Enhancement of OCTen faceimages by unsupervised deep learning.

The quality of optical coherence tomography (OCT) en face images is crucial for clinical visualization of early disease. As a three dimensional and coherent imaging, defocus and speckle noise are inevitable, which seriously affect evaluation of microstructure of bio-samples in OCT images. The deep learning has demonstrated great potential in OCT refocusing and denoising, but it is limited by the difficulty of sufficient paired training data. We proposed an unsupervised deep learning-based pipeline to enhance the quality of OCT en face images in this paper. The unregistered defocused conventional OCT images and focused speckle-free OCT images were collected by a home-made speckle modulating OCT system to construct the dataset. The image enhancement model was trained with the cycle training strategy. Finally, the speckle noise and defocus were both effectively improved. The experimental results on complex bio-samples indicated that the proposed method is effective and generalized in enhancing the quality of OCT en face images. The proposed unsupervised deep learning method helps to reduce the complexity of data construction, which is conducive to practical applications in OCT bio-sample imaging. .

Time Kinetics and prognosis roles of calcitonin after surgery for medullary thyroid carcinoma.

BACKGROUND: Medullary thyroid carcinoma (MTC) is a malignant tumor with low incidence. Currently, most studies have focused on the prognostic risk factors of MTC, whatever, time kinetic and risk factors related to calcitonin normalization (CN) and biochemical persistence/recurrence (BP) are yet to be elucidated. METHODS: A retrospective study was conducted for 190 MTC patients. Risk factors related to calcitonin normalization (CN) and biochemical persistence/recurrence (BP) were analyzed. The predictors of calcitonin normalization time (CNT) and biochemical persistent/recurrent time (BPT) were identified. Further, the prognostic roles of CNT and BPT were also demonstrated. RESULTS: The 5- and 10-year DFS were 86.7% and 70.2%, respectively. The 5- and 10-year OS were 97.6% and 78.8%, respectively. CN was achieved in 120 (63.2%) patients, whereas BP was presented in 76 (40.0%) patients at the last follow up. After curative surgery, 39 (32.5%) and 106 (88.3%) patients achieved CN within 1 week and 1 month. All patients who failed to achieve CN turned to BP over time and 32/70 of them developed structural recurrence. The median time of CNT and BPT was 1 month (1 day to 84 months) and 6 month (3 day to 63months), respectively. LNR > 0.23 and male gender were independent predictors for CN and BP. LNR > 0.23 (Hazard ratio (HR), 0.24; 95% CI,0.13-0.46; P < 0.01) and male gender (HR, 0.65; 95% CI, 0.42-0.99; P = 0.045) were independent predictors for longer CNT. LNR > 0.23 (HR,5.10; 95% CI,2.15-12.11; P < 0.01) was still the strongest independent predictor followed by preoperative serum Ctn > 1400ng/L (HR,2.34; 95% CI,1.29-4.25; P = 0.005) for shorter BPT. In survival analysis, primary tumor size > 2 cm (HR, 5.81; 95% CI,2.20-15.38; P < 0.01), CNT > 1 month (HR, 5.69; 95% CI, 1.17-27.61; P = 0.031) and multifocality (HR, 3.10; 95% CI, 1.45-6.65; P = 0.004) were independent predictor of DFS. CONCLUSION: Early changes of Ctn after curative surgery can predict the long-term risks of biochemical and structural recurrence, which provide a useful real-time prognostic information. LNR significantly affect the time kinetic of biochemical prognosis. Tumor burden and CNT play a crucial role in MTC survival, the intensity of follow-up must be tailored accordingly.

Changes of biochemical factors and the effect on recurrence of medullary thyroid carcinoma after surgery.

