Volume 33,Issue 11,2024 Table of Contents

1 Etiological analysis and clinical implications of locally advanced thyroid cancer

CHENG Ruochuan , LIU Wen , DONG Zhizhong

2024, 33(11):1751-1758. DOI: 10.7659/j.issn.1005-6947.2024.11.001

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Although the overall prognosis of thyroid cancer is favorable, some patients may still experience persistent, recurrent, or distant metastatic disease after initial standard treatment. Among them, patients with locally advanced thyroid cancer (LATC) have a poorer prognosis, making it a major cause of mortality in thyroid cancer. Analysis of etiology of LATC reveals that most LATC cases arise from the progression of differentiated thyroid cancer. Contributing factors include limitations in preoperative assessment, gradual downgrading of treatment intensity, and the widespread adoption of thermal ablation therapies. Therefore, early standardized management of low-risk thyroid cancer is essential to prevent the development of LATC.

2 Full-pregnancy-cycle management for women of childbearing age with differentiated thyroid cancer

GAO Rili , GUAN Haixia

2024, 33(11):1759-1765. DOI: 10.7659/j.issn.1005-6947.2024.11.002

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With the rising incidence of thyroid cancer, the number of women of childbearing age diagnosed with differentiated thyroid cancer (DTC) in China has significantly increased. Many in this group bear the responsibility of reproduction, which necessitates higher standards for the clinical management of DTC. Therefore, implementing full-pregnancy-cycle management (encompassing preconception, pregnancy, and postpartum phases) for women of childbearing age with DTC represents a new model of cancer health management tailored to China's national conditions and contemporary characteristics. This approach is of great significance in safeguarding the perinatal and long-term health of mothers and offspring, improving the standardization of DTC management, and enhancing patients' quality of life. Based on existing literature and guidelines, the authors outline specific practices for implementing full-pregnancy-cycle management, spanning the preconception, pregnancy, and postpartum phases. During the preconception phase, unnecessary delays in conception should be avoided, individualized treatment plans for DTC should be developed in alignment with reproductive goals, and thorough pre-pregnancy counseling should be provided. In the pregnancy phase, the focus is on continuing thyrotropin (TSH) suppressive therapy, guiding appropriate thyroid hormone medication use during pregnancy, and monitoring and following up on thyroid function and DTC progression. In the postpartum phase, it is essential to understand the safety of TSH suppressive therapy during lactation, monitor for the occurrence of postpartum thyroiditis, and address its impact on thyroid hormone therapy. It is hoped that this field will garner greater attention from multidisciplinary scholars, fostering collaboration to accumulate data, conduct long-term follow-up, and optimize specific strategies and pathways for full-pregnancy-cycle management, thereby promptly ensuring the best medical services to the target population.

3 Pathologic features and surgical treatment of noninvasive follicular thyroid neoplasm with papillary-like nuclear features: a report of 33 cases

CAI Wei , ZHAO Jing , LI Kaifu , ZHAO Ye , WANG Yajun , KANG Hua

2024, 33(11):1766-1774. DOI: 10.7659/j.issn.1005-6947.2024.11.003

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Background and Aims The incidence of papillary thyroid carcinoma (PTC) has shown a significant upward trend. Given its favorable prognosis, there is a growing trend toward de-escalating its treatment to improve patients' quality of life. Pathologists have renamed the encapsulated follicular variant of PTC with indolent biological behavior as noninvasive follicular thyroid neoplasm with papillary-like nuclear features (NIFTP), providing a theoretical basis for treatment de-escalation. However, challenges persist in the clinical pathological diagnosis of NIFTP, and it is still predominantly managed as classical PTC in most cases. This study was performed to explore the clinicopathologic diagnostic characteristics, surgical challenges, and prospects for de-escalation treatment of NIFTP.Methods The clinical data of 33 patients with thyroid disease who were admitted to Xuanwu Hospital Capital Medical University from November 2017 to December 2022 and confirmed as NIFTP by final paraffin pathology were retrospectively analyzed.Results Among the 33 NIFTP patients, there were 11 males and 22 females, with an average age of 50 years. Tumor sizes ranged from 0.6 to 7.5 cm. There were 31 cases of solitary NIFTP tumor and 2 cases of multifocal tumors (each involving 2 sites). Eleven patients had coexisting PTC (one lesion in each case), with 4 lesions located on the same side as the NIFTP and 7 on the opposite side. All patients underwent surgical treatment, including 27 cases of conventional open surgery and 6 cases of endoscopic surgery. Suspicious or potentially malignant lesions were treated according to PTC surgical principles (lobectomy of the affected side plus central compartment lymph node dissection on the same side). Preoperative ultrasonography revealed that the nodules were predominantly hypoechoic, relatively regular in shape, well-defined, often accompanied by calcifications, and had a longitudinal-to-transverse diameter ratio of <1. TI-RADS classifications were as follows: 5 cases as grade 3, 9 cases as grade 4a, and 11 cases as grade 4b or higher. Among 29 patients who underwent preoperative fine-needle aspiration, 1 case was diagnosed as atypia of undetermined significance/follicular lesion of undetermined significance (AUS/FLUS), 12 as follicular neoplasm/suspicious for follicular neoplasm (FN/SFN), 12 as suspicious for malignancy (SUS), and 4 as PTC. BRAF^V600Emutation testing was performed postoperatively in 25 cases, and 7 mutations were detected, all in cases with concomitant PTC.Conclusion The introduction of the NIFTP concept provides a foundation for de-escalation or individualized treatment of certain less aggressive thyroid tumors. However, the preoperative and intraoperative diagnosis of NIFTP remains challenging in clinical practice. More precise preoperative diagnostic criteria and methods are needed to enable surgeons to adjust treatment decisions accordingly.

