Risk Factors for Lymph Node Metastasis in Papillary Thyroid Carcinoma: A Retrospective Study.

At present, the risk factors of cervical lymph node metastasis (LNM) in papillary thyroid carcinoma (PTC) are still controversial. This study was aimed to investigate the risk factors of various types of LNM in PTC with tumor diameter>1 cm. The clinical data of 2216 PTC patients were retrospectively analyzed. Univariate and multivariate logistic regression models were used to analyze the risk factors of LNM. In addition, the receiver operator characteristic (ROC) curve was used to find the best cut-off value of CLNM for predicting LLNM. Finally, the independent risk factors of LLNM were used to construct the prediction of LLNM nomogram. Age≤55 years old, male, bilateral lobe tumors, ETE, 2-3 cm tumor diameters, and fasting plasma glucose (FPG) were independent risk factors for CLNM. The ROC curve showed that the best cut-off value was 2.5. Age, male, bilateral lobe tumors, tumor diameters≥2 cm and CLNM≥3 were significantly associated with LLNM , while CLNM=1 or 2 was a protective factor for LLNM. Only tumor diameters≥3 cm was significantly associated with skip LLNM. The nomogram model (C-index=0.745) can be used to predict LLNM in PTC patients and guide the clinical selection of appropriate treatment options. Patients with high risk factors should undergo prophylactic lymph node dissection. The nomogram we established has a good predictive ability for LLNM, and for high-risk groups, it is necessary to actively perform prophylactic lateral lymph node dissection.

Overexpressed ZC3H13 suppresses papillary thyroid carcinoma growth through m6A modification-mediated IQGAP1 degradation.

PURPOSE: The purpose of this study was to clarify the effect of ZC3H13 on the growth of papillary thyroid carcinoma (PTC). METHODS: Firstly, we used qRT-PCR and Western blot to compare the difference in the expression of ZC3H13 between normal thyroid epithelial cells and PTC cell lines. Then, ZC3H13 overexpression/knockout thyroid cancer cells were constructed by lentivirus transfection, and the effects of overexpression of ZC3H13 on the proliferation, migration and invasion of PTC cells were detected by CCK8 and transwell experiments. Lastly, MeRIP-qPCR, RIP and o Actinomycin D were used to verify that ZC3H13 regulated the expression of downstream target gene IQGAP1 through m6A modification. RESULTS: ZC3H13 expression was decreased in PTC cell lines BCPAP, KTC-1, k1, HTH83, and TPC-1. Proliferation, invasion, and migration of PTC cells were inhibited by overexpressed ZC3H13 but increased by knockdown of ZC3H13. IQGAP1 expression was suppressed by ZC3H13 overexpression but enhanced by ZC3H13 knockdown. In ZC3H13-overexpressed PTC cells, the m6A level of IQGAP1 mRNA was increased, and the IQGAP1 mRNA expression was decreased with the increasing time of Actinomycin D treatment. YTHDF2 enriched more IQGAP1 mRNA than IgG and knockdown of YTHDF2 reversed the effect of ZC3H13 overexpression on IQGAP1 mRNA stability. The xenograft tumor experiment in nude mice confirmed that the overexpression of ZC3H13 inhibited tumor growth, while overexpression of IQGAP1 could reverse the inhibitory effect of ZC3H13 overexpression on tumor growth. CONCLUSION: ZC3H13 mediates IQGAP1 mRNA degradation by promoting m6A modification of IQGAP1 mRNA, this provides a prospective therapeutic target for PTC.

CEBPB knockdown sensitizes nasopharyngeal carcinoma cells to cisplatin by promoting the expression of serine protease inhibitor Kazal-type 5.

