Abstract
To elucidate the clinicopathological features of follicular thyroid carcinoma (FTC) coexisting with papillary thyroid carcinoma (PTC) (FTC + PTC). We collected a total of 55 FTC + PTC patients (including 12 males [21.8%] and 43 females [78.2%]), with an average age of 47.6 years. In the FTC alone group, the average age was 52.3 years, and the proportion of females was 71.3%. The median age was 43.5 years, with an average age of 45 years in the PTC alone group. Compared with the tumors in the FTC alone group, FTC in the FTC + PTC group exhibited a smaller maximum diameter (49.1% measuring ≤2 cm), a younger patient age (70.9% younger than 55 years), an earlier tumor stage (94.5% in stages I–II), a lower incidence of recurrent cancer (n = 2, 3.6%), a lower frequency of distant metastasis (6.1%), and a lower proportion of “extensively invasive” subtype (12.7%) (all p < 0.05). Compared with the PTC alone group (n = 289), the FTC + PTC group had a higher proportion of PTC with a maximum diameter of ≤1 cm (72.5%), and the degree of invasion of thyroid extracellular tissue was less severe (all p < 0.05). No statistically significant differences were found in overall survival (OS), cancer-specific survival (CSS), and RFS between these two groups (the FTC or PTC alone group versus FTC + PTC group). In sum, FTC + PTC has some clinicopathological features.
Keywords: Follicular thyroid carcinoma (FTC) coexisting with papillary thyroid carcinoma (PTC), Prognosis, Distinct clinicopathological features
Graphical Abstract
Introduction
Follicular thyroid carcinoma (FTC): coexisting with papillary thyroid carcinoma (PTC) (FTC + PTC) is a rare thyroid malignancy, with limited reports in the literature. Its clinicopathological features and prognosis remain unclear, necessitating further systematic studies. The present study aimed to summarize the clinicopathological features of FTC + PTC, thereby adding to the limited literature and providing evidence in determining treatment strategies and predicting prognosis.
Materials and Methods
Clinical data
The clinicopathological data of 55 FTC + PTC patients, diagnosed in the Department of Pathology at the First Medical Center of the People’s Liberation Army (PLA) General Hospital between April 2012 and January 2025, were analyzed and compared with those of patients diagnosed with PTC alone (n = 289, who underwent surgical resection at the same center between July 2005 and November 2017) [1] or FTC alone (n = 181 and local undifferentiated carcinoma was not included, who underwent surgical resection at the same center between December 2005 and April 2021) [2]. The patients with PTC alone, the patients with FTC alone, the patients with FTC + PTC, all from the same pathological diagnostic center. In the FTC + PTC group, there were 43 females (78.2%) and 12 males (21.8%). The median age of the patients was 49 years, and the average age was 47.6 years. 16 patients (29.1%) were aged 55 years or older, while 39 patients (70.9%) were younger than 55 years. 2 cases of recurrent cancer had already recurred at the time of presentation, meaning that they had recurred after thyroid cancer surgery. Patients were followed up via telephone as of February 2025.
Due to its retrospective design, this study was exempt from informed consent according to the Declaration of Helsinki (2013 revised edition). The study protocol was approved by the ethics committee at our center.
At present, FTC is divided into minimally invasive type, encapsulated vascular infiltrating type and extensive infiltrating type. The extensive infiltrating type often lacks the capsule. The encapsulating vascular infiltrating type is usually accompanied by capsule infiltration, so the two types of minimally invasive type and encapsulating vascular infiltrating type were combined into one group in statistics.
Pathological sections and HE staining
Immediately following a thyroid surgery, the specimens were fixed in 4% neutral-buffered formalin for 12–24 hours. Subsequently, the tissue was sampled for dehydration and clearing in an automatic tissue dehydrator, embedded in paraffin, and cut into 4-μm-thickness sections. These sections were then subjected to hematoxylin and eosin (HE) staining, allowed to air-dry naturally, and finally observed under a microscope.
Statistical analysis
Data were analyzed using the SPSS statistical software (version 17.0). The Chi-square test was used to analyze the differences among the data in contingency tables. In order to facilitate statistics, 55 cases of the FTC alone group and the PTC alone group were randomly selected for the size of the thyroid gland to corresponding to 55 cases in the FTC + PTC group. The difference in the largest diameter of the unilateral thyroid gland subjected to pathology was analyzed using the one-way ANOVA test. Univariate survival analyses were based on the Kaplan-Meier survival function, and the survivals were compared using the log-rank test. A p value of less than 0.05 was considered statistically significant.
