Volume 29,Issue 11,2020 Table of Contents

1 Breakthrough through accumulation: suggestions and reflections on hierarchical quality management of thyroid cancer clinical database in China

CHENG Ruochuan , LIU Wen

2020, 29(11):1282-1292. DOI: 10.7659/j.issn.1005-6947.2020.11.001

[Abstract](819) [HTML](1227) [PDF 1.19 M](1354)

Abstract:
Clinical database construction has made great achievements in clinical research of thyroid tumors. Large database-based clinical studies lead the development and updating of guidelines, and promote the development of clinical practice in thyroid surgery. The thyroid cancer database construction starts relatively late in China. There is still a lack of high-quality evidence-based medicine data on Chinese population for thyroid cancer, as well as reference evidence for clinical guidelines. In recent years, the construction of thyroid tumor clinical database has increasingly developed depending on the evolution of internet technology and a large number of patients in China. However, due to the lack of quality control standards for database construction, and with the improvement of data availability, the risk of authenticity and integrity reduction is greatly increased during the process of various clinical information digitalizing. Based on experience and problems encountered during construction of thyroid tumor clinical database in the authors’ center, the authors present some preliminary ideas and suggestion on graded quality management of thyroid tumor clinical database. The process of database construction and application can be summarized as extracting the original information to convert the data for the final scientific research paper. The information characteristics of database were summarized as a step by step process of data acquisition on a scale of 0 to 3. The quality control of the data depends on the authenticity and availability of the data at the superior adjacent level. With the progressively transcriptions of information data, the data availability gradually increased to the level for scientific research application, while the authenticity gradually decreased. Database quality control is to ensure the authenticity of data as much as possible in the process of improving availability. Improving level-1 data quality is the foundation and key to improve the overall quality of the database, because that is at a higher risk of data loss during database construction. In order to improve the overall quality of the database, this paper shares some thoughts on data quality management from different aspects of medical record, including laboratory examination (level-1A), pathological report (level-1A), ultrasonic report (level-1B), and written record. In addition, we also propose structured level-1 medical record data recommendations. Over the years, clinical research of artificial intelligence diagnosis and disease prediction models based on big data has been carried out in full swing. However, the lack of satisfactory original database is difficult to improve later; the construction of a large database may lead to the embarrassing situation of “getting half the result with twice the effort”. This management problem may be ubiquitous in every specialized field and every national database construction. Therefore, the purpose of this paper is to call for the domestic colleagues pay attention to the quality control of the database and integrate the experiences of database construction from different centers, so as to brainstorm ideas and jointly develop a more reasonable hierarchical management of thyroid tumor clinical database in China.

2 Establishment of risk prediction model for axillary lymph node metastasis in breast cancer at early age based on clinicopathologic big data

SONG Wenjing , HE Xin , GONG Pengju , YANG Yan , WEI Lei , ZHANG Jingwei

2020, 29(11):1293-1302. DOI: 10.7659/j.issn.1005-6947.2020.11.002

[Abstract](820) [HTML](1231) [PDF 1.39 M](1195)

Abstract:
Background and Aims: Over the recent years, the incidence of breast cancer is increasingly shifting to younger population, which is more likely to develop axillary lymph node (ALN) metastasis. Therefore, this study was conducted to determine the influencing factors for ALN metastasis in young breast cancer patients using big-data platform of clinicopathologic information and establish a risk prediction models, so as to provide a reference for the clinical diagnosis and treatment of breast cancer in young adults.
Methods: The clinicopathologic data of young patients who were diagnosed with breast cancer and underwent ALN dissection between 2010 and 2015 were selected from the SEER database. The influencing factors for ALN metastasis were determined by univariate and multivariate analysis, and were subsequently visualized by nomogram. The ability of the nomogram to identify patients with different ALN status was quantized using the AUC/C-index. The internal verification of the prediction performance of the nomogram was estimated by bootstrap method (1 000 replicates with a random seed of 12). Furthermore, the data of young patients with newly diagnosed breast cancer from 2015 to 2017 in Zhongnan Hospital of Wuhan University were collected for external validation of the original model.
Results: A total of 23 778 young patients with breast cancer was recruited from the SEER database, 39.6% of whom had ALN metastasis. Univariate Logistic regression analysis showed that age, race, location of primary tumor, pathological grade, tumor size, and presence or absence of the chest wall or skin invasion as well as the status of ER, PR and HER-2 were significantly associated with ALN metastasis (all P<0.001). Multivariate Logistic regression analysis showed that age, race, and marital status, laterality, location of primary tumor and grade, tumor size, and presence or absence of the chest wall or skin invasion as well as the status of the ER, PR were independent influencing factors for ALN metastasis (all P<0.05), based on which, the risk prediction model was established. The calibration curve of internal validation indicated a good consistency between the predicted value calculated by the model and the real value (AUC/C-index=0.716). A total of 391 young patients with breast cancer were clinically enrolled as external validation dataset, and 49.9% of them were found to have ALN metastasis at initial diagnosis. The of external validation showed the good predictive ability of the model (AUC/C-index=0.798).
Conclusion: The risk prediction model developed using the SEER database for ALN metastasis in young patients with breast cancers has good predictive ability, and it can be used as a reference in clinical practice for estimating ALN metastasis of patients.

