Analysis of risk factors for lymph node metastasis in 241 patients with thyroid carcinoma and establishment of a prediction model.

This study aimed to identify risk factors for cervical lymph node metastasis (LNM) in papillary thyroid carcinoma (PTC) and develop a clinical prediction model. Retrospectively, data were collected from 348 PTC patients treated at the Second Affiliated Hospital of Nanchang University between January 2019 and December 2022, with 241 patients included in the final analyses. Patients with lateral cervical LNM were categorized into a metastasis group, and those without were in a non-metastasis group. The patients were divided into a training set (n=169) and a validation set (n=72) in a 7:3 ratio. Logistic and least absolute shrinkage and selection operator (LASSO) regression models were used to identify key factors associated with lateral cervical LNM and prognosis, enabling the construction of a predictive model. The model's validity was assessed via the Hosmer-Lemeshow Test, calibration curves, ROC curves, and decision curve analysis. The metastasis group exhibited higher proportions of males, multiple lesions, bilateral involvement, tumor diameter ≥1 cm, and elevated levels of PLR, LMR, and NLR (P<0.05). Logistic regression analysis revealed that gender, multiple lesions, affected side, and tumor diameter were associated with lateral cervical LNM (P<0.05). The predictive Nomogram model, which included factors like affected side, tumor diameter, capsular invasion, central LNM, PLR, and NLR, demonstrated strong predictive accuracy and clinical utility. Thus, this study provides a practical clinical tool through an accurate Nomogram model to assess lateral cervical LNM risk in PTC patients using logistic and LASSO regression analyses.

Effect of silencing CITED1 gene to regulate PI3K/AKT pathway on the biological function of PTC cells and its mechanism.

This study aims to investigate the effect of silencing the CITED1 gene to regulate the PI3K/AKT pathway on the biological function of papillary thyroid carcinoma (PTC) cells and its mechanism of action. Human PTC cells SW1736 were divided into 4 groups: control group, siCITED1 group, LY294002 group and siCITED1+LY294002 group. CITED1 was silenced by transfection with siCITED1 plasmid. The PI3K/AKT pathway was inhibited by LY294002 (5 µmmol/L). Each group was determined for cell proliferation, apoptosis and invasion capabilities, as well as PI3K/AKT transcription and protein expression levels. CITED1 mRNA and protein levels in the siCITED1 group and the siCITED1+LY294002 group were significantly lower than those in the control group (P < 0.05), and the two levels were not significantly different between the LY294002 group and the control group (P > 0.05). Compared with the control group, the siCITED1 group showed remarkably lower proliferation and invasion capabilities, and remarkably higher apoptosis rate (P < 0.05). There was no significant difference in proliferation, apoptosis and invasion capabilities between the LY294002 group and the siCITED1+LY294002 group (P > 0.05), both of which had significantly lower proliferation and invasion capabilities but significantly higher apoptosis rate than the siCITED1 group (P < 0.05). PI3K and AKT protein levels in the siCITED1 group were significantly lower than those in the control group (P < 0.05). The PI3K and AKT protein levels in the LY294002 group and the siCITED1+LY294002 group were not significantly different (P > 0.05), and were significantly lower than those in the siCITED1 group (P < 0.05). In conclusion: CITED1 silence may inhibit the progression of PTC cells by inhibiting the PI3K/AKT pathway.

A novel circular RNA, circSQSTM1, protects the endothelial function in atherosclerosis.

A novel circRNA named circSQSTM1 (hsa_circRNA_075320) was screened out in atorvastatin (ATV) stimulated endothelial cells (ECs) by our group. Considering the anti-atherosclerotic function of ATV, we hypothesized the circSQSTM1 could protect ECs functions in AS progression. The effects of circSQSTM1 on ECs inflammation, oxidative stress and autophagy were measured by qRT-PCR, Western blotting, monocyte-endothelial adhesion assay, dichloro-dihydro-fluorescein diacetate and mCherry-GFP-LC3 labeling. A luciferase reporter assay, RNA immunoprecipitation, MS2-tagging system and fluorescence in situ hybridization were performed to identify the biological functions of circSQSTM1. The partial left carotid artery ligation model and atherosclerosis model were established to analyze the effects of circSQSTM1 on atherosclerosis progression in vivo. Our results revealed that ATV induced the accumulation of circSQSTM1 in ECs via suppressing m6A modified degradation. In the cytoplasm, circSQSTM1 could relieve Sirt1 by competitively sponging miR-23b-3p. In the nucleus, circSQSTM1 directly interacts with eIF4A3 and promoting the efficient nuclear export of FOXO1 mRNA, which encodes FOXO1 transcription factor to directly activate Sirt1 promoter activity. Hence, circSQSTM1 reduced inflammation, inhibited oxidative stress and promoted autophagy by upregulating Sirt1 in ECs. Moreover, circSQSTM1 overexpression in ECs attenuated the progression of atherosclerosis in ApoE-/- mice. Taken together, the unique noncoding RNA known as circSQSTM1 took a protective role to the ECs in atherosclerosis.

