Establishment of an in situ model to explore the tumor immune microenvironment in head and neck squamous cell carcinoma.

OBJECTIVE: Establish an in situ model for investigating HNSCC, focusing on tumor growth, metastasis, and the immune microenvironment. METHODS: Generated a monoclonal SCCVII-ZsGreen cell line through lentiviral transfection. Selected monoclonal lines with growth rates similar to the original SCCVII for in vivo tumorigenesis. Monitored tumor development and metastasis through fluorescence in vivo imaging. Employed immunohistochemistry to assess immune cell distribution in the tumor microenvironment. RESULTS: SCCVII-ZsGreen exhibited comparable proliferation and in vivo tumorigenicity to SCCVII. In situ tumor formation on day 10, with cervical metastasis in C57BL/6 mice by day 16. No significant fluorescence signals in organs like liver and lungs, while SCCVII-ZsGreen presence confirmed in cervical lymph node metastases. Immunohistochemistry revealed CD4+ T, CD8+ T, B, and dendritic cells distribution, with minimal macrophages. CONCLUSION: Our model is a valuable tool for studying HNSCC occurrence, metastasis, and immune microenvironment. It allows dynamic observation of tumor development, aids preclinical drug experiments, and facilitates exploration of the tumor immune contexture.

IL-6 mediates olfactory dysfunction in a mouse model of allergic rhinitis.

BACKGROUND: Immune-inflammatory response is a key element in the occurrence and development of olfactory dysfunction (OD) in patients with allergic rhinitis (AR). As one of the core factors in immune-inflammatory responses, interleukin (IL)-6 is closely related to the pathogenesis of allergic diseases. It may also play an important role in OD induced by diseases, such as Sjögren's syndrome and coronavirus disease 2019. However, there is no study has reported its role in OD in AR. Thus, this study aimed to investigate the role of IL-6 in AR-related OD, in an attempt to discover a new target for the prevention and treatment of OD in patients with AR. METHODS: Differential expression analysis was performed using the public datasets GSE52804 and GSE140454 for AR, and differentially expressed genes (DEGs) were obtained by obtaining the intersection points between these two datasets. IL-6, a common differential factor, was obtained by intersecting the DEGs with the General Olfactory Sensitivity Database (GOSdb) again. A model of AR mice with OD was developed by sensitizing with ovalbumin (OVA) to verify the reliability of IL-6 as a key factor of OD in AR and explore the potential mechanisms. Furthermore, a supernatant and microglia co-culture model of nasal mucosa epithelial cells stimulated by the allergen house dust mite extract Derp1 was established to identify the cellular and molecular mechanisms of IL-6-mediated OD in AR. RESULTS: The level of IL-6 in the nasal mucosa and olfactory bulb of AR mice with OD significantly increased and showed a positive correlation with the expression of olfactory bulb microglia marker Iba-1 and the severity of OD. In-vitro experiments showed that the level of IL-6 significantly increased in the supernatant after the nasal mucosa epithelial cells were stimulated by Derp1, along with significantly decreased barrier function of the nasal mucosa. The expression levels of neuroinflammatory markers IL-1ß and INOS increased after a conditioned culture of microglia with the supernatant including IL-6. Then knockdown (KD) of IL-6R by small interfering RNA (siRNA), the expression of IL-1ß and INOS significantly diminished. CONCLUSION: IL-6 plays a key role in the occurrence and development of OD in AR, which may be related to its effect on olfactory bulb microglia-mediated neuroinflammation.

TMEM16A inhibits autophagy and promotes the invasion of hypopharyngeal squamous cell carcinoma through mTOR pathway.

