The clinicopathological features, treatment outcomes and follow-up results of 47 ectopic thyroid gland cases: a single-center retrospective study.

Background: Ectopic thyroid gland (ETG) is an uncommon clinical condition, presenting various challenges and limitations in its regulate diagnosis and treatment currently. This study aims to enhance our understanding of ETG and improve the strategies for its diagnosis and treatment. Methods: The retrospective single-center study was conducted, encompassing clinical data from ETG patients screened at our institution between 2013 and 2022. Patients were categorized based on the location of the disease, and follow-ups were performed on each. Results: This study included a total of 47 patients who were confirmed to hav confirmed to have ETG. Among them, we found 29 cases of accessory thyroid and 18 cases of aberrant thyroid. Furthermore, 42 cases exhibited the single ETG, while 5 cases displayed the double ETG. The distribution of the ETG was as follows: 20 were lingual, 10 were submandibular, 10 were lateral cervical, 4 were thoracic mediastinal, 1 was esophageal, and 7 were ovarian. Of these cases, 22 patients underwent surgery, 18 received thyroid hormone replacement therapy, and 7 were placed under observation. All patients were followed up for 59.4 (12-117) months. No significant abnormalities were detected at the conclusion of the follow-up period. Conclusion: ETG is frequently observed in the head and neck, particularly in lingual. Accessory thyroid glands are commonly reported, with most cases being single ETG. Notably, these glands usually do not manifest specific clinical symptoms. Therefore, the appropriate and comprehensive examinations during the initial diagnosis are crucial to avoid misdiagnosis. Treatment should be individualized, and long-term follow-up is essential for managing ETG effectively.

Efficacy and safety of radiofrequency ablation for primary and secondary hyperparathyroidism: a retrospective study.

There is now growing interest in the use of Ultrasound-guided radiofrequency ablation (RFA) to treat hyperparathyroidism. But the efficacy and limitations of this treatment have not been described in sufficient detail. Assessing and contrasting the effectiveness and safety of RFA in treating primary hyperparathyroidism (PHPT) and secondary hyperparathyroidism (SHPT). This retrospective study included 57 HPT patients (48 for PHPT and 9 for SHPT) who underwent RFA between January 2017 and April 2021. The serum intact parathyroid hormone (iPTH) and calcium, hyperplastic parathyroid volume, volume reduction rate (VRR) before and after RFA, clinical success rate, symptoms, and complications were analyzed and compared. In SHPT group, bone pain (7/9, 77.8%), skin pruritus (4/9, 44.4%), and multiple hyperplastic parathyroid glands (4/9, 44.4%) were more common compared to the PHPT group. After 12 months of follow-up, the serum iPTH, calcium, and the volume of PHPT and SHPT groups had decreased by more than 60%, 10%, and 90%, respectively (P < 0.05). In the VRR, 13 glands of SHPT (72.2%) and 42 glands of PHPT (87.5%) had achieved the clinical success. In addition, the preoperative and postoperative serum iPTH were higher in the SHPT group than in the PHPT group (P < 0.05). In terms of the serum iPTH and calcium, the PHPT group had substantially higher rates of clinical success, with 42 patients (87.5%) and 46 patients (95.8%) meeting the criteria, respectively compared to 3 patients (33.3%) and 6 patients (66.7%) of SHPT group (P < 0.05). After RFA, the clinical symptoms improved in both groups. The overall incidence of complications (hoarseness and postoperative hematoma) of RFA in the two groups was 10.5% (6/57), and hoarseness (3/9, 33.3%) of SHPT group was more common than PHPT group. All the complications were resolved spontaneously within 12 months after symptomatic treatments. In the treatment of PHPT and SHPT, ultrasound-guided RFA is both successful and safe. PHPT patients have better results in restoring normal iPTH by RFA, and have no considerable difference with the SHPT patients in terms of serum calcium, the volume of the ablation area, and the VRR.

Systematic analysis of the prognosis and immune infiltration of E2Fs in thyroid carcinoma.

