Predictive Value of Jugulo-omohyoid Lymph Nodes in Lateral Lymph Node Metastasis of Papillary Thyroid Cancer.

BACKGROUND: Jugulo-omohyoid lymph nodes (JOHLN) metastasis has proven to be associated with lateral lymph node metastasis (LLNM). This study aimed to reveal the clinical features and evaluate the predictive value of JOHLN in PTC to guide the extent of surgery. METHODS: A total of 550 patients pathologically diagnosed with PTC between October 2015 and January 2020, all of whom underwent thyroidectomy and lateral lymph node dissection, were included in this study. RESULTS: Thyroiditis, tumor location, tumor size, extra-thyroidal extension, extra-nodal extension, central lymph node metastasis (CLNM), and LLMM were associated with JOHLN. Male, upper lobe tumor, multifocality, extra-nodal extension, CLNM, and JOHLN metastasis were independent risk factors from LLNM. A nomogram based on predictors performed well. Nerve invasion contributed the most to the prediction model, followed by JOHLN metastasis. The area under the curve (AUC) was 0.855, and the p-value of the Hosmer-Lemeshow goodness of fit test was 0.18. Decision curve analysis showed that the nomogram was clinically helpful. CONCLUSION: JOLHN metastasis could be a clinically sensitive predictor of further LLM. A high-performance nomogram was established, which can provide an individual risk assessment of LNM and guide treatment decisions for patients.

The machine learning-based model for lateral lymph node metastasis of thyroid medullary carcinoma improved the prediction ability of occult metastasis.

BACKGROUND: For medullary thyroid carcinoma (MTC) with no positive findings in the lateral neck before surgery, whether prophylactic lateral neck dissection (LND) is needed remains controversial. A better way to predict occult metastasis in the lateral neck is needed. METHODS: From January 2010 to January 2022, patients who were diagnosed with MTC and underwent primary surgery at our hospital were retrospectively reviewed. We collected the patients' baseline characteristics, surgical procedure, and rescored the ultrasound images of the primary lesions using American College of Radiology (ACR) Thyroid Imaging, Reporting and Data System (TI-RADS). Regularized logistic regression, 5-fold cross-validation and decision curve analysis was applied for lateral lymph node metastasis (LLNM) model's development and validation. Then, we tested the predictive ability of the LLNM model for occult LLNM in cN0-1a patients. RESULTS: A total of 218 patients were enrolled. Five baseline characteristics and two TI-RADS features were identified as high-risk factors for LLNM: gender, baseline calcitonin (Ctn), tumor size, multifocality, and central lymph node (CLN) status, as well as TI-RADS margin and level. A LLNM model was developed and showed a good discrimination with 5-fold cross-validation mean area under curve (AUC) = 0.92 ± 0.03 in the test dataset. Among cN0-1a patients, our LLNM model achieved an AUC of 0.91 (95% CI, 0.88-0.94) for predicting occult LLNM, which was significantly higher than the AUCs of baseline Ctn (0.83) and CLN status (0.64). CONCLUSIONS: We developed a LLNM prediction model for MTC using machine learning based on clinical baseline characteristics and TI-RADS. Our model can predict occult LLNM for cN0-1a patients more accurately, then benefit the decision of prophylactic LND.

IGF2BP3 regulates the expression of RRM2 and promotes the progression of rheumatoid arthritis via RRM2/Akt/MMP-9 pathway.