4 Characteristics of cytokines and lymphocyte subsets in differentiated thyroid carcinoma patients and their relationship with prognosis

YU Feng , CHEN Liang , WANG Pei

2024, 33(11):1775-1785. DOI: 10.7659/j.issn.1005-6947.2024.11.004

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Background and Aims Differentiated thyroid carcinoma (DTC), comprising papillary thyroid carcinoma (PTC) and follicular thyroid carcinoma (FTC), is the most common type of thyroid cancer. While the majority of DTC patients have a favorable prognosis with standardized treatment, some experience capsular invasion and lymphatic metastasis, leading to poor outcomes. Studies have demonstrated the significant roles of inflammatory and immune factors in tumor progression, but systematic research on their involvement in DTC is lacking. This study aims to analyze the characteristics of cytokines and lymphocyte subsets in DTC patients and their relationships with prognosis.Methods DTC patients treated at the Departments of Thyroid and Breast Surgery of Suzhou Ninth People's Hospital and Ma'anshan 17th Metallurgical Hospital between May 2018 and May 2021 were included, comprising 43 PTC patients and 43 FTC patients. An additional 43 patients diagnosed with benign thyroid nodules (BTN) during the same period served as the control group. The levels of cytokines (TNF-α, IL-1β, IL-2, IL-6, IL-8, IL-10, IL-27) and counts of lymphocyte subsets (T lymphocytes, Ts cells, Th cells, B lymphocytes, NK cells) were compared among the three groups before treatment. The relations of cytokines and lymphocyte subsets with clinicopathologic characteristics in DTC patients were analyzed. Changes in cytokines and lymphocyte subsets in DTC patients after surgery were evaluated, and the predictive value of these factors for treatment outcomes was assessed.Results Comparisons among the groups showed that TNF-α, IL-1β, and IL-6 levels were higher in the PTC and FTC groups than that in the BTN group (all P<0.05), with no significant difference between the PTC and FTC groups (P>0.05); IL-2 and IL-8 levels had no significant differences among the three groups (P>0.05); IL-10 levels were lower in the PTC and FTC groups than that in the BTN group, and lower in the FTC group than that in the PTC group (all P<0.05); IL-27 levels were higher in the PTC and FTC groups than that in the BTN group, with higher levels in the PTC group than that in the FTC group (all P<0.05). No significant differences were observed among the three groups in the counts of T lymphocytes, B lymphocytes, or NK cells (all P>0.05); Ts cell counts were higher in the PTC and FTC groups than that in the BTN group and higher in the FTC group than in that the PTC group (all P<0.05); Th cell counts were lower in the PTC and FTC groups than that in the BTN group (both P<0.05), with no significant difference between the PTC and FTC groups (P>0.05). Analysis of relationships between these differential cytokines and lymphocyte subsets with clinicopathologic features of DTC patients revealed that older patients had higher IL-6 levels, patients in advanced stages had higher Ts cell counts, and those with BRAF mutations had lower IL-10 levels (all P<0.05). Postoperative levels of TNF-α, IL-6, IL-27, and Ts cell count were predictive of treatment outcomes in PTC patients (all P<0.05), with AUC values of 0.754, 0.784, 0.781, and 0.754, respectively. For FTC patients, postoperative IL-8, IL-27, and Ts cell count predicted treatment outcomes (all P<0.05), with AUC values of 0.707, 0.788, and 0.715, respectively. For all DTC patients, postoperative TNF-α, IL-27, and Ts cell count were predictive of treatment outcomes (all P<0.05), with AUC values of 0.742, 0.783, and 0.854, respectively.Conclusion Cytokine levels and lymphocyte subset counts exhibit specific characteristics in DTC patients and may be associated with clinicopathological features. Postoperative levels of certain cytokines and lymphocyte subsets have potential predictive value for treatment outcomes in DTC patients.

