Clinical Outcomes of Minimally Invasive Fixation with Pre‐Bent Elastic Stable Intramedullary Nails for the Treatment of Distal Radius Metaphyseal Diaphysis Junction Fractures in Children

Abstract

Objective

Although mini‐plate fixation is an attractive treatment option for distal radius metaphyseal diaphysis junction (DRMDJ) fractures in children, the benefits of minimally invasive fixation (MIF) with pre‐bent elastic stable intramedullary nails (MIF) remain underexplored. Therefore, this study aimed to evaluate the clinical efficacy of MIF administration in children with DRMDJ fractures.

Methods

This retrospective study enrolled 40 patients with DRMDJ fractures who underwent MIF or mini‐plate fixation from January 2016 to January 2021. Radiographic parameters, such as palmar inclination and ulnar deflection angle, were examined postoperatively to assess the anatomical reduction of the wrist joint. Clinical outcomes, including the range of wrist flexion and back extension, were examined to analyze the recovery of the wrist range of motion. Additionally, the Gartland–Werley scoring system was used to assess the recovery status of wrist function and healing condition. The student t‐test and χ² test were used to compare differences among groups.

Results

All included patients successfully underwent the operation and were followed up for 12–24 months. Patients in the MIF group had a smaller surgical incision length (0.49 ± 0.06 cm) compared to those in the mini‐plate fixation group (4.41 ± 0.73 cm) (t = 22.438, p = 0.000). Palmar inclination and ulnar deflection were within the normal range in patients of both groups, and the fractures were successfully anatomically reduced. Moreover, wrist flexion and back extension in the MIF group and mini‐plate group were (72.50° ± 0.64° vs. 70.18° ± 0.56°) and (59.55° ± 1.75° vs. 60.04° ± 1.37°), and differences were statistically significant (t = 2.708, p = 0.010 and t = 0.885, p = 0.382, respectively). Furthermore, MIF treatment resulted in a higher proportion of excellent Gartland–Werley scores (94.44%) than mini‐plate fixation (86.36%) (p = 0.390). In addition, one case in the mini‐plate fixation group experienced re‐fracture following the removal of the internal fixation, and the fracture healed after reduction and cast fixation. All patients achieved satisfactory bone healing without other complications.

Conclusion

Compared with mini‐plate fixation, MIF has the advantages of small incision length, superior range of motion of thr wrist joint, and better maintenance of the physiological radian, providing a promising approach for clinical and surgical treatment of DRMDJ fractures.

Compared with mini‐plates fixation, minimally invasive fixation combined with pre‐bent elastic stable intramedullary nails have the advantages of small scars, improve wrist joint range of motion, maintain the physiological radian and good curative effect, which provides a reference basis for clinical surgical treatment of DRMDJ fractures.

Introduction

Distal radius metaphyseal diaphysis junction (DRMDJ) fractures are among the most common fractures in children. It has been reported that between 35% and 45% of all pediatric fractures involve the radius, with over three‐quarters of these involving the distal radius. ¹ Its incidence peaks at 10 years of age. The goal of post‐fracture treatment is to restore the original shape and anatomy of the fractured bone through anatomical reduction, enabling early mobility with minimal soft tissue trauma. ² , ³ The standard treatment for DRMDJ fractures is closed reduction and cast fixation, which is the first‐line treatment option. ⁴ Nevertheless, surgical intervention is recommended for displaced and unstable fractures or cases with poor alignment after closed reduction. ⁵ Treatment decisions also depend on fracture characteristics and the preferences of the patient's family. Plate fixation has several benefits, including improved stability and bone shaft strength and maintenance of palmar inclination and ulnar deviation. For older children (>10 years old), open reduction and internal plate and screw fixation is the preferred choice, although this technique involves extensive periosteal peeling and carries a risk of tissue injury and can require larger surgical incisions.

Over the past 20 years have witnessed the widespread use of elastic stable intramedullary nails (ESIN) for the fixation of long bone fractures in children, particularly femoral and forearm fractures, which demonstrate favorable outcomes. ⁶ , ⁷ Pre‐bent ESIN fixation can preserve the physiological curvature of the bone, with additional advantages such as multi‐point support and high strength. ⁸ Earlier studies have shown the feasibility of this approach in the treatment of distal radial shaft fractures while retaining normal palmar inclination and ulnar deviation angles. ⁷ Emerging evidence also suggests that pre‐bent ESIN fixation could enhance the stability of radius reduction, improve fracture alignment, reduce the risk of secondary displacement of the distal fragment, and facilitate early rehabilitation of patients. ⁹ , ¹⁰ , ¹¹ Based on these findings, we speculate that ESIN may also offer potential benefits for DRMDJ fractures.

