Ischemia-inhibited ferric chelate reductase 1 improves ferroptosis-mediated intestinal ischemia injury via Hippo signaling.

The precise mechanism of ferroptosis as a regulatory cell death in intestinal ischemia injury induced by vascular intestinal obstruction (Vio) remains to be elucidated. Here, we evaluated iron levels, glutathione peroxidase 4 (GPX4) and Acyl-CoA synthetase long-chain family member 4 (ACSL4) changes after intestinal ischemia injury to validate ferroptosis. As an enzyme for Fe3+ reduction to Fe2+, Ferric Chelate Reductase 1 (FRRS1) is involved in the electron transport chain and the tricarboxylic acid (TCA) cycle in mitochondria. However, whether it is involved in ferroptosis and its role in intestinal ischemia injury need to be clarified. In the present study, FRRS1 was overexpressed in vivo and in vitro. The results showed that overexpression of FRRS1 prevented ischemia-induced iron levels, reactive oxygen species (ROS) production, lipid peroxidation, inflammatory responses, and cell death. Meanwhile, FRRS1 overexpression promoted GPX4 expression and suppressed ACSL4 levels. Further studies revealed that FRRS1 overexpression inhibited the activity of large tumor suppressor 1 (LATS1) / Yes-associated protein (YAP) / transcriptional co-activator with PDZ-binding motif (TAZ), a key component of Hippo signaling. In conclusion, this study demonstrates that FRRS1 is intimately involved in the inhibition of ferroptosis and thus protection of the intestine from intestinal ischemia injury, its downstream mechanism was related to Hippo signaling. These data provide new sight for the prevention and treatment of intestinal ischemia injury.

Effect of sodium bicarbonate Ringer's solution on lung injury in rats with traumatic hemorrhagic shock.

This study aimed to explore the impact of different pH values of resuscitation fluid on traumatic hemorrhagic shock (THS), focusing on their effects on glycocalyx and inflammation. A rat model of THS was induced by hemorrhage from a left femur fracture, while an oxygen-glucose deprivation/reoxygenation (OGD/R)-induced HULEC-5a cell model was considered as an in vitro THS model. The lung tissue pathology and glycocalyx structure were assessed through hematoxylin-eosin (H&E) staining and transmission electron microscope examination. The levels of glycocalyx-related factors and inflammation-related factors were determined by enzyme-linked immunosorbent assay (ELISA). The expression of glycocalyx-related proteins, cell junction-related proteins, and proteins involved in the PI3K/Akt/NF-κB signaling pathway was analyzed by western blot. The results showed that both sodium bicarbonate Ringer's solution (BRS) and lactate Ringer's solution (LRS) were effective in restoring mean arterial pressure and heart rate in THS rats. However, LRS has a stronger impact on promoting inflammation and damaging the glycocalyx compared with BRS. In OGD/R-induced HULEC-5a cells, a pH of 7.4 and 6.5 increased inflammation and disrupted the glycocalyx, while a pH of 8.1 had no significant effect on inflammation or glycocalyx. Furthermore, the PI3K/Akt/NF-κB signaling pathway was activated by fluid resuscitation and different pH values. However, the activating effect of BRS and pH 8.1 on the PI3K/Akt/NF-κB signaling pathway was milder compared with LRS and pH6.5. In conclusion, an alkaline recovery environment was more beneficial for the treatment of THS.

[Accurate tissue flap reconstruction method based on the quadratic surface developability for head and neck soft tissue defects].

Soft tissue defects resulting from head and neck tumor resection seriously impact the physical appearance and psychological well-being of patients. The complex curvature of the human head and neck poses a formidable challenge for maxillofacial surgeons to achieve precise aesthetic and functional restoration after surgery. To this end, a normal head and neck volunteer was selected as the subject of investigation. Employing Gaussian curvature analysis, combined with mechanical constraints and principal curvature analysis methods of soft tissue clinical treatment, a precise developable/non-developable area partition map of the head and neck surface was obtained, and a non-developable surface was constructed. Subsequently, a digital design method was proposed for the repair of head and neck soft tissue defects, and an in vitro simulated surgery experiment was conducted. Clinical verification was performed on a patient with tonsil tumor, and the results demonstrated that digital technology-designed flaps improved the accuracy and aesthetic outcome of head and neck soft tissue defect repair surgery. This study validates the feasibility of digital precision repair technology for soft tissue defects after head and neck tumor resection, which effectively assists surgeons in achieving precise flap transplantation reconstruction and improves patients' postoperative satisfaction.