Clinical efficacy of gasless submental-transoral endoscopic thyroidectomy with Kirschner wire suspension for papillary thyroid carcinoma.

PURPOSE: To analyze the clinical efficacy of gasless submental-transoral endoscopic thyroidectomy (ETE) with Kirschner wire suspension in patients with papillary thyroid carcinoma (PTC). METHODS: Retrospectively, we enrolled 112 patients with PTC who received treatment in The Second Affiliated Hospital of Nanchang University between December 2020 and December 2021. Among them, 60 cases (laparoscopic group) received gasless submental-transoral ETE with Kirschner wire suspension, and the other 52 cases (open group) were treated by traditional thyroidectomy. Surgical indicators (operative time (OT), intraoperative blood loss (IBL), and postoperative drainage volume (DV)), number of central lymph node (CLN) dissected, length of hospital stay (LOS), Visual Analogue Scale (VAS) score, aesthetic satisfaction score, and complications were observed and compared between the two groups. RESULTS: There was no significant difference between the two groups in OT (55.73±5.49 min vs. 55.00±7.79 min), IBL (20.67±7.75 mL vs. 23.08±6.24 mL), postoperative DV (33.17±15.09 mL vs. 39.52±19.22 mL), number of CLN dissected (5.54±2.75 vs. 5.43±3.15), LOS (3.63±0.69 d vs. 3.68±0.57 d), postoperative VAS score (3.19±1.07 points vs. 3.38±1.09 points), and total complication rate (3.85% vs. 8.33%; all P>0.05). However, the laparoscopic group exhibited a significantly higher aesthetic satisfaction score than the open group (7.10±1.46 points vs. 6.42±1.46 points; P<0.05). In addition, patients in both groups were followed up for at least 3 months, and no recurrence or metastasis was observed. CONCLUSIONS: Gasless submental-transoral ETE with Kirschner wire suspension offers comparable curative effect as traditional thyroidectomy and safety, but it provides superior esthetic results, making it a viable treatment option for patients with PTC.

KMT2B promotes SHPRH expression to regulate 131I sensitivity in thyroid carcinoma cells by affecting FYN protein stability.

Radioiodine (131I) is one of the most well-known and widely used targeted therapies. In thyroid carcinoma (THCA), it has been applied for more than eight decades and is still being utilized to eliminate remnants after resection and to reduce tumor metastases. Here, we aimed to investigate if lysine methyltransferase 2B (KMT2B) silencing could confer 131I resistance to THCA cells and the epigenetic mechanism behind. RT-qPCR, immunohistochemistry and western blot revealed that KMT2B was poorly expressed in THCA cells, and 131I resistance of cells led to a further decrease in KMT2B expression. EdU, colony formation, TUNEL, and tumor growth and metastasis assays showed that overexpression of KMT2B sensitized THCA cell to 131I and inhibited cell growth and metastasis. Further bioinformatics prediction and functional assay validation revealed that KMT2B elevated SHPRH expression via H3K4me3 modification in the SHPRH promoter, and that SHPRH modulated FYN ubiquitination, thereby promoting its protein degradation. We finally proved that the 131I-resistant cells regained resistance to 131I by FYN overexpression in the presence of KMT2B overexpression in vitro and in vivo. Therefore, we conclude that the overexpression of KMT2B represents a potential target for THCA therapy.

Roles of the SNHG7/microRNA­9­5p/DPP4 ceRNA network in the growth and 131I resistance of thyroid carcinoma cells through PI3K/Akt activation.

Radioactive iodine (RAI, 131I) therapy is the main treatment for thyroid carcinoma (TC). Long noncoding RNA (lncRNA)/microRNA (miR) competing endogenous RNA (ceRNA) networks have aroused great interest for their roles in gene expression. The present study aimed to investigate the effect of lncRNA SNHG7 on the growth and 131I resistance of TC. Differentially expressed lncRNAs in TC and paracancerous tissues were analyzed. The binding of miR­9­5p with small nucleolar RNA host gene 7 (SNHG7) and dipeptidyl­peptidase 4 (DPP4) was identified. Gain­ and loss­of­function analyses of SNHG7 and miR­9­5p were performed to determine their effects on the growth and 131I resistance of TC cells. The activity of the PI3K/Akt pathway was evaluated. Consequently, upregulated SNHG7 was revealed in TC tissues and correlated with 131I resistance. Silencing of SNHG7 or overexpressing miR­9­5p inhibited the growth and 131I resistance of TC cells. SNHG7 acted as a ceRNA of miR­9­5p to enhance DPP4 expression. Overexpressed SNHG7 increased DPP4 expression and activated the PI3K/Akt signaling pathway by sponging miR­9­5p. The in vitro results were reproduced in vivo. In summary, the present study provided evidence that the SNHG7/miR­9­5p/DPP4 ceRNA network could promote the growth and 131I resistance of TC cells via PI3K/Akt activation. The present study may offer novel options for TC treatment.

