Volume 30,Issue 5,2021 Table of Contents

1 Chinese expert consensus on thyroid day surgery (2021 Edition)

Chinese Association of Thyroid Oncology , Chinese Association of Head , Neck Oncology , Chinese Research Hospital Association Thyroid Disease Committee

2021, 30(5):499-509. DOI: 10.7659/j.issn.1005-6947.2021.05.001

[Abstract](945) [HTML](1629) [PDF 697.63 K](1147)

Abstract:
With over 60 years of development, day surgery (ambulatory surgery), for its efficiency, safety and economic benefits, has been widely carried out in countries with advanced medical technologies such as many European countries and the United States. However, the starting time of day surgery in China is relatively late, and there are few grade-A tertiary hospitals that are performing thyroid day surgery at present. As a result of the increasingly intensive use of the concept of enhanced recovery after surgery (ERAS) in all surgical fields in recent years, ERAS protocols have also been incorporated into the thyroid surgery practice, with remarkable results achieved. Furthermore, the application of various novel techniques in thyroid surgery also improves the surgical safety and reduces the incidence of postoperative complications. Among the total of 56 surgical procedures selected by the first recommendation of the Chinese Ambulatory Surgery Alliance (CASA), 4 types are thyroid procedures. Although there are still some controversies and difficulties in promoting thyroid day surgery in China caused by many factors, it is being gradually recognized and accepted by both the medical practitioners and patient parties, together with a great deal of valuable experience accumulated. Therefore, relevant domestic experts from the Chinese Association of Thyroid Oncology and the Chinese Association of Head and Neck Oncology as well as Chinese Research Hospital Association Thyroid Disease Committee jointly developed the Chinese expert consensus on thyroid day surgery (2021 Edition) after detailed discussions both online and offline, striving for perfection and reaching a general agreement.

2 Advances in treatment of triple-negative breast cancer

WU Songyang , JIANG Yizhou , SHAO Zhimin

2021, 30(5):510-521. DOI: 10.7659/j.issn.1005-6947.2021.05.002

[Abstract](351) [HTML](1357) [PDF 584.22 K](1191)

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Triple-negative breast cancer (TNBC) is the most malignant subtype of breast cancer with highly aggressive and heterogenous nature and a tendency towards early recurrence and metastasis. At present, chemotherapy remains the standard treatment of TNBC. However, with the rapid development of omics technologies and the increasing deepening of understanding towards the molecular biologic features of TNBC, researchers found that it is possible to classify TNBC into several subtypes, and to perform tailored treatment strategies based on the specific characteristics of its subtypes, and meanwhile to develop target drugs through discovering the novel therapeutic targets based on both intrinsic signals and extrinsic microenvironment of the cancer cells, and finally to add them into standard regimen after translational clinical trials. Targeted therapies based on molecular subtypes may become the future direction of precision treatment for TNBC.

3 Analysis of learning curve of complete endoscopic radical thyroidectomy via a gasless axillary approach

HUANG Hai , CHEN Xinxin , MA Yuyuan , QIAN Weifeng

2021, 30(5):522-530. DOI: 10.7659/j.issn.1005-6947.2021.05.003

[Abstract](489) [HTML](1000) [PDF 984.13 K](1005)

Abstract:
Background and Aims: Thyroid cancer is a common malignant tumor in clinical practice, for which surgery is the main treatment method. Endoscopic radical thyroidectomy via a gasless axillary approach is a feasible, safe and cosmetic surgical option, and is being increasingly carried out in our country. The purpose of this study was to investigate the learning curve of endoscopic radical thyroidectomy via a gasless axillary approach, and summarize the course of familiarizing and mastering this new procedure for surgeons, so as to provide a reference for the promotion and development of this procedure.
Methods: The clinical data of 40 patients with thyroid cancer undergoing total endoscopic radical thyroidectomy via a gasless axillary approach consecutively admitted from January 2019 to June 2020 were retrospectively analyzed. The changing trend graph of operative time and the CUSUM learning curve were modeled and analyzed, and the cut-off value of the learning curve was identified. Taking the cut-off value of the CUSUM learning curve as the threshold, the learning curve was divided into two stages, and then the general information and relevant clinical variables of patients in the two stages were compared.
Results: In the 40 patients, the operative time ranged from 65 to 150 min, with an average operative time of (107.50±26.38) min. The changing trend graph of operative time demonstrated that the operative time displayed an overall descending trend as the number of cases of operation increased. The fitting CUSUM curve reached a maximum value at the cumulative number of cases of operation up to 22. Taking the 22nd operated patient as the demarcation, the learning curve was divided into learning improvement stage and proficient mastery stage. There were no significant differences in terms of the general data between patients in learning improvement stage group (22 cases) and proficient mastery stage group (18 cases) (all P>0.05). The operative time of learning improvement stage group was significantly longer than that in proficient mastery stage group (129.09 min vs. 81.11 min, P<0.001). There were no significant differences with regard to the intraoperative blood loss, postoperative incision pain score, length of postoperative hospital stay and incidence of postoperative complications between the two groups (all P>0.05).
Conclusion: There is a significant learning curve for learning total endoscopic radical thyroidectomy via a gasless axillary approach. Mastering this procedure requires the accumulation of at least 22 operations. It is hoped that the results of this study can provide certain theoretical basis and help for general surgeons to uneventfully go through the plateau of the learning curve (transition from the learning improvement stage to the proficient mastery stage), and then familiarize and master this procedure.

