[The VeSFADS structural classification of vestibular disorders].

The issuing of International Classification of Vestibular Disorders（ICVD） by Brny society（2015） greatly facilitates the progress of vestibular medicine. The syndromic classification of vestibular disorders by ICVD enable the physician to narrow the spectrum of differential diagnosis for the vestibular disorder in clinical practice. However, the division of vestibular pathway, especially the central vestibular system, has not be classified yet in the ICVD（2015）. Central vertigo, being a group of heterogeneous disorders, may present diverse clinical spectrums. The misdiagnosis of central vestibular as well as peripheral vestibular disorders have been reported in the clinic practice. Therefore, the author by review study proposes a structural classification of vestibular disorders combined the Vestibular System Functional Anatomy Division with Syndromes（VeSFADS）. The VeSFADS classification of vestibular disorders could help the physician in clinical practice to narrow the spectrum of vestibular disorders, in addition to the syndromic classification, by the clinical feature of vestibular disorders from different division of vestibular system. And the VeSFADS classification of vestibular disorders may facilitate to clarify the clinical features of vestibular disorders at different Division of vestibular pathway.

Optimizing the PROTREC network-based missing protein prediction algorithm.

This article summarizes the PROTREC method and investigates the impact that the different hyper-parameters have on the task of missing protein prediction using PROTREC. We evaluate missing protein recovery rates using different PROTREC score selection approaches (MAX, MIN, MEDIAN, and MEAN), different PROTREC score thresholds, as well as different complex size thresholds. In addition, we included two additional cancer datasets in our analysis and introduced a new validation method to check both the robustness of the PROTREC method as well as the correctness of our analysis. Our analysis showed that the missing protein recovery rate can be improved by adopting PROTREC score selection operations of MIN, MEDIAN, and MEAN instead of the default MAX. However, this may come at a cost of reduced numbers of proteins predicted and validated. The users should therefore choose their hyper-parameters carefully to find a balance in the accuracy-quantity trade-off. We also explored the possibility of combining PROTREC with a p-value-based method (FCS) and demonstrated that PROTREC is able to perform well independently without any help from a p-value-based method. Furthermore, we conducted a downstream enrichment analysis to understand the biological pathways and protein networks within the cancerous tissues using the recovered proteins. Missing protein recovery rate using PROTREC can be improved by selecting a different PROTREC score selection method. Different PROTREC score selection methods and other hyper-parameters such as PROTREC score threshold and complex size threshold introduce accuracy-quantity trade-off. PROTREC is able to perform well independently of any filtering using a p-value-based method. Verification of the PROTREC method on additional cancer datasets. Downstream Enrichment Analysis to understand the biological pathways and protein networks in cancerous tissues.

Serological response and immune-related adverse events following COVID-19 vaccination in cancer patients treated with immune checkpoint inhibitors: A systematic review and meta-analysis.

With the popularity of Coronavirus disease 2019 (COVID-19) vaccine and the development of vaccination strategies, the impact of COVID-19 vaccine on cancer patients receiving immune checkpoint inhibitors (ICIs) is still unclear. In the systematic review and meta-analysis of patients with ICIs, we assessed the serological response of cancer patients receiving COVID-19 vaccine, and explored the risk of immune related adverse events (irAEs). We searched PubMed, EMBASE and Cochrane Library as of 10 June 2023, and included cancer patients who received ICIs and COVID-19 vaccine. The systematic review and meta-analysis include cohort study, cross-sectional study and case report. The outcome included the serological response, Spike-specific T-cell response, irAEs and rare adverse events. When possible, the data were analysed by random effect analysis, and the statistical heterogeneity was assessed by Q-test and I2 statistics. We explored the sources of heterogeneity through L'Abbe plots, Galbraith radial plots, and sensitivity analysis. The publication bias was evaluated by Egger's, Begg's linear regression test and funnel plot, and the impact of publication bias was further analysed by trim and fill method. 27 studies were eligible (19 cohort studies, 1 cross-sectional study and 7 case reports), involving 8331 patients (with 4724 receiving ICIs). Most studies used mRNA vaccine (BNT162b2 or mRNA-1273). Compared with cancer patients receiving chemotherapy, cancer patients receiving ICIs were significantly more likely to have seroconversion (RR = 1.05, 95%CI 1.01-1.10, P = 0.02). There were no statistically significant differences in seroconversion rates when comparing cancer patients receiving ICIs with controls without cancer (RR = 0.95, 95% CI 0.89-1.01, P = 0.09) or with cancer patients receiving targeted therapy (RR = 1.05, 95% CI 0.79-1.39, P = 0.75). The incidence of irAEs in patients receiving ICIs before and after COVID-19 vaccination was (21.96%, 95%CI 16.66%-28.94%) and (14.88%, 95%CI 8.65%-25.57%), respectively. The most common irAEs were endocrine abnormalities, skin disorders, etc. The certainty of evidence was low in cancer patients with ICIs, compared with those receiving chemotherapy, and very low versus controls without cancer. Cancer patients treated with ICIs seem to be able to receive COVID-19 vaccine safely without increasing the incidence of irAEs.

