INTRODUCTION
In 1970, Mckibbin[1] proposed the concept of combined anteversion for the first time, defining combined anteversion as the sum of acetabular or prosthetic anterior inclination and femoral anteversion and suggesting that the stability of the hip joint was optimal when the combined anteversion was between 30° and 40°. Lucas[2] argued that the ideal combined anteversion should be between 25° and 40°, and consequently proposed the application of combined anteversion technology in total hip arthroplasty (THA), as well as using the Coplanar test to determine the size of combined anteversion in THA. After 1976, a concept of the "safe zone" was widely cited[3-5]. Widmer et al[6] demonstrated the "safe zone" and obtained the calculation method for the optimal Angle of joint rake Angle using computer 3D model simulation. Later, Dorr et al[7] and Malik et al[8] argued that the satisfactory joint forward angle range was 25-50°, with an average of 37°, which clinicians have widely accepted. However, the range of normal femoral and acetabular anteversion is wide, with large ethnic and geographical differences[9-11]. Cho et al[12] studied 952 Korean patients and found that the combined anteversion of Korean females was 28.29° ± 14.30° (< 49 years old), 34.99° ± 10.62° (50-59 years old), 31.11° ± 11.52° (60-69 years old), 34.76° ± 10.86° (70-79 years old), and 34.57° ± 10.45° (> 80 years old). In males, the joint inclinations were 27.23° ± 15.11° (< 49 years old), 28.30° ± 11.23° (50-59 years old), 23.63° ± 11.77° (60-69 years old), 25.25° ± 11.02° (70-79 years old), and 23.72° ± 11.88° (> 80 years old). In their study on 86 Indian adults with normal hip joints, Maheshwari et al[13] showed that the femoral anteversion was 8° (6.5-10.0°), the acetabular anteversion was 19° (16.0-22.0°), and the combined anteversion was 27° (23.5-30.0°). Compared with the data obtained by Western scholars, the Indian adult femoral anteversion was 3-12° lower, and the combined anteversion was 3-5° lower. The average acetabular anteversion was similar but higher.
Murray[14] divided the measurement of acetabular anteversion into three definition methods: surgery, anatomy, and radiology[15]. Lewinnek et al[5] suggested safe zones for acetabular anteversion angles using radiographic measurements, i.e., radiological definitions. At present, the measurement methods of acetabular anteversion are commonly divided into the following categories: physical measurement, two-dimensional (2D) X-ray image measurement[16-18], multi-shot spiral computed tomography (CT) three-dimensional medical image, and computer-aided surgical navigation measurement[19,20]. Physical measurement, X-ray 2D image measurement, and computer-aided surgical navigation measurement have some limitations and errors. To some extent, the emergence of multi-slice spiral CT has made up for the defects contained in the above methods, so CT measurement has become the gold standard for evaluating acetabular anteversion[21]. However, even for CT measurements, a reference plane needs to be determined first, and the measurement of the forward inclination needs to be done on the acetabular cross-section perpendicular to the reference plane. The most commonly used reference planes are the coronal plane of the body and the anterior pelvic plane. The measurement method for the coronal plane used as the reference plane is as follows: first, the plane passing through the center of the femoral head is selected as the equatorial plane, and the acetabular anteversion angle is the lateral angle between the line of the anterior and posterior border of the acetabulum and the vertical line connecting the center of the bilateral femoral head on this plane[20,22]. The method for measuring the front plane of the pelvis as the reference plane involves changing the equatorial plane perpendicular to the coronal plane to the front plane of the pelvis. In a previous study, Zahn et al[23] found no statistical difference in acetabular anteversion relative to the coronal plane and pelvic anterior plane, which were 18.5° ± 4.6° and 18.3° ± 4.5° respectively.