Objective: Medullary thyroid carcinoma (MTC) is a rare malignancy secreting calcitonin (Ctn). We aimed to analyze the relationship between Ctn levels at different time points in patients with MTC, and evaluate its predictive effect on recurrence. Methods: A retrospective study of patients diagnosed with MTC in a large medical center were conducted in northern China. The interrelationships between preoperative Ctn, normalization of postoperative serum Ctn at the first month (NPS), and long-term biochemical cure as well as their predicting roles on structural recurrence were assessed. Results: A total of 212 patients were included in this study. The median follow-up time was 59.5 months. The 5- and 10-year cumulative disease-free survival rates were 81.5 % and 66.8 %, respectively. NPS (OR: 216.33, 95 % CI: 28.69-1631.09, P < 0.001) and absence of structural recurrence (OR: 61.71, 95 % CI: 3.90-975.31; P = 0.003) were associated with biochemical cure. Non-biochemical cure (OR: 28.76; 95 % CI: 2.84-290.86; P = 0.004, HR: 14.63, 95 % CI: 2.27-94.07, P = 0.005), larger tumor size (OR: 8.79, 95 % CI: 2.12-36.40, P = 0.003, HR: 5.41, 95 % CI: 2.04-14.37, P = 0.001), and multifocality (OR: 4.02, 95 % CI: 1.06-15.17, P = 0.040, HR: 3.00, 95 % CI: 1.18-7.60, P = 0.021) were unfavorable independent predictors of structural recurrence and disease-free survival. For sporadic MTC confined to the thyroid lobe, there was no difference in biochemical or structural prognosis between the different surgeries in the subgroup analysis. Conclusions: NPS, rather than preoperative Ctn, predicted long-term biochemical cure for MTC. Non-biochemical cure, larger tumor burden including larger tumor size and multifocality at initial surgery, served as worse prognostic predictors.

Analysis of Surgical Outcomes in Endoscopic-Assisted Lateral Neck Dissection.

BACKGROUND: Currently, endoscopic-assisted lateral neck dissection (EALND) is performed to reduce postoperative scarring of the anterior neck. This study aimed to compare surgical outcomes between EALND and conventional open lateral neck dissection (COLND) for papillary thyroid carcinoma (PTC) with lateral lymph node metastases (LNM). METHODS: The study reviewed 103 PTC patients who were classified on the basis of surgical type and statistically compared using propensity score matching analysis. RESULTS: The mean operation time is longer, and the cost of surgery is higher in the EALND group than COLND group (all p < 0.05). The numbers of retrieved and positive level II LNs, the rate of level II LNs detection between two groups do not differ significantly (all p > 0.05). The incidence of postoperative neck numbness is lower, and patients are more satisfied with postoperative neck scarring in the EALND group than COLND group (all p < 0.05). The common complications of two groups are transient recurrent laryngeal nerve injury and transient hypoparathyroidism. CONCLUSIONS: EALND is safe and feasible compared with COLND. The incision is more aesthetically satisfactory, which makes EALND a surgical approach for PTC patients with lateral LNM. LEVEL OF EVIDENCE: 3 Laryngoscope, 134:2221-2227, 2024.

Self super-resolution of optical coherence tomography images based on deep learning.

As a medical imaging modality, many researches have been devoted to improving the resolution of optical coherence tomography (OCT). We developed a deep-learning based OCT self super-resolution (OCT-SSR) pipeline to improve the axial resolution of OCT images based on the high-resolution and low-resolution spectral data collected by the OCT system. In this pipeline, the enhanced super-resolution asymmetric generative adversarial networks were built to improve the network outputs without increasing the complexity. The feasibility and effectiveness of the approach were demonstrated by experimental results on the images of the biological samples collected by the home-made spectral-domain OCT and swept-source OCT systems. More importantly, we found the sidelobes in the original images can be obviously suppressed while improving the resolution based on the OCT-SSR method, which can help to reduce pseudo-signal in OCT imaging when non-Gaussian spectra light source is used. We believe that the OCT-SSR method has broad prospects in breaking the limitation of the source bandwidth on the axial resolution of the OCT system.

PARP inhibitor shuts down the global translation of thyroid cancer through promoting Pol II binding to DIMT1 pause.