4 Using medial approach to recurrent laryngeal nerve during endoscopic thyroid lobectomy

ZHOU Zhenhua , LIU Xiping , YE Liang , SUN Ke , CHEN Jian , ZHOU Yong , JIANG Ximin , LI Zhidong , XU Shaozhong

2021, 30(5):531-536. DOI: 10.7659/j.issn.1005-6947.2021.05.004

[Abstract](445) [HTML](1070) [PDF 2.49 M](907)

Abstract:
Background and Aims: How to effectively expose and protect the recurrent laryngeal nerve (RLN) during endoscopic thyroid surgery, has always been a difficult and unavoidable part of this procedure. The conventional approaches to the RLN are usually divided into lateral, inferior, and superior approaches. Here, the authors introduce a medial approach to RLN during endoscopic thyroidectomy, and summarize its effects, so as to provide reference for surgeons in the same field.
Methods: The clinical and video data of 83 patients with papillary thyroid carcinoma undergoing endoscopic total thyroid lobectomy via the trans-thoracoareolar approach from January 2019 to November 2020 were retrospectively analyzed. Medial approach to the RLN was adopted in all patients during operation, namely, firstly to separate the loose parts of the ligament of Berry up to the tracheothyroid groove, to find the main trunk of the RLN and secondly, along the superficial surface of the RLN toward the superior direction, to cut the compact parts of the ligament of Berry from superficial to deep, to fully expose the main trunk of the RLN and the insertion point of the RLN into the larynx. The RLN exposure effect and the postoperative recovery of the patients were observed.
Results: The endoscopic procedures were successfully completed in all the 83 patients. A total of 130 RLNs were exposed, and the exposure rate was 100%, with complete exposure of the main trunk of the RLN and the insertion point of the RLN into the larynx in all cases. The time for unilateral RLN exposure was 4.2–15.6 min, with an average of 8.9 min. The intraoperative blood loss was 2–15 mL, with an average of 5.3 mL. After operation, transient RLN injury occurred in 3 patients (0.36%), and no permanent RLN injury was found in all patients.
Conclusion: In endoscopic thyroid surgery, using the medial approach can safely, efficiently and easily expose the whole course of the RLN, and reduce the incidence rates of RLN injuries. So, this approach is recommended to be used in clinical practice.

5 Analysis of risk factors and predictive variables for lateral cervical lymph node metastasis in papillary thyroid microcarcinoma

KONG Lingxin , WANG Zhaohua , YIN Wenbin , LI Huizheng ,

2021, 30(5):537-542. DOI: 10.7659/j.issn.1005-6947.2021.05.005

[Abstract](160) [HTML](1254) [PDF 459.67 K](979)

Abstract:
Background and Aims: The incidence of papillary thyroid microcarcinoma (PTMC) has been increasing over the past years, and the presence of lateral lymph node metastasis (LLNM) will affect the survival rates of patients. The purpose of this study was to investigate the risk factors and predictive variables for the occurrence of LLNM in PTMC, so as to provide reference for clinical diagnosis and treatment.
Methods: The clinical data of PTMC patients treated in Dalian Friendship Hospital from January 2015 to June 2020 were retrospectively analyzed. Except for the occurrence of LLNM, the clinical variables observed included sex, age, and the number, size, and location of tumor, as well as the affected glandular lobes, body mass index, and the presence or absence of thyroid capsule invasion, other concomitant thyroid diseases (Hashimoto's thyroiditis, nodular goiter), and combined central lymph node metastasis (CLNM).
Results: A total of 342 PTMC patients were enrolled, of whom, LLNM occurred in 33 cases (9.6%), CLNM occurred in 142 cases (41.5%), and 25 cases (7.3%) had both CLNM and LLNM. Of the 33 patients with LLNM, 8 cases (24.2%) had no CLNM. Univariate analysis showed that patients with male sex, tumor diameter ≥5 mm, capsule invasion and CLNM were more likely to develop LLNM (all P<0.05). Multivariate analysis showed that the number of CLNM was an independent risk factor for LLNM (OR=1.195, P<0.05). ROC analysis showed that the AUC of CLNM number for estimating LLNM was 0.621, and the cut-off value was 4.5, with a specificity of 0.897 and sensitivity of 0.103.
Conclusion: The number of CLNM is closely related to the LLNM in PTMC patients, which can provide certain quantitative reference for therapeutic lateral lymph node dissection.