Wolff proposed the femoral anteversion in the early 19th century, and subsequent studies confirmed a correlation between its value, the treatment type, and the recovery effect of the patient. Based on the in-depth research of an increasing number of clinical scholars, Billing[24] defined the range of femoral anteversion in 1954, i.e., the angle formed between the femoral neck axis and the condyle plane (frontal plane of femoral condyle), which further promoted the continuous in-depth study of femoral anteversion by clinical scholars. At present, there are many measurement methods for femoral anteversion. Various measurement methods for femoral anteversion have undergone a complex development process, from solid measurement, X-ray plain film, CT plain film, and other measurements to the current three-dimensional CT measurement: (1) The solid measurement method was first proposed by Rogers et al[25] in 1934. This method involves observing and measuring normal human femur specimens placed according to the physiological structure by traditional anatomical methods and obtaining the normal range of femoral neck forward tilt angle. By using the method of stereometric measurement, Broca defined the normal range of femoral neck tilt Angle as 2.0-38.0°, after which the clinicians revised the range of femoral neck tilt Angle to 11.9-25.0° by using the stereometric measurement. However, in 1948, Kingsley et al[26] measured the anterior inclination of the femoral neck by using the stereometry method on 638 normal human femur specimens, finding that the highest value of the normal range of femoral anteversion was < 25.0° which was widely recognized before, and led clinicians to conduct another round of research on the normal range of femoral anteversion. In 1989, Wedge et al[27] found a certain deviation in measuring femoral neck forward inclination using stereometry, i.e., there was a certain deviation between the actual midline of the femoral neck and the measured central axis. Further research on the femoral specimens revealed gender differences in femoral neck forward inclination. They argued that the average anterior inclination of the femur neck was 8.11°, while the average value of the male neck was only 7.94°, and the average value of the male and female neck was 8.02°. Moreover, Wedge et al[27] further defined the range of femoral anteversion, reporting that femoral anteversion > 10.0° was abnormal; (2) X-ray plain film measurement: although stereometry clearly defines the numerical range of femoral neck inclination through anatomical methods, it is challenging to apply to the measurement of femoral neck forward inclination in clinical patients as it requires observation and analysis of the femoral body, which also greatly limits the clinical application of stereometry. With the continuous improvement of clinical demand for the measurement of femoral anteversion, people have gradually applied imaging equipment to the measurement of femoral anteversion, in which plain X-ray film has the longest application history. In order to improve the accuracy of the measurement of femoral neck forward inclination, the measurement angle, patient position, calculation method, and irradiation method were also studied and reformed, e.g., in 1952, Dunn[28] analyzed the value of plain X-ray film in measuring the anterior inclination of the femoral neck by placing the patient into a supine position and requiring the patient to extend the femur 15° to both sides and bend the hip to 90° for X-ray platform irradiation. The angle value was projected on the plain X-ray film by comparing the anterior inclination of the femoral neck in the real position and the femoral specimen. Dunn[28] found that the increase in the value of femoral neck forward inclination could increase the deviation of X-ray measurement, i.e., the greater the value of femoral neck forward inclination, the greater the error of X-ray measurement. In 1953, Dunlap et al[29] team conducted a study on the factors affecting the measurement of femoral neck forward inclination by X-ray radiographs and found that factors such as femoral extension, femoral flexion, hip rotation, femoral shaft curvature, irradiation direction, and neck trunk angle could affect the measurement accuracy of X-ray radiographs; and (3) 2D CT measurement: with the development of imaging technology and equipment, CT has gradually been applied for measuring femoral anteversion Angle. Due to its advantages of good imaging effect, high-resolution density, and low extrinsic interference, CT has been widely used in clinical orthopedics. Many scholars have also studied the methods and influencing factors of 2D CT measurement of femoral anteversion Angle. For example, in 1978, Weiner et al[30] systematically measured the anterior inclination of the femoral neck in clinical patients using 2D CT and obtained an ideal distal section and transverse section of the femur. After processing the images of the two sections by computer technology, the anterior inclination of the femoral neck was measured, i.e., the angle between the condylar line and the femoral neck axis in the image. However, Weiner's team measured a difference of 6.0° between the femoral neck tilt and the X-ray. In 1987, Murphy et al[31] further optimized the method of 2D CT measurement of femoral anteversion. They selected two CT image planes and measured femoral anteversion based on Billing's definition of femoral anteversion, which greatly reduced the measurement error of 2D CT. Subsequently, in 1997, Hermann et al[32] and his team proposed to further reduce the error of 2D CT measurement of femoral anteversion by using mathematical formula correction. Their results showed an error between the value of femoral anteversion after correction and the reference value of only 0.1°. However, their measurement method had strict requirements on the patient's position, which is especially challenging for clinical patients, who are often unable to take the standard postural position due to pathological factors and pain-related factors, thus limiting the application range of this measurement method (Figure 1).