Purpose: To evaluate the diagnostic and prognostic utility of E2F transcription factors (E2Fs) in thyroid carcinoma (THCA) and their association with immune infiltration. Methods: The transcription and protein levels of E2Fs in THCA tissues were examined using the R language and the Human Protein Atlas (HPA) database in this research. We utilized the UALCAN and GEPIA2 databases to analyze the association between the level of E2Fs and the clinicopathological features of THCA. The prognostic utility of E2F expression in THCA was studied using the R language and the Gene Set Cancer Analysis (GSCA) database. Over-representation analysis (ORA) and gene set enrichment analysis (GSEA) were employed to analyze the effect of E2F family members. The TISIDB database and Tumor Immune Estimation Resource (TIMER) database were utilized to investigate the relationship between E2F expression and the level of immune infiltration in thyroid cancer. Results: E2Fs are highly conserved in thyroid carcinoma and rarely mutated. E2Fs are strongly expressed in THCA and are highly related with the clinicopathological stage of THCA. Patients with THCA have a poor prognosis when E2Fs are highly expressed. The function of E2Fs in THCA may be closely related to the renin-angiotensin system (Ras) signaling pathway, platelet-derived growth factor (PDGF) signaling pathway, apoptosis, and immune response. With regard to the immune infiltration, E2F expression and tumor-infiltrating lymphocytes exhibited a positive connection. Conclusion: The level of E2Fs is connected with the prognosis and immune infiltration level in THCA, revealing that E2Fs may be a prognostic and immune infiltration cell marker in THCA patients.

CCND1-associated ceRNA network reveal the critical pathway of TPRG1-AS1-hsa-miR-363-3p-MYO1B as a prognostic marker for head and neck squamous cell carcinoma.

Head and neck squamous cell carcinoma (HNSC) is one of the leading causes of cancer death globally, yet there are few useful biomarkers for early identification and prognostic prediction. Previous studies have confirmed that CCND1 amplification is closely associated with head and neck oncogenesis, and the present study explored the ceRNA network associated with CCND1. Gene expression profiling of the Head and Neck Squamous Cell Carcinoma (HNSC) project of The Cancer Genome Atlas (TCGA) program identified the TPRG1-AS1-hsa-miR-363-3P-MYO1B gene regulatory axis associated with CCND1. Further analysis of the database showed that MYOB was regulated by methylation in head and neck tumors, and functional enrichment analysis showed that MYO1B was involved in "actin filament organization" and "cadherin binding ". Immune infiltration analysis suggested that MYO1B may influence tumorigenesis and prognosis by regulating the immune microenvironment of HNSC. MYO1B enhanced tumor spread through the EMT approach, according to epithelial mesenchymal transition (EMT) characterisation. We analyzed both herbal and GSCALite databases and found that CCND1 and MYO1B have the potential as predictive biomarkers for the treatment of HNSC patients. RT-qPCR validated bioinformatic predictions of gene expression in vitro cell lines. In conclusion, we found a CCND1-related ceRNA network and identified the novel TPRG1-AS1-hsa-miR-363-3p-MYO1B pathway as a possible HNSC diagnostic biomarker and therapeutic target.

DTL is a Novel Downstream Gene of E2F1 that Promotes the Progression of Hepatocellular Carcinoma.

BACKGROUND: Hepatocellular carcinoma (HCC), one of the world's most prevalent malignancies, accounts for 90% of primary liver cancer cases. Recent studies have shown an increased expression of denticles E3 ubiquitin protein ligase homolog (DTL) in several different tumor types, but its function and regulatory mechanisms remain unclear. AIMS: This study aimed to investigate the expressions of the Cullin4 (CUL4) complex in HCC and elucidate the roles of DTL in HCC cells. METHODS: The relative expression of the CUL4 complex and its clinical significance were analyzed with The Cancer Genome Atlas (TCGA) data, and the level of DTL was confirmed by immunohistochemistry. The functions of DTL1 and upstream E2F1 were evaluated by a Western blot, MTT, transwell, and xenograft in HCC cell lines. RESULTS: The elevated mRNA expression of the CUL4 complex, including CUL4B, DDB1 (Damage Specific DNA Binding Protein 1), and DTL, was associated with the overall survival of HCC patients. We also found that the DTL protein was elevated in HCC tissues, and patients with highly expressed DTL and nucleus-located DTL had a poorer survival time. DTL knockdown significantly inhibited cancer proliferation, migration, and invasion. Further experiments showed that E2F1 was an upstream regulatory molecule of DTL, which was bound to the promoter of DTL, promoting the expression of DTL. CONCLUSION: The study results demonstrate that E2F1-DTL signaling promotes the growth, migration, and invasion of HCC cells, which provides new insights and a potential biological target for future HCC therapies.