6 Same-day skin-sparing mastectomy surgery with immediate prosthetic breast reconstruction for breast cancer: West China Hospital experience

FENG Yu , XIE Yanyan , LIANG Faqing , WEN Nan , ZHOU Jiao , ZHANG Songbo , LIU Xinran , HUANG Yixuan , QIU Mengxue , YANG Huanzuo , LU Qing , DU Zhenggui

2021, 30(5):543-550. DOI: 10.7659/j.issn.1005-6947.2021.05.006

[Abstract](293) [HTML](1231) [PDF 1.12 M](796)

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Background and Aims: Immediate breast reconstruction after mastectomy for breast cancer has become an important method of breast cancer surgical techniques, since it does not affect the treatment effect, and meanwhile, it can significantly improve the patients’ quality of life. Compared to other breast surgeries, mastectomy with reconstruction is more difficult to perform and time-consuming, so most breast cancer patients who need reconstruction are admitted to inpatient department for surgery and are properly observed for several days after operation. Here, the authors present the experience of 14 cases of breast cancer undergoing same-day immediate breast reconstruction in West China Hospital and discussed its safety and patients’ satisfaction.
Methods: The clinical data of 14 women with breast cancer undergoing same-day skin-sparing mastectomy surgery and immediate implant-based breast reconstruction from April 2020 to October 2020 in West China Hospital were reviewed. The data concerning doctor-patient requirement, surgical procedure, surgical safety, postoperative patients’ satisfaction and cautions for same-day reconstruction surgery were analyzed.
Results: The 14 patients had an average age of 42.6 years, and most of them were diagnosed as invasive breast cancer. The same-day skin-sparing mastectomy for breast cancer and immediate prosthetic breast reconstruction was successfully performed in all patients, including 10 cases of endoscopic reconstruction and 4 cases of open reconstruction. The operative time ranged from 146 to 215 min. During postoperative follow-up period for 3 to 9 months, no serious complications occurred, and only minor complications occurred in two patients, including one case of mild ischemia of flap and one case of seroma, and were all resolved after observation. According to Harris standard, the patients' satisfaction with the reconstructed breast were all expressed as excellent or good on postoperative 3 months. The BREAST-Q scores before and 3 months after operation were 62.2 and 59.6 for breast satisfaction, 59.9 and 51.0 for sexual well-being, 71.5 and 67.9 for psychosocial well-being, and 59.5 and 60.0 for physical well-being (chest), respectively.
Conclusion: Same-day skin-sparing mastectomy surgery with immediate prosthetic breast reconstruction on the basis of the routine breast cancer day surgery can obtain the same safety and satisfaction as inpatients, alleviate the hospitalization stress to a certain extent, increase the utilization rate of medical resources, and reduce the medical costs. So, it may have a broad application prospect.

7 Application value of serum miR-196a-5p and miR-339-5p expression levels in diagnosis of breast cancer

WU Yan , GAO Wenyu , GAO Suping , LI Zhihong

2021, 30(5):551-557. DOI: 10.7659/j.issn.1005-6947.2021.05.007

[Abstract](494) [HTML](973) [PDF 545.09 K](782)