Thyroid cancer has become the most frequent endocrine-related malignancy. Currently, a mounting body of evidences support the clinical strategies for extending the benefit of PARP inhibitors beyond BRCA-mutant cancers. However, the functions and molecular mechanisms of PARP inhibitors in thyroid cancers (TCs) are not fully understood. Here, on the one hand, we revealed that niraparib promotes the accumulation of DNA damage in TCs. On the other hand, we indicated that niraparib inhibits the transcription of DIMT1 through promoting Pol II pausing in a PAR-dependent manner, subsequently leading to a global translation inhibition in TCs. Meanwhile, we found that niraparib activates the NF-κB signaling pathway by inhibiting the PARylation of p65, which decreases its ubiquitination and degradation level through E3 ubiquitin ligase RNF146. Moreover, bortezomib (a small molecule inhibitor of the NF-κB signaling pathway) could significantly enhance the anti-tumor effect of niraparib on TCs in vitro and in vivo. Our findings provide mechanistic supports for the efficacy of PARP inhibitors in cancer cells lacking BRCA-mutant.

The survival outcomes of prophylactic lateral neck dissection for medullary thyroid carcinoma, a retrospective cohort study.

OBJECTIVES: The purpose of this study was to evaluate the benefits of prophylactic lymph node dissection in medullary thyroid carcinoma (MTC) patients without radiographically lateral neck metastases. DESIGN: Retrospective cohort study. SETTING: Tianjin Medical University Cancer Institute and Hospital. PARTICIPANTS: Patients who underwent primary surgery for MTC between 2011 and 2019 and without structural disease of the lateral neck preoperatively. MAIN OUTCOME MEASURES: Locoregional recurrence, disease-free survival (DFS), and overall survival (OS) were examined. RESULTS: The patients were divided into two groups: the central lymph node dissection (CLND) only group and the prophylactic lateral lymph node dissection (PLND) group, which included CLND and ipsilateral lateral lymph node dissection (LLND). A total of 89 patients were included: 71 patients in the CLND group and 18 patients in the PLND group. Although there were no significant differences in age, gender, multifocality, capsule invasion or TNM stage between the two groups, the tumour size and preoperative median calcitonin levels were different. The recurrence rate was 4.2% for the CLND group and 5.6% for the PLND group (p > 0.05). DFS among the CLND and PLND groups was 95.4% and 94.4%, and OS among the groups was 100% and 94.1% (p > 0.05) at 5 years. The biochemical cure rates were similar. CONCLUSIONS: PLND in the absence of structural disease of the lateral neck preoperatively is not associated with improved survival in patients with sporadic MTC.

Value of lymph node ratio as a prognostic factor of recurrence in medullary thyroid cancer.

Background and Objectives: The purpose of this study is to evaluate the relationship between lymph node status (the number of resected lymph nodes; the number of metastatic lymph nodes, LNM, and lymph node ratio, LNR) and biochemical recurrence, disease-free survival (DFS), as well as overall survival (OS) in medullary thyroid carcinoma (MTC). Methods: This study enrolled MTC patients at Tianjin Medical University Cancer Institute and Hospital between 2011 and 2019. We used Logistic regression analysis, Cox regression models and Kaplan-Meier test to identify risk factors influencing biochemical recurrence, DFS, and OS. Results: We identified 160 patients who satisfied the inclusion criteria from 2011 to 2019. We used ROC analysis to define the cut-off value of LNR with 0.24. Multifocality, preoperative calcitonin levels, pathologic N stage, resected lymph nodes, LNM, LNR, and the American Joint Committee on Cancer (AJCC) clinical stage were significant (P < 0.05) prognostic factors influencing biochemical cure. In univariable analyses, gross extrathyroidal extension, preoperative calcitonin levels, pathologic T classification, pathologic N stage, resected lymph nodes, LNM, LNR, AJCC clinical stage, and biochemical cure were significant (P < 0.05) factors of DFS. When the multivariable analysis was performed, LNR was identified as predictor of DFS (HR = 4.818, 95% CI [1.270-18.276]). Univariable Cox regression models reflected that tumor size, pathologic N stage, and LNR were predictor of OS. Furthermore, multivariable analysis manifested that LNR was predictor of OS (HR = 10.061, 95% CI [1.222-82.841]). Conclusions: This study illustrated that LNR was independent prognostic factor of DFS and OS in MTC. In addition, LNR influenced biochemical cure. Further investigations are needed to determine the optimal cut-off value for predicting prognosis.