3 Analysis of clinicopathologic characteristics of 518 young breast cancer patients from a single center in Hunan

YANG Yuan , WANG Shouman , CHEN Feiyu ,

2020, 29(11):1303-1310. DOI: 10.7659/j.issn.1005-6947.2020.11.003

[Abstract](747) [HTML](1211) [PDF 1.10 M](1158)

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Background and Aims: The incidence rate of breast cancer ranks first among all female malignant tumors, and the prognosis of breast cancer in young women is relatively poor. Young women with breast cancer require special attention because they often face unique physical, psychosocial and emotional issues. This study was conducted to investigate the clinicopathologic characteristics of breast cancer in young adults by analyzing the relevant data of 518 young breast cancer women from a single center in Hunan, so as to provide evidence for optimizing the treatment for this group of patients.
Methods: The records of 518 women aged ≤35 years with breast cancer undergoing surgical treatment in the Department of Breast Surgery of Xiangya Hospital, Central South University from January 2002 to April 2018 were retrospectively analyzed, and 435 women aged ≥65 year with breast cancer treated during the same period were served as control. The differences in clinical and pathologic features between the two groups of patients were compared. Furthermore, the distribution of molecular subtypes of the 518 patients were compared with those from previous studies in different breast cancer populations.
Results: Among the 518 young breast cancer women, the proportion of cases with age from 31 to 35 accounted for 69.5%, with a normal BMI (18.5–<25 kg/m2) accounted for 74.5%, 18.2% were nullipara, 3.3% had a family history of breast cancer, 63.7% underwent neoadjuvant chemotherapy, 77.03% were subjected to the modified radical mastectomy, 57.0% had a stage TNM II disease, 53.7% were found no lymph node metastasis, 80.5% were invasive ductal carcinomas of no special type, and luminal cancer was the main molecular subtype, with luminal A type accounting for 37.6% and luminal B type accounting for 29.2%. In young breast cancer women versus older breast cancer women, the distribution of molecular subtypes showed no significant difference (P>0.05), the proportion of cases with normal BMI was higher (74.5% vs. 60.9%), the proportion of cases with stage III–IV disease was higher (25.5% vs. 20.5%), the proportion of cases without lymph node metastasis was lower (53.7% vs. 66.2%), both breast-conserving surgery rate and proportion of cases with synchronous reconstructive surgery were higher (9.3% vs. 3.2%; 7.5% vs. 1.8%), and all the differences had statistical significance (all P<0.05). The distribution of molecular subtypes of the 518 patients were significantly different with those from the authors’ previous studies in the overall breast cancer population in Hunan province (both P=0.000), but was similar with those from studies in young breast cancer population in China’s Guangdong province and America (both P>0.05), and the differences occurred in the former was considered due to the changes in detection method and subtyping criteria.
Conclusion: Compared with elderly breast cancer women, young breast cancer women have a relatively rapid disease progression, are more likely to develop lymph node metastasis, and have higher requirements for breast-conserving surgery and breast reconstruction. Therefore, aggressive breast cancer screening to improve the early detection rates is still of great importance. Meanwhile, the breast-conserving rate should be further increased, and the breast reconstruction and fertility preservation technologies should be continuously developed.