Abstract:
Background and Aims: Studies have demonstrated that miR-196a-5p expression is increased while miR-339-5p expression is decreased in breast cancer cells, so they may probably be the therapeutic targets or diagnostic markers for breast cancer. Therefore, this study was conducted to evaluate the application values of serum levels of miR-196a-5p and miR-339-5p in diagnosis of breast cancer.
Methods: One hundred and seven patients with breast cancer (breast cancer group) treated during January 2016 to June 2017, along with 60 patients with benign breast disease (benign breast disease group) and 35 individuals undergoing healthy maintenance examination (healthy control group) during the same period were enrolled. The differences of serum levels of miR-196a-5p and miR-339-5p as well as the breast cancer-specific marker CA15-3 were compared among groups, and the diagnostic abilities of serum levels of the three indices were determined. In addition, the relationship between serum levels of miR-196a-5p and miR-339-5p in breast cancer patients as well as the associations of their levels with the clinicopathologic characteristics of breast cancer were also analyzed.
Results: In healthy control group, benign breast disease group and breast cancer group, the serum levels of miR-196a-5p and miR-339-5p were successively increased and decreased respectively, and the differences between groups were all statistically significant (all P<0.01). the serum CA15-3 level in breast cancer group was significantly higher than that in benign breast disease group and healthy control group (both P<0.01), but the difference between the latter two groups showed no statistical significance (P>0.05). The diagnostic abilities for breast cancer of both serum miR-196a-5p and miR-339-5p levels were significantly superior to that of serum CA15-3 level (Z=2.543, P<0.05; Z=2.190, P<0.05), but the diagnostic abilities between miR-196a-5p and miR-339-5p showed no significant difference (P>0.05). The AUC of the combined detection of miR-196a-5p and miR-339-5p for diagnosis of breast cancer was 0.937, with the sensitivity and specificity 91.6% and 88.3% respectively, which was significantly superior to that of either lone detection (miR-196a-5p: Z=3.044, P<0.01; miR-339-5p: Z=3.020, P<0.01). There was a negative correlation between the preoperative serum expression levels of miR-196a-5p and miR-339-5p in breast cancer patients (r=–0.764, P<0.01), and serum miR-196a-5p level was decreased while the serum miR-339-5p level was increased significant after surgery compared with those before surgery in breast cancer patients (both P<0.01). The serum levels of both miR-196a-5p and miR-339-5p in breast cancer patients were significantly associated with tumor diameter, lymph node metastasis, and TNM stage (all P<0.01).
Conclusion: The determination of serum levels of miR-196a-5p and miR-339-5p has high diagnostic value and also has a potential monitoring value for breast cancer. Both diagnostic abilities of miR-196a-5p and miR-339-5p are superior to that of CA15-3, and their combined detection can further increase the diagnostic efficacy.

8 Analysis of prognostic value of radiotherapy in patients with occult breast cancer based on SEER database

YANG Hongwei , LI Fangfang , HOU Lingmi , FAN Li , LIU Rui , HE Lingli , CHEN Maoshan

2021, 30(5):558-566. DOI: 10.7659/j.issn.1005-6947.2021.05.008

[Abstract](394) [HTML](1317) [PDF 529.53 K](982)

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Background and Aims: Occult breast cancer (OBC) is a rare clinical entity, and its biological behaviors are some different from those of common breast cancers. There is a lack of evidence of clinical research with large sample size for this kind of patients, and also the prognostic value of radiotherapy is still unclear. The purpose of this study was to evaluate the prognostic value of radiotherapy in OBC patients.
Methods: The clinical data of OBC patients diagnosed between 2010 and 2015 were extracted from the SEER database. A total of 693 patients were enrolled after the screening according to the inclusion and exclusion criteria. Patients were divided into the radiotherapy group and the non-radiotherapy group according to whether they had received radiotherapy. The breast cancer specific survival (BCSS) and overall survival (OS) were compared between the two groups of patients, the prognostic factors for BCSS and OS in OBC patients were determined, and the impacts of radiotherapy on OBC patients with different clinicopathologic characteristics were also analyzed.
Results: Among the 693 patients, radiotherapy group included 366 cases (52.8%) and non-radiotherapy group included 327 cases (47.2%). The median follow-up time was 59 months. In radiotherapy group and the non-radiotherapy group, the estimated 5-year BCSS was 89.33% and 82.08%, respectively, and the estimated 5-year OS was 87.75% and 75.75%, respectively, and both differences were statistically significant (χ2=7.33, P=0.007; χ2=15.61, P<0.001). Results of multivariate prognostic analysis by Cox proportional hazard mode showed that receiving radiotherapy or not, lymph node stage and hormone receptor status were independent influencing factors for BCSS of the patients, and receiving radiotherapy or not, age, lymph node stage and hormone receptor status were independent influencing factors for OS of the patients (all P<0.05); the BCSS (HR=0.46, 95% CI=0.30–0.70, P<0.001) and OS (HR=0.47, 95% CI=0.33–0.67, P<0.001) in OBC patients were significantly improved by radiotherapy. Stratified analyses based on clinicopathologic characteristics showed that radiotherapy significantly improved the BCSS in patients with estrogen receptor (ER)-negative expression (HR=0.33, 95% CI=0.19–0.59, P<0.001), progesterone receptor (PR)-negative expression (HR=0.33, 95% CI=0.19–0.55, P<0.001), HER-2-positive expression (HR=0.39, 95% CI=0.01–0.89, P=0.037), and without previous breast surgery (HR=0.30, 95% CI=0.16–0.54, P<0.001), or receiving chemotherapy (HR=0.39, 95% CI=0.24–0.64, P<0.001); radiotherapy significantly improved the OS in patients with ER-negative expression (HR=0.33, 95% CI=0.20–0.55, P<0.001), PR-negative expression (HR=0.34, 95% CI=0.22–0.54, P<0.001), and without previous breast surgery (HR=0.32, 95% CI=0.20–0.52, P<0.001) or undergoing chemotherapy (HR=0.39, 95% CI=0.26–0.60, P<0.001).
Conclusion: Radiotherapy can improve the BCSS and OS in OBC patients, especially in those with negative hormone receptor expression, having chemotherapy or without history of breast surgery. The local control value of radiotherapy in OBC patient remains to be studied.