Serine protease inhibitor Kazal-type 5 (SPINK5) has been indicated to act as a prognostic predictor for patients with head and neck squamous cell carcinoma. However, its specific role in nasopharyngeal carcinoma (NPC), a malignancy that has a high propensity for chemoresistance, remains largely obscure. We, thus, sought to investigate the importance of SPINK5 expression in regulating chemoresistance in NPC. Differentially expressed genes in NPC were screened using the cancer genome atlas-head and neck squamous cell carcinoma database and microarray analysis. SPINK5 was downregulated in NPC tissues and cells. After SPINK5 upregulation, the cells treated with cisplatin showed reduced cell survival and the ability to migrate, invade and metastasize. Mechanistically, the transcription factors regulating SPINK5 were queried through the JASPAR website, followed by dual-luciferase and Chromatin immunoprecipitation assay validation. CCAAT enhancer-binding protein (CEBP) beta (CEBPB) bound to the SPINK5 promoter region in NPC cells. The silencing of CEBPB enhanced the expression of SPINK5. CEBPB overexpression reversed the inhibitory effects of cisplatin on NPC cell malignant phenotype in the presence of SPINK5 overexpression. In conclusion, CEBPB silencing promoted chemoresistance of NPC cells via activating SPINK5, signifying that targeting CEBPB was a new approach to enhance the chemotherapy efficacy in NPC.

Inflammation Markers Have Important Value in Predicting Relapse in Patients with papillary thyroid carcinoma: A Long-Term Follow-Up Retrospective Study.

PURPOSE: Many markers of inflammation are increasingly found to have prognostic significance in some cancers. This study investigated the prognostic value of albumin/globulin (AGR), lymphocyte/monocyte ratio (LMR), and other inflammatory markers, including neutrophil/lymphocyte ratio (NLR) and platelet/lymphocyte ratio (PLR), in patients with papillary thyroid carcinoma (PTC). METHODS: We retrospectively analyzed the data of 764 patients newly diagnosed with PTC (608 women, 156 men) aged 10-83 years. Univariate and multivariate analyses were used to analyze recurrence rates and assess potential prognostic factors. Furthermore, we used random survival forests to construct a random survival forest score (RSFscore). The correlations between various inflammatory factors and traditional prognostic factors were analyzed. We also compared the areas under the curve (AUCs) of the RSFscore and 4 inflammation-based markers. RESULTS: AGR, NLR, PLR, and LMR were strongly associated with invasive clinicopathological features (tumor size, lesions, lymph node metastasis, and lymph node metastasis rate) and postoperative recurrence. In the multivariate analysis, AGR and LMR were independent prognostic markers for recurrent PTC. Higher NLR and PLR values indicated a higher risk of recurrence, while higher LMR and AGR values suggested a lower recurrence risk. The predictive power of the combined indicators was stronger than that of single indicators alone. CONCLUSION: Compared to the analysis of a single indicator, the combination of inflammatory markers was more helpful in determining the risk of PTC recurrence, which has an important impact on predicting patients' cancer-free survival and quality of life.

Combined prognostic value of preoperative serum thyrotrophin and thyroid hormone concentration in papillary thyroid cancer.

BACKGROUND: A growing number of studies have found a close association between thyroid hormones and thyrotrophin (TSH), and they also have prognostic significance in some cancer types; this study aimed to investigate the prognostic value of free triiodothyronine (fT3), free thyroxine (fT4), fT3/fT4, TSH, and their combination in patients with papillary thyroid carcinoma (PTC). METHODS: This study retrospectively analyzed the relevant data of 726 newly diagnosed PTC patients. Both univariate and multivariate analyses were used to predict the recurrence rate, and a risk score was established. In addition, with the use of a random survival forest, a random forest (RF) score was constructed. After calculating the area under the curve (AUC), the diagnostic efficacy of risk score, RF score, and four indicators was compared. RESULTS: fT3, fT4, fT3/fT4, and TSH were strongly associated with some invasive clinicopathological features and postoperative recurrence. Patients with high expression of fT4 and TSH have a high risk of recurrence. By contrast, patients with high expression of fT3 and fT3/fT4 have a low risk of recurrence. At the same time, the combined use of various indicators is more helpful for establishing an accurate diagnosis. By comparison, we found that the RF score was better than the risk score in terms of predicting the recurrence of PTC. CONCLUSION: The diagnostic accuracy of a combination of fT3, fT4, fT3/fT4, and TSH can help improve our clinical estimate of the risk of recurrent PTC, thus allowing the development of a more effective treatment plan for patients.