Figure 1 Femoral and acetabular anteversion in normal hip, total hip replacement, and developmental dysplasia of the hip.
DDH: Dysplasia of the hip; THA: Total hip arthroplasty.
Herein, we discuss the role of combined femoral and acetabular anteversion in pathological changes of hip dysplasia, total hip replacement, and redirectional hip preservation surgery.
CHANGES IN COMBINED ANTEVERSION IN DEVELOPMENTAL HIP DYSPLASIA
The main characteristics of developmental hip dysplasia are abnormal upper lateral margin of the acetabulum and poor covering of the femoral head, mainly due to abnormal changes in the growth and development of the tissues around the hip joint. These include the decreased coverage rate of the acetabulum to the femoral head and increased stress concentration of the femoral head, decreased stability of the joint, and the load on the acetabular edge, which in turn increase the contact stress of the external upper margin of the acetabular, and then lead to the injury of the hip glenoid lip and peripheral cartilage, finally inducing hip osteoarthritis[33-35].
The orientation and relative position of the femur and acetabulum affect the function and range of motion of the hip joint and pathological conditions such as osteoarthritis and femoral acetabular impaction[14,36-38]. In the process of bone growth, torsion deformation occurs due to the following reasons: since the epiphyseal plate has the lowest resistance to torsion, torsion load causes rotational deflection of the growth column around the epiphyseal plate[39]. As the bone matures, the standard position of the soft tissues around the hip changes during daily activities, shortening the hip sac and muscle on one side and lengthening the hip sac and muscle on the other. These asymmetrical changes in the soft tissue surrounding the hip can cause uneven torsional forces to be applied to the femur. It has been reported that the increase of femoral anteversion and combined anteversion participate in the pathogenesis of primary hip osteoarthritis[40-44], which is presumed to be caused by the exposure of the hip and the uneven distribution of force. In their prospective study on 37 consecutive hip joints (30 patients with developmental hip dislocation), Sankar et al[45] found that optimization of the femoral prosthesis may have a beneficial effect on acetabular development by redirecting the combined force of muscles around the proximal femur to the acetabulum. This superior force vector, together with the femoral head that points more directly towards the acetabulum, may improve the remodeling ability of the acetabulum. In children, the epiphysis pubis forms the anterior wall of the acetabulum, while the relatively small ischiatic epiphysis forms the posterior wall of the acetabulum. The anterior and posterior walls determine the anterior angle of the acetabulum in cross-section. Any defect in the anterior or posterior wall of the acetabulum may cause a change in acetabular anteversion. Multiple studies on acetabular anteversion of dysplasia of the hip (DDH) have found that the anterior wall of the hip is dysplastic, while the posterior wall is often convex rather than concave[46-48]. Jia et al[49] reviewed 90 patients with unilateral developmental hip dysplasia, finding that the pubic relative length of the affected hip was lower than that of the unaffected hip, which further confirms the prevalence of anterior wall dysplasia in the affected hip. They also observed that the posterior wall of the affected hip was more convex. Of note, in cross-section, the sciatic bone exhibited more lateral rotation at the affected hip than at the healthy hip, suggesting that excessive lateral rotation of the sciatic bone at the affected hip could cause lateral displacement of the posterior wall of the acetabulum, leading to increased acetabulum forward tilt. Therefore, they argued that in addition to anterior wall dysplasia and posterior wall protrusion, excessive ischium rotation in cross-section significantly contributed to increased acetabular anteversion. In 1925, Hilgenreiner[50] gave a radiological description of hip dysplasia, which included: (1) Abnormal shape of the acetabulum, increased angle of the acetabulum, loss of the concave top of the acetabulum, and blunt upper lateral margin of the acetabulum; (2) subluxation; and (3) delayed and reduced size of the femoral head epiphysis. Ishida[51] recognized that dysplasia was a direct X-ray manifestation, with increased acetabular inclination and loss of depression, increased acetabular index (> 30°), and complete Shenton's line, which included hip subluxation, i.e., incomplete contact between the femoral head and the