ProJect: a powerful mixed-model missing value imputation method.

Missing values (MVs) can adversely impact data analysis and machine-learning model development. We propose a novel mixed-model method for missing value imputation (MVI). This method, ProJect (short for Protein inJection), is a powerful and meaningful improvement over existing MVI methods such as Bayesian principal component analysis (PCA), probabilistic PCA, local least squares and quantile regression imputation of left-censored data. We rigorously tested ProJect on various high-throughput data types, including genomics and mass spectrometry (MS)-based proteomics. Specifically, we utilized renal cancer (RC) data acquired using DIA-SWATH, ovarian cancer (OC) data acquired using DIA-MS, bladder (BladderBatch) and glioblastoma (GBM) microarray gene expression dataset. Our results demonstrate that ProJect consistently performs better than other referenced MVI methods. It achieves the lowest normalized root mean square error (on average, scoring 45.92% less error in RC_C, 27.37% in RC_full, 29.22% in OC, 23.65% in BladderBatch and 20.20% in GBM relative to the closest competing method) and the Procrustes sum of squared error (Procrustes SS) (exhibits 79.71% less error in RC_C, 38.36% in RC full, 18.13% in OC, 74.74% in BladderBatch and 30.79% in GBM compared to the next best method). ProJect also leads with the highest correlation coefficient among all types of MV combinations (0.64% higher in RC_C, 0.24% in RC full, 0.55% in OC, 0.39% in BladderBatch and 0.27% in GBM versus the second-best performing method). ProJect's key strength is its ability to handle different types of MVs commonly found in real-world data. Unlike most MVI methods that are designed to handle only one type of MV, ProJect employs a decision-making algorithm that first determines if an MV is missing at random or missing not at random. It then employs targeted imputation strategies for each MV type, resulting in more accurate and reliable imputation outcomes. An R implementation of ProJect is available at https://github.com/miaomiao6606/ProJect.

Role and mechanism of FOXG1-related epigenetic modifications in cisplatin-induced hair cell damage.

Cisplatin is widely used in clinical tumor chemotherapy but has severe ototoxic side effects, including tinnitus and hearing damage. This study aimed to determine the molecular mechanism underlying cisplatin-induced ototoxicity. In this study, we used CBA/CaJ mice to establish an ototoxicity model of cisplatin-induced hair cell loss, and our results showed that cisplatin treatment could reduce FOXG1 expression and autophagy levels. Additionally, H3K9me2 levels increased in cochlear hair cells after cisplatin administration. Reduced FOXG1 expression caused decreased microRNA (miRNA) expression and autophagy levels, leading to reactive oxygen species (ROS) accumulation and cochlear hair cell death. Inhibiting miRNA expression decreased the autophagy levels of OC-1 cells and significantly increased cellular ROS levels and the apoptosis ratio in vitro. In vitro, overexpression of FOXG1 and its target miRNAs could rescue the cisplatin-induced decrease in autophagy, thereby reducing apoptosis. BIX01294 is an inhibitor of G9a, the enzyme in charge of H3K9me2, and can reduce hair cell damage and rescue the hearing loss caused by cisplatin in vivo. This study demonstrates that FOXG1-related epigenetics plays a role in cisplatin-induced ototoxicity through the autophagy pathway, providing new ideas and intervention targets for treating ototoxicity.