4 Clinical observation of using modified PCH regimen neoadjuvant therapy in young patients with treatment-na?ve locally advanced HER-2 positive breast cancer

ZHENG Xiangxin , WU Ji , GU Shucheng , JIANG Xiaoling , SHI Xiaohong , YUAN Mu , LU Bolin , QIU Xing , ZHANG Xuxu , BAI Jianyin , YANG Peng , GUAN Xiaoqing

2020, 29(11):1311-1318. DOI: 10.7659/j.issn.1005-6947.2020.11.004

[Abstract](271) [HTML](1203) [PDF 1.17 M](1044)

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Background and Aims: HER-2 positive breast cancer, especially the locally advanced HER-2 positive breast cancer in young patients, PCH regimen (paclitaxel + carboplatin + trastuzumab) is recommended for neoadjuvant therapy. However, the commonly used solvent paclitaxel is prepared with polyoxyethylene castor oil, which may cause the side effects such as allergic reactions, myelosuppression and peripheral neurotoxicity. Therefore, this study was designed to investigate the efficacy and safety of neoadjuvant therapy using the modified PCH regimen (albumin-bound paclitaxel + carboplatin + trastuzumab) in the treatment of young patients with initially diagnosed locally advanced HER-2 positive breast cancer.
Methods: Using a prospective protocol, the treatment-na?ve young females (aged from 18 to 40 years) diagnosed with locally advanced HER-2 positive breast cancer in the Department of Breast Surgery of Affiliated Suqian Hospital of Xuzhou Medical university from June 2016 to December 2018 were enrolled. The patients were assigned to two groups by random number table, and then underwent neoadjuvant therapy with PCH regimen (PCH group) or modified PCH regimen (PCH group). In all patients, the treatment responses and adverse reactions were evaluated after 6 cycles of chemotherapy, and then modified radical mastectomy was performed. Trastuzumab treatment was continued for a full year after operation, and the progression-free survival (PFS) and overall survival (OS) of the two groups of patients were compared.
Results: A total of 62 patients were enrolled, with 30 cases in PCH group and 32 cases in modified PCH group, and the preoperative data between the two groups of patients were comparable. After neoadjuvant therapy, complete clinical response (cCR) was obtained in 6 patients, complete pathological response was achieved in 2 patients, and partial response was found in 22 patients in PCH group, while 14 patients had cCR, 8 patients had pCR and 10 patients had PR in modified PCH group. Both cCR and pCR rates in modified PCH group were significantly higher than those in PCH group (43.8% vs. 20.0%, χ2=3.997, P=0.046; 25.0% vs. 6.7%, χ2=4.098, P=0.043). No treatment-associated death occurred in all patients during chemotherapy. The incidence of neutropenia in modified PCH group was significantly lower than that in PCH group (31.3% vs. 60%, χ2=5.168, P=0.023), while the incidence of peripheral sensory neurotoxicity in modified PCH group was significantly higher than that in PCH group (40.6% vs. 20.0%, χ2=3.997, P=0.046), but all reactions presented as numbness or tingling in hands or feet, and no neurotoxic reaction of 3 to 4 degree occurred in both groups. There were no significant differences between the two groups in other common adverse reactions such as nausea and vomiting, alopecia and rash (all P>0.05). The parameters of cardiac function of the two groups of patients were within the normal range during treatment. The median PFS time and the median OS time were 13.1 months and 35.4 months in modified PCH group, and were 7.8 months and 21.6 months in PCH group, and the difference had statistical significance (χ2=8.302, 8.557, P=0.005, 0.004).
Conclusion: In young patients with treatment-na?ve locally advanced HER-2 positive breast cancer, using the modified PCH regimen not only increases the cCR rate, but also improves the pCR rate to a certain extent compared with PCH regimen. The short-term efficacy in patients is satisfactory, with relatively mild adverse reactions. So, it is recommended to be used in clinical paractice.

5 Influence of degrees of myelosuppression following adjuvant chemotherapy on prognosis of patients with triple-negative breast cancer

ZHANG Yanwu , LI Shuaiping , NIU Yaodong , WANG Lu , ZHAN Xiangyu

2020, 29(11):1319-1326. DOI: 10.7659/j.issn.1005-6947.2020.11.005

[Abstract](315) [HTML](1180) [PDF 1.18 M](1241)