The purpose of this retrospective study was to: (i) explore the feasibility of pre‐bent ESIN treatment for this type of fracture; (ii) provide a comprehensive overview of the clinical efficacy and complications associated with the two surgical methods; and (iii) offer clinicians an alternative surgical approach for treating unstable DRMDJ fractures.

Patients and Methods

Study Design and Participants

This retrospective analysis included patients who underwent surgical treatment between January 2016 and January 2021, performed by the same surgical team at our hospital. Patients meeting the following inclusion criteria were included: (i) age < 16 years old; (ii) residual angulation ≥10° or malrotation ≥30° of the forearm after unsuccessful attempts of nonsurgical treatments or cast fixation; (iii) intact epiphyseal plate with complete fracture; (iv) closed fractures; and (v) follow‐up was not lost and was no less than 12 months. Exclusion criteria consisted of (i) open or comminuted fractures; (ii) concomitant nerve or vascular injuries; (iii) involvement of the growth plate; and (iv) pathological fractures. This retrospective study was approved by the Ethics Committee of Jiangnan Hospital, Zhejiang University of Traditional Chinese Medicine (Xiaoshan Hospital of Traditional Chinese Medicine, Hangzhou, China) (XSZYY2081115), and conducted in accordance with the tenets of the Declaration of Helsinki.

The children received symptomatic treatment, such as oral ibuprofen suspension for pain relief and elevation of the affected limbs to reduce swelling. Preoperative assessments were conducted to evaluate the surgical risk for each child.

Operative Procedure

All interventions were carried out according to the standard institutional procedure. All children were anesthetized with a combination of brachial plexus block with general anesthesia and placed in the supine position. They wore a lead coat for radiation protection. The affected limb was abducted and placed on the operating table.

Minimally Invasive Fixation Operation

Following traction of the child's forearm and wrist, the fracture end was rotated to correct rotation displacement and roof reduction before and after displacement. Alignment of the fracture was assessed under C‐arm fluoroscopy. A dorsal approach was employed based on the fracture condition, positioning the incision approximately 1.0 cm away from the growth plate. Then, a longitudinal incision of approximately 0.5 cm was made, exposing the muscles. A nail was inserted vertically, and drilled through the cortex at an angle of less than 30°. Elastic intramedullary nails procured from Double medical (Xiamen, Fujian, China), with a diameter of 2.5 mm or 2.0 mm, were selected according to the radius diameter. The elastic stable intramedullary nails were inserted into the medullary cavity and pushed to the fracture line to resist traction manipulation. The nail was pushed to the proximal end of the radius and then bent at the insertion point angle of approximately 30°. The elastic intramedullary nail was further pushed into the medullary cavity, ensuring the inclination was at the same level as the fracture, reducing its distal end to the metacarpal and ulnar side. The end of the needle was retained beneath the patient's skin (Figures 1 and 2).

FIGURE 1.

A 9‐year‐old male with a fracture of the distal end of the right ulna and radius caused by a high fall. (A, B) The distal end of the fracture shifted to the dorsal side. (C, D) Retrograde approach of elastic intramedullary nail crossing the fracture line with efficient reduction of the broken end. (E, F) At 5 weeks postoperatively, continuous cortical bone was observed in cast fixation, with acceptable callus growth. (G, H) The internal fixation was removed 8 months after surgery, the bone cortex was uninterrupted, and the wrist was well positioned.

FIGURE 2.

A 12‐year‐old male suffered left a distal radius metaphyseal diaphysis junction (DRMDJ) fracture caused by a car accident. (A, B) Cast fixation failed, and the fracture of the distal radius was displaced to the metacarpal and radial side. (C, D) Following postoperative cast fixation, the fracture was well aligned. (E, F) Four weeks after surgery, the position of the DRMDJ fracture was adequate, and callus growth was unremarkable. (G, H) The fracture healed 6 weeks postoperatively, and the cast was removed.

Mini‐Plate Fixation

A 5.0 cm incision was made on the metacarpal radius. Next, the skin, subcutaneous tissue, and deep fascia were sequentially exposed longitudinally. Then, the radial side of the flexor Carpi radialis was exposed while protecting the radial artery. The pronator muscle was separated and the fracture was exposed and fixed with a mini‐plate. Holes were drilled using a Kirschner needle (1.5–2.0 mm), and reaming was minimized. Then, a suitable 2.7 mm T‐shaped mini‐plate (Zimmer Biomet, Warsaw, IN, USA), with three screws at the distal end and two to three crews at the proximal end was inserted. The reduction of the radius was assessed via C‐arm imaging (Figure 3).