Evaluating network-based missing protein prediction using p-values, Bayes Factors, and probabilities.

Some prediction methods use probability to rank their predictions, while some other prediction methods do not rank their predictions and instead use [Formula: see text]-values to support their predictions. This disparity renders direct cross-comparison of these two kinds of methods difficult. In particular, approaches such as the Bayes Factor upper Bound (BFB) for [Formula: see text]-value conversion may not make correct assumptions for this kind of cross-comparisons. Here, using a well-established case study on renal cancer proteomics and in the context of missing protein prediction, we demonstrate how to compare these two kinds of prediction methods using two different strategies. The first strategy is based on false discovery rate (FDR) estimation, which does not make the same naïve assumptions as BFB conversions. The second strategy is a powerful approach which we colloquially call "home ground testing". Both strategies perform better than BFB conversions. Thus, we recommend comparing prediction methods by standardization to a common performance benchmark such as a global FDR. And where this is not possible, we recommend reciprocal "home ground testing".

PROSE: phenotype-specific network signatures from individual proteomic samples.

Proteomic studies characterize the protein composition of complex biological samples. Despite recent advancements in mass spectrometry instrumentation and computational tools, low proteome coverage and interpretability remains a challenge. To address this, we developed Proteome Support Vector Enrichment (PROSE), a fast, scalable and lightweight pipeline for scoring proteins based on orthogonal gene co-expression network matrices. PROSE utilizes simple protein lists as input, generating a standard enrichment score for all proteins, including undetected ones. In our benchmark with 7 other candidate prioritization techniques, PROSE shows high accuracy in missing protein prediction, with scores correlating strongly to corresponding gene expression data. As a further proof-of-concept, we applied PROSE to a reanalysis of the Cancer Cell Line Encyclopedia proteomics dataset, where it captures key phenotypic features, including gene dependency. We lastly demonstrated its applicability on a breast cancer clinical dataset, showing clustering by annotated molecular subtype and identification of putative drivers of triple-negative breast cancer. PROSE is available as a user-friendly Python module from https://github.com/bwbio/PROSE.

[Discussion on diagnosis and treatment of dizziness from cases].

Dizziness or vertigo is a common clinical symptom, and its underlying etiology is complex. Many clinicians are confused about its diagnosis and treatment. This article presents a case about chronic vestibular syndrome. And case appreciation and academic discussion are conducted by well-known domestic neurologists and otologists, so as to provide a good thinking model and basic ideas for the diagnosis and treatment of dizziness or vertigo, hoping to further improve the diagnosis and treatment level among clinicians.

AIM2 inflammasome activation may mediate high mobility group box 1 release in murine allergic rhinitis / Ativação do inflamassoma AIM2 pode mediar a liberação da proteína do grupo Box-1 de alta mobilidade no modelo murino de rinite alérgica

Abstract Introduction: High mobility group box 1 protein participates in the pathogenesis of allergic rhinitis. Activation of the inflammasome can mediate the release of high mobility group box 1. The role of the absent in melanoma 2 inflammasome in allergic rhinitis remains unclear. Objective: This study aimed to investigate the function of absent in melanoma 2 inflammasome in murine allergic rhinitis and the interaction between high mobility group box 1 and the absent in melanoma 2 inflammasome. Methods: A murine allergic rhinitis model was established using twenty Balb/c mice. Expression of the components of the absent in melanoma 2 inflammasome: absent in melanoma 2, apoptosis-associated speck-like protein containing a CARD (Asc), caspase-1 p20, and additional nod-like receptor family pyrin domain containing 3 (Nlrp3) were detected by western blotting during allergic rhinitis. Alterations of absent in melanoma 2, caspase-1, and high mobility group box 1 after ovalbumin challenge were demonstrated by immunohistochemistry. TdT-mediated dUTP Nick end labeling, TUNEL assay, and cleavage of caspase-3 and PARP-1 were used for the observation of pyroptosis. Results: Eosinophilia and goblet cell infiltration were observed in the nasal mucosa of mice in the allergic rhinitis group. Absent in melanoma 2, Asc, and caspase-1 p20 increased after ovalbumin exposure while Nlrp3 did not. High mobility group box 1 was released in the nasal mucosa of allergic rhinitis mice. TUNEL-positive cells increased in the epithelium and laminae propria, whereas cleavage of caspase-3 and PARP-1 was not observed. Conclusions: The absent in melanoma 2 inflammasome was activated and pyroptosis may occur in the nasal mucosa after ovalbumin treatment. These may contribute to the translocation of high mobility group box 1 and the development of allergic rhinitis.