9 Application of a novel minimally invasive endoscopic technique in treatment of breast abscess during lactation

WU Jun , WANG Ying , ZHANG Chaojie , LI Xinying

2021, 30(5):567-574. DOI: 10.7659/j.issn.1005-6947.2021.05.009

[Abstract](677) [HTML](1456) [PDF 1.84 M](1129)

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Background and Aims: For lactational mastitis developing into a breast abscess, the conventional treatment method is surgical incision and drainage. However, this traditional method has the disadvantages such as surgical invasiveness, severe pain during dressing change, long treatment time and apparent scars after wound healing, and even causes forced termination of lactation in some patients. Therefore, this study was attempt to use a novel minimally invasive endoscopic approach for the treatment of breast abscess during lactation period, and to analyze its efficacy.
Methods: The patients with lactational breast abscess meeting inclusion criteria admitted from February 2012 to February 2018 were enrolled, and were randomly allotted to two groups to undergo ultrasound-guided abscess puncture with endoscopic exploration and flushing plus catheter drainage (minimally invasive endoscopic group), and conventional open surgery with gauze drainage (conventional group). The relevant clinical efficacy variables were compared between the two groups of patients.
Results: A total of 97 patients were enrolled with 49 cases in minimally invasive endoscopic group and 48 cases in conventional group, and all patients were female. There were no significant differences in general data before treatment between the two groups of patients (all P>0.05). The frequency of dressing change, time to healing, treatment cost and postoperative cosmetic effect in minimally invasive endoscopic group were significantly superior to those in conventional group (all P<0.05); the surgical trauma and postoperative pain were significantly less, and the incidence rates of mammary duct fistula and milk regurgitation were significantly lower in minimally invasive endoscopic group than those in conventional group (all P<0.05). No recurrence occurred in both groups after treatment.
Conclusion: Minimally invasive endoscopic technique has demonstrable efficacy in the treatment of breast abscess during lactation, which can reduce postoperative pain and the frequency of dressing changes, shorten the treatment time as well as can decrease the treatment cost and the incidence rates of complications, with minimally invasive cosmetic results. So, it is recommended to be widely used in clinical practice.

10 Effects of naringenin on apoptosis and autophagy of thyroid cancer cells and its association with AMPK/mTORC1 pathway

ZHANG Zengling , SHI Gaoyang , ZHU Naihai , CHEN Tao

2021, 30(5):575-582. DOI: 10.7659/j.issn.1005-6947.2021.05.010

[Abstract](239) [HTML](1082) [PDF 1005.05 K](996)

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Background and Aims: Naringin (NAR) is a natural flavonoid compound, which can inhibit the growth of cells of cervical cancer, gastric cancer, tongue squamous cell carcinoma and liver cancer, but its effect on thyroid cancer cells is not clear. Therefore, this study was conducted to investigate the effects of NAR on thyroid cells, and to preliminarily analyze its mechanism, so as to provide a theoretical basis for research and development of drugs against thyroid cancer.
Methods: Thyroid cancer ACT-1 cells were cultured with different concentrations of NAR for different time periods, and then, the cell viability rates were determined by MTT assay to observe the time and concentration effects of NAR on ACT-1 cells, and calculate the IC50 values. Based on above experiment, the proper concentrations of NAR and proper time span were chosen to treat the ACT-1 cells. After that, the cell apoptosis was detected by Annexin V-FITC/PI staining, change in autophagic bodies was observed by green fluorescent protein (GFP)-labeled plasmid transfection, and the changes in expressions of the autophagy-associated proteins (LC3 I, LC3 II, p62) and proteins in the AMPK/mTORC1 pathway, as well as the influences of AMPK inhibitor on NAR actions were examined by Western blot analysis.
Results: The survival of ACT-1 cells was significantly suppressed in a time- and concentration dependent manner by NAR treatment (all P<0.05), and the IC50 values for 12, 24 and 48 h were 85.65, 50.12 and 38.94 μg/mL, respectively. In ACT-1 cells after treatment with the selected concentrations of 25, 50 and 100 μg/mL NAR, the apoptosis rates, numbers of autophagic bodies and the protein expression levels of LC3 II/LC3 I and p-AMPK/AMPK were significantly increased, and the protein expression levels of p62 and p-mTORC1/mTORC1 were significantly decreased, with a concentration-dependent manner (all P<0.05). In ACT-1 cells after treatment with 100 μg/mL NAR and simultaneous 25 μmol/L AMPK inhibitor, the above effects as well as the apoptosis-functional protein caspase-3 increasing effect of NAR on ACT-1 cells were all significantly suppressed (all P<0.05).
Conclusion: NAR can inhibit the proliferation and induce the apoptosis in thyroid cancer ACT-1 cells, which may be related to its regulating AMPK/mTORC1 signaling pathway and the enhancing autophagy.

