Development and Validation of a Prognostic Model to Predict Hearing Recovery for Patients With Chronic Otitis Media.

OBJECTIVE: To explore the factors affecting postoperative hearing recovery in chronic otitis media (COM) patients, establish a clinical prediction model for hearing recovery, and verify the accuracy of the model. METHODS: Data of patients with COM who were admitted to our hospital between January 1, 2012 and September 30, 2020 were retrospectively analyzed. We collected data on relevant clinicopathological characteristics of patients. The patients were randomly divided into the development cohort and validation cohorts. A postoperative air-bone gap (ABG) ≤20 dB was defined as successful hearing recovery. Univariate and multivariable logistic regression analyses were used to investigate the association of several prognostic factors with hearing recovery. These factors were then used to establish a nomogram. The model was subjected to bootstrap internal validation and performance evaluation in terms of discrimination, calibration, and clinical validity. RESULTS: This study included 2146 patients with COM: the development cohort comprised 1610 patients (mean [standard deviation; SD] age, 44.1 [14.7] years; 733 men [45.5%]) and the validation cohort included 536 patients (mean [SD] age, 42.9 [14.4] years; 234 men [43.7%]). Multivariable logistic regression analysis showed that age, duration of onset, styles of surgery (tympanoplasty, canal wall up-CWU, or canal wall down-CWD), ossicular prosthesis, granulation or calcified blocks around the ossicular chain, ossicular chain integrity, duration of drilling, eustachian tube dysfunction, mixed hearing loss, semicircular canal fistula, and second surgery were associated with hearing recovery. A nomogram based on these variables was constructed. The area under the curve was 0.797 (95% confidence interval [CI], 0.778-0.812) in the development cohort and 0.798 (95% CI, 0.7605-0.8355) in the validation cohort. CONCLUSIONS: This study demonstrated the various clinical factors correlated with hearing recovery in patients with COM. The nomogram developed with these data could provide personalized risk estimates of hearing recovery to enhance preoperative counseling and help to set realistic expectations in patients.

A network pharmacology approach to explore and validate the potential targets of ginsenoside on osteoporosis.

Background: Osteoporosis (OP) is determined as a chronic systemic bone disorder to increase the susceptibility to fracture. Ginsenosides have been found the anti-osteoporotic activity of in vivo and in vitro. However, its mechanism remains unknown.Methods: The potential mechanism of ginsenosides in anti-osteoporotic activity was identified by using network phamacology analysis. The active compounds of ginsenosides and their targets associated to OP were retrieved from Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform, Drug Bank, Pharmmapper, and Cytoscape. The Gene ontology (GO) enrichment analysis and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis target genes were performed in String, Phenopedia, DisGeNET database, and Metascape software. The protein to protein interaction were created by String database and Cytoscape software. The molecular docking was used to investigate the interactions between active coumpounds and potential targets by utilizing SwissDock tool, UCSF Chimera, and Pymol software. Results: A total of eight important active ingredients and 17 potential targets related to OP treatment were subjected to analyze. GO analysis showed the anti-osteoporosis targets of ginsenoside mainly play a role in the response to steroid hormone. KEGG enrichment analysis indicated that ginsenoside treats OP by osteoblast differentiation signal pathway. Lastly, the molecular docking outcomes indicated that ginsenoside rh2 had a good binding ability with four target proteins IL1B, TNF, IFNG, and NFKBIA. Conclusion: IL1B, TNF, IFNG, and NFKBIA are the most important targets and osteoblast differentiation is the most valuable signaling pathways in ginsenoside for the treatment of OP, which might be beneficial to elucidate the mechanism concerned to the action of ginsenoside and might supply a better understanding of its anti-OP effects.

The nonlinear association between albumin levels and risk of noninvasive fungal rhinosinusitis.

PURPOSE: The preoperative diagnosis of noninvasive fungal rhinosinusitis (NIFRS) is inaccurate, and biomarkers to assist the diagnosis are urgently needed. We aimed to evaluate the relationship between albumin levels and NIFRS to assist in early diagnosis. METHODS: Patients with NIFRS and chronic sinusitis were enrolled in this study. Appropriate statistical methods were used to determine whether there was a statistical difference between the groups. Subgroup analysis was performed to investigate the relationship between albumin levels and NIFRS, and a generalised additive model (GAM) was used to perform nonlinear relationships. RESULTS: A total of 620 patients were included, including 240 patients with NIFRS. A close relationship was found between albumin levels and NIFRS (P < 0.0001), and the low albumin group was associated with a higher incidence of NIFRS, which was reduced by 60 and 70% in the middle and high albumin groups, respectively. The subgroup analysis also demonstrated an association between albumin levels and NIFRS, except in patients with an alcohol history (P = 0.0665). Interestingly, a nonlinear relationship is observed according to the adjusted GAM. The inflection point was set at 37.0 g/L. A negative correlation was observed among patients with albumin > 37.0 g/L. When the albumin count was <37.0 g/L, the Y value obviously increased and was saturated at 70%, with no further significant increase. CONCLUSION: Albumin levels were significantly negatively correlated with the incidence of NIFRS, and the incidence increased markedly among patients with albumin < 37.0 g/L.

Analysis of Genetic Alteration Signatures and Prognostic Values of m6A Regulatory Genes in Head and Neck Squamous Cell Carcinoma.

