Risk prediction model construction for asthma after allergic rhinitis by blood immune T effector cells.

BACKGROUND: Allergic rhinitis (AR) and asthma (AS) are prevalent and frequently co-occurring respiratory diseases, with mutual influence on each other. They share similar etiology, pathogenesis, and pathological changes. Due to the anatomical continuity between the upper and lower respiratory tracts, allergic inflammation in the nasal cavity can readily propagate downwards, leading to bronchial inflammation and asthma. AR serves as a significant risk factor for AS by potentially inducing airway hyperresponsiveness in patients. Currently, there is a lack of reliable predictors for the progression from AR to AS. METHODS: In this exhaustive investigation, we reexamined peripheral blood single cell RNA sequencing datasets from patients with AS following AR and healthy individuals. In addition, we used the bulk RNA sequencing dataset as a validation lineup, which included AS, AR, and healthy controls. Using marker genes of related cell subtype, signatures predicting the progression of AR to AS were generated. RESULTS: We identified a subtype of immune-activating effector T cells that can distinguish patients with AS after AR. By combining specific marker genes of effector T cell subtype, we established prediction models of 16 markers. The model holds great promise for assessing AS risk in individuals with AR, providing innovative avenues for clinical diagnosis and treatment strategies. CONCLUSION: Subcluster T effector cells may play a key role in post-AR AS. Notably, ACTR3 and HSPA8 genes were significantly upregulated in the blood of AS patients compared to healthy patients.

Identification and validation of a novel signature based on cell-cell communication in head and neck squamous cell carcinoma by integrated analysis of single-cell transcriptome and bulk RNA-sequencing.

Background: The heterogeneous crosstalk between tumor cells and other cells in their microenvironment means a notable difference in clinical outcomes of head and neck squamous cell carcinoma (HNSCC). CD8+ T cells and macrophages are effector factors of the immune system, which have direct killing and phagocytosis effects on tumor cells. How the evolution of their role in the tumor microenvironment influences patients clinically remains a mystery. This study aims to investigate the complex communication networks in the HNSCC tumor immune microenvironment, elucidate the interactions between immune cells and tumors, and establish prognostic risk model. Methods: 20 HNSCC samples single-cell rna sequencing (scRNA-seq) data and bulk rna-seq data were derived from public databases. The "cellchat" R package was used to identify cell-to-cell communication networks and prognostic related genes, and then cell-cell communication (ccc) molecular subtypes were constructed by unsupervised clustering. Kaplan-Meier(K-M) survival analysis, clinical characteristics analysis, immune microenvironment analysis, immune cell infiltration analysis and CD8+T cell differentiation correlation analysis were performed. Finally, the ccc gene signature including APP, ALCAM, IL6, IL10 and CD6 was constructed based on univariate Cox analysis and multivariate Cox regression. Kaplan-Meier analysis and time-dependent receiver operating characteristic (ROC) analysis were used to evaluate the model in the train group and the validation group, respectively. Results: With CD8+T cells from naive to exhaustion state, significantly decreased expression of protective factor (CD6 gene) is associated with poorer prognosis in patients with HNSCC. The role of macrophages in the tumor microenvironment has been identified as tumor-associated macrophage (TAM), which can promote tumor proliferation and help tumor cells provide more nutrients and channels to facilitate tumor cell invasion and metastasis. In addition, based on the strength of all ccc in the tumor microenvironment, we identified five prognostic ccc gene signatures (cccgs), which were identified as independent prognostic factors by univariate and multivariate analysis. The predictive power of cccgs was well demonstrated in different clinical groups in train and test cohorts. Conclusion: Our study highlights the propensity for crosstalk between tumors and other cells and developed a novel signature on the basis of a strong association gene for cell communication that has a powerful ability to predict prognosis and immunotherapy response in patients with HNSCC. This may provide some guidance for developing diagnostic biomarkers for risk stratification and therapeutic targets for new therapeutic strategies.

Long Non-Coding RNA Small Nucleolar RNA Host Gene 4 Induced by Transcription Factor SP1 Promoted the Progression of Nasopharyngeal Carcinoma Through Modulating microRNA-510-5p/Centromere Protein F Axis.