Construction of a system for head and neck tumor traceless resection with non-inflatable transaxillary total endoscopic surgery.

Radical cure and functional preservation of tumors are the fundamental goals of surgical treatment of head and neck tumors, and the preservation of good aesthetics is a higher pursuit on this basis. Fully hiding the surgical incision and reducing the visibility of scars are important goals of cosmetic surgery. Using complete endoscopy for the head and neck is an effective method. CO2-free transaxillary total endoscopic surgery is a method with many advantages, which has been widely used in the resection of thyroid tumors, but for other parts and types of tumors in the head and neck, this surgical method is rarely used. The research team expanded its application scope and applied it to submandibular gland tumor resection and other head and neck surgeries for the first time. Through this exploration, it improved traction devices such as retractors, strictly limited the surgical indications, analyzed and summarized the key points, steps and methods of surgery, and built a treatment system for head and neck tumor surgery under complete endoscopy using the non-inflatable transaxillary approach. In this article, we introduce the system and select typical cases to share.

The incidence trends of oral cancers worldwide from 1988 to 2012 and the prediction up to 2030.

BACKGROUND: This paper aims to analyze the time trend of OCs incidence in 43 countries (1988-2012) and predict the incidence trend of OCs (2012-2030). METHODS: In the database for Cancer Incidence in Five Continents, the annual data on OCs incidence grouped by age and gender were obtained from 108 cancer registries in 43 countries. The age-standardized incidence rates were calculated, and the Bayesian age-period-cohort model was used to predict the incidence in 2030. RESULTS: South Asia and Oceania had the highest ASR in 1988 (9.24/100 000) and 2012 (6.74/100 000). It was predicted that India, Thailand, the United Kingdom, the Czech Republic, Austria, and Japan would be the countries with an increased incidence of OCs in 2030. CONCLUSION: Regional custom is an important factor affecting the incidence of OCs. According to our predictions., it is necessary to control risk factors according to local conditions and enhance screening and education.

SRPX2 promotes cancer cell proliferation and migration of papillary thyroid cancer.

Thyroid cancer is the endocrine tumor with the highest incidence at present. It originates from the thyroid follicular epithelium or follicular paraepithelial cells. There is an increasing incidence of thyroid cancer all over the world. We found that SRPX2 expression level was higher in papillary thyroid tumors than in normal thyroid tissues, and SRPX2 expression was closely related to tumor grade and clinical prognosis. Previous reports showed that SRPX2 could function by activating PI3K/AKT signaling pathway. In addition, in vitro experiments showed that SRPX2 promoted the proliferation and migration of papillary thyroid cancer (PTC). In conclusion, SRPX2 could promote the malignant development of PTC. This may be a potential treatment target for PTC.

Clinical application of endoscopic surgery using a gasless unilateral transaxillary approach in the treatment of primary hyperparathyroidism.

Objectives: To investigate the safety and feasibility of gasless axillary parathyroid surgery in the treatment of primary hyperparathyroidism. Methods: A total of 12 patients who received gasless axillary parathyroidectomy (endoscope group) and 14 patients who received traditional open parathyroidectomy (open group) from January 2019 to April 2022 were screened and included. The differences in baseline characteristics, surgical efficiency, incidence rate of complications, changes in biochemical indicators, and incision satisfaction between the two groups were analyzed and compared. Results: The proportion of young patients was higher in the endoscopic group than in the open group, and the difference was statistically significant [(41.33 ± 13.65) years vs. (58.00 ± 9.44) years, P < 0.01]. The differences in operation time, intra-operative blood loss, post-operative drainage volume, hospital stay, and surgical efficiency between the two groups yielded no statistical significance (P > 0.05). Patients in the open group had more significant neck pain 3 days after surgery (P = 0.046), but the degree of pain 3 months after surgery was the same in the 2 groups (P = 0.432). Evaluation of post-operative mature stage scar and incision satisfaction regarding aesthetics in the endoscope group were significantly superior to that in the open group [(1.92 ± 0.92) points vs. (0.92 ± 1.00) points, P = 0.017 and (1.57 ± 0.51) points vs. (1.00 ± 0.013) points, P = 0.013, respectively]. No statistical significance was found in terms of incidence rate of post-operative fever (P > 0.05). No temporary recurrent laryngeal nerve injury, post-operative bleeding, incision hematoma infection, or other complications were observed. Comparing the two groups, the extent of the level decrease of PTH was similar to that of serum calcium and phosphorus (P < 0.05), where most patients experienced transient hypocalcemia after operation yielding no significant difference in incidence (P = 0.225). During a follow-up period of 3 to 36 months, a total of 1 patient in the open group experienced recurrence at 10 months after surgery and was treated non-surgically. Conclusion: Gasless axillary approach to parathyroid surgery for primary hyperparathyroidism possesses good safety and patient satisfaction in terms of aesthetics.