acetabulum; widened teardrop-femoral head distance; decreased central edge angle; the fractures of Shenton's and Perkins lines located within the medial quarter of the proximal metaphyseal; dislocation of the hip, where the femoral head is not in contact with the acetabulum, the metaphyseal is located outside the Perkins line, and Shenton's line is broken. Sarban et al[52] analyzed the CT results of 27 patients with developmental hip dysplasia with early walking age (aged 18-48 months), finding that the acetabular index was positively correlated with the acetabular anteversion, the reduction of the central marginal angle was negatively correlated with the acetabular index, and the reduction of the central marginal angle was negatively correlated with the acetabular anteversion. There was no correlation between the anterior angle of the femur and other angles. In 2010, Mootha et al[53] continued to analyze and compare the magnetic resonance imaging (MRI) data of the dislocation side and the normal side in 45 children with DDH aged 12-48 months, finding no increase in the anterior inclination of the femur, while the acetabular on the dislocation side showed excessive anterior inclination. Sarban et al[52] used 2D CT to compare the mean acetabular inclination values of 19.8° (16-26°) for 25 dislocated hip joints and 16.7° (13-20°) for 19 subluxated hip joints. The acetabular inclination of 10 normal hips was 13.4° (9-22°). Statistical analysis of the acetabular inclination showed a significant difference between the three groups (univariate variance test, P < 0.05), and the acetabular inclination increased with the increase in DDH severity, while the femoral inclination remained constant. Jia et al[54] used CT to examine Chinese children with DDH aged 18-48 months and reported no difference in the anterior inclination of the femur on the dislocated side and the healthy side in Tonnis grade II and III dislocation; however, the anterior inclination of the acetabular side was greater than that of the normal hip. In grade III and IV dislocation, the joint inclination angle of the dislocated hip was larger than that of the healthy hip. In the grade III dislocation group, the increase in the joint inclination angle of the dislocated hip was mainly due to the excessive acetabular inclination angle, and there was no significant difference in the femur inclination angle between the dislocated hip and the healthy hip. In the grade IV dislocation group, both the acetabulum and the femur had excessive forward inclination, which led to an increase in joint forward inclination because these indices of the dislocated hip were greater than those of the unaffected hip. Unilateral hip dislocation occurred in all patients, although there was no statistical difference in the joint forward inclination of both hips at grade II dislocation, which suggests that in addition to the normal acetabular index and acetabular coverage, the normal acetabular inclination is also the key to maintaining hip stability because the acetabular inclination of a dislocated hip is significantly larger than that of an undislocated hip. Nonetheless, based on their MRI analysis of 73 hip joints, Duffy et al[55] found that the average acetabular anteversion of the affected group was 15°, ranging 5-30°, while the average acetabular anteversion of the non-affected group was 11°, ranging 0-20°, and there was no statistically significant difference between the two groups. Jacquemier et al[56] found that in 143 normal children aged 1 to 15 years, the acetabular anteversion was approximately 13°. The acetabular anteversion was 13.62° ± 5.931° in the 1-2-year-old group and 13.57° ± 3.651° in the 3-4-year-old group. Weiner et al[57] reported CT results of the hip joints from 170 normal children aged 6 months to 17 years, finding that the acetabular anteversion remained relatively constant, ranging 6-19°. Browning et al[58] reported increased acetabular anteversion on the dislocated side in patients with DDH. The acetabular anteversion of subluxation and complete dislocation in early-walking age DDH patients was 16.7° ± 1.91° and 19.8° ± 2.51°, respectively, both of which were significant compared to unaffected groups.
Hip preservation surgery can effectively treat childhood DDH[59-61], and THA is the most effective treatment after entering adulthood[62]. Through surgical treatment, pain and other discomfort symptoms caused by abnormal hip joints can be effectively relieved. Also, the limited functional activities of hip joints, such as flexion and extension, abduction and adduction, and internal and external rotation, can be restored, and patients can return to everyday activities.