FIGURE 3.

A 14‐year‐old male with a right a distal radius metaphyseal diaphysis junction (DRMDJ) fracture caused by a high fall. (A, B) The distal end of the fracture shifted to the metacarpal side with an angle exceeding 12°. (C, D) Antero‐lateral radiograph of the ulna and radius displaying satisfactory postoperative alignment of the fracture end. (E, F) At 11 months postoperatively, the internal fixation was removed, the fracture was healed, no deformity was identified, and the epiphysis was continuous and intact.

Postoperative Management

Absorbable sutures were utilized in all cases and did not require removal. After the operation, the forearm was immobilized in a cast and suspended in front of the chest. One day after the surgical procedure, a positive interphalangeal joint flexion–extension exercise was conducted. Pain degree, distal blood circulation, and sensation were regularly monitored, and appropriate symptomatic treatment was administered in a timely manner. The follow‐up period ranged between 12 and 24 months.

Clinical Evaluation

In both groups, the length of incision, the number of intraoperative fluoroscopies, and the duration of hospitalization were compared.

Fracture Healing Evaluation

The fracture healing rate was assessed through post‐operative radiographs, examining trabecular growth and continuity of bone cortex at 2, 4, 6, and 12 weeks and 6 months. The ulna and radius were examined in the anterior and lateral positions. No percussion pain was noted during the physical examination. Moreover, the radiograph displayed a blurred fracture line crossed by continuous trabeculae of bone, confirming complete healing and allowing for cast removal. The cast was typically kept on for around 3 to 4 weeks. Eight weeks after the removal of internal fixation, the anatomical morphology of the radius was visualized using X‐ray images.

Palmar Inclination and Ulnar Inclination Angle

Two months after the removal of internal fixation, a lateral X‐ray was used to examine the palmar inclination angle, which is indicative of the joint force exerted on the wrist. It measures the angle between the vertical line of the long axis of the radius and the line of the distal end of the radius. The normal range for this angle is typically between 10° and 15°. The ulnar inclination angle was determined by evaluating the angle between the vertical line of the longitudinal axis of the radius and the line connecting the farthest points of the ulnar and radial sides of the distal radius in anteroposterior wrist radiographs. The normal range for the ulnar inclination angle falls between 21° and 25°.

Wrist Flexion and Back Extension Range

Two months after the removal of internal fixation for DRMDJ fractures, the evaluation of wrist flexion and back extension activities becomes crucial in assessing the recovery. In this study, a special protractor (GemRed, Guilin, Guangxi, China) consisting of an axis, a fixed arm, and a moving arm was used. The axis was located on the radial styloid process of the radial side of the wrist joint. The fixed arm was aligned parallel to the radius, while the moving arm was parallel to the index finger and metacarpal. The angle of flexion and back extension was measured as the wrist joint performed these movements.

Gartland–Werley Score

The scores were evaluated 2 months after implantation of internal fixation and 2 months after its removal. The Gartland–Werley score was used to analyze clinical outcomes. This comprehensive scale includes evaluations of palmar inclination deformity, ulnar deviation deformity, subjective pain, wrist range of motion, nerve injury, and impairment of finger function due to cast. Each item was assigned a specific score. The scores were categorized into four levels, namely excellent (0–2), good (3–8), fair (9–20), and poor (≥21).

Statistical Analysis

Statistical analyses were conducted using SPSS 25.0 (SPSS, Chicago, IL, USA). Age, time from trauma to surgery, incision length, hospitalization duration, sagittal angle, wrist flexion, dorsiflexion, palmar inclination, and ulnar inclination were presented as median and standard deviations and analyzed using the t‐test. Gender, injured side, and Gartland–Werley score were analyzed using the χ² test. P < 0.05 was considered statistically significant.