Characterization of m6A methylation modifications and tumor microenvironment infiltration in thyroid cancer

Background Thyroid cancer (TC) is the most common endocrine malignancy worldwide, and immunotherapy is a new cancer treatment that stimulates and enhances the natural ability of the immune system to fight cancer cells. The role of RNA N6-methyladenosine (m6A) related genes in these challenges has recently become a research hotspot, but he potential role of m6A modifications in tumor microenvironment (TME) cell infiltration remains unknown. Purpose There is growing evidence that m6A plays a critical role in the regulation of gene expression by participating in important biological processes. A comprehensive analysis of the m6A regulator-mediated infiltration characteristics of the TME will help advance the understanding of immune regulation in thyroid tumors. Methods This study assessed m6A modification modes in 510 thyroid cancer samples from the Cancer Genome Atlas (TCGA) databases according to a comprehensive set of 24 m6A regulators. In this study, we analyzed the biological characteristics and m6A methylation modification patterns. Based on this, we constructed m6A signatures and analyzed m6A modification features in tumor somatic mutations and TCGA molecular subtypes. Results These modification modes were systematically linked to TME cell infiltration signatures. m6A modification patterns were comprehensively assessed and correlated with immune cell infiltration features in the TME. An unsupervised clustering approach was applied and three distinct m6A modification subtypes and three m6A-associated gene subtypes were identified. Additionally, three distinct m6A methylation modification modes were identified in the thyroid cancer samples. The TME profiles of the identified genetic subtypes were strongly congruent with the immuno-heat and immuno-cold phenotypes... (AU)

Immediate Repair With a Self-Gripping Retromuscular Mesh for Abdominal Wall Defect Following Tumor Resection.

Background: Prosthetic repair is always employed after large abdominal wall tumor resection, while chronic pain is one of the mesh-related complications after traumatic fixation. The objective of this research was to evaluate the outcomes of retromuscular repair with self-gripping mesh after abdominal wall tumor resection.Methods: The study was a monocentric retrospective analysis following STrengthening the Reporting of OBservational studies in Epidemiology (STROBE) statements of all patients with abdominal wall tumor >5 cm in diameter undergoing tumor excision and retromuscular repair with self-gripping mesh. Demographic, operative, early postoperative, and follow-up data were noted. Visual Analog Scale, ranging from 0 (no pain) to 10 (very severe pain), was used to estimate the wound pain.Results: 24 patients were included in this study, and the defect following tumor resection was 26.9±10.0 cm2. There was no tumor recurrence or incisional hernia in median follow-up of 20 months, and the mean VAS score was 0.4. Three had foreign body feeling and no one suffered chronic pain.Conclusions: Immediate repair with a self-gripping retromuscular mesh can be considered as an effective way to treat an abdominal wall defect after resecting an abdominal wall tumor.

Clinicopathological features and prognostic factors analysis of multiple synchronous distinct subtypes of primary thyroid carcinoma.

PURPOSE: To investigate the clinicopathological features, diagnosis, treatment, and prognosis of multiple synchronous distinct subtypes of primary thyroid carcinomas. METHODS: The clinical data of 68 cases of synchronous carcinomas of the thyroid (STC) admitted to the Department of Thyroid Surgery in our hospital from January 2013 to December 2021 were reviewed. According to the pathological type, they were divided into the Synchronous differentiated and differentiated thyroid Carcinoma (SDDTC) group (42 cases), the Synchronous medullary and differentiated thyroid Carcinoma (SMDTC) group (18 cases), and the Synchronous Anaplastic and differentiated thyroid Carcinoma (SADTC)group (8 cases). The diagnosis, treatment, and survival of patients in each group were analyzed. RESULTS: Women with coexisting thyroid cancer were predominant (59 cases). Most of the symptoms were found on physical examination (47.1%) and neck mass (45.6%). The median age of patients in the SDDTC group, SADTC group, and SMDTC group was 47.5 (28-74) years old, 68.5 (26-75) years old, and 56.5 (39-74) years old. The age of the SADTC group and SMDTC group was older than that of the SDDTC group (P = 0.04, P = 0.03), and the rate of lymph node metastasis in groups SADTC (62.5%) and SMDTC (55.6%) was higher than in group SDDTC (21.4%). The disease course time, tumor location, clinical stage, and mortality of the SADTC group were significantly different from those of the SDDTC group and SMDTC group (P < 0.05). The overall survival of patients with synchronous carcinomas of the thyroid was 6-105 months, and the median overall survival was 38.5 months. The tumor-free survival was 0-90 months, 19.1% of patients developed distant metastasis, 11.8% of patients had postoperative recurrence, as well as the survival rate was estimated 91.18%. Cox model multivariate analysis showed that cervical lateral lymph node metastasis and tumor stage III/IV were independent risk factors for progression-free survival(PFS). The comparison results of the survival curves showed that the overall survival (OS)of the patients in the SADTC group was significantly worse (P < 0.01), while there was no significant difference in the PFS of different pathological types (χ2 = 5.024, P = 0.081).The OS of different treatment methods was significantly different (P = 0.002), but there was no significant difference in OS between local recurrence and distant metastases with or without surgery (χ2 = 0.954, P = 0.329). CONCLUSIONS: The STC has relatively unique clinical characteristics, and most patients can get a better prognosis after radical surgery. Pathological type, lateral cervical lymph node metastasis, tumor stage, and treatment are important factors which affect the prognosis of the disease. Since there are two distinct tumors with different aggressiveness, treatment options, and prognosis, individualized management is required.