Multi-omics profiling of papillary thyroid microcarcinoma reveals different somatic mutations and a unique transcriptomic signature.

BACKGROUND: Papillary thyroid microcarcinoma (PTMC) incidence has significantly increased, and some cases still exhibit invasive traits. The entire molecular landscape of PTMC, which can offer hints for the etiology of cancer, is currently absent. METHODS: We compared our findings with those for PTMC in the TCGA by analyzing the largest study at the current stage of whole exome sequencing and RNA-sequencing data from 64 patients with PTMC. Then, we systematically demonstrated the differences between the two PTMC subtypes based on multi-omics analyses. Additionally, we created a molecular prediction model for the PTMC subtypes and validated them among TCGA patients for individualized integrative assessment. RESULTS: In addition to the presence of BRAF mutations and RET fusions in the TCGA cohort, we also discovered a new molecular signature named PTMC-inflammatory that implies a potential response to immune intervention, which is enriched with AFP mutations, IGH@-ext fusions, elevated immune-related genes, positive peroxidase antibody, and positive thyroglobulin antibody. Additionally, a molecular prediction model for the PTMC-inflammatory patients was created and validated among TCGA patients, while the prognosis for these patients is poor. CONCLUSIONS: Our findings comprehensively define the clinical and molecular features of PTMC and may inspire new therapeutic hypotheses.

Safety and effectiveness of carbon nanoparticles suspension-guided lymph node dissection during thyroidectomy in patients with thyroid papillary cancer: a prospective, multicenter, randomized, blank-controlled trial.

Objective: This study aimed to evaluate the effectiveness and safety of carbon nanoparticles-guided lymph node dissection during thyroidectomy in patients with papillary thyroid cancer(PTC). Methods: Clinical trials consisted of two subgroups: unilateral lobectomy (UL; n=283) and total thyroidectomy (TT; n=286). From each subgroup, the patients were randomly assigned to two groups: the carbon nanoparticle group and control group. Primary endpoints included parathyroid hormone (PTH) levels, number of lymph nodes (LNs) detected, number of tiny lymph nodes detected, and recognition and retention of the parathyroid glands. Secondary endpoint was recognition and protection of the recurrent laryngeal nerve. Results: A total of 569 patients with PTC were recruited. There were no statistically significant differences in demographics between the carbon nanoparticles and control groups (P > 0.05). In the UL subgroup, there were no significant differences in PTH levels between the two groups at preoperative, intraoperative, and postoperative day one, and postoperative month one (P>0.05). There was no significant difference in the serum Ca2+ levels between the two groups preoperatively and at postoperative month one (P>0.05). The number of lymph nodes dissected in the carbon nanoparticles group was significantly higher than that in the control group (P<0.0001). The detection rate of tiny lymph nodes in the carbon nanoparticles group was higher than that in the control group (P=0.0268). In the TT subgroup, there was no significant difference in PTH levels between the two groups at preoperative, intraoperative, and postoperative day one (P>0.05). However, the mean PTH level in the carbon nanoparticles group was significantly higher than that of the control group at postoperative month one (P=0.0368). There was no significant difference in the serum Ca2+ levels between the two groups preoperatively and at postoperative month one (P>0.05). There were no significant differences between the two groups in the number of dissected LNs (P>0.05) or the detection rate of tiny lymph nodes (P>0.05). No drug-related AE and complications due to the injection of carbon nanoparticles were recorded in this study. There were no significant differences between the two groups in terms of parathyroid preserved in situ and recurrent laryngeal nerve injury in the UL and TT subgroups. Conclusions: Carbon nanoparticles demonstrated efficacy and safety in thyroidectomy. The application of carbon nanoparticles could significantly facilitate the identification and clearance of LNs and the optimum preservation of parathyroid function. Clinical trial registration: https://www.chictr.org.cn/, identifier ChiCTR2300068502.