Results

General Information

A total of 40 patients were included in this study. Among them, 22 patients (20 males and two females) with an average age of 12.36 ± 2.55 years (range 6–15 years) underwent mini‐plate fixation, while 18 patients (15 males and 3 females) with a mean age of 11.66 ± 2.49 years (range 6–14 years) underwent fixation with pre‐bent elastic stable intramedullary nails. In the mini‐plate fixation group, there were 10 cases on the left side and 12 cases on the right side, while in the minimally invasive fixation (MIF) group, there were seven cases on the left side and 11 cases on the right side. The angular deformity of the DRMDJ fracture, measured using X‐ray, was similar in both groups (21.41° ± 3.14° vs. 21.56° ± 3.16° for the mini‐plate fixation group and MIF group, respectively). Moreover, the average time from injury to operation was 3.72 ± 0.76 days vs. 3.88 ± 0.75 days, respectively. The follow‐up period ranged from 12 to 24 months. Finally, there was no significant difference in baseline characteristics between the two groups (Table  1 ).

TABLE 1.

General information of 40 enrolled patients

Group	Cases	Gender		Age (y)	Part		Sagittal plane angula (°)	Time from trauma to surgery (d)
		M	F		L	R
Mini‐plate	22	20	2	12.36 ± 2.55	10	12	21.41 ± 3.14	3.72 ± 0.76
Pre‐bent elastic stable intramedullary nail	18	15	3	11.66 ± 2.49	7	11	21.56 ± 3.16	3.88 ± 0.75
Statistic		χ 2  = 0.519		t = 0.867	χ 2  = 0.175		t = 0.079	t = 0.666
p value		0.471		0.391	0.676		0.885	0.509

Intraoperative Observation

All included 40 patients who underwent surgery, and the postoperative fluoroscopy of the affected limb confirmed successful fixation of the radius with appropriate positioning of the mini‐plates and pre‐bent elastic stable intramedullary nails.

The average length of hospitalization period in the MIF group was significantly shorter than that in the mini‐plates group (8.16 ± 1.20 days vs. 10.13 ± 3.56 days) (p = 0.03). Furthermore, significant differences were observed in the incision length and the number of intraoperative fluoroscopies between the mini‐plate fixation group and the MIF group: the incision length was 4.41 ± 0.73 cm in the mini‐plates group, significantly longer than 0.49 ± 0.06 cm in the MIF group (p = 0.00); the number of intraoperative fluoroscopies was (3.40 ± 0.50 times) in the mini‐plates group, significantly lower than 5.55 ± 0.78 times in the MIF group (p = 0.00) (Table  2 ).

TABLE 2.

Comparison of intraoperative conditions and Gartland–Werley score analysis

Group	Hospitalization time (d)	Incision length (cm)	Intraoperative fluoroscopy (time)	Rate of excellent (%) Gartland–Werley score
Mini‐plate	10.13 ± 3.56	4.41 ± 0.73	3.40 ± 0.50	86.36 (19/22)
Pre‐bent elastic stable intramedullary nail	8.16 ± 1.20	0.49 ± 0.06	5.55 ± 0.78	94.44 (17/18)
Statistic	t = 2.239	t = 22.438	t = 10.48	χ2 = 0.718
p‐value	0.031	0.000	0.000	0.390

Palmar Inclination and Ulnar Deflection Angle Analysis

Two months after internal fixation removal surgery, radiographs were used to measure the palmar inclination and ulnar inclination angles. The palmar inclination angle in the mini‐plate fixation group and the MIF group was 12.48° ± 1.28° vs. 12.95° ± 1.32°, t = 0.01, p = 0.27, while the ulnar deflection angle was 23.64° ± 2.72° vs. 23.33° ± 1.73°, t = 0.42, p = 0.67, respectively, inferring that the wrist joints of patients in both groups healed well and were restored to the normal range, as indicated in Table  3 .

TABLE 3.

Comparison of post‐operative wrist mobility

	Ulnar Inclination(°)	Palmar inclination (°)	Flexion(°)	Back extension(°)
Miniplate	23.64 ± 2.72	12.48 ± 1.28	70.18 ± 0.56	60.04 ± 1.37
Pre‐bent elastically stable intramedullary nail	23.33 ± 1.73	12.95 ± 1.32	72.50 ± 0.64	59.55 ± 1.75
t‐value	0.423	0.019	2.708	0.885
p‐value	0.675	0.270	0.010	0.382

Wrist Flexion and Back Extension Range Analysis

Two months after internal fixation removal surgery, the wrist flexion angle in patients of the mini‐plate group and the MIF group was 70.18° ± 0.56° vs. 72.50° ± 0.64° (t = 2.70, p = 0.01), while the back extension angle was 60.04° ± 1.37° vs. 59.55° ± 1.75 (t = 0.88, p = 0.38), respectively. These findings suggest that fixation with pre‐bent elastic stable intramedullary nails resulted in superior wrist joint mobility compared to mini‐plate fixation (Table  3 ).

