Hypocalcemia is a common complication after total thyroidectomy (TT). Several studies have identified risk factors for early biochemical hypocalcemia, nevertheless, the noteworthy symptomatic hypocalcemia has not been considered. This study aims to construct an intuitive predictive model for biochemical and symptomatic hypocalcemia to assist individualized management. A retrospective study was conducted on thyroid cancer patients undergoing TT. Two separate patient cohorts were used for model development and external validation, respectively. Data were gathered to identify the risk factors for biochemical (serum calcium <8.0 mg/dL) and symptomatic hypocalcemia by logistic regression. A predictive model was visualized by a nomogram and validated internally and externally. Of 431 patients studied, 258 (59.9
Papillary thyroid carcinoma (PTC) is the main type of malignant tumor of the thyroid gland in adults. Huaier, a traditional Chinese medicinal agent, has demonstrated antitumor efficacy across diverse malignant neoplasms. However, the specific impact of huaier in PTC remains insufficiently elucidated. In this study, we explored the function of huaier in PTC. We treated a PTC cell line (TPC-1) with varying concentration gradients of huaier and we observed that huaier effectively inhibited the proliferation of TPC-1 cells with an IC50 of 2.538 mg/ml. Huaier also modulated the cell cycle of the TPC-1 cell line, and induced apoptosis in TPC-1. Huaier treatment inhibited migration and invasion of TPC-1 cells. Further studies showed that in TPC-1 cells, huaier treatment inhibited the expression of the MAPK and HSP27/STAT3/AKT signaling pathway. We subsequently demonstrated in a nude mouse model that huaier treatment inhibited the progression of PTC tumors. In summary, our data suggest that huaier can inhibit the proliferation, migration, and invasion of PTC cells in vitro and the progression of PTC tumors in vivo, and that this effect may be related to the MAPK and HSP27/STAT3/AKT signaling pathway; therefore, huaier extract is expected to be a new direction for the treatment of PTC.
Background:Papillary thyroid carcinoma (PTC) often metastasizes to lymph nodes, increasing recurrence risk and reducing survival. This study identifies predictors for contralateral central lymph node metastasis (Cont-CLNM) in unilateral PTC patients with ipsilateral lateral cervical lymph node metastasis (Ipsi-LLNM). Methods:We retrospectively analyzed data, preoperative ultrasound features, and thyroglobulin (Tg) levels in unilateral PTC patients with Ipsi-LLNM treated at the Thyroid Surgery Department of Nanjing Drum Tower Hospital from August 2017 to August 2024. Least absolute shrinkage and selection operator (LASSO) regression was used for variable selection, with independent t-tests and Chi-squared tests assessing differences. Logistic regression analyses identified risk factors for Cont-CLNM, and a nomogram was validated using 1,000 bootstrap resamples. Decision curve analysis (DCA) evaluated clinical impact. Results:Of 105 PTC patients, 56 (53.3%) had Cont-CLNM. LASSO regression identified three predictors: male sex, lymph node metastasis posterior to the recurrent laryngeal nerve (LN-prRLN), and elevated Tg levels. Multivariate regression confirmed these variables' association with Cont-CLNM. Internal validation yielded an area under the curve of 0.771 [95% confidence interval (CI): 0.684-0.857]. A nomogram was developed and validated through DCA. Conclusions:Our findings indicate that combining male gender, LN-prRLN, and Tg levels effectively predicts Cont-CLNM, providing a basis for risk assessment in unilateral PTC.