CREB3L1 promotes tumor growth and metastasis of anaplastic thyroid carcinoma by remodeling the tumor microenvironment.

Anaplastic thyroid carcinoma (ATC) is an extremely malignant type of endocrine cancer frequently accompanied by extrathyroidal extension or metastasis through mechanisms that remain elusive. We screened for the CREB3 transcription-factor family in a large cohort, consisting of four microarray datasets. This revealed that CREB3L1 was specifically up regulated in ATC tissues and negatively associated with overall survival of patients with thyroid cancer. Consistently, high expression of CREB3L1 was negatively correlated with progression-free survival in an independent cohort. CREB3L1 knockdown dramatically attenuated invasion of ATC cells, whereas overexpression of CREB3L1 facilitated the invasion of papillary thyroid carcinoma (PTC) cells. Loss of CREB3L1 inhibited metastasis and tumor growth of ATC xenografts in zebrafish and nude mouse model. Single-cell RNA-sequencing analysis revealed that CREB3L1 expression gradually increased during the neoplastic progression of a thyroid follicular epithelial cell to an ATC cell, accompanied by the activation of the extracellular matrix (ECM) signaling. CREB3L1 knockdown significantly decreased the expression of collagen subtypes in ATC cells and the fibrillar collagen in xenografts. Due to the loss of CREB3L1, ATC cells were unable to activate alpha-smooth muscle actin (α-SMA)-positive cancer-associated fibroblasts (CAFs). After CREB3L1 knockdown, the presence of CAFs inhibited the growth of ATC spheroids and the metastasis of ATC cells. Further cytokine array screening showed that ATC cells activated α-SMA-positive CAFs through CREB3L1-mediated IL-1α production. Moreover, KPNA2 mediated the nuclear translocation of CREB3L1, thus allowing it to activate downstream ECM signaling. These results demonstrate that CREB3L1 maintains the CAF-like property of ATC cells by activating the ECM signaling, which remodels the tumor stromal microenvironment and drives the malignancy of ATC.

Case report: Successful treatment of a rare case of combined parathyroid adenoma, cervical bronchogenic cyst, and tracheal diverticulum with gasless endoscopic resection of neck masses via an axillary approach: A case report and literature review.

Parathyroid adenoma (PA), one of the most common causes of hyperparathyroidism, generally involves a single parathyroid gland and is manifested as hyperparathyroidism. Bronchogenic cysts are rare congenital cystic lesions caused by a development malformation in bronchi during the embryonic period, which mostly occur in the lung and mediastinum, with an extremely low morbidity rate in the neck. A 27-year-old young female was found to suffer from hyperparathyroidism on routine physical examination, and further examination suggested a cystic lesion in the right inferior parathyroid area combined with a tracheal diverticulum. Therefore, she was initially diagnosed with cystic hyperplasia of the parathyroid glands complicated by a tracheal diverticulum. Gasless endoscopic resection of neck masses via an axillary approach was performed because of the high requirements for the surgical cosmetic effect of the patient. During the surgery, we observed that the preoperatively diagnosed cystic lesion was a combination of two masses, which were successfully resected under endoscopy. Based on the postoperative pathology and clinical features, the patient was eventually diagnosed with a rare case of triple diseases including PA, cervical bronchial cyst, and tracheal diverticulum. Now, the patient recovered well as per the follow-up with no signs of recurrence and was extremely satisfied with the cosmetic effect of the surgery.