Long non-coding RNAs (LncRNAs) are implicated with tumorigenesis and the development of nasopharyngeal carcinoma (NPC). Previous studies suggested that long non-coding RNA small nucleolar RNA host gene 4 (SNHG4) exerted oncogenic roles in various cancers. However, the function and molecular mechanism of SNHG4 in NPC have not been investigated. In our study, it was confirmed that the SNHG4 level was enriched in NPC tissues and cells. Functional assays indicated that SNHG4 depletion inhibited the proliferation and metastasis but promoted apoptosis of NPC cells. Furthermore, we identified miR-510-5p as a downstream gene of SNHG4 in NPC cells and SNHG4 upregulated CENPF expression by binding to miR-510-5p. Moreover, there was a positive (or negative) association between CENPF and SNHG4 (or miR-510-5p) expression in NPC. In addition, rescue experiments verified that CENPF overexpression or miR-510-5p silencing abrogated inhibitory effects on NPC tumorigenesis caused by SNHG4 deficiency. The study demonstrated that SNHG4 promoted NPC progression via miR-510-5p/CENPF axis, providing a novel potential therapeutic target for NPC treatments.

Identification of several senescence-associated genes signature in head and neck squamous cell carcinoma.

BACKGROUND: As one of the core aging processes, cellular senescence is associated with tumorigenesis, growth, and immune modulation in cancers. Nevertheless, the prognosis of senescence-associated genes (SAGs) signature in head and neck squamous cell carcinoma (HNSCC) remains to be further evaluated. METHODS: The transcriptome and corresponding clinical datasets of SAGs in patients with HNSCC were downloaded from public databases. A new prognostic SAGs signature was established with least absolute shrinkage and selection operator discussion. Patients with HNSCC were fallen into two risk groups based on each sample's risk mark and the cutoff point. The survival analysis was extended to determine the predictive accuracy of the SAGs signature. Furthermore, the evaluation of SAGs signature was made according to clinicopathological characteristics, survival state, the infiltration of inflammatory cells, and efficacy of immunotherapy. RESULTS: 41 SAGs were recognized and adopted to establish the forecast signature. The survival analysis indicated that patients with HNSCC in the high-senescent score group had significantly reduced overall survival compared with those in the low-senescent score group. It was certified that the risk score of SAGs signature was a separate predicting agent for HNSCC applying Cox regression analysis. According to functional analysis, some immune-associated pathways were increased in the low-senescent score group significantly. High-senescent score group was correlated with poor clinicopathological characteristics, given less the infiltration of inflammatory cells state and worse immunotherapeutic effect. CONCLUSION: A new SAG signature predicting result and response to immunotherapy of HNSCC was identified. Cellular senescence may be a hidden target for HNSCC.

Efficacy of balloon dilatation of the eustachian tube in patients with refractory otitis media with effusion after radiotherapy for nasopharyngeal carcinoma.

PURPOSE: To investigate the efficacy of balloon dilatation of the eustachian tube (BDET) in patients with refractory otitis media with effusion (OME) after radiotherapy for nasopharyngeal carcinoma. MATERIALS AND METHODS: A total of 58 patients (74 ears) who had received BDET for treatment of refractory OME after radiotherapy for nasopharyngeal carcinoma were enrolled. The efficacy was evaluated by seven-item eustachian tube scores (ETS-7), tympanogram type and air-bone gap, and the total effective rate was also calculated. All patients were followed up for 2 years. RESULTS: ETS-7 scores at every postoperative visit were significantly higher than preoperative scores (all P < 0.05). ETS-7 score 6 months after surgery was the highest, which declined sharply from the 6th to the 24th month after surgery. Air-bone gap from the 1st to the 18th month after surgery was significantly smaller than preoperative one (all P < 0.05). Air-bone gap 6 months after surgery was the smallest, followed by that 12 months after surgery. The improvement in tympanogram type 6 months after surgery was the highest. The improvement of tympanogram type declined sharply from 12 to 24 months after surgery. According to evaluation of efficacy, only one patient completely recovered, and five patients partially recovered during the 2-year follow-up. CONCLUSION: BDET can only significantly improve efficacy of refractory OME after radiotherapy for nasopharyngeal carcinoma for a certain period of time during the 2-year follow-up.

Long noncoding RNA MAGI2-AS3/miR-218-5p/GDPD5/SEC61A1 axis drives cellular proliferation and migration and confers cisplatin resistance in nasopharyngeal carcinoma.