Results
Clinicopathological features of FTC in the FTC + PTC group
In 55 cases, FTC and PTC carcinoma tissues were seen (Figs. 1–6). The FTCs in FTC + PTC patients sized 0.3 cm–6.8 cm, with an average maximum diameter of 2.3 cm and a median diameter of 2.5 cm. FTCs with ≥2 foci accounted for 9.1% (5/55). Lymph node metastasis was observed in 5.5% (3/55) of FTC cases. Notably, four patients with no lymph node examination were considered to have no lymph node metastasis. One patient had distant metastasis to sacrum, which was found one month before thyroid surgery; one case was found to have brain metastasis and surgical resection 3 weeks before thyroid surgery; one patient was found to have metastases to the sacrum and lungs during thyroid surgery. During the follow-up period, one patient died due to metastases to multiple bones and lung (overall survival of 90 months).
Fig. 1. Hematoxylin and eosin (HE) staining of follicular thyroid carcinoma (FTC) coexisting with papillary thyroid carcinoma (PTC). (A) Monofocal tiny PTC (indicated by black arrow). The lesion was surrounded by Hashimoto’s thyroiditis, along with follicular tumors of undetermined malignant potential (FT-UMP) (white arrow); (B) FTC (×100 magnification). The lesion invaded the capsule and blood vessels (black arrows); (C) Magnified view (×250) of the PTC in (A), revealing a small number of papillary structures; (D) Magnified view (×300) of the FTC in (B), showing tightly packed follicles. The cytoplasm of the cell was abundant, the cytoplasm was lightly stained and pale red, the nucleus was round and oval, and a few nucleoli were visible.
Fig. 2. Histological images of follicular thyroid carcinoma with papillary thyroid carcinoma. (A) Microinvasive FTC with extracapsular invasion, capsular thickening with calcifications, tumor size 1 cm, located on the left thyroid gland. (B) Papillary thyroid carcinoma (2 lesions) with gravel formation, tumor size 0.4–0.8 cm, the larger cancer tissue invaded the thyroid envelope, located on the right side. (C) showed a follicular tumor with undetermined malignant potential in the surrounding thyroid gland with a size of 0.3 × 0.3 × 0.2 cm. (D) showed follicular tumors of undetermined malignant potential (higher fold of (C)) with dense follicles.
Fig. 3. Histological images of follicular thyroid carcinoma with papillary thyroid carcinoma. (A–C) Thyroid follicular carcinoma was located on the left thyroid gland, the follicles were small and dense, and the carcinoma tissue invaded the thyroid envelope (indicated by black arrow). (D) Papillary thyroid carcinoma was located on the right side of the thyroid gland, with a maximum diameter of 0.8 cm.
Fig. 4. Histological images of follicular thyroid carcinoma with papillary thyroid carcinoma. (A) Microinvasive follicular carcinoma with intravascular thrombus and FTC on the right side. (B) showed follicles of varying sizes in FTC. (C) The small PTC on the left had a maximum diameter of 0.5 cm. (D) High Power Field of PTC in (C), papillary structure can be seen.
Fig. 5. Images of the combination of follicular thyroid carcinoma and papillary thyroid carcinoma. (A) A slice showed 4 follicular tumors of different sizes (around cancerous tissue). (B) A slice showed a microinvasive follicular carcinoma (white arrow, 2 cm in size) and a tiny papillary thyroid carcinoma (black arrow, 0.3 cm in size), surrounded by Hashimoto’s thyroiditis. (C) A slice showed 2 microscopic papillary thyroid carcinomas (black arrow and dotted arrow), about 0.1 cm in size, and follicular adenoma (white arrow). (D) showed the magnification of PTC in (C) (the black arrow).
Fig. 6. Histological images of follicular thyroid carcinoma with papillary thyroid carcinoma. (A) Follicular thyroid carcinoma (FTC). The follicles were of varying sizes, most of which were small. (B) FTC metastases in lymph nodes (black arrow indicated FTC, and white arrow indicated residual lymphoid tissue).