Kin17 facilitates thyroid cancer cell proliferation, migration, and invasion by activating p38 MAPK signaling pathway.

Kin17 DNA and RNA binding protein (Kin17) is an extremely conserved nuclear protein that is almost expressed in every type of mammal cells. Recently, Kin17 has been implicated into the regulation of tumorigenesis of diverse human cancers. However, its functions in thyroid cancer (TC) are still largely unexplored. Kin17 mRNA and protein level were tested by qRT-PCR and western blot, respectively. Effects of Kin17 on TC cell proliferation were estimated by colony formation assay and flow cytometry analysis in vitro as well as by in vivo tumor growth experiment. TC cell migratory and invasive capacities were assessed via wound-healing and transwell experiments. Epithelial-mesenchymal transition (EMT)-related proteins (E-cadherin and N-cadherin) and p38 MAPAK signaling pathway-related proteins (p-p38, p38, Cyclin D1, and p27) were examined via western blot. Kin17 was remarkably increased in TC tissue samples and cell lines at both mRNA and protein levels compared to normal tissue and control cell line. Knockdown of Kin17 obviously repressed TC cell proliferation, arrested cell cycle, and inhibited TC cell migration and invasion in vitro, while overexpression of Kin17 produced opposite effects. Kin17 knockdown suppressed p38 MAPK signaling pathway, while Kin17 overexpression activated this pathway. Treatment of p38 agonist (p79350) abolished the repressive effects of sh-Kin17 on TC cell proliferation, migration, and invasion, as well as on p38 pathway. Kin17 knockdown was also found to enhance the sensitivity of Doxorubicin of TC cells. In addition, Kin17 knockdown in vivo also markedly repressed TC tumor growth and p38 pathway. Kin17 functioned as an oncogene of TC by activating p38 MAPK signaling pathway.

Identification and validation of m6A RNA methylation regulators with clinical prognostic value in Papillary thyroid cancer.

BACKGROUND: Papillary thyroid cancer (PTC) is a type of malignant tumor with excellent prognosis, accounting for more than 80% of thyroid cancer. Recently, numerous studies illustrated the importance of N 6-methyladenosine (m6A) RNA modification to tumorigenesis, but it has never been reported in PTC. METHODS: We downloaded data from The Cancer Genome Atlas (TCGA) and analyzed RNA expression, single nucleotide polymorphisms (SNPs) and copy number variations (CNVs) of 19 m6A RNA methylation regulators in PTC. Then we used nonnegative matrix factorization (NMF) to cluster patients into two m6A subtypes and compared them in overall survival (OS) and disease-free survival (DFS). The Weighted correlation network analysis (WGCNA) and univariate Cox proportional hazard model (CoxPH) were used to select genes for the construction of a m6A-related signature. The accuracy and prognostic value of this signature were validated by using receiver operating characteristic (ROC) curves, K-M (Kaplan-Meier) survival analysis, univariant and multivariant analyses. RESULTS: CNVs and differential expression of m6A regulators were observed in PTC patients. Especially IGF2BP2 (Insulin-like growth factor 2 mRNA binding protein 2), which was most significantly overexpressed in tumor tissue. We chose 4 genes in the m6A-related module from WGCNA: IGF2BP2, STT3A, MTHFD1 and GSTM4, and used them to construct a m6A-related signature. The prognostic value of this signature was validated, and risk scores provided by the signature was the independent prognostic factor for PTC. A nomogram was also provided for clinical usage. CONCLUSIONS: We performed a comprehensive evaluation of the m6A RNA modification landscape of PTC and explored its underlying mechanisms. Our m6A-related signature was of great significance in predicting the DFS of patients with PTC. And IGF2BP2 was a gene worthy for further analysis as its strong correlation with DFS and clinical phenotypes of PTC.