Abstract:
Background and Aims: Triple-negative breast cancer (TNBC) is a subtype of breast cancer with poor prognosis. Due to the lack of endocrine therapy and anti-HER-2 therapy targets, adjuvant chemotherapy is its main treatment strategy. As one of the most common side effects of chemotherapy, bone marrow suppression has an unclear effect on the prognosis of TNBC. This study was conducted to investigate the effect of the degree of bone marrow suppression on the prognosis of TNBC after adjuvant chemotherapy.
Methods: According to the inclusion and exclusion criteria, the clinical, pathological and follow-up data of patients with TNBC who underwent adjuvant chemotherapy with epirubicin and cyclophosphamide followed by docetaxel (EC-T) regimen in the Department of Breast of the Third Affiliated Hospital of Zhengzhou University from January 2012 to December 2017 collected for a retrospective analysis. Based on the WHO classification criteria for acute and subacute toxicity of anticancer drugs, the enrolled patients were divided into mild group (degree 0–II) and severe group (degree III–IV) according to the degree of bone marrow suppression after chemotherapy. The clinicopathologic features, disease-free survival (DFS), local-regional recurrence-free survival (LRFS), distant recurrence-free survival (DRFS) and total survival (OS) were compared between the two groups of patients.
Results: A total of 168 patients were included with 102 cases in mild group and 66 cases in severe group. There were no statistical differences in the baseline clinicopathologic characteristics between the two groups of patients (all P>0.05). The median follow-up time for mild group was 66.5 (22-95) months, and for severe group was 67.5 (28-96) months. There were 38 and 15 DFS events in mild group and severe group respectively, and the median DFS in mild group was 84 months, while severe group did not reach a median DFS; 20 and 8 OS events occurred in mild group and severe group respectively, and neither group achieved a median OS; 17 and 8 LRFS events were recorded in mild group and severe group respectively, and neither group reached a median LRFS; there were 27 and 10 DRFS events in mild group and severe group respectively, and neither group reached a median DRFS. Survival analysis showed that the 5-year DFS rate of severe group was higher than that of mild group (78.3% vs. 69.2%, HR=0.45, P=0.037); there was no significant difference in the 5-year OS rate between severe group and mild group (91.1% vs. 83.3%, HR=0.602, P=0.183; no statistical difference in the 5-year LRFS rate between severe group and mild group (89.1% vs. 83.3%, HR=0.625, P=0.270); the 5-year DRFS rate of severe group was higher than that of mild group (85.5% vs. 77.0%, HR=0.41, P=0.048).
Conclusion: TNBC patients with grade III–IV myelosuppression during adjuvant chemotherapy with EC-T regimen have a better prognosis than those with grade 0–II myelosuppression, suggesting that chemotherapy-induced hematological toxicity can be regarded as a sign of the effectiveness of chemotherapy, and is helpful for prognosis estimation and treatment decision making. For patients with only mild bone marrow suppression, following more intense treatment may be required. The issue that needs attention is that severe myelosuppression will increase the risk of neutropenic fever and infection, so the pros and cons must be weighed, and strict monitoring as well as symptomatic treatment must be offered.

6 Expressions of survivin and NF-κB in invasive ductal breast cancer and their clinical significance

WANG Jianjun , XU Xiaoyan , FENG Zhikun , YANG Jinhua

2020, 29(11):1327-1335. DOI: 10.7659/j.issn.1005-6947.2020.11.006

[Abstract](197) [HTML](1269) [PDF 1.32 M](1290)

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Background and Aims: Tumor invasion and metastasis are the main causes of death in breast cancer. The study of molecular markers of breast cancer is helpful for diagnosis and prognosis estimation. The relationship between apoptotic gene survivin and nuclear transcription factor NF-κB in breast cancer tissue is still unclear. This study was conducted to investigate the expressions of survivin and NF-κB protein in breast invasive ductal carcinoma and their relations with the clinicopathologic features, molecular subtypes and prognosis of the patients, so as to expand the understanding and knowledge of the pathogenesis for breast cancer and provide new strategies for the treatment and prevention of breast cancer.
Methods: Eighty patients with invasive ductal breast cancer who underwent surgical treatment in the People's Hospital of Zhengzhou from May 2015 to May 2017 and had confirmed pathological diagnosis and complete clinical data were selected as study objects. The expressions of survivin and NF-κB protein in the tumor and adjacent tissues from the patients were determined by immunohistochemical staining. The relations of survivin and NF-κB protein expressions with the clinicopathologic variables and molecular subtypes as well as prognosis of the patients were analyzed by statistical methods.
Results: The positive expression rates of both survivin and NF-κB protein in cancer were significantly higher than those in adjacent tissue (53.75% vs. 11.25%; 56.25% vs. 8.75%, both P<0.05). Both expressions of survivin and NF-κB were associated with histological grade, lymph node status and TNM stage, and both expressions were increased in breast cancer tissue of poor differentiation, positive lymph node metastasis, advanced TNM stages and non-luminal subtypes (all P<0.05); meanwhile, the co-overexpression rates of survivin and NF-κB were higher in breast cancer tissue of poor differentiation, positive lymph node metastasis, advanced TNM stages and non-luminal subtypes (all P<0.05). There was a positive correlation between survivin and NF-κB expressions (r=0.546, P=0.000). Survival analysis showed that the 5-year disease-free survival rate of patients with either high survivin or NF-κB expression was lower than those of the patients with corresponding low expression, and the 5-year disease-free survival rate of patients with co-overexpression of survivin and NF-κB was lower than that of the patients with either high survivin or NF-κB expression alone as well as patients with co-downexpression of survivin and NF-κB (all P<0.05). Cox regression analysis showed that NF-κB, co-expression of survivin and NF-κB, tumor diameter, differentiation and lymph node metastasis were independent risk factors for the prognosis of patients with invasive ductal breast cancer (all P<0.05).
Conclusion: The expressions of survivin and NF-κB protein in invasive ductal breast cancer tissue are closely related to the malignant clinicopathologic features and unfavorable prognosis of the patients, and furthermore, there may be a synergistic action between survivin and NF-κB in promoting the occurrence and development of breast cancer.

