CBCT analysis of the incidence of maxillary lateral incisor dens invaginatus and its impact on periodontal supporting tissues

Abstract

Background

Dens invaginatus is a developmental abnormality originating from tooth development, including coronal invaginatus and radicular invaginatus. The reported incidence varies greatly due to diagnostic techniques, classification criteria and race. The incidence of dens invaginatus in China was not clear, and the impact of dens invaginatus on periodontal support tissue were rarely reported. This study aims to clarify the incidence of maxillary lateral incisor dens invaginatus and its impact on periodontal supporting tissues.

Methods

From the cone-beam computed tomography database, images of 212 maxillary lateral incisors from 106 Chinese patients were selected. Teeth that met the Oehlers classification criteria for coronal invaginatus were recorded as coronal invaginatus, and teeth with radicular cystoid invaginatus or radicular groove were classified as radicular dens invaginatus. The complexity of radicular groove was determined by Gu’s classification standard. Both of coronal invaginatus and radicular dens invaginatus were recorded as dens invaginatus. For 15 patients with unilateral radicular dens invaginatus, the periodontal ligament area of the affected teeth and the corresponding natural teeth in the same jaw were measured and compared.

Results

The overall incidence of maxillary lateral incisor invaginatus in China is 25.0%. The incidence of coronal invaginatus is 12.3%, and the incidence of radicular dens invaginatus is 14.6%. No significant differences were observed between genders or sides. In this study, all radicular dens invaginatus exhibited as radicular groove, of which 87.1% were Gu type I, 9.7% were Gu type II, and 3.2% were Gu type III. Although the difference was not statistically significant, the average periodontal ligament area of the maxillary lateral incisor with radicular dens invaginatus was 148.93 ± 35.62mm², smaller than that of the control teeth (152.28 ± 40.22mm²).

Conclusions

The dens invaginatus of the maxillary lateral incisor is common. There is no significant difference in the incidence between genders or between sides. The main manifestation of the radicular dens invaginatus is the radicular groove (Gu’s type I). This anatomical abnormality may reduce the periodontal ligament area. The presence of the additional root of the maxillary lateral incisor is not rare and was supposed to be highly concerned by dentists.

Background

Dens invaginatus is a common developmental malformation of teeth, which arises from excessive proliferation and infolding of enamel organ or epithelial root sheath into the dental papilla during tooth development. Dens invaginatus mostly occurs in the maxillary lateral incisor [1, 2]. It is often accompanied by poor prognosis and multidisciplinary complex therapy, thus has been widely concerned. However, due to the complex and concealed anatomical morphology, the term and classification criteria are constantly updated, and the research is also affected by race, sample size, and diagnostic techniques, so the incidence of dens invaginatus remains unclear [3, 4].

Since Busch first proposed the term "dens in dente" in 1897, the term and classification standards for dens invaginatus have been continuously updated with the deepening of scholars' understanding [1, 5, 6]. Nowadays, scholars generally agree that dens invaginatus can be divided into two major categories: coronal dens invaginatus and radicular dens invaginatus. Coronal dens invaginatus could be classified using the Oehlers’ classification standard [7], while radicular dens invaginatus could be classified as radicular cystoid invaginatus [8] and radicular groove using the Gu’s classification standard [9, 10]. According to the Oehlers’ classification of coronal invaginatus, the incidence of coronal dens invaginatus in maxillary lateral incisors detected by cone-beam computed tomography (CBCT) is approximately 2.35% to 8.86% [11, 12]. Compared with coronal dens invaginatus, the classification of radicular dens invaginatus was proposed later. So far, few studies have used Gu’s classification standard to describe radicular dens invaginatus [3, 13–15]. Limited research showed that the incidence of radicular dens invaginatus in maxillary lateral incisors may be 2.3% to 4.9%, while there have been no reports on the incidence of radicular dens invaginatus in Chinese patients.

Most previous literature on dens invaginatus were case reports, that is, try to retain natural teeth as much as possible by improving diagnostic techniques, using microscope, and applying various biological materials. Clinical observations have revealed that dens invaginatus often lead to serious endodontic and periodontal infections [16–19]. Dens invaginatus teeth have natural anatomical defects, and the invaginatus sites are easy to retain plaque but difficult to clean. Bacteria in the oral cavity could quickly infiltrate and infect the periodontal tissue through this access, and the abnormal root surface lacks the anatomical basis for periodontal tissue regeneration. Therefore, even if the endodontic treatment could achieve good effect, the accompanying periodontal damage may determine hopeless prognosis of the tooth. It is important to clarify the impact of dens invaginatus teeth on periodontal tissue [20, 21]. However, the reports of systematic clinical research and basic research were extremely scarce.