Overexpression of miR-146a-5p Ameliorates Inflammation and Autophagy in TLCs-Induced AR42J Cell Model of Acute Pancreatitis by Inhibiting IRAK1/TRAF6/NF-κB Pathway.

MicroRNA-146a-5p (miR-146a-5p) has been shown to mediate the inflammatory responses and autophagy in many diseases; however, its role in acute pancreatitis (AP) is not clear. OBJECTIVE: To determine the expression and role of miR-146a-5p in taurolithocholic acid-3-sulphate (TLCs) induced-AR42J cell model of AP. METHODS: Quantitative reverse transcription polymerase chain reaction, western blot, enzyme linked immunosorbent assay (ELISA), miRNA mimics or vectors or small interfering RNAs transfection and dual-luciferase reporter assay were employed in this study. RESULTS: miR-146a-5p was concentration-dependently decreased; while, interleukin-1 receptor associated kinase 1 (IRAK1) and tumor necrosis factor receptor associated factor 6 (TRAF6) were concentration-dependently increased after TLCs treatment. TLCs induced high levels of tumor necrosis factor-α (TNF-α) and interleukin-6 (IL-6) and impaired autophagy characterized as increased of LC3-II/I and decreased expression of p62. Overex-presion of miR-146a-5p and knockdown of IRAK1/TRAF6 inhibited TLCs-induced inflammation and autophagy. Luciferase assay confirmed miR-146a-5p can directly target IRAK1 and TRAF6. The expression of p-NF-κB p65 was increased by TLCs, decreased by miR-146a-5p overexpression and IRAK1/ TRAF6 knockdown but increased after upregulation of IRAK1/TRAF6. CONCLUSIONS: Overexpression of miR-146a-5p ameliorates inflammation and autophagy in TLCs-treated AR42J cells by inhibiting IRAK1/ TRAF6/NF-κB pathway.

Bioinformatics analysis of downstream circRNAs and miRNAs regulated by Runt-related transcription factor 1 in papillary thyroid carcinoma.

Background: This study sought to clarify the role of Runt-related transcription factor 1's (RUNX1's) regulation of downstream circular ribonucleic acid (circRNA) in the occurrence and development of papillary thyroid carcinoma (PTC) and to explore its mechanism of action. Methods: The levels of RUNX1 were analyzed in PTC tumor tissues and adjacent non-tumor tissues in different types and at different stages via reverse-transcription quantitative polymerase chain reaction (RT-qPCR). The expression pattern and functional role of RUNX1 were analyzed in PTC cells via RT-qPCR, Western blotting, and Transwell assays. This study explored the differential expression of circRNA and microRNA (miRNA) in cells after knocking down RUNX1 through high-throughput sequencing and examined the changes in downstream signaling pathways through Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analyses. Results: RUNX1 was upregulated in PTC tissues, and the expression levels of RUNX1 were related to PTC stage. The knockdown of RUNX1 inhibited the proliferation, migration, and invasion of cells. The high-throughput sequencing results showed that after RUNX1 knockdown, 29 circRNAs (11 upregulated and 18 downregulated) and 20 miRNAs (8 upregulated and 12 downregulated) had the most significant differential expression. The GO analysis of the differential circRNA downstream genes showed that the iron channel-related pathways, endosomal transport, learning, and memory pathways had the largest number of differential genes, and the most significant changes. The KEGG analysis showed that there were 2 pathways with P values <0.05; that is, the glycosaminoglycan synthesis and transcription dysregulation pathways. The GO analysis of the differential miRNA downstream genes showed that the protein binding and cytoplasmic pathways had the largest number of differential genes and the greatest level of difference. The KEGG analysis showed that the tumor-related pathways, phosphatidylinositol-3-kinase and protein kinase B, glycoprotein, cytoskeleton, Ras, and Rap1 pathways changed the most significantly. Conclusions: RUNX1 is highly expressed in PTC. We conducted high-throughput sequencing to analyze the effect of knocking down RUNX1 on the levels of circRNA and miRNA in PTC. The GO and KEGG analyses revealed that the iron channel-related pathways, endosomal transport, learning and memory, glycosaminoglycan synthesis, and transcriptional disorder-related signaling pathways were enriched.