11 Expression of circular RNA FBXW7 in triple-negative breast cancer and its clinical significance

HUANG Jun , GAO Guanfeng , ZENG Yan , TANG Hailin , YANG Fengjiao

2021, 30(5):583-590. DOI: 10.7659/j.issn.1005-6947.2021.05.011

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Background and Aims: Circular RNAs are a class of important regulatory elements that are involved in many cancer processes. It was reported that circular RNA FBXW7 (RNA circFBXW7) plays a tumor suppressor role in glioma through encoding a novel protein. However, its function and action mechanism in triple-negative breast cancer (TNBC) is still unclear. Therefore, this study was conducted to investigate the role of circFBXW7 in TNBC and its clinical significance.
Methods: The fresh specimens of tumor tissues from 240 TNBC patients and their clinical data were collected. the related prognosis data were also collected. The expression levels of circFBXW7 in these samples were detected by qRT-PCR, the relationship between circFBXW7 expression and the prognosis of TNBC patients was analyzed by Kaplan-Meier method, and the prognostic factors for TNBC patients were determined by Cox regression analysis. In TNBC cell lines MDA-MB-231 and HCC1806 after circFBXW7 over-expression, the changes in proliferation, migration and invasion abilities as well as miR-197-3p expression were examined by CCK8 assay and Transwell chamber assay. In above two types of cells after circFBXW7 knockdown and simultaneous miR-197-3p inhibitor transfection, the changes in proliferation and invasion abilities were measured by colony formation assay and Transwell chamber assay, respectively.
Results: The average expression level of circFBXW7 in the tumor tissues from the 240 TNBC patients was 1.043±0.268. Using 1.043 as a threshold value, the results of grouped analysis showed that both overall survival and disease-free survival in patients with low circFBXW7 expression were significantly shorter than those in patients with high circFBXW7 expression (both P<0.05); the circFBXW7 expression, histological grade and TNM classification were independent influencing factors for the prognosis of TNBC patients (all P<0.05). The results of cytological studies showed that the proliferation, migration and invasion abilities as well as the miR-197-3p expression levels of MDA-MB-231 and HCC1806 cells were significantly reduced after circFBXW7 over-expression (all P<0.05); the increased proliferation and invasion abilities of MDA-MB-231 and HCC1806 cells induced by circFBXW7 knockdown were reversed by simultaneous miR-197-3p inhibitor transfection (both P<0.05).
Conclusion: The circFBXW7 expression plays a suppressing role in TNBC, and the mechanism may be associated with its competitive binding miR-197-3p and thereby inhibit the proliferation and invasion of TNBC cells. It may be a novel prognostic biomarker and a potential therapeutic target for TNBC.

12 Association of expressions of runt-related transcription factor 2 and matrix metalloproteinase 3 with the invasiveness of breast cancer

HOU Chen

2021, 30(5):591-599. DOI: 10.7659/j.issn.1005-6947.2021.05.012

[Abstract](374) [HTML](1092) [PDF 788.10 K](775)