Previous studies have indicated that transmembrane protein 16A (TMEM16A) plays a crucial role in the pathogenesis and progression of various tumors by influencing multiple signaling pathways. However, the role of TMEM16A in regulating autophagy via the mammalian target of rapamycin (mTOR) pathway and its impact on the development of hypopharyngeal squamous cell carcinoma (HSCC) remain unclear. Immunohistochemistry and western blotting were used to assess the expression of TMEM16A in HSCC tissues and metastatic lymph nodes. Manipulation of TMEM16A expression levels was achieved in the FaDu cell line through overexpression or knockdown, followed by assessment of its biological effects using cell colony formation, wound healing, transwell, and invasion assays. Additionally, apoptosis and autophagy-related proteins, as well as autophagosome formation, were evaluated through western blotting, transmission electron microscopy, and immunofluorescence following TMEM16A knockdown or overexpression in FaDu cells. Our study revealed significantly elevated levels of TMEM16A in both HSCC tissues and metastatic lymph nodes compared to normal tissues. In vitro experiments demonstrated that silencing TMEM16A led to a notable suppression of HSCC cell proliferation, invasion, and migration. Furthermore, TMEM16A silencing effectively inhibited tumor growth in xenografted mice. Subsequent investigations indicated that knockdown of TMEM16A in HSCC cells could suppress mTOR activation, thereby triggering autophagic cell death by upregulating sequestosome-1 (SQSTM1/P62) and microtubule-associated protein light chain 3 II (LC3II). This study highlights the crucial role of TMEM16A in modulating autophagy in HSCC, suggesting its potential as a therapeutic target for the treatment of this malignancy.

Anlotinib suppressed tumor cell proliferation and migration in hypopharyngeal carcinoma.

OBJECTIVE: The purpose of this study is to study the in-vitro effects of multitarget inhibitor anlotinib on hypopharyngeal cancer cell proliferation and cell migration, and the underlying mechanism, which will provide new drug choices for hypopharyngeal cancer treatment. METHODS: The Hypopharyngeal cancer Fadu cells were treated with anlotinib at a concentration of 0, 5, and 10 µmoL/L, respectively. Cell counting kit-8 and the colony-forming assay were used to detect the inhibition of cell proliferation. Wound-healing assay and transwell assay were used to detect the migration and invasion ability of cells. Flow cytometry was used to detect the effects of anlotinib on cell cycle and apoptosis. RT-qPCR and Western blot were used to measure gene expression levels. RESULTS: CCK-8 and colony-forming assay showed that anlotinib could significantly inhibit cell proliferative activity. Wound-healing assay and transwell assay showed that anlotinib could inhibit cell migration and scratch. These results showed that anlotinib has obvious antitumor activity. Flow cell cycle experiment showed that anlotinib could promote Fadu cell apoptosis and block the G2/M phase for inhibiting cell proliferation. In addition, anlotinib decreased the expression of HIF-1α. CONCLUSIONS: Anlotinib has an excellent suppressing effect on the proliferation, migration, and invasion of hypopharyngeal cancer Fadu cells in-vitro. Moreover, it can play an anti-tumor role through blocking cell cycle G2/M and promoting apoptosis, which may be related to the decrease of HIF-1a expression. Our study would provide a potential treatment method for patients with hypopharyngeal cancer. LEVEL OF EVIDENCE: Level 3.

P2X7 receptor of olfactory bulb microglia plays a pathogenic role in stress-related depression in mice with allergic rhinitis.

The aim of this study was to explore the role and mechanism of the olfactory bulb (OB) microglial P2X7 receptor (P2X7R) in allergic rhinitis (AR)-related depression, with the objective of identifying a potential clinical target. An AR mouse model was induced using ovalbumin (OVA), while chronic stress was employed to induce depression. The study used P2X7R-specific antagonists and OB microglia-specific P2X7R knockdown mice as crucial tools. The results showed that mice in the OVA + stress group exhibited more pronounced depressive-like phenotypes. Furthermore, there was an observed increase in microglial activation in the OB, followed by a rise in the level of inflammation. The pharmacological inhibition of P2X7R significantly mitigated the depression-like phenotype and the OB inflammatory response in OVA + stress mice. Notably, the specific knockdown of microglial P2X7R in the OB resulted in a similar effect, possibly linked to the regulation of IL-1ß via the "ATP-P2X7R-Caspase 1" axis. These findings collectively demonstrate that microglial P2X7R in the OB acts as a direct effector molecule in AR-related depression, and its inhibition may offer a novel strategy for clinical prevention and treatment.

Cell type-specific molecular mechanisms and implications of necroptosis in inflammatory respiratory diseases.