The maximum diameter of FTC in the FTC + PTC group was significantly smaller than that observed in the FTC alone group (p ≤ 0.001). Only 3 patients in the FTC + PTC group were in TNM stage IV, indicating an earlier disease stage compared to the FTC along group (Table 1). Univariate survival analysis showed no statistically significant differences in cancer-specific survival (CSS) (104.000 ± 9.899 months versus 120.688 ± 5.956 months, p = 0.205) or overall survival (OS) (104.000 ± 9.899 months versus 115.872 ± 6.097 months, p = 0.110) or relapse-free survival (RFS) was significantly longer in FTC + PTC group than in FTC alone group (97.681 ± 6.394 months versus 103.895 ± 6.728 months, p = 0.228) (Fig. 7) between FTC + PTC group and FTC alone group.
Table 1. Comparison of clinicopathological features between the FTC + PTC group and FTC alone group.
| FTC + PTC group |
FTC alone group |
χ2 value | p value | ||
|---|---|---|---|---|---|
| FTC TNM stage | Stage I–II | 52 (94.5%) | 119 (65.7%) | 17.531 | <0.001 |
| Stage III–IV | 3 (5.5%) | 62 (34.3%) | |||
| FTC size | ≤2 cm | 27 (49.1%) | 13 (11.6%) | 28.452 | <0.001 |
| >2 cm | 28 (50.9%) | 99 (88.4%)& | |||
| Age (yrs) | <55 | 39 (70.9%) | 83 (45.9%) | 10.062 | 0.001 |
| ≥55 | 16 (29.1%) | 98 (54.1%) | |||
| Gender | Female | 43 (78.2%) | 129 (71.3%) | 1.019 | 0.313 |
| Male | 12 (21.8%) | 52 (28.7%) | |||
| Number of FTC foci | Monofocal | 50 (90.9%) | 105 (80.2%) | 3.227 | 0.072 |
| ≥2 | 5 (9.1%) | 26 (19.8%)* | |||
| Recurrent cancer (including metastases) |
None | 53 (96.4%) | 115 (63.5%) | 22.162 | <0.001 |
| Yes | 2 (3.6%) | 66 (36.5%) | |||
| Postoperative recurrence (including metastasis and death) |
None | 44 (89.8%) | 114 (79.2%) | 2.782 | 0.095 |
| Yes | 5 (10.2%)Θ | 30 (20.8%)Θ | |||
| Distant metastases | None | 46 (93.9%) | 111 (61.3%) | 18.859 | <0.001 |
| Yes | 3 (6.1%)Θ | 70 (38.7%) | |||
| Subtype | Minimally invasive and encapsulated angioinvasive | 48 (87.3%) | 95 (63.8%) | 10.597 | 0.001 |
| Extensively invasive | 7 (12.7%) | 54 (36.2%) | |||
| Excision method | Completely resected | 55 (100.0%) | 132 (84.6%) | 9.548 | 0.002 |
| Partially excised and unresected | 0 (0.0%) | 24 (15.4%) | |||
| FTC lymph node metastasis | None | 52 (94.5%) | 53 (94.6%) | 0.000 | 1.000 |
| Yes | 3 (5.5%) | 3 (5.4%)# |
& Tumor size information was lacking in 69 patients in the FTC alone group due to puncture/consulted cases reasons.
* The number of primary lesions was unknown in 50 patients in the FTC alone group because the samples were identified as metastatic or puncture specimens. Additionally, the number of lesions was also unclear in one carcinoma patient who underwent consultation.
Θ In the study, 37 patients in the FTC alone group were lost to follow-up. Six patients were lost to follow-up in the FTC + PTC group.
# Lymph nodes were not sent for pathology in 125 patients in the FTC alone group due to the following reasons: (i) Preoperative clinical examinations did not indicate suspicious lymph node metastasis; (ii) the surgical approach for FTC disabled pathology; and (iii) tissues were obtained by puncture in some cases.
Fig. 7. Survival outcomes of patients with FTC + PTC. (A) The survival curve of relapse-free survival (RFS) was higher, but not statistically significant in the FTC + PTC group than in the FTC alone group (p = 0.228); (B) Cancer-specific survival (CSS) showed no statistically significant differences between the two groups (p=0.205).
In the FTC + PTC group, FTC was located on the right side in 31 cases (4 case involving isthmus), in the left side in 23 cases (7 cases involving isthmus), and in both sides in 1 case.
In addition, the size of the surgically resected thyroid gland showed significant difference between FTC alone group and FTC + PTC group (p < 0.001), and it was larger in the FTC alone group.