Characterization of m6A methylation modifications and tumor microenvironment infiltration in thyroid cancer.

BACKGROUND: Thyroid cancer (TC) is the most common endocrine malignancy worldwide, and immunotherapy is a new cancer treatment that stimulates and enhances the natural ability of the immune system to fight cancer cells. The role of RNA N6-methyladenosine (m6A) related genes in these challenges has recently become a research hotspot, but he potential role of m6A modifications in tumor microenvironment (TME) cell infiltration remains unknown. PURPOSE: There is growing evidence that m6A plays a critical role in the regulation of gene expression by participating in important biological processes. A comprehensive analysis of the m6A regulator-mediated infiltration characteristics of the TME will help advance the understanding of immune regulation in thyroid tumors. METHODS: This study assessed m6A modification modes in 510 thyroid cancer samples from the Cancer Genome Atlas (TCGA) databases according to a comprehensive set of 24 m6A regulators. In this study, we analyzed the biological characteristics and m6A methylation modification patterns. Based on this, we constructed m6A signatures and analyzed m6A modification features in tumor somatic mutations and TCGA molecular subtypes. RESULTS: These modification modes were systematically linked to TME cell infiltration signatures. m6A modification patterns were comprehensively assessed and correlated with immune cell infiltration features in the TME. An unsupervised clustering approach was applied and three distinct m6A modification subtypes and three m6A-associated gene subtypes were identified. Additionally, three distinct m6A methylation modification modes were identified in the thyroid cancer samples. The TME profiles of the identified genetic subtypes were strongly congruent with the immuno-heat and immuno-cold phenotypes. CONCLUSIONS: The results revealed that m6A modifications play an integral role in the diversity and complexity of thyroid carcinomas. Evaluating the m6A modification patterns of individual tumors will create more efficient immunotherapeutic strategies. A comprehensive analysis of the role of TME in thyroid cancer provides a research idea for studying the effect of m6A epigenetics on thyroid tumors and their immune microenvironment.

Non-Apoptotic Programmed Cell Death in Thyroid Diseases.

Thyroid disorders are among the most common endocrinological conditions. As the prevalence of thyroid diseases increases annually, the exploration of thyroid disease mechanisms and the development of treatments are also gradually improving. With the gradual advancement of therapies, non-apoptotic programmed cell death (NAPCD) has immense potential in inflammatory and neoplastic diseases. Autophagy, pyroptosis, ferroptosis, and immunogenic cell death are all classical NAPCD. In this paper, we have compiled the recent mechanistic investigations of thyroid diseases and established the considerable progress by NAPCD in thyroid diseases. Furthermore, we have elucidated the role of various types of NAPCD in different thyroid disorders. This will help us to better understand the pathophysiology of thyroid-related disorders and identify new targets and mechanisms of drug resistance, which may facilitate the development of novel diagnostic and therapeutic strategies for patients with thyroid diseases. Here, we have reviewed the advances in the role of NAPCD in the occurrence, progression, and prognosis of thyroid diseases, and highlighted future research prospects in this area.

THBS1, a fatty acid-related metabolic gene, can promote the development of laryngeal cancer.