Necroptosis is generally considered as an inflammatory cell death form. The core regulators of necroptotic signaling are receptor-interacting serine-threonine protein kinases 1 (RIPK1) and RIPK3, and the executioner, mixed lineage kinase domain-like pseudokinase (MLKL). Evidence demonstrates that necroptosis contributes profoundly to inflammatory respiratory diseases that are common public health problem. Necroptosis occurs in nearly all pulmonary cell types in the settings of inflammatory respiratory diseases. The influence of necroptosis on cells varies depending upon the type of cells, tissues, organs, etc., which is an important factor to consider. Thus, in this review, we briefly summarize the current state of knowledge regarding the biology of necroptosis, and focus on the key molecular mechanisms that define the necroptosis status of specific cell types in inflammatory respiratory diseases. We also discuss the clinical potential of small molecular inhibitors of necroptosis in treating inflammatory respiratory diseases, and describe the pathological processes that engage cross talk between necroptosis and other cell death pathways in the context of respiratory inflammation. The rapid advancement of single-cell technologies will help understand the key mechanisms underlying cell type-specific necroptosis that are critical to effectively treat pathogenic lung infections and inflammatory respiratory diseases.

Development and Validation of a Computed Tomography-Based Radiomics Nomogram for the Preoperative Prediction of Central Lymph Node Metastasis in Papillary Thyroid Microcarcinoma.

RATIONALE AND OBJECTIVES: This study aims to develop and validate a computed tomography (CT)-based radiomics nomogram for pre-operatively predicting central lymph node metastasis (CLNM) in patients with papillary thyroid microcarcinoma (PTMC) and explore the underlying biological basis by using RNA sequencing data. METHODS: This study trained 452 PTMC patients across two hospitals from January 2012 to December 2020. The sets were randomly divided into the training (n = 339), internal test (n = 86), external test (n = 27) sets. Radiomics features were extracted from primary lesion's pre-operative CT images for each patient. After screening for features, five algorithms such as K-nearest neighbor, logistics regression, linear-support vector machine (SVM), Gaussian SVM, and polynomial SVM were used to establish the radiomics models. The performance of these five algorithms was evaluated and compared directly to radiologist's interpretation (CT-reported lymph node status). The radiomics signature score (Rad-score) was generated using a linear combination of the selected features. By combining the clinical risk factors and Rad score, a radiomics nomogram was established and compared with Rad-score and clinical model. The performance of the nomogram was evaluated based on the receiver operating characteristic (ROC) curve, calibration curve, and the decision curve analysis (DCA). The potential biological basis of nomogram was revealed by performing genetic analysis based on the RNA sequencing data. RESULTS: A total of 25 radiomic features were ultimately selected to train the machine learning models, and the five machine learning models outperformed the radiologists' interpretation by achieving area under the ROC curves (AUCs) ranging from 0.606 to 0.730 in the internal test set. By incorporating the Rad score and clinical risk factors (sex, age, tumor-diameter, and CT-reported lymph node status), this nomogram achieved AUCs of 0.800 and 0.803 in the internal and external test set, which were higher than that of the Rad-score and clinical model, respectively. Calibration curves and DCA also showed that the nomogram had good performance. As for the biological basis exploration, in patients predicted by nomogram to be PTC patients with CLMN, 109 genes were dysregulated, and some of them were associated with pathways and biological processes such as tumor angiogenesis. CONCLUSION: This radiomics nomogram successfully identified CLNM on pretreatment imaging across multiple institutions, exceeding the diagnostic ability of radiologists and had the potential to be integrated into clinical decision making as a non-invasive pre-operative tool.

Meta-analysis of the relationship between montelukast use and neuropsychiatric events in patients with allergic airway disease.