5 The application value of BRAF^V600E gene mutation testing in fine-needle aspiration biopsy diagnosed benign thyroid nodules

CAI Wenqing , CUI Can , LIU Jie , CHEN Zhuo , HAN Xinran , WU Ke , LIU Meiqi , WU Jing , LIU Xiaoli

2024, 33(11):1786-1793. DOI: 10.7659/j.issn.1005-6947.2024.11.005

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Background and Aims Fine-needle aspiration cytology (FNA) has limitations due to the small sample size obtained, including nondiagnostic specimens, indeterminate cytological results, and false-negative or false-positive results, potentially leading to misdiagnosis or missed diagnoses. The BRAF gene mutation, specifically BRAF^V600E, is a specific biomarker for papillary thyroid carcinoma (PTC). However, studies on its diagnostic value in FNA benign high-risk thyroid nodules are limited. This study was conducted to further explore the clinical value of adding BRAF^V600Emutation testing in FNA benign thyroid nodules.Methods A retrospective analysis was conducted on the clinical data of 549 patients who underwent 668 ultrasound evaluations indicating high risk of PTC and were classified as TIRADS categories 4-5 thyroid nodules at the Thyroid Surgery Department of China-Japan Union Hospital of Jilin University from January 2019 to September 2022. All patients underwent surgical treatment, and paraffin pathological examination was performed on resected tissues after surgery. Based on inclusion and exclusion criteria, 84 FNA benign thyroid nodules were included in this study. The clinicopathologic characteristics of nodules with BRAF^V600E mutations were analyzed. Using postoperative pathology as the gold standard, the diagnostic performance of BRAF^V600E mutation testing in FNA benign nodules was assessed.Results Among the 84 FNA benign thyroid nodules, 44 (52.4%) tested positive for the BRAF^V600E mutation. Patients with BRAF^V600E-positive nodules were more likely to be younger than 45 years (56.8% vs. 35.0%, P=0.045), and their nodules had a smaller median long diameter compared to the BRAF^V600E-negative group (0.49 cm vs. 0.61 cm, P=0.024). Postoperative pathology revealed 63 PTC nodules and 21 benign nodules. PTC nodules had a smaller median long diameter than benign nodules (0.50 cm vs. 0.70 cm, P=0.004) and a higher proportion of nodules <1 cm (95.2% vs. 71.4%, P=0.007), with a higher BRAF^V600E mutation rate (68.3% vs. 4.8%, P<0.001). In terms of the ultrasound characteristics of thyroid nodules, BRAF^V600E-positive nodules showed a significantly higher rate of blurred/irregular margins than the negative group (86.4% vs. 60.0%, P=0.006). Similarly, PTC nodules showed a higher rate of blurred/irregular margins compared to benign nodules (81.0% vs. 52.4%, P=0.010). Multivariate Logistic regression analysis indicated that BRAF^V600E-positive thyroid nodules had a 39.184-fold higher risk of being diagnosed as PTC compared to BRAF^V600E-negative nodules (P=0.001), with BRAF^V600E mutation being an independent risk factor for PTC diagnosis. The sensitivity, specificity, positive predictive value, negative predictive value, and accuracy of BRAF^V600E mutation testing for PTC diagnosis were 69.3%, 95.2%, 97.7%, 50.0%, and 75.0%, respectively.Conclusion BRAF^V600E mutation testing demonstrates high positive predictive value and accuracy, and can reduce the risk of missed PTC diagnoses among FNA-reported benign thyroid nodules. It is recommended that thyroid nodules with highly suspicious ultrasound features and TIRADS categories 4-5 undergo combined FNA and BRAF^V600E mutation testing.

6 Anatomy and localization of the recurrent laryngeal nerve using the middle cervical fascia as a landmark

PENG Yang , JIANG Linshan , LONG Zhimin , LIU Shengchun , CAI Ming

2024, 33(11):1794-1802. DOI: 10.7659/j.issn.1005-6947.2024.11.006

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Background and Aims The success of thyroid surgery largely depends on an accurate understanding and proper handling of cervical anatomical structures. As a key anatomical landmark, the middle cervical fascia plays a critical role in thyroid lobe resection and precise identification of the recurrent laryngeal nerve (RLN) during thyroid surgery. However, existing anatomical literature provides limited descriptions of the middle cervical fascia and surrounding spaces. This study was performed to explore the anatomical characteristics of the middle cervical fascia and its adjacent spaces in detail, providing more accurate anatomical evidence and practical guidance to improve the safety and efficacy of thyroid surgery.Methods First, systematic anatomical studies were conducted on formalin-fixed cadaveric specimens. During the dissections, the structural features of the middle cervical fascia and its surrounding spaces were meticulously recorded, with special attention to its relationships with the thyroid gland, common carotid artery, and infrahyoid muscles. Second, real-time observations and records were made during thyroid surgery on patients with thyroid cancer. The appearance of the middle cervical fascia and changes in related anatomical structures were documented during surgery.Results Both cadaveric dissections and intraoperative observations revealed that the middle cervical fascia is closely attached to the thyroid gland medially, while laterally it extends across the surface of the common carotid artery to the infrahyoid muscles. When the fascial plane was incised, important structures such as adipose tissue, lymph nodes, RLN, middle thyroid vein, inferior thyroid artery, and inferior thyroid vein were clearly observed. Additionally, it was found that the RLN is enveloped by a thin layer of fascia and adipose tissue. Intraoperative findings showed that RLN exposure techniques based on the middle cervical fascia significantly facilitated RLN identification and improved surgical efficacy.Conclusion The middle cervical fascia is a key supportive structure on the thyroid surface and an independent fascial plane critical for tissue dissection and precise RLN exposure during thyroid surgery. A deeper understanding of the anatomy of the middle cervical fascia and its surrounding spaces is essential for ensuring the safety and effectiveness of thyroid surgery.