ObjectiveTo compare the differences among patients with papillary thyroid carcinoma (PTC) whose right lateral lymph node biopsy results indicating positive (pN1b) or negative lymph node metastasis (pN0 or pN1a) so as to explore whether there is a high risk of long-term metastasis in right lateral lymph node among patients who are classified as pN0 or pN1a at present. Only those whose preoperative ultrasound result indicating lymph node metastasis in the right lateral region (cN1b) are included. Meanwhile, to establish predictive models to help clinicians distinguish high-risk and low-risk populations and adopt different follow-up strategies.MethodsA retrospective analysis was conducted on clinical data of patients who underwent right neck side area biopsy or dissection (cN1b) at the Affiliated Drum Tower Hospital, Medical School of Nanjing University from January 2017 to August 2022 to establish a predictive model. The model will then be validated on patients who undergo right neck lateral area biopsy or clearance from September 2022 to August 2023. Data including demographic characteristics, pathological results, and laboratory examinations were collected. The predictive model was established and evaluated by SPSS 26.0 and R 4.3.1.ResultThis study includes a total of 316 patients diagnosed with papillary thyroid carcinoma and with preoperative ultrasound indicating lymph node metastasis in the neck lateral compartment (cN1b), who were treated at the Affiliated Drum Tower Hospital, Medical School of Nanjing University from January 2017 to August 2023. The training set included 264 patients, and the validation set included 52 patients.The area under the ROC curve for the prediction model is 0.83, with a diagnostic optimal threshold of 0.595. At this threshold, the model achieves a sensitivity of 81.6% and a specificity of 75.2%. Similar results were obtained when utilizing the model on the validation set.ConclusionThere are distinct disparities in demographics, pathological result, and laboratory examinations that can differentiate between high-risk and low-risk populations for lymph node metastasis in the right lateral region. These differences can be effectively identified by developing predictive models.
Artificial intelligence applications in oncology imaging often struggle with diagnosing rare tumors. We identify significant gaps in detecting uncommon thyroid cancer types with ultrasound, where scarce data leads to frequent misdiagnosis. Traditional augmentation strategies do not capture the unique disease variations, hindering model training and performance. To overcome this, we propose a text-driven generative method that fuses clinical insights with image generation, producing synthetic samples that realistically reflect rare subtypes. In rigorous evaluations, our approach achieves substantial gains in diagnostic metrics, surpasses existing methods in authenticity and diversity measures, and generalizes effectively to other private and public datasets with various rare cancers. In this work, we demonstrate that text-guided image augmentation substantially enhances model accuracy and robustness for rare tumor detection, offering a promising avenue for more reliable and widespread clinical adoption.
Objective To compare the differences among patients with papillary thyroid cancer (PTC) whose rapid intraoperative biopsy results indicating positive (pN1b) or negative lymph node metastasis while their preoperative ultrasound result indicating lymph node metastasis in the right lateral region (cN1b) without exception so as to explore whether there is a high risk of long-term metastasis in patients with papillary thyroid cancer (PTC) who have no lymph node metastasis (pN1a or pN0) as indicated by rapid intraoperative biopsy results at present. Meanwhile, to establish predictive models to help clinicians distinguish and screen high-risk populations and adopt different follow-up strategies. Method A retrospective analysis was conducted on clinical data of patients who underwent right neck side area biopsy or dissection (cN1b) at the Affiliated Drum Tower Hospital, Medical School of Nanjing University from January 2017 to August 2022 to establish a predictive model.The model will then be validated on patients who undergo right neck lateral area biopsy or clearance from September 2022 to August 2023. Data including demographic characteristics, pathological results, and laboratory examinations were collected. The predictive model was established and evaluated by SPSS 26.0 and R 4.3.1. Result This study includes a total of 316 patients diagnosed with papillary thyroid carcinoma and with preoperative ultrasound indicating lymph node metastasis in the neck lateral compartment (cN1b), who were treated at the Affiliated Drum Tower Hospital, Medical School of Nanjing University from January 2017 to August 2023. The training set included 264 patients, and the validation set included 52 patients.The area under the ROC curve for the prediction model is 0.83, with a diagnostic optimal threshold of 0.595. At this threshold, the model achieves a sensitivity of 81.6% and a specificity of 75.2%. Similar results were obtained when utilizing the model on the validation set. Age ≤ 55 years, male, tumor maximum diameter > 1.35cm, metastasis to non-lymph node posterior to right recurrent laryngeal nerve (NLN-prRLN), metastasis to lymph node posterior to right recurrent laryngeal nerve (LN-prRLN), tetraiodothyronine (TT4) ≤ 89nmol/L, and thyroglobulin (TG) > 37.5µg/L are independent risk factors for right lateral lymph node metastasis. Conclusion There are distinct disparities in demographics, pathological result, and laboratory examinations that can differentiate between high-risk and low-risk populations for lymph node metastasis in the right lateral region. These differences can be effectively identified by developing predictive models. The resulting prediction model based on these results demonstrates a high level of accuracy and can assist clinical doctors to make appropriate clinical decisions to pick out individuals who need preventive lymph node dissection in the right neck side area or to increase postoperative follow-up frequency, in order to reduce the recurrence of the malignant tumor and improve long-term prognosis.