Currently, digital dentistry has replaced traditional methods of measuring the surface area of the root [22]. The use of three-dimensional scanning, Cone Beam Computed Tomography, and high-resolution CT combined with three-dimensional reconstruction software such as Amira or Mimics could accurately measure the data of teeth and the alveolar bone, revolutionizing the measurement methods of soft and hard tissues and providing strong technical support for clinical evaluation [23, 24].

In this study, we first evaluated the incidences of the maxillary lateral incisor coronal dens invaginatus and radicular dens invaginatus in Chinese patients, and then selected patients with unilateral radicular dens invaginatus, using computer software to calculate and compare the periodontal ligament area of the invaginatus tooth and the control tooth in the same jaw, to explore the effect of this developmental malformation on periodontal support tissues. The findings of this study may provide some theoretical support for the clinical management of patients with dens invaginatus.

Methods

The sample size was determined as follows. The expected incidence rate is estimated to be 2.8% from the previous literature, the allowable error is 5%, α = 0.05, and the confidence interval is 95%. The sample size is calculated by Power Analysis and Sample Size (PASS) Software (NCSS, LLC. Kaysville, Utah, USA), and the sample size is 212.

Inclusion criteria were as follows: 1) Chinese patients over 18 years old; 2) clear CBCT images without artifacts; 3) presence of bilateral maxillary lateral incisors; 4) intact morphology of the maxillary lateral incisor, continuous enamel image, and no filling image.

Exclusion criteria were as follows: 1) severe deep overbite, crowding, and other malocclusion deformities that affect the radiographic evaluation of tooth anatomy; 2) the presence of restoration, dental calculus, and other factors that affect the evaluation of anatomical morphology.

From the CBCT database of the Department of Stomatology, Beijing Friendship Hospital, 106 cases of CBCT images of patients who met the inclusion and exclusion criteria since November 2022 were collected, including 212 maxillary lateral incisors.

All images were taken by a senior radiologist in the Department of Stomatology, Beijing Friendship Hospital, Capital Medical University with the same CBCT machine (NewTom 5G Version FP, QR S.r.l, Italy) under the conditions of 0.3 mm voxel size, 0.3 mm slice thickness, 110 kV, 5 mA, scan time 3.6 s, and scan range 18 cm × 16 cm. After obtaining anonymous imaging data, the researchers reconstructed the image on a 1280 × 1024 computer display screen under indoor light. The distance between the observer and the display screen was about 30 cm. The observation was conducted by two dental clinicians, both of whom had more than 10 years of experience in CBCT observation. When the measurement results of two researchers were inconsistent, the image was submitted to the third radiologist for judgement. The researchers observed the target teeth in the sagittal, coronal, and cross-sectional directions. The following indicators were measured and recorded.

1. Coronal invaginatus. Oehlers classification [7], that is, Oehlers Type I: invaginatus limited to the crown, not reaching the level of the enamel-cementum junction (CEJ); Oehlers Type II: invaginatus extends below the CEJ, penetrates into the root but does not reach the periapical tissue, ending in a blind pocket not communicating with periodontium; Oehlers Type III: complete invaginatus, invaginatus extends below the CEJ, penetrating through the root. Coronal invaginatus does not involve the root surface. According to the classification of Gu and Lin et al., the radicular groove originating from cingulum were recorded as radicular dens invaginatus [9, 10].

The imaging manifestation were as follows, the enamel was reflexed on the sagittal plane, or the enamel image was linear or vacuolar protruding into the dentin on the cross section. If the enamel invagination of lingual carina was continuous with the palatal radicular groove, it was assigned to the root invaginatus group.