BACKGROUND: Rheumatoid arthritis (RA) is a common inflammatory and autoimmune disease. Ribonucleotide Reductase Regulatory Subunit M2 (RRM2) is a crucial and a rate-limiting enzyme responsible for deoxynucleotide triphosphate(dNTP) production. We have found a high expression level of RRM2 in patients with RA, but the molecular mechanism of its action remains unclear. METHODS: We analyzed the expression of hub genes in RA using GSE77298 datasets downloaded from Gene Expression Omnibus database. RRM2 and insulin-like growth factor-2 messenger ribonucleic acid (mRNA)-binding protein 3 (IGF2BP3) gene knockdown was achieved by infection with lentiviruses. The expression of RRM2, IGF2BP3, matrix metalloproteinase (MMP)-1, and MMP-9 were detected via western blotting assay. Cell viability was detected via 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay. MeRIP-qRT-PCR was performed to test the interaction of IGF2BP3 and RRM2 mRNA via m6A modification. Cell proliferation was determined by clone formation assay. Migration and invasion assays were performed using transwell Boyden chamber. RESULTS: RRM2 and IGF2BP3 were highly expressed in clinical specimens and tumor necrosis factor alpha (TNF-α) and interleukin (IL)-1ß-stimulated synovial cells. RRM2 and IGF2BP3 knockdown inhibited the proliferation, migration, and invasion of MH7A cells. The inhibitory effects of IGF2BP3 knockdown were effectively reversed by simultaneously overexpressing RRM2 in MH7A cells. By analyzing N6-methyladenosine (m6A)2Target database, five m6A regulatory target binding sites for IGF2BP3 were identified in RRM2 mRNA, suggesting a direct relationship between IGF2BP3 and RRM2 mRNA. Additionally, in RRM2 small hairpin (sh)RNA lentivirus-infected cells, the levels of phosphorylated Akt and MMP-9 were significantly decreased compared with control shRNA lentivirus-infected cells. CONCLUSION: The present study demonstrated that RRM2 promoted the Akt phosphorylation leading to high expression of MMP-9 to promote the migration and invasive capacities of MH7A cells. Overall, IGF2BP promotes the expression of RRM2, and regulates the migration and invasion of MH7A cells via Akt/MMP-9 pathway to promote RA progression.

Identifying the Best Candidate for Primary Tumor Resection in Patients With Advanced Osteosarcoma.

OBJECTIVES: Not all patients with stage III and IV osteosarcoma who undergo surgery to remove the primary tumor will benefit from surgery; therefore, we developed a nomogram model to test the hypothesis that only a subset of patients will benefit from surgery. METHODS: 412 patients were screened from the Surveillance, Epidemiology and End Results (SEER) database. Subsequently, 1:1 propensity score matching (PSM) was used to screen and balance confounders. We first made the hypothesis that patients who underwent the procedure would benefit more. A multivariate Cox model was used to explore the independent influencing factors of CSS in two groups (benefit group and non-benefit group) and constructed nomograms with predicted prognosis. Finally, receiver operating characteristic (ROC) curves, calibration curves, and decision curve analysis (DCA) were used to verify the performance of the nomogram. RESULTS: Of these patients, approximately 110 did not undergo primary tumour resection. After passing PSM, they were divided into a surgical group and a non-surgical group. Age, primary site and chemotherapy as calculated independent factors were used to construct a nomogra. The predicted nomogram showed good consistency in terms of the ROC curve and the calibration curve, and the DCA curve showed a certain clinical utility. Finally, dividing the surgical patients into surgical beneficiaries and surgical non-beneficiaries, a Kaplan-Meier analysis showed that the nomogram can identify patients with osteosarcoma who can benefit from surgery. CONCLUSION: A practical predictive model was established to determine whether patients with stage III or IV osteosarcoma would benefit from surgery.

Combining radiomics with thyroid imaging reporting and data system to predict lateral cervical lymph node metastases in medullary thyroid cancer.

BACKGROUND: Medullary Thyroid Carcinoma (MTC) is a rare type of thyroid cancer. Accurate prediction of lateral cervical lymph node metastases (LCLNM) in MTC patients can help guide surgical decisions and ensure that patients receive the most appropriate and effective surgery. To our knowledge, no studies have been published that use radiomics analysis to forecast LCLNM in MTC patients. The purpose of this study is to develop a radiomics combined with thyroid imaging reporting and data system (TI-RADS) model that can use preoperative thyroid ultrasound images to noninvasively predict the LCLNM status of MTC. METHODS: We retrospectively included 218 MTC patients who were confirmed from postoperative pathology as LCLNM negative (n=111) and positive (n=107). Ultrasound features were selected using the Student's t-test, while radiomics features are first extracted from preoperative thyroid ultrasound images, and then a two-step feature selection approach was used to select features. These features are then used to establish three regularized logistic regression models, namely the TI-RADS model (TM), the radiomics model (RM), and the radiomics-TI-RADS model (RTM), in 5-fold cross-validation to determine the likelihood of the LCLNM. The Delong's test and decision curve analysis (DCA) were used to evaluate and compare the performance of the models. RESULTS: The ultrasound features of margin and TI-RADS level, and a total of 12 selected radiomics features, were significantly different between the LCLNM negative and positive groups (p<0.05). The TM, RM, and RTM yielded an averaged AUC of 0.68±0.05, 0.78±0.06, and 0.82±0.05 in the 5-fold cross-validation dataset, respectively. RM and RTM are statistically better than TM (p<0.05 and p<0.001) according to Delong test. DCA demonstrates that RTM brings more benefit than TM and RM. CONCLUSIONS: We have developed a joint radiomics-based model for noninvasive prediction of the LCLNM in MTC patients solely using preoperative thyroid ultrasound imaging. It has the potential to be used as a complementary tool to help guide treatment decisions for this rare form of thyroid cancer.