Special role of JUN in papillary thyroid carcinoma based on bioinformatics analysis.

BACKGROUND: Papillary thyroid carcinoma (PTC) is the most common malignancy in thyroid tissue, and the number of patients with PTC has been increasing in recent years. Discovering the mechanism of PTC genesis and progression and finding new potential diagnostic biomarkers/therapeutic target genes of PTC are of great significance. METHODS: In this work, the datasets GSE3467 and GSE3678 were downloaded from the Gene Expression Omnibus (GEO) database. Differentially expressed genes (DEGs) were identified with the limma package in R. GO function and KEGG pathway enrichment were conducted with DAVID tool. The interaction network of the DEGs and other genes was performed with Cytoscape plugin BisoGenet, while clustering analysis was performed with Cytoscape plugin ClusterOne. RESULTS: A total of 1800 overlapped DEGs were detected in two datasets. Enrichment analysis of the DEGs found that the top three enriched GO terms in three ontologies and four significantly enriched KEGG pathways were mainly concerned with intercellular junction and extracellular matrix components. Interaction network analysis found that transcription factor hepatocyte nuclear factor 4, alpha (HNF4A) and DEG JUN had higher connection degrees. Clustering analysis indicated that two function modules, in which JUN was playing a central role, were highly relevant to PTC genesis and progression. CONCLUSIONS: JUN may be used as a specific diagnostic biomarker/therapeutic molecular target of PTC. However, further experiments are still needed to confirm our results.

Development of a novel dynamic nomogram for predicting overall survival in anaplastic thyroid cancer patients with distant metastasis: a population-based study based on the SEER database.

Background: Anaplastic thyroid cancer (ATC) is highly invasive, prone to distant metastasis (DM), and has a very poor prognosis. This study aims to construct an accurate survival prediction model for ATC patients with DM, providing reference for comprehensive assessment and treatment planning. Methods: We extracted data of ATC patients with DM diagnosed between 2004 and 2019 from the SEER database, randomly dividing them into a training set and a validation set in a ratio of 7:3. Univariate and multivariate Cox regression analyses were sequentially performed on the training set to identify independent prognostic factors for overall survival (OS) and construct nomograms for 3-month, 6-month, and 8-month OS for ATC patients with DM based on all identified independent prognostic factors. Receiver operating characteristic (ROC) curve analysis, decision curve analysis (DCA) curve analysis, and calibration curves were separately plotted on the training and validation sets to demonstrate the model's performance. Furthermore, patients were stratified into high- and low-risk groups based on their risk scores, and the Kaplan-Meier (KM) survival curves were used to illustrate the survival differences between the two groups. Results: A total of 322 patients were included in this study. Univariate and multivariate Cox regression analyses identified five independent prognostic factors for OS in ATC patients with DM: surgery, tumor size, age, chemotherapy, and radiotherapy. Nomograms for 3-month, 6-month, and 8-month OS were established based on these factors. The training set AUC values (3-month AUC: 0.767, 6-month AUC: 0.789, 8-month AUC: 0.795) and validation set AUC values (3-month AUC: 0.753, 6-month AUC: 0.798, 8-month AUC: 0.806) as well as the calibration curves demonstrated excellent applicability and accuracy of the model. Additionally, the DCA curves indicated substantial clinical net benefit of the model. The KM curves also confirmed the model's excellent stratification ability for patient OS. Conclusion: The nomogram developed in this study accurately predicts OS for ATC patients with DM. It can assist clinicians in formulating appropriate treatment strategies for these patients.

Photoactivation Inducing Multifunctional Coupling of Fluorophore for Efficient Tumor Therapy In Situ.