Due to the absence of definitive diagnostic criteria, there remains a lack of consensus regarding the risk assessment of central lymph node metastasis (CLNM) and the necessity for prophylactic lymph node surgery in ultrasound-diagnosed thyroid cancer. The localization of thyroid nodules is a recognized predictor of CLNM; however, quantifying this relationship is challenging due to variable measurements. In this study, we developed a differential isomorphism-based alignment method combined with a graph transformer to accurately extract localization and morphological information of thyroid nodules, thereby predicting CLNM. We collected 88,796 ultrasound images from 48,969 patients who underwent central lymph node (CLN) surgery and utilized these images to train our predictive model, ACE-Net. Furthermore, we employed an interpretable methodology to explore the factors influencing CLNM and generated a risk heatmap to visually represent the distribution of CLNM risk across different thyroid regions. ACE-Net demonstrated superior performance in 6 external multicenter tests (AUC = 0.826), surpassing the predictive accuracy of human experts (accuracy = 0.561). The risk heatmap enabled the identification of high-risk areas for CLNM, likely correlating with lymphatic metastatic pathways. Additionally, it was observed that the likelihood of metastasis exceeded 80% when the nodal margin’s minimum distance from the thyroid capsule was less than 1.25 mm. ACE-Net’s capacity to effectively predict CLNM and provide interpretable disease-related insights can importantly reduce unnecessary lymph node dissections by 37.9%, without missing positive cases, thus offering a valuable tool for clinical decision-making.
BACKGROUND:Hashimoto's thyroiditis is a chronic autoimmune inflammatory disease with a high prevalence and currently lacks effective treatment options. Previous preclinical and clinical trials have established mesenchymal stem cells (MSCs) as a promising therapeutic approach; however, there is limited research on MSC treatment for Hashimoto's thyroiditis, and the underlying molecular mechanisms remain unclear. METHODS:MSCs isolated from 4 to 6-week-old Lewis rats were employed for thyroiditis treatment. The efficacy of MSCs was assessed through histological and serological parameters. Molecular mechanisms of MSC therapy for Hashimoto's thyroiditis were explored by examining macrophage presence within thyroid tissue and relevant pathways. RESULTS:In this study, we observed elevated oxidative stress and endoplasmic reticulum stress within the thyroid tissue of Hashimoto's thyroiditis patients, and MSC therapy effectively mitigated this process. Furthermore, we found that the therapeutic potential of MSCs in the EAT model depended on the STING pathway. MSCs reduced endoplasmic reticulum stress and inflammasome levels within the thyroid tissue by modulating the STING pathway. Additionally, MSCs inhibited the expression of IRE1α in thyroid tissue macrophages, thereby reducing the polarization of M1-type macrophages CONCLUSIONS: The STING pathway appears to be a crucial mechanism by which MSCs modulate macrophage polarization in thyroid tissue, offering a potential treatment for thyroiditis.
Background: The present study aimed to construct a novel pyroptosis-related gene signature to predict the prognosis of papillary thyroid cancer (PTC). Methods: The gene expression level and survival and prognosis information of PTC were obtained from TCGA. The differentially expressed pyroptosis-related genes (DEPs) between cancer and control groups were selected, followed by subtype analysis. A prognostic model was built using LASSO regression analysis. The samples were then divided into high- and low-risk groups, and the differences in immune cell distribution in different risk groups were compared. The chemical drugs associated with genes in the prognostic model were extracted from the Comparative Toxicogenomics Database. Results: A total of 31 DEPs were selected, and 3 different subtypes were obtained. A prognostic model based on 6 pyroptosis-related genes was constructed. The risk grouping was significantly correlated with the actual prognosis, and the model was found to be an independent prognostic factor. Six immune cells with significant differences in distribution in different risk groups were screened. CGP52608 could target four genes in the prognostic model, including GSDMB, NLRC4, IL1A, and IL6. Conclusion: The present study constructed a pyroptosis-related gene signature that could predict the prognosis of PTC. Additionally, this signature was correlated with tumor immunity.