7 Medial versus lateral approach for recurrent laryngeal nerve exposure in anterior chest approach endoscopic radical thyroidectomy

ZHOU Zhenhua , SUN Ke , CHEN Jia , CHEN Jian , LI Qing , XU Shaozhong , JIANG Ximin , ZHOU Yong , LIU Xiping

2024, 33(11):1803-1812. DOI: 10.7659/j.issn.1005-6947.2024.11.007

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Background and Aims Recurrent laryngeal nerve (RLN) injury during endoscopic thyroid cancer radical surgery significantly affects postoperative recovery and quality of life. Avoiding RLN injury has always been a key concern during thyroid surgeries. Choosing an appropriate and safe approach to expose the RLN in endoscopic thyroid cancer surgery may reduce the risk of RLN injury. However, the optimal approach for RLN exposure in endoscopic thyroid cancer radical surgery through the anterior chest approach remains inconclusive. This study was performed to compare the surgical outcomes of using the medial and lateral approaches to expose the RLN in endoscopic thyroid cancer surgery through the anterior chest approach, so as to provide reference for clinical practice.Methods The clinical data of 85 patients who underwent endoscopic thyroid cancer radical surgery (ipsilateral lobectomy and ipsilateral central lymph node dissection) via the anterior chest approach at Zhuzhou Hospital Affiliated to Xiangya Medical College, Central South University, from January 2020 to January 2023 were retrospectively analyzed. Among the patients, medial approach was used in 45 cases (medial approach group) and lateral approach was used for RLN exposure in 40 cases (lateral approach group). The main clinical variables were compared between the two groups.Results No statistically significant differences were found in baseline data between the two groups (all P>0.05). Both groups successfully completed endoscopic thyroidectomy via the anterior chest approach with complete RLN exposure at the main trunk and its entry into the larynx. The RLN exposure time and endoscopic surgery time in the medial approach group were significantly shorter than those in the lateral approach group (both P<0.05). Intraoperative blood loss was significantly less in the medial approach group compared to the lateral approach group (P<0.05). There were no cases of transient RLN injury in the medial approach group, whereas 5 cases of transient RLN injury occurred in the lateral approach group, with a statistically significant difference (P<0.05). The medial approach group had fewer cases of thyroid tissue residue at the Berry's ligament and transient hypoparathyroidism than the lateral approach group, but the differences were not statistically significant (both P>0.05). There were no statistically significant differences between the two groups in postoperative hospital stay or postoperative drainage volume (both P>0.05).Conclusion The medial approach for RLN exposure in endoscopic thyroid cancer surgery is safe and feasible. Compared to the lateral approach, it allows faster RLN exposure, effectively reduces the risk of transient RLN injury, decreases intraoperative blood loss and operative time, and may also reduce the incidence of transient hypoparathyroidism and thyroid tissue residue to some extent.

8 Analysis of association between papillary thyroid carcinoma and negative emotions

WANG Liuhuan , LI Sirui , ZENG Liqin , XIA Chen , LU Yunxia

2024, 33(11):1813-1824. DOI: 10.7659/j.issn.1005-6947.2024.11.008

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Background and Aims Papillary thyroid carcinoma (PTC) generally has a good prognosis, leading to relatively limited research on the psychological status of PTC patients. However, animal studies have shown that PTC is associated with negative emotions, which may adversely affect the prognosis of the disease. Therefore, this study was performed to explore the relationship between PTC and negative emotions, focusing on anxiety and depression, to understand their association and provide information for clinical practice and research.Methods Patients diagnosed with PTC after surgery in the Department of Thyroid Surgery at the Second Affiliated Hospital of Nanchang University from June 2021 to April 2022 were selected as the observation group. Healthy volunteers without a history of thyroid disease or thyroid surgery during the same period were selected as the control group. The emotional status of the subjects in the past year was assessed using a general questionnaire, the self-rating anxiety scale (SAS), and the self-rating depression scale (SDS). Multivariable Logistic regression was used to analyze the connection of anxiety and depression to the risk of developing PTC.Results Comparing the four components of SAS, there was no significant difference in the motor tension scores between the observation group and the control group (P=0.496). However, the observation group had significantly higher scores in psychological emotions, neurofunctional disorders, somatic symptoms, and the total SAS score compared to the control group (all P<0.05). Comparing the four components of SDS, there were no significant differences in psychological emotions and psychomotor scores between the two groups (both P>0.05). However, the observation group had significantly higher scores in somatic disorders, psychological disorders, and the total SDS score compared to the control group (all P<0.05). Multivariable Logistic regression analysis of the 20 items of SAS showed that anxiety, panic, insanity, tremors, somatic pain, numbness in hands and feet, palpitations, nightmares, and sleep disturbances were associated with the risk of PTC. Multivariable Logistic regression analysis of the 20 items of SDS indicated that somatic and psychological disorder scores were related to the risk of PTC.Conclusion Negative emotions are associated with the occurrence and development of PTC, and there may be mutual influences between them. Therefore, attention should be given to the psychological well-being of both healthy individuals and PTC patients. The mechanisms underlying the association between negative emotions and PTC require further exploration.