To Explore the Inhibitory Mechanism of Quercetin in Thyroid Papillary Carcinoma through Network Pharmacology and Experiments.

Quercetin, a flavonoid with anti-inflammatory and anticancer properties, is expected to be an innovative anticancer therapeutic agent for papillary thyroid carcinoma (PTC). However, the downstream signaling pathways that mediate quercetin-dependent anticancer properties remain to be deciphered. Herein, potential targets of quercetin were screened with several bioinformatic avenues including PharmMapper, Gene Expression Omnibus (GEO) database, protein-protein interaction (PPI) network, and molecular docking. Besides, western blot, CCK-8 transwell analysis of migration and invasion, flow cytometric analysis, and colony formation assays were performed to investigate the underlying mechanism. We found four core nodes (MMP9, JUN, SPP1, and HMOX1) by constructing a PPI network with 23 common targets. Through functional enrichment analysis, we confirmed that the above four target genes are enriched in the TNF, PI3K-AKT, and NF-κB signaling pathways, which are involved in the inflammatory microenvironment and inhibit the development and progression of tumors. Furthermore, molecular docking results demonstrated that quercetin shows strong binding efficiency with the proteins encoded by these 4 key proteins. Finally, quercetin displayed strong antitumor efficacy in PTC cell lines. In this research, we demonstrated the application of network pharmacology in evaluating the mechanisms of action and molecular targets of quercetin, which regulates a variety of proteins and signaling pathways in PTC. These data might explain the mechanism underlying the anticancer effects of quercetin in PTC.

Anlotinib in patients with medullary thyroid carcinoma with negative prognostic factors: A sub-analysis based on the ALTER01031 study.

Background: Medullary thyroid carcinoma (MTC) is a rare type of thyroid cancer; however, it accounted for 13.4% of the disease-specific mortalities. ALTER01031 (NCT02586350) was a randomised, placebo-controlled phase 2b trial that evaluated the efficacy and safety of anlotinib in locally advanced or metastatic MTC. This post hoc analysis aimed to evaluate the efficacy and safety of anlotinib in older patients and those with bone metastases using ALTER01031. Methods: In ALTER01031, anlotinib significantly prolonged the median progression-free survival (PFS) from 11.1 months to 20.7 months compared with placebo in the whole population. Patients who were older (≥ 50 years) or had bone metastases were selected. PFS and overall survival (OS) were estimated and compared between patients receiving anlotinib or placebo in each subgroup. A sub-analysis of tumour response and safety was also performed. Results: Patients with older age or bone metastases experienced rapid disease progression as the median PFS was 6.8 months and 7.0 months respectively in the placebo group. Anlotinib significantly improved the median PFS to 17.5 months (P = 0.002) and 20.7 months (P = 0.029) with hazard ratio (HR) of 0.31 (95% CI, 0.15-0.68) and 0.44 (95% CI, 0.20-0.94) compared with placebo. Significant benefit in OS was observed in patients with older age after a longer follow-up (HR = 0.47 [95% CI, 0.22-0.99], P = 0.041). The safety profile of these subgroups was similar to that of the entire population. Conclusion: This sub-analysis demonstrated significant survival benefits and favourable safety of anlotinib in patients with MTC who had old age or bone metastases, supporting the feasibility of anlotinib in these patients.

Classification of neck tissues in OCT images by using convolutional neural network.