Use of montelukast, as a cause of neuropsychiatric events, in patients with asthma or allergic rhinitis is controversial, and comprehensive statistical analyses verifying this relationship remain lacking. To better understand the relationship between montelukast and neuropsychiatric events, it is vital to guide patients in the effective use of the drug, especially in children whose mothers are concerned about its side effects. In this study, randomized controlled trials (RCTs) investigating montelukast and neuropsychiatric events were retrieved from a literature search of the Medline (1966 to February 2023), Embase (1974 to February 2023), Web of Science, and other related databases. After screening, 18 RCTs were ultimately included in a meta-analysis to merge statistics, which demonstrated no significant increase in neuropsychiatric events compared with placebo. A similar pattern of adverse neuropsychiatric events was observed in patients grouped according to age, with headache being the most common adverse neuropsychiatric event. Overall, montelukast did not significantly increase neuropsychiatric events in patients with allergic rhinitis and/or asthma compared with placebo. Large-sample RCTs are needed to verify the association between neuropsychiatric events and montelukast use in children, and attention is also devoted to FDA warnings.

Construction and validation of a prognostic nine-gene signature associated with radiosensitivity in head and neck squamous cell carcinoma.

Background: Radiotherapy is an effective treatment for head and neck squamous cell carcinoma (HNSCC), however how to predict the prognosis is not clear. Methods: Here we collected 262 radiosensitivity-associated genes, screened and constructed a prognostic nine-gene risk model through univariate COX, lasso regression, stepwise regression and multivariate COX analysis for transcriptome and clinical information of HNSCC patients obtained from the cancer genome atlas (TCGA) and gene expression omnibus (GEO) databases. Results: The reliability and robustness of the risk model were verified by receiver operating characteristic (ROC) curves, risk maps, and Kaplan-Meier (KM) curves analysis. Differences in immune cell infiltration and immune-related pathway enrichment between high-risk and low-risk subgroups were determined by multiple immune infiltration analyses. Meanwhile, the mutation map and the responses to immunotherapy were also differentiated by the prognostic nine-gene signature associated with radiosensitivity. These nine genes expression in HNSCC was verified in the Human Protein Atlas (HPA) database. After that, these nine genes expression was verified to be related to radiation resistance through in-vitro cell experiments. Conclusions: All results showed that the nine-gene signature associated with radiosensitivity is a potential prognostic indicator for HNSCC patients after radiotherapy and provides potential gene targets for enhancing the efficacy of radiotherapy.

Brain response in asthma: the role of "lung-brain" axis mediated by neuroimmune crosstalk.

In addition to typical respiratory symptoms, patients with asthma are frequently accompanied by cognitive decline, mood disorders (anxiety and depression), sleep disorders, olfactory disorders, and other brain response manifestations, all of which worsen asthma symptoms, form a vicious cycle, and exacerbate the burden on families and society. Therefore, studying the mechanism of neurological symptoms in patients with asthma is necessary to identify the appropriate preventative and therapeutic measures. In order to provide a comprehensive reference for related research, we compiled the pertinent literature, systematically summarized the latest research progress of asthma and its brain response, and attempted to reveal the possible "lung-brain" crosstalk mechanism and treatment methods at the onset of asthma, which will promote more related research to provide asthmatic patients with neurological symptoms new hope.

m6A methylation reader IGF2BP2 activates endothelial cells to promote angiogenesis and metastasis of lung adenocarcinoma.

BACKGROUND: Lung adenocarcinoma (LUAD) is a common type of lung cancer with a high risk of metastasis, but the exact molecular mechanisms of metastasis are not yet understood. METHODS: This study acquired single-cell transcriptomics profiling of 11 distal normal lung tissues, 11 primary LUAD tissues, and 4 metastatic LUAD tissues from the GSE131907 dataset. The lung multicellular ecosystems were characterized at a single-cell resolution, and the potential mechanisms underlying angiogenesis and metastasis of LUAD were explored. RESULTS: We constructed a global single-cell landscape of 93,610 cells from primary and metastatic LUAD and found that IGF2BP2 was specifically expressed both in a LUAD cell subpopulation (termed as LUAD_IGF2BP2), and an endothelial cell subpopulation (termed as En_IGF2BP2). The LUAD_IGF2BP2 subpopulation progressively formed and dominated the ecology of metastatic LUAD during metastatic evolution. IGF2BP2 was preferentially secreted by exosomes in the LUAD_IGF2BP2 subpopulation, which was absorbed by the En_IGF2BP2 subpopulation in the tumor microenvironment. Subsequently, IGF2BP2 improved the RNA stability of FLT4 through m6A modification, thereby activating the PI3K-Akt signaling pathway, and eventually promoting angiogenesis and metastasis. Analysis of clinical data showed that IGF2BP2 was linked with poor overall survival and relapse-free survival for LUAD patients. CONCLUSIONS: Overall, these findings provide a novel insight into the multicellular ecosystems of primary and metastatic LUAD, and demonstrate that a specific LUAD_IGF2BP2 subpopulation is a key orchestrator promoting angiogenesis and metastasis, with implications for the gene regulatory mechanisms of LUAD metastatic evolution, representing themselves as potential antiangiogenic targets.