Novel computer-aided reconstruction of soft tissue defects following resection of oral and oropharyngeal squamous cell carcinoma.

BACKGROUND: Reconstruction of soft tissue defects following surgical tumor resection is important for quality of life in cancer patients with oral and oropharyngeal squamous cell carcinoma (SCC). This study presents a novel computer-aided reconstruction of soft tissue (CARST) technology employed with these patients. METHODS: We first described the CARST technology in detail in a report of a 34-year-old male patient with locally invasive right-sided tongue SCC following a nearly total glossectomy and reported the postoperative outcomes. This digital technology was applied to construct a 3D model from CT images, which was used to delineate surgical resection boundaries and design a personalized reconstruction of the soft tissue defect. A nonuniform rational B-spline (NURBS) was generated and applied to transform the 3D model into a 2D flap-cutting guide printed out using a 3D printer. We then reported a case-series study on oral and oropharyngeal SCC patients who were randomly assigned to receive the CARST (n = 15) or a traditional soft tissue reconstruction (n = 15). Clinicopathological features and short- and long-term postoperative outcomes between the two groups were compared. RESULTS: The patient with the tongue SCC had a successful CARST following surgical tumor resection without any complications. His speech and swallowing functions recovered well after surgery and he experienced no significant changes to his appearance following recovery. There was no recurrence within a 3-year follow-up period. Results of the case-series study showed that the CARST group had significantly shorter operative and post-operation hospital-stay time, a higher flap utilization rate, and a trend of less and milder postoperative complications, and they experienced no significant difference in intraoperative blood loss and long-term outcomes compared to the traditional group. CONCLUSION: CARST is a safer and more efficient personalized technology of soft tissue reconstruction following surgical tumor resection in patients with oral and oropharyngeal SCC.

Molecular characterization of vascular intestinal obstruction using whole-exome sequencing.

Background: Vascular intestinal obstruction is a rare intestinal disease with a rapid progression, poor prognosis, and high mortality. This study aimed to identify several mutations associated with vascular intestinal obstruction. Methods: Whole-exome sequencing (WES) was performed on the peripheral blood of 9 sporadic patients with acute vascular intestinal obstruction. The mutation genes in each patient and the mutation genes shared by all 9 patients were identified. Next, a functional annotation analysis and a protein-protein interaction (PPI) analysis of the shared mutation genes in the 9 patients were performed. Copy number variations (CNVs) were identified using the open-source software CNV kit. Results: In total, all 9 patients shared 112 mutation genes. The Reactome database revealed 2 significantly enriched pathways, the O-linked glycosylation of the mucins (MUCs), and the termination of the O-glycan biosynthesis. MUC5AC was the protein with the highest degree in the PPI network. After searching the TiGER database, the keratin 18 (KRT18), MUC4, and MUC3A genes were found to be significantly more highly expressed in the colon tissues than the other tissues. Additionally, ArfGAP with dual PH domains 1 (ADAP1), cytochrome P450 family 2 subfamily W member 1 (CYP2W1), and transmembrane protein 184A (TMEM184A) were found to be highly expressed in colon tissues. The expression levels of several candidate genes between the vascular intestinal obstruction and normal control patients were measured by quantitative real-time polymerase chain reaction (qRT-PCR). Conclusions: Our study identified multiple mutations in 4 genes (i.e., MUC3A, MUC5AC, MUC16, and KRT18), and the CYP2W1 deletion. Our findings extend understandings of the potential pathological mechanism of vascular intestinal obstruction.

Investigating the Association Between rs2439302 Polymorphism and Thyroid Cancer: A Systematic Review and Meta-Analysis.