Distinct risk factors of lateral lymph node metastasis in patients with papillary thyroid cancer based on age stratification.

INTRODUCTION: Studies have revealed that age is associated with the risk of lateral lymph node metastasis (LLNM) in papillary thyroid cancer (PTC). This study aimed to identify the optimal cut point of age for a more precise prediction model of LLNM and to reveal differences in risk factors between patients of distinct age stages. METHODS: A total of 499 patients who had undergone thyroidectomy and lateral neck dissection (LND) for PTC were enrolled. The locally weighted scatterplot smoothing (LOWESS) curve and the 'changepoint' package were used to identify the optimal age cut point using R. Multivariate logistic regression analysis was performed to identify independent risk factors of LLNM in each group divided by age. RESULTS: Younger patients were more likely to have LLNM, and the optimal cut points of age to stratify the risk of LLNM were 30 and 45 years old. Central lymph node metastasis (CLNM) was a prominent risk factor for further LNM in all patients. Apart from CLNM, sex(p = 0.033), tumor size(p = 0.027), and tumor location(p = 0.020) were independent predictors for patients younger than 30 years old; tumor location(p = 0.013), extra-thyroidal extension(p < 0.001), and extra-nodal extension(p = 0.042) were independent risk factors for patients older than 45 years old. CONCLUSIONS: Our study could be interpreted as an implication for a change in surgical management. LND should be more actively performed when CLNM is confirmed; for younger patients with tumors in the upper lobe and older patients with extra-thyroidal extension tumors, more aggressive detection of the lateral neck might be considered.

Targeting gut microbial nitrogen recycling and cellular uptake of ammonium to improve bortezomib resistance in multiple myeloma.

The gut microbiome has been found to play a crucial role in the treatment of multiple myeloma (MM), which is still considered incurable due to drug resistance. In previous studies, we demonstrated that intestinal nitrogen-recycling bacteria are enriched in patients with MM. However, their role in MM relapse remains unclear. This study highlights the specific enrichment of Citrobacter freundii (C. freundii) in patients with relapsed MM. Through fecal microbial transplantation experiments, we demonstrate that C. freundii plays a critical role in inducing drug resistance in MM by increasing levels of circulating ammonium. The ammonium enters MM cells through the transmembrane channel protein SLC12A2, promoting chromosomal instability and drug resistance by stabilizing the NEK2 protein. We show that furosemide sodium, a loop diuretic, downregulates SLC12A2, thereby inhibiting ammonium uptake by MM cells and improving progression-free survival and curative effect scores. These findings provide new therapeutic targets and strategies for the intervention of MM progression and drug resistance.

Comprehensive analysis of single-cell and bulk RNA-sequencing data identifies B cell marker genes signature that predicts prognosis and analysis of immune checkpoints expression in head and neck squamous cell carcinoma.

Recent studies have shown that B cells and the associated tertiary lymphoid structures (TLS) correlate with the response of patients to immune checkpoint inhibitors (ICIs) and predict overall survival (OS) in cancer patients. We screened 145 B cell marker genes (BCMG) by a comprehensive analysis of single-cell RNA-sequencing (scRNA-seq) data of head and neck squamous cell carcinoma (HNSC) from the Gene Expression Omnibus (GEO) database. The BCMG signature (BCMGS) was established using The Cancer Genome Atlas (TCGA) dataset of HNSC and verified in four independent datasets. The multivariate Cox regression analysis identified the signature as an independent prognostic factor. A prognostic nomogram was constructed with independent prognostic factors using the TCGA dataset. GO and KEGG analysis revealed the underlying signaling pathways related to this signature. Study of immune profiles showed that patients in the low-risk group presented discriminative immune-cell infiltrations. Furthermore, the low-risk group was featured by higher TCR and BCR diversity, which suggested that low-risk patients may be more sensitive to ICIs. Immunohistochemistry was performed, and we found that high expression of FTH1 was significantly correlated with poor OS (P = 0.025). The expression of TIM-3, LAG-3 and PD-1 was positively correlated and associated with better OS in HNSC. However, there was no statistically significant difference between PD-L1, PD-L2, CTLA-4, TIGIT and prognosis. The BCMGS was a promising prognostic biomarker in HNSC, which may help to interpret the responses to immunotherapy and provide a new perspective for future research on the treatment in HNSC.