Laryngeal cancer is the second most prevalent head and neck tumor and it is one of the most common malignancies of the upper respiratory tract. Fatty acid metabolism affects cancer cell biology in several ways, and alterations in fatty acid metabolism are characteristic of both tumorigenesis and metastasis. Despite advances in laryngeal cancer diagnosis and treatment over the years, there has been no significant improvement in survival or mortality. Studying the role of fatty acid metabolism-related genes in laryngeal cancer will facilitate our search for valuable biomarkers to guide prognostic management and treatment selection. We constructed a prognostic risk score model for fatty acid metabolism-related genes by downloading and analyzing laryngeal cancers from the TCGA and GEO databases. We predicted survival outcomes of laryngeal cancer patients using a prognostic risk score model of fatty acid metabolism-related genes and analyzed the resistance of laryngeal cancer in different individuals to multiple drugs. In addition, the relationship between the prognostic risk score model and cellular infiltration characteristics of the tumor microenvironment were investigated. Through the prognostic risk scoring model, the genes with risk-prompting effect and related to prognosis were screened out for further research. Through the study of gene expression levels in the TCGA database, we screened out 120 differentially expressed fatty acid metabolism genes. LASSO-Cox and Cox regression analyses identified nine genes associated with prognosis to construct a prognostic risk score model for genes related to fatty acid metabolism. Both TCGA and GEO confirmed that samples in the high-risk score group had a worse prognosis than those in the low-risk score group. We found significant differences between the high-risk and low-risk groups for 22 drugs (P < 0.05). In addition, we found differences in immune cell infiltration between the different risk score groups. Finally, through the risk assessment model, combined with multiple databases, THBS1, a high-risk and prognosis-related gene, was screened. We also found that THBS1 could promote the migration, invasion and proliferation of laryngeal cancer cells by constructing THBS1 knockout cell lines. In our study, we identified key fatty acid-related genes differentially expressed in laryngeal carcinoma that can be used to adequately predict prognosis using a comprehensive bioinformatic experimental approach. It was also found that THBS1, a high-risk and prognosis-related gene, may regulate the occurrence and development of laryngeal cancer through fatty acid metabolism, which has further helped us to explore the role of fatty acid metabolism genes in laryngeal cancer.

"Micro" Extrathyroidal Extension in Risk Stratification for Papillary Thyroid Carcinoma: Should It Be in the Intermediate-Risk or High-Risk Group? A Single-Center Retrospective Study.

Introduction: Currently, there is no consensus on the specific effect of Extrathyroidal Extension (ETE) on prognosis. The purpose of our study was to study the relationship between different states of ETE and its disease-free survival rate and to determine the basic standard of Micro ETE (tumor extends through capsule only) in risk stratification. Material and Methods: We conducted a retrospective and single-center study that included the clinical data of all papillary thyroid carcinoma (PTC) patients with ETE in our hospital from 2013 to 2017 and followed them up after rigorous screening. According to ETE state, it is divided into four groups: Microscopic, Micro, Minimal, Macro. Kaplan-Meier method was used to calculate disease-free survival (DFS). Log-rank test was used to compare the differences between the groups and to polt the survival curves. P<0.05 was considered statistically significant. Micro ETE was included in different risk stratification subgroups and their DFS was compared. Results: A total of 436 patients were included: Microscopic group N=50 (11.47%), Micro group N=74 (16.97%), Minimal group N=135 (30.96%), and Macro group N=177 (40.60%). The frequency of ETE was in strap muscles N=191, trachea N=114, laryngeal recurrent nerve N=92, and capsule N=74, etc. The 5-year DFS rate in Micro group was 95.3%, higher than that in Macro group (P<0.05). The 5-year DFS rate of Micro ETE was 90.0% in the intermediate-risk group and 84.9% in the high-risk group when Micro ETE was included in different risk stratification subgroups. Conclusion: Micro ETE deserves more attention, has a batter prognosis than Macro ETE, and may have little effect on recurrence. It seems more appropriate to treat Micro ETE as the intermediate-risk group in risk stratification.

The clinical significance of BRAFV600E mutations in pediatric papillary thyroid carcinomas.