P2X7 receptor of microglia in olfactory bulb mediates the pathogenesis of olfactory dysfunction in a mouse model of allergic rhinitis.

The pathogenesis of allergic rhinitis (AR)-related olfactory dysfunction (OD) remains unknown. Inhibiting microglial response in olfactory bulb (OB) can ameliorate AR-related OD, but no precise targets have been available. In this study, we established a mouse model of ovalbumin (OVA)-induced AR and combined with the application of P2X7 receptor (P2X7R)-specific antagonists and cell culture in conditioned medium to investigate the role and mechanism of OB microglial P2X7R in AR-related OD. Serum IgE and IL-5 levels determined via ELISA and federated the number of nose-scratching to affirm the success of OVA-induced AR mouse model. Buried food pellet test was used to evaluate the olfactory function of mice. The changes of IBA1, GFAP, P2X7R, IL-1ß, IL-1Ra, and CASPASE 1 were detected by quantitative polymerase chain reaction and western blotting. The levels of adenosine triphosphate (ATP) were determined by the commercialized kit. The morphological changes of microglia were assessed using immunofluorescence staining and Sholl analysis. Findings showed that AR-related OD was associated with OB microglia-mediated imbalance between IL-1ß and IL-1Ra. Treatment with BBG improved the olfactory function in AR mice with restoring the balance between IL-1ß and IL-1Ra. In vitro, the conditioned medium obtained after HNEpC treatment with Der p1 could activate HMC3 to arise inflammatory reaction basing on "ATP-P2X7R-Caspase 1" axis, while inhibition of its P2X7R suppressed the reaction. In brief, microglial P2X7R in OB is a direct effector molecule in AR-related OD and inhibition of it may be a new strategy for the treatment of AR-related OD.

IL-1ß and Allergy: Focusing on Its Role in Allergic Rhinitis.

Allergic rhinitis (AR) is a chronic upper airway immune-inflammation response mediated by immunoglobulin E (IgE) to allergens and can seriously affect the quality of life and work efficiency. Previous studies have shown that interleukin-1ß (IL-1ß) acts as a key cytokine to participate in and promote the occurrence and development of allergic diseases. It has been proposed that IL-1ß may be a potential biomarker of AR. However, its definitive role and potential mechanism in AR have not been fully elucidated, and the clinical sample collection and detection methods were inconsistent among different studies, which have limited the use of IL-1ß as a clinical diagnosis and treatment marker for AR. This article systematically summarizes the research advances in the roles of IL-1ß in allergic diseases, focusing on the changes of IL-1ß in AR and the possible interventions. In addition, based on the findings by our team, we provided new insights into the use of IL-1ß in AR diagnosis and treatment, in an attempt to further promote the clinical application of IL-1ß in AR and other allergic diseases.

Applying a nomogram based on preoperative CT to predict early recurrence of laryngeal squamous cell carcinoma after surgery.