7 Relationship between microRNA-186-5p with its target gene CLDN18 and recurrence risk of papillary thyroid carcinoma

WANG Xin , XU Han , FAN Peizhi , ZHANG Chaojie , ZENG Jie

2020, 29(11):1336-1345. DOI: 10.7659/j.issn.1005-6947.2020.11.007

[Abstract](270) [HTML](1039) [PDF 4.29 M](1084)

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Background and Aims: MicroRNAs (miRNAs) play important roles in the process of occurrence and development of tumors, and different miRNA expression profiles may be closely connected to the different biological characteristics of tumors. Therefore, this study was conducted to screen the miRNAs associated with the risk of recurrence of papillary thyroid carcinoma (PTC) by analyzing the differentially expressed miRNAs between PTC patients with different recurrence risks, and investigate their action mechanisms.
Methods: The differentially expressed miRNAs in serum exosomes from PTC patients with low or intermediate-high recurrence risk were determined by microarray analysis, and then the differentially expressed miRNAs were verified in the PTC tissues by qRT-PCR method. The differentially expressed miRNAs associated with the invasion ability of PTC cells were picked up by Transwell assay. The potential target genes of the selected miRNAs were predicted using OncomiR online database. Subsequently, the relationship between the cell invasion ability-associated miRNAs and the predicted target genes were revealed through analyzing the changes in the relevant protein expressions (Western blot analysis) and invasion ability (Transwell assay) of the PTC cells using both overexpression and knock-down strategies. Finally, further confirmation was performed by analyzing the clinical samples of PTC in the TCGA database through GEPIA website.
Results: The results of microarray analysis showed that the expressions of 4 miRNAs (miR-186-5p, miR-532-3p, miR-199b-3p, and miR-3158-5p) were up-regulated and one miRNA (miR-3605-5p) was down-regulated in serum exosomes from PTC patients with intermediate-high recurrence risk compared with PTC patients with PTC patients with low recurrence risk (all P<0.05). The verification by qRT-PCR analysis of the tissue specimens revealed that the expressions of miR-186-5p and miR-3158-5p were up-regulated in the tumor tissues of PTC tissues with intermediate-high recurrence risk (both P<0.05). The results of Transwell assay demonstrated that the invasion ability of PTC cells was significantly enhanced by miR-186-5p overexpression, and was significantly weakened by miR-186-5p knock-down (both P<0.05), but the invasion ability PTC cells was not significantly affected by changing the expression level of miR-3158-5p (both P>0.05). PRDX6, S100PBP, CLDN18, and MAP2 were predicted as the potential target genes of miR-186-5p using OncomiR online software. The results of Western blot analysis showed that the protein expression of CLDN18 was significantly decreased after miR-186-5p overexpression, and the opposite was true after miR-186-5p knock-down (both P<0.05), but the protein expressions of the other 3 genes were not significantly affected by changing the expression level of miR-3158-5p. The results of Transwell assay showed that the invasion ability of PTC cells was significantly reduced by CLDN18 overexpression, and was significantly increased by CLDN18 knock-down, moreover, the effects of miR-3158-5p overexpression or knock-down exerted on PTC cells were reversed by simultaneous CLDN18 overexpression or knock-down (all P<0.05).
Conclusion: The increased miR-186-5p expression may be closely related to the recurrence risk of PTC, and the mechanism may be probably associated with its regulating the expression of downstream CLDN18 gene and thereby affecting the invasion ability of PTC cells.