This study aimed to review the clinical significance of BRAFV600E mutations in pediatric papillary thyroid carcinoma (PTC). From 2018 to 2021, 392 pediatric thyroid operations were performed in the first affiliated Hospital of Zhengzhou University. Of these, 169 patients underwent their first operation in our hospital and were histopathologically diagnosed as papillary thyroid carcinoma. BRAFV600E gene mutation detection was performed in these 169 pediatric patients to investigate the correlation between BRAF gene mutations and clinicopathological features. Ninety-seven of our 169 patients had a BRAFV600E mutation, with a mutation rate of 57.4%. The incidence of BRAFV600E was higher in boys than in girls, and in the 13-18-year age group as compared with the 6-12-year age group (P < 0.05). The positivity rate of BRAFV600E in unilateral PTC (67.7%) was significantly higher than the ones in bilateral PTC (28.9%). The occurrence of diffuse microcalcification of the thyroid negatively correlated with the presence of BRAFV600E mutations. BRAFV600E mutations were found more frequently in patients with smaller tumor size, a lack of multifocality, lower TSH levels and central lymph node metastasis. During the follow-up time, 70 patients were treated with iodine-131. Eight patients required a second surgery (All had cervical lymph node recurrence). BRAFV600E mutations do not suggest a more aggressive course in papillary thyroid carcinoma in pediatric patients in the short term.

A Systematic Pan-Cancer Analysis of YY1 Aberrations and their Relationship with Clinical Outcome, Tumor Microenvironment, and Therapeutic Targets.

Yin-Yang 1 (YY1) has a crucial function in the development of several malignancies, according to recent research. However, nothing is known about its aberrant expression and prognostic significance in human pan-cancer. We first explored the potential carcinogenic effect of YY1 in 33 cancers using the cancer genome atlas (TCGA) project and gene expression omnibus (GEO) datasets in this research. Then, we contained a variety of elements, for instance, gene expression, the state of survival, gene alterations, protein phosphorylation, immune infiltration, and related cellular pathways, and used a series of bioinformatics methods to investigate the underlying molecular mechanism of YY1 in the etiology or clinical prognosis of various malignancies. In most malignancies, YY1 was expressed at high levels, and the level of YY1 expression was statistically associated with the prognosis of tumor patients. The S118 site of YY1 implied higher phosphorylation expression in breast cancer, colon cancer, uterine corpus endometrial carcinoma (UCEC), and lung adenocarcinoma (LUAD) tumor tissues, but lower phosphorylation levels in ovarian cancer and clear cell carcinoma tumor tissues. For S247, higher phosphorylation levels were found in colon cancer, UCEC, and LUAD tumor tissue, and lower phosphorylation expression was found in clear cell carcinoma tumor tissue. In TCGA database, YY1 expression in BRCA, BRCA-LumA, BRCA-LumB, CESC, CHOL, COAD, ESCA, HNSC, HNSC-HPV-, KIRP, LGG, LIHC, and PAAD tumor tissues was a statistically significant positive connection of the estimated infiltration value of cancer-associated fibroblasts but a negative correlation in TGCT. In addition, the functional mechanism of YY1 also involves viral carcinogenesis and ribonucleic acid (RNA) metabolism related functions. Our first pan-cancer analysis offers a pretty comprehensive knowledge of YY1's oncogenic involvement in various cancers.

CircNRIP1 Exerts Oncogenic Functions in Papillary Thyroid Carcinoma by Sponging miR-653-5p and Regulating PBX3 Expression.

Background: Circular RNA circ_0004771 (termed circNRIP1) was identified by RNA-Seq previously and was elevated in papillary thyroid carcinoma (PTC) tissues. A series of studies also showed that circNRIP1 was upregulated in some tumors and could promote the malignant progression of tumors. This research intended to focus on the role of circNRIP1 in PTC progression and explore the mechanisms underlying circNRIP1 functions. Methods: RT-PCR or western blot determined circNRIP1, miR-653-5p, and pre-B-cell leukemia homeobox 3 (PBX3) expression. EdU, CCK-8, Tunel, and transwell assays determined cell proliferation, apoptosis, invasion, and migration, respectively. Luciferase reporter assay, RNA immunoprecipitation (RIP), and RNA pull down assays clarified the target relation between miR-653-5p and circNRIP1 or PBX3. Xenograft models were applied to explore the role of circNRIP1 in vivo. Results: circNRIP1 significantly increased in PTC tissues and PTC cell lines than that in normal ones. Higher circNRIP1 expression was associated with the TNM stage and poorer overall survival. circNRIP1 knockdown attenuated the malignant progression of PTC, specifically by inhibiting proliferation and invasion/migration and promoting apoptosis. circNRIP1 was a miR-653-5p sponge; miR-653-5p knockdown reversed the suppressive role of circNRIP1 silence in PTC progression. PBX3, a target of miR-653-5p, was positively medicated through circNRIP1 via competitively sponging miR-653-5p. Knockdown of circNRIP1 attenuated the PTC tumor progression via miR-653-5p/PBX3 axis. Conclusion: Silencing of circNRIP1 suppressed PTC development via miR-653-5p elevation and PBX3 reduction, providing a novel perspective for understanding PTC pathogenesis.