PURPOSE: To identify the value of a computed tomography (CT)-based radiomics model to predict probability of early recurrence (ER) in patients diagnosed with laryngeal squamous cell carcinoma (LSCC) after surgery. MATERIALS AND METHOD: Pre-operative CT scans of 140 LSCC patients treated by surgery are reviewed and selected. These patients are randomly split into the training set (n = 97) and test set (n = 43). The regions of interest of each patient were delineated manually by two senior radiologists. Radiomics features are extracted from CT images acquired in non-enhanced, arterial, and venous phases. Variance threshold, one-way ANOVA, and least absolute shrinkage and selection operator algorithm are used for feature selection. Then, radiomics models are built with five algorithms namely, k-nearest neighbor (KNN), logistic regression (LR), linear support vector machine (LSVM), radial basis function SVM (RSVM), and polynomial SVM (PSVM). Clinical factors are selected using univariate and multivariate logistic regressions. Last, a radiomics nomogram incorporating the radiomics signature and clinical factors is built to predict ER and its efficiency is evaluated by receiver operating characteristic (ROC) curve and calibration curve. Decision curve analysis (DCA) is also used to evaluate clinical usefulness. RESULTS: Four features are remarkably associated with ER in patients with LSCC. Applying to test set, the area under the ROC curves (AUCs) of KNN, LR, LSVM, RSVM, and PSVM are 0.936, 0.855, 0.845, 0.829, and 0.794, respectively. The radiomics nomogram shows better discrimination (with AUC: 0.939, 95% CI: 0.867-0.989) than the best radiomics model and the clinical model. Predicted and actual ERs in the calibration curves are in good agreement. DCA shows that the radiomics nomogram is clinically useful. CONCLUSION: The radiomics nomogram, as a noninvasive prediction tool, exhibits favorable performance for ER prediction of LSCC patients after surgery.

Long non-coding RNA FAM239A promotes tumor cell proliferation and migration by regulating tyrosine phosphatase Src homology 2 domain-containing phosphatase 2 in head and neck squamous cell carcinoma.

OBJECTIVE: Head and neck squamous cell carcinoma (HNSCC), is one of the malignant tumors with high recurrence and metastasis. The family with sequence similarity (FAM) of non-coding RNAs promoted tumorigenesis and metastasis. But so far, long non-coding RNA (lncRNA) FAM239A's function in HNSCC regulation remains unclear. This study aimed to explore the lncRNA FAM239A function and regulation mechanism in HNSCC cell proliferation and migration. DESIGN: The expression level of lncRNA FAM239A and tyrosine phosphatase Src homology 2 domain-containing phosphatase 2 (SHP2) in HNSCC tumor tissue was tested by quantitative polymerase chain reaction. The cell proliferation and migration were tested by cell counting kit 8, kinetic live cell assay, and wound healing assay. The differential expression of SHP2 and immune infiltration in HNSCC were analyzed in the tumor immune estimation response and human protein atlas databases. And the survival analysis of SHP2 in HNSCC was analyzed in the gene expression profiling interactive analysis 2 databases. The SHP2 expression was tested by western blotting when lncRNA FAM239A overexpression and knockdown. RESULTS: LncRNA FAM239A and SHP2 were ectopically expressed in HNSCC tumor tissue. Cell proliferation and wound healing assays showed that lncRNA FAM239A promoted tumor cell proliferation and migration. SHP2 was overexpressed in HNSCC tumor tissue by database analyses, and the higher SHP2 expression caused poorer overall survival and disease-free survival in HNSCC patients. SHP2 expression was positively regulated by lncRNA FAM239A. CONCLUSIONS: LncRNA FAM239A promoted HNSCC cell proliferation and migration through upregulating SHP2 expression, which potentially provided new regulators for HNSCC.

Brain response in allergic rhinitis: Profile and proposal.

In addition to typical nasal symptoms, patients with allergic rhinitis (AR) will further lead to symptoms related to brain function such as hyposmia, anxiety, depression, cognitive impairment, memory loss, etc., which seriously affect the quality of life of patients and bring a heavy burden to the patient's family and society. Some scholars have speculated that there may be potential "nose-brain communication" mechanism in AR that rely on neuro-immunity. This mechanism plays an important role in AR-associated brain response process. However, no study has directly demonstrated which neural circuits will change in the connection between the nose and brain during the onset of AR, and the mechanism which underlines this question is also lack. Focusing on the topic of "nose-brain communication", this paper systematically summarizes the latest research progress between AR and related brain responses and discusses the mechanism of AR-related neurological phenotypes. Hope new diagnostic and therapeutic targets to ameliorate the brain function-related symptoms and improve the quality of life of AR patients will be developed.

Evaluating hypopharyngeal carcinoma using narrow band imaging and oxygen-injected laryngoscope: New technique.