Identification and classification of surrounding neck tissues are very important in thyroid surgery. The advantages of optical coherence tomography (OCT), high resolution, non-invasion, and non-destruction make it have great potential in identifying different neck tissues during thyroidectomy. We studied the automatic classification for neck tissues in OCT images based on convolutional neural network in this paper. OCT images of five kinds of neck tissues were collected firstly by our home-made swept source (SS-OCT) system, and a dataset was built for neural network training. Three image classification neural networks: LeNet, VGGNet, and ResNet, were used to train and test the dataset. The impact of transfer learning on the classification of neck tissue OCT images was also studied. Through the comparison of accuracy, it was found that ResNet has the best classification accuracy among the three networks. In addition, transfer learning did not significantly improve the accuracy, but it can somewhat accelerate the convergence of the network and shorten the network training time.

Preoperative supplementation of calcitriol and calcium relieves symptom and extent of hypocalcemia in patients undergoing total thyroidectomy and bilateral central compartment neck dissection: A prospective, randomized, open-label, parallel-controlled clinical study.

Background: Hypocalcemia is the most common complication that challenges surgeons performing total thyroidectomy. Conventional postoperative calcium and calcitriol supplement has been reportedly effective; however, a time lag has been reported before taking effect. Therefore, the role of preoperative strategy is yet to be determined. Study design: In this prospective, randomized, open-label, parallel-controlled phase II clinical study (registration number: ChiCTR2200059815), a short-term preoperative administration of calcitriol and calcium was proposed in 210 patients undergoing total thyroidectomy and bilateral central compartment neck dissection. Patients were recruited and randomized (1:1:1) into three groups: (A) combined (preoperative calcitriol and calcium), (B) calcium only (preoperative calcium only), and (C) control (no preoperative intervention). Finally, a total of 172 patients were qualified for final analysis. Results: Our data showed that 16 of 63 patients (25.4%) in the combined group had symptomatic hypocalcemia, whereas more patients from the control group (25 of 57 patients, 43.9%, P = 0.033) had symptomatic hypocalcemia. Further, the postoperative calcium level in the combined group is higher than in the control group (2.15 ± 0.15 vs. 2.09 ± 0.15 mmol/L, P = 0.031). Moreover, patients from the combined group showed lower calcium rates of <2.00 mmol/L (12.7% vs. 28.1%, P = 0.036). Remarkably, compared with the control group, patients with transient hypoparathyroidism in the combined group showed fewer rates for both symptomatic and biochemical hypocalcemia (28.6% vs. 61.1% for symptomatic hypocalcemia; 47.6% vs. 75% for biochemical hypocalcemia). Patients without transient hypoparathyroidism in all three groups showed no significant difference in rates for either symptomatic or biochemical hypocalcemia, indicating that this preoperative strategy is only effective for patients with transient hypoparathyroidism. We did not observe such beneficial effects in patients from the calcium group. Conclusions: Preoperative administration of calcitriol and calcium could reduce symptomatic and biochemical hypocalcemia, especially for those with transient hypoparathyroidism. Moreover, this maneuver could be recommended as a clinical routine in patients undergoing total thyroidectomy and bilateral central compartment neck dissection. Clinical Trial Registration: http://www.chictr.org.cn/edit.aspx?pid=164316&htm=4, identifier ChiCTR2200059815.

Digital refocusing based on deep learning in optical coherence tomography.

We present a deep learning-based digital refocusing approach to extend depth of focus for optical coherence tomography (OCT) in this paper. We built pixel-level registered pairs of en face low-resolution (LR) and high-resolution (HR) OCT images based on experimental data and introduced the receptive field block into the generative adversarial networks to learn the complex mapping relationship between LR-HR image pairs. It was demonstrated by results of phantom and biological samples that the lateral resolutions of OCT images were improved in a large imaging depth clearly. We firmly believe deep learning methods have broad prospects in optimizing OCT imaging.

Relationship Between Thyroid Autoantibodies and Recurrence of Papillary Thyroid Carcinoma in Children and Adolescents.