Photoactivatable molecules, with high-precision spatialtemporal control, have largely promoted bioimaging and phototherapy applications of fluorescent dyes. Here, the first photoactivatable sensor (BI) is described that can be triggered by broad excitation light (405-660 nm), which further undergoes intersystem crossing and H-atom transfer processes to forming superoxide anion radicals (O2 -•) and carbon radicals. Particularly, the photoinduced gain of carbon-centered radicals (BI•) allows for radical-radical coupling to afford the combined crosslink product (BI─BI), which would be oxidized in the presence of O2 -• to produce an extended conjugate system with near infrared emission (820 nm). Besides, the photochemically generated product (Cy─BI) possesses ultra-high photothermal conversion efficiency up to 90.9%, which optimized phototherapy potential. What's more, Western Blot assay reveals that both BI and the photoproduct Cy─BI can efficiently inhibit the expression of CHK1, and the irradiation of BI and Cy─BI further induces apoptosis and ultimately enhances the phototherapeutic effects. Thus, the combination of cell cycle block inducing apoptosis, photodynamic therapy and photothermal therapy treatments significantly suppress solid tumor in vivo antitumor efficacy explorations. This is a novel finding in developing photoactivatable molecules, as well as the broad applicability of photoimaging and phototherapy in tumor-related areas.

TP63 transcriptionally regulates SLC7A5 to suppress ferroptosis in head and neck squamous cell carcinoma.

Background: Most head and neck squamous cell carcinoma (HNSCC) patients are diagnosed at an advanced local stage. While immunotherapy has improved survival rates, only a minority of patients respond durably to targeted immunotherapies, posing substantial clinical challenges. We investigated the heterogeneity of the tumor microenvironment in HNSCC cohorts before and after immunotherapy by analyzing single-cell RNA sequencing (scRNA-seq) data and bulk RNA sequencing datasets retrieved from public databases. Methods: We constructed a single-cell transcriptome landscape of HNSCC patients before and after immunotherapy and analyzed the cellular composition, developmental trajectories, gene regulatory networks, and communication patterns of different cell type subpopulations. Additionally, we assessed the expression levels of relevant indicators in HNSCC cells via western blot, ELISA, and fluorescent probe techniques. Results: At the single-cell level, we identified a subpopulation of TP63+ SLC7A5+ HNSCC that exhibited a ferroptosis-resistant phenotype. This subpopulation suppresses ferroptosis in malignant cells through the transcriptional upregulation of SLC7A5 mediated by high TP63 expression, thereby promoting tumor growth and resistance to immunotherapy. The experimental results demonstrated that the overexpression of TP63 upregulated the expression of SLC7A5 and suppressed the concentrations of Fe2+ and ROS in HNSCC cells. By integrating bulk transcriptome data, we developed a clinical scoring model based on TP63 and SLC7A5, which are closely associated with tumor stage, revealing the significant prognostic efficacy of the TP63+ SLC7A5+ HNSCC-mediated ferroptosis mechanism in HNSCC patients. Conclusion: Our research elucidates the TME in HNSCC before and after immunotherapy, revealing a novel mechanism by which TP63+ SLC7A5+ HNSCC inhibits ferroptosis and enhances tumor resistance via TP63-induced SLC7A5 upregulation. These insights lay the foundation for the development of more effective treatments for HNSCC.

Implications of m5C modifications in ribosomal proteins on oxidative stress, metabolic reprogramming, and immune responses in patients with mid-to-late-stage head and neck squamous cell carcinoma: Insights from nanopore sequencing.