Resumo Introdução: A proteína do grupo Box-1 de alta mobilidade participa da patogênese da rinite alérgica. A ativação do inflamassoma pode mediar a liberação de proteína do grupo Box-1 de alta mobilidade. O papel do inflamassoma ausente no melanoma 2 na rinite alérgica permanece incerto. Objetivo: Investigar a função do inflamassoma ausente no melanoma 2 em um modelo murino de rinite alérgica e a interação entre a proteína do grupo Box-1 de alta mobilidade e o inflamassoma ausente no melanoma 2. Método: Um modelo murino de rinite alérgica foi estabelecido com 20 camundongos Balb/c. A expressão dos componentes do inflamassoma ausente no melanoma 2, da proteína speck-like associada à apoptose com CARD (Asc), da caspase-1 p20 e do domínio de pirina da família NLR adicional com 3 (Nlrp3) foi detectada por western blotting durante a rinite alérgica. Alterações de inflamassoma ausente no melanoma 2, na caspase-1 e na proteína do grupo Box-1 de alta mobilidade após o teste de provocação com ovalbumina foram demonstradas por imuno-histoquímica. O ensaio dUTP Nick-End Labeling mediado por TdT, TUNEL e clivagem de caspase-3 e PARP-1 foram usados para a observação de piroptose. Resultados: Eosinofilia e infiltração de células caliciformes foram observadas na mucosa nasal de camundongos do grupo rinite alérgica. Inflamassoma ausente no melanoma 2, Asc e caspase-1 p20 aumentou após a exposição à ovalbumina, enquanto Nlrp3 não aumentou. A proteína do grupo Box-1 de alta mobilidade foi liberada na mucosa nasal de camundongos com rinite alérgica. As células TUNEL-positivas aumentaram no epitélio e na lâmina própria, enquanto a clivagem da caspase-3 e a PARP-1 não foram observadas. Conclusão: O inflamassoma ausente no melanoma 2 foi ativado e pode ocorrer piroptose na mucosa nasal após o tratamento com ovalbumina. Esses fatores podem contribuir para a translocação de proteína do grupo Box-1 de alta mobilidade e o desenvolvimento de rinite alérgica.

Resolving missing protein problems using functional class scoring.

Despite technological advances in proteomics, incomplete coverage and inconsistency issues persist, resulting in "data holes". These data holes cause the missing protein problem (MPP), where relevant proteins are persistently unobserved, or sporadically observed across samples, hindering biomarker discovery and proper functional characterization. Network-based approaches can provide powerful solutions for resolving these issues. Functional Class Scoring (FCS) is one such method that uses protein complex information to recover missing proteins with weak support. However, FCS has not been evaluated on more recent proteomic technologies with higher coverage, and there is no clear way to evaluate its performance. To address these issues, we devised a more rigorous evaluation schema based on cross-verification between technical replicates and evaluated its performance on data acquired under recent Data-Independent Acquisition (DIA) technologies (viz. SWATH). Although cross-replicate examination reveals some inconsistencies amongst same-class samples, tissue-differentiating signal is nonetheless strongly conserved, confirming that FCS selects for biologically meaningful networks. We also report that predicted missing proteins are statistically significant based on FCS p values. Despite limited cross-replicate verification rates, the predicted missing proteins as a whole have higher peptide support than non-predicted proteins. FCS also predicts missing proteins that are often lost due to weak specific peptide support.

Construction and analysis of a ceRNA network and patterns of immune infiltration in chronic rhinosinusitis with nasal polyps: based on data mining and experimental verification.