Clinicopathological features of PTC in the FTC + PTC group (Table 2)
Table 2. Comparison of clinicopathological features between the FTC + PTC group and PTC alone group.
| PTC alone group | FTC + PTC groupβ | χ2 value | p value | ||
|---|---|---|---|---|---|
| Age (yrs) | <55 | 233 (80.6%) | 39 (70.9%) | 2.634 | 0.105 |
| ≥55 | 56 (19.4%) | 16 (29.1%) | |||
| Gender | Female | 189 (65.4%) | 43 (78.2%) | 3.439 | 0.064 |
| Male | 100 (34.6%) | 12 (21.8%) | |||
| Recurrent cancer | None | 281 (97.2%) | 53 (96.4%) | 0.000 | 1.000 |
| Yes | 8 (2.8%) | 2 (3.6%) | |||
| Postoperative recurrence (including metastasis and death) | None | 164 (71.9%) | 44 (89.8%) | 6.883 | 0.009 |
| Yes | 64 (28.1%) | 5 (10.2%)Θ | |||
| PTC lymph node metastasis | None | 171 (59.2%) | 34 (61.8%) | 0.135 | 0.714 |
| Yes | 118 (40.8%) | 21 (38.2%) | |||
| PTC stage | Stage I | 256 (88.6%) | 47 (85.5%) | 0.430 | 0.512 |
| Stage II–IV | 33 (11.4%) | 8 (14.5%) | |||
| Number of PTC foci | Monofocal | 165 (57.1%) | 27 (50.9%) | 0.688 | 0.407 |
| ≥2 | 124 (42.9%) | 26 (49.1%)* | |||
| PTC maximum diameter | ≤1 cm | 92 (31.8%) | 37 (72.5%) | 30.520 | <0.001 |
| >1 cm | 197 (68.2%) | 14 (27.5%)& | |||
| PTC capsular invasion | None | 43 (14.9%) | 13 (25.0%) | 11.532 | 0.003 |
| Invasion of the capsule | 78 (27.0%) | 22 (42.3%) | |||
| Invasion of fat and striated muscles | 168 (58.1%) | 17 (32.7%)※ |
β The clinicopathological data for the FTC + PTC group predominantly reflected PTC features, although the postoperative recurrence/metastasis and deaths were the number of the whole FTC + PTC group.
Θ In the study, 61 patients in the PTC alone group were lost to follow-up. Six patients were lost to follow-up in the FTC + PTC group.
* Two cases were excluded from the analysis: (i) in one case, PTC metastasis was identified in a lymph node, yet no definite PTC component was detected after the sampling of the entire thyroid tissue. The possibility of FTC accompanied by small or occult PTC could not be ruled out; (ii) in the another patient, which was a case undergoing consultation, the number of foci was not explicitly documented.
& Data regarding the maximum diameter were missing in four cases: (i) One case corresponded to the aforementioned exclusion (i) *; and (ii) information on the size of the PTC was not available in three cases undergoing consultations.
※ Three cases lacked information regarding capsular invasion: (i) One case corresponded to the aforementioned exclusion (i) *; and (ii) information on PTC capsular invasion was not provided in the remaining two cases undergoing consultations.
Microscopically, PTC in the FTC + PTC group sized <0.1 cm–3.0 cm. The average and median maximum diameter of PTC in this group were 1.1 cm and 1.0 cm, respectively. Tumor size data of PTC were not available in 4 cases. PTC lymph node metastasis was detected in 21 cases.
The PTC lesions were monofocal in 27 cases and multifocal in 26 cases (26/53, 49.1%; bifocal in 16 cases and trifocal or more in 9 cases). One patient was considered to have occult PTC, whereas the foci were unclear in another patient (the case undergoing consultation).
The PTC in the FTC + PTC group showed differences in clinicopathological features when compared with the PTC alone group, as shown in Table 2.
Nevertheless, the survival outcomes were not significantly different between the FTC + PTC group and PTC alone group: CSS, 104.000 ± 9.899 months versus 195.969 ± 2.395 months (p = 0.382); OS, 104.000 ± 9.899 months versus 97.681 ± 6.394 months (p = 0.420); and RFS, 106.538 ± 5.247 months versus 157.996 ± 5.096 months (p = 0.622).
