Differential alternative splicing landscape identifies potentially functional RNA binding proteins in early embryonic development in mammals.

Alternative splicing (AS) as one of the important post-transcriptional regulatory mechanisms has been poorly studied during embryogenesis. In this study, we comprehensively collected and analyzed the transcriptome data of early embryos from human and mouse. We found that AS plays an important role in this process and predicted candidate RNA binding protein (RBP) regulators that are associated with reproductive development. The predicted RBPs such as EIF4A3, MAK16, SRSF2, and UTP23 were found to be associated with reproductive disorders. By Smart-seq2 sequencing analysis, we identified 5445 aberrant alternative splicing events in Eif4a3-knockdown embryos. These events were preferentially associated with RNA processing. In conclusion, our work on the landscape and potential function of alternative splicing events will boost further investigation of detailed mechanisms and key factors regulating mammalian early embryo development and promote the inspiration of pharmaceutical approaches for disorders in this crucial biology process.

Function of microRNA­124 in the pathogenesis of cancer (Review).

Non­coding RNAs with a length of 22­24 nt are known as microRNAs (miRNAs or miRs), which are critical regulators of protein translation. Over the past 10 years, the roles of miRNAs have been extensively investigated in several human cancer types. There is evidence to indicate that miRNAs regulate gene expression by concentrating on a number of substances that have an impact on the physiology and development of cancer cells. Thus, miRNAs as regarded as effective targets for further studies on the design of novel therapeutic strategies. Hepatocellular carcinoma, breast, prostate, and ovarian cancer are only a few of the cancers that miR­124 suppresses. Furthermore, it has been shown that miR­124 is linked to the development and aggressive spread of malignancies. The aim of the present review was to clarify and highlight the role of miR­124 in the development and progression of cancer, emphasizing recent research illustrating how miR­124 has been used as a therapeutic agent against cancer, as well as the diagnostic potential, regulatory mechanisms and clinical application of miR­124.

Global, regional, and national prevalence of hearing loss from 1990 to 2019: A trend and health inequality analyses based on the Global Burden of Disease Study 2019.

As a severe public health issue, hearing loss has caused an increasingly disease burden, especially in the elderly population. Hearing loss may inevitably induce asymmetric hearing, which makes it difficult for elderly individuals to locate sound sources, therefore resulting in increased postural instability and falling risk. To emphasize the public health emergence of hearing loss, we investigated the temporal trend of prevalence of hearing loss over the last 30 years and further predicted its changes in the next 20 years, decomposed the trend according to demographic factors and epidemiological changes, and quantified the cross-country healthy inequalities, using the Global Burden of Diseases, Injuries, and Risk Factors Study (GBD) 2019. In 2019, there were more than 140 million cases of hearing loss worldwide, a 93.89% increase from 70 million cases in 1990. The age-standardized rate (ASR) also increased with an estimated annual percentage change of 0.08% per year. Population growth and aging are the major drivers contributing to the changes, accounting for 60.83% and 35.35%. Of note, the contribution of aging varies showing a gradual increasing trend with sociodemographic index (SDI) elevating. Also notable, there were significant health inequalities across 204 countries and territories, with slope index of inequality rising over time. Projection of the global burden of hearing loss from 2020 to 2040 indicated progressive increases in both case number and ASR. These reflect the heavy disease burden of hearing loss that needed more targeted and efficient strategies in its prevention and management.

A predictive model of immune infiltration and prognosis of head and neck squamous cell carcinoma based on cell adhesion-related genes: including molecular biological validation.

Background: Focal adhesion serves as a bridge between tumour cells and the extracellular matrix (ECM) and has multiple roles in tumour invasion, migration, and therapeutic resistance. However, studies on focal adhesion-related genes (FARGs) in head and neck squamous cell carcinoma (HNSCC) are limited. Methods: Data on HNSCC samples were obtained from The Cancer Genome Atlas and GSE41613 datasets, and 199 FARGs were obtained from the Molecular Signatures database. The integrated datasets' dimensions were reduced by the use of cluster analysis, which was also used to classify patients with HNSCC into subclusters. A FARG signature model was developed and utilized to calculate each patient's risk score using least extreme shrinkage and selection operator regression analysis. The risk score was done to quantify the subgroups of all patients. We evaluated the model's value for prognostic prediction, immune infiltration status, and therapeutic response in HNSCC. Preliminary molecular and biological experiments were performed to verify these results. Results: Two different HNSCC molecular subtypes were identified according to FARGs, and patients with C2 had a shorter overall survival (OS) than those with C1. We constructed an FARG signature comprising nine genes. We constructed a FARG signature consisting of nine genes. Patients with higher risk scores calculated from the FARG signature had a lower OS, and the FARG signature was considered an independent prognostic factor for HNSCC in univariate and multivariate analyses. FARGs are associated with immune cell invasion, gene mutation status, and chemosensitivity. Finally, we observed an abnormal overexpression of MAPK9 in HNSCC tissues, and MAPK9 knockdown greatly impeded the proliferation, migration, and invasion of HNSCC cells. Conclusion: The FARG signature can provide reliable prognostic prediction for patients with HNSCC. Apart from that, the genes in this model were related to immune invasion, gene mutation status, and chemosensitivity, which may provide new ideas for targeted therapies for HNSCC.