8 Effects of naringenin on proliferation, invasion, migration and apoptosis in human and mouse breast cancer cells

LI Linfang , YANG Qian , ZHANG Yuanyuan , YANG Huaixia , MA Ting

2020, 29(11):1346-1356. DOI: 10.7659/j.issn.1005-6947.2020.11.008

[Abstract](590) [HTML](1171) [PDF 5.19 M](1209)

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Background and Aims: Naringenin (NAR) is a natural flavonoid monomer, which has been proven to have anti-cancer effects against ovarian cancer, rectal cancer, and lung cancer. However, its effect on breast cancer is unclear. Therefore, this study was conducted to observe the effect of NAR on the proliferation, migration, invasion and apoptosis in breast cancer cells from different species, and preliminarily analyze the mechanism, so as to provide theoretical and experimental basis for the development of relevant drugs for breast cancer.
Methods: The in vitro cultured human breast cancer MCF-7 cells and mouse breast cancer 4T1 cells were uses as study objects. The two types of cells were divided into two concentrations (100–200 μg/mL) of NAR treatment groups and control group, respectively, and the cells in control group were treated with DMSO. The changes in cell viabilities after above treatment for different times (24, 48 and 72 h) were measured by CCK-8 assay. The colony formation, migration and invasion abilities and apoptosis after above treatment for 24 h were detected by colony-forming assay, cell scratch assay, Transwell invasion assay and Hoechst apoptosis staining assay, respectively, and the expressions of Akt, the apoptosis- and cell cycle-related proteins and the endothelial-mesenchymal transition (EMT)-related molecules were determined by Western blot analysis.
Results: Compared with corresponding control group, the cell viabilities in the two types of breast cancer cells were significantly decreased after NAR treatment, with a certain time and concentration dependence (all P<0.01). Compared with corresponding control group, the relative colony formation rates, wound healing rates and the number of invading cells were significantly reduced, while the apoptotic rates were significantly increased in the two types of breast cancer cells after NAR treatment (all P<0.01); the protein expressions of Akt, Bcl-2, CDK4, cyclin D1, and MMP-9 were significantly down-regulated, while the Bax expressions were significantly up-regulated (all P<0.01).
Conclusion: NAR can effectively inhibit the proliferation, migration and invasion while promote apoptosis in both human breast cancer cells and mouse breast cancer cells. The mechanism may be related to its inhibiting the Akt pathway and regulating the cell cycle and the EMT process.

9 Clinical observation of impacts of different types of thyroid surgery on parathyroid function

WU Runzhang , YUAN Sheng , LIU Yong , LI Guan , ZHANG Donghai , ZHANG Chaojie

2020, 29(11):1357-1363. DOI: 10.7659/j.issn.1005-6947.2020.11.009

[Abstract](236) [HTML](1174) [PDF 1.33 M](1020)

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Background and Aims: Surgery plays an important role in the treatment of thyroid disease, and hypoparathyroidism is one of the common complications of thyroid surgery. However, different kinds of thyroid pathologies have different indications for different types of thyroid surgery, which may exert different impacts on parathyroid function. This study was conducted to investigate the differential influences of different types of thyroid surgery on parathyroid function and analyze the reasons.
Methods: The clinical data of 319 eligible patients who underwent thyroid surgeries from April 2017 to March 2019 were retrospectively analyzed. Of the patients, 111 cases underwent unilateral thyroid lobectomy (unilateral resection group), 107 cases underwent bilateral thyroid lobectomy (bilateral resection group), 71 cases underwent bilateral thyroid lobectomy with central lymph node dissection (bilateral resection plus level VI dissection group), and 30 cases underwent bilateral thyroid lobectomy with central and lateral neck dissection (bilateral resection plus level II–VI dissection group). During the operation, 1-2 points on the capsule around the affected side close to the isthmic region were selected, and 0.1-0.2 mL of nanocarbon suspension was injected at each point. Meticulous capsular dissection technique was adopted in all patients for in-situ preservation of the parathyroid glands. If the parathyroid glands failed to be retained in situ, they were immediately cut into pieces or homogenates and reimplanted into the sternocleidomastoid muscle. The changes in parathyroid hormone (PTH) and blood calcium levels before and after surgery as well as the incidence rates of postoperative hypoparathyroidism and hypocalcemia among groups of patients were observed and compared.
Results: The preoperative general data and PTH and blood calcium levels showed no significant differences among groups (all P>0.05). After surgery, both PTH and blood calcium levels were significantly decreased in all groups compared with their preoperative levels (all P<0.01), but their decreasing amplitudes were significantly magnified with the expansion of surgical scope, namely unilateral resection group < bilateral resection group < bilateral resection plus level VI dissection group < bilateral resection plus level II–VI dissection group, and all differences had statistical significance (all P<0.05). The incidence rates of hypoparathyroidism and hypocalcemia were likewise increased with the expansion of surgical scope, and in unilateral resection group, bilateral resection group, bilateral resection plus level VI dissection group and bilateral resection plus level II–VI dissection group, the incidence of hypoparathyroidism was 9.9%, 32.7%, 56.3% and 73.3%, and the incidence of hypocalcemia was 0, 1.9%, 19.7% and 50.0%, respectively. Follow-up was conducted for 24 weeks in all patients, and no permanent hypoparathyroidism was noted.
Conclusion: All kinds of thyroid surgery have certain impacts on the parathyroid function, and the possibility of parathyroid injury and risk of the occurrence of hypoparathyroidism will increase with the expansion of the surgical scope. So, the protective measures for parathyroid glands should be adopted in all thyroid surgeries, with meticulous dissection and reduced interference in the blood supply of the parathyroid glands, and thereby to decrease the incidence of hypoparathyroidism as far as possible.