Gartland–Werley Score Analyses

No patient in either group complained of wrist function limitation. Based on the comprehensive scores, the mini‐plates group and the MIF group were rated as excellent (n = 19, 17), good (n = 3, 1), fair (n = 0, 0), or poor (n = 0, 0). Notably, the proportion of patients with an excellent Gartland–Werley grade was higher in the MIF group compared with the mini‐plates group (94.44% vs. 86.36%, p = 0.390). There was no significant difference between the two groups (Table  2 ).

Complications

No postoperative complications, such as infection, neuromuscular injury, shortening deformity, and bone nonunion, were observed in either the mini‐plate fixation group or the MIF group. The degree of bone healing was deemed satisfactory. However, one case of re‐fracture occurred after the removal of internal fixation in the mini‐plate group. Due to a residual angulation of 5° in the re‐fracture, the patient underwent treatment involving reduction and cast fixation for 5 weeks, which led to significant healing and a satisfactory outcome in the recovery process. There was no needle withdrawal of the pre‐bent elastic stable intramedullary nail, and no revision surgery was required in either group.

Discussion

In the present study, our findings showed that all patients achieved satisfactory wrist function following intervention with pre‐bent ESIN or mini‐plate treatment. The pre‐bent ESIN group exhibited superior benefits in terms of minimizing soft tissue trauma and facilitating internal fixation removal. Statistical analysis revealed no significant differences in angle and malrotation between the pre‐bent ESIN group and the mini‐plate group. Moreover, the utilization of pre‐bent ESIN enabled enhanced joint mobility and restoration of anatomical function. Consequently, our findings insinuated that ESIN fixation outperforms mini‐plate fixation in the treatment of DRMDJ fractures.

Advantages and Disadvantages of Elastic Stable Intramedullary Nails

The ESIN technique guarantees relative stability through the implementation of three‐point fixation, ¹² which facilitates proper alignment and tension of the interosseous membrane while preserving the natural curvature of the distal radius. ¹³ Angled insertion of the nail helps eliminate its springiness and promotes fracture healing. ⁴ , ¹⁴ In this study, retrograde needle insertion was adopted to simplify the operation, reduce the risk of nerve injury, and prevent damage to the epiphyseal plate. ¹⁵ , ¹⁶ ESIN is a minimally invasive technique that requires simplified nursing care and minimizes damage to soft tissue. ¹⁷ , ¹⁸ , ¹⁹ However, the pre‐bent ESIN group has a few drawbacks, such as nail loosening, nail tract infection, and other frequent complications. ²⁰ , ²¹ It is worth noting that the use of fluoroscopy with ESIN requires a higher number of exposures, which leads to increased radiation exposure. Implementing protective measures such as wearing a lead coat is essential for reducing radiation exposure. In addition, ultrasound‐guided elastic intramedullary nails can serve as a viable alternative. ²²

The mini‐plate procedure offers improved visibility and facilitates anatomical reduction, ¹⁵ whereas it necessitates a larger incision, resulting in greater surgical trauma and bleeding. More importantly, the mini‐plate technique may lead to serious peeling of the periosteum, which can affect the blood supply to the fracture site; and the use of multiple screws increases the risk of damaging the epiphyseal plate. ²³ Meanwhile, improper plate fixation may result in a displaced distal radioulnar joint, compromising the wrist joint stability. ²⁴ , ²⁵

Applications of Pre‐Bent Elastic Stable Intramedullary Nails

Distal radius metaphyseal diaphysis junction fractures are largely caused by indirect violence, resulting in a lower prevalence of comminuted fractures. For most types of fractures, pre‐bent ESIN fixation has shown favorable outcomes (e.g., for transverse and oblique fractures). However, in some cases, plate or Kirschner wire fixation may be required (e.g., for open or multiple fractures). (Figure 4).

FIGURE 4.

Manual reduction is the first choice. Most fractures can achieve good alignment after pre‐bent elastic stable intramedullary nails (ESIN). The above types may not be applicable to pre‐bent ESIN. (A) If the fracture line is close to the epiphyseal plate, Kirschner wire fixation should be used. (B, C, D) For open fractures, multi‐segment fractures, spiral fractures, and comminuted fractures, plate fixation can be used.