Effectiveness of the recurrent laryngeal nerve monitoring during endoscopic thyroid surgery: systematic review and meta-analysis.

BACKGROUND: Thyroid disease is a common endocrine disorder, and thyroid surgeries and postoperative complications have increased recently. This study aimed to explore the effectiveness of intraoperative nerve monitoring (IONM) in endoscopic thyroid surgery using subgroup analysis and determine confounding factors. MATERIALS AND METHODS: Two researchers individually searched for relevant studies published till November 2022 in the PubMed, Embase, Web of Science and Cochrane Library databases. Eventually, eight studies met the inclusion criteria. Heterogeneity was assessed using the Cochran's Q test, and a funnel plot was implemented to evaluate publication bias. The odds ratio or risk difference were calculated using fixed-effects models. The weighted mean difference of continuous variables was calculated. Subgroup analysis was performed according to the disease type. RESULTS: Eight eligible papers included 915 patients and 1242 exposed nerves. The frequencies of transient, permanent and total recurrent laryngeal nerve (RLN) palsy were 2.64, 0.19 and 2.83%, respectively, in the IONM group and 6.15, 0.75 and 6.90%, respectively, in the conventional exposure group. In addition, analysis of the secondary outcome indicators for the average total length of surgery, localisation time of the RLN, recognition rate of the superior laryngeal nerve and length of incision revealed that IONM reduced the localisation time of the RLN and increased the identification rate of the superior laryngeal nerve. Subgroup analysis showed that IONM significantly reduced the incidence of RLN palsy in patients with malignancies. CONCLUSIONS: The use of IONM significantly reduced the incidence of transient RLN palsy during endoscopic thyroid surgery, but it did not significantly reduce the incidence of permanent RLN palsy. However, the reduction in the total RLN palsy was statistically significant. In addition, IONM can effectively reduce the location time of the RLN and increase the recognition rate of the superior laryngeal nerve. Therefore, the application of IONM for malignant tumours is recommended.

Development and validation of an online nomogram for predicting the outcome of open tracheotomy decannulation: a two-center retrospective analysis.

BACKGROUND: Tracheotomy decannulation is critical for patients in the intensive care unit (ICU) to recover. In this study, we developed and validated an intuitive nomogram to predict the success rate of tracheotomy decannulation. METHODS: We collected the data of 627 ICU patients before open tracheotomy decannulation from two medical institutions, including 466 patients (135 success and 331 failure) from the First Affiliated Hospital of Anhui Medical University as a training cohort, and 161 patients (57 success and 104 failure) from the Second Affiliated Hospital of Anhui Medical University as an external validation cohort. A least absolute shrinkage and multivariate logistic regression analysis were performed to determine the independent risk factors and construct the nomogram. The area under the receiver operating characteristic curve (AUC) was used to assess discrimination and the calibration plots were used to assess consistency. The clinical application was assessed using decision curve analysis and the clinical impact curve. RESULTS: 7 independent risk factors were eventually included in the prediction model. The AUC of the training cohort, internal validation and external validation were 0.932, 0.926, and 0.915, showing good discrimination. The model performed well in terms of calibration, decision curve analysis, and clinical impact curves. The superior performance of the model was also confirmed by external validation. CONCLUSION: This nomogram can help ICU physicians identify high-risk patients for decannulation and plan their pre-decannulation treatment accordingly.

An ion-channel-gene-based prediction model for head and neck squamous cell carcinoma: Prognostic assessment and treatment guidance.

Purpose: Head and neck squamous cell carcinoma (HNSCC) is a very diverse malignancy with a poor prognosis. The purpose of this study was to develop a new signature based on 12 ion channel genes to predict the outcome and immune status of HNSCC patients. Methods: Clinicopathological information and gene sequencing data of HNSCC patients were generated from the Cancer Genome Atlas and Gene Expression Omnibus databases. A set of 323 ion channel genes was obtained from the HUGO Gene Nomenclature Committee database and literature review. Using univariate Cox regression analysis, the ion channel genes related to HNSCC prognosis were identified. A prognostic signature and nomogram were then created using machine learning methods. Kaplan-Meier analysis was used to explore the relevance of the risk scores and overall survival (OS). We also investigated the association between risk scores, tumor immune infiltration, and gene mutational status. Finally, we detected the expression levels of the signature genes by quantitative real-time polymerase chain reaction, western blotting, and immunohistochemistry. Results: We separated the patients into high- and low-risk groups according to the risk scores computed based on these 12 ion channel genes, and the OS of the low-risk group was significantly longer (p<0.001). The area under the curve for predicting 3-year survival was 0.729. Univariate and multivariate analyses showed that the 12-ion-channel-gene risk model was an independent prognostic factor. We also developed a nomogram model based on risk scores and clinicopathological variables to forecast outcomes. Furthermore, immune cell infiltration, gene mutation status, immunotherapy response, and chemotherapeutic treatment sensitivity were all linked to risk scores. Moreover, high expression levels of ANO1, AQP9, and BEST2 were detected in HNSCC tissues, whereas AQP5, SCNN1G, and SCN4A expression was low in HNSCC tissues, as determined by experiments. Conclusion: The 12-ion-channel-gene prognostic signatures have been demonstrated to be highly efficient in predicting the prognosis, immune microenvironment, gene mutation status, immunotherapy response, and chemotherapeutic sensitivity of HNSCC patients.