OBJECTIVE: To evaluate the diagnostic value of narrow band imaging (NBI) endoscopic classification for hypopharyngeal lesions and to lay the groundwork for practical applications of oxygen-injected laryngoscope for hypopharyngeal carcinoma (HC). METHODS: A total of 140 subjects with suspected 146 hypopharyngeal lesions were selected for pathological examination. Subsequently, NBI and white light imaging (WLI) endoscopy were performed to observe and classify lesions into 7 types according to our modified NBI classification. Pathological results were used as the gold standard to assess the diagnostic value of the NBI classification. The value of oxygen-injected laryngoscope for accurate assessment of lesion extension was evaluated based on the exposure of hypopharyngeal lesions before and after use. RESULTS: The accuracy, sensitivity, and negative predictive value of NBI endoscopy in diagnosing hypopharyngeal lesions were 95.9 %, 96.7 %, and 84.6 %, respectively, which were higher than those of WLI mode (p < 0.05). NBI endoscopy was more accurate than WLI in diagnosing malignant lesions (p < 0.05), especially for high-grade dysplasia (HGD) (p < 0.05). There was remarkable consistency between NBI classification and pathological results (Kappa = 0.855). Type Va and type Vb-c accounted for 72.7 % and 92.8 % of HGD and invasive carcinoma, respectively. Moreover, the oxygen-injected laryngoscope was found to provide a more accurate assessment of HC extension (P < 0.001). CONCLUSION: We propose a more appropriate NBI endoscopic classification for hypopharyngeal lesions, which can effectively improve diagnostic accuracy, especially for the early diagnosis of hypopharyngeal cancer. Moreover, the application of oxygen-injected laryngoscope is essential for the accurate assessment of HC and has a high clinical utility.

Laryngeal extra-skeletal Ewing sarcoma treated with DC-CTL immunotherapy: A case report and review of the literature.

Extra-skeletal Ewing sarcoma (EES) is a rare sarcoma composed primarily of small round cells, capable of metastasizing and relapsing. Few cases of EES originating from the larynx have been reported, and no publications regarding laryngeal EES treated with dendritic cells-cytotoxic T lymphocytes (DC-CTL) immunotherapy have been found. We described a 29-year-old woman with a mass found in the larynx. Diffuse small round cells with scanty cytoplasm shown by histology test and extremely positive staining of CD99 revealed by immunohistochemistry helped determine the diagnosis of laryngeal EES. The patient survived for seven years with no signs of recurrence or metastasis after six cycles of DC-CTL immunotherapy based on traditional treatments. This case indicates that DC-CTL immunotherapy could be considered a new option for treating EES.

Application of Neurotoxin-Induced Animal Models in the Study of Parkinson's Disease-Related Depression: Profile and Proposal.

Depression can be a non-motor symptom, a risk factor, and even a co-morbidity of Parkinson's disease (PD). In either case, depression seriously affects the quality of life of PD patients. Unfortunately, at present, a large number of clinical and basic studies focused on the pathophysiological mechanism of PD and the prevention and treatment of motor symptoms. Although there has been increasing attention to PD-related depression, it is difficult to achieve early detection and early intervention, because the clinical guidelines mostly refer to depression developed after or accompanied by motor impairments. Why is there such a dilemma? This is because there has been no suitable preclinical animal model for studying the relationship between depression and PD, and the assessment of depressive behavior in PD preclinical models is as well a very challenging task since it is not free from the confounding from the motor impairment. As a common method to simulate PD symptoms, neurotoxin-induced PD models have been widely used. Studies have found that neurotoxin-induced PD model animals could exhibit depression-like behaviors, which sometimes manifested earlier than motor impairments. Therefore, there have been attempts to establish the PD-related depression model by neurotoxin induction. However, due to a lack of unified protocol, the reported results were diverse. For the purpose of further promoting the improvement and optimization of the animal models and the study of PD-related depression, we reviewed the establishment and evaluation strategies of the current animal models of PD-related depression based on both the existing literature and our own research experience, and discussed the possible mechanism and interventions, in order to provide a reference for future research in this area.