9 Gender- and age-related differential genes and pathways in cervical lymph node metastasis of papillary thyroid carcinoma

CHU Bingfeng , HU Yingjun

2024, 33(11):1825-1834. DOI: 10.7659/j.issn.1005-6947.2024.11.009

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Background and Aims Thyroid cancer is the most common malignant tumor of the endocrine system, with papillary thyroid carcinoma (PTC) being the predominant subtype. PTC mainly metastasizes via cervical lymph nodes. Clinical observations and some studies have indicated that young male PTC patients are more prone to cervical lymph node metastasis. This study aims to analyze the risk factors for cervical lymph node metastasis and explore the differentially expressed genes and associated signaling pathways in PTC patients across different genders and age groups.Methods The clinical data of PTC patients who underwent surgical treatment at the Department of General Surgery, Xinhua Hospital, Shanghai Jiao Tong University School of Medicine, and the Huangpu Branch of Shanghai Ninth People's Hospital, Shanghai Jiao Tong University School of Medicine, from January 2015 to October 2018 were collected. Risk factors for cervical lymph node metastasis were analyzed. The TCGA database was used to identify differentially expressed genes and related pathways in male and ≤45-year-old PTC patients compared to their female and >45-year-old counterparts, respectively. Functional validation of selected differentially expressed genes was performed in cellular studies.Results A total of 1 071 PTC patients were included, of whom 209 (19.5%) had cervical lymph node metastasis. Univariate analysis showed that male patients had a higher rate of cervical lymph node metastasis than female patients (χ²=5.990, P<0.05), and patients ≤45 years old had a higher metastasis rate than those >45 years old (χ²=28.969, P<0.05). Multivariate analysis identified male gender and age ≤45 years as independent risk factors for cervical lymph node metastasis (both P< 0.05). A total of 443 and 477 differentially expressed genes were identified in male and ≤45-year-old PTC patients, respectively, using the TCGA database. GO analysis revealed that the differentially expressed genes in these patients were primarily enriched in immune-related biological processes, such as complement activation via the classical pathway and immunoglobulin-mediated humoral immune response. KEGG pathway analysis indicated that these differentially expressed genes were associated with metabolic pathways, including pancreatic secretion, thyroid hormone synthesis, and fat digestion and absorption. Based on fold-change and pathway analysis, IGF2 and IGF2BP1 were selected for functional validation. Knockdown of IGF2 and IGF2BP1 significantly reduced the migration ability of thyroid cancer cell lines BCPAP and KTC-1 (both P< 0.05).Conclusion Male gender and age ≤45 years are independent risk factors for cervical lymph node metastasis in PTC. The underlying mechanisms may involve multiple immune-related or endocrine metabolism-associated signaling pathways, highlighting the need for more rigorous examination and management of cervical lymph nodes in young male patients. Further research on IGF2 and IGF2BP1 may provide new therapeutic targets for thyroid cancer and cervical lymph node metastasis.

10 Impact of PIM1 overexpression on the metabolomics of papillary thyroid carcinoma cells and its significance

WANG Jiaqi , XU Qianqian , TANG Xi , ZHU Xin

2024, 33(11):1835-1845. DOI: 10.7659/j.issn.1005-6947.2024.11.010

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Background and Aims The oncogene PIM1, encoding a constitutively active serine/threonine kinase, is upregulated in various tumors and closely associated with tumorigenesis and progression. Our previous studies have confirmed the oncogenic role of PIM1 in thyroid cancer, demonstrating its impact on tumor development, progression, and prognosis. This study was conducted to investigate the metabolic characteristics of papillary thyroid carcinoma (PTC) cells overexpressing PIM1 using metabolomics analysis, providing a basis for further exploring how PIM1 regulates metabolic processes in PTC.Methods A PIM1 overexpression plasmid was constructed, and a stably transfected PTC cell line (BCPAP) was established. The overexpression of PIM1 was verified by qRT-PCR and Western blot. Metabolomics analysis of PIM1-overexpressing BCPAP cells (PIM1-OE) and control cells transfected with an empty vector (NC) was performed using liquid chromatography-mass spectrometry (LC-MS). Differential metabolites and metabolic pathways were identified and screened through multivariate statistical analysis and the KEGG database. Bioinformatics analysis was conducted to explore the relationship between PIM1, associated metabolic pathways, and the prognosis of thyroid cancer patients.Results The mRNA and protein levels of PIM1 were significantly upregulated in the PIM1-OE BCPAP cells (both P<0.05). Metabolomics analysis identified changes in 41 intracellular metabolites in PIM1-OE cells, with 15 metabolites showing significant differences, including L-aspartic acid, succinic acid, L-threonine, L-tryptophan, betaine, 2-dehydropantothenate, 3-indoleacetonitrile, D-octopine, indole, N-acetylglutamic acid, creatine, pantothenic acid, uremic acid, N-acetyl-L-aspartic acid, and hydroxyphosphono-pyruvic acid (all P<0.05). KEGG database analysis revealed significant alterations in 31 metabolic pathways, with 4 pathways—alanine, aspartate and glutamate metabolism; tryptophan metabolism; glycine, serine, and threonine metabolism; and arginine and proline metabolism—being notably affected, showing decreased activity (all P<0.05). Bioinformatics analysis indicated that high PIM1 expression and reduced activity in the glycine, serine, and threonine metabolic pathways were associated with significantly decreased overall survival in thyroid cancer patients (both P<0.05).Conclusion PIM1 may influence multiple metabolic pathways by regulating the levels of various amino acids, including aspartic acid, succinic acid, and tryptophan, thereby altering the metabolic state of PTC and promoting its development and progression. Among these, changes in the glycine, serine, and threonine metabolic pathways may be closely associated with patient prognosis.