Background: Numerous studies reported connection between papillary thyroid carcinoma (PTC) and thyroid autoantibody in adults, but few of them have investigated whether there is a similar link in children and adolescents. The purpose of this research was to explore the relationship between clinicopathological features, prognosis and preoperative thyroid peroxidase antibody (TPOAb) as well as thyroglobulin antibody (TgAb) status in children and adolescents with PTC. Methods: This study retrospectively reviewed 179 patients of PTC who underwent a thyroidectomy from January 2000 to June 2021 at Tianjin Medical University Cancer Hospital. We compared preoperative TgAb and TPOAb status with the clinicopathological features and prognosis of children and adolescents with PTC in different age groups. Results: Patients with positive preoperative TPOAb and TgAb had lower recurrence rate in the younger group (P = 0.006, 0.047, respectively). Patients with positive TPOAb preoperatively had normal level of preoperative Tg and less cervical LNM than patients with negative TPOAb in children and adolescents (P < 0.05). Positive TPOAb preoperatively of PTC patients had a longer median DFS (113.4 months) than negative TPOAb (64.9 months) (P = 0.009, log-rank). Univariate analyses showed age, maximal tumor size, T stage, multifocality, lateral LNM and N staging were predictors for cancer recurrence in children and adolescents (P<0.05). Cox regression analysis found younger age (HR 0.224, P < 0.001), lateral LNM (HR 0.137, P = 0.010), N stage (HR 30.356, P < 0.001) were independent risk factors for recurrence. Conclusions: Our study found that presence of preoperative TPOAb and TgAb could serve as novel prognostic factors for predicting recurrence of PTC in children.

Surgical selection and prognostic analysis in patients with unilateral sporadic medullary thyroid carcinoma.

PURPOSE: The extent of thyroid surgery and cervical lymph node dissection of unilateral sporadic medullary thyroid carcinoma (sMTC) is still controversial, and the aim of this study was to investigate whether hemithyroidectomy was adequate as a locally curative surgery for patients with unilateral sMTC. METHODS: This study is a retrospective case series of patients with sMTC who underwent curative total thyroidectomy or hemithyroidectomy in our institution from January 2011 to December 2019. RESULTS: In total, 129 patients who met the inclusion criteria were enrolled including 49 (38.0%) patients who underwent total thyroidectomy and 80 (62.0%) patients who underwent hemithyroidectomy. About 80 (62.0%) patients achieved a biochemical cure (BC), whereas there was no significant difference between two groups in biochemical cure rate (61.2% versus 62.5%, P = 0.885). A logistic regression analysis showed a strong negative correlation between the factors of preoperative calcitonin level and pTNM stage and biochemical cure. In the log-rank test, no significant difference in OS (P = 0.314) and DFS (P = 0.409) was found between the two surgical groups. Lateral cervical lymph node metastasis and pTNM stage were significant prognostic factors affecting DFS in univariate analysis; moreover, absence of biochemical cure, tumor size ≥ 4 cm and lateral cervical lymph node metastasis were independent risk factors of unilateral sMTC patients in our analysis. CONCLUSION: For patients with unilateral sMTC, hemithyroidectomy was adequate as a locally curative surgery, because the patients underwent total thyroidectomy did not benefit more from it in the aspects of BC/OS/RFS, while the postoperative increasing incidence rate of postoperative hypocalcemia could not improve patients' quality of life.

Ultrasound features of medullary thyroid cancer as predictors of biological behavior.