In the FTC + PTC group, PTC was located on both sides in 19 cases (14 cases involving isthmus), on the right side in 21 cases (11 case involving isthmus), and on the left side in 14 cases (5 case involving isthmus). The left or right side of PTC in the remaining 1 case was unknown, here’s why: PTC was only found in the metastatic lymph nodes, and no PTC was found in the thyroid gland after extensive sampling (probably occult PTC).
Furthermore, the FTC + PTC group had significantly larger size of the surgically resected unilateral thyroid gland compared with that in the PTC alone group (p < 0.001).
Features of the thyroid glands adjacent to the malignant tissues
Mixed lesions were identified in 20 patients, including nodular goiter accompanied by adenoma in 8 patients and nodular goiter accompanied by Hashimoto’s thyroiditis or chronic lymphocytic thyroiditis in 5 patients. One case of Hashimoto’s thyroiditis was accompanied by borderline follicular tumors, and one case of multiple follicular adenomas was accompanied by borderline follicular tumors. In the remaining 5 patients with mixed lesions, three or more lesions were detected, including two cases of Hashimoto’s thyroiditis accompanied by nodular goiter and follicular adenomas (along with a follicular tumor of uncertain malignant potential [FT-UMP] in one case), two cases of nodular goiter accompanied by adenoma and FT-UMP, and one case of Hashimoto’s thyroiditis was found with follicular adenoma and FT-UMP.
The conditions in the remaining 35 cases: (i) simple follicular adenoma (n = 3); One patient had two undetermined malignant potential well-differentiated tumors (n = 1). (ii) simple nodular goiter (n = 4). (iii) simple autoimmune inflammation (Hashimoto’s thyroiditis or lymphocytic thyroiditis, n = 8). (iv) 7 cases with varying follicular sizes, including 1 case with atypical follicular epithelial hyperplasia. (v) unremarkable conditions (n = 12).
Thus, 36.4% (20/55) of patients had follicular tumors in the thyroid gland near malignant tissue (including 8 cases of borderline follicular tumors), while 21 patients had nodular goiter and 16 cases of Hashimoto’s thyroiditis or chronic lymphocytic thyroiditis, some of which presented as mixed specimens (Graphical Abstract).
Graphical Abstract. FTC in the FTC + PTC group exhibited a smaller maximum diameter (a median diameter of 2.5 cm), FTC was mostly located on the right side in 31 cases (A), and a lower proportion of “extensively invasive” subtype. Compared with the PTC alone group, the FTC + PTC group had a slightly high incidence of multifocal PTC with 49.1% (A), and the majority of PTC was on the right side and both sides. Higher proportion of PTC with a maximum diameter of ≤1 cm (72.5%), and the degree of invasion of thyroid extracellular tissue was less severe. The thyroid lesions surrounding cancer were complex. 36.4% of the patients had follicular tumors (including FT-UMP), 16 cases Hashimoto’s thyroiditis or chronic lymphocytic thyroiditis, while 21 patients had nodular goiter (B).
Discussion
PTC can co-exist with FTC and the incidence of FTC + PTC is low. Since the first case was reported in 2013 [3], fewer than 30 sporadic cases have been documented [4-7]. Chen et al. [4] described 10 FTC + PTC cases, including 7 females and 3 males aged 28–70 years with a mean age of 50.7 years. Similarly, our patients aged from 25 to 75 years, with an average age of 47.6 years. Our cohort represented the largest case series to date, comprising 55 cases. The proportion of females was 78.2%. It was indicated that monofocal lesion was predominant in FTC [4]; similarly, most patients in our cohort had monofocal lesion, and only 5 patients had multifocal lesions (≥2). Furthermore, FTCs predominantly occurred on the right side. PTC exhibited a slight predilection for right side (21 cases), next there were 19 cases on both sides and 14 cases on the left side.
Compared with the tumors in the FTC alone group, FTC in the FTC + PTC group exhibited a smaller maximum diameter (49.1% measuring ≤2 cm), a younger patient age (70.9% younger than 55 years), an earlier tumor stage (91.7% in stage I–II), reduced frequency of distant metastases, and a smaller proportion of extensively invasive carcinomas.
The significant enlargement of the thyroid gland led to timely medical attention for patients, and the increase in preoperative diagnosis rate of thyroid cancer led to timely surgery for FTC + PTC patients, resulting in a smaller FTC and a smaller PTC. These might be related to early detection and prompt surgical interventions and partly related to early identification during a PTC surgery. In some patients with mixed lesions, the unique features of FTC + PTC may facilitate its early detection.