BACKGROUND:The current study aimed to investigate the molecular mechanism of long non-coding RNA (lncRNA) MEG3 in the development of breast cancer. METHODS:The regulating relationships among lncRNA MEG3, miRNA-330 and CNN1 were predicted by bioinformatics analysis of breast cancer samples in the Cancer Genome Atlas database. The differential expression of lncRNA MEG3, miRNA-330 and CNN1 was first validated in breast cancer tissues and cells. The effects of lncRNA MEG3 on breast cancer malignant properties were evaluated by manipulating its expression in MCF-7 and BT-474 cells. Rescue experiments, dual-luciferase assays, and RNA immunoprecipitation (RIP) experiments were further used to validate the relationships among lncRNA MEG3, miRNA-330 and CNN1. RESULTS:Bioinformatics analysis showed that lncRNA MEGs and CNN1 were significantly downregulated in breast cancer tissues, while miR-330 was upregulated. These differential expressions were further validated in our cohort of breast cancer samples. High expression levels of lncRNA MEG3 and CNN1 as well as low expression of miR-330 were significantly associated with favorable overall survival. Overexpression of lncRNA MEG3 significantly inhibited cell viability, migration and invasion, decreased cells in S stage and promoted cell apoptosis. Dual-luciferase reporter gene assay and RIP experiments showed that lncRNA MEG3 could directly bind to miR-330. Moreover, miR-330 mimics on the basis of lncRNA MEG3 overexpression ameliorated the tumor-suppressing effects of lncRNA MEG3 in breast cancer malignant properties by decreasing CNN1 expression. CONCLUSION:Our study indicated lncRNA MEG3 is a breast cancer suppressor by regulating miR-330/CNN1 axis.
Background Although the long-term prognosis of papillary thyroid cancer (PTC) is favorable, distant metastasis significantly compromises the prognosis and quality of life for patients with PTC. The Cadherin family plays a pivotal role in tumor metastasis; however, the involvement of Cadherin 4 (CDH4) in the metastatic cascade remains elusive. Methods The expression and subcellular localization of CDH4 were determined through immunohistochemistry, immunofluorescence, and western blot analyses. The impact of CDH4 on cell migration, invasion, angiogenesis, and metastasis was assessed using transwell assays, tube formation assays, and animal experiments. Immunoprecipitation assay and mass spectrometry were employed to examine protein associations. The influence of CDH4 on the subcellular expression of β-catenin and active β-catenin was investigated via western blotting and immunofluorescence. Protein stability and ubiquitination assay were employed to verify the impact of CDH4 on β-catenin degradation. Rescue experiments were performed to ensure the significance of CDH4 in regulating nuclear β-catenin signaling. Results CDH4 was found to be significantly overexpressed in PTC tissues and predominantly localized in the cytoplasm. Furthermore, the overexpression of CDH4 in tumor tissues is associated with lymph node metastasis in PTC patients. Cytosolic CDH4 promoted the migration, invasion, and lung metastasis of PTC cells and stimulated the angiogenesis and tumorigenesis of PTC; however, this effect could be reversed by Tegavivint, an antagonist of β-catenin. Mechanistically, cytosolic CDH4 disrupted the interaction between β-catenin and β-TrCP1, consequently impeding the ubiquitination process of β-catenin and activating the nuclear β-catenin signaling. Conclusions CDH4 induces PTC angiogenesis and metastasis via the inhibition of β-TrCP1-dependent ubiquitination of β-Catenin.