Tim-4 expressing monocytes as a novel indicator to assess disease activity and severity of ulcerative colitis.

AIMS: The dysregulation of the immune response has been shown to be involved in ulcerative colitis (UC) pathogenesis. Tim-4 is a potential regulator of the immune system which plays key roles in multiple autoimmune diseases. However, whether it is involved in UC remains unclear. The aim of this research was to determine the expression of Tim-4 on circulating monocytes and its clinical significance in UC patients. MAIN METHODS: In total, 36 UC patients and 34 healthy controls (HCs) were enrolled in this study. The frequencies of CD14+Tim-4+ cells, regulatory T cells (Treg) and CD14+HLA-DR-/low myeloid-derived suppressor cells (MDSCs) in the peripheral blood were determined by flow cytometry. Serum IL-6 levels were determined by chemiluminescence immunoassay. KEY FINDINGS: The percentage of CD14+Tim-4+ cells was higher in UC patients than in HCs. The frequency of Treg cells was significantly decreased, while that of MDSCs was significantly increased in UC patients. The frequency of CD14+Tim-4+ cells was significantly elevated in subjects with high severity, high number of defecations per day, high UC disease activity index Mayo score, high IgG, and high levels of inflammatory markers. And the percentages of Tim-4-expressing monocytes were significantly decreased in UC patients that received a 3-week treatment with mesalazine. Furthermore, the frequency of CD14+Tim-4+ cells was also positively correlated with MDSCs and negatively correlated with Treg cells. SIGNIFICANCE: CD14+Tim-4+ cells was elevated in UC patients and could be a novel indicator to assess disease severity and activity of UC.

Aberrant alteration of follicular T helper cells in ulcerative colitis patients and its correlations with interleukin-21 and B cell subsets.

Patients with ulcerative colitis (UC) are at increased risk of developing colitis-associated colon cancer. Accumulating evidence suggests that follicular T helper (TFH) cells play a crucial role in the pathogenic process of autoimmune diseases. However, little is known about the role of TFH cells in the development of UC. To investigate the role of TFH cells in the development of UC, the number of TFH cells, the level of interleukin-21 (IL-21), the numbers of B cell subsets, and clinical parameters were detected in peripheral blood from 31 UC patients and 29 healthy controls. TFH cells and the level of IL-21 were significantly higher in UC patients than in the healthy controls. A positive correlation between TFH and IL-21 cells was found in UC patients. Moreover, aberrant frequencies of different subsets of B cells were observed in UC patients, and a positive correlation was found between CD38CD19 B cells and TFH cells and between CD86CD19 B cells and TFH cells. A high number of TFH cells were positively associated with Mayo score, serum C-reaction protein (CRP) and serum IgG in UC patients. Our data indicate that TFH cells and IL-21 are involved in the pathogenesis of UC.

LncRNA CASC2 expression is down- regulated in papillary thyroid cancer and promotes cell invasion by affecting EMT pathway.

BACKGROUND: Long non-coding RNAs (lncRNAs) were recently identified as crucial regulators of papillary thyroid cancer (PTC). However, the clinical role and regulatory functions of lncRNA cancer susceptibility candidate 2 (CASC2) in PTC remain unknown. METHODS: LncRNA CASC2 expression was examined in plasma samples from 68 PTC patients and 39 patients with nodular goiter (NG). Cell proliferation, migration and invasion abilities were evaluated using CCK8 assay and transwell migration and invasion assay. QRT-PCR and western blot analysis were performed to detect the expression of epithelial-to-mesenchymal (EMT) markers ZEB1, E-cadherin and vimentin in PTC cells. RESULTS: We demonstrated that lncRNA CASC2 expression was significantly downregulated in tumor tissues and plasma samples in patients with PTC compared with those in nodular goiters (P< 0.05). Decreased plasma lncRNA CASC2 expression associated with lymph node metastasis (LNM) of PTC patients and was identified as an independent risk for patients with LNM (P< 0.05). Furthermore, functional assays demonstrated that overexpression of lncRNA CASC2 inhibited cell proliferation, migration and invasion of PTC. Moreover, we demonstrated that overexpression of lncRNA CASC2 suppressed cell epithelial-mesenchymal transition (EMT) process of PTC by increasing the E-cadherin expression, but downregulating ZEB1 and N-cadherin expression. CONCLUSIONS: Thus, these results indicated that lncRNA CASC2 was a predictor for LNM of PTC patients and may serve as a potential target of PTC treatment.