In addition, the OS, CSS and RFS showed no significant differences between the FTC + PTC group and the FTC or PTC alone group. As majority of our cases were diagnosed in recent years, the short follow-up periods might impact our conclusion.
The larger number of FTC + PTC cases occurring in recent years may be attributed to multiple factors: (i) The socioeconomic development, medical advances, and popularization of health check-ups have led to a rise in thyroid screenings, facilitating early detection of thyroid lesions. Most of the cases in this group were found by health check-ups. (ii) Medical advancements have improved the preoperative diagnosis rate of thyroid cancer. (iii) Pathologists’ awareness of comorbid cancer has been enhanced, leading to earlier diagnosis.
The FTC + PTC group had a slightly high incidence of multifocal PTC (49.1%). Similarly, it was reported that half (5/10) of the cases were multifocal [4]. In contrast, the reported incidence of multifocal PTC in patients with PTC alone ranged from 37.2% to 41.1% [8-10]. Thus, the incidence of multifocal PTC slightly escalated in FTC + PTC patients, necessitating careful surveillance. Furthermore, PTC in our FTC + PTC group exhibited a smaller maximum diameter, with the majority (72.5%) of tumors having a maximum diameter of ≤1 cm. The incidence of extracapsule-soft tissue invasion was even lower. However, no significant differences were observed in RFS, OS, and CSS.
In the present study, 36.4% of the patients presented with follicular adenomas and borderline follicular tumors in the thyroid glands adjacent to the malignant tissues, and there was also a high incidence of nodular goiter lesions or autoimmune thyroiditis, highlighting the complexity of thyroid conditions in FTC + PTC cases, in particular the high incidence of follicular adenomas and borderline follicular tumors.
Among the FTC + PTC cases, the lower proportion of extensively-invasive FTC and the smaller maximum diameter of PTC were primarily attributed to early detection and early treatment, and the reasons for this may be as follows: (i) The thyroid glands around FTC + PTC were often complicated with other lesions such as nodular goiter, follicular adenoma/follicular tumors, and Hashimoto’s thyroiditis. These lesions, along with FTC + PTC itself, led to a significant increase in the volume of the thyroid gland, prompting patients for timely medical consultation. (ii) FTC + PTC had a larger maximum diameter of the unilateral thyroid gland submitted for pathology than PTC alone. Its large size urged patients to seek medical examinations early. (iii) The existence of a PTC component contributed to a high rate of preoperative clinical diagnosis of thyroid cancer, leading to early surgery. PTC had distinct ultrasound features including unclear borders, calcifications, and aspect ratio >1 and therefore can be diagnosed or highly suspected preoperatively. The PTC component contributed to a high preoperative diagnosis rate and elevated cancer suspicion, prompting FTC + PTC patients for early surgical intervention. (iv) The high preoperative diagnosis rate of thyroid cancer facilitated early treatment (including early surgery) in FTC + PTC patients. (v) Due to the presence of follicular adenomas/follicular tumors in some FTC + PTC patients, extensive sampling was required so as to identify small FTCs and small PTCs after surgery, and the small FTCs were often not the extensively-invasive type. Missed diagnoses can be avoided. (vi) Finally, early surgery resulted in a smaller proportion of extensively-invasive FTC in FTC + PTC and smaller maximum diameter of both FTC and PTC.
To sum up, FTC + PTC had some clinicopathological features, including small tumor size. The incidence of PTC invasion in extramembrane tissues in FTC + PTC group was lower than that in the PTC alone group, and the rate of recurrence was lower after surgery. Comparing with FTC alone, FTC + PTC had younger age, less extensive infiltration type, less distant metastases, and early stage, a general trend toward a favorable prognosis. These features may be associated with early detection and early surgery. Multiple sampling will help to enhance lesion detection and reduce missed diagnoses. We need to study more cases in the future.
Contributor Information
Li Ying, Email: libao7706@126.com.
Shi Huai-yin, Email: shihuaiyin@sina.com.
Disclosure
All the authors declare that there was no conflict of interest.
Support Fund: 2024 Science and Technology Innovation Guidance Project of Bengbu City (2024ZD0051); Excellent Scientific Research and Innovation Team of Anhui Universities (2024AH010021)
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