• 2.Radicular dens invaginatus. There are two major categories: the radicular cystoid invaginatus within the enlarged root [8] and the radicular groove [10]. The classification standard for the radicular groove is, Type I: the radicular groove is short, apically not beyond the coronal third of the root; Type II: the radicular groove exceeds beyond coronal third, corresponding to a normal or simple root canal; Type III: the radicular groove exceeds beyond the coronal third, corresponding to a complex root canal system. When the radicular groove is deep enough to separate the root, an additional root may present, which may contain additional root canals. Imaging manifestations included a root surface depression on the cross section, with or without root canal structure abnormalities.
• 3.Dens invaginatus. Both of coronal invaginatus and radicular invaginatus was recorded as dens invaginatus.
• 4.Periodontal ligament area. The periodontal ligament area of both maxillary lateral incisors in the unilateral radicular invaginatus group was measured. The three-dimensional image of the root was obtained by CBCT scanning, and the image was imported into DICOM format for three-dimensional reconstruction. Mimics software (version 13.0, materialise NV, Leuven, Belgium) was used to manually segment the periodontal ligament of bilateral maxillary lateral incisors in patients with unilateral radicular invaginatus. The segmentation standard of periodontal ligament was the area where the root overlaps with the surrounding alveolar bone (Fig. 1 A-D). After segmentation, three-dimensional mask images of periodontal ligament were generated and smoothed with the same smoothness. The processing parameters were Iterations = 8, and Smooth factor = 0.5 (Fig. 1E, F). All three-dimensional mask images of periodontal ligament were collected and imported into 3-matic software (version 13.0, materialise NV, Leuven, Belgium) to measure the surface area of periodontal ligament.

Fig. 1.

Measurement of periodontal ligament area in patients with unilateral maxillary lateral incisor invaginatus. A & B, Three-dimensional axial images of the invaginatus tooth (A) and the contralateral tooth of the same jaw (B) of the same patient; C & D, The periodontal ligament area of the invaginatus tooth (C) and the contralateral tooth (D) of the same jaw was manually separated. Green was the periodontal ligament area of the invaginatus tooth, and yellow was the periodontal ligament area of the control tooth; E & F, Three-dimensional MASK after separation of the periodontal membrane of the invaginatus tooth (E) and the control tooth (F)

Statistical analysis

Statistical analysis of the results was performed using SPSS 26.0 software. The Chi-square test was used to analyze the differences in dens invaginatus between genders and between sides, and paired t test was used to analyze the differences of periodontal ligament area between invaginatus teeth and non-invaginatus teeth in the same patient. A significant difference was defined as P < 0.05.

Results

General description

A total of 106 patients (36 males and 79 females) were included in this study, with an average age of 34 ± 12 years (the minimum age was 18 and the maximum age was 74). A total of 212 maxillary lateral incisors were observed. The overall incidence of dens invaginatus was 25.0% (53/212). The incidence of radicular invaginatus was 14.6% (31/212) (Fig. 2A-C). An additional root (0.5%) was found in one maxillary lateral incisor, as shown in Fig. 2C. The incidence of coronal invaginatus was 12.3% (26/212), all of which were Oehlers Type I (Fig. 2D). In 4 maxillary lateral incisors, coronal invaginatus and radicular invaginatus occurred simultaneously (Table 1).

Fig. 2.

Typical images of the maxillary lateral incisor with coronal and radicular dens invaginatus in this study. A Gu type I of radicular dens invaginatus; B Gu type II of radicular dens invaginatus, and the invaginatus ended at mid-root; C Gu type III of radicular dens invaginatus, with an additional root; D Typical images of Oehlers coronal invaginatus in cross and sagittal planes. Yellow arrows indicate the invaginatus sites

Table 1.

Dens Invaginatus Distribution of 212 Maxillary Lateral Incisors

Tissue Origin	Classification	Tooth number	Percentage (%)
Coronal Invaginatus	Not Detected	186	87.7
	Oehlers Type I	26	12.3
	Oehlers Type II	0	0.0
	Oehlers Type III	0	0.0
Radicular Invaginatus	Not Detected	181	85.4
	Oehlers Type	0	0.0
	Gu Type I	27	12.7
	Gu Type II	3	1.4
	Gu Type III	1	0.5

Among 31 maxillary lateral incisors with radicular invaginatus, no Oehlers' root enlargement with a cystoid invaginatus was observed. All were classified as radicular groove according to Gu's classification. Among them, 27 teeth were type I (accounting for 87.1% of all radicular invaginatus teeth); 3 teeth were type II (accounting for 9.7% of all radicular invaginatus teeth); and one tooth exhibited additional roots, which belonged to type III (accounting for 3.2% of all radicular invaginatus teeth). Figure 3 shows the details.

Fig. 3.