Comparison of various surgical incisions in parotidectomy: A systematic review and network meta-analysis.

Background: This network meta-analysis aimed to comprehensively compare the operative and postoperative outcomes of different parotidectomy incisions. Methods: Embase, PubMed, Web of Science, and Cochrane Central Register of Controlled Trials were searched up to April 2022. A complete Bayesian network meta-analysis was performed using the Markov Monte Carlo method in OpenBUGS. Results: Seventeen studies with 1609 patients were included. Thirteen were retrospective cohort studies, three were prospective cohort studies, and one was a randomized controlled study. The quality of evidence was rated as very low in most comparisons. The incision satisfaction score of the modified facelift incision (MFI), retroauricular hairline incision (RAHI), V-shaped incision (VI) were higher than that of the modified Blair incision (MBI) (MBI vs. MFI: mean difference [MD] -1.39; 95% credible interval [CrI] -2.23, -0.57) (MBI vs. RAHI: MD -2.25; 95% CrI -3.40, -1.12) (MBI vs. VI: MD -2.58; 95% CrI -3.71, -1.46); the tumor size treated by VI was smaller than that by MBI (MD 5.15; 95% CrI 0.76, 9.38) and MFI (MD 5.16; 95% CrI 0.34, 9.86); and the risk of transient facial palsy in the MFI was lower than that in the MBI (OR 2.13; 95% CrI 1.28, 3.64). There were no differences in operation time, drainage volume, wound infection, hematoma, salivary complications, Frey syndrome, or permanent facial palsy between incision types. Conclusion: The traditional MBI is frequently used for large tumor volumes, but the incision satisfaction score is low and postoperative complication control is poor. However, emerging incisions performed well in terms of incision satisfaction scores and control of complications. More randomized controlled trials are needed to compare the different parotidectomy incisions. Patients should be fully informed about the characteristics of each incision to make the most informed decision, along with the physician's advice. Systematic Review Registration: PROSPERO, identifier CRD42022331756.

A New Online Dynamic Nomogram: Construction and Validation of an Assistant Decision-Making Model for Laryngeal Squamous Cell Carcinoma.

Background: Laryngeal squamous cell carcinoma (LSCC) is the most common type of head and neck squamous cell carcinoma. However, there are currently no reliable biomarkers for the diagnosis and prognosis of LSCC. Thus, this study aimed to identify the independent risk factors and develop and validate a new dynamic web-based nomogram that can predict auxiliary laryngeal carcinogenesis. Methods: Data on the medical history of 221 patients who were recently diagnosed with LSCC and 359 who were recently diagnosed with benign laryngeal lesions (BLLs) at the First Affiliated Hospital of Anhui Medical University were retrospectively reviewed. Using the bootstrap method, 580 patients were divided in a 7:3 ratio into a training cohort (LSCC, 158 patients; BLL, 250 patients) and an internal validation cohort (LSCC, 63 patients; BLL, 109 patients). In addition, a retrospective analysis of 31 patients with LSCC and 54 patients with BLL from Fuyang Hospital affiliated with Anhui Medical University was performed as an external validation cohort. In the training cohort, the relevant indices were initially screened using univariate analysis. Then, least absolute shrinkage and selection operator logistic analysis was used to evaluate the significant potential independent risk factors (P<0.05); a dynamic online diagnostic nomogram, whose discrimination was evaluated using the area under the ROC curve (AUC), was constructed, while the consistency was evaluated using calibration plots. Its clinical application was evaluated by performing a decision curve analysis (DCA) and validated by internal validation of the training set and external validation of the validation set. Results: Five independent risk factors, sex (odds ratio [OR]: 6.779, P<0.001), age (OR: 9.257, P<0.001), smoking (OR: 2.321, P=0.005), red blood cell width distribution (OR: 2.698, P=0.001), albumin (OR: 0.487, P=0.012), were screened from the results of the multivariate logistic analysis of the training cohort and included in the LSCC diagnostic nomogram. The nomogram predicted LSCC with AUC values of 0.894 in the training cohort, 0.907 in the internal testing cohort, and 0.966 in the external validation cohort. The calibration curve also proved that the nomogram predicted outcomes were close to the ideal curve, the predicted outcomes were consistent with the real outcomes, and the DCA curve showed that all patients could benefit. This finding was also confirmed in the validation cohort. Conclusion: An online nomogram for LSCC was constructed with good predictive performance, which can be used as a practical approach for the personalized early screening and auxiliary diagnosis of the potential risk factors and assist physicians in making a personalized diagnosis and treatment for patients.