10 Analysis of prediction indicators and prediction model construction for severity of liver fibrosis

LI Zhecheng , HUANG Yun , ZHANG Zeyu , LI Juanni , HU Kuan , WANG Zhiming

2020, 29(11):1364-1369. DOI: 10.7659/j.issn.1005-6947.2020.11.010

[Abstract](294) [HTML](1097) [PDF 1.11 M](1278)

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Background and Aims: The severity of liver fibrosis is closely related to the incidence of complications after hepatectomy. Thus, a comprehensive and accurate preoperative assessment of the patient’s liver fibrosis is of great importance for surgical procedure selection and prognosis of patients. Thus, this study was aimed to explore whether certain indicators or a prediction model constructed from these indicators can accurately and comprehensively predict the severity of liver fibrosis in patients.
Methods: The clinical data of 106 patients who underwent hepatectomy from September 2018 to December 2019 were collected for retrospective analysis, and those patients were divided into none/low-stage fibrosis group (50 patients) and high-stage fibrosis group (56 patients) based on the histological classification of liver fibrosis (Laennec staging system). Firstly, all the tested indexes of the two groups of patients were assessed by univariate analysis, and then those with significant differences were included in the multivariate regression analysis to screen out the independent prediction indicators and establish an integrated prediction model. Finally, the receiver operating characteristic (ROC) curve was established to evaluate the predictive efficacy of the independent predictive indicators and the integrated prediction model.
Results: Results of univariate analysis showed that there were significant differences between the two groups in terms of white blood cell (WBC), platelet (PLT), prothrombin time (PT), creatine (Cr), indocyanine green retention rate at 15 minutes (ICG15), width of portal vein and velocity of portal blood flow (all P<0.05). Results of multivariate regression analysis revealed that ICG15 and the width of portal vein were independent predictors for high-stage liver fibrosis (both P<0.05), and the established integrated predictive model based on the two variables was Logit (P)=–6.026+0.44×ICG15+0.299×width of portal vein. Moreover, the area under ROC curve (AUC) of the integrated predictive model was 0.88, with a sensitivity of 89.3% and a specificity of 74% at the cut-off value of 0.359. The predictive efficacy of the integrated prediction model was superior to either prediction indicator alone.
Conclusion: ICG15 and the width of portal vein are independent evaluation indicators for the severity of liver fibrosis, and the integrated prediction model combined with ICG15 and portal vein width offers more accurate preoperative assessment of the severity of liver fibrosis in patients, which has certain clinical reference value.

11 Research progress of the relationship between circular RNAs and thyroid cancer

CHEN Song , GAO Qingjun , ZHAO Daiwei

2020, 29(11):1370-1375. DOI: 10.7659/j.issn.1005-6947.2020.11.011

[Abstract](310) [HTML](1072) [PDF 528.08 K](1038)

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Circular RNAs (circRNAs) are a class of newly discovered endogenous non-coding RNAs and are widely expressed in various mammalian tissues or cells. Compared to traditional linear RNAs, circRNAs have strong stability due to the closed-loop structures which are resistant to RNA exonuclease and terminator exonuclease mediated degradation, and can be detected in the serum, urine, saliva and other body fluids. A large number of reports have reported that circRNAs participate in various biological processes such as embryonic development of organisms and cell proliferation, differentiation, and apoptosis through the circRNA-microRNA (miRNA)-mRNA network, and are also related to the occurrence, invasion and metastasis of tumors. Recent studies have confirmed that there is dysregulation of circRNA expressions in thyroid cancer tissue. The dysregulated circRNAs participate in the occurrence and development of thyroid cancer by acting as a molecular sponge of miRNAs to regulate the expression of downstream target genes. Here, the authors based on review of the research progress of circRNAs, address the expression of circRNAs in thyroid cancer and their roles and action mechanisms in the occurrence, development and metastasis of thyroid cancer.