Recent studies have revealed the significant role of the competing endogenous RNA (ceRNA) network in human diseases. However, systematic analysis of the ceRNA mechanism in chronic rhinosinusitis with nasal polyps (CRSwNP) is limited. In this study, we constructed a competitive endogenous RNA (ceRNA) network and identified a potential regulatory axis in CRSwNP based on bioinformatics analysis and experimental verification. We obtained lncRNA, miRNA, and mRNA expression profiles from the Gene Expression Omnibus. After analysis of CRSwNP patients and the control groups, we identified 565 DE-lncRNAs, 23 DE-miRNAs, and 1799 DE-mRNAs by the DESeq2 R package or limma R package. Enrichment analysis of 1799 DE-mRNAs showed that CRSwNP was associated with inflammation and immunity. Moreover, we identified 21 lncRNAs, 8 miRNAs and 8 mRNAs to construct the lncRNA-miRNA-mRNA ceRNA network. A potential MIAT/miR-125a/IRF4 axis was determined according to the degree and positive correlation between a lncRNA and its competitive endogenous mRNAs. The GSEA results suggested that IRF4 may be involved in immune cell infiltration. The validation of another dataset confirmed that MIAT and IRF4 were differentially expressed between the CRSwNP and control groups. The area under the ROC curve (AUC) of MIAT and IRF4 was 0.944. The CIBERSORT analysis revealed that eosinophils and M2 macrophages may be involved in the CRSwNP process. MIAT was correlated with dendritic cells and M2 macrophages, and IRF4 was correlated with dendritic cells. Finally, to validate the key genes, we performed in-silico validation using another dataset and experimental validation using immunohistochemistry, immunofluorescence, and Western blot. In summary, the constructed novel MIAT/miR-125a/IRF4 axis may play a critical role in the development and progression of CRSwNP. We believe that the ceRNA network and immune cell infiltration could offer further insight into novel molecular therapeutic targets for CRSwNP.

High Expression Levels of SIGLEC9 Indicate Poor Outcomes of Glioma and Correlate With Immune Cell Infiltration.

Objective: This study aimed to investigate the diagnostic value and underlying mechanisms of sialic acid-binding Ig-like lectin 9 (SIGLEC9) in gliomas. Patients and Methods: The Cancer Genome Atlas (TCGA) and the Chinese Glioma Genome Atlas (CGGA) databases were used to analyze the association of SIGLEC9 expression levels with tumor stages and survival probability. Immunohistochemical staining of SIGLEC9 and survival analysis were performed in 177 glioma patients. Furthermore, related mechanisms were discovered about SIGLEC9 in glioma tumorigenesis, and we reveal how SIGLEC9 functions in macrophages through single-cell analysis. Results: TCGA and CGGA databases indicated that patients with high SIGLEC9 expression manifested a significantly shorter survival probability than those with low SIGLEC9 expression. SIGLEC9 was upregulated significantly in malignant pathological types, such as grade III, grade IV, mesenchymal subtype, and isocitrate dehydrogenase wild-type gliomas. The immunohistochemical staining of tissue sections from 177 glioma patients showed that high-SIGLEC9-expression patients manifested a significantly shorter survival probability than low-SIGLEC9-expression patients with age ≧60 years, grade IV, glioblastoma multiforme, alpha thalassemia/intellectual disability syndrome X-linked loss, and without radiotherapy or chemotherapy. Furthermore, the SIGLEC9 expression level was positively correlated with myeloid-derived suppressor cell infiltration and neutrophil activation. The SIGLEC9 expression was also positively correlated with major immune checkpoints, such as LAIR1, HAVCR2, CD86, and LGALS9. Through single-cell analysis, we found that the SIGLEC9 gene is related to the ability of macrophages to process antigens and the proliferation of macrophages. Conclusion: These findings suggested that SIGLEC9 is a diagnostic marker of poor outcomes in glioma and might serve as a potential immunotherapy target for glioma patients in the future.

Palmatine Derivatives as Potential Antiplatelet Aggregation Agents via Protein Kinase G/Vasodilator-Stimulated Phosphoprotein and Phosphatidylinositol 3-Kinase/Akt Phosphorylation.