FTO Prevents Thyroid Cancer Progression by SLC7A11 m6A Methylation in a Ferroptosis-Dependent Manner.

N6 methyladenosine (m6A) modification serves as a novel epigenetic regulatory mechanism that is heavily implicated in the heredity of tumors. Meanwhile, fat mass and obesity-associated protein (FTO) has the potential to affect the regulation of m6A modification in the mRNA of key oncogenes as well as tumor suppressor genes that facilitate tumor progression. In our study, FTO was downregulated in papillary thyroid carcinoma (PTC) tissues. The role of FTO in PTC was assessed by Cell Counting Kit-8 analysis, cell scratch, migration, invasion experiment, flow cytometry apoptosis analysis, and nude mouse experiment. In addition to RNA-Seq and meRIP-Seq, luciferase reporting and mutation analysis have also identified SLC7A11 as the potential FTO regulatory gene. Moreover, X-ray electron microscopy, glutathione (GSH)/oxidized GSH, GPX, malondialdehyde determination, and western blot helped confirmed that FTO inhibited the development of PTC by downregulating the expression of SLC7A11 through ferroptosis. Finally, a rescue experiment was employed to clarify the relationship between FTO and its specific target gene SLC7A11. FTO is able to inhibit the occurrence of PTC by downregulating SLC7A11 in m6A independently, and it functions as a tumor suppressor gene in PTC. These findings could contribute to our understanding of the tumor malignancy regulated by m6A and might lead to new insights for potential biomarkers and therapeutic targets for the treatment of thyroid papillary carcinoma.

DNMT3a-Mediated Enterocyte Barrier Dysfunction Contributes to Ulcerative Colitis via Facilitating the Interaction of Enterocytes and B Cells.

Objective: Dysfunction of the enterocyte barrier is associated with the development of ulcerative colitis (UC). This study was aimed at exploring the effect of DNMT3a on enterocyte barrier function in the progression of UC and the underlying mechanism. Method: Mice were given 3.5% dextran sodium sulphate (DSS) in drinking water to induce colitis. The primary intestinal epithelial cells (IECs) were isolated and treated with lipopolysaccharide (LPS) to establish an in vitro inflammatory model. We detected mouse clinical symptoms, histopathological damage, enterocyte barrier function, B cell differentiation, DNA methylation level, and cytokine production. Subsequently, the effect of DNMT3a from IECs on B cell differentiation was explored by a cocultural experiment. Result: DSS treatment significantly reduced the body weight and colonic length, increased disease activity index (DAI), and aggravated histopathological damage. In addition, DSS treatment induced downregulation of tight junction (TJ) protein, anti-inflammatory cytokines (IL-10 and TGF-ß), and the number of anti-inflammatory B cells (CD1d+) in intestinal epithelial tissues, while upregulated proinflammatory cytokines (IL-6 and TNF-α), proinflammatory B cells (CD138+), and DNA methylation level. Further in vitro results revealed that DNMT3a silencing or TNFSF13 overexpression in IECs partly abolished the result of LPS-induced epithelial barrier dysfunction, as well as abrogated the effect of IEC-regulated B cell differentiation, while si-TACI transfection reversed these effects. Moreover, DNMT3a silencing decreased TNFSF13 methylation level and induced CD1d+ B cell differentiation, and the si-TNFSF13 transfection reversed the trend of B cell differentiation but did not affect TNFSF13 methylation level. Conclusion: Our study suggests that DNMT3a induces enterocyte barrier dysfunction to aggravate UC progression via TNFSF13-mediated interaction of enterocyte and B cells.

Overexpression of DUOX2 mediates doxorubicin resistance and predicts prognosis of pancreatic cancer.