12 Research progress of prophylactic central lymph node dissection in cN0 papillary thyroid cancer

SHI Shuai , FU Yantao

2020, 29(11):1376-1384. DOI: 10.7659/j.issn.1005-6947.2020.11.012

[Abstract](904) [HTML](1247) [PDF 1.13 M](1125)

Abstract:
In recent years, thyroid cancer has become the most prevalent endocrine cancer in the world, in which papillary thyroid cancer (PTC) is the most common type, accounting for about 90% of all thyroid cancers. Although PTC has a favorable prognosis, some PTC patients will develop early lymph node metastasis, especially the central lymph node metastasis (CLNM), with metastasis rate of 21.2% to 64.1%. For patients with confirmed CLNM, performing central lymph node dissection (CLND) has been becoming widely accepted by domestic and international scholars. However, as for CN0 tumor, there is still controversial about whether or not prophylactic CLND should be performed as well as the surgical scope. China’s guideline for differentiated thyroid cancer suggests that ipsilateral CLND should be performed for patients with cN0 PTC on the premise of the effective technical guarantee. However, the latest guideline of the American Thyroid Association points out that prophylactic CLND is ineffective in improving long-term survival, but may increase the incidence of complications. So, whether or not performing a prophylactic CLND for cN0 PTC patients failed to reach a agreement. Here, the authors address the issues concerning the related factors, metastasis patterns, imaging evaluation and technical innovation of CLNM.

13 Research progress of UBR5 gene in the biology of malignant tumors

PANG Jian , LIAO Liqiu , WANG Shouman

2020, 29(11):1385-1390. DOI: 10.7659/j.issn.1005-6947.2020.11.013

[Abstract](801) [HTML](1042) [PDF 1.06 M](1175)

Abstract:
UBR5 gene is a tumor-related gene that has attracted much attention in recent years. So far, it has been found to affect the biological behavior of tumors in many aspects such as cell cycle regulation, apoptosis regulation, tumor suppressor gene regulation, invasion and metastasis regulation. UBR5 was also found to be associated with chemotherapy sensitivity and prognosis of patients with various cancers. The TCGA database shows that UBR5 is abnormally expressed in many cancer types and is related to the biological behavior of tumors, but its specific mechanism of action has not yet been fully elucidated. With further investigation into the UBR5 gene, the knowledge about its regulatory mechanism in cancer will become increasingly clear, which will provide more information with regard to molecular diagnosis and targeted therapy of cancers, as well as prognostic assessment for patients. Here, the authors based on review of the latest studies at home and abroad address the UBR5 in terms of its gene structure and physiological function, and its regulatory effects and predictive value in tumor.

14 Risk assessment tools for venous thromboembolism recurrence: current status and research progress

LIN Pan , TIAN Lingyun , HE Ailan , GAO Huimin , SU Yanan , YANG Qiuhong , LI Wan , TANG Hongying , LI Yinglan ,

2020, 29(11):1391-1398. DOI: 10.7659/j.issn.1005-6947.2020.11.014

[Abstract](268) [HTML](1018) [PDF 1.10 M](1267)

Abstract:
The high recurrence rate of venous thromboembolism (VTE) seriously affects the patients’ quality of life, and also increases the disease burden and healthcare risks. However, the VTE recurrence can be prevented to a large extent. Accurate assessment of the risk of VTE recurrence in patients and stratifying the risks of the VTE recurrence is the first step for medical workers to prevent and control VTE recurrence. Here, the authors address the current status of VTE recurrence and its risk factors, and overview the risk assessment tools of VTE recurrence in foreign countries, so as to improve medical workers’ cognition of the current status of VTE recurrence and its risk factors, and provide practical guidance for assessment of VTE recurrence risk, and reference for medical safety warning and risk management of VTE recurrence.

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Volume 29,Issue 11,2020 Table of Contents

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