Sixty palmatine (PMT) derivatives were synthesized and evaluated for antiplatelet aggregation taking berberine as the lead, and the structure-activity relationship was first systematically described. Among them, compound 2v showed the best potency in reducing adenosine diphosphate (ADP)-induced platelet aggregation in a dose-dependent manner. It greatly suppressed ADP-induced platelet aggregation, activation, and Akt phosphorylation in vitro and ex vivo after oral administration to mice. It also effectively inhibited carrageenan-induced thrombus formation in the mouse tail and lung, as well as reduced the serum P-selectin level. Compound 2v might simultaneously bind to protein kinase G to improve vasodilator-stimulated phosphoprotein phosphorylation and bind to phosphatidylinositol 3-kinase to inhibit Akt phosphorylation, which synergically reduced platelet aggregation, thereby achieving antithrombotic efficacy. Therefore, PMT derivatives constituted a novel family of antiplatelet aggregation agents with the advantage of a good safety profile, worthy of further investigation.

Developing a pyroptosis-related gene signature to better predict the prognosis and immune status of patients with head and neck squamous cell carcinoma.

Chronic inflammation may promote the incidence and development of neoplasms. As a pro-inflammatory death pathway, pyroptosis could induce normal cells to transform into cancerous cells, but the potential effect of pyroptosis in head and neck squamous cell carcinoma (HNSCC) remains unclear. This study developed and evaluated a pyroptosis-related gene signature to predict the prognosis and immune status of patients with HNSCC. The gene expression, mutation information, and clinical characteristics of HNSCC were extracted from TCGA to establish a comprehensive genome database (GEO). Based on LASSO Cox regression model, nine pyroptosis-related genes (TTLL1, TRIML2, DYNC1I1, KLHL35, CAMK2N1, TNFRSF18, GLDC, SPINK5, and DKK1) were used to construct a pyroptosis-related gene signature, which had good ability to predict the prognosis of HNSCC. Furthermore, the expression of nine pyroptosis-related genes in HNSCC and paracancerous tissues was detected by quantitative real-time PCR (qRT-PCR). The potential immunotherapeutic features and drug sensitivity prediction of this signature were also explored. Because pyroptosis regulators play an important role in HNSCC development and prognoses, further exploration might assist in identifying new biomarkers and predictors of prognosis to benefit clinical identification and management.

AIM2 inflammasome activation may mediate high mobility group box 1 release in murine allergic rhinitis.

INTRODUCTION: High mobility group box 1 protein participates in the pathogenesis of allergic rhinitis. Activation of the inflammasome can mediate the release of high mobility group box 1. The role of the absent in melanoma 2 inflammasome in allergic rhinitis remains unclear. OBJECTIVE: This study aimed to investigate the function of absent in melanoma 2 inflammasome in murine allergic rhinitis and the interaction between high mobility group box 1 and the absent in melanoma 2 inflammasome. METHODS: A murine allergic rhinitis model was established using twenty Balb/c mice. Expression of the components of the absent in melanoma 2 inflammasome: absent in melanoma 2, apoptosis-associated speck-like protein containing a CARD (Asc), caspase-1 p20, and additional nod-like receptor family pyrin domain containing 3 (Nlrp3) were detected by western blotting during allergic rhinitis. Alterations of absent in melanoma 2, caspase-1, and high mobility group box 1 after ovalbumin challenge were demonstrated by immunohistochemistry. TdT-mediated dUTP Nick end labeling, TUNEL assay, and cleavage of caspase-3 and PARP-1 were used for the observation of pyroptosis. RESULTS: Eosinophilia and goblet cell infiltration were observed in the nasal mucosa of mice in the allergic rhinitis group. Absent in melanoma 2, Asc, and caspase-1 p20 increased after ovalbumin exposure while Nlrp3 did not. High mobility group box 1 was released in the nasal mucosa of allergic rhinitis mice. TUNEL-positive cells increased in the epithelium and laminae propria, whereas cleavage of caspase-3 and PARP-1 was not observed. CONCLUSIONS: The absent in melanoma 2 inflammasome was activated and pyroptosis may occur in the nasal mucosa after ovalbumin treatment. These may contribute to the translocation of high mobility group box 1 and the development of allergic rhinitis.