The minimal number of examined lymph nodes for accurate nodal staging and favorable prognosis in T1-2 supraglottic laryngeal squamous cell carcinoma.

OBJECTIVE: The study aimed to investigate the minimal number of examined lymph nodes (ELNs) for accurate assessment of lymph node status and favorable prognosis in patients with stage T1-2 supraglottic laryngeal squamous cell carcinoma (LSCC) who received radical resection. METHODS: Patients with stage T1-2 supraglottic LSCC from the Surveillance, Epidemiology, and End Results (SEER) database and the Chinese Academy of Medical Sciences, Cancer Hospital/National Cancer Center (NCC) were reviewed. The association of the ELN count with the identification of nodal metastasis and overall survival (OS) was analyzed using a multivariate regression model. Locally weighted scatterplot smoothing fitting curve and the 'changepoint' package were adopted to identify the optimal cut points using R. RESULTS: A total of 429 patients from the SEER database and 53 patients from NCC were enrolled. The probability of identifying nodal metastasis was positively related to the ELN count. For patients diagnosed with pathological stage N0 (pN0) disease, the mortality risks rapidly decreased when the amount of ELNs exceeded ten, and those with ELNs >10 had better OS. CONCLUSION: An adequate amount of ELNs benefits precise nodal staging in patients with stage T1-2 supraglottic LSCC. Ten lymph nodes are the minimum number of ELNs. For pN0 patients, an ELN count ≤10 is an unfavorable prognostic factor.

Revision total hip arthroplasty using a fluted, tapered, modular stem follow-up method for a mean of three years: A preliminary study.

Objective: This study aimed to evaluate the results and complications related to revision total hip arthroplasty within a short-to-medium follow up period. Methods: From January 2016 to January 2020, we reviewed 31 prosthetic hip arthroplasty stem revisions using a fluted, tapered modular stem with distal fixation. The median age of the patients was 74.55-79 years. The survival rate was 100%, and there were no re-revisions. The Harris hip score improved from an average of 36.5 ± 7.8 before surgery to 81.8 ± 6.2 at the final follow-up. Results: The average final follow-up was 36 (24-60) months. During this time, there was no periprosthetic infection, no prosthesis loosening or breakage, and no sciatic nerve injury. Complications included four (12.9%) intraoperative fractures and eight (25.8%) dislocations that had no stem fractures. The postoperative limb was lengthened by 17.8 ± 9.8 mm. In most cases, bone regeneration was an early and important finding. Three cases underwent extended trochanteric osteotomy, and bone healing was achieved by the final follow-up. Conclusion: The modular tapered stem reviewed in this study was very versatile, could be used in most femoral revision cases, and allowed for rapid bone reconstruction. However, a long-term follow-up study is needed to confirm these results.

Endovascular Treatment of Superior Mesenteric Artery Pseudoaneurysm Due to Infective Endocarditis With Stent-Graft.

PURPOSE: To report a successful case of pseudoaneurysm of the superior mesenteric artery (SMA) caused by infected endocarditis treated with a covered stent. CASE REPORT: A patient was diagnosed with infective endocarditis and 2 months later a proximal SMA pseudoaneurysm was identified on computed tomography. Daptomycin was started on admission and continued for approximately 4 months until the inflammatory markers normalized, and then the SMA pseudoaneurysm was successfully excluded with a stent-graft and antibiotics were continued for 1 year after the procedure. There were no associated complications or recurrences at the 3-year follow-up. CONCLUSION: Placing a covered stent with a full course of antibiotics before and after surgery may be a successful alternative to open surgery in the treatment of pseudoaneurysms of the SMA due to infective endocarditis. CLINICAL IMPACT: This case report reports a rare case of pseudoaneurysm of the superior mesenteric artery due to infective endocarditis, which was successfully treated with an overlapping stent and confirmed by complete imaging data at a three-year follow-up. This report suggests that endovascular treatment may be an alternative to open surgery in the treatment of pseudoaneurysms of the superior mesenteric artery caused by infective endocarditis.