Genetic alteration involving N6-methyladenosine (m6A) regulatory genes is a frequent characteristic of multiple tumors. Nevertheless, little is known regarding their genetic alteration signatures and prognostic values in head and neck squamous cell carcinoma (HNSCC). In this study, RNA sequence profiles and copy number variation (CNV) data of 506 HNSCC patients were downloaded from The Cancer Genome Atlas (TCGA) database. Correlation analysis involving alteration of m6A regulatory genes, clinicopathological characteristics, and patient survival was performed using R language. The results suggest that alteration of m6A regulatory genes was correlated with clinical staging. Patients with high expression of ALKBH5, FTO, METTL14, WTAP, YTHDC1, YTHDF1, and YTHDF2 had poor overall survival (OS) than those with low expression. Univariate and multivariate Cox regression analyses showed that ALKBH5 and YTHDC2 were independent risk factors for OS. However, patients with high YTHDC2 expression had better OS. Moreover, according to machine learning results, YTHDC2 was found to be the most important gene among the 10 m6A regulators. Additionally, high expression of YTHDC2 was correlated with activation of apoptosis and ubiquitin-mediated proteolysis. Here, we identified alterations to m6A regulatory genes in HNSCC for the first time and found that seven m6A regulators were associated with poor prognosis, especially ALKBH5, whereas YTHDC2 was associated with better prognosis. These m6A-related regulators could act as novel prognostic biomarkers for HNSCC. Our findings provide clues for understanding RNA epigenetic modifications in HNSCC.

Identification of Key Modules, Hub Genes, and Noncoding RNAs in Chronic Rhinosinusitis with Nasal Polyps by Weighted Gene Coexpression Network Analysis.

Chronic rhinosinusitis with nasal polyps (CRSwNP) is a chronic inflammatory disease with relatively easy recurrence. However, the precise molecular mechanisms of this disease are poorly known. Based on gene sequencing data obtained from the Gene Expression Omnibus (GEO) database, we constructed coexpression networks by weighted gene coexpression network analysis (WGCNA). Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analyses were performed by the Database for Annotation, Visualization, and Integrated Discovery (DAVID). The core gene of pathogenesis, CRSwNP, was screened by protein-protein interaction data (PPI) from the HPRD database. Unsupervised clustering was applied to screen hub genes related to the phenotype of CRSwNP. Blue and turquoise modules were found to be most significantly related to the pathogenicity of CRSwNP. Functional enrichment analysis showed that cell proliferation in the blue modules, the apoptotic process in the turquoise module, and the cancer pathway in both modules were mostly significantly correlated with the development of CRSwNP. The noncoding RNAs (long noncoding RNA and microRNA) and the top 10 core genes in each module were found to be associated with the pathogenesis of CRSwNP. A total of nine hub genes were identified to be related to the CRSwNP phenotype. By qRT-PCR analysis, AKT1, CDH1, PIK3R1, CBL, LRP1, MALAT1, and XIST were proven to be associated with the pathogenesis of CRSwNP. AGR2, FAM3D, PIP, DSE, and TMC were identified to be related to the CRSwNP phenotype. Further exploration of these genes will reveal more important information about the mechanisms of CRSwNP.

Physiological Ischemic Training Promotes Brain Collateral Formation and Improves Functions in Patients with Acute Cerebral Infarction.

OBJECTIVES: To observe the effectiveness and mechanisms of physiological ischemic training (PIT) on brain cerebral collateral formation and functional recovery in patients with acute cerebral infarction. METHODS: 20 eligible patients with acute cerebral infarction were randomly assigned to either PIT group (n = 10) or Control group (n = 10). Both groups received 4 weeks of routine rehabilitation therapy, while an additional session of PIT, which consisted of 10 times of maximal voluntary isometric handgrip for 1 min followed by 1 min rest, was prescribed for patients in the PIT groups. Each patient was trained with four sections a day and 5 days a week for 4 weeks. The Fugl-Meyer Assessment (FMA), the Modified Barthel Index (MBI), and the short-form 36-item health survey questionnaire (SF-36) were applied for the evaluation of motor impairment, activity of daily living, and quality of life at the baseline and endpoint. MRI was applied to detect the collateral formation in the brain. The concentration of vascular endothelial growth factor (VEGF) and endothelial progenitor cells (EPCs) number in plasma were also tested at the endpoint. RESULTS: Demographic data were consistent between experimental groups. At the endpoint, the scores of the FMA, MBI, and SF-36 were significantly higher than that at baseline. As compared to the Control group, the score of FMA and SF-36 in PIT group was significantly higher, while no significant difference was detected between groups in terms of MBI. Both groups had significantly higher cerebral blood flow (CBF) level at endpoint as compared to that at baseline. Moreover, the CBF level was even higher in the PIT group as compared to that in the Control group after 4 weeks of training. The same situations were also found in the plasma VEGF and EPCs assessment. In addition, positive correlations were found between FMA score and CBF level (r = 0.686, p < 0.01), CBF level and VEGF concentration (r = 0.675, p < 0.01), and VEGF concentration and EPC number (r = 0.722, p < 0.01). CONCLUSION: PIT may be effective in increasing the expression of VEGF and recruitment of EPCs and in turn promote the formation of brain collateral circulation. The positive correlations may demonstrate a potential association between biological and functional parameters, and PIT may be able to improve the motor function, activity of daily living, and quality of life in patients with stroke.

[Vapor extraction technology in oil contaminated soil remediation].

In order to study the Vapor Extraction Technology that can be applied to China, on the basis of mechanism analysis of Vapor Extraction Technology for oil-contaminated soil, a simplified and practical contaminant removal model to simulate the soil remediation time was presented. With the typical unsaturated soils in North of China, the effects of the vapor flow rate, soil water content and quality on the remediation process were studied. The results showed that the best value of flow velocity was existed, and water content had different influence on different kinds of soil, for silty soil, the efficiency of remediation enhanced with water content increase, but there was a reverse result for clayey soil. Through one-dimension soil column experiments, the results showed that these factors had different effects on remediation time. The research using the soil column apparatus show that the predicted results were validated and the applied conditions of this model were qualified.