BACKGROUND: Nasopharyngeal carcinoma (NPC), a subclass of neck and head cancers, is the predominant cause of cancer-associated death globally. LncRNA MAGI2-AS3 has been previously reported to be associated with multiple cancers, but its molecular mechanism in NPC has not been fully explained. Hence, the purpose of this study is to identify the role and regulatory mechanism of MAGI2-AS3 in NPC. METHODS: Reverse-transcription quantitative polymerase chain reaction (RT-qPCR) and Western blot (WB) were employed to examine gene levels. The biologic function of MAGI2-AS3 in NPC was estimated by cell counting, EdU, Transwell, and WB assays. Luciferase reporter and radioimmunoprecipitation (RIP) assays were carried out to determine the combination between miR-218-5p and MAGI2-AS3, GDPD5, and SEC61A1. RESULTS: MAGI2-AS3 is expressed at a high level in NPC cell lines. Moreover, MAGI2-AS3 knockdown-suppressed NPC progression in vitro and in vivo. Furthermore, MAGI2-AS3 functioned as a competing endogenous RNA (ceRNA) by sponging miR-218-5p to increase the expression of GDPD5 in NPC. Importantly, it was found that MAGI2-AS3 regulated NPC progression and cisplatin resistance via modulating GDPD5. In addition, MAGI2-AS3 could also promote the proliferation and migration in NPC cells by regulating SEC61A1. CONCLUSION: MAGI2-AS3/miR-218-5p/GDPD5/SEC61A1 axis drove cell proliferation, migration, and epithelial-mesenchymal transition, and conferred cisplatin resistance in NPC, which may provide a novel insight into the development of NPC.

Efficacy of combination therapy in adolescent and adult patients with total-deafness sudden sensorineural hearing loss.

BACKGROUND: Combination therapy is the first-line option for total-deafness sudden sensorineural hearing loss (SSNHL). Age may act as a crucial prognostic factor. OBJECTIVE: The aim of this study was to compare efficacy of combination therapy between adolescent and adult patients with total-deafness SSNHL. MATERIALS AND METHODS: Twenty-five adolescent patients (adolescent group) and 106 adult patients (adult group) with total-deafness SSNHL were recruited. All the recruited patients underwent initial treatment with batroxobin, methylprednisolone, and gastrodin. After 10-day treatment, hearing outcomes were determined by pure-tone average measured by audiometry. Moreover, the total effective rates in the hearing recovery and improvement of tinnitus were calculated. RESULTS: There existed no significant difference between two groups in the total effective rate of the hearing recovery (p = .110). However, a significant difference was found in the total effective rate of improvement of tinnitus between two groups (p = .016). Both adolescent and adult patients could receive the optimal hearing gains at 500 Hz (20.2 ± 13.3 and 23.1 ± 13.9dB, respectively), followed by those at 1000 Hz (18.8 ± 12.5 and 22.7 ± 14.8dB, respectively). Yet, adult patients could get better hearing gains only at 500 Hz than adolescent patients (p = .02). CONCLUSION: Compared with adult patients, adolescent patients with total-deafness SSNHL undergoing combination therapy may be less likely to have hearing recovery and the improvement of tinnitus.

Prognostic value of elevated KDM5B expression in patients with laryngeal squamous cell carcinoma.

Previous studies confirmed that KDM5B expression is dysregulated in most human tumors. However, KDM5B expression in human laryngeal squamous cell carcinoma (HLSCC) has not been reported. In this paper, the relationship between KDM5B expression and clinical features of HLSCC is clarified, and its prognostic value in HLSCC patients is evaluated. In our study, KDM5B expression was examined by immunohistochemical analysis in 63 HLSCC clinical tissue samples and 20 adjacent normal tissue samples. Subsequently, the relationship between KDM5B expression and clinicopathologic factors in 63 HLSCC patients was clarified, and its prognostic value was evaluated according to Cox model analysis. Our results showed that KDM5B was over-expressed in HLSCC cells and over-expression of KDM5B was related to the histologic type, clinical stages, lymph node metastasis, and recurrence of tumor. Furthermore, over-expression of KDM5B had poor five-year overall survival in HLSCC patients. The result of a multivariate analysis indicated that over-expression of KDM5B was an independent risk factor for poor prognosis. These results indicated that over-expression of KDM5B was closely correlated with tumorigenesis, metastasis, and poor overall survival in HLSCC patients. Furthermore, KDM5B might serve as a specific and novel prognostic biomarker in HLSCC patients.

Comparison of intratympanic dexamethasone therapy and hyperbaric oxygen therapy for the salvage treatment of refractory high-frequency sudden sensorineural hearing loss.

OBJECTIVE: This study aimed to compare the efficacy of intratympanic dexamethasone (ITD) therapy and hyperbaric oxygen(HBO) therapy for the salvage treatment of patients with high-frequency sudden sensorineural hearing loss (SSNHL) after the failure of conventional therapy. MATERIALS AND METHODS: 104 refractory high-frequency SSNHL patients were enrolled in our study. Among them, 31 received ITD alone (ITD group), 32 received HBO alone (HBO group) and 41 received no salvage therapies (control group). Hearing outcomes were determined by pure-tone average measured by audiometry. The total effective rates in the hearing recovery and improvement of tinnitus were calculated before and after salvage treatment. RESULTS: There was no significant difference of the total effective rates in the hearing recovery between ITD and HBO group (p = 0.368). However, ITD therapy showed much better improvements of tinnitus than HBO therapy (p = 0.039). After ITD and HBO therapy, there were no significant differences in hearing gains at 2 and 4 KHz between ITD and HBO group (p = 0.468 and 0.934, respectively). Nevertheless, ITD therapy showed significant improvements of hearing gains at 8 KHz (p = 0.049) compared to that of HBO therapy. CONCLUSION: ITD therapy may have better improvements of tinnitus and hearing gains at 8 KHz than HBO therapy in patients with refractory high-frequency SSNHL.