The Optimal Age Threshold for Stratifying the Risks of Disease Progression in Patients with Highly Suspicious Sub-centimeter Thyroid Nodules.

PURPOSE: The study aimed to identify the value and optimal age cutoff to predict the progression of highly suspicious thyroid nodules ≤ 10 mm during active surveillance (AS), and to reveal distinct risk factors in patients of different ages. METHODS: A total of 779 patients with highly suspicious thyroid nodules were enrolled and followed up by ultrasonography. Locally weighted scatterplot smoothing (LOWESS) and the package 'changepoint' were used to identify the optimal age cutoffs using R. Multivariate Cox regression was performed to identify independent prognostic factors in each patient group divided according to age. RESULTS: Age was an independent predictor of nodule progression (P = 0.038). The optimal age cutoff to stratify the risk of nodule progression was 30 years. Younger patients were more likely to have progression of nodules during AS (P < 0.001), including enlargement of nodule size (P = 0.011) and new lesion occurrence (P < 0.001). Nodule size was identified as a risk factor for disease progression in patients younger than 30 years old (P = 0.008, OR 7.946, 95% CI 1.715-36.820), while multifocality (P = 0.018, OR 2.315, 95% CI 1.155-4.639) and thyroiditis (P = 0.028, OR 2.265, 95% CI 1.092-4.699) were independent predictors in patients over 30 years old. CONCLUSIONS: Highly suspicious thyroid nodules ≤ 10 mm in young patients tended to be more progressive. The predictors of disease progression were distinct in patients of different ages.

The optimal number of examined lymph nodes for accurate nodal staging and favorable prognosis of oral tongue squamous cell carcinoma.

OBJECTIVE: The study aimed to determine the optimal count of examined lymph nodes (ELN) for accurate assessment of lymph node status and favorable long-term survival in patients with oral tongue squamous cell carcinoma (OTSCC) who received radical resection. METHODS: Patients with OTSCC who received radical resection between 2004 and 2015 were enrolled from the Surveillance, Epidemiology, and End Results database (SEER) and were randomly divided into two cohorts. The association of ELN count with nodal migration and overall survival (OS) was analyzed using a multivariate regression model with the adjustment of relevant factors. Locally weighted scatterplot smoothing (LOWESS) and 'strucchange' package were adopted to identify the optimal cut points using R. RESULTS: A total of 2077 patients were included in this study. The optimal cut points of ELN count for accurate nodal staging and favorable OS were 19 and 15, respectively. The probability of detecting positive lymph nodes (PLN) significantly increased in patients with ELN count ≥ 19 in comparison to those with ELN count < 19 (training set, P < 0.001; validation set, P = 0.012). A better postoperative prognosis was observed in patients with ELN count ≥ 15 than those with fewer ELN (training set, P = 0.001, OR: 0.765; validation set, P = 0.016, OR: 0.678). CONCLUSION: The optimal cut point of ELN count to ensure the accuracy of nodal staging and to achieve a favorable postoperative prognosis were 19 and 15, respectively. The ELN count beyond the cutoff values might improve the accuracy of cancer staging and OS.

Survival and long-term quality-of-life of concurrent chemoradiotherapy versus surgery followed by radiotherapy with or without concurrent chemotherapy for the treatment of resectable stage III/IV hypopharyngeal carcinoma.