Autoimmune thyroiditis (AITD) is a prevalent autoimmune disorder characterized by the immune system’s attack on thyroid tissue, potentially leading to thyroid dysfunction, with a current lack of effective treatment modalities. Lactoferrin, a crucial functional dietary component obtainable from food sources, primarily exists in mammalian milk. We aim to investigate whether dietary supplementation with lactoferrin can protect the thyroid in Experimental Autoimmune Thyroiditis (EAT) rats. Our study reveals significantly elevated levels of oxidative stress (OS) and endoplasmic reticulum stress (ERS) in the AITD. Lactoferrin markedly reduces OS and infiltration of inflammatory cells in the thyroid tissue of EAT rats. Furthermore, lactoferrin inhibits ERS levels in the thyroid of EAT rats and alleviates cellular apoptosis. In vivo and in vitro experiments elucidate that its protective effect is primarily achieved through the inhibition of mTOR signaling pathway activation. In summary, lactoferrin, a nutrient readily obtainable from food sources, appears to be effective in mitigating thyroid damage in AITD. LTF alleviate autoimmune thyroiditis.
Background:Papillary thyroid carcinoma (PTC) is the most common malignant tumor of the thyroid gland, with lymph node metastasis significantly affecting patient prognosis. In recent years, body mass index (BMI) has garnered widespread attention as a potential factor influencing cancer development. This study aimed to explore the relationship between BMI and lymph node metastasis in patients with PTC, particularly focusing on the risk of metastasis in the lateral and central neck compartments. Methods:This retrospective study comprised 993 patients who underwent surgical treatment and were pathologically confirmed to have PTC. Patient BMI data were collected, and their relationship with lymph node metastasis in the lateral and central neck compartments was analyzed. Logistic regression models were employed to analyze the correlation between BMI and lymph node metastasis. Results:The study found a significant correlation between BMI and the risk of lateral neck lymph node metastasis in patients (P=0.008), along with a corresponding increase in extrathyroidal extension risk (P=0.02). While elevated BMI did not directly increase the risk of central compartment metastasis, a significant increase was observed in the number of central compartment lymph node metastases (P=0.009) and their proportion among the total central compartment lymph nodes (P=0.01) in patients with higher BMI. Additionally, multifocality, age, and gender were identified as risk factors for lateral neck lymph node metastasis, whereas Hashimoto's thyroiditis did not exhibit a similar impact. Conclusions:This study highlights that higher BMI is an important risk factor for lateral neck lymph node metastasis in patients with PTC and may exacerbate the severity of central compartment lymph node metastasis. These findings underscore the importance of considering BMI in the management of thyroid cancer and provide data support for future prevention and intervention strategies.
OBJECTIVE:Identifying early predictive indicators of symptomatic hypocalcemia in patients after thyroidectomy with neck lymph node dissection can help to identify high-risk patients, provide timely intervention, and improve prognosis. METHODS:A retrospective analysis of all relevant information was conducted for patients who underwent total thyroidectomy with neck lymph node dissection at our hospital between April 2021 and September 2022. The primary outcome measure was symptomatic hypocalcemia. RESULTS:Of the 210 patients who underwent total thyroidectomy with l neck lymph node dissection, 76 patients (36%) experienced symptoms of hypocalcemia. The analysis confirmed that the rate of parathyroid hormone (PTH) decline (OR = 238.414, 95%CI: 51.904-1095.114, P = 0.000) was an independent risk factor for symptomatic hypocalcemia after total thyroidectomy with neck lymph node dissection. The ROC curve indicated that a PTH decline cutoff value of 0.7425 was significantly correlated with symptoms of hypocalcemia, with a sensitivity of 89% and specificity of 69%, which could effectively predict symptomatic hypocalcemia. CONCLUSION:A PTH decline rate greater than the cutoff value of 0.7425 is a predictive factor for symptomatic hypocalcemia in adults and may be considered as a high-risk patient and actively managed to supplement calcium as soon as possible to ensure patient safety.