MicroRNA-200a mediates nasopharyngeal carcinoma cell proliferation through the activation of nuclear factor-κB.

In nasopharyngeal carcinoma (NPC), the nuclear factor-κB (NF-κB) signaling pathway is highly active. The constitutive activation of NF-κB prompts malignant cell proliferation, and microRNAs are considered an important mediator in regulating the NF-κB signaling pathway. The current study investigated the effect of microRNA-200a (miR-200a) on NF-κB activation. Reverse transcription-quantitative polymerase chain reaction was used to quantify the relative level of miR-200a in NPC tissue samples and CNE2 cells. An MTT assay was used to investigate the effect of miR-200a on cell proliferation. To investigate the activation of NF-κB, western blotting was used to measure the protein levels of NF-κB and its downstream targets. To identify the target genes of miR-200a, a luciferase reporter assay was used. The current study demonstrated that miR-200a was upregulated in NPC tissue samples and cell lines. Overexpression of miR-200a resulted in the proliferation of CNE2 cells. Western blot analysis indicated that the protein levels of p65 increased when CNE2 cells were transfected with miR-200a mimics. Additionally, the downstream targets of miR-200a were upregulated, including vascular cell adhesion molecule, intercellular adhesion molecule and monocyte chemoattractant protein-1. The luciferase assay indicated that IκBα was the target gene of miR-200a. In conclusion, miR-200a was demonstrated to enhance NPC cell proliferation by activating the NF-κB signaling pathway.

[OSAHS patient gas up-take cross-sectional area nasopharynx sound reflection examination and significance].

OBJECTIVE: To explore a simple and accurate method for localization of upper airway obstruction in patients with obstructive sleep apnea-hypopnea syndrome (OSAHS) and provide instructions for surgical treatment. METHOD: Fifty OSAHS patients confirmed by PSG underwent acoustic rhinometric and pharyngometric assessment by Eccovision. The parameters were recorded, including nasal minimal cross-sectional area (NMCA), distance of MCA from the nostril (DCAN), minimum cross-sectional area at the nasal valve(MCA), nasal resistance (NR) and nasal volume from 0 to 6 cm from the nostril (NCV), as well as pharyngeal cross-sectional area (CSA) and volume from 4.8 to 15.0 cm. The sensitivity and specificity of acoustic rhinometry and pharyngometry on localization of airway obstruction was determined by a comprehensive imaging and endoscopic study. RESULT: In 50 cases with severe OSAHS, NMCA, DCAN, MCA, NCV, NR were (0.61 +/- 0.35) cm2, (2.06 +/- 0.12) cm, (0.87 +/- 0.12) cm2, (9.24 +/- 2.31)cm3 and (0.51 +/- 0.32)kPa/(L x min), respectively. Pharyngeal CSA and volume were statistically significantly lower than that in control group (P < 0.01). The value of DCAN was (2.06 +/- 0.12) cm, (9.50 +/- 4.08) cm, (13.10 +/- 2.52) cm in type I II, III patient, respectively. Compared with the control group, the difference was statistically significant. CONCLUSION: Acoustic rhinometry and pharyngometry is a simple and safe method in localization of airway obstruction in patients with OSAHS.

[Applied anatomy study of optic canal by transnasal endoscopy].

OBJECTIVE: To provide transnasal endoscopic optic canal decompression with the anatomic reference. METHOD: 15 samples of the adult corpse wet specimen (30 sides for the optic canal) were examined under the endoscope to scrutinize the regional anatomy of the optic canal. RESULT: distance between the spina nasalis anterior and the midpoint of optic canal medial wall is (61.02 +/- 5.83) mm, and the angle between spina nasalis anterior and the midpoint of optic canal medial wall is (45.1 +/- 4.81) degrees. The medial wall of optic canal is longest, with an average length of (11.61 +/- 1.58) mm; the lateral wall of optic canal is thickest, and the medial wall thinnest. 10 traumatic blind patient underwent endoscopic optic canal decompression with satisfactory outcome. CONCLUSION: The regional anatomy of the optic canal under endoscope is of importance to endoscopic optic canal decompression. Which is microinvasive with direct approach and clear view thus is widely used in clinical practice.