11 Risk factor for plasma cell mastitis and construction of a nomogram prediction model

MA Xiaowen , ZHANG Feng , SUN Yiming

2024, 33(11):1846-1853. DOI: 10.7659/j.issn.1005-6947.2024.11.011

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Background and Aims The risk factors for plasma cell mastitis (PCM) remain unclear. The disease is characterized by acute onset, rapid progression, prolonged course, lack of specific drugs, and high recurrence rates despite current clinical treatments using both Western and traditional Chinese medicine. Identifying and minimizing the risk factors for PCM to achieve early prevention has become a critical focus. This study investigated the risk factors associated with PCM and established a nomogram prediction model to estimate the probability of PCM occurrence in at-risk populations, providing guidance for disease prevention.Methods The clinical data from 82 PCM patients (study group) treated in the Breast Surgery Department of Hangzhou Obstetrics and Gynecology Hospital between January 2019 and January 2022 were retrospectively collected. Additionally, 82 middle-aged and young women who underwent health check-ups during the same period and had no breast diseases were randomly selected as the control group. Univariate and multivariate Logistic regression analyses were used to identify risk factors for PCM. A nomogram model predicting PCM risk was developed, and the receiver operating characteristic (ROC) curve, calibration curve, and concordance index (C-index) were used to evaluate its predictive performance.Results All patients in the study group had a history of abortion and/or childbirth, with a postpartum/post-abortion onset interval ranging from 1 to 7 years, averaging (3.37±1.91) years. Univariate analysis revealed significant differences between the two groups in body mass index, proportion of nipple retraction, number of pregnancies, history of trauma (including massage or lactation promotion), and lipid levels (all P<0.05). Multivariate Logistic regression analysis identified nipple retraction (OR=0.074, 95% CI=0.023-0.239, P=0.000), ≥3 pregnancies (OR=0.047, 95% CI=0.008-0.288, P=0.001), and history of trauma (OR=0.153, 95% CI=0.059-0.399, P=0.000) as independent risk factors for PCM. The nomogram model constructed based on these factors demonstrated a C-index of 0.855, indicating moderate accuracy. The calibration curve, generated using the "Boot" method, showed good agreement with the ideal curve. The area under the ROC curve was 0.855 (95% CI=0.800-0.910).Conclusion Nipple retraction, history of trauma, and the number of pregnancies are closely associated with PCM occurrence. The established nomogram prediction model exhibits moderate accuracy and good performance. It can be used clinically to predict the risk of PCM in women during high-incidence periods. It provides a quantitative estimation of disease probability, which can serve as a basis for offering targeted prevention recommendations to high-risk individuals.

12 Network pharmacology and bioinformatics analysis of the mechanism of kaempferol in the treatment of breast cancer and construction of a mechanism-related prognostic model