BACKGROUND: Dysregulation of the nicotinamide adenine dinucleotide phosphate (NADPH) oxidase (NOX) family is frequently observed in cancers and associated with their development and progression. However, the expression, role, and clinical significance of the NOX family members in pancreatic cancer remain unexplored. METHODS: The expression levels of the 7 NOX family genes were analyzed in Gene Expression Omnibus (GEO) datasets. The messenger RNA (mRNA) expression and gene alterations were explored using The Cancer Genome Atlas (TCGA) data portal. Clinical significance analyses of the NOX family genes were conducted among pancreatic cancer patients. The expression and prognostic value of dual oxidase 2 (DUOX2) were then validated by reverse transcription-quantitative polymerase chain reaction (RT-qPCR) and immunohistochemistry (IHC) in an independent validation cohort. The function of DUOX2 was analyzed by gene set enrichment analysis (GSEA) and its effect on the chemosensitivity of pancreatic cancer cells was detected by Cell Counting Kit-8 (CCK-8) assay. RESULTS: Results showed that NOX1, NOX2 (CYBB), NOX4, DUOX1, and DUOX2 were upregulated, while NOX3 and NOX5 were downregulated in pancreatic cancer tissues compared with nontumor tissues. Genomic alteration analysis demonstrated that deregulation of NOX family genes was partially caused by genomic alterations. Survival analyses showed that only DUOX2 was associated with overall survival (OS) and relapse-free survival (RFS) of pancreatic cancer patients. The DUOX2 gene was observed to be markedly overexpressed in pancreatic cancer. In the GSEA results for pancreatic cancer patients, DUOX2 was significantly associated with oxidoreductase activity acting on nicotinamide adenine dinucleotide hydrogen (NADH) or NADPH and uridine 5'-diphospho-glucuronosyltansferase (UDP) glycosyltransferase activity. Knockdown of DUOX2 in pancreatic cancer cells increased their sensitivity to doxorubicin. CONCLUSIONS: Overexpression of DUOX2 is correlated with prognosis and recurrence in pancreatic cancer patients and acts as a good marker for pancreatic cancer course prediction; furthermore, DUOX2 might be a therapeutic target for pancreatic cancer patients.

Safety and Efficacy of Ultrasound-Guided Radiofrequency Ablation for Benign Nonfunctional Thyroid Nodules in Children: A Retrospective Study of 62 Patients with Over Four Years of Follow-Up.

Background: Image-guided radiofrequency ablation (RFA) for benign nonfunctional thyroid nodules in adults has been shown to be effective and safe, but few trials address the use of RFA in children. Therefore, this study was designed to assess the efficacy and safety of RFA application to benign nonfunctional thyroid nodules in children. Methods: A retrospective study of RFA for 70 benign nonfunctional thyroid nodules in 62 children with four-year follow-up was conducted. Volume reduction ratio (VRR), technique efficacy, regrowth rate, symptom score, and cosmetic score were calculated to evaluate the efficacy. Complications and side effects were recorded. Logistic regression analysis was performed to identify risk factors, and subgroup analyses were performed. Results: Patients were followed up for at least four years (59.1 ± 10.5 months, range 48-85 months). After RFA treatment, the VRR and technique efficacy rates were highest at the first year* (77.5% and 91.4%, respectively) but decreased by four years (55.1% and 81.4%, respectively). The symptom score decreased from 4.0 ± 2.1* to 0.8 ± 1.6 (Z = -6.82, p < 0.001), and the cosmetic score decreased from 3.3 ± 0.7 to 1.3 ± 0.9 (Z = -7.0, p < 0.001).* The nodule regrowth rate was 22.9%, of which 56.3% of cases represented loss of efficacy. In the cases of loss of efficacy, 66.7% had greater volume than their initial presentation. Patients who received a second RFA treatment due to loss of efficacy lost efficacy again. Bilateral nodules, low vascularity, and low cystic components were independent risk factors correlating with technique efficacy. Bilateral nodules correlated with low VRR, low efficacy rate, and high regrowth rate. Nodules with a higher proportion of cystic components had higher VRR. The overall complication rate was 4.8%. Conclusions: RFA was effective in reducing the volume of benign nonfunctional thyroid nodules in children, providing significant symptomatic relief with a good safety profile during short- and long-term follow-up. RFA is a good minimally invasive treatment modality for selected pediatric patients, and it may not be appropriate for the treatment of bilateral thyroid nodules in children.