Background and Aims: The extent of surgical treatment for most patients with thyroid cancer (TC) remains controversial and varies widely. As an emerging technology, genetic testing facilitates tumor typing and disease progression monitoring and is expected to influence the choice of surgical approach for patients with TC. Recent genome-wide association studies (GWASs) have identified that rs2439302 (8p12) variants near NRG1 are associated with TC risk; however, the results remain inconclusive. Therefore, we aimed to perform a meta-analysis to clarify the association between rs2439302 variants and the risk of TC. Methods: We search eligible studies using Pubmed, Scopus, Embase, Web of Science, and Cochrane library by July 2021. We analyzed the pooled OR and the corresponding 95% confidence interval (95% CI) of the included studies and then conducted subgroup analysis according to the ethnicity. We also performed a sensitivity analysis to validate the findings. Results: This meta-analysis finally included 7 studies involving 6,090 cases and 14,461 controls. Results showed that the G allele of the rs2439302 polymorphism was a significant risk factor of TC in Allele (G/C), Dominant (GG+GC/CC), Recessive (GG/GC+CC), Homozygote (GG/CC), Heterozygote (GC/CC) models, with pooled ORs of 1.38 (95%CI, 1.31-1.45), 1.51 (95%CI, 1.41-1.62), 1.52 (95%CI, 1.40-1.66), 1.90 (95%CI, 1.71-2.10), and 1.40 (95%CI, 1.30-1.51), respectively. The subgroup analysis showed that rs2439302 polymorphism was associated with higher TC risk in different ethnicities with OR > 1. The sensitivity analysis exhibited that the results were stable by omitting any included studies. Conclusions: The study revealed that rs2439302 variants were associated with higher TC risk and may have a major influence on the choice of operative approach for patients with TC.

A signature of circadian rhythm genes in driving anaplastic thyroid carcinoma malignant progression.

BACKGROUND: Anaplastic thyroid carcinoma (ATC) was a rare and extremely malignant endocrine cancer. Recently, dysregulation of circadian rhythm genes was demonstrated to play an essential role in tumor progression, while its exact role and mechanism in ATC remained poorly clear. METHODS: 4 ATC-related datasets were integrated to screen for differentially expressed circadian rhythm genes (DE-CRGs). Thereafter, Multiscale Embedded Gene Co-expression Network Analysis (MEGENA) and network enrichment analysis were conducted to investigate the dynamic characteristics of circadian rhythm genes. Next, Lasso-logistic model and immunohistochemistry were applied for determining the candidates. Finally, cell biological experiments and gene set enrichment analysis (GSEA) were used to confirm the roles of NPAS2 in ATC. RESULTS: 25 DE-CRGs were firstly identified in ATC. These DE-CRGs mainly regulated mitotic nuclear division, cytokinesis and DNA replication signals. Notably, NPAS2, CSNK1E, NAMPT, TYMS, SERPINE1, TOP2A, JUN, EGR3 and HEBP1 were identified as the dynamic signature in the malignant progression of ATC, which were confirmed by prognostic analysis. Furthermore, NPAS2 was found to be significantly up-regulated in ATC through clinical samples and cell experiments. Silencing NPAS2 effectively inhibited the proliferation, migration and invasion of ATC cells. GSEA showed that high expression of NPAS2 was mainly associated with cell cycle and focal adhesion, and silencing of NPAS2 suppressed these signals in our experiments. CONCLUSIONS: In summary, we found a dynamic 9-DE-CRGs signature in ATC. And the aberrant expression of NPAS2 drove the malignant phenotypes of ATC, which facilitated to deepen our understanding of the roles of circadian rhythm genes in ATC.

Number of Positive Lymph Nodes Combined with the Logarithmic Ratio of Positive Lymph Nodes predicts Survival in Patients with Non-Metastatic Larynx Squamous Cell Carcinoma.

Background: Logarithmic ratio of positive lymph nodes (LODDS), number of positive lymph nodes (NPLN), and number of lymph nodes to positive lymph nodes (pLNR) are three lymph node classifications; however, their function in prognosis is unclear. Purpose: To establish and validate an optimal nomogram according to the comparison among the 7th TNM stage of American Joint Committee on Cancer (AJCC) and the three lymph node classifications. Methods: A total of 881 patients from the Surveillance, Epidemiology and End Result (SEER database) with T1-4N1-3M0 in laryngeal squamous cell carcinoma from 2000 to 2018 were involved. The enrolled patients were allocated randomly into a training cohort and a validation cohort. Univariate cox regression analysis and multivariable cox regression analysis were applied to explore the predictors. The Akaike Information Criterion (AIC) and Harrell's concordance index (C-index) were to measure the predictive value and the accuracy of the prognostic models. Moreover, integrated discrimination improvement (IDI) and net reclassification index (NRI) were also used to assess the predictive abilities to models. According to the optimal model, nomograms were established and compared with 7th TNM stage of AJCC via the decision curve analysis. Results: NPLN, LODDS, and pLNR were three predictors for the overall and cancer-specific survival in the larynx squamous cell carcinoma. According to the AIC, C-index, IDI, and NRI, the model of NPLN combined with LODDS was assumed as the optimal prognostic model. Moreover, the decision curve analysis suggested that the nomogram demonstrated a better predictive performance, compared with the 7th AJCC TNM stage. Conclusion: The proposed nomograms we constructed for larynx squamous cell carcinoma has potential in the prediction of patients after surgery.