Background: Head and Neck Squamous Cell Carcinoma (HNSCC) is a malignancy characterized by a high incidence and recurrence rate. 5-methylcytosine (m5C) RNA modification is a common alteration affecting cancer progression; however, how m5C operates within the tumor microenvironment of HNSCC remains to be elucidated. Methods: We conducted Nanopore sequencing on 3 pairs of cancer and paracancerous tissues from mid- and late-stage HNSCC, obtaining 132 upregulated genes (transcriptomically upregulated, m5C elevated) and 129 downregulated genes (transcriptomically downregulated, m5C reduced). Subsequent Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analyses were performed; a differential gene interaction network (PPI) was constructed, revealing the interactions of each gene with others in the network. Co-expression analysis was performed on the genes within the PPI, unveiling their expression and regulatory relationships. Through GSVA analysis, variations in related pathways under different states were identified. Furthermore, results of m5C in lncRNA were screened, followed by target gene prediction. Results: Sequencing results from the 3 pairs of mid- and late-stage HNSCC cancer and paracancerous tissues demonstrated that RPS27A, RPL8, and the lncRNAs including differentiation antagonizing nonprotein coding RNA (DANCR), DCST1 antisense RNA 1 (CCDC144NL-AS1), Growth Arrest-Specific Transcript 5 (GAS5), Nuclear Paraspeckle Assembly Transcript 1 (NEAT1), and Small Nucleolar RNA Host Gene 3 (SNHG3), etc., under m5Cregulation, have close connections with surrounding genes. The differentially m5Cmodified genes are primarily involved in ribosomal protein synthesis, oxidative stress response, metabolic reprogramming, immunity, and other life processes; pathways like mitochondrial protein import and photodynamic therapy induced unfolded protein response are upregulated in the tumor, while pathways, including the classic P53, are suppressed. Analysis on m5C-regulated long non-coding RNAs (lncRNAs) revealed tight associations with RPS27A and RPL8 as well. Conclusion: Our study identifies the key factors and signaling pathways involving m5C in HNSCC. The findings suggest that ribosome-related genes might regulate ribosomal protein synthesis, oxidative stress response, metabolic reprogramming, and immune response through m5C RNA modification by means like hypoxia and ferroptosis, thereby playing a pivotal role in the onset and progression of HNSCC. Hence, attention should be paid to the role of ribosomes in HNSCC. These findings may facilitate the precision and individualized treatment of patients with mid- and late-stage HNSCC in clinical settings.

Construction of an index system of core competence assessment for otolaryngology nurse specialists in China: A Delphi study.

BACKGROUND: Clinical nurse specialists play a vital role in the work quality, patient safety and team development of nurses. However, there is currently no prior study constructing the index of core competence assessment for otolaryngology Nurse Specialists. OBJECTIVES: To establish an index system for the evaluation of Chinese otolaryngology Nurse Specialists' core competence. DESIGN: A Delphi study. SETTINGS: The study was mainly conducted in a university-affiliated hospital in China. PARTICIPANTS: Twenty-two experts with otolaryngology knowledge and practical experience from different regions and organizations in China. METHODS: We used literature reviews and expert meetings to establish a draft index system . Subsequently, a two-round Delphi survey was utilized to consult opinions from 22 experts about the index for the evaluation of otolaryngology nurse specialists' core competence and provide qualitative comments on their ratings. Consensus was predefined as a mean important score of 4.0 or above and a coefficient of variation is not above 0.25 among the participants. RESULTS: The final evaluation indexes of the core competencies for otolaryngology Nurse Specialists included 5 first-level indexes (clinical competence, critical thinking competence, leadership, professional development competence, professionalism), 19 second-level indexes, and 85 third-level indexes. The effective response rates of the two expert consultation rounds were 100 %. The expert authority coefficients were 0.864 and 0.859 in the first and second rounds of consultation, respectively. In the second round of consultation, the first, second and third indexes of Kendall's coefficient of concordance were 0.357, 0.330, and 0.232, respectively (P < 0.001). CONCLUSIONS: The constructed evaluation indexes of the core competencies of otolaryngology Nurse Specialists are scientific, reasonable, comprehensive, and specific and may provide references for the training and evaluation of otolaryngology Nurse Specialists.

Mitochondrial-related genes markers that predict survival in patients with head and neck squamous cell carcinoma affect immunomodulation through hypoxia, glycolysis, and angiogenesis pathways.