OBJECTIVE: We evaluated the utility of concurrent chemoradiotherapy (CCRT) compared to surgery followed by adjuvant radiotherapy (with or without concurrent chemotherapy) (SRT) in terms of improving the life expectancy and quality-of-life (QOL) of patients with stage III/IV hypopharyngeal squamous cell carcinomas (HPSCCs). METHODS: From January 2010 to July 2018, a total of 299 patients with stage III/IV HPSCC who received surgery followed by adjuvant radiotherapy (with or without concurrent chemotherapy) (SRT, n = 111), or concurrent chemoradiotherapy (CCRT, n = 188) in our hospital were included. We measured overall survival (OS) and disease-free survival (DFS). We used the EORTC QLQ-C30, QLQ-H&N35, and Voice handicap index-30 (VHI-30) instruments to assess the long-term QOL. RESULTS: The OS and DFS afforded by SRT were significantly better than those associated with CCRT (p = 0.039; p = 0.048 respectively), especially for stage N2-N3 patients. CCRT patients experienced better speech outcomes. CONCLUSION: For resectable stage III/IV HPSCC patients, appropriate treatment plans should be selected comprehensively considering survival rate, QOL, patient preference and multidisciplinary treatment.

Evaluation of serum B7-H3 expression, ultrasound and clinical characteristics to predict the risk of cervical lymph node metastases in papillary thyroid carcinoma by nomogram.

BACKGROUND: Improving the preoperative diagnosis of cervical lymph node metastasis (LNM) will help improve the clinical outcomes of papillary thyroid carcinoma (PTC) patients. B7-H3, as an immune checkpoint of the B7 family, is highly expressed in PTC tissues and related to LNM and prognosis. We aimed to explore the clinical values of serum B7-H3 (sB7-H3) in predicting LNM in PTC by a nomogram prediction model. METHODS: From September 2019 to May 2021, a total of 344 PTC patients with primary surgery in our hospital were enrolled in this research. Enzyme-linked Immunosorbent Assay (ELISA) was used to detect sB7-H3 from the peripheral blood of PTC patients and normal controls. We created a nomogram prediction model in combination with sB7-H3 expression, clinical and ultrasound characteristics to predict LNM in the early stage. RESULTS: Gender (p = 0.001), age (p = 0.015), tumor size (p < 0.001), number of tumors (p = 0.021) and sB7-H3 expression (p = 0.003) were independent risk factors for LNM in PTC. All the factors were included in the nomogram. The area under the curve (AUC) was 73.9% (95% CI, 68.12%-79.69%). CONCLUSION: The nomogram is helpful in assessing the risk of LNM in PTC. sB7-H3 has excellent potential in predicting LNM in patients with PTC as an adjunctive ultrasound tool.

Machine learning models predict overall survival and progression free survival of non-surgical esophageal cancer patients with chemoradiotherapy based on CT image radiomics signatures.

PURPOSE: To construct machine learning models for predicting progression free survival (PFS) and overall survival (OS) with esophageal squamous cell carcinoma (ESCC) patients. METHODS: 204 ESCC patients were randomly divided into training cohort (n = 143) and test cohort (n = 61) according to the ratio of 7:3. Two radiomics models were constructed by radiomics features, which were selected by LASSO Cox model to predict PFS and OS, respectively. Clinical features were selected by univariate and multivariate Cox proportional hazards model (p < 0.05). Combined radiomics and clinical model was developed by selected clinical and radiomics features. The receiver operating characteristic curve, Kaplan Meier curve and nomogram were used to display the capability of constructed models. RESULTS: There were 944 radiomics features extracted based on volume of interest in CT images. There were six radiomics features and seven clinical features for PFS prediction and three radiomics features and three clinical features for OS prediction; The radiomics models showed general performance in training cohort and test cohort for prediction for prediction PFS (AUC, 0.664, 0.676. C-index, 0.65, 0.64) and OS (AUC, 0.634, 0.646.C-index, 0.64, 0.65). The combined models displayed high performance in training cohort and test cohort for prediction PFS (AUC, 0.856, 0.833. C-index, 0.81, 0.79) and OS (AUC, 0.742, 0.768. C-index, 0.72, 0.71). CONCLUSION: We developed combined radiomics and clinical machine learning models with better performance than radiomics or clinical alone, which were used to accurate predict 3 years PFS and OS of non-surgical ESCC patients. The prediction results could provide a reference for clinical decision.

PROSER2 is a poor prognostic biomarker for patients with osteosarcoma and promotes proliferation, migration and invasion of osteosarcoma cells.