[In vitro study on the individual binding ability of omalizumab with free IgE].

Objective:To investigate the individual binding ability of omalizumab to free IgE and its effect on omalizumab action. Methods:A total of 28 serum samples were collected from patients with allergic rhinitis and divided into groups with high, medium and low concentrations of free IgE. Different doses of omalizumab were administered in vitro for inhibitory binding. Enzyme linked immunosorbent assay was used to detect changes in serum free IgE after inhibition. The inhibition constant of omalizumab on serum free IgE was calculated. At the same time, the binding ability of omalizumab and individual free IgE was analyzed. Results:In general, when 100% serum free IgE was inhibited, the omalizumab required was positively correlated with the original serum free IgE concentration（9.500±7.207, 8.636±7.375, and 0.786±0.857 for the high, medium, and low IgE concentration groups, respectively）. The dose of omalizumab required for inhibition of 50% free IgE in serum was significantly lower（0.049±0.071, 0.046±0.077, 0.048±0.048 in the high, medium, and low IgE concentrations groups, respectively）. The 100% and 50% inhibition constants of serum free IgE in different individuals were different to some extent. Conclusion:Overall, the amount of omalizumab required to achieve the same inhibitory effect is proportional to the IgE concentration. In some sensitive patients, partial binding inhibition of free IgE can occur even when omalizumab is administered at less than the recommended dose. The binding ability of serum free IgE and omalizumab was different in different individuals. If this factor is used as a reference for the individual dose of omalizumab in clinical medicine, it is possible to achieve the expected efficacy more accurately.

Stem Cell-Based Therapies in Hearing Loss.

In recent years, neural stem cell transplantation has received widespread attention as a new treatment method for supplementing specific cells damaged by disease, such as neurodegenerative diseases. A number of studies have proved that the transplantation of neural stem cells in multiple organs has an important therapeutic effect on activation and regeneration of cells, and restore damaged neurons. This article describes the methods for inducing the differentiation of endogenous and exogenous stem cells, the implantation operation and regulation of exogenous stem cells after implanted into the inner ear, and it elaborates the relevant signal pathways of stem cells in the inner ear, as well as the clinical application of various new materials. At present, stem cell therapy still has limitations, but the role of this technology in the treatment of hearing diseases has been widely recognized. With the development of related research, stem cell therapy will play a greater role in the treatment of diseases related to the inner ear.

Genetic variants of cell cycle pathway genes are associated with head and neck squamous cell carcinoma in the Chinese population.

Genetic alterations in the cell cycle pathway are common in head and neck squamous cell carcinoma (HNSCC). We identified four novel HNSCC susceptibility loci (CDKN1C rs452338, CDK4 rs2072052, E2F2 rs3820028 and E2F2 rs2075993) through a two-stage matched case-control study. There was a combined effect among the four single nucleotide polymorphisms (SNPs), as the number of risk genotypes increased, the risk of HNSCC displayed an increasing trend (Ptrend < 0.001). And there were multiplicative interactions between rs452338 and rs2072052, rs2072052 and rs3820028, rs2072052 and rs2075993. Functional bioinformatics analysis and dual-luciferase reporter assay revealed that E2F2 rs2075993 T>C reduced the stability of E2F2 3'-UTR secondary structure and affected the binding of E2F2 to miR-940, which was up-regulated in HNSCC tumor tissues (P = 2.9e-8) and was correlated with poor overall survival of HNSCC (HR = 1.39, 95% CI = 1.02-1.90). In vitro assays, we discovered that the expression of miR-940 was regulated by METTL3, and miR-940 promoted the proliferation, migration and invasion, and inhibited the senescence and autophagy of tumor cells. In terms of mechanism, compared with rs2075993 allele T, we found that the protective variant rs2075993 allele C interfered with the translational inhibition of E2F2 by miR-940, resulting in increased expression of E2F2 protein, which further reduced the proliferation, migration, invasion, and increased the senescence of tumor cells.