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Background and Aims: Runt-related transcription factor 2 (RUNX2) and its target gene matrix metalloproteinase 3 (MMP-3) are highly expressed in breast cancer tissue and related to tumor metastasis, but whether RUNX2 can affect the invasion and metastasis of breast cancer cells by regulating MMP-3 gene transcription is unclear. This study was conducted to analyze the relationship between RUNX2 and MMP-3 mRNA levels in breast cancer tissues by bioinformatics approaches, and observe the effect of RUNX2 expression on the transcription level of MMP-3 gene and the invasion ability in breast cancer cells.
Methods: The mRNA expression data of RUNX2 and MMP-3 as well as the relevant survival data in 1 092 breast cancer patients were obtained through cBioPortal database, and the correlation between RUNX2 and MMP-3 mRNA levels was analyzed. According to the median of RUNX2 and MMP-3 mRNA levels, the patients were divided into high and low RUNX2 or MMP-3 expression groups, and the association of RUNX2 and MMP-3 expression levels with the distant metastasis-free survival (DMFS) of the patients were analyzed by Kaplan Meier Plotter. The breast cancer MDA-MB-231 and BT-549 cells were transfected with RUNX2 siRNA or RUNX2 overexpression plasmids respectively, and then, the mRNA and protein expression levels were determined by qRT-PCR and Western blot. the potential binding site of RUNX2 in MMP-3 promoter was predicted by bioinformatics software, and then was verified in vitro by ChIP-PCR and double luciferase report system. The relations of RUNX2 and MMP-3 expression levels with the invasion ability of breast cancer cells were analyzed in MDA-MB-231 and BT-549 cells transfected with RUNX2 overexpression plasmid and MMP-3 siRNA by Transwell assay.
Results: There was a positive correlation between the mRNA levels of MMP-3 and RUNX2 in breast cancer (r=0.304 2, P<0.000 1). The DMFS in patients with high RUNX2 expression or high MMP-3 expression was lower than in patients with the corresponding low expression (P=0.034, P=0.013). In MDA-MB-231 cells, both mRNA transcription level and protein level of MMP-3 were decreased after down-regulating RUNX2 expression; and the MMP-3 mRNA and protein levels were increased in MDA-MB-231 and BT-549 cells after up-regulating RUNX2 expression. Results of bioinformatics analysis show that there was a possible binding site of RUNX2 in MMP-3 promoter sequence (5'-ACCACA-3'), and direct binding of RUNX2 to MMP-3 gene promoter region was confirmed by ChIP-PCR and double luciferase report system. The invasion abilities of both MDA-MB-231 and BT-549 cells were significantly increased after RUNX2 overexpression, and these effects were abolished by simultaneous down-regulation of MMP-3 expression (all P<0.05).
Conclusion: RUNX2 enhances the invasion ability of breast cancer cells possibly by regulating the transcription of MMP-3 gene, and the patients with high RUNX2 and MMP-3 expressions may face a poor prognosis. RUNX2 may be a potential target for the treatment of breast cancer.

13 Parathyroid autotransplantation in total thyroidectomy: current status and considerations

DONG Zhizhong , LIU Wen , CHENG Ruochuan

2021, 30(5):600-605. DOI: 10.7659/j.issn.1005-6947.2021.05.013

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Hypoparathyroidism is one of the most common complications after thyroidectomy, which not only increases the hospitalization time and medical cost, but also leads to reduced postoperative quality of life of patients. Both surgeons and patients hope to avoid the occurrence of permanent hypoparathyroidism as far as possible, so parathyroid autotransplantation as a simple and easy prevention strategy is widely used in thyroidectomy. However, the functional effectiveness of the transplanted parathyroid is not clear, and whether parathyroid gland should be transplanted during operation is still controversial. Aafter literature review, the authors address the application of parathyroid autotransplantation in total thyroidectomy.

14 Relationship between Hashimoto's thyroiditis and papillary thyroid carcinoma: recent progress

SU Duntao , OUYANG hui , LI Xinying

2021, 30(5):606-612. DOI: 10.7659/j.issn.1005-6947.2021.05.014

[Abstract](249) [HTML](1178) [PDF 474.47 K](1109)