Our study demonstrated that pre‐bent ESIN fixation was superior to mini‐plate fixation in terms of facilitating fracture healing, limiting soft tissue injury, and retaining the original hematoma. A previous study by H Schell et al. also highlighted primitive hematomas in promoting fracture healing through angiogenesis and increased osteoclast activity. ²⁶ , ²⁷ As expected, pre‐bent ESIN promoted fracture healing. Further, the removal of ESIN is easier compared to plates and is associated with a lower risk of re‐fracture. ²⁸ Re‐fractures have been reported in several studies and are generally associated with internal fixation time. In this study, no instances of re‐fracture were observed in the MIF group, and the incidence of re‐fracture after internal fixation for more than 8 months was low. ²⁹

Pediatric fractures present specific challenges, as they are not merely scaled‐down versions of fractures in adults. For instance, pediatric bones have limited strength for achieving stability with screws compared to adult bones. ³⁰ Additionally, compliance with postoperative instructions may be relatively lower in adolescents, increasing the risk of unintentional injury to the affected limb. Considering these factors, the use of a cast after surgery provides additional external stability, complementing the internal fixation provided by the plate. ⁷ This approach aligns with the principle of pediatric fracture fixation, which emphasizes the use of internal fixation and strong external fixation to ensure optimal healing and minimize complications.

Special attention should be given to the implementation of ESIN. The surgical position of ESIN is carefully chosen on the dorsal side of the distal radius, where there are no critical nerves or blood vessels in close proximity. It is easier to enter the needle when the assistant is pulling the forearm. It is crucial to ensure that the distal end of the nail is positioned adjacent to the cortical bone without excessive bending. The ESIN should be at an angle of 30°, aligning with the position of the fracture line and maintaining parallel orientation to promote optimal outcomes.

Limitations and Strengths

While our study provided compelling evidence of the therapeutic effect of pre‐bent ESIN for unstable DRMDJ fractures, it is important to consider several limitations when interpreting the results. The study cohort comprised a small number of patients, emphasizing the need for large‐scale case studies to validate the advantages of this approach for unstable DRMDJ fractures. This treatment approach is predominantly applied to children and may not be applicable to adults. Furthermore, the clinical applicability of this technique is limited by the lack of biomechanical data regarding the stability provided by ESIN. Further biomechanical analysis is necessary to accurately identify the indications for this approach. Future studies can explore the potential application of this technique for other fractures, such as ulnar fractures with similar physiological curvatures. Although no complications were identified in this study, long‐term follow‐up observation may be required to assess the treatment's sustained effectiveness.

In summary, this preliminary study demonstrated that utilizing pre‐bent elastic stable intramedullary nails for fixation is an effective and reliable therapeutic treatment strategy for DRMDJ fractures. However, future prospective studies are necessary to validate the findings of this study.

Conclusions

To sum up, the use of pre‐bent elastic stable intramedullary nails for the treatment of unstable DRMDJ fractures, known as MIF, is a safe and effective strategy, with notable significant advantages over mini‐plate fixation. This technique may also be applicable to ulnar and forearm fractures due to their similar physiological curvature. Nonetheless, additional large‐scale case studies and prospective research are needed to confirm the advantages of MIF and explore its potential indications.

Author Contributions

Dr. Limeng Yang, Prof. Hongfeng Ruan, and Dr. Wei Zhuang contributed to the conception of the study and drafted the original manuscript; Dr. Qing Li, Dr. Hua Zhou, and Dr. Wei Zhuang performed all surgical treatments. Dr. Shuqin Wang, Dr. Jindi Xu, Dr. Kai Wang, and Dr. Changzong Deng collected and analyzed the data.

Funding Information

This study was financially supported by Natural Science Foundation of Zhejiang Province (No. LY22H270003), National Natural Science Foundation of China (No. 82174140), Hangzhou Health Science and Technology Project (No. B20210628), Zhejiang Medical and Health Science and Technology Project (No. 2023ZL134) (No. 2023ZL606) (No. 2019KY547). Research Project of Zhejiang Chinese Medical University Affiliated Hospital (No.: 2022FSYYZZ05), Zhejiang Chinese Medical University School‐level Education and Teaching Reform Project (No.: CY22001).

Conflict of Interest Statement

All named authors have no conflicts of interest to disclose in relation to this article.

Ethics Statement

The studies involving human participants were reviewed and approved by the ethics committee of Jiangnan Hospital Affiliated with the Zhejiang University of Traditional Chinese Medicine (Hangzhou Xiaoshan Hospital of Traditional Chinese Medicine). (XSZYY2081115). Written informed consent to participate in this study was provided by the participants' legal guardian/next of kin.