Distribution of 31 radicular invaginatus maxillary lateral incisors. The left figure shows the proportion of Types I, II, and III according to Gu's classification, while the right figure shows the location of the radicular groove. DP, Distal palatal; MP, Mesial palatal; P, Palatal

Figure 3 also shows the distribution of the sites where radicular groove occurs: 17 teeth have radicular grooves located at the mesial palatal site (accounting for 54.8%), 3 teeth have them located at the mid-palatal site (accounting for 9.7%), and 11 teeth have them located at the distal palatal site (accounting for 35.5%).

Difference in the incidence of maxillary lateral incisor invaginatus between sides and between genders

In this study, the incidence of maxillary lateral incisor dens invaginatus on the left and right sides was 22.6% (24/106) and 27.4% (29/106), respectively. The incidence of coronal invaginatus on the left and right sides was 12.3% (13/106) and 12.3% (13/106), respectively. The incidence of radicular dens invaginatus on the left and right sides was 12.3% (13/106) and 17.0% (18/106), respectively. The above differences were not statistically significant (P > 0.05).

The incidence of maxillary lateral incisor invaginatus in males and females was 27.8% (20/72) and 23.6% (33/140), respectively. The incidence of coronal invaginatus in males and females was 9.7% (7/72) and 13.8% (19/140), respectively. The incidence of radicular dens invaginatus in males and females was 19.4% (14/72) and 12.1% (17/140), respectively. The incidences of genders were no difference on statistics (P > 0.05). The relevant data were present in Table 2.

Table 2.

Distribution of Maxillary Lateral Incisor Invaginatus between Sides and Genders (n = 212)

	Side			Gender
	Left (n = 106)	Right (n = 106)	P	Male (n = 72)	Femal (n = 140)	P
Dens invaginatus	24	29	0.428	20	33	0.503
Coronal invaginatus	13	13	1.000	7	19	0.418
Radicular invaginatus	13	18	0.114	14	17	0.312

The impact of radicular invaginatus on periodontal supporting tissues

Among the 23 patients with maxillary lateral incisor radicular dens invaginatus, 15 patients with maxillary lateral incisor root invaginatus occurred at one side, and 8 patients with root invaginatus occurred at both sides. To explore the effect of radicular dens invaginatus on periodontal ligament area, we used computer software to calculate and compare the bilateral maxillary lateral incisor periodontal ligament area of the 15 patients with unilateral radicular invaginatus. The results showed that, although the difference between the two was not statistically significant (P > 0.05), the average area of the maxillary lateral incisor with radicular dens invaginatus was 148.93 ± 35.62mm², smaller than that of the control tooth in the same jaw (152.28 ± 40.22mm²).

Discussion

This study systematically evaluated the incidence and characteristics of maxillary lateral incisor dens invaginatus in China on CBCT images according to Oehlers’ classification and Gu’s classification, and analyzed the impact of radicular invaginatus on periodontal supporting tissues preliminarily.

The diagnosis and classification criteria for dens invaginatus are constantly updated, and the reported incidence varies greatly due to the choice of diagnostic techniques and race. In terms of diagnosis and classification criteria, this study selected Oehlers' classification criteria to determine coronal invaginatus, which has been widely accepted [7]. The radicular dens invaginatus is categorized into two main types: radicular cystoid invaginatus [8] and radicular groove, with the severity of radicular groove assessed using the Gu’ classification [9]. The Gu’s classification is relatively clear and closely related to clinical prognosis.

In terms of diagnostic techniques, previous studies have used imaging methods such as periapical films, panoramic radiographs, and CBCT to identify dens invaginatus. In clinical practice, periapical films are the most commonly used diagnostic method, but they are prone to misdiagnosis for dens invaginatus [25]. Capar et al. reported that CBCT could significantly improve the detection rate of dens invaginatus. By observing the rendered panoramic images of 300 Turkish patients, the detection rate of tooth invagination was 3%, while three-dimensional observation could improve this detection rate to 10.7% [26]. Thus, this study chose CBCT images to identify dens invaginatus.

As shown in Table 1, the incidence of coronal invaginatus is 12.3% and the incidence of radicular invaginatus is 14.6%. For a more comprehensive evaluation, we also calculated the incidence of coronal or radicular invaginatus in maxillary lateral incisors, with a value of 25.0%. In 2023, a meta-analysis summarized the incidence of coronal invaginatus in anterior teeth using CBCT, ranging from 1.1% to 13.5%, with the maxillary lateral incisors being the most affected teeth [11]. In our study, the incidence of coronal invaginatus was 12.3% (26/212). The relatively high incidence may be due to smaller voxel size (0.3 mm) and smaller slice thickness (0.3 mm) during CBCT acquirement. As for the incidence of radicular invaginatus, there are very few related articles, especially those that refer to the Gu’s classification. The limited data reported the incidence of 2.3%—7.3% [3, 13–15]. However, all the relative subjects were Caucasian. In our study, the subjects were Mongolian, and the incidence of radicular invaginatus is 14.6% (31/212). Our findings suggested that, besides the impact of different CBCT setting parameters, radicular invaginatus may occur more frequently in Mongolian.