Abstract:
The association between Hashimoto's thyroiditis (HT) and papillary thyroid carcinoma (PTC) and whether HT can promote the occurrence and development of PTC have been a controversial topic for many years. In recent years, many studies have confirmed that there is a close relationship between HT and the occurrence and development of PTC. Tumorigenesis can be regarded as the joint outcome of the abnormal features of tumor cells, the influences of the formation of tumor microenvironment and external environmental factors. HT is considered as a chronic inflammatory reaction, and various inflammatory cells infiltrating around the thyroid gland of HT patients will damage the DNA of interstitial cells, leading to the wrong repair of DNA, thus promoting the occurrence of PTC. Tumor microenvironment plays a key role in different stages of tumorigenesis and development of tumors by affecting immune surveillance and tumor diffusion. Chemokines produced by PTC-associated macrophages and mast leukocytes can induce the production of various immune cells. The complex interaction between infiltrating immune cells and PTC cells has become an important factor affecting the occurrence and development of PTC. In terms of molecular mechanism, HT promoting the occurrence and development of PTC is related to RET gene rearrangement, p63 protein expression, RAS, BRAF gene mutation and PI3K/Akt expression. In the aspect of immune mechanism, CD3+, CD4+ and Th17 cells were found to play important roles in the occurrence and development of PTC. As for the endocrine aspect, the increase of thyroid-stimulating hormone (TSH) caused by long-term HT is also an independent risk factor for the occurrence, development, and postoperative recurrence of PTC. As regards to the big clinical data, HT is an independent risk factor for PTC, and the incidence rate of PTC was significantly higher in patients with HT. At the same time, the prevalence of HT in patients with PTC was significantly higher than that in patients without PTC. Paraffin pathology found that patients with PTC nodules and concomitant HT had better clinicopathologic features and prognosis than those with lone PTC nodules. The patients with PTC and HT had a higher incidence of multifocality of malignant nodules, but the patients with PTC and HT had a lower incidence of central lymph node metastasis, smaller nodule diameter and lower incidence of distant metastasis. The mutation rate of BRAFV600E gene was lower in PTC nodules of these patients, which indicate that HT have a good protective effect on the prognosis of PTC patients. The correlation between HT and PTC is a hot topic in thyroid research. In recent years, many scholars have conducted a lot of studies on the molecular mechanism. Relevant clinical features can further guide clinicians to judge the clinical characteristics and prognosis of PTC patients. Fully understanding the correlation between HT and PTC will help to deepen the understanding of the pathogenesis of PTC and provide new ideas and methods for immunotherapy of PTC.

15 Research progress of molecular detection technologies based on FNAB in diagnosis of thyroid nodules

ZHOU Wulin , CHENG Xiaoming , LU Junyuan , HOU Zeyu , LIU Shengshan

2021, 30(5):613-621. DOI: 10.7659/j.issn.1005-6947.2021.05.015

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Abstract:
With the advent of various detection technologies, the detection rate of thyroid nodules has increased significantly. Although most thyroid nodules are benign, the determination between benign and malignant lesions is still a challenge for clinicians. All patients with suspicious thyroid nodules should undergo neck ultrasound. Thyroid ultrasound can assess the characteristics of nodules, and some thyroid nodules have ultrasound signs of suspicious malignancy. However, these features lack accuracy and cannot clearly diagnose benign and malignant nodules. The current guidelines still recommend ultrasound-guided fine needle aspiration biopsy (FNAB) as the first choice for evaluating benign and malignant thyroid nodules. FNAB is a cost-effective diagnostic tool. Due to its small trauma, high sensitivity and specificity, it can be used to evaluate the nature of thyroid nodules before surgery and has become one of the indispensable clinical examination methods. In recent years, domestic reports about FNAB have been increasing. Domestic and foreign guidelines regarding FNAB indications are still controversial. At the same time, due to its own limitations, the full implementation of FNAB technology requires strict control of the indications and accurate interpretation of the pathological results of puncture. Although FNAB is the most commonly used diagnostic technique for preoperative evaluation of thyroid nodules, there are still gray area nodules that require further diagnostic studies. In order to formulate a reasonable surgical plan and judge the prognosis, the guidelines recommend that thyroid-stimulating hormone (TSH) levels can be measured before surgery. FNAB is a simple and relatively non-invasive technique, but it can also produce corresponding complications. The complications of FNAB are mainly related to the position of the thyroid nodule, the diameter of the puncture needle, and the operating experience of the puncture physician, of which, the severity is relatively light, and most are self-limiting. Scholars have been trying to find a new method to accurately diagnose thyroid cancer for atypical lesions or follicular lesions that cannot be diagnosed or whose meaning is not clear. Molecular biology methods are currently the best choice. Molecular biology methods confirm the malignancy of thyroid tumor biopsy by detecting driver mutations of specific thyroid tumor susceptibility genes, such as BRAF and RAS oncogene mutations, RET/PTC rearrangement and TERT mutation detection, thereby improving the efficiency of preoperative diagnosis. The most common metastatic site of papillary thyroid carcinoma is local lymph nodes. Although FNAB has diagnostic value for abnormal lymph nodes, small or cystic lymph nodes may not be diagnosed due to lack of tumor cells. Detection of thyroglobulin content in the washing fluid of fine needle aspiration biopsy of suspicious cervical lymph nodes can be used as an auxiliary means of cytological diagnosis. The author believes that the multi-level diagnostic system of FNAB combined with molecular biology can improve the accuracy of preoperative diagnosis and is of great value in guiding treatment and judging prognosis.

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