APPLICATION OF COMBINED ANTEVERSION IN THA
Currently, for THA in patients with developmental hip dysplasia, the accepted optimal intraoperative combined anteversion range is 25-50°, i.e., 20-30° for men and 30-45° for women. Posterior dislocation is more likely to occur if the combined anteversion is < 25°, while anterior dislocation is more likely if the combined anteversion is > 50°. Zhang et al[63] studied 35 patients with developmental hip dysplasia (47 hips) who underwent THA and found that the average femoral anteversion was 20.7° before surgery and 18.6° after surgery. The average acetabular inclination angle before surgery was 22.9°, and the average postoperative acetabular inclination angle was 20.6°. The mean joint anterior angle before surgery was 43.7°, and the mean joint anterior angle after surgery was 39.2°. Postoperative joint forward inclination ranged from 25° to 50°, except for one joint forward inclination of 57.6°. Imai et al[64] studied 65 patients with developmental hip dysplasia (65 hips), reporting a preoperative combined anteversion of 50.5° ± 7.2°. The combined postoperative tilt angle was 41.3° ± 8.6°, and it was considered that it could usually be kept within the safe range. Zhang et al[65] also studied 34 patients with developmental hip dysplasia (40 hips), finding that the combined anteversion after THA was 43.46° ± 8.37° and suggesting that the combined anteversion had a significant impact on the function of the hip joint. Therefore, applying combined anteversion in the treatment of DDH is of great importance, and a good combined anteversion can provide satisfactory function of the hip joint and improve the patient’s quality of life.
In THA, good placement and insertion angle of the prosthesis are very important as the service life of the prosthesis is limited, and the wear of the prosthesis can only be reduced by maintaining good prosthesis correspondence. In adult patients with developmental hip dysplasia, due to long-term poor stress between the acetabulum and the femoral head, the acetabulum tilt increases, the acetabulum becomes shallow, the femoral neck trunk angle increases, and the femoral neck tilt variation, the femoral head reduction deformity and the anatomical changes of the proximal femoral pulp cavity result in abnormal hip joint anatomy[66,67]. Therefore, patients with hip dysplasia have many types of malformations, both femur and acetabular[68-71]. Various deformities caused by DDH not only increase the difficulty of correct placement and angle of the prosthesis during THA, making it more difficult for DDH patients to perform THA than regular patients[71-74] but also affect the stability and joint function of artificial joint[71,75]. If the individual surgical plan is not developed according to the anatomical characteristics of the hip joint of the patients with developmental hip dysplasia before THA, it can likely cause poor placement and Angle implantation of THA prosthesis. Due to poor placement and angle implantation of THA prostheses, the incidence of postoperative complications such as hip prosthesis impingement, loosening, and wear increases[76]. Numerous studies have shown that the complications that lead to the failure of THA, such as prosthesis dislocation, are related to the poor placement angle of the prosthesis. In their study, Biedermann et al[77] measured the angle of the acetabular cup in 132 patients with postoperative prosthesis dislocation and found that the direction and position of the acetabular cup were significantly correlated with the occurrence of prosthesis dislocation after THA. Di Schino et al[78] and Sanchez-Sotelo et al[79] reported a significant increase in dislocation rate in DDH patients due to increased femoral and acetabular anteversion. Therefore, the angle and placement of the prosthesis are of critical importance in THA. A good implant position and implantation Angle can reduce the occurrence of complications, such as joint instability and premature loosening of the implant, and at the same time, can increase the firm fixation and bone growth of the implant, reduce wear and loosening, and extend the life of the implant[77,80,81]. Therefore, finding the appropriate prosthetic position and Angle for patients with DDH is necessary.
Yoshimine[82], Malik et al[8], and Dorr et al[7] demonstrated that the "safe zone" of combined anteversion (CA) for acetabular and femoral stem prostheses was 25-50°, and the average joint forward Angle was 37°. Before Lucas[2] emphasized the importance of using the CA technology in THA, the primary focus was on the rake angle of the cup. However, Komeno et al[22] supported the concept of CA by comparing 20 cases of dislocated hips after hip replacement with 18 cases of non-dislocated hips. They concluded that the postoperative dislocation rate was not unilaterally affected by acetabular or femur but by CA. Through CT scanning of 76 patients with sufficient symptoms to receive periacetabular osteotomy and 50 normal hip joints, Kohno et al[83] concluded that early hip pain in patients with DDH was related to combined anteversion and that the optimal combined anteversion should be considered when performing periacetabular osteotomy. Nakashima et al[84] reported that using CA technology in cementless THA can effectively reduce the occurrence of postoperative dislocation.
Therefore, the application of combined anteversion in DDH THA is of great significance for the correct installation position and angle of the prosthesis. Satisfactory combined anteversion can prevent the occurrence of postoperative prosthesis dislocation, granting patients satisfactory function of the hip joint after surgery and subsequently improving their quality of life.