Lysyl oxidase promotes anaplastic thyroid carcinoma cell proliferation and metastasis mediated via BMP1.

BACKGROUND: Anaplastic thyroid carcinoma (ATC) is an extremely aggressive solid tumor with no effective treatment at present. Because of the rapid growth and aggressiveness, nearly all patients die within six months after developing ATC. Hence, more research regarding novel therapeutic targets for ATC is urgently needed. METHODS: Single-cell RNA sequencing data and microarray data of ATC were retrieved from the Gene Expression Omnibus (GEO) database. Cell clustering was performed using the Seurat package. Then, differential expression and functional enrichment analyses were performed. Gene set enrichment analysis (GSEA) was further used to investigate the functional enrichment of lysyl oxidase (LOX) and bone morphogenetic protein-1 (BMP1). The expression levels of LOX and BMP1 were measured using quantitative real-time PCR and Western blot. LOX and BMP1 were knocked down using si-RNAs. Cell proliferation was evaluated by the CCK-8 and clone formation assays. Cell migration and invasion were assessed by the wound healing assay and Transwell assay, respectively. RESULTS: LOX was upregulated at the single-cell level, as well as in ATC tissues and cell lines. LOX knockdown significantly inhibited ATC cell proliferation. Furthermore, the migration and invasion of ATC cells were remarkably inhibited after LOX inhibition. In addition, BMP1 regulated LOX expression in 8505C cells, while BMP1 overexpression restored the LOX activity blocked by the LOX inhibitor BAPN. BMP1 could also induce the cell proliferation and metastasis of ATC. CONCLUSIONS: LOX/BMP1 mediates the malignant progression of ATC, highlighting the potential application of LOX/BMP1 in the treatment of ATC. This study provides new insights for efficient therapeutic agents based on the LOX/BMP1 axis.

Transoral versus gasless transaxillary endoscopic thyroidectomy: a comparative study.

This study aimed to compare the surgical safety and outcomes of the transoral endoscopic thyroidectomy vestibular approach (TOETVA) and gasless endoscopic thyroidectomy transaxillary approach (GETTA). This retrospective study assessed 150 patients managed with the TOETVA at the Yantai Yuhuangding hospital and 150 patients managed via the GETTA at the Zhenjiang Provincial People's Hospital. The procedures were compared in terms of workspace creation time, operating time, complications, post-operative complaints, cosmetic satisfaction, and the efficacy of central neck lymph-node dissection. There was no significant between-group difference in terms of post-operative complications. The average workspace creation and operating times were significantly shorter for GETTA than for TOETVA (P values for both < 0.001). The average number of lymph nodes dissected from the central compartment of the neck was higher in the TOETVA group than in the GETTA group (7.2 ± 4.6 vs. 3.9 ± 3.0, P < 0.001). The mean swallowing impairment index-6 scores at 1 month were significantly lower in the GETTA group than in the TOETVA group (1.5 ± 1.2 vs 2.6 ± 1.4, P < 0.001). Over 97% of all patients (both groups) were either satisfied or very satisfied with the cervical cosmetic outcomes at 3 months post-surgery (P = 0.099). TOETVA and GETTA are both safe procedures with good cervical cosmetic outcomes for well-selected patients. Although TOETVA is more efficacious in terms of central lymph nodes dissection, GETTA has a greater time-cost advantage.

Exosomal hsa-miR-129-2 and hsa-miR-889 from a 6-microRNA Signature Might be a Potential Biomarker for Predicting the Prognosis of Papillary Thyroid Carcinoma.