PURPOSE:The purpose of this study was to investigate the impact of autofluorescence technology on postoperative parathyroid function and short-term outcomes in patients undergoing thyroid surgery. METHODS:A total of 546 patients were included in the study, with 287 in the conventional treatment group and 259 in the autofluorescence group. Both groups underwent central lymph node dissection, which is known to affect parathyroid function. Short-term outcomes, including rates of postoperative hypocalcemia and parathyroid dysfunction, serum calcium and PTH levels on the first postoperative day, as well as the need for calcium supplementation, were analyzed. A multivariable analysis was also conducted to assess the impact of autofluorescence on postoperative parathyroid dysfunction, considering factors such as age, BMI, and preoperative calcium levels. RESULTS:The autofluorescence group demonstrated significantly lower rates of postoperative hypocalcemia and parathyroid dysfunction compared to the conventional treatment group. The autofluorescence group also had better serum calcium and PTH levels on the first postoperative day, and a reduced need for calcium supplementation. Surprisingly, the use of autofluorescence technology did not prolong surgical time; instead, it led to a shorter hospitalization duration. The multivariable analysis showed that autofluorescence significantly reduced the risk of postoperative parathyroid dysfunction, while factors such as age, BMI, and preoperative calcium levels did not show a significant correlation. CONCLUSION:This study provides evidence that autofluorescence technology can improve the preservation of parathyroid function during thyroid surgery, leading to better short-term outcomes and reduced postoperative complications. The findings highlight the potential of autofluorescence as a valuable tool in the management of parathyroid hypofunction. Further research and validation are needed to establish the routine use of autofluorescence technology in the thyroid.
Background:There is much debate on the optimal treatment approach of papillary thyroid carcinoma (PTC). Different guidelines base recommendations on various risk factors. While diagnosing the various risk factors is difficult due to the technical limitations, intraoperative frozen section (IFS) may be a feasible method. We aim to real-time evaluate the multiple risk factors, including lymph node metastasis (LNM), extrathyroidal extension (ETE), multifocality using IFS, and then identify a more effective surgical plan, which may help avoid the need for a second surgery and improve prognosis of patients. Methods:We retrospectively reviewed the medical records of 364 patients from January 1, 2021 to December 31, 2021. All the patients were initially recommended to undergo a hemithyroidectomy (HT) with isthmusectomy and ipsilateral central compartment neck dissection (CCND). IFS would be executed immediately. Further total thyroidectomies (TTs) would be performed if: (I) results of IFS showed >5 LNM, or (II) there are 1≤ LNM ≤5 but with ETE and/or multifocal carcinoma. The patients were divided and investigated according to the extent of surgery. Results:Based on the results of IFS, 72 patients underwent TT. The TT group displayed larger average tumor diameter, greater age, higher average body mass index (BMI), and elevated incidence of hypertension and hyperlipidemia compared to the HT group. The sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV) of IFS were 77.61%, 100%, 100%, and 88.46%, respectively. Conclusions:IFS is a highly reliable procedure. Comprehensively evaluating central compartment LNM, ETE, and multifocal carcinoma through IFS helps identify a more reasonable surgical option under the current clinical consensus, which may thus help avoid the need for a second surgery.
Purpose To explore the key genes and molecular pathways in the progression of thyroid papillary carcinoma (PTC) promoted by testosterone using RNA-sequencing technology, and to provide new drug targets for improving the therapeutic effect of PTC. Methods Orchiectomy (ORX) was carried out to construct ORX mouse models. TPC-1 cells were subcutaneously injected for PTC formation in mice, and the tumor tissues were collected for RNA-seq. The key genes were screened by bioinformatics technology. Tnnt1 expression in PTC cells was knocked down or overexpressed by transfection. Cell counting kit-8 (CCK-8), colony formation assay, scratch assay and transwell assay were adopted, respectively, for the detection of cell proliferation, colony formation, migration and invasion. Besides, quantification real-time polymerase chain reaction (qRT-PCR) and western blot were utilized to determine the mRNA and protein expression levels of genes in tissues or cells. Results Both estradiol and testosterone promoted the growth of PTC xenografts. The key gene Tnnt1 was screened and obtained by bioinformatics technology. Functional analysis revealed that overexpression of Tnnt1 could markedly promote the proliferation, colony formation, migration, invasion, and epithelial-to-mesenchymal transition (EMT) process of PTC cells, as well as could activate p38/JNK pathway. In addition, si-Tnt1 was able to inhibit the cancer-promoting effect of testosterone. Conclusion Based on the outcomes of bioinformatics and basic experiments, it is found that testosterone can promote malignant behaviors such as growth, migration, invasion and EMT process of PTC by up-regulating Tnnt1 expression. In addition, the function of testosterone may be achieved by activating p38/JNK signaling pathway.
