurcation apex after aneurysm removal, which confirmed the idea that aneurysm formation aims to decrease the hemodynamic stresses. Moreover, the hemodynamic profiles on the line showed some typical features. Before aneurysm removal, the hemodynamic stresses on the line across the aneurysm dome were maintained significantly constantly low with few fluctuations. After aneurysm removal, the total pressure was the maximal whereas all the other hemodynamic stresses were extremely low at the DFIC on the line across the bifurcation apex. With blood flowing towards either the ACA or the MCA branch, the total pressure dropped quickly while two peaks of hemodynamic stresses appeared as the flow speed was significantly increased. To explore where exactly the aneurysm was initiated, five short lines were used to sample the hemodynamic stresses on the ICA bifurcation, with line 1 on the ACA branch, line 2 at one peak of hemodynamic stresses, line 3 at the DFIC, line 4 at the other peak, and line 5 on the MCA branch. Lines 2–4 were located at the DFIC area circled by the aneurysm neck, whereas lines 1 and 5 were outside the aneurysm scope. The hemodynamic parameters on peak 2 of line 4 were all significantly greater than those on line 3 at the middle of the DFIC or line 5 on the MCA branch except for the total pressure on line 3. On line 2 at peak 1, the dynamic and total pressure, vorticity, WSS, strain rate, and cell Reynolds number were significantly greater (P<0.0001) than those on line 3 at the DFIC or line 1 on the smaller ACA except for the total pressure on line 3.

At the ICA bifurcation wall, the blood flow is perpendicular to the wall and is divided at the DFIC. At the DFIC, the flow directly impinges the wall, the flow speed is quickly decreased to the minimal, and some of the kinetic energy carried by the quickly moving flow is thus transformed to the potential energy of pressure, leading to significantly increased pressure. This explains why the total pressure at the DFIC is the maximal while all the other hemodynamic stresses are the minimal. After the blood flow hits the DFIC, it moves quickly towards either the ACA or MCA branch. During the transition from direct impinging on the bifurcation wall, the flow becomes more turbulent but will become laminar after entering the straight arterial segment. As the blood flow becomes laminar and the speed is increased to the greatest, two peaks of hemodynamic stresses appear, and an aneurysm is thus probably initiated at the peaks of hemodynamic stresses. In sampling the hemodynamic stresses with five short lines, lines 1 and 5 were located outside the aneurysm scope on the ACA and MCA branch, respectively, and the hemodynamic stresses on these two lines were significantly lower than those on lines 2 and 4 with peak hemodynamic stresses. The lower hemodynamic stresses on lines 1 and 5 were thus not able to catalyze an aneurysm. On line 3 at the DFIC, the total pressure was the maximal whereas all the other hemodynamic stresses were significantly lower than those on line 4 of peak 2. Although the turbulence parameters were significantly greater on line 3 at the DFIC than on line 2 of peak 1, the other wall hemodynamic stresses such as the dynamic pressure, WSS, vorticity, strain rate, and cell Reynolds number were all significantly lower on line 3 than those on line 2. At the DFIC, the total pressure was the maximal while the other hemodynamic stresses including WSS were the minimal. This may suggest that high wall hemodynamic stresses on line 2 or 4 are probably the culprit of aneurysm formation, and lines 2 and 4 are probably the site of aneurysm initiation.

Shear stress and pressure are two mechanical forces acting on arterial wall, with the pressure being perpendicular to the arterial luminal surface and the shear stress being parallel to it (25-27). In straight arterial segments, the blood flow is pulsatile and moving forward, and the WSS and arterial stretch have well-defined directions to induce appropriate feedback to minimize the magnitude of these forces, thus maintaining arterial homeostasis in hemodynamic stresses. Nonetheless, at arterial bifurcations and bends, the blood flow is disturbed with constantly changing flow directions, which cannot induce appropriate feedback to activate cellular reaction and minimize the hemodynamic stresses, thus creating some undesirable pathological signaling responses to damage the arterial wall (25). The diameter of arterial lumen changes with variation of flow magnitude to maintain the WSS within a narrow physiological range (27-29). Sudden increases in blood flow and WSS may significantly enhance the expression of matrix metalloproteinase (MMP)-2 and MMP-9 by smooth muscle cells and endothelial cells to cause arterial injury (27,30,31). Low WSS can only cause intimal hyperplasia and vascular wall thickening (21,32,33). At the DFIC, even though the total pressure was the highest, the WSS was the minimal, and the DFIC was thus not the site of aneurysm initiation because of the low shear stress. At the peaks of hemodynamic stresses, the WSS was the highest while the total pressure remained very high. High WSS induces endothelial cell damage and predisposes the arterial wall to destructive aneurysm remodeling (34,35). After the arterial wall is damaged and weakened by high shear stress, high total pressure will further push the weakened arterial wall outwards to form an aneurysm. This is probably the mechanism of aneurysm formation at the peaks of hemodynamic stresses.