XIAO Meiling , YI Jia'ning , YANG Xiaochen , YU Jie , HUANG Ting , ZENG Jie

2024, 33(11):1854-1865. DOI: 10.7659/j.issn.1005-6947.2024.11.012

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Background and Aims Kaempferol is a natural flavonoid compound that can regulate various processes and activities associated with cancer, such as the cell cycle, oxidative stress, apoptosis, proliferation, metastasis, and angiogenesis. Its potential for treating breast cancer has been validated in some studies, but its mechanism of action remains unclear. Therefore, this study was conducted to explore the potential targets and pathways of kaempferol in the treatment of breast cancer and establish a prognostic model.Methods Using network pharmacology and bioinformatics approaches, the intersection targets of kaempferol for the treatment of breast cancer were obtained from databases such as HERB, GeneCards, STRING, PubChem, RCSB PDB, and TCGA. Protein interaction, GO analysis, and KEGG pathway enrichment analysis were performed, followed by molecular docking for validation. Prognostic-related genes were identified through LASSO-Cox regression analysis to establish a risk score model. The prognostic analysis for each gene, and the correlation between risk score and immune infiltration were analyzed.Results Network pharmacology analysis identified 55 intersection targets. Protein interaction analysis revealed five potential key genes (Akt1, Bcl2, CASP3, ESR1, AR). GO analysis showed that kaempferol treatment of breast cancer involved 1 604 biological process entries, 20 cellular component entries, and 121 molecular function entries. KEGG pathway enrichment mainly included pathways related to chemical carcinogenesis, reactive oxygen species signaling, AGE-RAGE signaling in diabetic complications, TNF signaling, and IL-17 signaling. Molecular docking results indicated that kaempferol had a strong affinity for key targets, with the best binding effect observed with ESR1 (-9.1 kcal/mol). Ten prognostic genes (Bcl2, CYP1B1, DPP4, GSTM1, GSTM2, MMP1, NCOA2, NOS2, NR1I3, PTGS2) were obtained through LASSO-Cox regression analysis, and a risk score model was established. The AUC of this model for predicting breast cancer patient prognosis was greater than 0.5. Single-gene survival analysis indicated that higher expression of Bcl2 (HR=0.61, 95% CI=0.43-0.86, P=0.005), CYP1B1 (HR=0.68, 95% CI=0.49-0.94, P=0.022), GSTM1 (HR=0.68, 95% CI=0.47-0.98, P=0.037), GSTM2 (HR=0.64, 95% CI=0.46-0.90, P=0.010), and PTGS2 (HR=0.62, 95% CI=0.44-0.86, P=0.005) correlated with a higher overall survival (OS), while higher expression of MMP1 (HR=1.72, 95% CI=1.22-2.41, P=0.002), NCOA2 (HR=1.71, 95% CI=1.12-2.60, P=0.013), NOS2 (HR=1.67, 95% CI=1.20-2.32, P=0.002), and NR1I3 (HR=1.69, 95% CI=1.21-2.37, P=0.002) was associated with worse OS. The risk score was negatively correlated with the infiltration of T cells, CD8⁺ T cells, myeloid dendritic cells, NK cells, and B cells, and positively correlated with monocyte/macrophage infiltration (all P<0.05).Conclusion Kaempferol exerts therapeutic effects on breast cancer through multiple targets and pathways. The prognostic genes identified based on its related targets, along with the established prognostic model, can guide clinical treatment of breast cancer. The correlation between the prognostic model and immune infiltration provides direction for future experimental studies.

13 Multidisciplinary treatment of locally advanced thyroid cancer: a case report

FU Yantao , WU Guangzhi , LIU Yanxi , ZHANG Daqi , LI Jingting

2024, 33(11):1866-1873. DOI: 10.7659/j.issn.1005-6947.2024.11.013

[Abstract](12) [HTML](6) [PDF 1.49 M](179)

Abstract:
Differentiated thyroid carcinoma (DTC) is the most common endocrine tumor, characterized by high incidence, low recurrence rate, and low mortality. Locally advanced thyroid cancer (LATC) is rare in clinical practice, with poor prognosis, and is one of the leading causes of death among thyroid cancer patients. In August 2024, the Thyroid Surgery Department of China-Japan Union Hospital of Jilin University admitted a 61-year-old male patient with a history of "neck mass surgery 16 years ago and progressive enlargement with ulceration of the mass over the past 3 months." Physical examination revealed an irregularly shaped mass measuring approximately 12 cm × 12 cm in the left supraclavicular fossa, with a dark red surface, ulceration, bleeding, and necrotic exudate in some areas. After admission, a multidisciplinary team (MDT) consultation was initiated, and the patient underwent his fifth surgery, which included resection of the left cervical mass, left cervical lymphadenectomy, resection of a submental mass, and free flap transplantation. The patient was discharged on postoperative day 10 in good condition. One month after surgery, a follow-up ultrasound at our hospital showed no significant abnormalities in the neck, with good healing of the local skin and survival of the transplanted flap. This article reviews the MDT treatment process of this LATC case and summarizes the characteristics of LATC based on domestic and international literature, providing experience and references for the comprehensive treatment of this disease.

14 Applications of medical imaging artificial intelligence in the diagnosis and treatment of thyroid cancer: current status and future prospects

LIU Caiguang , MO Qu , XIAO Yi , ZHAO Min

2024, 33(11):1874-1882. DOI: 10.7659/j.issn.1005-6947.2024.11.014

[Abstract](10) [HTML](4) [PDF 684.97 K](98)