Mitochondria play a crucial role in the occurrence and development of tumors. We used mitochondria-related genes for consistent clustering to identify three stable molecular subtypes of head and neck squamous cell carcinoma (HNSCC) with different prognoses, mutations, and immune characteristics. Significant differences were observed in clinical characteristics, immune microenvironment, immune cell infiltration, and immune cell scores. TP53 was the most significantly mutated; cell cycle-related pathways and tumorigenesis-related pathways were activated in different subtypes. Risk modeling was conducted using a multifactor stepwise regression method, and nine genes were identified as mitochondria-related genes affecting prognosis (DKK1, EFNB2, ITGA5, AREG, EPHX3, CHGB, P4HA1, CCND1, and JCHAIN). Risk score calculations revealed significant differences in prognosis, immune cell scores, immune cell infiltration, and responses to conventional chemotherapy drugs. Glycolysis, angiogenesis, hypoxia, and tumor-related pathways were positively correlated with the RiskScore. Clinical samples were subjected to qPCR to validate the results. In this work, we constructed a prognostic model based on the mitochondrial correlation score, which well reflects the risk and positive factors for the prognosis of patients with HNSCC. This model can be used to guide individualized adjuvant and immunotherapy in patients with HNSCC.

Prediction model of cervical lymph node metastasis based on clinicopathological characteristics of papillary thyroid carcinoma: a dual-center retrospective study.

Background: The overall prevalence of papillary thyroid carcinoma (PTC) patients is expanding along with an ongoing increase in thyroid cancer incidence. Patients with PTC who have lymph node metastases have a poor prognosis and a high death rate. There is an urgent need for indicators that can predict lymph node metastasis (LNM) before surgery as current imaging techniques, such as ultrasonography, do not have sufficient sensitivity to detect LNM. To predict independent risk factors for Central lymph node metastasis (CLNM) or Lateral lymph node metastasis (LLNM), we therefore developed two nomograms based on CLNM and LLNM, separately. Methods: In two centers, the Second Affiliated Hospital of Nanchang University and Yichun People's Hospital, we retrospectively analyzed clinicopathological characteristics of PTC patients. We utilized multivariate analysis to screen for variables that might be suspiciously related to CLNM or LLNM. Furthermore, we developed nomograms to graphically depict the independent risk valuables connected to lymph node metastasis in PTC patients. Result: Ultimately, 6068 PTC patients in all were included in the research. Six factors, including age<45, male, mETE, TSH>1.418, tumor size>4cm, and location (multicentric and lobe), were observed to be related to CLNM. Age<45, male, mETE (minimal extrathyroidal extension), multifocality, TSH≥2.910, CLNM positive, and tumor size>4cm were regarded as related risk factors for LLNM. The two nomograms developed subsequently proved to have good predictive power with 0.706 and 0.818 and demonstrated good clinical guidance functionality with clinical decision curves and impact curves. Conclusion: Based on the successful establishment of this dual-institution-based visual nomogram model, we found that some clinical features are highly correlated with cervical lymph node metastasis, including CLNM and LLNM, which will better help clinicians make individualized clinical decisions for more effectively rationalizing managing PTC patients.

Analysis of transcriptional factors and regulation networks in laryngeal squamous cell carcinoma patients with lymph node metastasis.

The present study was to identify and quantitate differentially expressed proteins in laryngeal squamous cell carcinoma (LSCC) tissues with or without lymph node metastasis and to explore transcriptional factors and regulation networks associated with the process. Tissue specimens were taken from 20 patients with LSCC, including 10 cases of LSCC without metastasis LSCC (N0) and 10 cases of LSCC with metastasis LSCC (Nx). Among the 643 unique proteins identified by using iTRAQ labeling and quantitative proteomic technology, 389 proteins showed an abundance change in LSCC (Nx) as compared to LSCC (N0). Cytoskeleton remodeling, cell adhesion, and immune response activation were found to be the main processes in LSCC metastasis. The construction of transcription regulation networks identified key transcription regulators for lymph node metastasis of LSCC, including Sp1, c-myc, and p53, which may affect LSCC metastasis through the epithelial-mesenchymal transition. Furthermore, our results suggest that ubiquitination may be a critical factor in the networks. The present study provides insights into transcriptional factors and regulation networks involved in LSCC metastasis, which may lead to new strategies for treatment of LSCC metastasis.

Viscosity-sensitive NIR probe for in vivo imaging of early-stage hepatic fibrosis.