In this study, no cases of radicular cystoid invaginatus in the enlarged root were observed. All of 31 radicular dens invaginatus exhibited radicular grooves. More than 90% (90.3%) of the radicular grooves occurred at the mesial or distal palatal sites, and nearly 90% (87.1%) of the radicular grooves ended within the coronal third of the root (Fig. 3). It is worth noting that one tooth of Gu’s type III was present, with an additional root (Fig. 2B). A root furcation was observed between the additional root and the main root. Once this furcation involvement became three or four degrees, the prognosis of this dens invaginatus tooth may be poor, just like posterior teeth with penetrating furcation involvement. This article is followed by a case of combined endo-periodontal disease of a maxillary lateral incisor with an additional root. Interestingly, through sequential treatment, the separation of periodontal and periapical lesions was achieved, which may obtain more autologous bone regeneration and more definite periodontal new attachment (Fig. 4).

Fig. 4.

Endo-periodontal therapy of a Gu’s type III tooth with an additional root. A, fistula presentation after initial therapy; B, palatal gingiva was dark red; C, an additional root; D, the depth of infrabony pocket was 8 mm; E, additional root resection; F, endodontic filling; G, the additional root was 9 mm in length with root canal; H, 5 months after resection, the fistula disappeared; I, PD was 8 mm at the palatal site; J, the depth of mesial infrabony defect was 5 mm; K, new bone was obtained after root resection in the mid-root; L; the depth of palatal infrabony defect was 3 mm; M, bone graft and membrane overlay. N, suture after periodontal regeneration surgery; O, 9 months after regeneration, mesial PD was 5 mm; P; palatal PD was 3 mm; Q, the original infrabony defect was filled with new alveolar bone; R, apicectomy; S; suture after apicectomy; T, 8 months after the completion of endo-periodontal therapy, PD was 3 mm in the mesial; U, PD was 2 mm in the palatal; V, periapical film (V₁) and CBCT (V₂) of tooth 22 at first visit; W, radiological examination, periapical film (W₁) and CBCT (W₂), at 5 months after additional root resection; X, periapical film immediately after periodontal regeneration surgery; Y, periapical film before apicectomy; Z, 8 months after completion of endo-periodontal surgery. Yellow arrows show substantial bone generation after root resection

Previous reports on dens invaginatus were mostly single or several case reports. That is, using a variety of combined treatment methods, such as root canal therapy, root resection, root surface treatment, bone graft, guided tissue regeneration and even intentional replantation, to control infection and increase the attachment of periodontal support tissue as much as possible. For invaginatus deep to the apex, there were also reports of extraction [27–33].

The above case reports showed that clinicians have already realized that the invaginatus site is an area where bacteria are easy to stay and difficult to be controlled, and oral pathogenic bacteria could destroy the tooth and periodontal tissue through this access quickly, leading to caries, pulpitis, periapical lesion and periodontal support tissue loss. In 2021, Tan et al. obtained the microbiota from the radicular groove of four replanted teeth and sequenced it. The results showed that the bacterial communities at this site had dual characteristics of pulp and periodontal infections, suggesting that the radicular groove may be a bacteria bank and play an interaction bridge between the root apex and tooth cervix [34]. For endodontic treatment, there may be small hidden channels between the invaginatus area and the pulp tissue, often accompanied by complex root canal system morphology, which brings great challenges to infection control and reduces the prognosis of root canal therapy seriously. For periodontal prognosis, the root surface groove naturally lacks normal periodontal attachment. As a result, even after root surface treatment and filling of various types of biomaterials, it is difficult to form effective new attachment after regenerative surgery at the radicular groove surface, worsening the periodontal prognosis.