BACKGROUND: Medullary thyroid cancer (MTC) has more aggressive behavior and poor prognosis. Ultrasound (US) has facilitated the qualitative diagnosis of thyroid nodules, however, some MTC may be diagnosed as a benign nodule on ultrasound because ultrasound features of malignancy are lacking. The aim of the study was to investigate the association between ultrasound features and biological behavior of MTC. METHODS: Ultrasound findings and medical records of patients with MTC between Jan 2015 to Jun 2017 were retrospectively reviewed at Tianjin Medical University Cancer Institute and Hospital. MTC were categorized using modified TI-RADS classification, then were classified as "malignant" (m-MTC) or "US-low-suspicious" (l-MTC). We compared the biological behavior between the two groups, and further analyzed the risk factors for the recurrence. RESULTS: A total of 78 patients were enrolled, of which 55 m-MTC (70.5%) and 23 l-MTC (29.5%) were identified. The N staging of the m-MTC was significantly higher than that of l-MTC(P = 0.000). The preoperative serum Ct level in m-MTC were significantly higher than that of l-MTC(P = 0.035). Biochemical cure were more frequent in l-MTC than that of m-MTC (P = 0.002). Disease recurrence rates were 19.7% (14 of 71). Disease recurrence was more frequent in m-MTC than that of l-MTC (P = 0.013). Disease recurrence was positively associated with extrathyroid extension (P = 0.047), N staging (P = 0.003), preoperative serum Ct level (P = 0.009) and negatively associated with biochemical cure(P = 0.000). In multivariable Cox regression analysis, extrathyroid extension and biochemical cure were independent risk factors for recurrence of MTC. CONCLUSIONS: L-MTC has a more indolent character than m-MTC. The extrathyroid extension and biochemical cure were independent risk factors for recurrence of MTC.

LDHA induces EMT gene transcription and regulates autophagy to promote the metastasis and tumorigenesis of papillary thyroid carcinoma.

Papillary thyroid carcinoma (PTC) is one of the most common kinds of endocrine-related cancer and has a heterogeneous prognosis. Metabolic reprogramming is one of the hallmarks of cancers. Aberrant glucose metabolism is associated with malignant biological behavior. However, the functions and mechanisms of glucose metabolism genes in PTC are not fully understood. Thus, data from The Cancer Genome Atlas database were analyzed, and lactate dehydrogenase A (LDHA) was determined to be a potential novel diagnostic and therapeutic target for PTCs. The research objective was to investigate the expression of LDHA in PTCs and to explore the main functions and relative mechanisms of LDHA in PTCs. Higher expression levels of LDHA were found in PTC tissues than in normal thyroid tissues at both the mRNA and protein levels. Higher expression levels of LDHA were correlated with aggressive clinicopathological features and poor prognosis. Moreover, we found that LDHA not only promoted PTC migration and invasion but also enhanced tumor growth both in vitro and in vivo. In addition, we revealed that the metabolic products of LDHA catalyzed induced the epithelial-mesenchymal transition process by increasing the relative gene H3K27 acetylation. Moreover, LDHA knockdown activated the AMPK pathway and induced protective autophagy. An autophagy inhibitor significantly enhanced the antitumor effect of FX11. These results suggested that LDHA enhanced the cell metastasis and proliferation of PTCs and may therefore become a potential therapeutic target for PTCs.

A CRISPR-Cas9-Based Near-Infrared Upconversion-Activated DNA Methylation Editing System.

DNA methylation is a kind of a crucial epigenetic marker orchestrating gene expression, molecular function, and cellular phenotype. However, manipulating the methylation status of specific genes remains challenging. Here, a clustered regularly interspaced palindromic repeats-Cas9-based near-infrared upconversion-activated DNA methylation editing system (CNAMS) was designed for the optogenetic editing of DNA methylation. The fusion proteins of photosensitive CRY2PHR, the catalytic domain of DNMT3A or TET1, and the fusion proteins for CIBN and catalytically inactive Cas9 (dCas9) were engineered. The CNAMS could control DNA methylation editing in response to blue light, thus allowing methylation editing in a spatiotemporal manner. Furthermore, after combination with upconversion nanoparticles, the spectral sensitivity of DNA methylation editing was extended from the blue light to near-infrared (NIR) light, providing the possibility for remote DNA methylation editing. These results demonstrated a meaningful step forward toward realizing the specific editing of DNA methylation, suggesting the wide utility of our CNAMS for functional studies on epigenetic regulation and potential therapeutic strategies for related diseases.