Herein, a viscosity-sensitive and hepatic-targeted NIR fluorescent probe has been developed for early diagnosis of hepatic fibrosis. Importantly, we observed increased liver viscosity upon CCl4-induced hepatotoxicity and decreased liver viscosity after metformin treatment, which confirmed its high clinical application prospects.

Identification and validation of a prognostic model based on ferroptosis-associated genes in head and neck squamous cancer.

Ferroptosis is that under the action of ferrous iron or ester oxygenase, unsaturated fatty acids highly expressed on the cell membrane are catalyzed to undergo lipid peroxidation, thereby inducing cell death. In this study, we used ferroptosis marker genes to identify 3 stable molecular subtypes (C1, C2, C3) with distinct prognostic, mutational, and immune signatures by consensus clustering; TP53, CDKN2A, etc. Have higher mutation frequencies in the three subtypes. C3 has a better prognosis, while the C1 subtype has a worse prognosis. WGCNA is used to identify molecular subtype-related gene modules.After filting, we obtained a total of 540 genes related to the module feature vector (correlation>0.7).We performed univariate COX regression analysis on these genes, and identified a total of 97 genes (p < 0.05) that had a greater impact on prognosis, including 8 ''Risk" and 89 ''Protective" genes. After using lasso regression, we identified 8 genes (ZNF566, ZNF541, TMEM150C, PPAN, PGLYRP4, ENDOU, RPL23 and MALSU1) as ferroptosis-related genes affecting prognosis. The ferroptosis prognosis-related risk score (FPRS) was calculated for each sample in TCGA-HNSC dataset. The results showed that FPRS was negatively correlated with prognosis.The activated pathways in the PFRS-high group mainly include immune-related pathways and invasion-related pathways. We assessed the extent of immune cell infiltration in patients in our TCGA-HNSC cohort by using the expression levels of gene markers in immune cells. The FPRS-high group had a higher level of immune cell infiltration. We found that the expression of immune checkpoints was significantly up-regulated in the FPRS-low group and the FPRS-high group had a higher probability of immune escape and a lower probability of benefiting from immunotherapy. In this work, we constructed a scoring Ferroptosis-related prognostic model that can well reflect risk and positive factors for prognosis in patients with head and neck squamous cell carcinoma. It can be used to guide individualized adjuvant therapy and chemotherapy for patients with head and neck cancer. Therefore, it has a good survival prediction ability and provides an important reference for clinical treatment.

Fasting serum glucose and lymph node metastasis in non-diabetic PTC patients: a 10-Year multicenter retrospective study.

Background: Mostly current studies are limited to the impact of lymph node metastasis(LNM) on the prognosis of papillary thyroid cancer(PTC) or the impact of glucose metabolism on the occurrence of PTC, but no one has paid attention to the connection between fasting serum glucose(FSG) and LNM. The purpose of our study was to explore the relationship between FSG and LNM in non-diabetic PTC patients. Methods: In this study, we performed a multicenter, retrospective study on 6034 non-diabetic patients with PTC. The associations of FSG with three types of LNM including central lymph node metastasis (CLNM), lateral cervical lymph node metastasis (LLNM) and both were estimated. Results: Compared with PTC patients without LNM, those with LNM had higher FSG. We also found that FSG was associated with tumor extension, maximum tumor diameter and TSH. In order to further explore the association between FSG and different types of LNM, we analyzed three groups of data separately. Our study reveals that by comparing FSG between patients without LNM and patients with three LNM types, it was statistically different in the PTC patients with CLNM and the PTC patients with CLNM combined with LLNM. Conclusion: Our study provides evidence for the association of FSG and LNM in non-diabetic PTC patients, with a gradual increase in FSG over the course of the PTC from no lymph node metastasis to CLNM combined with LLNM. Meanwhile, higher FSG is a risk factor for CLNM and CLNM combined with LLNM. In the future, FSG might be used as an indicator for lymph node dissection in PTC patients. However, larger relative studies are needed.