BACKGROUND: Papillary thyroid carcinoma (PTC) is a subtype of thyroid cancer with increasing incidence over time. OBJECTIVE: This study aimed to build a risk score (RS) system for PTC patients. METHODS: PTC microRNA (miRNA) and messenger RNA (mRNA) expression data were extracted from The Cancer Genome Atlas (TCGA) database. The 491 PTC samples were randomly divided into training and validation sets. Using the limma software package, differentially expressed mRNAs (DEGs) and miRNAs (DEMs) between the tumor and control groups were screened. In order to construct an RS system, a survival package was used to select independent miRNAs related to prognosis. Enrichment analysis was performed, and a miRNA-mRNA co-expression network was constructed. High-throughput sequencing was also used to verify the prognostic miRNAs in exosomes. RESULTS: We found 1363 DEGs and 171 DEMs between the tumor and control groups. After identifying 26 DEMs significantly related to prognosis, 6 independent prognosis-associated miRNAs were selected to build an RS system. The areas under the curves of the overall survival rates of the training, validation, and entire sets were 0.847, 0.772, and 0.819, respectively. By conducting pathway analysis using the miRNA-mRNA co-expression network, one overlapping factor and five overlapping pathways were obtained. In addition, high-throughput sequencing revealed that the hsa-miR-129-2, hsa-miR-548j, hsa-miR-6734, and hsa-miR-889 expression levels in TCGA tumor tissues and exosomes were consistent, and those of hsa-miR-129-2 and hsa-miR- 889 between patients and controls were significantly different in exosomes. CONCLUSION: The six-miRNA RS system in exosomes may comprise independent signatures for predicting PTC patient prognosis.

Effect of miR-21-3p on lung injury in rats with traumatic hemorrhagic shock resuscitated with sodium bicarbonate Ringer's solution.

Background: Restricted fluid resuscitation is the most important early method for treating traumatic hemorrhagic shock (THS). This study sought to explore whether micro ribonucleic acid (miR)-21-3p affected resuscitated THS rats by regulating the glycocalyx and inflammation. Methods: MiRNAs extracted from the lung tissues were analyzed by miRNA microarray assays. A rat model of THS was induced by hemorrhage from a left femur fracture. The pathological change in the lung tissues and glycocalyx structure was observed by hematoxylin and eosin staining and a transmission electron microscope examination. The miR-21-3p expression in the lung tissues and serum was detected by real-time quantitative polymerase chain reaction (RT-qPCR). The levels of glycocalyx-related factors and inflammation-related factors were determined by enzyme linked immunosorbent assays. The expression of glycocalyx-related proteins, cell junction-related proteins, and the phosphatidylinositol 3-kinase (PI3K)/protein kinase B (Akt)/nuclear factor kappa B (NF-κB) signaling pathway-related proteins was analyzed by Western blot. Results: After RT-qPCR verification, the variation trend of miR-21-3p was in line with expected trends. The mean arterial pressure (MAP) and heart rate (HR) were decreased, and the lung injury and damage to the glycocalyx were all aggravated in the THS rats resuscitated with sodium bicarbonate Ringer's solution (BRS) or sodium lactate Ringer's solution (LRS). The expression of miR-21-3p was decreased in the THS rats resuscitated with BRS and increased in the THS rats resuscitated with LRS, and the upregulation of miR-21-3p further decreased the MAP and HR, and increased the levels of syndecan-1 (SDC-1), heparanase-1 (HPA1), interleukin (IL)-6, IL-1ß, and tumor necrosis factor alpha (TNF-α) in the serum of the THS rats resuscitated with BRS. The upregulation of miR-21-3p also increased the expression of SDC-1, HPA1, ß-catenin, matrix metallopeptidase (MMP)2, and MMP9, but decreased the expression of E-cadherin (E-cad) and activated the PI3K/Akt/NF-κB signaling pathway in the THS rats resuscitated with BRS and transfected with miR-21-3p compared to that of the THS rats resuscitated with BRS and transfected with miR-negative control (NC). Conclusions: miR-21-3p promoted inflammation and glycocalyx damage by activating the PI3K/Akt/NF-κB signaling pathway, thereby aggravating the lung injury in the THS rats resuscitated with BRS.