Abstract:
Thyroid cancer is the most common malignant tumor of the endocrine system, and its incidence has been steadily increasing in recent years. Papillary thyroid carcinoma (PTC) and follicular thyroid carcinoma (FTC), collectively known as differentiated thyroid cancer (DTC), account for approximately 95% of thyroid cancer cases. Imaging examinations such as ultrasound, computed tomography (CT), magnetic resonance imaging (MRI), single-photon emission computed tomography (SPECT/CT), and positron emission tomography (PET/CT) play a critical role in the diagnosis, staging, risk stratification, and treatment of DTC. However, the analysis of imaging results heavily depends on the skills and experience of the physician, making the interpretation prone to errors due to factors such as image volume, complexity, and subjective judgment, particularly under high workloads. Additionally, objective factors like equipment resolution and the limitations of human vision can also affect diagnostic accuracy. Artificial intelligence (AI), a technology that simulates, extends, and enhances human intelligence, has gradually been applied in the medical field. In the diagnosis and treatment of DTC, AI technologies such as machine learning and deep learning, as well as radiomics, have been utilized. These technologies are primarily applied in the diagnosis and differential diagnosis of DTC, staging assessments, prediction of genetic mutations, and iodine-131 therapy for DTC. The application of AI and radiomics holds great promise for improving diagnostic accuracy, enabling precise staging, predicting genetic mutations with higher precision, and optimizing treatment strategies for DTC. This advancement is expected to facilitate accurate diagnosis and personalized treatment, maximizing benefits for patients.

15 Role of m⁶A methylation modification in the occurrence and development of thyroid cancer: a review of research progress

TIAN Hongyou , CHENG Lu , REN Yan , GUO Jinyi , MA Jiaxiang , SONG Ailin

2024, 33(11):1883-1889. DOI: 10.7659/j.issn.1005-6947.2024.11.015

[Abstract](14) [HTML](4) [PDF 645.02 K](134)

Abstract:
Thyroid cancer (TC) is the most common endocrine malignancy. Although most patients have a favorable prognosis following standardized treatment, a subset experiences rapid disease progression and poor outcomes. Recent studies have identified N6-methyladenosine (m⁶A) methylation as the most prevalent RNA modification, which regulates RNA transcription, maturation, degradation, and stability, playing a role throughout the tumorigenesis process. Consequently, m⁶A methylation has been extensively studied in tumor treatment and prevention. Changes in m⁶A levels can lead to abnormal activation or inhibition of oncogenes or tumor suppressor genes in TC, thereby contributing to its initiation and progression. This review summarizes the concept of m⁶A methylation, the components and functions of its regulatory factors, its role in the development and progression of TC, and its implications for treatment and prognosis.

16 "De-escalation" strategy in axillary management of early breast cancer: current status and progress

SHAO Xinyu , PENG Shuai , LIAO Liqiu

2024, 33(11):1890-1896. DOI: 10.7659/j.issn.1005-6947.2024.11.016

[Abstract](5) [HTML](4) [PDF 629.15 K](111)

Abstract:
The assessment of axillary lymph node metastasis in early-stage breast cancer is crucial for disease staging, adjuvant treatment decision-making, regional control, and prognosis estimation. However, the approach to axillary management has shown a "de-escalation" trend. For clinically node-negative (cN0) early-stage breast cancer, sentinel lymph node biopsy (SLNB) has replaced axillary lymph node dissection (ALND) as the standard procedure for axillary staging. If sentinel lymph nodes are negative, patients can forgo ALND. Even in cases of low-burden sentinel lymph node metastasis, ALND may be omitted with effective systemic therapy and regional radiotherapy. Some cN0 early-stage breast cancer patients may qualify to avoid axillary surgery altogether, but patient selection requires greater precision. For patients with clinically node-positive (cN1) early-stage breast cancer, neoadjuvant therapy can downstage them to cN0, allowing SLNB to replace ALND. Preliminary data on false negatives and safety are available, but many issues with SLNB post-neoadjuvant therapy remain unresolved, requiring further clinical research. In the future, with the advancement and application of functional imaging and predictive models, assessments of oncologic characteristics, metastatic burden, and treatment response in early-stage breast cancer will become more accurate. Axillary management for early-stage breast cancer will become more precise, and de-escalation will be safer.

17 Estrogen metabolism and postmenopausal breast cancer: clinical research progress

ZHANG Yanshou , YANG Zhifen , ZHENG Lihua , LIU Yunjiang

2024, 33(11):1897-1903. DOI: 10.7659/j.issn.1005-6947.2024.11.017

[Abstract](6) [HTML](4) [PDF 639.05 K](126)

Abstract:
Endogenous estrogen is currently considered a major risk factor for postmenopausal breast cancer. Under the catalysis of various enzymes, estrogen interacts through multiple metabolic pathways to produce various metabolites. The imbalance of estrogen and its metabolites in the body can induce physiological changes that may play a dual role in the development of breast cancer. However, due to the relatively low estrogen levels in postmenopausal women and the limitations of existing measurement methods in terms of specificity, accuracy, and reproducibility, the precise role of different estrogen metabolic pathways and their metabolites in the etiology of postmenopausal breast cancer remains unclear. Therefore, a deeper understanding of the estrogen metabolism pathways and their metabolites in the occurrence and progression of postmenopausal breast cancer may provide new insights for its prevention and treatment. Here, the authors review recent research progress on estrogen metabolism and postmenopausal breast cancer.

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Volume 33,Issue 11,2024 Table of Contents

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