However, so far, only few studies reported the impact of radicular invaginatus on periodontal tissues. Limited results showed that the infection index, such as gingival index, plaque index, and bleeding index at the groove site were more severe than control sites [20, 21]. Periodontal ligament area is the key to periodontal prognosis. This study attempted to analyze whether radicular invaginatus is accompanied by a reduction of the periodontal ligament area using a split-mouth control method. The results show that the periodontal ligament area of the maxillary lateral incisor with radicular invaginatus is smaller than that of the control tooth of the same name on the same jaw (148.93 ± 35.62mm² Vs. 152.28 ± 40.22mm²). Although this difference may not be statistically significant due to the small sample size, the results provide a quantitative analysis of the periodontal ligament area of the affected and control teeth, providing a theoretical basis for the phenomenon of radicular invaginatus accompanied by a reduction in periodontal support tissues.

A typical Case of additional root

A 21-year-old female patient complained of recurrent gingival abscess of maxillary left anterior tooth for five years. The complaining tooth was treated with root canal therapy in another hospital five years ago, however, the symptoms still recurred and worsened within half a year. The patient was under orthodontic treatment in another hospital when she first came to our department.

The examination showed that, a fistula was detected in the labial mucosa of tooth 22 and a furcation structure may present in the palatal site. The probing depth (PD) was 8 mm at the furcation site, and the degree of mobility was III. The radiograph demonstrated an additional root in the mesial site. The alveolar bone around the additional root was widely resorpted to the apex, and only the distal alveolar bone was present (Fig. 4 A, B, V₁, V₂).

The tooth 22 were diagnosed as “endodontic/periodontic lesion” and “Gu type III radicular invaginatus”. The orthodontic treatment was suspended. Six weeks after re-root canal therapy and supra- and subgingival scaling, the fistula was still present. The flap of 22 was elevated. A palatal additional root was present, the depth of infrabony pocket was 8 mm. The additional root resection and radiculoplasty were performed (Fig. 4 C-F). There was a root canal in the additional root (Fig. 4G).

Five months after the additional root resection surgery, the fistula disappeared, and the mobility reduced from III degree to I degree (Fig. 4H, I). Imaging examination demonstrated that, alveolar bone regeneration was obtained around palatal mid-root, in a shape of “collar”, 2 mm wide approximately, separating the periodontal from periapical lesions. Periapical density increased compared with that before (Fig. 4 W₁, W₂). Periodontal regeneration surgery was performed. The depth of infrabony pocket was reduced from 8 to 3 mm. Bio-collagen (Geistlich, Switzerland) was implanted into the infrabony defect, covered with Bio-Gide membrane (Geistlich, Switzerland, Fig. 4 J-N, X). The tooth was splinted with the adjacent teeth (Super-Bond C&B, Japan).

Fourteen months after root resection and 9 months after periodontal regeneration surgery, apicoectomy was performed because the periapical lesion was still large. During reentry, that the original infrabony defect was filled with new alveolar bone can be detected (Fig. 4 Q-S).

Eight months after the completion of the combined endo-periodontal therapy, the patient complained no discomfort. The periodontal status of tooth 22 was healthy, with PD of 2–3 mm, and mobility of I degree (Fig. 4 T, U). Periapical film demonstrated new bone trabecula around the tooth, and the periapical lesion improved significantly (Fig. 4 Z).

Conclusion

The overall incidence of maxillary lateral incisor dens invaginatus in China is 25.0%, the incidence of coronal invaginatus is 12.3%, and the incidence of radicular dens invaginatus is 14.6%. There is no significant difference between genders and sides. The main presence of radicular dens invaginatus is the radicular groove, classified as Type I by Gu. This anatomical abnormality may reduce the periodontal ligament area. The presence of an additional root in maxillary lateral incisors is not rare, and clinicians should keep a wary eye on that.

Abbreviations

CBCT

Cone-beam computed tomography

PD

Probing depth

Authors’ contributions

Wang Y designed the work, acquired the data, analyzed the data, and revised the manuscript. Su S and Chen X acquired and analyzed the data. Jia X designed the work, analyzed the data, drafted, and revised the manuscript. All authors read and approved the final manuscript.

Funding

This study was supported by Beijing Hospitals Authority Youth Programme (Grant No. QML20230120).

Data availability

All data generated or analysed during this study are included in this article.

Declarations

Ethics approval and consent to participate

All the procedures of the study were in accordance with the Declaration of Helsinki and approved by Bioethics Committee of Beijing Friendship Hospital, Capital Medical University (approval No. 2024-P2-158). Bioethics Committee of Beijing Friendship Hospital, Capital Medical University has exempted the need for informed consent.

Consent for publication

Not applicable.

Competing interests

The authors declare no competing interests.