Proline- and serine-rich 2 (PROSER2) is encoded by the 47th open reading frame on human chromosome 10. Bioinformatic analysis has shown PROSER2 was significantly correlated with prognostic outcome of osteosarcoma patients. Its role in the progression and metastasis of human osteosarcoma has not been elucidated until now. Bioinformatics analysis was performed on 101 patients with osteosarcoma from The Cancer Genome Atlas database. High levels of PROSER2 were associated with a poor prognosis in patients with osteosarcoma. PROSER2 expression was significantly upregulated in clinical specimens from patients with osteosarcoma and osteosarcoma cell lines. MTT assay was performed to test the cell viability and Transwell assay was used to test the migration and invasion of MG63 cells. PROSER2 knockdown inhibited the viability, migration and invasion of MG63 cells. Gene Set Enrichment Analysis and Gene Ontology/Kyoto Encyclopedia of Genes and Genomes analysis showed that the differentially expressed genes were primarily involved in 'calcium signaling pathway' and 'Wnt signaling' in patients with osteosarcoma and high PROSER2 expression. Western blotting analysis revealed that PROSER2 regulated migration and invasion of osteosarcoma via the Wnt/nuclear factor of activated T-cells (NFAT)c1 signaling pathway. In conclusion, PROSER2 promoted the proliferation, migration and invasion of osteosarcoma cells via the Wnt/Ca2+/NFATc1 signaling pathway by increasing nuclear localization of NFATc1.

Deep learning based on ultrasound to differentiate pathologically proven atypical and typical medullary thyroid carcinoma from follicular thyroid adenoma.

OBJECTIVES: To investigate the feasibility and value of deep learning based on grayscale ultrasonography in the differentiation of pathologically proven atypical and typical medullary thyroid carcinoma (MTC) from follicular thyroid adenoma (FTA). METHODS: The preoperative 770 ultrasound images consisted of 354 MTCs (66% were typical MTCs with a high suspicion sonographic pattern, 34% were atypical MTCs with a suspicion pattern of intermediate or less) and 416 FTAs. All images were delineated manually by a senior sonographer to achieve the regions of interest. Two deep neural networks of ResNet-34 and ResNet-18 were performed on the training set (n = 690). The test data set (n = 80) was subsequently evaluated by the two models and two sonographers, their diagnostic performances and misdiagnosis lesions were compared and analyzed. RESULTS: The ResNet-34 model shows higher diagnostic ability than the junior sonographer with an area under the receiver operating curve of 0.992 (95% CI: 0.840-0.970)versus 0.754 (95% CI:0.645-0.843). Moreover, 12 of 16 atypical MTCs were successfully identified by the ResNet-34, which is significantly better than the senior and junior sonographer, suggesting that these patients could benefit from timely serological examination and surgical strategy at an earlier stage. CONCLUSION: Deep learning to differentiate MTC from FTA on grayscale ultrasound may be a useful diagnostic support tool, especially in atypical MTC and FTA. Moreover, the computing time of deep learning is short, which will help to incorporate it into real-time ultrasound diagnosis.

A nomogram to predict lateral lymph node metastases in lateral neck in patients with medullary thyroid cancer.

Background: Medullary thyroid cancer (MTC) can only be cured by surgery, but the management of lateral lymph nodes is controversial, especially for patients with cN0+cN1a. To address this challenge, we developed a multivariate logistic regression model to predict lateral lymph node metastases (LNM). Methods: We retrospectively collected clinical data from 124 consecutive MTC patients who underwent initial surgery at our institution. The data of 82 patients (from 2010 to 2018) and 42 patients (from January 2019 to November 2019) were used as the training set for building the model and as the test set for validating the model, respectively. Results: In the training group, the multivariate analyses indicated that male and MTC patients with higher preoperative basal calcitonin levels were more likely to have lateral LNM (P = 0.007 and 0.005, respectively). Multifocal lesions and suspected lateral LNM in preoperative ultrasound (US) were independent risk factors (P = 0.032 and 0.002, respectively). The identified risk factors were incorporated into a multivariate logistic regression model to generate the nomogram, which showed good discrimination (C-index = 0.963, 95% confidence interval [CI]: 0.9286-0.9972). Our model was validated with an excellent result in the test set and even superior to the training set (C-index = 0.964, 95% CI: 0.9121-1.000). Conclusion: Higher preoperative basal calcitonin level, male sex, multifocal lesions, and lateral lymph node involvement suspicion on US are risk factors for lateral LNM. Our model and nomogram will objectively and accurately predict lateral LNM in patients with MTC.