Purpose Sex hormones are thought to be responsible for the unique gender differences in papillary thyroid cancer(PTC). Most previous studies on these have focused on the expression of estrogen receptors, or have been limited to animal studies. The aim of our study was to explore the relationship between serum sex hormones and the pathological features of PTC in the clinical setting, as further evidence of the role of sex hormones in PTC. Methods Retrospective data analysis of patients who underwent thyroid surgery at the Department of Thyroid Surgery, Nanjing Drum Tower Hospital from January 2022 to September 2022 Correlation between serum sex hormone and pathological features was analyzed in male patients and in menopausal female patients. Serum sex hormones include luteinizing hormone(LH), follicle stimulating hormone(FSH), estradiol(E 2 ), total testosterone(TT), progesterone(P), and prolactin(PRL). Tumor pathological characteristics include the number and size of tumor, presence of extrathyroidal extension(ETE), presence of lymph node metastasis(LNM). Results Preoperative serum E2 in male patients was positively correlated with tumor size in PTC, LH was negatively correlated with LNM, while TT and P were negatively correlated with ETE. Similar findings were not observed in menopausal female patients. Conclusion We observed that serum sex hormones correlate with the pathological features of PTC in male patients, for the first time in a clinical study. High serum estrogens may be a risk factor for PTC, while androgens are the opposite. This somewhat corroborates previous research and provides new variables for future PTC prediction models.
BACKGROUND:Anaplastic thyroid cancer (ATC) is a highly aggressive malignancy with dismal prognosis. This study aimed to identify the independent risk factors and construct a readily-to-use nomogram to predict the probability of early death in ATC patients. METHOD:Patients diagnosed with ATC between 2004 and 2015 from the Surveillance, Epidemiology, and End Results (SEER) database were enrolled in this study for model development and internal validation. Univariate and multivariate logistic regression analyses were conducted to identify independent risk factors for early death of ATC. Nomograms for predicting the probability of all-cause early death (ACED) and cancer-specific early death (CSED) of ATC were subsequently developed. The performance of the nomograms was comprehensively evaluated and validated in an internal cohort. RESULT:A total of 696 ATC patients were included in this study, of which 488 patients in the training cohort and 208 patients in the validation cohort. The univariate and multivariate logistic regression analyses identified five independent factors (tumor size, M stage, surgery, radiotherapy and chemotherapy) in the ACED model and six variables in the CSED (gender, tumor size, M stage, surgery, radiotherapy and chemotherapy) model for the establishment of the nomograms. Calibration curves and receiver operating characteristic (ROC) curves showed satisfactory efficacy and consistency both in the training (ACED: AUC values: 0.814 (0.776-0.852); CSED: 0.778 (0.736-0.820)) and validation sets (ACED: 0.762 (0.696-0.827); CSED: 0.745 (0.678-0.812)). In addition, the decision curve analysis (DCA) demonstrated the favorable potential of the two nomograms in clinical application. CONCLUSION:The two nomograms assist clinicians to identify risk factors and predict the early death probability among ATC patients, thus guide individualized treatment to improve the prognosis.
Epithelial-mesenchymal transition (EMT) is the culprit of tumor invasion and metastasis. As a critical transcription factor that induces EMT, snail is of great importance in tumor progression, and knocking down its expression by small interfering RNA (siRNA) may inhibit tumor metastasis. Herein, we developed a core-shelled bioinspired low-density lipoprotein (bio-LDL) in which snail siRNA-loaded calcium phosphate nanoparticles were wrapped as the core and doxorubicin was embedded in the outer phospholipids modified with a synthetic peptide of apoB100 targeting LDL receptor-abundant tumor cells. Bio-LDL exhibited pH-responsive release, lysosomal escape ability, enhanced cytotoxicity and apoptotic induction. Bio-LDL could significantly inhibit the expression of snail and regulate EMT-related proteins to reduce tumor migration and invasion in vitro. Bio-LDL also displayed favorable tumor targeting and synergistic inhibition of tumor growth and metastasis in vivo. Therefore, the multifunctional bio-LDL will be a promising co-delivery vector and holds potential value for clinical translation.