APPLICATION OF COMBINED ANTEVERSION IN HIP PRESERVATION SURGERY
In triple pelvic osteotomy for DDH, the acetabular can be replaced in multiple directions due to complete amputation of the pubic, ischiatic, and iliac bones. Moreover, it is essential to maintain a normal acetabular anteversion because increased acetabular anteversion is associated with hip instability[85], which can lead to hip pain and hip osteoarthropathy[86-89]. Shepherd analyzed Magnetic resonance images, in-vivo gait data, and musculoskeletal models of 14 children with DDH, they found increasing anteversion leads to an increase in forces exerted by the hip flexor and abductor muscles, thereby resulting in alterations of joint reaction forces[90]. In a study of 90 patients with unilateral DDH, Jia et al[49] concluded that based on an accurate assessment of acetabular anteversion and a careful analysis of the potential causes of acetabular anteversion using CT, an individualized treatment plan should be considered before triple osteotomy to prevent surgical and postoperative problems.
Tönnis et al[91,92] emphasized the importance of maintaining a normal acetabular forward angle during a triple osteotomy. They recommended placing a vertical guide Kirschner's needle in the acetabular segment to monitor intraoperative transverse rotation and suggested that a reduced acetabular forward angle (< 15 degrees) may reduce limb pronation and lead to premature osteoarthropathy. The classic pelvic osteotomy for the correction of hip dysplasia (Salter osteotomy, triple osteotomy) is prone to a reduction in acetabular inclination due to the nature of the three-dimensional correction. In addition to reducing acetabular forward inclination, the increased external rotation during reorientation may result in acetabular backward inclination and significant under-coverage of the rear. Lee et al reported this complication after Salter osteotomy in postoperative CT scan, and Kim et al[93] after triple osteotomy. The potential individual differences in acetabular anteversion in patients with acetabular dysplasia and the effect of corrective surgery on acetabular anteversion should be understood before pelvic redirected osteotomy or corrective osteotomy. A thorough evaluation of each hip joint, including transverse anatomical analysis, is recommended for preoperative planning to ensure correct intraoperative positioning. Evaluation of acetabular anteversion is important in planning a redirected pelvic osteotomy. In their study, Sarban et al[52] found that acetabular inclination increased with the severity of DDH, but femoral inclination remained the same, thus suggesting that femoral and acetabular inclination should be evaluated before DDH surgery. When planning periacetabular osteotomy for patients with hip dysplasia[94,95], a three-dimensional evaluation of hip joint morphology should be conducted, and the correction should be made according to individual differences in acetabular and femur morphology[88,96-98].
In their study on 86 Indian adults with normal hip joints, Maheshwari et al[13] showed that the mean anterior inclination of the femur was 8° (6.5-10.0°), the mean anterior inclination of the acetabular was 19° (16.0-22.0°), and the mean combined anteversion was 27° (23.5-30.0°). Compared with the data obtained by Western scholars, the Indian adult femoral anteversion is 3-12° lower, and the combined anteversion is 3-5° lower. The average value of acetabular anteversion is similar but still relatively high. Therefore, it is believed that lower femoral anteversion (rather than acetabular anteversion) is the main determinant accounting for this difference. This finding has been reported by Reikerås et al[40] in hip osteoarthritis. Hu et al[99] reviewed 208 DDH patients who underwent THA and concluded that the diversity and dispersion of femoral anteversion hinder preoperative planning, which leads to challenging decision-making in optimizing combined anteversion during surgery. However, Kohno et al[83] found that the increase in femoral anteversion and acetabular anteversion jointly contributed to the development of hip osteoarthritis. They also argued that optimal combined anteversion should be considered in periacetabular osteotomy.
CONCLUSION
The assessment of femoral and acetabular anteversion independently is insufficient to guide hip preservation surgeries such as triple osteotomy and periacetabular osteotomy, nor can it serve as a reference indicator for THA. However, when combined, anteversion measurements hold significant value in guiding both hip preservation surgeries and artificial hip replacements, ensuring postoperative stability and satisfactory joint function. We recommend that combined anteversion should be utilized as a crucial parameter for surgical planning and clinical efficacy evaluation in hip preservation treatment and THA.
Provenance and peer review: Invited article; Externally peer reviewed.
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Specialty type: Anatomy and morphology
Country/Territory of origin: China
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P-Reviewer: Oommen AT, India S-Editor: Zhang H L-Editor: A P-Editor: Zhao YQ