The outcomes of our study were consistent with those of other studies (1-3,6). In one study evaluating the relationship of hemodynamic parameters with the formation of aneurysms at the anterior communicating artery bifurcation (1), it was found that the hemodynamic parameters (dynamic pressure, total pressure, WSS, vorticity, and strain rate) on the aneurysm dome were significantly decreased compared with those on the arterial wall of aneurysm location after virtual aneurysm removal. This indicated that greater hemodynamic stresses initiated the anterior communicating artery aneurysm on the vascular bifurcation apex and that formation of the anterior communicating artery aneurysm is closely associated with and functions to decrease the locally-abnormally enhanced hemodynamic stresses. In one study assessing the relationship of arterial branch angles with cerebral aneurysms at major arterial bifurcations (bifurcations of ACA, MCA, basilar artery, and ICA) (3), similar findings were achieved, with the hemodynamic parameters (dynamic pressure, total pressure, WSS, vorticity, and strain rate) on the aneurysm dome significantly decreased compared with those on the arterial wall after virtual aneurysm removal, suggesting that the branch forming a smaller angle with the parent artery is associated with abnormally-enhanced hemodynamic stresses to initiate aneurysms at the bifurcation apex. Guo et al. investigated the relationship of hemodynamic stresses with aneurysm formation on major cerebral arterial bifurcations (6) and confirmed the above findings, with the conclusion of greater hemodynamic stresses initiating aneurysms on major cerebral arterial bifurcations. Moreover, for aneurysms at arterial bends, Guo et al. obtained similar findings that aneurysms at the ICA bends are caused by direct flow impingement and increased hemodynamic stresses, and smaller arterial bending angles result in abnormally enhanced hemodynamic stresses to initiate an aneurysm near the flow impingement area (2).

Analysis of the aneurysm dome with strong and weak hemodynamic stresses demonstrated that the hemodynamic stresses on the stronger part was significantly greater than those on the weaker part, which may indicate continued expansion and growth of the aneurysm at the stronger parts based on the above analysis.

The strength of this study was virtual removal of the bifurcation aneurysm and compared the hemodynamic parameters on the aneurysm dome and the bifurcation apex after virtual aneurysm removal. This approach had eliminated all other confounding factors, and compared with before aneurysm removal, the only difference was the presence of bifurcation aneurysm. Thus, significantly decreased hemodynamic parameters were found on the aneurysm dome compared with on the bifurcation apex before aneurysm removal or formation.

This study has some limitations, including the retrospective one-center study design, the small cohort of patients, that only Chinese patients were enrolled, and the lack of randomization and control group of patients without ICA bifurcation aneurysms, which may all affect the generalization of the outcomes. Moreover, in this study with finite element CFD models, the rigid walls were applied to the ICA bifurcation and adjacent arteries. We did not apply the fluid-structure interaction method because additional factors had to be considered. In the CFD simulation, we focused on the patterns and effect of hemodynamic parameters on the rigid walls of cerebral arteries, which will eliminate other irrelevant factors. The use of rigid walls in numerical simulation may fail to capture the dynamic changes during each cardiac cycle (36); however, the use of rigid walls in finite element models of large and medium arteries has been justified (37-39). We and other researchers have been using the finite element method in the simulation of cerebrovascular diseases (1-3,6,9,20,40,41). The outcomes of this study should be generalized with caution because of the above limitations. Future prospective, multi-center, randomized, controlled studies with a large cohort of patients and multiple races of ethnicities are required to overcome the above limitations and to yield better outcomes.

Conclusions

ICA bifurcation aneurysm formation is closely associated with significantly decreased hemodynamic stresses, and aneurysm formation likely functions to decrease the abnormally-enhanced hemodynamic parameters on the bifurcation apex caused by direct flow impingement.

Acknowledgments

None.

Footnote

Reporting Checklist: The authors have completed the STROBE reporting checklist. Available at https://qims.amegroups.com/article/view/10.21037/qims-2025-389/rc

Data Sharing Statement: Available at https://qims.amegroups.com/article/view/10.21037/qims-2025-389/dss

Funding: This study was supported by funding from Hebei Provincial Health Commission’s 2024 Medical Science Research Project Plan (ID 20240303).

Conflicts of Interest: All authors have completed the ICMJE uniform disclosure form (available at https://qims.amegroups.com/article/view/10.21037/qims-2025-389/coif). The authors have no conflicts of interest to declare.

Ethical Statement: The authors are accountable for all aspects of the work in ensuring that questions related to the accuracy or integrity of any part of the work are appropriately investigated and resolved. The study was conducted in accordance with the Declaration of Helsinki and its subsequent amendments. The study was approved by institutional ethics board of Shijiazhuang People’s Hospital (No. 20220128) and informed consent was taken from all the patients.

Open Access Statement: This is an Open Access article distributed in accordance with the Creative Commons Attribution-NonCommercial-NoDerivs 4.0 International License (CC BY-NC-ND 4.0), which permits the non-commercial replication and distribution of the article with the strict proviso that no changes or edits are made and the original work is properly cited (including links to both the formal publication through the relevant DOI and the license). See: https://creativecommons.org/licenses/by-nc-nd/4.0/.

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